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)

Amlodipine is a long-acting dihydropyridine-based Ca2+ channel blocker, developed for use on a once-daily basis. Experiments using hearts from amlodipine-pretreated rats were undertaken to further test the hypothesis that Ca2+ channel blockers can be used as prophylactic therapy to reduce the severity of the mechanical and biochemical consequences of ischemia and reperfusion. Amlodipine was given intravenously, 0.25 mg/kg, 5 hours before excising the hearts. Ischemia (global) was induced at 37 degrees C for 10, 30 or 60 minutes, and was followed by reperfusion. Protection was quantitated in terms of functional recovery, adenosine triphosphate and creatine phosphate retention, tissue acidosis and Ca2+ gain. The results show that amlodipine pretreatment supplied protection, provided that the ischemic episode did not exceed 30 minutes. The protection resulted in improved recovery of peak developed tension on reperfusion, reduced Ca2+ gain, retention of tissue adenosine triphosphate and creatine phosphate, and reduced acidosis.
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PMID:Amlodipine pretreatment and the ischemic heart. 253 Aug 87

The objective of this study was to characterize the effect of prostacyclin (PGI2) on ventricular function following total global ischemia in isolated working rat hearts and to investigate the mechanism of its action. Ischemia was initiated for 10, 15, 20 or 25 min with or without treatment with PGI2. Increasing durations of ischemia resulted in a progressive decline in high energy phosphate (HEP) stores, an elevation in tissue lactate, and incomplete recovery of function with reperfusion. Prostacyclin at either 1 or 10 ng/ml had no effect on HEP levels or total adenine nucleotides, and tissue lactate was not significantly affected by PGI2 in hearts made ischemic for 10 to 20 min, but both PGI2 concentrations significantly elevated lactate levels after 25 min ischemia. Reperfusion recovery of left ventricular function was complete following 10 and 15 min ischemia, but incomplete recovery was evident following 20 min ischemia (77% of pre-ischemic function); and although PGI2 had no direct effect on the function of aerobically perfused hearts, recovery of aortic flow with 1 ng/ml PGI2 after 20 min of ischemia was reduced to approximately 20% (P less than 0.01). This depression in recovery was associated with significantly increased lactate levels during reperfusion. At a concentration of 10 ng/ml PGI2 did not depress ventricular recovery or elevate lactate content after 20 min ischemia. When hearts made ischemic for 20 min were analyzed, a significant negative correlation was found between ventricular recovery (aortic flow rate) and lactate concentration; however, no correlation existed between recovery and ATP levels. After 25 min of ischemia, five of eight (62.5%) untreated hearts demonstrated some degree of ventricular recovery, however, only two of ten hearts studied demonstrated any measurable functional recovery with either PGI2 concentration. This effect of PGI2 to reduce or prevent recovery of ventricular function following either 20 or 25 min of ischemia as well as the corresponding elevation in lactate levels was prevented by treatment with the calcium channel blocker verapamil. This study therefore shows that PGI2 at critical low concentrations can depress left ventricular recovery following total ischemia. This effect of PGI2 becomes more pronounced as ischemia duration is prolonged and is associated with elevated tissue lactate levels. The studies with verapamil suggest that PGI2 may be acting via the slow calcium channel to increase lactate levels and depress ventricular recovery following prolonged periods of ischemia.
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PMID:Inhibition of post-ischemic ventricular recovery by low concentrations of prostacyclin in isolated working rat hearts: dependency on concentration, ischemia duration, calcium and relationship to myocardial energy metabolism. 266 90

The purpose of this study is to evaluate the myocardial protective effects of two types of solution during heart transplantation procedure following cold storage in Collins' solution. Based on the concept whether the ischemic time during the procedure is an extension of heart storage or is an usual aortic cross-clamped ischemic time, we compared the effects of our cardioplegic solution (Group I) and Collins' solution (Group II) using isolated working rat heart model. After 30 minutes of global ischemia at 25 degrees C following 2 hours of cold storage, the hearts in Group I exhibited better functional recovery than those in Group II (% recovery of cardiac output was 61.1 +/- 5.4% in Group I and 42.4 +/- 7.4% in Group II, p less than 0.01). In Group II, marked elevation of coronary vascular resistance occurred on reperfusion. CPK release during reperfusion period was greater in Group II (0.41 +/- 0.24 IU/15 min/heart in Group I, 1.92 +/- 1.25 IU/15 min/heart in Group II, p less than 0.01). Myocardial metabolites contents (ATP, TAN, creatine phosphate and lactate) and energy charge were not significantly different between two groups. We conclude that it is harmful to ischemic myocardium to use Collins' solution as myocardial protection during transplantation procedure even if following cold storage in Collins' solution.
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PMID:[Myocardial protection during transplantation procedure following cold storage in Collins' solution]. 267 Nov 86

Nuclear magnetic resonance (NMR) has contributed considerably to our understanding of experimental acute renal failure. Changes in energy metabolism which are caused by ischemia, urinary obstruction, and nephrotoxic drugs have been characterized with NMR spectroscopy. Data from our laboratory and others utilizing 31P NMR have demonstrated that levels of adenosine triphosphate fall rapidly with ischemia, and that the ability of the kidney to regenerate ATP correlates with ultimate functional recovery. Additionally, development of intracellular acidosis appears to occur early with ischemia and may, if severe enough, predict poor functional recovery. Urinary obstruction is associated with the rapid development of a large peak resonating in the phosphodiester region of the P-31 NMR kidney spectrum which is attributable to increases in urinary inorganic phosphate. Nephrotoxic acute renal failure with a variety of nephrotoxins is associated with little to no changes in high energy phosphates. Renal transplant allograft rejection is associated with energy metabolic changes similar to those seen with ischemia; however, the intracellular pH remains normal. These findings allow causes of experimental acute renal failure to be differentiated among each other in both native and transplanted kidneys. With recent advances in NMR software and hardware, the application of this methodology to human acute renal failure is now possible.
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PMID:Contributions of nuclear magnetic resonance to study of acute renal failure. 269 84

The adenosine triphosphate (ATP) content of isolated Langendorff-perfused rat hearts may be increased by more than 40% above the normal value by a 2-h perfusion with adenosine (15 mumol/l). This metabolic manipulation was used to investigate the hypothetical relationship between total tissue ATP content and ischaemia-induced contractile failure, ischaemic contracture and post-ischaemic functional recovery. Adenosine perfused hearts were submitted to 20 min of normothermic ischaemia and reperfused for 45 min with or without adenosine. Control experiments were performed with adenosine-free preischaemic perfusion. In identically designed experiments the tissue-protective effect of diltiazem (0.5 mumol/l) was determined and compared with the experiments with adenosine. At the end of 120 min of preischaemic perfusion, the ATP content of the adenosine treated hearts was 34.3 +/- 1.8 mumol/g dry weight (control = 23.6 +/- 1.9 mumol/g, p less than 0.01). After a period of 20 min of normothermic ischaemia, the ATP content of the adenosine hearts decreased to 13.3 +/- .4 mumol/g, whereas ATP fell to 8.3 +/- 1.6 mumol/g in the control hearts. The creatine phosphate (CP) levels of adenosine hearts were significantly lower than those of the control group before ischaemia, but did not show major differences following ischaemia. During ischaemia, the contractile activity measured via an intraventricular balloon catheter, as well as ischaemic contracture did not differ between the adenosine and control hearts. The inclusion of diltiazem into the perfusate significantly delayed the onset of contracture. After 45 min of reperfusion, ATP contents of adenosine and control hearts reached similar values (8.4 +/- 2.3 and 8.3 +/- 2.9 mumol/g, respectively). Inclusion of adenosine (15 mumol/l in the reperfusion perfusate of the adenosine experiments prevented a further decrease, but did not increase tissue ATP content. CP values of all groups showed a partial recovery upon reperfusion, they did not differ significantly. Contractile recovery was equal in all experimental groups except for the diltiazem treated hearts, which showed during the first 10 min of reperfusion an improved mechanical performance. It is concluded that total tissue ATP is not necessarily a good indicator of functional capabilities under conditions of normothermic ischaemia and reperfusion in the isolated rat heart.
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PMID:Adenosine-induced increase in myocardial ATP: are there beneficial effects for the ischaemic myocardium? 281 49

The presynaptic changes caused by 4-aminopyridine were studied in the electric organ of Torpedo marmorata, in the resting state and during the period following transmission of a single giant discharge. Incubation with 4-aminopyridine provoked a 30-40% decrease in the density of synaptic vesicles in nerve terminals, and a similar decrease in the content of vesicular and free acetylcholine. These changes were not observed when 4-aminopyridine was applied in a low-calcium, high-magnesium solution. In the standard medium, 4-aminopyridine treated junctions were able to generate a giant electrical discharge of long duration in response to a single stimulus. During the seconds and minutes following the giant discharge, the number of synaptic vesicles was not found to be significantly altered in the whole population of nerve terminals. However, new membranous structures--looking like sacs with double membranes encircling a part of cytoplasm--were seen in approximately 25% of nerve endings; in those terminals, the number of synaptic vesicles was significantly decreased. At this stage, the junctions had not recovered their capability to generate a second giant discharge of full size and the yield of acetylcholine, adenosine 5'-triphosphate (ATP) and creatine phosphate was diminished. Thirty minutes after the single discharge, the functional recovery was achieved and the membranous sacs had disappeared; but the levels of acetylcholine, ATP and creatine phosphate were still not restored.
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PMID:Presynaptic effects of 4-aminopyridine and changes following a single giant impulse at the Torpedo nerve-electroplaque junction. 282 80

The purpose of this study was to (1) relate myocardial high-energy phosphate stores to functional recovery after ischemia and reperfusion, (2) assess the bioenergetics and functional influence of clinically relevant myocardial hypothermia, and (3) examine tissue pH as an independent indicator of postischemic recovery of function. Rabbit hearts were perfused via a modified Langendorff technique, monitored for developed pressure (DP) and left ventricular end-diastolic pressure (LVEDP) via an isovolumic left ventricular balloon catheter, and placed in a Brucker NMR magnet (4.7 tesla) to measure phosphocreatine (PCr), adenosine triphosphate (ATP), and pH. Hearts underwent 1 hour of global ischemia at 7 degrees, 17 degrees, 27 degrees and 37 degrees C initiated by one dose of K+ cardioplegia followed by 30 minutes of reperfusion. After reperfusion, DP (expressed as a percentage of preischemic control) and LVEDP (mm Hg) in 7 degrees and 17 degrees C hearts were no different (96 + 5% vs 97 +/- 3%; 5 +/- 2 mm Hg vs 6 +/- 2 mm Hg; p = NS), but were better (p less than 0.01) than 27 degree hearts (72 +/- 6%, 17 +/- 6 mm Hg) and 37 degree hearts (31 +/- 7%, 60 +/- 6 mm Hg). PCr was severely depleted in all groups. ATP was 90 +/- 7% and 87 +/- 5% of preischemic control in the 7 degree and 17 degree hearts, which was significantly better than the 68 +/- 3% and 21 +/- 3% in the 27 degree and 37 degree groups (p less than 0.01). The pH at end ischemia was 6.83, 6.89, 6.54, and 5.86 for the 7 degree, 17 degree, 27 degree, and 37 degree hearts, respectively (7 degrees vs 27 degrees or 37 degrees, p less than 0.01; 17 degrees vs 27 degrees or 37 degrees, p less than 0.01). Linear regression of DP on end-ischemic ATP (EIATP) and end-ischemic pH revealed: DP = 0.96 (EIATP) + 20 (r = 0.92) and DP = 60 (pH) -317 (r = 0.86). We conclude that (1) end-ischemic ATP predicts recovery of ventricular function, and, furthermore, there appears a threshold ATP concentration (80% of control) below which full recovery of function will not occur; (2) end-ischemic pH predicts recovery of ventricular function; (3) 7 degrees C hypothermic ischemia does not cause a clinically significant cold injury; and (4) in a single-dose crystalloid cardioplegia model, end-ischemic pH is linearly related to recovery of function (r = 0.86).
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PMID:Optimal hypothermic preservation of arrested myocardium in isolated perfused rabbit hearts: a 31P NMR study. 291 97

To investigate whether addition of Ca2+ antagonists adds to the beneficial effects of thrombolysis we studied recovery of regional myocardial performance in pigs, in which occlusive thrombi were induced by electrical stimulation, with and without addition of nifedipine to the thrombolytic agent. To this end, four different groups of animals with thrombotic coronary occlusion were studied. Groups 1 and 2 received either saline or intracoronary nifedipine (0.1 micrograms.kg-1.min-1) 15 min after coronary artery occlusion. Groups 3 and 4 were treated with the thrombolytic agent plasmin which was infused directly into the left anterior descending coronary artery (LADCA) at a rate of 2 U.min-1. The animals in group 4 also received intracoronary nifedipine. 4 h after thrombus formation the animals were sacrificed. No important differences in systemic hemodynamics were observed between the four groups of animals. Reperfusion occurred only in the animals which received plasmin, with or without nifedipine. After intracoronary plasmin regional blood flow increased from 7 +/- 2 to 40 +/- 7 ml.min-1.100 g-1 in the LADCA-perfused subepicardial and from 9 +/- 2 to 30 +/- 6 ml.min-1.100 g-1 in the LADCA-perfused subendocardial layers. The combination of plasmin and nifedipine increased flow to the LADCA-perfused subepicardial layers from 8 +/- 2 to 74 +/- 21 ml.min-1.100 g-1 and that to the subendocardial layers from 8 +/- 2 to 57 +/- 16 ml.min-1.100 g-1 (in both cases: p less than 0.05 vs. plasmin alone). However, addition of nifedipine did not enhance recovery of regional myocardial function or high-energy phosphate metabolism. Because reperfusion was accompanied by a high ventricular ectopic activity, the question may be raised of whether reperfusion of ischemic myocardium which does not result in functional recovery could be deleterious.
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PMID:Coronary thrombolysis with and without nifedipine in pigs. 297 Aug 39

Currently, for practical clinical purposes, the preservation of donor hearts is limited to about 4 h. Transplantation must be finished within this period to assure complete functional recovery upon reperfusion. From the clinical setting it is well known that hypothermia results in a better myocardial preservation during ischemia. During ischemia, rapid catabolism of high-energy phosphates (e.g., ATP and creatine phosphate) occurs. The purpose of this study was to investigate the influence of temperature during a 24-h preservation period on the rate of catabolism of ATP and on the rate of accumulation of breakdown products (ADP, AMP, adenosine, inosine, hypoxanthine, and xanthine). For this purpose, hearts were excised and stored for 24 h at 0.5 degrees, 12 degrees, or 18 degrees C. In addition, the effect of initial cardioplegic arrest was compared with simple normothermic excision of the heart followed by 24 h in cold storage. It was found that the higher the storage temperature, the higher the rate of catabolism of high-energy phosphates and, hence, after 24 h, the lower the final ATP level and the higher the level of breakdown products, mainly nucleosides. It was also found that the initial cardioplegic arrest strongly benefits the preservation of high-energy phosphates as a result of the ATP-sparing effect.
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PMID:Optimal storage temperature and benefit of hypothermic cardioplegic arrest for long-term preservation of donor hearts: a study in the dog. 307 13

Missing the moment for application of ventricular assist devices (VAD) may be one of the major causes of multiple organ failure in patients who are to be weaned from cardiopulmonary bypass (CPB) with the aid of VAD. To determine the optimal timing for application of VAD in such patients, we examined the effect of a CPB assist on cardiac functional recovery from severe global ischemia using an experimental canine system. In the present study we created myocardial ischemia by clamping the aorta for 20 minutes (Group I; N = 7) or 45 minutes (Group II; N = 11) under normothermic CPB. The reliability of the method in creating severe cardiac failure was confirmed by testing the levels of adenosine triphosphate (ATP), creatine phosphate (CP), and lactate. After reperfusion of the myocardium, the heart was assisted by a totally vented CPB. The left ventricular end-systolic pressure-volume relationship (Emax), which is a load-independent index of contractility, was obtained every 15 minutes for up to 120 minutes of reperfusion. The Emax revealed that the function of the damaged heart recovers exponentially with time after reperfusion. From curves of the functional recovery of the heart, CPB support appeared to be beneficial for the first 60 minutes after reperfusion, and aided in the recovery of cardiac function in hearts damaged by global myocardial ischemia. However, CPB assist thereafter may not be effective in further improving cardiac function. We therefore concluded that the decision to use VAD should be determined by cardiac function by 60 minutes of reperfusion to avoid prolonging CPB time.
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PMID:Optimal timing for application of ventricular assist devices in patients who cannot be weaned from cardiopulmonary bypass. An experimental study. 319 47


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