Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The objective of this study was to evaluate the effects of three sulphydryl (SH) compounds, N-acetylcysteine (NAC), cysteine (Cys) and cystamine, on functional recovery and ventricular arrhythmias (VF) in stunned myocardium in the isolated perfused heart of the rat. 2. Hearts (n = 7-8 per group) were perfused by the Langendorff procedure for 20 min to stabilize and then assigned to one of five groups: saline, sham, NAC, Cys and cystamine. After the stabilizing period, the drugs (at 3.6 microM min-1) or their vehicle (saline) were infused into coronary vessels throughout the experimental period. Ten min after administration of drugs, the left anterior descending coronary artery (LAD) was ligatured for 20 min and then untied to reperfuse for 30 min. In the sham group, a ligature was placed around the LAD but not tied. 3. NAC and Cys had a significant effect in attenuating myocardial stunning: the percentage recovery of rate-pressure product measured 30 min after reperfusion as an index of heart function, was improved with the NAC (98.3 +/- 4.5) and Cys groups (104.0 +/- 6.5) compared with the saline (only 73.6 +/- 3.8, P < 0.01) group. Cystamine did not show these beneficial effects. This may be due to the difference in chemical structure between NAC, Cys and cystamine since the latter does not have a free SH group with a disulphide bond formed. This phenomenon suggests that a free SH group is essential for the protective effects of compounds like NAC and Cys in myocardial injury. 4. NAC and Cys prevented the fall in coronary flow during the LAD occlusion and enhanced coronary flow during reperfusion but cystamine did not have such a beneficial effect. 5. The incidence of VF in the saline, cystamine, Cys and NAC groups was 6/8 (75.0%), 4/7 (57.1%), 3/8 (37.5%) and 2/7 (28.6%), respectively, and no significant differences (P > 0.05) were noted between the saline- and drug-treated groups. 6. An in vitro study with electron spin resonance indicated that Cys effectively scavenged the hydroxyl radical (-OH) generated by Fenton's reaction but did not scavenge superoxide generated in an irradiated riboflavin system. NAC and cystamine showed a scavenging effect on -OH to a certain extent but this effect did not reach statistical significance (P > 0.05 vs saline). 7. Our results demonstrate that NAC and Cys treatment before ischaemia and reperfusion can reduce myocardial stunning. This beneficial effect may be mainly due to their ability to preserve and enhance coronary flow during coronary occlusion and reperfusion and in part due to scavenging -OH and/or replenishing intracellular glutathione. The results also indicate that the condition of coronary perfusion can produce a great impact on postischaemic ventricular performance.
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PMID:Beneficial effects of N-acetylcysteine and cysteine in stunned myocardium in perfused rat heart. 136 25

Thirty-three canine hearts were isolated after initial cardioplegia and preserved for 6 hours in 4 degrees C saline solution with intermittent infusion of cardioprotective solution every hour. Reperfusion was observed for 2 hours under normothermic cross-circulation. Hearts were divided into five groups depending on the agent(s) added to the K(+)-Mg2+ cardioplegic solution (K(+)-Mg(2+)-CP) infused. Control hearts (n = 6) received K(+)-Mg(2+)-CP solution alone; group I (n = 7) received lidocaine, 200 mg/L, added to the K(+)-Mg(2+)-CP solution; group II (n = 7) received betamethasone (250 mg/L) added to the formula for group I; group III (n = 6) received diltiazem (200 micrograms/L) added to the formula for group II; group IV (n = 7) received aprotinin (150 KIU/L) added to the formula of group III. Coronary sinus MB fraction of creatine kinase level was significantly decreased at 60 and 120 minutes of reperfusion in group II, as was mitochondrial aspartate aminotransferase level at 2 hours of reperfusion. Lysosomal enzyme release decreased in group IV. Myocardial adenosine triphosphate levels and total adenine nucleotides showed no significant difference among the groups at the end of reperfusion; however, myocardial adenosine diphosphate and adenosine monophosphate levels during reperfusion increased significantly in group I, and myocardial adenosine diphosphate and adenosine monophosphate levels at the end of reperfusion in groups I and IV were significantly higher than those of the control. Calcium overload, which was lowest in group II, was not completely prevented during reperfusion in any group. Left ventricular end-systolic pressure volume relationship in group II showed the "best" functional recovery. In addition, the ultrastructure of the left ventricular myocardium was well preserved in all groups. These results suggest that membrane stabilization with lidocaine and betamethasone affords beneficial effects on myocardial biochemical and functional viability. Diltiazem appears to be less effective in preventing calcium overload during ischemia-reperfusion, and protease inhibition with aprotinin (150 KIU/ml) seems to be highly effective in suppressing lysosomal enzyme activation-release and maintaining myocardial adenosine diphosphate and adenosine monophosphate levels.
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PMID:Heart preservation: analysis of cardioprotective infusate characteristics. Membrane stabilization, calcium antagonism, and protease inhibition on myocardial viability: a biochemical, ultrastructural, functional study. 137 28

During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia.
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PMID:Amino acid substrate preloading and postischemic myocardial recovery. 140 15

The purpose of the study is to investigate the effects of protease inhibitor (Nafamostat mesilate: NM) upon myocardial protection. Hearts were subjected to 20 min working control perfusion followed by 3 min cardioplegic infusion with the St. Thomas Cardioplegic Solution (ST) contained various concentrations of NM, and global ischemia for 33 min at 37 degrees C (Exp. 1) or 150 min at 20 degrees C (Exp. 2). Hearts were then converted to Langendorff reperfusion (the leakage of Creatine Kinase (CK) and Cathepsin B (Cat-B) ware measured) and 20 min working reperfusion. Various concentrations of NM added during Langendorff reperfusion (Exp. 3). During working perfusion cardiac functions (aortic flow (AoF), coronary flow (CoF), heart rate (HR), aortic pressure (AoP)) were measured, and expressed as the percent recovery of pre-ischemic control value. Post-ischemic recovery of AoF (%AoF) showed the bell-shaped dose-response curve, and the optimal dose was 3 microM (Exp. 1) and 10 microM (Exp. 2) respectively. There was a significant (p < 0.05) increase of %AoF in optimal dose compared with that in controls (64.2 +/- 1.2% vs 52.3 +/- 2.5% in Exp. 1, 68.9 +/- 3.1% vs 54.1 +/- 1.4% in Exp. 2). These increase of functional recovery reflected in the values for CK and Cat-B leakage. The addition of NM in ST reduced CK and Cat-B leakage significantly in the concentration of 5 microM (in Exp. 1) and 10 microM (in Exp. 2) respectively. But the addition of NM in reperfusate did not reduced CK leakage significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effects of protease inhibitor upon the ischemia-reperfusion injury]. 143 2

Cells subjected to increases in temperature induce the expression of several proteins known as heat shock or stress proteins. This process enhances the cell's ability to overcome the effects of further stress. In this respect, the effects of heat stress have been reported to protect the hearts of rats following ischaemia and reperfusion. We have confirmed and extended this observation, not only using different indices of myocardial injury but also in another species, namely the rabbit. Animals were anaesthetized and the body temperature raised to 42 degrees C for a 15-min period. Controls were treated in the same way but without heating. Twenty-four hours later the rabbits were re-anaesthetized and the hearts removed for either heat stress protein analysis or perfusion with Krebs buffer using an isolated perfused heart apparatus. Hearts were subjected to 60 min of low flow (1 ml/min) ischaemia followed by 30 min of reperfusion. All hearts subjected to heat stress showed an enhanced recovery of function upon reperfusion as measured by improvements in developed pressure (27.3 +/- 3.6 vs 16.3 +/- 3.0 mmHg) and diastolic pressure (37.3 +/- 7.4 vs 54.7 +/- 3.1 mmHg). In addition, creatine kinase release, associated with reperfusion, was significantly reduced in the heat-stressed hearts (532 +/- 102 vs 1138 +/- 73 mU/min/g wet wt). Myocardial accumulation and release of oxidized glutathione, an index of oxidative stress, was significantly reduced in the heat-stressed group (0.003 +/- 0.003 vs 0.376 +/- 0.113 nmol/min/g wet wt). The improved metabolic status of the reperfused heat-stressed hearts was further demonstrated by a significant conservation in the levels of ATP (6.1 +/- 0.9 vs 2.8 +/- 0.8 mumol/g dry wt) and CP (36.9 +/- 6.4 vs 16.4 +/- 5.1 mumol/g dry wt). Finally, isolated mitochondrial function in terms of respiratory control index (RCI) was maintained in the heat-stressed hearts (9.2 +/- 0.9 vs 5.7 +/- 0.2) and overloading with calcium was reduced. These data extend the hypothesis that heat stress protects the heart following ischaemia and reperfusion in this in vitro model, in a way as yet undetermined.
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PMID:The protective role of heat stress in the ischaemic and reperfused rabbit myocardium. 143 16

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n = 8) or normocalcemic Fluosol cardioplegia (group 2, n = 8). Cold cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater (p = 0.0001) in group 1 (31.8 +/- 6.3 micrograms.min-1 x g-1) than in group 2 (-0.59 +/- 0.1 microgram.min-1 x g-1), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluosol cardioplegia results in complete functional recovery: a comparison with blood cardioplegia. 144 1

Depletion of high-energy phosphates, accumulation of inorganic phosphate and intracellular acidosis have each been proposed as important events in the transition from reversible to irreversible ischemic injury. To assess whether each variable is predictive of functional recovery on reperfusion, these were measured in the isolated isovolumic rat heart using 31P NMR. Perfused hearts were subjected to either 10, 12 or 40 min of normothermic ischemia followed by 40 min of reperfusion. Hearts were then freeze-clamped for further analysis of phosphate metabolites by NMR and ion chromatography. High-energy phosphates, Pi, phosphomonoesters and pH were measured by 31P NMR spectroscopy at 2 minute intervals. Heart rate and developed pressure were monitored simultaneously. All hearts undergoing 10 min of ischemia and 40% of hearts subjected to 12 min of ischemia demonstrated good functional recovery. The remainder of hearts ischemic for 12 min went into contracture on reperfusion with little return of function. Hearts subject to 40 min of ischemia went into ischemic contracture and showed no recovery on reperfusion. Intracellular pH, [ATP], and [Pi] measured prior to reperfusion did not predict the extent of recovery. However, phosphomonoesters were detected prior to reperfusion in all hearts that did not recover well, but were not observed in hearts that showed good mechanical recovery. Analysis of tissue extracts by 31P NMR and ion chromatography indicated that the most prominent components of the phosphomonoesters were glucose 6-phosphate, alpha-glycerol phosphate and AMP. In conclusion, of the various phosphorus metabolites that can be measured by 31P NMR, only one group, the phosphomonoesters, was predictive of functional recovery.
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PMID:Predicting functional recovery from ischemia in the rat myocardium. 148 87

The experiments in the present study were designed to address two issues: Is it possible to manipulate intramyocardial pH in neonatal hearts with different buffers in cardioplegic solution and, if so, do differences in intramyocardial pH during ischemia influence functional recovery? Isolated working hearts from 7- to 10-day-old rabbits underwent 60 minutes of cardioplegic arrest at 37 degrees C with cardioplegic washouts at the onset of ischemia and at 30 minutes. Hearts were reperfused with oxygenated physiologic saline solution (pH = 7.4), returned to the working mode for 30 minutes, and hemodynamic measurements were obtained to compare with baseline values. Intramyocardial pH was held constant during the ischemic interval by infusing cardioplegic solution containing different buffers: histidine (pK 6.0 at 37 degrees C), bicarbonate (pK 6.4), or tromethamine (pK 8.1). The intramyocardial pH was measured continuously with a Khuri glass electrode system (Vascular Technology, Inc., North Chelmsford, Mass.). Cardioplegic solutions buffered to pH values of 6.0 (histidine), 7.4 (bicarbonate), and 8.0 (tromethamine) were associated with ischemic intramyocardial pH values of 6.3 +/- 0.03, 7.02 +/- 0.05, and 7.88 +/- 0.06, respectively. Functional recovery was best in the acidic (histidine) and worst in the basic (tromethamine) groups. Recoveries of developed pressure, the rate of rise of pressure over time, and aortic flow were significantly better for each parameter in the bicarbonate-treated compared with the tromethamine-treated hearts (p less than 0.005). Recovery in the histidine group, however, was superior to that in both the bicarbonate-treated and the tromethamine-treated hearts (p less than 0.005). Regression analysis demonstrated that a significant inverse relationship existed between functional recovery and intramyocardial pH, supporting the conclusions that intramyocardial pH is an important determinant of functional recovery in the neonatal heart and that acidic conditions during normothermic ischemia optimize preservation of myocardial function.
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PMID:The effect of intramyocardial pH on functional recovery in neonatal hearts receiving St. Thomas' Hospital cardioplegic solution during global ischemia. 149 95

We have compared the protective properties of three cardioplegic solutions (St. Thomas' Hospital, University of Wisconsin, and Bretschneider) for the long-term hypothermic preservation of the rat heart. Hearts (n = 8 per group) were excised and arrested by an infusion (10 ml at 4 degrees C) of cardioplegic solution. After 4, 6, or 8 hours of storage at 4 degrees C, they were reperfused in the Langendorff mode for 15 minutes and then in the working mode for 20 minutes. After 4 hours of storage, postischemic cardiac output in the St. Thomas' and Wisconsin groups was 68.8 +/- 4.6 and 63.7 +/- 3.0 ml/min, respectively (NS); nonischemic aerobic control cardiac output was 83.2 +/- 2.6 ml/min. In the Bretschneider group, cardiac output was only 43.4 +/- 3.6 ml/min (p less than 0.05 compared to the other groups). Extending storage to 6 or 8 hours led to further decreases in recovery of function in all groups (cardiac output in the St. Thomas' and Wisconsin groups was 53.7 +/- 3.2 and 52.2 +/- 5.1 ml/min after 6 hours and 39.9 +/- 2.2 and 45.8 +/- 2.5 ml/min after 8 hours, respectively; NS). With the Bretschneider solution the cardiac output was again lower (37.6 +/- 3.0 and 22.3 +/- 4.1 ml/min, respectively). Creatine kinase leakage tended to be greater in the Bretschneider group, but adenosine triphosphate and creatine phosphate contents were well preserved in all groups. In further studies, hearts (n = 8 per group) were infused with the three solutions and stored at 4 degrees C for 8 or 10 hours; they were then heterotopically transplanted into the abdomens of homozygous recipients. After 24 hours of reperfusion, the hearts were excised and taken for ex vivo functional and metabolic studies. Recovery of contractile function was similar in all groups, but the tissue content of adenosine triphosphate tended to be greater in the St. Thomas' and Wisconsin groups (15.0 +/- 1.5 and 14.7 +/- 1.0 mumol/gm dry weight in the 8-hour storage groups and 12.1 +/- 1.2 and 11.7 +/- 0.8 mumol/gm dry weight in the 10-hour storage groups, respectively) than in the Bretschneider groups (12.3 +/- 0.9 and 9.1 +/- 1.6 mumol/gm dry weight, respectively). Creatine phosphate content recovered completely in all groups. We conclude that all three solutions afford similar protection to the hypothermically stored rat heart, but that the St. Thomas' Hospital and University of Wisconsin solutions are marginally superior to the Bretschneider solution.
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PMID:Long-term hypothermic storage of the mammalian heart for transplantation: a comparison of three cardioplegic solutions. 149 25

Continuous hypothermic low-flow infusion of cardioplegic or other preservation solutions has been advocated for extending the maximum duration of storage of donor hearts for transplantation. We report the effect of varying the pressure during continuous infusion of St. Thomas' Hospital cardioplegic solution on functional recovery after long-term storage. Isolated working rat hearts (six per group) were aerobically perfused (20 minutes), and control indexes of cardiac function were measured; hypothermic ischemic arrest was then induced by a 3-minute infusion (60 cm H2O) of cold (7.5 degrees C) St. Thomas' Hospital cardioplegic solution. Hearts were then stored for 8 hours at 7.5 degrees C, either immersed in St. Thomas' Hospital cardioplegic solution (noninfused control) or continuously infused at varying infusion pressures with St. Thomas' Hospital cardioplegic solution, which had been both oxygenated and supplemented by the addition of glucose (11.1 mmol/L). After 8 hours of hypothermic ischemia, the rate of cardioplegic infusion was measured as an index of vascular resistance. The hearts were then reperfused (Langendorff) for 30 minutes during which creatine kinase leakage was measured. The hearts were then converted to working preparations for 20 minutes, and the recovery of contractile function was measured and expressed as a percentage of the preischemic control value. In hearts that had been subjected to continuous infusion at 6, 10, 20, 30, 40, and 60 cm H2O, the recoveries of aortic flow were 0% (p less than 0.05), 38.6% +/- 5.1% (p less than 0.05), 36.2% +/- 3.6% (p less than 0.05), 14.0% +/- 8.0%, 5.8% +/- 2.9%, and 9.9% +/- 4.7%, respectively, and the postischemic leakage of creatine kinase was 98.7 +/- 19.5 (p less than 0.05), 26.2 +/- 4.2, 15.5 +/- 3.4, 30.4 +/- 11.1, 109.8 +/- 21.8 (p less than 0.05), and 136.0 +/- 14.1 (p less than 0.05) IU/30 min/gm dry weight, respectively. In contrast, in noninfused control hearts the recovery of aortic flow was 11.1% +/- 7.5%, and creatine kinase leakage was 58.9 +/- 8.7 IU/30 min/gm dry weight. In conclusion, maximum myocardial preservation was obtained with continuous low-flow hypothermic cardioplegic infusion at pressures between 10 and 20 cm H2O.
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PMID:Long-term preservation of the heart: the effect of infusion pressure during continuous hypothermic cardioplegia. 149 29


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