Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) content of isolated and aerobically perfused rabbit hearts. Both drugs failed to modify the myocardial redox state. At concentrations > 10(-6) M, zofenopril, but not captopril, caused a reduction in myocardial NE content. At 10(-4) M, both drugs caused a reduction in developed pressure and an increase in diastolic pressure and release of creatine phosphokinase (CPK). Second we investigated their effects on ischemic and reperfused myocardium. Both drugs exerted a cardioprotection; zofenopril was always more potent than captopril. Recovery of developed pressure on reperfusion improved, and peak release of NE was reduced, as was release of CPK. Calcium homeostasis and mitochondrial function were maintained. Captopril had no effect on occurrence of oxidative stress during reperfusion, whereas zofenopril reduced it. In hearts treated with the converting enzyme inhibitors, peak release of NE was correlated to mitochondrial calcium content, production of ATP, and recovery of mechanical function on reperfusion. These data suggest that the cardioprotective effect of zofenopril and captopril is independent of hemodynamic changes or reduction of the toxicity of oxygen free radicals and that it could be related to a reduction in release of NE.
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PMID:Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: insight into its mechanism of action. 128 Jul 30

In the isolated working rat heart model, we studied metabolic and hemodynamic effects of 5- and 30-min global ischemia followed by reperfusion and assessed the potentially beneficial effect of captopril 80 micrograms/ml added throughout the experiment. Creatine kinase (CK) and catecholamines were measured in coronary effluent. De novo eicosanoids (prostaglandin E2) synthesis was assessed in endocardial explants. Hemodynamic alterations occurred after 30-min ischemia and were reflected most dramatically by a reduction in cardiac output (CO 72 +/- 10% of baseline values in captopril vs. 68 +/- 16% in controls) without significant differences as a result of treatment. Captopril shortened reperfusion ventricular fibrillation (VF) duration (6.9 +/- 1.2 vs. 13.6 +/- 8.7 min, p less than 0.05) but had no effect on VF incidence. No differences occurred in norepinephrine (NE) outflow, whereas total CK release was greater in controls. Five controls versus none of the treated hearts (p less than 0.05) released trace amounts of epinephrine during reperfusion. Increased de novo PGE2 synthesis was demonstrated after 5-min I (465 +/- 168 vs. 238 +/- 75 pg/100 mg tissue per hour, p less than 0.01). Captopril stimulated production of PGE2 in normoxic hearts (p less than 0.02), but the difference was no more apparent in ischemic hearts. We conclude that captopril produces some biochemical and electrophysiologic evidence of myocardial salvage, but these effects are not sufficient to induce hemodynamic improvement after global ischemia and reperfusion.
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PMID:Effects of captopril on metabolic and hemodynamic alterations in global ischemia and reperfusion in the isolated working rat heart. 137 8

The effects of captopril on myocardial segment function in different degrees of transient coronary occlusion were studied using ultrasonic dimension gauges in 15 open-chest dogs. The occlusion procedures (OP) were performed on the left anterior descending coronary artery (LAD) in eight dogs and on the left circumflex coronary artery (Cx) in seven dogs. To measure the changes in segment shortening in the subendocardium we used eight dogs (ischemic and control zones: four dogs LAD and four dogs Cx). To measure the changes in wall thickening we used seven dogs (ischemic and control zones: three dogs LAD and four dogs Cx). Total coronary OP lasting 1 min and partial OP (70-80%) lasting 1 min and 2 min 30 s, before and after captopril (0.25 mg/kg i.v.) were performed. Left ventricular pressure, dP/dt, coronary flow, and ECG were monitored. Total coronary OP (1 min) changed segment shortening (18% LAD; 14% Cx) and wall thickening (19% LAD; 18% Cx) to values of dyskinesis (-3% and -4% for shortening; -6% and -5% for thickening). Captopril improved regional function maintaining positive values for shortening (4% LAD; 3% Cx) and thickening (0.3% LAD; 4% Cx). Similar responses were obtained during partial OP and captopril. Results suggest that captopril produced a significant improvement in the regional function parameters affected by ischemia both in total and partial obstructions.
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PMID:Effects of captopril on regional segment motion during acute coronary occlusion. 161 21

The adjunctive use of angiotensin-converting enzyme (ACE) inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation, and increase prostacyclin and bradykinin levels. In the chronic phase, ventricular remodeling may be attenuated. At present, a large number of controlled clinical trials mainly focusing on the effects of ACE inhibition in the chronic phase are underway. Only a few studies concentrate on the effect of acute intervention with ACE inhibitors in ischemia-reperfusion, i.e., thrombolysis in myocardial infarction. In April 1990 under auspices of the Interuniversity Cardiology Institute of the Netherlands, a large nationwide acute intervention trial with captopril in 280 patients receiving thrombolytic therapy was started, the Captopril and Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of ACE inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring and neurohumoral measurements immediately on thrombolysis and during the first year after myocardial infarction.
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PMID:Early intervention with angiotensin-converting enzyme inhibitors during thrombolytic therapy in acute myocardial infarction: rationale and design of captopril and thrombolysis study. CATS investigators group. 174 15

We previously reported concentration-dependent protection of captopril against ischemia-reperfusion injury in the isolated rat heart. In order to study these effects in vivo, we developed a closed-chest pig model. Reversible occlusion of the left coronary artery was achieved with a PTCA catheter during one hour. Captopril (C) i.v. was given in two different concentrations (0.6 mg/kg/10 min + 0.3 mg/kg/2 hr and 6 mg/kg/10 min + 3.0 mg/kg/2 hr) during the experiments to 11 and 10 pigs, respectively, versus 12 controls, who received only saline. Due to malignant ventricular arrhythmias, nine pigs died during ischemia. At the end of the reperfusion period of two hours, eight pigs were alive in each group. In the C-treated pigs, maximum creatine kinase after two hours of reperfusion was significantly lowered to 6,337 +/- 709 U/L in the high dose group versus 8,285 +/- 851 U/L in the low dose group and 9,635 +/- 1,115 U/L in the saline group. A reduction of local inosine overflow in the coronary sinus was seen. Maximum noradrenaline overflow after 5 min reperfusion diminished dose-dependently to 695 +/- 284 and 3,129 +/- 1,728 pg/ml in the C treated groups versus 4,693 +/- 2,277 pg/ml in the saline group. Mean arterial blood pressure and cardiac output decreased significantly during ischemia and reperfusion, but no significant differences occurred between the treated and untreated groups. Reperfusion arrhythmias, mainly accelerated idioventricular rhythm disturbances, were comparable among the three groups. We conclude that in vivo administration of C reduces myocardial damage upon reperfusion after one hour of ischemia in a dose-dependent way.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Concentration-dependent protection by captopril against myocardial damage during ischemia and reperfusion in a closed chest pig model. 244 Nov 99

Captopril, an angiotensin converting enzyme inhibitor, has been shown to increase prostaglandin production by an as yet unknown mechanism, which this study was designed to explore. Isolated rat heart was perfused by the Langendorff technique for 15 minutes in the presence or absence of captopril. Ischemia was then induced for 60 minutes by terminating the coronary flow, followed by 60 minutes of reperfusion. Our results indicate that captopril stimulated prostaglandin and thromboxane production, but it inhibited malonaldehyde formation. Coronary flow and high energy phosphate compounds were increased, but lactate dehydrogenase and creatine kinase release decreased, demonstrating cardioprotective effects. Captopril also inhibited the production of hydroxyl radical in the heart during reperfusion, suggesting that stimulated prostaglandin production may be linked with the generation of free radicals via the eicosanoid system.
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PMID:Enhanced prostaglandin production in the ischemic-reperfused myocardium by captopril linked with its free radical scavenging action. 269 79

The protective effect of angiotensin-converting enzyme inhibitors (ACEI) on myocardial ischemia and reperfusion damage was estimated in rat hearts, both in vivo and in vitro. Enalapril 2.5 mg/kg ip pretreatment at 24 and 5 h before coronary occlusion, significantly blunted the rise of CPK (445 +/- 151 vs 649 +/- 244 mu/ml, P less than 0.05) and improved electrocardiogram (ECG) 8 h after coronary occlusion. In global ischemia and reperfusion ex vivo, enalapril improved contractility (0.9 +/- 0.2 vs 0.3 +/- 0.3 g, P less than 0.05) and coronary flow (15.6 +/- 3.3 vs 11.9 +/- 3.1 ml/min/g, P less than 0.05), shortened significantly the duration of reperfusion arrhythmia (3.1 +/- 2.7 vs 9.7 +/- 8.1 min, P less than 0.05). In Langendorffs heart, captopril remarkably preserved force of contraction (2.1 +/- 0.4 vs 1.4 +/- 0.4 g, P less than 0.01) and coronary flow (2.7 +/- 0.5 vs 3.6 +/- 0.9 ml/min/g, P less than 0.05) in segmental infarction deteriorated by angiotensin I. Captopril 10(-5) M infusion reduced the release of CPK (435 +/- 112 vs 640 +/- 123 mu/min coronary flow, P less than 0.05). This action was almost completely abolished by pretreating and infusing with indomethacin. As a positive control, prostacyclin 5 X 10(-7) M infusion further reduced the release of CPK to 330 +/- 77 mu/min. It is concluded that angiotensin-converting enzyme inhibitor can protect both myocardial ischemia and reperfusion damage in rat hearts. The mechanism of protection was ascribed to reduced production of angiotensin II by ACE inhibition and increased prostacyclin release in the myocardium.
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PMID:Protective effects of captopril and enalapril on myocardial ischemia and reperfusion damage of rat. 282 45

The effect of captopril on energy-rich phosphates and pH during normothermic ischemic arrest, hypothermic cardioplegic arrest and subsequent reperfusion was investigated in the isolated rat heart using 31P-nuclear magnetic resonance. The hearts remained in the probe during all perfusion procedures and captopril (80 ml.l-1) treatment was started directly after cannulation. After normothermic ischemic arrest (15 min), the ATP content of captopril-treated hearts was not significantly different from that of untreated hearts (53 +/- 9% and 52 +/- 8%, respectively). Accumulation of inorganic phosphate at the end of ischemia was significantly less in treated hearts, suggesting a higher end-ischemic nucleotide content in treated hearts. Hypothermic cardioplegic arrest (St. Thomas' Hospital solution, 4 degrees C) lasted for 3 h at 10 degrees C. Adenosine triphosphate in untreated hearts was significantly lower at the end of ischemia; 36 +/- 6% compared to 53 +/- 9% for untreated hearts. Adenosine triphosphate in untreated hearts recovered to 76 +/- 9% after normothermic ischemia and to 72 +/- 7% after hypothermic ischemia at the end of 30 min reperfusion. Captopril significantly improved adenosine triphosphate recovery in both treated groups; 89 +/- 4% after normothermic and 83 +/- 4% hypothermic ischemia. We conclude that captopril has a beneficial effect on recovery of adenosine triphosphate both after normothermic and after hypothermic ischemia.
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PMID:Captopril improves recovery of adenosine triphosphate during reperfusion of the ischemic isolated rat heart; a 31-phosphorus-nuclear magnetic resonance study. 306 91

Captopril, an angiotensin-converting enzyme inhibitor, was used as a protective agent before and after 90 min of renal warm ischemia in rats. At a dose of 1 mg/kg, it was able to lower the postoperative serum creatinine values significantly (from 6.3 to 2.5 mg% on the 2nd postoperative day) in unilaterally nephrectomized animals. Increasing the dose to 4 and 8 mg/kg or combining captopril with hypertonic mannitol (10 ml/kg of a 15% aqueous solution) did not improve these figures significantly. The same magnitude of protection was obtained when captopril was given either before or just after the ischemia. In terms of mortality the differences among unprotected and protected groups were very important: only 6 of 24 unprotected animals survived the 5th postoperative day while 42 of 44 protected animals survived.
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PMID:Captopril: a protective agent in renal warm ischemia in rats. 388 89

Captopril was perfused through isolated rat hearts; its effects after local ischemia and reperfusion were assessed. Upon reperfusion all untreated (10 out of 10) but only 4 (out of 10) captopril-treated (80 micrograms/ml) hearts fibrillated (P less than 0.02). Purine overflow increased upon reperfusion but was reduced by captopril (597 +/- 62 and 333 +/- 41 nmol/min gdwt respectively; P less than 0.05). The pressure-rate index and the apex displacement were severely impaired after 30 min of reperfusion (32 +/- 16 and 10 +/- 5% respectively of initial values) but captopril reduced the injury of mechanical function (60 +/- 8; P less than 0.05 and 61 +/- 11; P less than 0.05 respectively). These results show that captopril reduces ventricular fibrillation and the loss of high energy phosphate nucleotides and thereby partly maintains mechanical function impaired by ischemia and reperfusion.
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PMID:Captopril reduces purine loss and reperfusion arrhythmias in the rat heart after coronary artery occlusion. 637 6


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