Cardioprotective effect of preconditioning is more efficient than postconditioning in rats submitted to cardiac ischemia and reperfusion

Abstract Purpose: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. Methods: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis. Results: After reestablishment of coronary blood flow, we observed variations of the ECG trace with increased incidence of ventricular arrhythmia (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%) in cardiac I/R group. The comparison between I/R + preIC group with I/R group demonstrated significant reduction in VA incidence to 28%, AVB to 0% and lethality to 14%. The comparison of I/R + postIC group with I/R group was observed significance reduction in AVB incidence to 25% and lethality to 25%. Conclusion: The preconditioning strategies produce cardioprotection more efficient that postconditioning against myocardial dysfunctions and lethality by cardiac ischemia and reperfusion.

Paclitaxel enhances the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged rat / 中华心血管病杂志

Objective@#To investigate if paclitaxel can enhance the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged ratand explore related mechanism.@*Methods@#Primary cardiomyocytes of Sprague-Dawley rats were isolated by trypsin and divided into 5 groups(n=6 each): control group, hypoxia injury group, hypoxia preconditioning group, paclitaxel group,and paclitaxel+hypoxia preconditioning group. The structure of microtubules and the expression of hypoxia-inducible factor-1α(HIF-1α) were analyzed by immunofluorescence staining. The Langendorff isolated heart perfusion model was applied in 4 groups: hypoxia reperfusion injury group, hypoxia preconditioning group, paclitaxel group, and paclitaxel+hypoxia preconditioning group. Each group was further divided into elderly subgroup and adult subgroup (n=6 each). Left ventricular developed pressure and maximum rate of rise in left ventricular pressure were analyzed.@*Results@#(1) Primary cardiomyocyte experiments showed that the myocardial tubular microtubule structure in control group was intact and evenly stained; most of the microtubules in the hypoxia-injured group were absent and the tubular tissue was broken; the hypoxia-induced damage on microtubule structure was smaller in the hypoxic preconditioning group compared with the hypoxic injury group (microtubule staining was not uniform, and the lattice structure was broken, but not that obvious as in the hypoxia group); the tubular structure of the microtubules of the paclitaxel group was basically complete, and the staining was basically uniform.The integrity of tubular structure was maintained to some extent, similar to a normal microtubule structure in paclitaxel+hypoxia preconditioning group. The expression of HIF-1α in the cytoplasm and nucleus was very low in the control group, which was evidenced in both cytoplasm and nucleus in the hypoxic injury group.The expression was further increased in hypoxic preconditioning group, significant nuclear HIF-1 expression was found in the paclitaxel group, the expression was aggregated in the nucleus in the Paclitaxel+ hypoxia preconditioning group. (2)In Langendorff isolated heart perfusion model, left ventricular developed pressure was similar between the elderly subgroup and the adult subgroup at the end of the infusion,after precondition, 5 minutes of reperfusion, 30 minutes of reperfusion, and 60 minutes of reperfusion in the hypoxic injury group (all P> 0.05).In the hypoxic injury group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((15.63±4.88) mmHg (1 mmHg=0.133 kPa) vs. (95.63±22.14)mmHg and (17.31±2.75)mmHg vs. (91.00±9.58)mmHg, respectively,all P<0.05). In the hypoxic preconditioning group, the adult subgroup had higher left ventricular developed pressure at 5 and 30 minutes of reperfusion when compared with the elderly subgroup((7.13±1.02) mmHg vs. (3.75±1.06)mmHg and (43.94±3.21)mmHg vs.(16.31±1.54)mmHg, respectively,all P<0.01). In the paclitaxel group, the adult subgroup had higher left ventricular developed pressure at 30 and 60 minutes of reperfusion when compared with the elderly subgroup((44.31±7.59)mmHg vs. (5.44±1.21)mmHg, (51.56±6.03)mmHg vs. (22.19±5.14)mmHg, respectively, all P<0.01). In the paclitaxel+hypoxia preconditioning group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((18.63±4.30)mmHg vs. (99.94±8.23) mmHg, P<0.01; (49.69±5.34)mmHg vs. (95.31±5.26)mmHg, P<0.05). Meanwhile, the adult subgroup had higher left ventricular developed pressure at 30 minutes of reperfusion when compared with the elderly subgroup((49.69±5.34)mmHg vs. (18.63±4.33)mmHg, P<0.01).The adult subgroup had higher change rate of maximum rate of rise in left ventricular pressure at 60 minutes of reperfusion when compared with the elderly subgroup in hypoxia preconditioning group, paclitaxel group, and paclitaxel combined hypoxia preconditioning group((62.83±3.92)% vs. (33.33±3.20)%, (44.17±2.32)% vs. (36.67±2.88)%, (72.50±2.66)% vs. (53.17±2.56)%, respectively,all P<0.01).@*Conclusion@#Paclitaxel can enhance the myocardial protective effect of myocardial ischemia preconditioning through stabilizing microtubules of cardiomyocytes and promoting HIF-1α localization in the nucleus.

Protective Effect of Ischemic Preconditioning on Myocardium Against Remote Tissue Injury Following Transient Focal Cerebral Ischemia in Diabetic Rats / Efeito Protetor do Pré-Condicionamento Isquêmico no Miocárdio Contra Lesão Remota de Tecidos após Isquemia Cerebral Focal Transitória em Ratos Diabéticos

Abstract Background: Remote ischemic preconditioning (IPreC) could provide tissue-protective effect at a remote site by anti-inflammatory, neuronal, and humoral signaling pathways. Objectives: The aim of the study was to investigate the possible protective effects of remote IPreC on myocardium after transient middle cerebral artery occlusion (MCAo) in streptozotocin- induced diabetic (STZ) and non-diabetic rats. Methods: 48 male Spraque Dawley rats were divided into eight groups: Sham, STZ, IPreC, MCAo, IPreC+MCAo, STZ+IPreC, STZ+MCAo and STZ+IPreC+MCAo groups. We induced transient MCAo seven days after STZ-induced diabetes, and performed IPreC 72 hours before transient MCAo. Remote myocardial injury was investigated histopathologically. Bax, Bcl2 and caspase-3 protein levels were measured by Western blot analysis. Total antioxidant status (TAS), total oxidant status (TOS) of myocardial tissue were measured by colorimetric assay. Oxidative stress index(OSI) was calculated as TOS-to-TAS ratio. For all statistical analysis, p values < 0.05 were considered significant. Results: We observed serious damage including necrosis, congestion and mononuclear cell infiltration in myocardial tissue of the diabetic and ischemic groups. In these groups TOS and OSI levels were significantly higher; TAS levels were lower than those of IPreC related groups (p < 0.05). IPreC had markedly improved histopathological alterations and increased TAS levels in IPreC+MCAo and STZ+IPreC+MCAo compared to MCAo and STZ+MCAo groups (p < 0.05). In non-diabetic rats, MCAo activated apoptotic cell death via increasing Bax/Bcl2 ratio and caspase-3 levels. IPreC reduced apoptotic cell death by suppressing pro-apoptotic proteins. Diabetes markedly increased apoptotic protein levels and the effect did not reversed by IPreC. Conclusions: We could suggest that IPreC attenuates myocardial injury via ameliorating histological findings, activating antioxidant mechanisms, and inducing antiapoptotic activity in diabetic rats.

Resumo Fundamentos: O pré-condicionamento isquêmico remoto (IPreC) poderia fornecer efeito protetor de tecido em um local remoto por vias de sinalização anti-inflamatórias, neuronais e humorais. Objetivos: O objetivo do estudo foi investigar os possíveis efeitos protetores do IPreC remoto no miocárdio após a oclusão transitória da artéria cerebral média (MCAo) em ratos com diabetes induzida por estreptozotocina (STZ) e ratos não diabéticos. Métodos: 48 ratos Spraque Dawley machos foram divididos em oito grupos: grupos Sham, STZ, IPreC, MCAo, IPreC + MCAo, STZ + IPreC, STZ + MCAo e STZ + IPreC + MCAo. Induzimos MCAo sete dias após a diabetes induzida por STZ e realizamos IPreC 72 horas antes do MCAo. A lesão miocárdica remota foi investigada histopatologicamente. Os níveis de proteína Bax, Bcl2 e caspase-3 foram medidos pela análise Western Blot. O estado de antioxidante total (TAS), e o estado de oxidação total (TOS) do tecido miocárdico foram medidos por meio de um estudo colorimétrico. O índice de estresse oxidativo (OSI) foi calculado como a relação TOS-TAS. Para todas as análises estatísticas, os valores de p < 0,05 foram considerados significativos. Resultados: Observamos danos graves, incluindo necrose, congestão e infiltração de células mononucleares no tecido miocárdico dos grupos diabético e isquêmico. Nesses grupos os níveis de TOS e OSI foram significativamente maiores; os níveis de TAS foram inferiores aos dos grupos relacionados com IPreC (p < 0,05). O IPreC melhorou marcadamente as alterações histopatológicas e aumentou os níveis de TAS em IPreC + MCAo e STZ + IPreC + MCAo em comparação com os grupos MCAo e STZ + MCAo (p < 0,05). Em ratos não diabéticos, MCAo activou a morte celular apoptótica através do aumento da relação Bax / Bcl2 e dos níveis de caspase-3. IPreC reduziu a morte celular apoptótica pela supressão de proteínas pró-apoptóticas. O diabetes aumentou acentuadamente os níveis de proteína apoptótica e o efeito não foi revertido pelo IPreC. Conclusões: Podemos sugerir que o IPreC atenua a lesão miocárdica através da melhora dos achados histológicos, ativando mecanismos antioxidantes e induzindo atividade antiapoptótica em ratos diabéticos.

Is Local Nitric Oxide Availability Responsible for Myocardial Salvage after Remote Preconditioning? / A Disponibilidade de Óxido Nítrico Local é Responsável por Resgate Miocárdio após Pré-Condicionamento Remoto?

Abstract Background: Remote ischemic preconditioning (RIPC) represents an attractive therapy for myocardial protection, particularly when ischemic events can be anticipated. Although several hypothetic mechanisms have been proposed, no definite molecular pathways have been elucidated. Objective: We evaluated the effect of brachial circulation cuff occlusion on myocardial ischemic tolerance, necrosis, and nitric oxide (NO) in patients with ischemic heart disease undergoing elective percutaneous coronary interventions (PCI). Methods: 46 patients were randomly allocated into two groups: control and RIPC before PCI procedures. Electrocardiographic analysis, serum concentrations of troponin I (cTn-I) were measured at baseline and 24 hours after PCI. A blood sample from the atherosclerotic plaque was drawn to determine nitrate and nitrites. Results: RIPC increased the availability of NO in the stented coronary artery. Control patients presented a small but significant increase in cTn-I, whilst it remained unchanged in preconditioned group. The preconditioning maneuver not only preserved but also enhanced the sum of R waves. Conclusions: RIPC induced an intracoronary increase of NO levels associated with a decrease in myocardial damage (measured as no increase in cTn-I) with electrocardiographic increases in the sum of R waves, suggesting an improved myocardium after elective PCI.

Resumo Fundamento: Pré-condicionamento isquêmico remoto (PCIR) é uma terapia para proteção miocárdica, em particular quando é possível prever eventos isquêmicos. Embora vários mecanismos hipotéticos tenham sido propostos, nenhuma via molecular definitiva foi elucidada. Objetivo: Avaliar o efeito da oclusão da circulação braquial com manguito sobre a tolerância à isquemia miocárdica, a necrose miocárdica e a biodisponibilidade de óxido nítrico (NO) em pacientes com cardiopatia isquêmica submetidos a intervenção coronariana percutânea (ICP) eletiva. Métodos: 46 pacientes foram alocados aleatoriamente em dois grupos: controle e PCIR antes da ICP. Análise eletrocardiográfica e medidas da concentração sérica de troponina I (cTn-I) foram realizadas na condição basal e 24 horas após ICP. Coletou-se amostra de sangue da placa aterosclerótica para determinar os níveis de nitratos e nitritos. Resultados: O PCIR aumentou a disponibilidade de NO na artéria coronária que recebeu o stent. O grupo controle apresentou um aumento pequeno, mas significativo, da cTn-I, que permaneceu inalterada no grupo pré-condicionado. O pré-condicionamento não só preservou, como melhorou o somatório de ondas R no eletrocardiograma. Conclusões: O PCIR induziu aumento intracoronariano dos níveis de NO associado com redução do dano miocárdico (medido como aumento da cTn-I) e com aumento do somatório de ondas R, sugerindo melhora miocárdica após ICP eletiva.

Influence of sufentanil preconditioning on early cognitive function and myocardial protection in patients undergoing on-pump CABG / 心血管康复医学杂志

Objective:To observe influence of preoperative sufentanil delayed preconditioning (SPC) on perioperative cogni‐tive function and myocardial protection effect in patients undergoing on -pump coronary artery bypass grafting (OP‐CABG) .Methods:A total of 60 patients undergoing selective OPCABG were randomly and equally divided into sufentanil group (SPC group) and routine treatment control group (control group) ,blood sample was collected before operation ,1h , 6h ,12h ,24h and 48h after aorta declamping to measure level of cardiac troponin I (cTnT );and all patients received neu‐ropsychological assessment before and 7d after operation .Results:Compared with control group ,there was significant re‐ductions in serum cTnI levels [1h:(23.66 ± 3.15) ng/ml vs .(14.96 ± 2.13) ng/ml] in sufentanil group from 1h after aor‐ta declamping to 48h after CABG ,P<0.05 all .The inotropic agent usage score on 12h ,24h and 48h after entering ICU of sufentanil group was significantly lower than that of control group [12h:(6.4 ± 0.6) scores vs .(8.4 ± 0.6) scores] , P<0.05 all .Incidence rate of postoperative cognitive dysfunction (POCD) in sufentanil group was significantly lower than that of control group (13.3% vs .30.0% ,P=0.041) .Conclusion:Preoperative sufentanil delayed preconditioning posses‐ses myocardial protection effect , and reduce incidence rate of cognitive dysfunction so also possesses certain brain protection in patients undergoing on-pump coronary artery bypass grafting .

Cardioprotection induced by hypoxic preconditioning and ischemic preconditioning in in vivo hearts of dogs：using double CPB circuits / 中华麻醉学杂志

Objective To evaluate the cardioprotection induced by ischemic preconditioning ( IPC) and hypoxic preconditioning ( HPC) which were carried out by using the double cardiopulmonary bypass ( CPB) circuits in in vivo hearts of dogs. Methods Eighteen healthy male dogs, weighing 17?5-24?5 kg, aged 13-24 months, were divided into 3 groups ( n=6 each) using a random number table: my?ocardial ischemia?reperfusion group (group I∕R), IPC group and HPC group. The double CPB circuits were established as follows: systemic and coronary circulation, and independent systemic and coronary cir?culation was carried out. In group IPC, the aorta was clamped, and the coronary circulation pump was sus?pended for 5 min followed by 5 min opening, repeating for 3 cycles. In group HPC, the aorta was clamped, the coronary circulation was started, and pure nitrogen was insufflated for 5 min followed by 5 min of oxygen insufflation, repeating for 3 cycles. CPB was performed for 1 h starting from the time point immediately after IPC or HPC. Before splitting of sternum ( T1 ) , after establishment of double CPB circuits ( T2 ) , at the end of preconditioning ( T3 ) , and at 60 and 120 min after restoration of spontaneous heart beat ( T4,5 ) , heat rate, mean arterial pressure, central venous pressure, left ventricular end?systolic pres?sure, left ventricular end?diastolic pressure and the maximum rate of increase∕decrease of left ventricular pressure were recorded. Blood samples were collected from the right internal jugular vein at T1 and T4,5 for determination of serum cardiac troponin I concentrations. The animals were sacrificed after determination of the parameter or after blood sampling at T5 , myocardial specimens were obtained for examination of the ul?trastructure and for detection of apoptosis in cardiomyocytes, and apoptosis index was calculated. Before aortic clamping, immediately after aortic unclamping and at 30 min after aortic unclamping, myocardial specimens were obtained for determination of ATP contents in cardiomyocytes. Results Compared with I∕R group, left ventricular end?systolic pressure was significantly increased, and the serum cardiac troponin I concentrations were significantly decreased at T4,5 , the myocardial ATP contents were significantly in?creased immediately after aortic unclamping and at 30 min after aortic unclamping, apoptosis index was sig?nificantly decreased ( P<0?05 or 0?01) , and the pathological changes were significantly attenuated in IPC and HPC groups. Compared with group IPC, the myocardial ATP contents were significantly increased (P<0?05), and the pathological changes were attenuated in group HPC. Conclusion Both HPC and IPC can exert cardioprotection when carried out by using the double CPB circuits, and HPC provides better cardioprotection than IPC in in vivo hearts of dogs.

Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart / Efeitos da isquemia e pré-condicionamento com omeprazol na recuperação funcional do coração isolado de rato

Abstract Objective: The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion. Methods: The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG) after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped) for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC) were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC) hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion. Results: Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion. Conclusion: Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible. .

Resumo Objetivo: O objetivo deste estudo foi comparar os efeitos protetores de efeitos protetores isquêmicos e potenciais de précondicionamento farmacológico com omeprazol no coração isolado de rato submetido à isquemia/reperfusão. Métodos: Os corações de ratos albinos Wistar machos foram excisados e perfundidos em um aparelho de Langendorff. No grupo controle (grupo I), após o período de estabilização, os corações foram submetidos à isquemia global (a perfusão foi totalmente interrompida) por 20 minutos e 30 minutos de reperfusão. Corações do grupo II (IPC) foram submetidos a précondicionamento isquêmico com duração de 5 minutos antes de 20 minutos de isquemia e 30 minutos de reperfusão. No terceiro grupo (OPC), corações foram submetidos a pré-condicionamento com duração de 5 minutos com 100 μM de omeprazol, e, então, submetidos a 20 minutos de isquemia e 30 minutos de reperfusão. Resultados: A administração de omeprazol antes da indução da isquemia teve efeito protetor sobre a recuperação funcional do miocárdio especialmente em relação aos valores de pressão sistólica ventricular esquerda e dp/dt max. Também os nossos achados são de que os valores de fluxo coronário não se alteraram entre os grupos OPC e IPC no último ponto de reperfusão. Conclusão: Com base nos nossos resultados, o pré-condicionamento isquêmico poderia ser usado como primeira janela de proteção após a lesão isquêmica, especialmente porque todos os parâmetros analisados apresentam tendência contínua de recuperação da função do miocárdio. Por outro lado, o pré-condicionamento induzido com omeprazol apresenta tendência repentina de recuperação com proteção miocárdio positiva, embora menos efetiva da obtida com o pré-condicionamento isquêmico. Devemos considerar que o omeprazol pode ser usado em muitas circunstâncias clínicas em que o pinçamento coronariano direto para pré-condicionamento isquêmico não é possível. .

Effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Eighty New York Heart Association (NYHA) class Ⅱ or Ⅲ patients of both sexes,aged 21-59 years,scheduled for cardiac valve replacement with CPB,were randomly divided into four groups (n =20 each):normal saline control group (group C),ulinastatin preconditioning group (group U1),ulinastatin postconditioning group (group U2) and ulinastatin preconditioning plus postconditioning group (group U3).In group U1,uinastatin 20000 U/kg was infused via the central vein at 500-1000 U·kg-1 · min-1 after endotracheal intubation until 10 minutes before blocking the ascending aorta.In group U2,ulinastatin 10000 U/kg was infused via the aortic root at 4000-5000 U· kg-1 · min-1 at 5-7 minutes before opening the aorta.In group U3,ulinastatin preconditioning and postconditioning were performed as described in groups U1 and U2.In group C,the same volume of normal saline was infused instead of ulinastatin.Blood samples were taken from the radial artery at 10 minutes before blocking the ascending aorta,40 minutes after blocking the ascending aorta,45 minutes after opening the aorta and at the end of operation for determination of plasma concentrations of tumor necrosis factor-alpha (TNF-α) and soluble tumor necrosis factor receptor 1 (sTNF-R1).Myocardial tissues were obtained from the right atrial appendage at 45 minutes after opening the aorta for determination of the expression of TNF-α,bcl-2,bax,caspase-3,and apoptosis.The bcl-2/bax ratio and apoptotic index were calculated.Results Plasma concentrations of TNF-α and sTNF-R1 and the expression of TNF-α,bax,caspase-3 and apoptotic index were lower and the expression of bcl-2 and bcl-2/bax ratio were higher in groups U1,U2 and U3 than in group C and they were lower in group U3 than in groups U1 and U2 (P ＜ 0.05).Conclusion Ulinastatin postconditioning can inhibit myocardial apoptosis in patients undergoing cardiac valve replacement with CPB,and the efficacy of combination of ulinastatin preconditioning and postconditioning is stronger than that of ulinastatin postconditioning.The mechanism is involved in balancing the expression of bax and bcl-2 and down-regulating the expression of TNF-α and its receptor.

Myocardial protective effect of ischemic preconditioning in patients undergoing open heart surgery: a meta-analysis / 中华麻醉学杂志

Objective To systematically review the myocardial protective effect of ischemic preconditioning in patients undergoing open heart surgery.Methods PubMed,EMBASE,Highwire,CENTREN and its affiliated clinical trial registration data center,CBM and CNKI were searched to identify all randomized controlled trials involving the myocardial protective effect of ischemic preconditioning in patients undergoing open heart surgery under general anesthesia.The quality of the studies was evaluated by the method recommended by Cochrane Collaboration.Evaluation indexes included the incidences of postoperative cardiac death,myocardial infarction and ventricular arrhythmias and postoperative inotropic drug requirement.Meta-analysis was conducted using the Cochrane Collaboration's RevMan 5.0 software.Results Twelve randomized controlled trials (8 high-quality trials and 4 medium-quality trials) involving 626 patients were included in our Meta-analysis.Meta-analysis indicated that ischemic proconditioning significantly reduced the incidence of postoperative ventricular arrhythmias and postoperative inotropic drug requirement (P ＜ 0.05) and had no effect on the incidences of postoperative cardiac death and myocardial infarction (P ＞ 0.05).Conclusion Ischemic preconditioning can reduce the postoperative ventricular arrhythmias and have no effect on postoperative cardiac death and myocardial infarction in patients undergoing open heart surgery.

Role of silent information regulator 1 in ischemic preconditioning-induced alleviation of myocardial ischemia-reperfusion injury / 中华麻醉学杂志

Objective To evaluate the role of silent information regulator 1 (SIRT1) in ischemic preconditioning (IPC)-induced alleviation of myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty-eight male Sprague-Dawley rats,aged 12 weeks,weighing 200-250 g,were randomly divided into 4 groups (n =12 each):sham operation group (S group),I/R group,IPC group and IPC + SIRT1 inhibitor ex527 group (IPC + ex527 group).Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.IPC was induced by 3 episodes of 5 min occlusion of left anterior descending branch at 5 min intervals before myocardial ischemia.SIRT1 inhibitor ex527 1 μg/kg was injected intravenously 15 min before myocardial ischemia and at 1 min before reperfusion.Blood samples were collected before myocardial ischemia and at 120 min of reperfusion for measurement of serum TNF-α and IL-6 concentrations by ELISA.The rats were then sacrificed and myocardial specimens were obtained for determination of myocardial lactic dehydrogenase (LDH) and creatine kinase MB (CK-MB) activities,SIRT1 expression and acetylation of NF-κB p65.Results Compared with S group,the serum TNF-α and IL-6 concentrations at 120 min of reperfusion,and myocardial LDH and CK-MB activities and acetylation of NF-κB p65 were significantly increased,and SIRT1 expression was down-regulated in I/R and IPC + ex527 groups (P ＜ 0.05).Compared with I/R group,the serum TNF-α and IL6 concentrations at 120 min of reperfusion,and myocardial LDH and CK-MB activities and acetylation of NF-κB p65 were significantly decreased,SIRT1 expression was up-upregulated in group IPC (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group IPC + ex527 (P ＞ 0.05).Compared with IPC group,the serum TNF-α and IL-6 concentrations at 120 min of reperfusion,and myocardial LDH and CK-MB activities and acetylation of NF-κB p65 were significantly increased,and SIRT1 expression was down-regulated in group IPC + ex527 (P ＜ 0.05).Conclusion SIRT1 is involved in IPC-induced alleviation of myocardial I/R injury in rats.

Effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Eighty NYHA class Ⅱ or Ⅲ patients of both sexes,aged 21-59,scheduled for cardiac valve replacement with CPB,were randomly divided into 4 groups ( n =20 each):normal saline control group ( group C ),ulinastatin preconditioning group ( group U1 ),ulinastatin postconditioning group (group U2 ) and ulinastatin preconditioning plus postconditioning group(group U3 ).In group U1,uinastatin 20 000U/kg was infused via central vein at 500-1000 U·kg-1 ·min-1 from after tracheal intubation until 10 min before ascending aortic cross-clamping.In group U2,ulinastatin 10 000 U/kg was perfused via aortic root at 4000-5000 U· kg-1 · min-1 at 5-7 min before aortic unclamping.In group U3,ulinastatin preconditioning and postconditioning were performed as described in groups U1 and U2.In group C same volume normal saline was infused instead of ulinastatin.Blood samples were taken from radial artery at 10 min before ascending aortic cross-clamping,40 min after ascending aortic cross-clamping,45 min after aortic unclamping and the end of operation for determination of plasma concentrations of TNF-α and soluble tumor necrosis factor receptor 1 (sTNF-R1).Myocardial tissues were obtained from right atrial appendage at 45 min after aortic unclamping for determination the expression of TNF-d,Bcl-2,Bax and caspase-3 and apoptosis.The Bcl-2/Bax ratio and apoptotic index were calculated.Results Plasma concentrations of TNF-α and sTNF-R1 and the expression of TNF-α,Bax,caspase-3 and apoptotic index were lower,the expression of Bcl-2 and Bcl-2/Bax ratio were higher in groups U1,U2 and U3 thah group C and in group U3 than groups U1,U2 ( P ＜ 0.05 ).Conclusion Ulinastatin postconditioning can inhibit myocardial apoptosis in patients undergoing cardiac valve replacement with CPB,and efficacy of combination of ulinastatin preconditioning and postconditioning is stronger than that of ulinastatin postconditioning.The mechanism is involved in balancing the expression of Bax and Bcl-2 and down-regulating the expression of TNF-α and its receptor.

Effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To investigate the effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion (I/R) in rats. Methods Fifty healthy male Wistar rats weighing 250-280 g were randomly divided into 5 groups (n = 10 each) : sham operation group (group S) , I/R group, sevoflurane preconditioning group (group Spr), sevoflurane postconditioning group (group Spo)and combination of sevoflurane preconditioning and postconditioning group (group Spr + po). Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion in anesthetized rats. In group S the anterior descending branch was only exposed but not ligated. Group Spr received 15 min inhalation of 2.5 % sevoflurane and 15 min wash-out 30 min before ischemia. Group Spo received 5 min inhalation of 2.5% sevoflurane 1 min before reperfusion. Arterial blood samples were taken at 2 h of reperfusion for determination of the levels of MB isoenzyme of creatine kinase (CK-MB) , lactate dehydrogenase (LDH) , cardiac troponin I (cTnI), thromboxane B2(TXB2), and 6-keto-prostaglandin (6-keto-PGF1α) and platelet maximum aggregation rate. TXB2/6-keto-PGF1α ratio was calculated. The myocardial tissues were taken for microscopic examination. Mitochondria] injury was assessed by using Flameng score and stereology (Specific surface, δ and Numerical density on area, NA) .Results Compared with group S, the levels of CK-MB, LDH, cTnI, TXE2 and 6-ketoPGF1α, TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly increased, while δ and NA were significantly decreased in group I/R (P < 0.05 or 0.01) . The levels of CK-MB,LDH and cTnI, TXB2/6-keto-PGF1α ratio and Flameng score were significantly lower, and 6-keto-PGF1α level, δand NA were significantly higher in Spr and Spo groups than in group I/R ( P < 0.05 or 0.01) . The levels of CKMB, LDH, cTnI and TXB2 , TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly lower and 6-keto-PGF1α level,δ and NA were significantly higher in group Spr + po than in Spr and Spo groups(P < 0.05). Conclusion Sevoflurane preconditioning-postconditioning can reduce myocardial I/R injury through inhibiting the release of thromboxane A2 and promoting the release of prostaglandin I2 in rats.

Ischemic postconditioning protects cardiomyocytes against ischemia/reperfusion injury by inducing MIP2

Cardiomyocytes can resist ischemia/reperfusion (I/R) injury through ischemic postconditioning (IPoC) which is repetitive ischemia induced during the onset of reperfusion. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a member of the WD-40 family proteins, we previously showed that MIP2 was up-regulated during ischemic preconditioning (IPC). As IPC and IPoC engaged similar molecular mechanisms in cardioprotection, this study aimed to elucidate whether MIP2 was up-regulated during IPoC and contributed to IPoC-mediated protection against I/R injury. The experiment was conducted on two models, an in vivo open chest rat coronary artery occlusion model and an in vitro model with H9c2 myogenic cells. In both models, 3 groups were constituted and randomly designated as the sham, I/R and IPoC/hypoxia postconditioning (HPoC) groups. In the IPoC group, after 45 min of ischemia, hearts were allowed three cycles of reperfusion/ischemia phases (each of 30 s duration) followed by reperfusion. In the HPoC group, after 6 h of hypoxia, H9c2 cells were subjected to three cycles of 10 minute reoxygenation and 10 minute hypoxia followed by reoxygenation. IPoC significantly reduced the infarct size, plasma level of Lactate dehydrogenase and creatine kinase MB in rats. 12 h after the reperfusion, MIP2 mRNA levels in the IPoC group were 10 folds that of the sham group and 1.4 folds that of the I/R group. Increased expression of MIP2 mRNA and attenuation of apoptosis were similarly observed in the HPoC group in the in vitro model. These effects were blunted by transfection with MIP2 siRNA in the H9c2 cells. This study demonstrated that IPoC induced protection was associated with increased expression of MIP2. Both MIP2 overexpression and MIP2 suppression can influence the IPoC induced protection.

Escore eletrocardiográfico: aplicação em ergometria para avaliação do precondicionamento isquêmico / Electrocardiographic score: application in exercise test for the assessment of ischemic preconditioning / Escore electrocardiográfico: aplicación en ergometría para evaluación del preacondicionamiento isquémico

FUNDAMENTO: O tempo para 1,0 mm de depressão do segmento ST (T-1,0 mm), adotado para caracterizar o precondicionamento isquêmico (PCI) em testes ergométricos sequenciais, é consistente e reprodutível, porém, possui várias limitações. OBJETIVO: Aplicar um escore eletrocardiográfico de isquemia miocárdica em testes ergométricos sequenciais, comparando-o com o clássico índice T-1,0 mm. MÉTODOS: Avaliamos 61 pacientes, com idade média de 62,2 ± 7,5 anos, sendo 86,9 por cento homens. Foram analisados 151 exames, sendo 116 de pacientes que completaram duas fases de avaliação. A primeira fase compreendia dois testes ergométricos sequenciais para documentação do PCI e a segunda fase, após uma semana, mais dois testes sob efeito de repaglinida. Dois observadores aplicaram o escore de forma cega. RESULTADOS: Observou-se concordância perfeita inter e intraobservador (Kendall Tau-b = 0,96, p < 0,0001, Kendall Tau-b = 0,98,p < 0,0001, respectivamente). Os valores de sensibilidade, especificidade, valor preditivo negativo, valor preditivo positivo e acurácia foram de 72,41 por cento, 89,29 por cento, 75,8 por cento, 87,5 por cento e 81,0 por cento, respectivamente. CONCLUSÃO: O escore de isquemia é um método consistente e reprodutível para documentação do PCI, representando uma alternativa factível ao índice T-1,0 mm.

BACKGROUND: The time for 1.0 mm ST-segment depression (T-1.0mm) adopted to characterize ischemic preconditioning (IPC) in sequential exercise tests is consistent and reproducible; however, it has several limitations. OBJECTIVE: To apply an electrocardiographic score of myocardial ischemia in sequential exercise tests, comparing it to the conventional T-1.0 mm index. METHODS: Sixty one patients with mean age of 62.2 ± 7.5 years were evaluated; 86.9 percent were males. A total of 151 tests were analyzed, 116 of which were from patients who completed two assessment phases. The first phase comprised two sequential exercise tests for the documentation of IPC; the second phase, initiated one week later, comprised two more tests carried out under the effect of repaglinide. Two observers who were blind to the tests applied the score. RESULTS: Perfect inter and intraobserver agreement was found (Kendall tau-b = 0.96, p < 0.0001, and Kendall tau-b = 0.98, p < 0.0001, respectively). Values of sensitivity and specificity, negative predictive value, positive predictive value and accuracy were 72.41 percent, 89.29 percent, 75.8 percent, 87.5 percent and 81.0 percent, respectively. CONCLUSION: The ischemic score is a consistent and reproducible method for the documentation of IPC, and is a feasible alternative to T-1.0 mm.

FUNDAMENTO: El tiempo para 1,0 mm de depresión del segmento ST (T-1,0 mm), adoptado para caracterizar el preacondicionamiento isquémico (PCI) en test ergométricos secuenciales, es consistente y reproducible, sin embargo, posee varias limitaciones. OBJETIVO: Aplicar un escore electrocardiográfico de isquemia miocárdica en test ergométricos secuenciales, comparándolo al clásico índice T-1,0 mm. MÉTODOS: Evaluamos 61 pacientes, con edad media de 62,2 ± 7,5 años, siendo 86,9 por ciento hombres. Fueron analizados 151 exámenes, siendo 116 de pacientes que completaron dos fases de evaluación. La primera fase comprendía dos test ergométricos secuenciales para documentación del PCI y la segunda fase, después de una semana, más dos test bajo efecto de repaglinida. Dos observadores aplicaron el escore de forma ciega. RESULTADOS: Se observó concordancia perfecta inter y intraobservador (Kendall Tau-b = 0,96, p < 0,0001, Kendall Tau-b = 0,98,p < 0,0001, respectivamente). Los valores de sensibilidad, especificidad, valor predictivo negativo, valor predictivo positivo y precisión fueron de 72,41 por ciento, 89,29 por ciento, 75,8 por ciento, 87,5 por ciento y 81,0 por ciento, respectivamente. CONCLUSIÓN: El escore de isquemia es un método consistente y reproducible para documentación del PCI, representando una alternativa factible al índice T-1,0 mm.

Proteção da recuperação funcional do miocárdio pelo omeprazol após isquemia-reperfusão em corações isolados de ratos / Myocardium functional recovery protection by omeprazole after ischemia-reperfusion in isolated rat hearts

OBJETIVO: Analisar efeitos do omeprazol na proteção da recuperação funcional de corações isolados de ratos submetidos à lesão de isquemia-reperfusão. MÉTODOS: Foram estudados 12 ratos Wistar, peso corpóreo médio de 280g. Após anestesia com injeção intra-abdominal de 10mg de cetamina e 2mg de xilazina, os corações foram removidos e mantidos em perfusão com solução Krebs-Henseleit (95 por centoO2 e 5 por cento CO2, 37ºC, 110-120mmHg de pressão de perfusão e pressão diastólica de 8 mmHg) em sistema Langendorff, modificado, descartável, modelo FCSFA-ServCor (Comex Ltda.). Os seis corações do Grupo I (GI) e os seis do Grupo II (GII) foram submetidos a 20 minutos de isquemia e 30 minutos de reperfusão. Nos corações do Grupo II, imediatamente antes da isquemia, foram administrados via perfusão coronária 200mcg de omeprazol. Foram controlados frequência cardíaca (FC), fluxo coronário (FCo), pressão sistólica (PS), +dP/dt e -dP/dt, após estabilização (t0) e no final da reperfusão (t30). Empregou-se método não paramétrico de Kruskal-Wallis (P<0,05) para análise estatística dos dados. RESULTADOS: Não ocorreram diferenças (P>0,05) entre os valores de FCo e FC nos dois grupos. No final do período de reperfusão (t30), foram significantes (P<0,05) as variações da PS reduzida para 28,0±3,6 por cento do valor inicial (t0) no Grupo I e para 79.0±5,9 por cento no Grupo II; a +dP/dtmax declinou para 31,0±5,6 por cento no GI, mantendo-se em 99,4±11,2 por cento (P<0,05) no GII e a -dP/dtmax declinou para 26,0±7,3 por cento no GI, mantendo-se em 82,0±2, 2 por cento no GII (P<0,05). CONCLUSÃO: A administração do omeprazol antes da indução da isquemia coronária protegeu significantemente a recuperação funcional do miocárdio.

OBJECTIVE: To evaluate the myocardium contractility alterations of isolated hearts of rats, submitted to ischemia and reperfusion with and without administration of the omeprazole. METHODS: Twelve Wistar breed rats with 270g mean body weight was studied. After anesthesia by intraperitoneal injection of ketamine 10mg and xylazine 2mg, their hearts were removed and perfused with Krebs-Henseleit solution (95 percent of O2 and 5 percent of CO2, 37ºC, 110-120 mmHg perfusion pressure, 8 mmHg ventricular diastolic pressure) in the São Francisco de Assis disposable Langendorff system model Comex Ltda, MG. The six hearts of Group I (GI) and of the Group II (GII) were submitted to 20 min ischemia and 30 min reperfusion. In GII hearts, intracoronary injection of omeprazole 200 mcg was done immediately before the ischemia period induction. The following parameters were registered after the stabilization period (t0), and after the reperfusion period (t30): heart rate (HR), coronary flow (CoF), systolic pressure (SP), +dP/dt and -dP/dt. The Kruskal-Wallis test (P<0.05) was applied to statistical analysis. RESULTS: There were no significant differences (P>0.05) between groups among HR and CoF values. Differences (P<0.05) occurred between groups, I e II after the reperfusion period (t30) regarding systolic pressure reduced for 28.0±3.6 percent in the control group GI and for 79.0±5.9 percent in GII; The +dP/dtmax declined to be only 31.0±5.6 percent in GI, preserving 99.4±11.2 percent values in GII (P<0.05). The t30 -dP/dtmax values were GI 26.0±7.3 percent and GII 82.0±2.2 percent (P<0.05). CONCLUSION: The omeprazole administration before ischemia induction significantly protected the myocardium function recovery.

Effects of ischemic preconditioning versus ischemic postconditioning on myocardial ischemia-reperfusion-induced inflammatory response in rats / 中华麻醉学杂志

Objective To compare the effects of ischemic preconditioning versus ischemic postconditioning on myocardial ischemia-reperfusion (I/R)-induced inflammatory response in rats. Methods Forty male SD rats weighing 290-320 g were randomly divided into 4 groups ( n = 10 each): Ⅰ group sham operatin (group S); Ⅱ group I/R; Ⅲ group ischemic preconditioning (group IPC) and Ⅳ group ischemic postconditioning (group IPOC).Myocardial I/R was induced by 30 min ligation of left anterior descending branch (LAD) of coronary artery followed by reperfusion. In group IPC myocardial I/R was preceded by 3 cycles of ischemia followed by reperfusion (each lasting 5 min) while in group IPOC 3 cycles of I/R (each lasting 10 s) was started at the end of 30 min myocardial ischemia. MAP, HR and RPP ( MAP × HR) were recorded before (baseline) and at 1 and 20 min of ischemia and 60, 120 and 180 min of reperfusion. Venous blood samples were collected at 30 and 180 min of reperfusion for determination of serum concentrations of TNF-α, IL-6, high-mobility group box 1 (HMGB1) and cTnI. The animals were sacrificed at 180 min of reperfusion and the myocardial infarct size was measured. Results Myocardial I/R significantly decreased MAP and RPP and increased myocarcial infarct size, serum concentrations of TNF-α, IL-6,HMGB1 and cTnI in group I/R as compmed with group S. Ischemic pre- and postconditioning significantly increased MAP and reduced myocardial infarct size and I/R-induced increase in serum TNF-α, HMGB1 and cTnI concentrations in group Ⅲ and Ⅳ as compared with group Ⅱ (I/R). The myocardial infarct size was significantly larger and the serum concentrations of TNF-α, IL-6 and HMGB1 were significantly higher in ischemic postconditioning group than in the preconditioning group. Conclusion Ischemic preconditioning is more effective in attenuating the myocardial I/R-induced inflammatory response than the ischemic postconditioning.

Role of cyclooxygenase-2 and mitochondrial KATP channels in sufentanil preconditioning-induced delayed cardioprotection against myocardial ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the role of cyclooxygenase-2(COX-2)and mitochondrial adenosine tuiphosphate sensitive potassium channels (mito-KATP channels) in sufentanil preconditioning-induced delayed cardiopreteetion against myocardial ischemia-reperfnsion (I/R) injury in rats. Methods Seventy-two adult male Wistsr rats weighing 250-300 g were randomly divided into 6 groups ( n =12 each). Group Ⅰ,Ⅱ,Ⅲ were preconditioned with intraperitoneal (IP) normal saline (NS) 1 ml/kg while group Ⅳ,Ⅴ,Ⅵ with IP sufentanil 20 μg/kg at 24 h before myocardial ischemia. Group Ⅱ and Ⅴ were given IP NS-398 ( COX-2 inhibitor) 5 mg/kg at 30 rain before myocardial ischemla while group Ⅲ and Ⅵ were given intravenous 5-HD (mito-KATP channelblocker) 10 mg/kg at 10 min before ischemia or before being killed. Six animals in each group underwent 45 min myocardial ischemia followed by 120 min reperfusion, while the other six animals in each group were killed immediately before ischemia for determination of myocardial COX-2 expression and myocardial PGF2 and PGF1α content. Myocardial ischemia was induced by occlusion of left anterior descending branch (LAD) of coronary artety for 45 rain followed by 120 min reperfusion. MAP and HR were recorded immediately before ischemia (T0), at 15, 30, 45 rain of ischemia (T1-3) and at 30, 60, 90, 120 vain of reperfusion (T4-7). Heart rate-blood pressure product (RPP) was calculated. Arterial blood samples were obtained at T0.3 and T7 for measurement of plasma CK-MB activity. The animals were killed at the end of 120 nan reperfusion. The hearts were removed for determination of myocardial infarct area (IA) and area at risk (AAR). LA/AAR was calculated. Results There was no significant difference in HR, MAP and RPP at all time points among the 6 groups. Preconditioning with sufentanil significantly decreased plasma CK-MB activity at T3 and T7 and IA/AAR in group Ⅳ as compared with group Ⅰ.Myocardial COX-2 expression was up-regulated and PGE2 and PGF1α, contents were elevated by sufentanil preconditioning in group Ⅳ as eomared with control group (Ⅰ). In group Ⅴ and Ⅳ preconditioning with NS-398/5-HD significantly increased plasma CK-MB concentration and IS/AAB as compared with group Ⅳ, indicating involvement of COX-2 and mito-KATP channels in the sufentanil-induced delayed cardioprotection.The myocardial PGE2 and PGF1α contents were significantly reduced in group Ⅴ as compared with group Ⅳ. There was no significant difference in the myocardial COX-2 expression among group Ⅳ, Ⅴ and Ⅵ. Conclusion Both COX-2 and mito-KATP channels are involved in sufentanil preconditioning-induced delayed cardiopmtection.

Role of mitochondrial permeability transition pore in attenuation of myocardial ischemia-reperfusion injury by delayed preconditioning with sevoflurane in rats / 中华麻醉学杂志

Objective To investigate the role of mitochondrial permeability transition pore (mPTP) in attenuation of myocardial ischemia-reperfusion (I/R) injury by delayed preconditioning with sevoflurane in rats.Methods Eighty male SD rats, weighing 250-300 g, were randomly assigned into 5 groups ( n = 16 each): Ⅰsham operation group (group S), Ⅱ group I/R, Ⅲ sevoflurane delayed preconditioning group (group SP), Ⅳ the mPTP opener atractyloside + sevoflurane delayed preconditioning group (group A + SP), and Ⅴ atractyloside group (group A). Myocardial I/R was induced by ligation of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion in group I/R, SP, A + SP and A. In group SP and A + SP, 2.5%sevoflurane was inhaled for 1 h, while pure oxygen was inhaled for 1 h in the other groups, and then myocardial ischemia was performed 24 h later. In group A + SP and A, atractyloside 5 mg/kg was injected intravenously via caudal vein 15 min before ischemia. Blood samples were taken from carotid arteries for detection of serum cardiac troponin-Ⅰ (cTnI) concentrations at the end of reperfusion. Then the rats were sacrificed and hearts removed. The myocardial infarct size (IS) and expression of Bcl-2 and Bax in the myocardium were determined. Myocardial ultrastructure was examined with the electron microscope. Results Serum cTnI concentrations and Bax expression were significantly higher, the myocardial IS was significantly larger and Bcl-2 expression was significantly lower in the other groups than in group S ( P ＜ 0.05). Serum cTnI concentrations and Bax expression were significantly lower, the myocardial IS was significantly smaller and Bcl-2 expression was significantly higher in group SP than in group I/R ( P ＜ 0.05). Microscopic examination showed less damage in group SP than in group I/R. The protection provided by sevoflurane preconditioning was abolished by atractyloside. Conclusion Inhibition of mPTP opening can result in an up-regulation of Bcl-2 expression and down-regulation of Bax expression, which plays a role in attenuation of myocardial I/R injury by delayed preconditioning with sevoflurane in rats.

The protective effect of sufentainil on rat myocardial ischemia-reperfusion injury and caspase-3 / 中华胸心血管外科杂志

Objective To investigate the effect of Sufentainil on myocardial ischemia-reperfusion injury and caspase-3 to rat heart. Methods Ninety Wistar rats weighing 200-300g were randomly divided into 3 groups(n=30):sham group(group S), ischemia-reperfusion group (group I/R)and Sufentainil group (group SF). Each group was divided into 3 subgroups according to the time phases at 30, 60 and 120min(n=10).In group I/R and group S the animals were received normal saline intravenously. In group SF sufentainil 5μg/kg NS 20ml was given. After 24 h, all animals were anesthetized with intraperitioneal 20% urethane 1 mg/kg, intubated and mechanically ventilated. The chest was opened and heart exposed via thoracotomy.In group S , left artery anterior descending artery(LAD) was not ocluded. While in I/R and SF group myocardial ischemia was introduced by clamping LAD for40 min. The animals were killed at 30, 60 and 120 min of reperfusion respectively(n=10each). Cardiac tropoin I(cTnI), expression of caspase-3 and apoptosis of cell in heart tissues were measured at the same time.Ultrastructure of myocardium taking the from apex was examined by electron microscopy at the end of 120 min reperfusion. Results Compared with group S, the concentration of cTnI was increased in the other 2 groups(P<0.05).cTnI was significantly lower in group SF than in group I/R(P<0.05). Expression of caspase-3 and apoptosis index induced by myocardial reperfusion were attenuatated in group SF(P<0.05). The damage of myocardial ultrastructure caused by myocardial I/R were also significantly improved in group SF. Conclusion Sufentainil may relieve the heart cellular apoptosis by decreasing caspase-3expressing.

The effect of Ras protein on the delayed myocardial protection of Lovastatin preconditioning in the ischemia and reperfused rat hearts / 中国医师杂志

Objective To investigate the effect of Ras protein on the delayed myocardial protection of Lovastatin preconditioning in the ischemic and reperfused rat hearts.Methods 24 Sprague-Dawley male rats were randomly and evenly divided into three groups,model control group,N group and Lovastatin group.Lovastatin group was treated with 15mg Lovastatin per a kilogram once a day,N group treated with the same dose of Lovastatin with Lovastatin group and L-NAME 30mg per a kilogram once a day.Rat models of I/R were established with coronary occlusion 30 minutes and reperfusion 30 minutes of the left anterior descending artery after two-week's administration.The expression of Ras-GTPase protein in the heart tissue was determined and myocardial apoptosis was detected in all groups.Results The number of TUNEL positive myocardial nuclei in L group was remarkably reduced,compared with C group(t=2.32,P＜0.05).Ras-GTPase protein in the heart tissue was significantly inhibited in the L and N group,compared with C group(t=2.25,P＜0.05).Conclusion Lovastatin may have the delayed protective effect on the ischemie and reperfused rat heart,which effect may be correlated with inhibition of RasGTPase protein during the period of ischemia and reperfusion.Its protective effect was not correlated with NO.