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)

Impaired coronary flow during postischemic reperfusion may limit functional recovery. In the present studies we used the heterotopically transplanted rat heart and the isolated working rat heart to assess whether adenosine, given during reperfusion, could improve either the rate or the extent of postischemic recovery. Hearts were arrested (2 minutes at 4 degrees C) with the St. Thomas' Hospital cardioplegic solution and stored by immersion in the same solution for 8 hours at 4 degrees C. Hearts were then transplanted into the abdomen of homozygous recipients. Immediately before reperfusion, adenosine (0.5 ml of a 1 mumol/L solution, equivalent to 0.13 micrograms) was injected into the left ventricle (control rats received an equivalent amount of saline). Hearts were reperfused in vivo for 30 minutes or 24 hours, after which they were excised and perfused (Langendorff) for 20 minutes for the assessment of function. They were then freeze clamped and taken for metabolic analysis. After 50 minutes of reperfusion, left ventricular developed pressure was 75 +/- 5 mm Hg (4 mm Hg end-diastolic pressure) in the adenosine group versus 61 +/- 4 mm Hg in the control group (p less than 0.05); however, after 24 hours function was identical in the two groups (52 +/- 4 versus 52 +/- 3 mm Hg). After 50 minutes of reperfusion coronary flow was greater in the adenosine group (11.0 +/- 0.4 versus 9.7 +/- 0.4 ml/min in control rats; p less than 0.05), a difference that was sustained for 24 hours (12.8 +/- 0.3 versus 11.4 +/- 0.4 ml/min in control rats; p less than 0.05). Adenosine triphosphate and creatine phosphate contents recovered to similar extents in control and adenosine groups after both 50 minutes and 24 hours of reperfusion. In further studies with an identical storage protocol (8 hours at 4 degrees C), hearts were not transplanted but were reperfused with crystalloid medium in the Langendorff mode for 15 minutes (creatine kinase leakage measured) and in the working mode for 180 minutes. In an attempt to mimic the heterotopic transplant protocol, adenosine (1 mumol/L) was included in the perfusion fluid for the first 2 minutes of reperfusion. Similar results to those of the transplant studies were obtained, with coronary flow being consistently improved in the adenosine group; however, this benefit was lost after only 2 hours of reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Exogenous adenosine accelerates recovery of cardiac function and improves coronary flow after long-term hypothermic storage and transplantation. 161 1

Using NADH fluorometry to monitor myocardial metabolism, the mechanism of reperfusion injury was investigated after the delivery of an experimental reperfusate. Using an isolated working heart preparation, rat hearts underwent 15 min of global ischemia at 37 degrees C. Following the ischemic insult, an oxygenated enriched reperfusion solution was given for 5 min. The hearts were then returned to a working state and aortic flow recorded to evaluate recovery. NADH levels were monitored throughout the experiment with a fluorometer and glycogen, AMP, ADP, and ATP were measured biochemically pre- and postischemia, after reperfusion and after recovery. In this study, reperfusion injury was best abated by an enriched reperfusate. Our results indicate the mechanism for this amelioration is not high-energy phosphate replenishment. Rather, as indicated by NADH fluorescence, the hearts attain an intermediate level of metabolism that permits glycogen to be restored and functional recovery to be improved.
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PMID:Monitoring myocardial reperfusion injury with NADH fluorometry. 161 62

Isolated working rat hearts were exposed to 25 min ischemia, and functional recovery was assessed by aortic flow (AoF) and rate-pressure product (RPP) to evaluate the beneficial effects of potassium (20 mM) induced arrest (K-arrest) prior to ischemia. K-arrest improved the recovery of function after 30 min of reperfusion compared with the control group (%AoF: 68 +/- 6 vs 0%, %RPP: 90 +/- 3% vs 60 +/- 3%, p less than 0.01). The accumulation of Ca++ at the end of reperfusion was less in hearts with K-arrest (2.2 +/- 0.1 vs 4.5 +/- 0.3 mumol/g dry, p less than 0.01). There was no difference between the two groups in high energy phosphate content at the end of ischemia. The increase in intracellular Na+ (Nai) during ischemia was reduced in hearts with K-arrest (delta: 19 vs 46 mumol/g dry), and the level of intracellular K+ (Ki) was higher at the end of ischemia in hearts with K-arrest (341 +/- 4 vs 318 +/- 2 mumol/g dry, p less than 0.01). During the first 5 min of reperfusion, the level of Ki in K-arrested hearts jumped to a higher level than in the control group (delta: 15 vs 2 mumol/g dry, p less than 0.01). The level of Nai was lower in hearts with K-arrest after 5 min of reperfusion. These data suggested that K-arrest might preserve the activity of Na+/K+ ATPase during ischemia and early reperfusion, and that it attenuated the increase in Nai during ischemia and reperfusion, which resulted in less Ca++ overload during reperfusion via the Na+/Ca++ exchange mechanism and led to improved recovery.
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PMID:[Mechanism of myocardial protection with potassium arrest in isolated ischemic rat hearts]. 166 47

The metabolic basis for the enhanced tolerance of immature hearts to ischemia remains to be elucidated. Loss of high-energy phosphate nucleotides occurs during ischemia/reperfusion in mature (adult) hearts through the breakdown of adenosine triphosphate, diphosphate, and monophosphate (nondiffusible) to adenosine (freely diffusible). However, previous work has shown that after ischemia nondiffusible nucleotides are better retained by immature (neonatal) hearts than by mature hearts. The enzyme responsible for the conversion of adenosine monophosphate to adenosine is 5'-nucleotidase. We therefore hypothesized lower activity of this enzyme in neonatal than in adult myocardium. The purposes of this study were (1) to document 5'-nucleotidase activities in neonatal and adult rabbit myocardium and (2) to correlate differences of 5'-nucleotidase activity with functional recovery from ischemia. Neonatal (5- to 10-day-old) and adult (4- to 6-month-old) rabbit hearts were isolated and perfused (retrograde Langendorff). A left ventricular balloon measured functional parameters. Hearts were subjected to 20 minutes of global 37 degrees C ischemia and 10 minutes of reperfusion followed by freeze clamping. Tissue homogenates were assayed for 5'-nucleotidase by the linked formation of nicotinamide-adenine dinucleotide at 340 nm (Arkesteijn method). Postischemic recovery of developed pressure was 86% +/- 3% in neonates (n = 5) versus 38% +/- 3% in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). 5'-Nucleotidase activity was 4400 +/- 1208 nmol/min/gm in neonates (n = 5) versus 13,938 +/- 830 nmol/min/gm in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). We conclude that (1) 5'-nucleotidase activity is 68% lower in neonatal than in adult myocardium and (2) functional recovery after ischemia inversely relates to 5'-nucleotidase activity.
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PMID:Cardiac 5'-nucleotidase activity increases with age and inversely relates to recovery from ischemia. 173 85

We tested the effects of glucose and oxygen in cardioplegic solutions on myocardial protection in the isolated perfused working rat heart. Recovery from 2 hours' hypothermic (8 degrees C) cardioplegic arrest was examined in 93 hearts. Cardioplegic solution, which was delivered every 15 minutes, was supplemented with glucose 28 mmol/L as a substrate or sucrose 28 mmol/L as a nonmetabolizable osmotic control; it was equilibrated with either 98% oxygen or 98% nitrogen, both with 2% carbon dioxide. Four combinations of hyperkalemic cardioplegic solution were studied: nitrogen-sucrose, nitrogen-glucose, oxygen-sucrose, and oxygen-glucose. During hypothermic arrest, oxygenation of cardioplegic solution greatly reduced myocardial lactate production and prevented ischemic contracture as indicated by coronary vascular resistance. Glucose increased lactate production modestly but significantly only when the cardioplegic solution was nitrogenated. Although end-arrest myocardial adenosine triphosphate and creatine phosphate were greatly increased by oxygenation of cardioplegic solution (p less than 0.005), we could not detect improved preservation of these high-energy phosphates by glucose. Averaged over reperfusion, percent recovery of cardiac output for the nitrogen-sucrose, nitrogen-glucose, oxygen-sucrose, and oxygen-glucose solutions was 32.3% +/- 6.1%, 45.9% +/- 4.6%, 44.5% +/- 4.6%, and 62.2% +/- 4.5%, respectively. Oxygenation of the glucose solution or addition of glucose to the oxygenated solution significantly improved recovery of cardiac output. The benefits of glucose and oxygen were additive, so that the oxygen-glucose cardioplegic solution provided the best functional recovery. We conclude that the addition of glucose to the fully oxygenated multidose cold cardioplegic solution improves functional recovery without increasing lactate production during arrest.
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PMID:Benefits of glucose and oxygen in multidose cold cardioplegia. 173 87

Experimental evidence indicates that calcium antagonists enhance the recovery of contractile function in canine myocardium stunned by a brief, 15-minute episode of transient coronary artery occlusion. In fact, both nifedipine and verapamil have been shown to improve systolic contraction, even when treatment was delayed, that is, when the agents were administered 30 minutes after reperfusion. The beneficial effects of delayed treatment were not a consequence of myocardial high-energy phosphate preservation. Furthermore, as low-dose intracoronary nifedipine enhanced the recovery of function in the absence of systemic hemodynamic or coronary vasodilatory effects, the improved function associated with delayed administration of calcium antagonists could not be attributed solely to afterload reduction or increased coronary blood flow. These data suggest that calcium-channel blockers exert a direct effect on the previously ischemic tissue, perhaps by subtle modulation of calcium transport or flux within the stunned myocytes. Although the precise mechanism of action of these agents remain unresolved, these intriguing experimental results raise the possibility that calcium antagonists may provide a clinically useful means of attenuating postischemic dysfunction of viable myocardium salvaged by thrombolysis, angioplasty, or cardiopulmonary bypass. The potential role of calcium-channel blockers in these clinical instances of stunned myocardium awaits further evaluation.
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PMID:Calcium antagonists and stunned myocardium: importance for clinicians? 175 42

Although University of Wisconsin cold storage solution provides excellent preservation for the pancreas, the kidney, and the liver after extended cold ischemic storage, its ability to preserve the heart for extended cold storage periods is not yet proved. This study was carried out to evaluate the effect of University of Wisconsin solution on heart preservation and to compare it to modified St. Thomas' solution II with respect to the capacity to preserve high-energy phosphates and contractile function in pig hearts. Hearts were arrested with either University of Wisconsin cold storage solution or St. Thomas' solution II (10 ml/kg) and kept ischemic at 12 degrees C or 4 degrees C for 8 hours. Functional recovery after the preservation period was assessed by means of ventricular function curves of the isovolumically contracting Langendorff model perfused with modified Krebs-Henseleit solution. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to monitor high-energy phosphates and intracellular pH during preservation and reperfusion. At 12 degrees C, hearts arrested and preserved with University of Wisconsin solution showed a rapid decrease in phosphocreatine and adenosine triphosphate. With St. Thomas' solution, phosphocreatine and adenosine triphosphate decreased slowly. Functional recovery was poorer with University of Wisconsin solution than with St. Thomas' solution. Hearts preserved at 4 degrees C with either solution showed no significant differences in high-energy phosphate content and functional recovery. Rigorous control of the low temperature (4 degrees C) is necessary when University of Wisconsin solution is used for heart preservation.
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PMID:A comparison of UW cold storage solution and St. Thomas' solution II: a 31P NMR and functional study of isolated porcine hearts. 175 64

Human heart preservation for transplantation commonly involves infusion of cold cardioplegic solutions and subsequent immersion in the same solution. The objectives of the present study were (1) to establish the temporal relationship between storage time (at 10 degrees C) and the postischemic recovery of function in the isolated rat heart, (2) to assess, by metabolic and functional measurements, whether storing the heart in fluid as opposed to moist air had any effect on the viability of the preparation, and (3) to ascertain the optimal storage temperature. Isolated rat hearts (at least 6 in each group) were infused for 3 minutes with St. Thomas' Hospital cardioplegic solution No. 2 at 10 degrees C, stored at 10 degrees C for 6, 12, 18, or 24 hours, and then reperfused at 37 degrees C. Mechanical function, assessed by construction of pressure-volume curves (balloon volumes: 20, 40, 60, 80, 100, and 120 microliters), was measured before ischemia and storage and after 60 minutes of reperfusion. Function deteriorated in a time-dependent manner; thus at a balloon volume of 60 microliters the recovery of left ventricular developed pressure was 84.2% +/- 5.3% after 6 hours (p = not significant when compared with preischemic control); 69.1 +/- 3.3% after 12 hours (p less than 0.05); 55.6% +/- 4.4% after 18 hours (p less than 0.05), and 53.0% +/- 6.8% (p less than 0.05) after 24 hours of storage. Other indices of cardiac function, together with creatine kinase leakage and high-energy phosphate content, supported these observations. Since the recovery of the left ventricular developed pressure balloon volume curves were essentially flat after 18 and 24 hours of storage, either 6 or 12 hours of storage were therefore used in subsequent studies. Comparison of storage environment (hearts either immersed in St. Thomas Hospital cardioplegic solution No. 2 or suspended in moist air at 10 degrees C for 6 or 12 hours) revealed no significant differences in functional recovery between the groups. Thus hearts recovered 94.9% +/- 3.5% and 113.7% +/- 12.4%, respectively, after 6 hours of storage and 71.6% +/- 2.4% and 54.2% +/- 7.9%, respectively, after 12 hours of storage. Enzyme leakage and tissue water gain were also similar in both groups of hearts. Finally, hearts (n = 6 per group) were subjected to 12 hours' storage at 1.0 degree, 5.0 degrees, 7.5 degrees, 10.0 degrees, 12.5 degrees, 15.0 degrees, and 20.0 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Long-term preservation of the mammalian myocardium. Effect of storage medium and temperature on the vulnerability to tissue injury. 186 98

Working rat hearts were perfused for 15 minutes at 37 degrees C before switching to a Langendorff perfusion (60 mm Hg aortic pressure) at 10 degrees C for 40 minutes of hypothermic arrest. Ventricular function was allowed to recover for 15 minutes at 37 degrees C by reestablishing the prehypothermic conditions. The perfusate was Krebs-Henseleit bicarbonate buffer containing 3% bovine serum albumin and either glucose (11 mmol/L) or glucose (11 mmol/L) plus palmitate (1.2 mmol/L) and gassed with 95% O2 and 5% CO2. In hearts receiving glucose alone as substrate, coronary flow was maintained constant during the 40 minutes of hypothermic arrest and returned to prehypothermic rates with rewarming. Ventricular function, as estimated by peak systolic pressure and heart rate, recovered to the prehypothermic level. When palmitate was added, coronary flow decreased continuously throughout the hypothermic perfusion (22% decrease by 40 minutes), and ventricular pressure development was lower throughout the rewarming perfusion. Tissue levels of adenosine triphosphate and creatine phosphate were well maintained and long-chain acyl coenzyme A and acyl carnitine decreased during hypothermia regardless of the substrate provided. With rewarming, tissue levels of adenosine triphosphate and creatine phosphate decreased in those hearts receiving palmitate. Omission of fatty acid either during hypothermia or during the first 5 minutes of rewarming improved recovery of function. Addition of oxfenicine to inhibit fatty acid oxidation, or inhibition of Ca2+ overload by verapamil and low perfusate Ca2+, prevented the effects of palmitate on ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fatty acids suppress recovery of heart function after hypothermic perfusion. 192 62

The purpose of this work was to evaluate the biochemical changes in the myocardial cell using cardioplegia supplemented with creatine phosphate (CP). Many previous studies have demonstrated the beneficial effect of CP on the ischemic myocardium and its mechanism of action has been assumed to be mainly extracellular. Based on the assumption that CP could also exert some influence on myocardial cellular metabolism, this investigation was carried out. Forty patients undergoing mitral valve replacement were divided into two groups: group 1 was treated with standard cardioplegic solution, and group 2 was treated with cardioplegic solution enriched with CP at a concentration of 10 mmol/L. Samples of papillary muscle, obtained from the removed valve, were studied by means of biochemical methods in order to assess the enzyme activities and the metabolites of the different biochemical pathways related to energy metabolism in the myocardial cell. One papillary muscle sample was used to determine enzyme activities spectrophotometrically; another was used to evaluate metabolite concentrations by spectrophotometric or spectrophotofluorimetric methods. The rate of spontaneous functional recovery after rewarming and weaning from cardiopulmonary bypass (CPB) also was evaluated. In group 2, the Vmax of enzymatic activities was significantly greater (hexokinase, malate dehydrogenase, glutamate dehydrogenase, total NADH cytochrome c reductase) and a better functional state of the heart was observed after CPB. On the basis of the clinical and biochemical data, it is concluded that the myocardium was better preserved when CP was added to the cardioplegic solution. Therefore, the results suggest a possible interaction of exogenous CP with cellular metabolism.
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PMID:Biochemical changes induced in the myocardial cell during cardioplegic arrest supplemented with creatine phosphate. 193 52


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