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)

Coenzyme Q10 (CoQ10, ubiquinone) has been shown to be protective against myocardial ischemia/reperfusion induced injury. The purpose of this study was to investigate the effect of CoQ10 added to cold cristalloid cardioplegia on hypothermic ischemia and normothermic reperfusion using an isolated working rat heart. Hearts (n = 6-9/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. This was followed by a 3-min infusion of St. Thomas' Hospital cardioplegic solution containing various concentrations of CoQ10 (0, 1, 3, 6, 12, and 58 mumol/L). Hearts were then subjected to 180 min of hypothermic (20 degrees C) global ischemia and 35 min of normothermic (37 degrees C) reperfusion (15 min Langendorff, 20 min working). Ventricular fibrillation (Vf) upon reperfusion was irreversible in the 12 and 58 mumol/ L CoQ10 groups (4/6 and 3/6, respectively). In the hearts which Vf upon reperfusion was not irreversible, the percent recovery of aortic flow (%AF) was 43.3 +/- 5.4% (n = 9) in the control group versus 31.6 +/- 7.7% (n = 6), 38.0 +/- 12.0% (n = 6), 27.2 +/- 6.9% (n = 6), 31.3% (n = 2), and 30.4 +/- 14.2% (n = 3) in the 1, 3, 6, 12, and 58 mumol/L CoQ10 groups, respectively. Creatine kinase leakage during Langendorff reperfusion tended to be greater in the 12 and 58 mumol/L CoQ10 groups than in the control group. Thus, CoQ10 in the cold cristalloid cardioplegic solution induced irreversible Vf upon reperfusion and failed to improve functional recoveries following hypothermic global ischemia.
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PMID:[The effect of coenzyme Q10 and cold cristalloid cardioplegia on hypothermic global ischemia]. 896 87

Diabetes increases the incidence of cardiovascular disease as well as the complications of myocardial infarction. Studies using animal models of diabetes have demonstrated that the metabolic alterations occurring at the myocyte level may contribute to the severity of ischemic injury in diabetic hearts. Of the several mechanisms being investigated to understand the pathogenesis of diabetic complications, the increased metabolism of glucose via the polyol pathway has received considerable attention. Deviant metabolic regulation due to increased flux through aldose reductase in diabetic hearts may influence the ability of the myocardium to withstand ischemia insult. To determine if aldose reductase inhibition improves tolerance to ischemia, hearts from acute type I diabetic and nondiabetic control rats were isolated and retrograde perfused. Each group was exposed to 1 micromol/l zopolrestat, a specific inhibitor of aldose reductase, for 10 min, followed by 20 min of global ischemia and 60 min of reperfusion in the absence of zopolrestat. Zopolrestat reduced sorbitol levels before ischemia in diabetic hearts. The cytosolic redox state (NADH/NAD+), as measured by lactate-to-pyruvate ratios, was significantly lowered under baseline, ischemic, and reperfusion conditions in diabetic hearts perfused with zopolrestat. In these diabetic hearts, ATP was significantly higher in zopolrestat hearts during ischemia, as were phosphocreatine and left ventricular-developed pressure on reperfusion. Zopolrestat provided similar metabolic and functional benefits in nondiabetic hearts. Creatine kinase release was reduced by approximately 50% in both nondiabetic and diabetic hearts treated with zopolrestat. These data indicate that inhibition of aldose reductase activity preserves high-energy phosphates, maintains a lower cytosolic NADH/NAD+ ratio, and markedly protects both diabetic and nondiabetic hearts during ischemia and reperfusion.
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PMID:Aldose reductase inhibition protects diabetic and nondiabetic rat hearts from ischemic injury. 900 Jul 7

We studied the effect of acute myocardial infarction and late reperfusion on myocardial collagen in a closed chest porcine model, to investigate if any collagen degradation could be detected in blood samples and myocardium. Sixteen 60-80 kg pigs were used with six animals serving as controls and 10 submitted to ischemia-reperfusion. In the ischemia-reperfusion group the left anterior descending coronary artery was occluded for 6 h by inflation of a percutaneous transluminal coronary angioplasty balloon followed by reperfusion for 3 h. Blood samples were taken from the aorta and the coronary sinus and analyzed for creatine kinase and collagen degradation products, i.e. the N-terminal propeptide of procollagen type III (PIIINP) and C-terminal pyridinoline cross-linked telopeptide of collagen type I (ICTP). Myocardial tissue samples were analyzed for content of hydroxyproline, collagen volume fraction and amount of extractable PIIINP/dry weight. Transmission electron microscopy of biopsies was performed to evaluate myocytes and collagen structure outside and within the infarct zone. Creatine kinase showed a statistically significant increase during ischemia and reperfusion but we found no evidence of release of collagen degradation products either during ischemia or reperfusion compared with control. Myocardial content of hydroxyproline, collagen volume fraction and extractable PIIINP/dry weight did not differ between groups. Transmission electron microscopy of biopsies from the infarct zone showed myocyte damage but no visible evidence of collagen degradation when photos were evaluated blindly. In this porcine model of acute myocardial infarction and late reperfusion no release of collagen degradation products from the myocardium or any decrease in or damage to myocardial collagen was detected.
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PMID:Ischemia and reperfusion of the porcine myocardium: effect on collagen. 904 44

Creatine kinase (CK) isoenzymes MM, MB, and BB are located primarily in the cell cytosol, and increased CKMB in plasma is the hallmark of myocardial infarction. However, whether CK is released with reversible ischemic injury remains controversial. Here, we assessed plasma CK activity--cytosolic and mitochondrial CK--in serial samples (every 10 min for 60 min, then hourly or every 4 h for 48 h) from 46 conscious dogs after transient or sustained coronary occlusion. Four dogs were sham-operated (controls); four underwent sustained coronary occlusion (96 h); and 38 underwent transient coronary occlusion (10-40 min) followed by 48 h of reperfusion. In postmortem histological examination of the dogs' hearts by light and electron microscopy, we looked for ischemia or necrosis. The presence of cell swelling and glycogen depletion was indicative of ischemia, whereas the added presence of cell disruption indicated necrosis. Coronary occlusion for > or = 20 min consistently increased plasma mitochondrial and total CK activity and produced histologically evident myocardial necrosis. In contrast, after 10 to 15 min of coronary occlusion, 12 of 14 animals, despite extensive severe reversible ischemia, showed no increase in plasma CK; the remaining 2, which had increased plasma CK, had subendocardial necrosis. Thus, cytosolic or mitochondrial CK is released from the heart only when there has been irreversible myocardial injury-a finding with significant diagnostic and therapeutic implications.
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PMID:Reversible myocardial ischemic injury is not associated with increased creatine kinase activity in plasma. 906 90

The myocardial protective effect of phosphate diester linkage of vitamin E and vitamin C (EPC-K1), a new hydroxyl radical scavenger, was investigated in an isolated working rat heart model. Initially, 0.25-3.0 micrograms/ml of EPC-K1 was given to non-ischemic heart to examine the effect of EPC-K1. Cardiac function did not change until 3.0 micrograms/ml EPC-K1 administration, however percent change of aortic flow prior to treatment (%AF) decreased significantly with 3.0 micrograms/ml and hearts were arrested with 5.0 micrograms/ml. Creatine kinase (CK) leakage did not change until 0.5 microgram/ml, however significantly increased over 1.0 microgram/ml. In the second protocol, EPC-K1 was applied before 15 min of ischemia at 37 degrees C. The %AF recovered significantly with 0.5 and 1.0 microgram/ml (81.2 +/- 3.1% and 75.2 +/- 4.1% vs. 57.2 +/- 3.1% in the control group), but hearts did not start to beat with 2.0 micrograms/ml. CK leakage was suppressed with 0.5 microgram/ml, although not significantly. In the third protocol, 0.5 microgram/ml of EPC-K1, which had the best protective effect before ischemia, was administered during reperfusion after 15 min of ischemia at 37 degrees C. The %AF (64.7 +/- 5.1%) was significantly higher than in the control group (57.2 +/- 3.1%), but was significantly less than in the pre-ischemic EPC-K1 group (81.2 +/- 3.0%). Thus, EPC-K1 had a myocardial protective effect at an appropriate dose, especially when given before ischemia. However, EPC-K1 showed myocardial toxicity at a high dose, therefore use of the correct dose will be important.
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PMID:[Effect of phosphate diester linkage of vitamin E and vitamin C (EPC-K1) on myocardial ischemia reperfusion injury in the isolated working rat heart]. 917 Aug 67

Preconditioning is commonly induced by a brief ischemic insult; myocardial stretch can trigger this protection by an unknown mechanism. Myocardial stretch preconditions the in vivo canine heart; however, the existence of a stretch-induced protection in the rat heart remains unknown. The purpose of this study was to test this myocardial protection induced, in isolated working rat heart, by global ischemia and stretch initiated by a transient increase in the left ventricle (LV). Isolated rat hearts underwent 30 min of global ischemia followed by 30 min of reperfusion. Before this, hearts received a 15-min period of either no intervention (control; C), 5 min of global ischemia + 10 min of reperfusion (preconditioning; PC) or 5 min of stretch + 10 min with no intervention (stretch; S). Stretch was induced by a transient increase in LV preload from 5 to 20 cm H2O. LV work started under a afterload of 80 cm H2O. Control, PC, and S hearts received either no drug (untreated) or staurosporine (50 nM), a protein kinase C inhibitor, before the "preconditioning" period. Creatine kinase (CK) release, ventricular fibrillation during reperfusion, and postischemic recovery of contractile function (aortic flow) were the end points of the study. In the S group, the abrupt increase in preload resulted in a significant increase of aortic flow (42 +/- 2 to 47 +/- 2 ml/min; p < 0.05). During the 30-min reperfusion period, control hearts displayed a poor recovery of contractile functions (8 +/- 3 ml/min, 30 min after reflow, versus 40 +/- 2 ml/min at baseline; p < 0.05). Both untreated PC and S groups exhibited a significant reduction in CK release, incidence of ventricular fibrillation (55% of control hearts developed persistent VF vs. 6% in both the PC and S groups), and postischemic dysfunction during reperfusion (p < 0.05 vs. control). Staurosporine prevented these beneficial effects in PC and S groups. Our study suggests that myocardial protection can be induced by stretch in the isolated working rat heart, likely through activation of protein kinase C. In conclusion, our results show that ischemic preconditioning and stretch had comparable favorable effect on functional recovery after a sustained ischemic insult in the isolated rat heart.
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PMID:Beneficial actions of preconditioning and stretch on postischemic contractile function of isolated working rat heart: effects of staurosporine. 926 46

The detection of elevated cardiac enzyme levels and the occurrence of electrocardiographic (ECG) abnormalities after revascularization procedures have been the subject of recent controversy. This report represents an effort to achieve a consensus among a group of researchers with data on this subject. Creatine kinase (CK) or CK-MB isoenzyme (CK-MB) elevations occur in 5% to 30% of patients after a percutaneous intervention and commonly during coronary artery bypass graft surgery (CABG). Although Q wave formation is rare, other ECG changes are common. The rate of detection is highly dependent on the intensity of enzyme and ECG measurement. Because most events occur without the development of a Q wave, the ECG will not definitively diagnose them; even the ECG criteria for Q wave formation signifying an important clinical event have been variable. At least 10 studies evaluating > 10,000 patients undergoing percutaneous intervention have demonstrated that elevation of CK or CK-MB is associated not only with a higher mortality, but also with a higher risk of subsequent cardiac events and higher cost. Efforts to identify a specific cutoff value below which the prognosis is not impaired have not been successful. Rather, the risk of adverse outcomes increases with any elevation of CK or CK-MB and increases further in proportion to the level of intervention. This information complements similar previous data on CABG. Obtaining preprocedural and postprocedural ECGs and measurement of serial cardiac enzymes after revascularization are recommended. Patients with enzyme levels elevated more than threefold above the upper limit of normal or with ECG changes diagnostic for Q wave myocardial infarction (MI) should be treated as patients with an MI. Patients with more modest elevations should be observed carefully. Clinical trials should ensure systematic evaluation for myocardial necrosis, with attention paid to multivariable analysis of risk factors for poor long-term outcome, to determine the extent to which enzyme elevation is an independent risk factor after considering clinical history, coronary anatomy, left ventricular function and clinical evidence of ischemia. In addition, tracking of enzyme levels in clinical trials is needed to determine whether interventions that reduce periprocedural enzyme elevation also improve mortality.
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PMID:Myonecrosis after revascularization procedures. 946 62

The study was designed to clarify whether captopril, an angiotensin-coverting enzyme inhibitor, will reduce the injury of global ischaemia and reperfusion after cardioplegic arrest in isolated guinea pig hearts, in a modified Langendorff model. The hearts were randomly allocated into four groups (n = 10 in each) and subjected to 90 min of normothermic global ischemia, followed by 30 min of reperfusion; in all groups, cardioplegic arrest was achieved by administering St. Thomas's Hospital cardioplegic solution (STHCS). The first group was utilized as the control group. In the second group, captopril (200 mumol/L) was added to STHCS. In the third group, oral pretreatment was carried out (0.3 mg/kg captopril was given twice a day for 10 days). In the fourth group, oral pretreatment was achieved and captopril-enriched solution was applied in the first 5 min of reperfusion. Although the study groups showed better recovery of contractility than the control group, in the fourth group the hearts had the best left ventricular contractile function, where contractile force (g contractility/g heart weight) was 55.4% +/- 3.8% of the preischameic values. Groups I, II, and III achieved 31.0% +/- 3.2%, 41.6% +/- 3.8%, and 48.3% +/- 3.9% of their preischaemic contractile force values. Creatine kinase leakage was significantly lower and postischaemic coronary flows, too, were significantly higher in the fourth group. Coronary flow after reperfusion increased from 48.5 +/- 6.7 to 65.2 +/- 7.1 ml/min g heart in group 4 (p < 0.05). Myocardial lipid peroxides and glutathione contents showed that there was a correlation between the depletion of myocardial glutathione content and increased lipid peroxidation. These preliminary results showed that: the addition of captopril to reperfusion solution and oral preconditioning improved post-ischameic myocardial function and decreased myocardial injury.
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PMID:Beneficial effect of captopril against ischaemia-reperfusion injury in isolated guinea pig hearts. 958 63

1. The aim of this study was to investigate the effects of enalapril maleate on ischemia-reperfusion injury of the myocardium, after cardioplegic arrest in isolated guinea pig hearts, in a modified Langendorff model. 2. Animals were subjected to 90 min of normothermic global ischemia, followed by 30 min of reperfusion. Cardioplegic arrest was achieved by administering St. Thomas Hospital cardioplegic solution (STHCS). 3. The hearts were randomly allocated into four groups (n=8 in each group). The first group was utilized as control. In the second group, oral pretreatment was made (0.2 mg/kg enalapril maleat was given twice a day for 10 days). In the third group, enalapril maleat (1 micromol/l) was added to STHCS. In the fourth group, hearts were arrested with enalapril maleat-enriched STHCS, and enalapril maleat-enriched (1 micromol/l) Krebs-Henseleit solution was applied during the reperfusion period. 4. Although the study groups showed better recovery of contractility than did the control group, in the last group, the hearts had the best recovery of left ventricular systolic function, where dp/dt maximum was 89.7+/-6.9% of the preischemic values. Group 1, group 2 and group 3 achieved 44.2+/-4.5%, 79.4+/-5.8% and 68.1+/-6.7% of their preischemic dp/dt values. A similar observation was found for left ventricular developed pressure (LVDP); LVDP values were 52.4+/-2.1% (in group 1), 79.6+/-2.8% (in group 2), 72.8+/-4.6% (in group 3) and 86.7+/-5.8% (in group 4) of control after reperfusion. Creatine kinase leakage was significantly lower and postischemic coronary flows were significantly higher in group 4. 5. We concluded that usage of enalapril maleat in the reperfusion period was more effective for improving myocardial recovery after cardioplegic arrest. The additional protective effects of enalapril maleat not only were by angiotensin-converting-enzyme-inhibition-dependent coronary vasodilation and thiol-dependent limitation of oxidative injury, but could also be related to an oxygen-free-radical-scavenging effect.
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PMID:Attenuation of ischemia--reperfusion injury by enalapril maleat. 968 60

Creatine kinase reaction rates were measured by magnetisation transfer technique in the brain of healthy adult and aged rats and in the rats with mild or severe chronic cerebral ischemia. These measurements indicated that the rate constant of the creatine kinase reaction is significantly reduced in the case of chronic brain ischemia in aged rats. In contrast, occlusion of both carotid arteries in adult rats produced a slight increase in the reaction rate 4 weeks after occlusion. At the same time, corresponding conventional phosphorus magnetic resonance spectra showed negligible changes in signal intensities.
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PMID:Creatine kinase reaction rates in rat brain during chronic ischemia. 1005 Sep 42


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