The effects of methanol extract of Galium verum L on cardiac redox state in hypertensive rats

Abstract The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.

Effects of ultrafine particulates on cardiac function in rat isolated heart / 北京大学学报(医学版)

OBJECTIVE@#To evaluate whether ultrafine particulates (UFPs) have direct deleterious effects on cardiac function through activating MAPK signaling.@*METHODS@#Langendorff-perfused Sprague-Dawley rat hearts were randomly divided into 2 groups (n=10/each group). In control group, the rat hearts were perfused with Tyrode's buffer for 40 min; in UFPs-treated group, the hearts were perfused with UFPs at a concentration of 12.5 mg/L. Cardiac function was determined by measuring left ventricular developed pressure (LVDP), left ventricular peak rate of contraction and relaxation (±dp/dtmax) and coronary flow (CF). The levels of malondialdehyde (MDA), superoxide dismutase (SOD), total anti-oxidant capacity (TAOC) were detected in order to evaluate cardiac oxidative stress via the thiobarbituric acid assay, water soluble tetrazolium salt assay and colorimetry, respectively. The expressions of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium were observed using immunohistochemical staining and Western blots.@*RESULTS@#No significant changes in cardiac function were detected before and after the perfusion in control group while UFPs perfused hearts showed a decline in cardiac function in a time-dependent manner (all P < 0.05). In UFPs-treated group, LVDP, +dp/dtmax, -dp/dtmax and CF were statistically reduced from (82.6±2.1) mmHg, (1 624±113) mmHg/s, (1 565±116) mmHg/s, (12.0±0.2) mL/min to (56.8±4.4) mmHg, (1 066±177) mmHg/s, (1 082±134) mmHg/s, (8.7±0.3) mL/min (all P < 0.05), respectively. Furthermore, The comparison between the two groups observed that UFPs perfusion caused a significant decrease in cardiac function at 30 and 40 min compared with the control group (all P < 0.05). At the end of the perfusion, the level of MDA was increased from (0.98±0.14) nmol/L to (1.95±0.18) nmol/L, while SOD and TAOC were reduced from (12.50±1.87) U/mL and (6.83±1.16) U/mL to (6.50 ±1.04) U/mL and (3.67±0.82) U/mL (all P < 0.001) in UFPs group, respectively. In coincidence with these changes, immunohistochemistry and Western blots results showed that the levels of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium significantly increased in UFPs group as compared with control group (all P < 0.05).@*CONCLUSION@#The results of this study demonstrated that the short-term exposure of UFPs to the isolated rat hearts has direct and acute toxic effects on cardiac function, probably related to attenuation of anti-oxidative capacity and activation of MAPK signaling pathways.

Dose-dependent Cardiac Dysfunction and Structural Damage in Rats after Shortwave Radiation / 生物医学与环境科学（英文）

Objective@#To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment.@*Methods@#One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca , glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy.@*Results@#The results showed that the 5, 10, and 30 mW/cm shortwave radiation caused a significant increased in the levels of Ca , AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation.@*Conclusion@#Shortwave radiation of 5, 10, and 30 mW/cm can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.

Decreased c-kit and miR-21 gene expression in rat heart failure / 基础医学与临床

Objective To explore mechanism ( s) is dynamic expression and internal relations of c-kit gene and miR-21 in rat ventricular remodeling .Methods SD rats( n=140) were randomly divided into normal control group ( n=15 ) and heart failure model group ( n=125 ) .Heart failure model:4 mg/kg intraperitoneal injection of adria-mycin.To detect the cardiac function of rats in eight weeks , proving the heart failure .Then harvest the rat heart , frozen section , using immunohistochemistry and immunofluorescence color to detect the expression changes of miR-21 and c-kit in myocardial tissue .Results The emergence of the pathological changes of cardiac muscle cells after myocardial infarction in the heart failure groups and the control group didn't appear the myocardial infarction and heart failure .Immunohistochemistry and immunofluorescence show that miR-21 positive cells in normal and heart failure myocardium mainly express in vascular endothelium ,a few myocardial cells and stem cells , and endocardial expressing quantity fell more than epicardial;c-kit positive cells tend to cluster together , mainly gather in the epi-cardial and its nearby , and the expressing quantity decrease significantly after heart failure .A small number of cells exsit miR-21 and c-kit common expression in both groups ( P<0.05 ) .Conclusions The decreased expression of c-kit and miR-21 is highly related to rats heart failure and left ventricular remodeling .

Vitamin C enhanced myocardial differentiation of dedifferentiated fat cells / 中国病理生理杂志

[ ABSTRACT] AIM:In order to observe the myocardial differentiation capacity of the dedifferentiated fat ( DFAT) cells treated with vitamin C in vitro.METHODS: DFAT cells were dedifferentiated from the mature rat adipocytes with ceiling adherent culture.The DFAT cells of passage 3 were used in the study.Vitamin C and/or neonatal rat heart tissue lysate were added into the culture medium to induce myocardial differentiation for 3 weeks.The cell morphology was ob-served under microscope.The myocardial-specific markers, such as cTnT, GATA-4 and NKx2.5, were examined by the methods of immunofluorescence, PCR and Western blot.RESULTS:Mature rat adipocytes dedifferentiated into fibroblast-like DFAT cells after ceiling adherent culture.The DFAT cells spontaneously differentiated into cardiomyocyte-like cells under normal culture condition with a low incidence.After treated with neonatal rat heart cell lysate, the DFAT cells be-came cardiomyocyte-like cells that had bigger size, longer shape and myotubule-structure.The expression of cTnT, GATA-4 and NKx2.5 was remarkably increased at both mRNA and protein levels as compared with the normal cultured DFAT cells.The expression of cTnT, GATA-4 and NKx2.5 was further increased in DFAT cells after treating with vitamin C.No spontaneous beating cell was observed.CONCLUSION:Vitamin C enhances the differentiation of DFAT cells into cardio-myocyte-like cells.

Free radical reactions of a naturally occurring flavone baicalein and possible mechanisms towards its membrane protective properties.

Baicalein (5, 6, 7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally occurring flavone present in some of the medicinal plants is known for its potential therapeutic effects, such as cardioprotective, anticancer and anti-inflammatory properties. However, detailed role and mechanisms behind its protective properties against different generators for oxidative stress have not been examined. In the present study, we investigated the possible protective ability of baicalein against the membrane damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the mechanisms involved using pulse radiolysis technique. Baicalein offered efficient protection even at a concentration of 10 M towards membrane damage caused by lipid peroxidation induced by the -radiation, peroxyl radicals, ascorbate-Fe2+ and peroxynitrite in rat liver mitochondria and heart homogenate. To elucidate its reaction mechanisms with biologically relevant radicals, transient absorption spectroscopy employing pulse radiolysis technique was used. Baicalein showed fairly high rate constants (3.7 × 109, 1.3 × 109 and 8.0 × 108 dm3 mol-1 s-1 for hydroxyl, azidyl and alkylchloroperoxyl radicals, respectively), suggesting that baicalein can act as an effective scavenger of these radicals. In each case, the phenoxyl radical of baicalein was generated. Thus, it was evident that the phenolic moiety of baicalein was responsible for the free radical scavenging process. Baicalein also reacts with linoleic acid peroxyl radical (LOO·), indicating its ability to act as a chain breaking antioxidant. Peroxynitrite-mediated radicals were shown to be reactive towards baicalein and the bimolecular rate constants were 2.5 × 107 and 3 × 108 dm3 mol-1 s-1 for ·NO2 and CO3·- radicals, respectively. In conclusion, our results revealed the potential of baicalein in protecting mitochondrial membrane against oxidative damage induced by the four different agents. We propose that the protective effect is mediated via scavenging of primary and secondary radicals generated during oxidative stress.

Effect of propofol on cardiac function and gene expression after ischemic-reperfusion in isolated rat heart / 대한마취과학회지

BACKGROUND: The aim of this study was to examine the cardiac function and transcriptional response of the heart to propofol after ischemia-reperfusion. METHODS: Rat hearts were Langendorff-perfused using the modified Krebs-Henseleit buffer, and took 20 min stabilizing periods, 40 min ischemia periods, and then 120 min reperfusion period. The hearts were divided into 5 groups; Control: 180 min perfusion after stabilization, Ischemic: 40 min global ischemia after stabilization, followed by 120 min reperfusion, Pre: 2 micrometer propofol treatment was preformed only before ischemia, Post: 2 micrometer propofol treatment was performed only during reperfusion after ischemia, Pre/Post: 2 micrometer propofol treatment was performed both before and after ischemia. The measurement for cardiac performances, such as left ventricular developed pressure (LVDP), rate of left ventricular pressure generation (dP/dt), heart rate, and coronary flow were obtained. The expression profiles of isolated mRNA were determined by using Agilent microarray and real time-polymerase chain reaction (RT-PCR) was used to confirm the microarray results for a subset of genes. RESULTS: The Post group showed better LVDP and dP/dt than the Ischemic group. But there were no significant differences in heart rate and coronary flow among the groups. On the results of RT-PCR, the expressions of Abcc9, Bard1, and Casp4 were increased, but the expressions of Lyz, Casp8, and Timp1 were decreased in the Post group compared with the Ischemic group. CONCLUSIONS: This study suggests that 2 micrometer propofol may provide cardioprotective effect, and modulate gene expression such as apoptosis, and K(ATP) ion channel related-genes during reperfusion in the isolated rat hearts.

Effect of propofol on cardiac function and gene expression after ischemic-reperfusion in isolated rat heart / 대한마취과학회지

BACKGROUND: The aim of this study was to examine the cardiac function and transcriptional response of the heart to propofol after ischemia-reperfusion. METHODS: Rat hearts were Langendorff-perfused using the modified Krebs-Henseleit buffer, and took 20 min stabilizing periods, 40 min ischemia periods, and then 120 min reperfusion period. The hearts were divided into 5 groups; Control: 180 min perfusion after stabilization, Ischemic: 40 min global ischemia after stabilization, followed by 120 min reperfusion, Pre: 2 micrometer propofol treatment was preformed only before ischemia, Post: 2 micrometer propofol treatment was performed only during reperfusion after ischemia, Pre/Post: 2 micrometer propofol treatment was performed both before and after ischemia. The measurement for cardiac performances, such as left ventricular developed pressure (LVDP), rate of left ventricular pressure generation (dP/dt), heart rate, and coronary flow were obtained. The expression profiles of isolated mRNA were determined by using Agilent microarray and real time-polymerase chain reaction (RT-PCR) was used to confirm the microarray results for a subset of genes. RESULTS: The Post group showed better LVDP and dP/dt than the Ischemic group. But there were no significant differences in heart rate and coronary flow among the groups. On the results of RT-PCR, the expressions of Abcc9, Bard1, and Casp4 were increased, but the expressions of Lyz, Casp8, and Timp1 were decreased in the Post group compared with the Ischemic group. CONCLUSIONS: This study suggests that 2 micrometer propofol may provide cardioprotective effect, and modulate gene expression such as apoptosis, and K(ATP) ion channel related-genes during reperfusion in the isolated rat hearts.

Obesity induces upregulation of genes involved in myocardial Ca2+ handling

Obesity is a complex multifactorial disorder that is often associated with cardiovascular diseases. Research on experimental models has suggested that cardiac dysfunction in obesity might be related to alterations in myocardial intracellular calcium (Ca2+) handling. However, information about the expression of Ca2+-related genes that lead to this abnormality is scarce. We evaluated the effects of obesity induced by a high-fat diet in the expression of Ca2+-related genes, focusing the L-type Ca2+ channel (Cacna1c), sarcolemmal Na+/Ca2+ exchanger (NCX), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor (RyR2), and phospholamban (PLB) mRNA in rat myocardium. Male 30-day-old Wistar rats were fed a standard (control) or high-fat diet (obese) for 15 weeks. Obesity was defined as increased percent of body fat in carcass. The mRNA expression of Ca2+-related genes in the left ventricle was measured by RT-PCR. Compared with control rats, the obese rats had increased percent of body fat, area under the curve for glucose, and leptin and insulin plasma concentrations. Obesity also caused an increase in the levels of SERCA2a, RyR2 and PLB mRNA (P < 0.05) but did not modify the mRNA levels of Cacna1c and NCX. These findings show that obesity induced by high-fat diet causes cardiac upregulation of Ca2+ transport_related genes in the sarcoplasmic reticulum.

Anti-ischemic Effect of Polygala Tenuifolia in Isolated Rat Heart

Polygala tenuifolia (PT) is one of the most well-known traditional herbal medicines in Korea which is commonly used for the treatment of cardiovascular symptoms. The anti-ischemic effects of PT in isolated rat heart was investigated by analyzing changes in blood pressure, aortic flow, coronary flow, and cardiac output. And, its underlying mechanism was examined by quantitating intracellular calcium content in rat neonatal cardiomyocytes. Rats were divided into two groups: an ischemia-induced group without any treatment, and an ischemia-induced group treated with PT. Ischemia of isolated heart was induced by stopping the supply of oxygen and buffer for 10 min. The isolated heart was exposed to PT for the first 5 min of 10 min ischemia. PT treatment significantly prevented the decreases of perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, hemodynamics (except heart rate) of the PT-treated group was significantly recovered 60 min after reperfusion compared to the control group (systolic aortic pressure: 83.3% vs. 64.9%, aortic flow volume: 69.5% vs. 48.7%, coronary flow volume: 77.7% vs. 58.4%, and cardiac output: 71.6% vs. 51.2%, p<0.01). As for the underlying mechanism, PT significantly prevented intracellular calcium increase which was induced by isoproterenol (p<0.01), suggesting that the anti-ischemic effect of PT is mediated by inhibition of intracellular calcium increase.

The Effects of Ischemic Preconditioning and K(ATP) channel Activation on the Expression of the PKC-epsilon, NF-kappaB and AP-1 in Ischemia-reperfused Rat Heart / 체질인류학회지

This study was aimed to elucidate the effects of K(ATP) activation during IPC on the PKC-epsilon, NF-kappaB and AP-1 in ischemia-reperfused rat hearts. SD male rats weighting from 300 to 350 g were split into 9 groups, such as sham control (S), IPC, 3 cycles of 5 min ischemia and 5 min reperfusion, continuous preconditioning (CP), 8 cycles of 5 min ischemia and 5 min reperfusion, K(ATP) opening (KO) with pinacidil (1.0 mg/kg), K(ATP) blocking with glibenclamide (1.0 mg/kg) injection, ischemia (IS), 30 min ischemia, IPC followed by IS, 8) K(ATP) blocking and IPC followed by IS (KB+IPC+IS), IS and K(ATP) opening (KO+IS). Heart were subjected to ligation of left descending coronary artery and reperfusion in groups of IPC, CP, IS with or without IPC. Immunohistochemistry and Western blotting for PKC-epsilon, NF-kappaB and AP-1 were performed at 3, 6, 24 hours after reperfusion or treatment. Immunoreactivities against PKC-epsilon antibody were observed stronger in the groups of IPC, KO, IPC+IS and KO+IS than groups of KB, IS and KB+IPC+IS. NF-kappaB activation and translocation were only observed in the groups of including 30 min ischemia and reperfusion. AP-1 activation and translocation were opposite to the results of PKC-epsilon activation. In the group of CP, KB, IS and KB+IPC+IS, reactivities of AP-1 antibody were stronger than IPC+IS, KO+IS, and weaker in the groups of S, IPC and KO. These results suggest that K(ATP) opening with IPC or pharmacological methods may direct effect on the PKC-epsilon activation and that K(ATP) blocking has effect on the AP-1 activation and translocation in the heart of ischemiareperfused of rats.

Heterogeneity of the SR-dependent Inward Na+-Ca2+ Exchange Current in the Heavily Ca2+-buffered Rat Ventricular Myocytes

Voltage-sensitive release mechanism was pharmacologically dissected from the Ca2+-induced Ca2+ release in the SR Ca2+ release in the rat ventricular myocytes patch-clamped in a whole-cell mode. SR Ca2+ release process was monitored by using forward-mode Na+-Ca2+ exchange after restriction of the interactions between Ca2+ from SR and Na+-Ca2+ exchange within micro-domains with heavy cytosolic Ca2+ buffering with 10 mM BAPTA. During stimulation every 10 s with a pulse roughly mimicking action potential, the initial outward current gradually turned into a huge inward current of -12.9+/-0.5 pA/pF. From the inward current, two different inward INCXs were identified. One was 10 muM ryanodine-sensitive, constituting 14.2+/-2.3%. It was completely blocked by CdCl2 (0.1 mM and 0.5 mM) and by Na+-depletion. The other was identified by 5 mM NiCl2 after suppression of ICaL and ryanodine receptor, constituting 14.8+/-1.6%. This latter was blocked by either 10 mM caffeine-induced SR Ca2+-depletion or 1 mM tetracaine. IV-relationships illustrated that the latter was activated until the peak in 30~35 mV lower voltages than the former. Overall, it was concluded that the SR Ca2+ release process in the rat ventricular myocytes is mediated by the voltage-sensitive release mechanism in addition to the Ca2+-induced-Ca2+ release.

Comparisons of Myocardial Protective Effects of Sevoflurane at Different Concentrations against Ischemia in Isolated Rat Heart / 대한마취과학회지

BACKGROUND: Sevoflurane, a newly developed halogenated inhalation anesthetic agent shows myocardial protective effects against global ischemia like other inhalation agents. We investigated differences between pharmacologic preconditioning effects at various concentrations of sevoflurane. METHODS: Forty male Sprague-Dawley rats were subdivided into 4 groups (each n = 10). All groups underwent the same procedure (Langendorff preparation, 30 minutes ischemia and 60 minutes reperfusion) except for the concentrations of sevoflurane. The control group received no sevoflurane treatment. The sevo 1.6% group was given 1.6% sevoflurane before ischemia, the sevo 205% group was given 2.05% sevoflurane before ischemia, and the sevo 2.5% group was given 2.5% sevoflurane before ischemia. Hemodynamic parameters of all groups were recorded through a thin, saline-filled latex balloon and a transducer. Coronary flows were also measured. All hearts were stained by triphenyl tetrazolium to measure infarct size. RESULTS: The sevoflurane administered groups showed higher left ventricular end systolic pressures and lower left ventricular end diastolic pressures than the control group after ischemia and reperfusion. The dP/dtMAX of the sevoflurane administration groups showed a more rapid recovery pattern after ischemia than the control. But no differences were found between the sevoflurane administered groups. Infarct sizes in the sevoflurane administered groups were smaller than those in the control group, and there were no significant differences between the sevoflurane administered groups. CONCLUSIONS: Sevoflurane (even below one MAC) administration before myocardial ischemia has a superb cardioprotective effects, i.e., rapid recovery of left ventricular fuctions, less stiffness development, and a reduced infarct size. There were no significant differences between the sevoflurane administered groups.

The Myocardial Protective Effects of Desflurane on Global Ischemia in Isolated Rat Heart via KATP Channel Activation / 대한마취과학회지

BACKGROUND: In experimental models, several volatile anesthetics have been found to beneficially mimic ischemic preconditioning (IPC) during ischemia and reperfusion. These effects of IPC and volatile anesthetics are mediated by KATP channels, the authors examined following hypothesis: Desflurane administration before myocardial ischemia, has pharmacologic preconditioning effects on the myocardium (better functional recovory, and reduced infarct size), and these effects are mediated by KATP channel activation. METHODS: Isolated Sprague-Dawley rat hearts (n = 40) were perfused at a constant pressure with oxygenated modified Kreb's solution. After a stabilization period, they were subdivided into four groups; group 1 to 4. Group 1 underwent 30 minutes of global ischemia and 60 minutes of reperfusion. Group 2 received an ischemic preconditioning period before global ischemia and reperfusion as group 1. In group 3, 6.8 vol% desflurane was added to the perfusion medium for 15 minutes and a 5 minutes wash-out period was introduced before global ischemia and reperfusion. In group 4, during the 6.8 vol% desflurane administration, glibenclamide was injected at a constant rate, before global ischemia and reperfusion. In each group, isovolumetric left ventricular pressure (LVP), heart rate and the maximun rate of change of the ventricular pressure (dP/dtmax) were measured using a thin, saline-filled latex balloon and a transducer. Coronary flow and the LDH level of effluent were measured at 5, 30, 60 minutes after reperfusion. All hearts were stained with triphenyl tetrazolium to determine infarct size. RESULTS: Desflurane administration before global ischemia showed protective effects, like IPC, on functional recovery and infarct reduction. LVP was less depressed in group 3 and group 2. dP/dtmax in group 2 recovered after global ischemia to some degree, but remained slightly depressed in group 3. Decreased heart rate and coronary flow were observed in groups 2, 3 and 4. LDH showed a decreasing pattern in group 2 and 3. Infarct size was smaller in groups 2 and 3 than in groups 1 and 4. These benefical effects of desflurane were blocked by glibenclamide administration. CONCLUSIONS: Desflurane was found to have beneficial effects, and mimicked IPC by preservaing LVP, reducing infarct size, and the degree of cardiac enzyme release. These beneficial effects were abolished by administering the KATP channel blocker, glibenclamide. The protecitve effects of desflurane administration against myocardial ischemia were mediated by KATP channels.

Effects of Long-term Atenolol Treatment on Cardiac Adrenoreceptors in Rats / 中国药房

PURPOSE: To know whether the cardiac function of the patients with heart disease is impaired or improved after long-term taking ?-AR antagonists. METHODS: After giving the rats ?-AR selective antagonist, atenolol, for 12wk, the method of radioligand binding assay and the experiment of isolated left-atrium contractive function were carried out to observe the quantity and distribution of ?-AR, its subtypes, ?-AR, and the change of left - atrium contractive function. RESULTS: After long-term administration of atenolol, there were no any obvious changes in ?-AR, the density of the total ?-AR, ?1-AR, and the proportion of ?2-AR in tota1 amount of ?-AR, but the con centrat ion - response cu rves shi fted l e ftwa rd s si gn ifi cant ly as compared with control group- The PA2 value of isoprotenol(ISO) - induced positive inotropic effect after antagonized by ?1-AR selective antagonist CGP20712A in atenolol group was increased significantly as compared with control group. But the PKB value after antagonized by ICI 118511 showed no obvious difference between two groups. HPLC detection showed that the level of plasma atenolol was 3. 5pmol/L in atenolol group and the leveIs of plasma norepinephrine had no significant difference between two groups. But the level of plasma adrenaline in atenolol group was obviously lower than that in control group. CONCLUSIO- N: The long-term administration of ?l-AR antagonist will cause significant increase of the sensitivity of heart ?-AR, especially ?1-AR to excitant ISO. But the number of ?-AR and its subtypes did not change significantly. Besides, after the long-term administration of ?1-AR antagonist atenolol, the level of plasma adrenaline in rats was much lower than that in control group.

Effect of C1 esterase inhibitor on the cardiac dysfunction following ischemia and reperfusion in the isolated perfused rat heart

Complement-mediated neutrophil activation has been hypothesized to be an important mechanism of reperfusion injury. It has been proposed that C1 esterase inhibitor (C1 INH) may prevent the complement-dependent activation of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium. Therefore, The effect of C1 INH was examined in neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of C1 INH (5 mg/Kg) to I/R hearts in the presence of PMNs (100 X 106) and homologous plasma improved coronary flow and preserved cardiac contractile function (p<0.001) in comparison to those I/R hearts receiving only vehicle. In addition, C1 INH significantly (p<0.001) reduced PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective cardioprotective agent inhibits leukocyte-endothelial interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.

Effects of Ischemic preconditioning on the Post-ischemic Myocardial Dysfunction and Coronary Flow in the Isolated Rat Hearts

BACKGROUND: Brief episodic ischemias prior to subsequent prolonged ischemia limit infarct size and attenuate the reperfusion arrythmia. But the effect of ischemic preconditioning on post-ischemic myocardial dysfunction, coronary flow and nitric oxide (NO) remains unclear. METHODS: To investigate the effect of ischemic preconditioning on myocardial function and coronary flow during reperfusion after 15 minutes of global myocardial ischemia, 30 isolated hearts of Sprague-Dowley rats were perfused under constant pressure. Two episodes of three minutes global ischemia followed by 12 minutes of reflow were employed to precondition the hearts. The hearts were randomized to one of three groups : group I had no preconditioning, group II had preconditioning, group III had preconditioning as well as L-arginine pretreatment. Left ventricular developed pressure (LVDP), LV dp/dt, perfused coronary flow, concentration of NO and heart rate were continuously measured. RESULTS: In preconditioning groups (Group II, Group III), LVDP decreased during reflow and was lower than that of the control group. LV dp/dt decreased after reflow and gradually recovered with time but recovered was less in preconditioning groups. Coronary flow increased in the first few minutes after reflow in all groups, but decreased gradually. The decrease of coronary flow was greater in preconditioning groups. NO increased during the first 10 minutes after reflow and then decreased. In preconditioning groups, NO tends to be lower than that in the non-preconditioning group. CONCLUSION: Ischemic preconditioning was not beneficial to post-ischemic myocardial dysfunction, coronary flow and NO concentration in the flow. Cummulative effect of stunning due to repetitive ischemia for preconditioning may be an explanation for worse post-ischemic myocardial dysfunction and coronary flow in preconditioning groups.

Effects of Ischemic preconditioning on the Post-ischemic Myocardial Dysfunction and Coronary Flow in the Isolated Rat Hearts

BACKGROUND: Brief episodic ischemias prior to subsequent prolonged ischemia limit infarct size and attenuate the reperfusion arrythmia. But the effect of ischemic preconditioning on post-ischemic myocardial dysfunction, coronary flow and nitric oxide (NO) remains unclear. METHODS: To investigate the effect of ischemic preconditioning on myocardial function and coronary flow during reperfusion after 15 minutes of global myocardial ischemia, 30 isolated hearts of Sprague-Dowley rats were perfused under constant pressure. Two episodes of three minutes global ischemia followed by 12 minutes of reflow were employed to precondition the hearts. The hearts were randomized to one of three groups : group I had no preconditioning, group II had preconditioning, group III had preconditioning as well as L-arginine pretreatment. Left ventricular developed pressure (LVDP), LV dp/dt, perfused coronary flow, concentration of NO and heart rate were continuously measured. RESULTS: In preconditioning groups (Group II, Group III), LVDP decreased during reflow and was lower than that of the control group. LV dp/dt decreased after reflow and gradually recovered with time but recovered was less in preconditioning groups. Coronary flow increased in the first few minutes after reflow in all groups, but decreased gradually. The decrease of coronary flow was greater in preconditioning groups. NO increased during the first 10 minutes after reflow and then decreased. In preconditioning groups, NO tends to be lower than that in the non-preconditioning group. CONCLUSION: Ischemic preconditioning was not beneficial to post-ischemic myocardial dysfunction, coronary flow and NO concentration in the flow. Cummulative effect of stunning due to repetitive ischemia for preconditioning may be an explanation for worse post-ischemic myocardial dysfunction and coronary flow in preconditioning groups.

Effects of verapamil in cardioplegic perfusates on the ischemic myocardium in isolated rat heart / 대한흉부외과학회지

Using isolated rat heart preparations, we observed the protective effects of verapamil cardioplegia on ischemic myocardial injury. Isolated rat hearts were subjected to global ischemia at 25degrees C. Twenty four isolated Sprague Dawley rat hearts underwent 30 minutes of the retrograde nonworking perfusion with Krebs-Henseleit buffer solution followed by 25degrees C cardioplegic solution(St. Thomas' Hospital Cardioplegic Solution) for 60 minutes. Before ischemic arrest, rat hearts were treated with cold cardioplegic solution in control group(n=12) and cold cardioplegic solution with verapamil(1mg/L) in experimental group(n=12). After 60 minutes of ischemia, hemodynamic and biochemical parameters such as heart rate, left ventricular pressure(LVP), +dp/dt max, coronary flow and creatine phosphokinase(CPK) were measured before giving cardioplegia and 30 minutes after reperfusion. Verapamil group exhibited greater recovery of heart rate, LVP, +dp/dt max, coronary flow and CPK than control group(p<0.05).

Protective effects of ischemic preconditioning with normothermia or hypothermia on schemia/reperfusion in-jury in isolated rat hearts / 中国介入心脏病学杂志

Using isolated rat hearts perfused on a langendorff apparatus,ischemic preconditioning (IP) was investigated with 5 min normothermic (at 37℃) or hypothermic (at 30 ℃) ischemia, followed by 10 min of reperfusion before the arrest period, as an adjunct to St. Thomas crystalloid cardioplegia during 180 min ischemia. After basline functional data were obtained, IP was induced 1 control hearts underwent no IP. Results showed that IP improved functional recovery from ischemia during 45 min reperfusion in normothermic ischemic preconditioning group (NP) comparing with normothermic control (NC),P