RESUMO
We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure.
Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração , Coração Artificial , Falência Renal Crônica/cirurgia , Transplante de Rim , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Fluxo PulsátilRESUMO
Despite successful surgical revascularization of ischemic limbs, a local and systemic reperfusion injury may occur after normal blood reperfusion. Recent experimental and clinical application of controlled limb reperfusion in Europe has demonstrated superior results, with lower morbidity and mortality. This new surgical technique includes modification of the reperfusate (calcium, pH, substrates, osmolarity, free radical scavenger) and the circumstances of initial reperfusion (time, temperature, pressure). This report describes the first application of controlled limb reperfusion after reperfusion injury. A 16-year-old boy underwent femoral access cardiopulmonary bypass for repeat cardiac repair with an ischemic time of 245 minutes. Postoperatively, severe ischemia/reperfusion syndrome developed with muscle contracture, immobility, and anesthesia of the right leg with a second ischemic time of about 6 hours. The systemic creatine phosphokinase level was 88,000 U/L; myoglobin was 27,000 ng/mL. He underwent controlled limb reperfusion by withdrawing blood from the aorta and mixing it with a crystalloid solution (calcium-reduced, hyperosmolar, hyperglycemic, alkalotic, glutamate- and aspartate-enriched, and containing a free radical scavenger) under controlled conditions (blood:crystalloid solution 6:1, for 30 minutes, reperfusion pressure < 50 mm Hg, and normothermia) before establishing normal blood reperfusion. Metabolic data from the central and femoral vein demonstrated a significant reduction of all previous elevated enzyme levels, avoidance of hyperkalemia, normalization of acidosis, and avoidance of systemic reperfusion injury with no multiorgan failure. Limb salvage was accomplished and functional recovery almost complete. To the authors' knowledge, this is the first application of controlled limb reperfusion reported in North America. With this surgical technique we were able to prevent metabolic local and systemic reperfusion changes after prolonged ischemia and also reduced previous reperfusion changes. This report confirms former experimental data, and further clinical studies are warranted.
Assuntos
Músculo Esquelético/lesões , Traumatismo por Reperfusão , Adolescente , Extremidades/cirurgia , Humanos , Masculino , Músculo Esquelético/cirurgia , Reperfusão , Traumatismo por Reperfusão/cirurgiaRESUMO
Optimal preservation of the myocardium remains a major concern in clinical and experimental heart transplantation. The present study compared the efficacy of University of Wisconsin (UW) and Celsior preservation solution with respect to myocardial performance, epicardial and microvascular endothelial vasomotor function and myocardial expression of endothelin and nitric oxide synthases in humans. Forty-one cardiac transplant recipients received either UW (n = 20) or Celsior (n = 21) preserved hearts. Catecholamine and vasodilator requirements were assessed within the first 5 postoperative days. Left ventricular performance and endothelial function was assessed 1 month after transplantation. Endothelin and nitric oxide synthase gene expression were detected in myocardial biopsy samples. Celsior preserved hearts required significantly more catecholamines and vasodilators within the first 5 postoperative days. Myocardial performance and endothelial function were comparable 1 month after transplantation. Total ischemic time correlated with impaired endothelial function in the Celsior but not in the UW group. Endothelin and inducible nitric oxide synthase gene expression were significantly higher in the Celsior group. The results of the study show that both solutions provide myocardial protection with regard to left ventricular performance and endothelial function 1 month after cardiac transplantation. The necessity for higher vasodilator and catecholamine therapy in Celsior preserved hearts suggests post-ischemic myocardial stunning within the first 5 postoperative days. The positive correlation between impaired endothelial function and total ischemic time in the Celsior group requires longitudinal investigation in particular with regard to the development of allograft vasculopathy.
Assuntos
Transplante de Coração/fisiologia , Coração , Hemodinâmica , Soluções para Preservação de Órgãos , Adenosina , Adulto , Alopurinol , Pressão Sanguínea , Catecolaminas/uso terapêutico , Dissacarídeos , Eletrólitos , Endotelinas/sangue , Endotelinas/genética , Endotélio Vascular/fisiologia , Feminino , Glutamatos , Glutationa , Histidina , Humanos , Insulina , Masculino , Manitol , Pessoa de Meia-Idade , Contração Miocárdica , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Preservação de Órgãos/métodos , Reação em Cadeia da Polimerase , Estudos Prospectivos , Rafinose , Análise de Regressão , Doadores de Tecidos/estatística & dados numéricos , Vasodilatadores/uso terapêuticoRESUMO
Current myocardial protection techniques in cyanotic immature hearts are not optimal. Despite successful surgical correction of congenital cardiac defects causing hypoxemia, myocardial dysfunction remains the leading cause of postoperative mortality. New studies indicate that the intraoperative reintroduction of molecular oxygen on cardiopulmonary bypass causes a reoxygenation injury leading to postoperative cardiac dysfunction. Biochemical and functional changes of reoxygenation injury can be avoided by several methods aimed at reducing oxygen free radical production and nitric oxide release. The present investigation provides an overview of our current understanding of pathogenesis, implication, and treatment of myocardial reoxygenation injury. New surgical concepts of myocardial protection including normoxic CPB and controlled reoxygenation are introduced.
Assuntos
Parada Cardíaca Induzida , Hipóxia/fisiopatologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Oxigênio/administração & dosagem , Animais , Antioxidantes/análise , Ponte Cardiopulmonar , Humanos , Hipóxia/metabolismo , Peroxidação de Lipídeos , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/terapia , Miocárdio/metabolismo , Óxido Nítrico/biossínteseAssuntos
Neoplasias do Apêndice/diagnóstico , Tumor Carcinoide/diagnóstico , Apendicectomia , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Tumor Carcinoide/secundário , Tumor Carcinoide/cirurgia , Pré-Escolar , Colectomia , Diagnóstico Diferencial , Feminino , Humanos , Metástase LinfáticaRESUMO
BACKGROUND: Hypoxemic developing hearts are susceptible to oxygen-mediated damage that occurs after reintroduction of molecular oxygen. This unintended hypoxemic/reoxygenation injury leads to lipid peroxidation and membrane damage and may contribute to postoperative cardiac dysfunction. Biochemical and functional status are improved by delaying reoxygenation on cardiopulmonary bypass (CPB) until cardioplegic arrest. METHODS: Six immature piglets (3 to 5 kg) without hypoxemia underwent 30 minutes of cardioplegic arrest during 1 hour of CPB. Fourteen others underwent 2 hours of hypoxemia on ventilator before reoxygenation on CPB. Reflecting our clinical routine, 9 were reoxygenated on CPB for 5 minutes followed by 30 minutes of cardioplegic arrest and 25 minutes of reperfusion. The other 5 were put on hypoxemic CPB for 5 minutes, before being reoxygenated during cardioplegic arrest for 30 minutes followed by 25 minutes of reperfusion. RESULTS: Cardioplegic arrest (no hypoxemia group) caused no functional or biochemical changes. In contrast, by preceding hypoxemia with subsequent reoxygenation on CPB (no treatment group) we found 39.5% decrease in antioxidant reserve capacity, 1,212% increase in myocardial conjugated diene production, significant increase in coronary sinus blood conjugated dienes, and an 81% reduction of left ventricular contractility, all of which were statistically significant (p < 0.05) when compared with the no hypoxemia group. Conversely, delaying reoxygenation until cardioplegic arrest (treatment group) resulted in 33.1% improvement in antioxidant reserve capacity, 91.7% less conjugated diene production, lower coronary sinus blood conjugated diene levels, and a 95% improved contractility, all of which were significant (p < 0.05) when compared with the no treatment group. CONCLUSIONS: A reoxygenation injury associated with lipid peroxidation and decreased postbypass contractility occurs in cyanotic immature hearts when reoxygenated on CPB. Delaying reoxygenation until cardioplegic arrest by starting CPB with ambient partial pressure of oxygen results in significantly improved myocardial status.
Assuntos
Ponte Cardiopulmonar , Parada Cardíaca Induzida , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Oxigênio/administração & dosagem , Respiração Artificial/métodos , Animais , Antioxidantes/análise , Membrana Celular/patologia , Vasos Coronários , Cianose/fisiopatologia , Modelos Animais de Doenças , Coração/fisiopatologia , Hipóxia/fisiopatologia , Peroxidação de Lipídeos , Contração Miocárdica/fisiologia , Reperfusão Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , SuínosRESUMO
OBJECTIVE: Hyperoxic cardiopulmonary bypass is widely used during cardiac operations in the adult. This management may cause oxygenation injury induced by oxygen-derived free radicals and nitric oxide. Oxidative damage may be significantly limited by maintaining a more physiologic oxygen tension strategy (normoxic cardiopulmonary bypass). METHODS: During elective coronary artery bypass grafting, 40 consecutive patients underwent either hyperoxic (oxygen tension = 400 mm Hg) or normoxic (oxygen tension = 140 mm Hg) cardiopulmonary bypass. At the beginning and the end of bypass this study assessed polymorphonuclear leukocyte elastase, nitrate, creatine kinase, and lactic dehydrogenase, antioxidant levels, and malondialdehyde in coronary sinus blood. Cardiac index was measured before and after cardiopulmonary bypass. RESULTS: There was no difference between groups with regard to age, sex, severity of disease, ejection fraction, number of grafts, duration of cardiopulmonary bypass, or ischemic time. Hyperoxic bypass resulted in higher levels of polymorphonuclear leukocyte elastase (377 +/- 34 vs 171 +/- 32 ng/ml, p = 0.0001), creatine kinase 672 +/- 130 vs 293 +/- 21 U/L, p = 0.002), lactic dehydrogenase (553 +/- 48 vs 301 +/- 12 U/L, p = 0.003), antioxidants (1.97 +/- 0.10 vs 1.41 +/- 0.11 mmol/L, p = 0.01), malondialdehyde (1.36 +/- 0.1 micromol/L,p = 0.005), and nitrate (19.3 +/- 2.9 vs 10.1 +/- 2.1 micromol/L, p = 0.002), as well as reduction in lung vital capacity (66% +/- 2% vs 81% +/- 1%,p = 0.01) and forced 1-second expiratory volume (63% +/- 10% vs 93% +/- 4%, p = 0.005) compared with normoxic management. Cardiac index after cardiopulmonary bypass at low filling pressure was similar between groups (3.1 +/- 0.2 vs 3.3 +/- 0.3 L/min per square meter). [Data are mean +/- standard error (analysis of variance), with p values compared with an oxygen tension of 400 mm Hg.] CONCLUSIONS: Hyperoxic cardiopulmonary bypass during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide. These adverse effects can be markedly limited by reduced oxygen tension management. The concept of normoxic cardiopulmonary bypass may be applied to surgical advantage during cardiac operations.
Assuntos
Ponte Cardiopulmonar , Ponte de Artéria Coronária , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Óxido Nítrico/sangue , Estresse Oxidativo , Adulto , Doença das Coronárias/cirurgia , Creatina Quinase/sangue , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Elastase de Leucócito/sangue , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Neutrófilos/enzimologia , Oxigenoterapia , Período Pós-Operatório , Espécies Reativas de Oxigênio/metabolismo , Explosão Respiratória , Testes de Função Respiratória , Estudos Retrospectivos , Função Ventricular EsquerdaRESUMO
Reintroduction of high levels of molecular oxygen after a hypoxic period is followed by a burst of nitric oxide (NO), peroxynitrite, and oxygen free radicals (OFR), which are highly cytotoxic. This study indicates that hyperoxic reoxygenation of cyanotic immature hearts on cardiopulmonary bypass (CPB) induces a reoxygenation injury and that, by reducing NO and OFR production during institution of CPB with subsequent reoxygenation under blood cardioplegic arrest, this oxygen-related damage can be avoided and biochemical and functional status improved. Of 25 immature piglets (3-5 kg, two to three weeks old), 6 underwent one hour of CPB including thirty minutes of aortic clamping with substrate-enriched modified blood cardioplegia (hypocalcemic, alkalotic, and hyperosmolar; warm induction-cold replenishment-warm reperfusion) without preceding hypoxia (controls). Nineteen others were made hypoxic (arterial [Po2] 20-30 mmHg) for up to two hours by lowering the fraction of inspired oxygen (FIO2) on ventilator. These hypoxic piglets were then reoxygenated on CPB at different Po2 levels (hyperoxic, normoxic, or hypoxic) for five minutes, followed by the aforementioned blood cardioplegic (BCP) arrest regimen. Myocardial conjugated diene (CD) production as a marker of lipid peroxidation, and NO production, determined as its spontaneous oxidation products, nitrite (NO2-) and nitrate (NO3-), were assessed during blood cardioplegic induction, and antioxidant reserve capacity was determined by incubating myocardium in the oxidant t-butylhydroperoxide (t-BHP). Myocardial function was evaluated from end-systolic elastance (Ees, conductance catheter). Blood cardioplegic arrest caused no functional or biochemical changes in normoxic control immature piglets. In contrast, brief reoxygenation at PO2 > 400 mmHg, followed by BCP-arrest (hyperoxic) resulted in marked CD production (42 +/- 4 vs 3 +/- 1 A233 nm/minute/100 g; P < 0.05), and NO production (4500 +/- 500 vs 450 +/- 32 mmol/minute/100 g; P < 0.05) during blood cardioplegic induction, reduced antioxidant reserve capacity (malondialdehyde [MDA] at 4.0 mM of t-BHP: 1342 +/- 59 vs 958 +/- 50 nM/g protein; P < 0.05), and caused profound myocardial dysfunction; Ees recovered only 21 +/- 2% (vs 104 +/- 7; P < 0.05), despite the blood cardioplegic regimen shown to be cardioprotective in control normoxic piglets. Conversely, controlling initial PO2 to normoxic (100 mmHg) or hypoxic (20-30 mmHg) levels reduced lipid peroxidation (CD production 16 +/- 2, 2 +/- 1 A233nm/minute/100 g) and NO production (1264 +/- 736, 270 +/- 182 mmol/minute/100 g), restored antioxidant reserve capacity (MDA at 4.0 mM of t-BHP: 940 +/- 95, 982 +/- 88 nM/g protein), and allowed significant functional recovery (58 +/- 11% and 83 +/- 8%), in a PO2-dependent fashion. The authors conclude that reoxygenation of hypoxemic immature hearts by initiating hyperoxic CPB causes oxidant-related damage characterized by lipid peroxidation, enhanced NO production, and reduced antioxidants, leading to functional depression that nullifies the cardioprotective effects of blood cardioplegia. These detrimental effects can be reduced in a PO2-dependent fashion by controlling initial PO2 on CPB and subsequent reoxygenation during blood cardioplegic arrest.
Assuntos
Ponte Cardiopulmonar , Parada Cardíaca Induzida , Cardiopatias Congênitas/cirurgia , Hipóxia , Óxido Nítrico/fisiologia , Animais , Animais Recém-Nascidos , Cianose , Radicais Livres , Hipóxia/terapia , Peroxidação de Lipídeos , Miocárdio/metabolismo , Óxido Nítrico/biossíntese , Consumo de Oxigênio , SuínosRESUMO
This study tests the hypothesis that abrupt reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass produces an unintended reoxygenation injury that: (i) nullifies the cardioprotective effects of blood cardioplegia; and (ii) is avoidable by adding the antioxidants, N-(2-mercaptopropionyl)-glycine (MPG) plus catalase to the cardiopulmonary bypass prime. Twenty immature piglets (aged 2-3 weeks) underwent 30 min of blood cardioplegic arrest (BCP) with standard clinical blood cardioplegia (hypocalcaemic, alkalotic, hyperosmolar, substrate-enriched). Six piglets remained normoxaemic (BCP). Fourteen others were made hypoxic (PO2 20-30 mmHg) for up to 2 h by lowering ventilator FiO2 (5-7%) before undergoing reoxygenation on cardiopulmonary bypass at PO2 400 mmHg. In eight animals, the pump prime was not supplemented with antioxidants (Reox + BCP), whereas MPG (80 mg/kg) and catalase (CAT; 5 mg/kg) were added to the pump prime in the other six (MPG/CAT). Myocardial function (end-systolic elastance, conductance catheter), oxidant damage (myocardial conjugated diene production), oxygen consumption and antioxidant reserve capacity were evaluated. Blood cardioplegic arrest caused no functional or biochemical changes in controls without preceding hypoxia. In contrast, hypoxia and reoxygenation in animals undergoing the same blood cardioplegic protocol (Reox + BCP) caused profound myocardial dysfunction, as end-systolic elastance recovered only to 21(2)% (P < 0.05 versus control) of baseline values. Additionally, it reduced antioxidant reserve capacity (malondialdehyde, MDA at 4.0 mM of t-BHP: 1342(59) (P < 0.05 versus control) versus 788(53) mmol/g protein), and led to significantly greater production of conjugated dienes during warm induction (42(4.4) (P < 0.05 versus control) versus 3.3(1.4) A233 nm/100 g per min) and reperfusion (22(2.7) (P < 0.005 versus control) versus 2(0.6) A233 nm/100 g per min). Conversely, supplementation of MPG plus catalase to the pump prime reduced lipid peroxidation (conjugated diene production during warm induction: 22.3(7) A233 nm/100 g per min P < 0.05 versus Reox + BCP), restored antioxidant reserve capacity (MDA at 4.0 M of t-BHP: 975(139) mmol/g protein P < 0.05 versus Reox + BCP) and allowed almost complete functional recovery (80(8)%). Abrupt reoxygenation of hypoxaemic immature hearts on cardiopulmonary bypass causes oxidant damage, nullifies the cardioprotective effects of blood cardioplegia, and leads to reduced myocardial contractility. Antioxidant supplementation of the cardiopulmonary bypass prime avoids these detrimental effects, and results in improved biochemical and functional status.
Assuntos
Antioxidantes/farmacologia , Soluções Cardioplégicas , Ponte Cardiopulmonar , Catalase/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Tiopronina/farmacologia , Animais , Animais Recém-Nascidos , Hemodinâmica , Peroxidação de Lipídeos , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Consumo de Oxigênio , Período Pós-Operatório , Suínos , Função Ventricular EsquerdaRESUMO
BACKGROUND: Previous research has shown that the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is a major determinant of plasma ACE activity. It has been suggested that persons with the DD genotype (those who express, on average, the highest levels of circulating ACE) have an increased risk for myocardial infarction and coronary artery disease, particularly if they are otherwise at low risk. Subsequent studies, however, have not confirmed that ACE I/D gene polymorphism is a risk factor for coronary artery disease and myocardial infarction. OBJECTIVE: To investigate the association between the I/D polymorphism of the ACE gene and the risk for coronary artery disease and myocardial infarction in patients in whom coronary artery disease status was documented by angiography. DESIGN: Cross-sectional study. SETTING: University medical center. PATIENTS: 209 male case-patients with coronary artery disease and 92 male controls without coronary artery disease, as documented by coronary angiography. MEASUREMENTS: Assessment of the cardiac risk profile by questionnaire; classification of patients by the degree of coronary artery stenosis; levels of lipoproteins, apolipoproteins, and fibrinogen; and ACE I/D gene polymorphism assessed by polymerase chain reaction amplification. RESULTS: Plasma ACE activity was significantly associated with ACE I/D gene polymorphism. The ACE genotype was not associated with the presence of coronary artery disease or myocardial infarction. If a recessive effect of the D allele was assumed (DD compared with DI and II), the relative risk was 1.00 (95% CI, 0.76 to 1.30) for coronary artery disease and 1.03 (CI, 0.77 to 1.38) for myocardial infarction. Results of analyses were also negative when a dominant effect of the D allele was assumed and when low-risk subgroups were examined. The established risk factors age and apolipoprotein B level emerged as the most important risk predictors in multivariate analyses, followed by diastolic blood pressure and fasting glucose levels. CONCLUSIONS: In an angiographically defined study sample, ACE I/D gene polymorphism was not associated with an increased risk for coronary artery disease or myocardial infarction, despite its effects on plasma ACE activity.
Assuntos
Doença das Coronárias/enzimologia , Genótipo , Infarto do Miocárdio/enzimologia , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Idoso , Doença das Coronárias/sangue , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Razão de Chances , Peptidil Dipeptidase A/sangue , Análise de Regressão , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Cardiopulmonary bypass (CPB) per se alters many factors simultaneously, including free radical generation, which suggests that conventional hyperoxic CPB may produce oxidative injury in the infantile heart and lung. This study tests the hypothesis that CPB provokes oxidative cardiopulmonary changes and pulmonary endothelial dysfunction in immature piglets that can be prevented by free radical scavengers. We studied 15 2- to 3-week-old piglets. Five served as a control without CPB. Ten piglets underwent 60 min of CPB with a membrane oxygenator (Sarns). In 5 of these 10, the bypass prime was supplemented with N-mercaptopropionylglycine (MPG: 80 mg/kg) plus catalase (50,000 U/kg), whereas the others were not treated. Pre- and post-bypass cardiopulmonary function was measured in terms of left ventricular end-systolic elastance [Ees] by a conductance catheter, the arterial/alveolar pO2 ratio (a/A ratio) and static lung compliance. Conjugated dienes (A233 nm/mg lipid) were measured to detect lipid peroxidation in heart and lung tissue, and myocardial antioxidant reserve capacity [malondialdehyde (MDA) production in cardiac tissue incubated with the oxidant t-butyl hydroperoxide (t-BHP)] was assessed to detect oxidative changes. Pulmonary vascular resistance (PVR) and transpulmonary nitric oxide (NO) production were measured to assess pulmonary endothelial injury. Myocardial antioxidant reserve capacity was significantly reduced after 60 min of CPB, compared to control animals (MDA 779 +/- 100 vs 470 +/- 30 nmol/g protein, p < 0.05 at t-BHP 2.0 mmol/L), without evidence of lipid peroxidation or myocardial dysfunction. Pulmonary vascular resistance after CPB was dramatically increased (83 +/- 12 to 212 +/- 30, p < 0.05) without any change in lung function. In parallel to pulmonary vasoconstriction, NO production was significantly decreased after CPB (from 8.8 +/- 1.4 to 2.5 +/- 0.5 mmol/min/kg, p < 0.05). The addition of antioxidants (MPG+catalase) to the prime significantly improved myocardial antioxidant status (MDA: 604 +/- 30 vs 779 +/- 100 nmol/g protein, p < 0.05) and pulmonary vascular resistance (114 +/- 29 vs 212 +/- 30, p < 0.05 vs no-treatment group). In conclusion, the present study confirms that 1) Cardiopulmonary bypass produces substantial oxidative stress in normal immature myocardium, as assessed by reduced antioxidant reserve capacity; 2) CPB impairs pulmonary endothelial function, characterized by NO production, resulting in pulmonary vasoconstriction; and 3) These deleterious effects can be prevented by the addition of antioxidants (MPG/catalase) to the pump prime.
Assuntos
Antioxidantes/administração & dosagem , Ponte Cardiopulmonar/efeitos adversos , Estresse Oxidativo , Animais , Catalase/administração & dosagem , Radicais Livres , Humanos , Suínos , Tiopronina/administração & dosagemRESUMO
BACKGROUND: Pulmonary hypertension is a serious complication after cardiopulmonary bypass (CPB). This study tests the hypothesis that CPB provokes oxidant-mediated pulmonary endothelial dysfunction, leading to reduced nitric oxide (NO) production and pulmonary vasoconstriction. METHODS: Twelve piglets underwent 2 hours of CPB. In 6 of them, CPB prime was supplemented with N-mercaptopropionylglycine and catalase, whereas the others were not treated. Left and right ventricular function were evaluated from end-systolic elastance and Starling analysis. Pulmonary vascular resistance and transpulmonary NO production (measuring NO2-, NO3-) were determined to assess pulmonary endothelial function. RESULTS: Cardiopulmonary bypass caused a significant increase in pulmonary vascular resistance (83 +/- 12 to 212 +/- 30 dynes.cm-5.s kg-1, p < 0.05), associated with a reduction of NO production (8.8 +/- 1.4 to 2.5 +/- 0.5 mumol/min, p < 0.05) and depressed right ventricular function (56 +/- 12% of control), whereas N-mercaptopropionylglycine and catalase added to the CPB allowed a substantial improvement of these deleterious effects of CPB. CONCLUSIONS: Cardiopulmonary bypass impairs pulmonary NO production, resulting in pulmonary vasoconstriction and right ventricular dysfunction, which can be reduced by antioxidants. These findings imply the validity of NO inhalation therapy for postoperative pulmonary hypertension as a supplementation of endogenous endothelium-derived relaxing factor.
Assuntos
Ponte Cardiopulmonar , Óxido Nítrico/biossíntese , Artéria Pulmonar/fisiopatologia , Vasoconstrição , Animais , Antioxidantes/farmacologia , Ponte Cardiopulmonar/efeitos adversos , Catalase/farmacologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hipertensão Pulmonar/etiologia , Nitratos/sangue , Óxido Nítrico/sangue , Nitritos/sangue , Oxidantes/metabolismo , Artéria Pulmonar/metabolismo , Suínos , Tiopronina/farmacologia , Resistência Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Disfunção Ventricular Direita/etiologia , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacosRESUMO
Severe local and systemic complications may occur after revascularization of extremities exposed to prolonged complete or incomplete ischaemia. These complications may be reduced by controlling the reperfusate and the circumstances of the reperfusion period. Ten adult German domestic pigs were exposed to 6 h of incomplete limb ischaemia by occlusion of the left iliac artery. To simulate the clinical situation of embolectomy, the occlusive snares were released after the ischaemic period in five pigs and normal blood flow developed with systemic pressure (uncontrolled reperfusion). In the other five pigs, a controlled reperfusate was delivered at controlled pressure before establishing normal blood reperfusion (controlled reperfusion). At the end of the observation period (90 min after start of reperfusion), the group with controlled reperfusion had a lower mean(s.e.m.) tissue water content (81.8(0.7) versus 84.3(0.7) per cent, P < 0.05, a greater increase in tissue adenosine 5'-triphosphate compared with values at the end of ischaemia (6.2(1.5) versus -2.5(1.8) mumol per g protein, P < 0.03), a higher tissue pH (7.2(0.1) versus 6.8(0.1), P < 0.03), a smaller temperature decrease (0.3(0.2) versus 1.2(0.3) degrees C, P < 0.05), lower concentrations of creatine kinase (355.0(87.5) versus 624.4(73.4) units/l, P < 0.05) and lactate dehydrogenase (LDH) (369.5(42.5) versus 538.4(39.2 units/l, P < 0.03) in the femoral vein blood and lower LDH concentrations (356.5(48.9) versus 546.0(37.8 units/l, P < 0.03) in central venous blood. These data indicate that severe local and systemic damage occurs with uncontrolled (normal blood) reperfusion even after incomplete limb ischaemia, and that these changes can be reduced by delivering a controlled reperfusate under controlled conditions.
Assuntos
Membro Posterior/irrigação sanguínea , Artéria Ilíaca/fisiologia , Isquemia/fisiopatologia , Reperfusão/métodos , Trifosfato de Adenosina/metabolismo , Animais , Velocidade do Fluxo Sanguíneo , Temperatura Corporal , Água Corporal/metabolismo , Creatina Quinase/metabolismo , Metabolismo Energético , Glucose/metabolismo , Hemodinâmica , Concentração de Íons de Hidrogênio , Isquemia/metabolismo , L-Lactato Desidrogenase/metabolismo , Consumo de Oxigênio , Potássio/metabolismo , SuínosRESUMO
HYPOTHESIS: Severe limb ischemia in patients having cardiac operations may occur after intraaortic balloon pump insertion, prolonged femoral vessel cannulation, percutaneous cardiopulmonary bypass, dissecting aneurysms, or emboli. Normal blood reperfusion can cause a postischemic syndrome that increases morbidity and mortality. This clinical study is based on an experimental infrastructure patterned after controlled cardiac reperfusion. (1) It tests the hypothesis that controlled limb reperfusion (i.e., modifying the composition of the initial reperfusate and the conditions of reperfusion) reduces the local and systemic complications seen after normal blood reperfusion. (2) It reports initial clinical application of this strategy in three cardiac surgery centers. METHODS: Controlled limb reperfusion was applied to 19 patients with signs of severe prolonged unilateral or bilateral ischemia (including paralysis, anesthesia, and muscle contracture); six patients (32%) were in cardiogenic shock. The mean ischemic duration was 26 +/- 6 hours. The reperfusion method includes a 30-minute infusion into the distal vessels of a normothermic reperfusate solution mixed with the patient's arterial blood (obtained proximal to the obstruction) in a 6:1 blood/reperfusate ratio. Data are mean +/- standard error of the mean. RESULTS: Sixteen patients (84%) survived with salvaged and functional limbs at the time of discharge. No renal, cardiac, pulmonary, cerebral, or hemodynamic complications developed in the survivors. The three deaths occurred in patients undergoing controlled limb reperfusion while in profound postoperative cardiogenic shock; neither postischemic edema nor contracture developed in any of them. CONCLUSIONS: These findings show that controlled limb reperfusion can be applied readily with standard equipment that is used for cardiac surgery and may salvage limbs while reducing postreperfusion morbidity and mortality.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Isquemia/terapia , Perna (Membro)/irrigação sanguínea , Complicações Pós-Operatórias/terapia , Reperfusão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Choque Cardiogênico/etiologia , Resultado do TratamentoRESUMO
Our previous studies in isolated rat hindlimbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in-vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of twenty pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 hours and served as controls. Fourteen other pigs underwent 6 hours of complete infrarenal occlusion. Thereafter, embolectomy was stimulated in 8 pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In 6 other pigs, control of the composition of the reperfusate and control of the conditions of reperfusion was done during the first 30 min, followed by normal blood reperfusion. Six hours of infrarenal aortic occlusion lead to a severe decrease in high energy phosphates and muscle temperature and a slight increase in creating kinase (CK) and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive edema developed (80.6% vs. 76.6%, p < 0.0009), the tissue showed a marked decrease in oxygen consumption (7.3 +/- 1.1 vs. 14.3 +/- 2.5 mL )2/100 g/min, p < 0.02), glucose consumption (0.19 +/- 0.06 vs. 0.51 +/- 0.03 mg/100 g/min, p < 0.06), tissue ATP (18.3 +/- 1.9 vs. 36.1 +/- 0.9 mumol/g protein, p < 0.000001), total adenine nucleotides (26.3 +/- 2.6 vs. 45.8 +/- 1.5 mumol/g protein, p < 0.00001), muscle pH (5.9 +/- 0.1 vs. 7.3 +/- 0.1, p < 0.000006) and total calcium in the femoral vein (2. +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, p < 0.002). Furthermore, a massive increase was seen in CK concentration (12,743 +/- 2,562 vs. 513 +/- 80 U/L, p < 0.0003), potassium (7.9 +/- 0.3 vs. 4.4 +/- 0.2 mmol/L, p < 0.000001) and muscle rigidity (60 +/- 11 vs. 122 +/- 1 degree, p < 0.00008). In sharp contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion resulted in normal water content (77.6 +/- 0.4 vs. 76.8 +/- 0.3%), oxygen consumption (13.2 +/- 1.6 vs. 14.9 +/- 3.2 mL O2/100 g/min), glucose consumption (0.58 +/- 0.18 vs. 0.46 +/- 0.11 mg/100 g/min), flow (5.4 +/- 1.1 vs. 4.6 +/- 4.6 +/- 0.5 mL/100 g/min) and muscle rigidity (106 +/- 4 vs. 122 +/- 1 degree). Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content (78% vs. 57% of control), less tissue acidosis (6.6 +/- 0.2 vs. 5.9 +/- 0.1, p < 0.002), severely reduced CK release (2,618 +/- 702 vs. 12,743 +/- 2.562, p < 0.02) and potassium release (5.1 +/- 0.3 vs. 7.9 +/- 0.3 mmol/L, p < 0.0002) as compared to normal blood reperfusion. In conclusion this study shows that 6 hours of acute infrarenal aortic occlusion will result in a severe reperfusion injury (postischemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.