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)

The interstitial transudate was investigated in isolated perfused rat hearts. Capillary permeability and the kinetics of interstitial uptake and release were characterized using four different marker molecules (mol wt 522 to 2 X 10(6)). The half-time (t1/2) values (less than 30 to 170 s) and the interstitial concentration after 30 min (100-44% of arterial concentration) reflected the order and inverse order of their molecular weights, respectively. Creatine kinase (CK) and glutathione (GSH) were measured during control state, hypoxia, and anoxia, followed by reoxygenation. Interstitial concentrations of CK and GSH were higher by a factor of 100 and 8, respectively, compared with the venous effluent. During hypoxia (PO2 = 110 mmHg, i.e., O2 supply = 30% of demand) and reoxygenation there was a significant increase only in the interstitial (not venous) release of CK and GSH, which was further increased during anoxia. Ischemia (75 min) and reperfusion cause no interstitial release of lysosomal (acid phosphatase) and mitochondrial (glutamate dehydrogenase) enzymes despite a massive loss of cytosolic enzymes. Examination of the interstitial transudate allows characterization of capillary transfer and provides a very sensitive measure of sarcolemmal release phenomena.
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PMID:Intra- and extracellular markers in interstitial transudate of perfused rat hearts. 245 35

Reperfusion of ischemic myocardium is associated with phospholipid degradation and corresponding changes in membrane fluidity. Dexamethasone (1.25 mg/kg i.v.) was evaluated in the pig, with pretreatment of the animal 1 1/2 hours before ischemic insult. The isolated perfused in vivo pig heart model was subjected to 60 minutes of regional ischemia of the left anterior descending coronary artery. The ischemic heart was then subjected to 60 minutes of global hypothermic cardioplegic arrest followed by 60 minutes of reperfusion, including reperfusion of the ischemic left anterior descending coronary artery region. Phospholipase A2, arachidonic acid, total free fatty acids, myocardial microviscosity, coronary blood flow, myocardial oxygen consumption, creatine kinase release, and regional and global myocardial function were measured. Dexamethasone pretreatment resulted in dramatic inhibition of phospholipase A2 activity accompanied by a reduction in arachidonic acid and total free fatty acid levels. Myocardial microviscosity (the inverse of membrane fluidity) was significantly increased only in untreated animals. Coronary blood flow and myocardial oxygen consumption were maintained at preischemic levels only in the dexamethasone-treated animals and were significantly reduced in the control group. Creatine kinase release increased nearly six times in control animals only while remaining stable in the dexamethasone-treated group, and regional and global myocardial contractility and compliance were improved dramatically in the dexamethasone-treated animals. These results indicate that dexamethasone enhances myocardial function by preserving membrane structure through inhibition of phospholipase activation, thereby preventing phospholipid degradation and maintaining membrane integrity and fluidity.
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PMID:Steroid-induced myocardial preservation is associated with decreased cell membrane microviscosity. 250 6

At present, many investigations of myocardial function following ischemic insults concentrate on the modalities of reperfusion rather than on the mode of preservation. In this study, we tried to define the effect of reperfusion using warm blood cardioplegia (WBC) after medium-term (3 h) cold global ischemia, as required in cardiac transplantation. Twenty-one porcine hearts were harvested after preservation with cold cardioplegia (St. Thomas Hospital solution) and topical cooling. Normothermic reperfusion with blood was initiated after 3 h of ischemia utilizing a special extracorporeal pump circuit. Twelve hearts served as controls (group A), while substrate-enriched WBC was applied during the initial 20 min of reperfusion in nine hearts (group B). Hearts in both groups were then studied for myocardial function and metabolism under both working and nonworking conditions for a maximum of 180 min. In the nonworking mode, left ventricular dp/dt was significantly higher in group B than in group A at 15 min (2201 +/- 785 mm Hg/sec vs 1515 +/- 732 mm Hg/sec) and at 180 min (1730 +/- 471 mm Hg/sec vs 836 +/- 147 mm Hg/sec; P less than 0.05). After 3 h, lactate production was significantly higher in group A (371 +/- 45 mg/dl) than in group B (108 +/- 44 mg/dl; P less than 0.05). Creatine kinase release into the coronary sinus was also significantly elevated in group A at 15 min (2807 +/- 1478 IU/l vs 1148 +/- 1272 IU/l; P less than 0.05). Similarly, the hemodynamic data obtained under working conditions in group B were superior to those in group A.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of controlled reperfusion in porcine hearts submitted to three hours of cold global ischemia. 278 68

The objective of this study was to evaluate different approaches to the diagnosis of post-operative myocardial infarction. A total of 232 patients, mostly hypertensive and/or diabetic patients, who were undergoing elective non-cardiac surgery were evaluated pre-operatively. They were followed serially from the day of operation to discharge or the sixth post-operative day with daily clinical evaluations, electrocardiograms, creatine kinase and creatine kinase isoenzymes. In total 22% (51/232) of the patients had post-operative ECG changes in two or more leads. Only 1% developed new Q waves; most of the changes involved changes in the T or ST segments. Seventy percent of patients who had changes in their electrocardiogram were completely asymptomatic. The highest risk of ECG changes or symptoms occurred on the day of operation and the first post-operative day; evidence of post-operative infarction was infrequent after the second post-operative day. Creatine kinase levels rose an average of 250-300 IU on the first and second post-operative day (also the peak time for post-operative ECG changes), reducing its utility as an adjunct to the diagnosis of post-operative infarctions. Importantly, 52% (12/23) of the patients who had greater than or equal to 5% MB isoenzyme had neither ECG changes nor symptoms; the diagnosis of a myocardial infarction should not be made in these patients. In summary, most patients who experience ischemia or infarction post-operatively are asymptomatic. Symptoms should not be required for the diagnosis of post-operative infarction. Seemingly minor differences in criteria can produce major discrepancies in post-operative myocardial infarction rates (from 1 to 9%). The development of a final set of criteria will require further study but the diagnosis of post-operative infarction should probably be based on ECG changes, their duration and consistency, and the association of a positive MB fraction.
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PMID:The post-operative electrocardiogram and creatine kinase: implications for diagnosis of myocardial infarction after non-cardiac surgery. 291 84

The effects of the converting enzyme inhibitor captopril on the susceptibility of the heart to ventricular arrhythmias following ischemia, both in vitro and in vivo, were studied. In isolated rat hearts, captopril, administered either before or at the end of ischemia, reduced ventricular fibrillation upon reperfusion after 15 minutes of local ischemia. Reduction of purine overflow, improvement in contractility, and increase in coronary blood flow occurred concomitantly. In vivo, a closed-chest pig model was used to determine the effects of captopril, administered at the end of ischemia and continued orally, on the susceptibility to ventricular arrhythmias during the chronic phase of myocardial infarction. Myocardial ischemia was induced by 60-minute inflation of a balloon catheter in the left anterior descending coronary artery. Upon reperfusion, an accelerated idioventricular rhythm occurred, both in 10 untreated and in 10 captopril-treated animals. Creatine kinase levels during the reperfusion period were significantly lower after captopril treatment. Two weeks after the short-term experiments, monomorphic ventricular tachycardia could be induced with programmed electrical stimulation in six of eight surviving untreated pigs. In contrast, in none of the six surviving captopril-treated animals was ventricular tachycardia inducible. Thus, early intervention with captopril during the development phase of myocardial infarction may have beneficial effects on the subsequent development of ventricular arrhythmias. Salvage of ischemic myocardium, improvement in ventricular function, beneficial effects on coronary flow, and decreased activity of the sympathetic nervous system may all contribute.
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PMID:Protective effects of captopril against ischemia/reperfusion-induced ventricular arrhythmias in vitro and in vivo. 306 1

There is often a large difference between volumes of crystalloid cardioplegic solution used clinically (2 to 4 ml/gm myocardium) and experimentally (in rat heart preparations, volumes of 30 ml/gm or more are used). In an attempt to reconcile these differences and define the minimum volume and/or duration of infusion of the St. Thomas' Hospital cardioplegic solution consistent with maximal myocardial protection, we have used the isolated working rat heart to characterize the relationships between myocardial protection and (1) the duration of cardioplegic infusion and (2) the volume of cardioplegic infusion. Hearts (n = 6 per group, weighing 0.90 +/- 0.06 gm) were subjected to 0, 5, 10, 15, 30, 45, 60, 120, 180, 240, or 300 seconds of cardioplegic infusion (mean infusion volumes = 0, 1.3 +/- 0.1, 2.0 +/- 0.1, 2.8 +/- 0.2, 5.0 +/- 0.1, 8.3 +/- 0.2, 10.5 +/- 0.8, 21.8 +/- 2.1, 22.7 +/- 1.3, 32.3 +/- 2.1, and 39.1 +/- 1.8 ml per heart, respectively) before 30 minutes of normothermic ischemia. They recovered 3.9% +/- 2.3%, 9.7% +/- 5.0%, 22.8% +/- 5.8%, 34.6% +/- 4.6%, 54.7% +/- 6.6%, 64.0% +/- 5.0%, 67.4% +/- 4.0%, 56.6% +/- 11.1%, 60.0% +/- 5.8%, 51.6% +/- 7.0%, and 68.0% +/- 7.8% of their preischemic cardiac output on reperfusion. Creatine kinase leakage, tissue adenosine triphosphate and creatine phosphate content, and other indices of cardiac function supported this observation. To assess volume of infusion rather than duration, we infused hearts (n = 6 per group) with 1.0, 1.5, or 2.0 ml of cardioplegic solution over 120 seconds. Although recovery of cardiac output with 2.0 ml (56.2% +/- 6.8%) was not significantly different from that (56.6% +/- 11.1%) observed with large volumes of solution (21.9 +/- 2.1 ml), infusion of 1.5 and 1.0 ml resulted in poor recovery of cardiac output (40.1% +/- 4.6% and 21.8% +/- 3.9%, respectively). To assess duration (with low volumes) rather than volume of infusion, we infused hearts (n = 6 per group) with 2.0 ml of cardioplegic solution over 10, 30, 60, or 120 seconds. Maximal protection was observed with 30, 60, and 120 seconds of infusion (recovery of cardiac output = 56.7% +/- 5.9%, 45.1% +/- 7.9%, and 56.2% +/- 6.8%, respectively). Our results suggest that, for maximum myocardial protection, the St. Thomas' Hospital solution should be infused at a rate of not less than 2.0 ml/gm wet weight of heart and that the duration of infusion should be not less than 30 seconds.
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PMID:Optimal myocardial protection during crystalloid cardioplegia. Interrelationship between volume and duration of infusion. 253 Apr 4

The effect of oxygenation (100% oxygen) of the St. Thomas' Hospital cardioplegic solutions No. 1 (MacCarthy) and No.2 (Plegisol, Abbott Laboratories, North Chicago, Ill.) was examined in the isolated working rat heart subjected to long periods (3 hours for studies with solution No. 1 and 4 hours for studies with solution No. 2) of hypothermic (20 degrees C) ischemic arrest with multidose (every 30 minutes) cardioplegic infusion. At the aortic infusion point the oxygen tension of the oxygenated solutions (measured at 20 degrees C) was in the range of 320 to 560 mm Hg whereas that of the nonoxygenated solutions was less than 150 mm Hg. Twenty hearts (10 oxygenated and 10 nonoxygenated) were studied for each solution. The studies with solution No. 1 demonstrated that oxygenation led to a significant (p less than 0.05) reduction in the incidence of persistent ventricular fibrillation during postischemic reperfusion. Oxygenation of the cardioplegic solution also improved postischemic functional recovery so that the recovery of aortic flow was improved from 18.7% +/- 8.9% (of its preischemic control level) in the nonoxygenated group to 54.6% +/- 6.6% in the oxygenated group (p less than 0.025). Creatine kinase leakage was also significantly reduced from 27.5 +/- 4.8 to 9.9 +/- 0.6 IU/15 min/gm dry weight (p less than 0.005). Studies with solution No. 2 indicated that protection was better than with solution No. 1, even in the absence of oxygenation. A better degree of functional recovery was obtained after 4 hours of arrest with solution No. 2 than that obtained after only 3 hours of arrest with solution No. 1, and persistent ventricular ventricular fibrillation was never observed with solution No. 2. However, despite the superior performance with solution No. 2, further improvements could be obtained by oxygenation, with that time from the onset of reperfusion to the return of regular sinus rhythm being reduced from 55 +/- 8 to 35 +/- 2 seconds (p less than 0.01), postischemic recovery of aortic flow increasing from 59.8% +/- 7.4% to 85.7% +/- 2.5% (p less than 0.005), and creatine kinase leakage being reduced from 38.1 +/- 7.3 to 16.2 +/- 1.5 IU/15 min/gm dry weight (p less than 0.005). It is concluded that oxygenation of the St. Thomas' Hospital cardioplegic solutions improves their ability to protect the heart against long periods of ischemia and that this is manifested by improved postischemic electrical stability, functional recovery, and reduced creatine kinase leakage.
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PMID:Improved myocardial protection by oxygenation of St. Thomas' Hospital cardioplegic solutions. Studies in the rat. 333 23

Oxygen-derived free radicals and intracellular calcium overload have been implicated as mediators of myocardial ischemia/reperfusion injury. We hypothesized that free radical scavengers or calcium channel blockers could enhance the protection afforded the isolated, working rat heart by crystalloid cardioplegia against this type of injury at 37 degrees C. Hearts from 42 male rats in seven groups (n = 6) were studied in an isolated, working heart preparation measuring aortic flow (ml/min/gm dry wt), peak systolic pressure (mm Hg), coronary artery flow (ml/min/gm dry wt), and calculated coronary vascular resistance (dyne.sec.cm-5/gm dry wt). Creatine kinase and lactate dehydrogenase release were measured before ischemia and at various times during the postischemic reperfusion period. Time-matched control hearts (group 1) were perfused for 2 hours. After finding that 30 minutes of ischemia and 10 minutes of reperfusion (group 2) produced significant (p less than 0.01) functional impairment that was completely protected (group 3) by a preischemic bolus of St. Thomas' Hospital cardioplegic solution, we again found significant (p less than 0.01) functional impairment after 40 minutes of ischemia and 10 minutes (group 4) or 20 minutes (group 5) of reperfusion despite a preischemic bolus of St. Thomas' Hospital cardioplegic solution. Diltiazem (10 mg/L) plus St. Thomas' Hospital cardioplegic solution (group 6) did not significantly (p less than 0.01) enhance functional recovery. Addition of superoxide dismutase plus catalase (200 microns/ml) (group 7) produced marked improvement in functional recovery that did not differ significantly (p less than 0.01) from control results (group 1). The creatine kinase and lactate dehydrogenase data strongly supported the preceding functional data. Coronary flow and vascular resistance were not significantly (p less than 0.01) changed from control values in any group. We conclude that the addition of superoxide dismutase and catalase but not diltiazem to St. Thomas' Hospital cardioplegic solution can significantly enhance myocardial protection against normothermic ischemia/reperfusion injury. This implicates oxygen-derived free radicals as mediators of this type of injury.
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PMID:Enhancement of crystalloid cardioplegic protection against global normothermic ischemia by superoxide dismutase plus catalase but not diltiazem in the isolated, working rat heart. 336 28

We evaluated the efficacy of intracoronary administration of verapamil hydrochloride in reducing myocardial injury during acute ischemia and reperfusion. Ischemia was induced by 30% and 45% reductions of circumflex arterial blood flow for successive 2-hour periods. A reperfusion period (1 hour and 45 minutes) followed ischemia upon deflation of a pneumatic occluder. Verapamil (30 micrograms/kg) was slowly injected into the circumflex artery as a bolus 15 minutes after each blood flow reduction step. To prevent verapamil-induced decreases in heart rate, ventricular pacing was established at 170 beats/min before a baseline period and maintained throughout the protocol. Creatine kinase activities (international units per milligram protein) measured in samples obtained from posterior papillary muscles were 15 +/- 1 (mean +/- SEM) and 10 +/- 2 for animals receiving verapamil or its saline vehicle, respectively (p less than 0.05). Quantitative morphometry was performed on left ventricular myocardium after staining with p-nitro blue tetrazolium. Intracoronary administration of verapamil reduced the extent of left ventricular infarction, as disclosed by positive tetrazolium staining of the tissue, from 34 +/- 4% of the left ventricle in vehicle-treated animals to 21 +/- 4% of the left ventricle in verapamil-treated animals (p less than 0.05). We conclude that intracoronary administration of verapamil reduced the extent of myocardial infarction acutely, independent of increases in blood flow through the circumflex coronary artery or decreases in heart rate. Administration of verapamil was not associated with decreases in ventricular afterload, the pressure-rate index, cardiac output, or the maximum rate of pressure development in the left ventricle. Verapamil treatment of animals subjected to ischemia was not associated with sustained elevations of left atrial pressure to values above those measured in animals receiving the vehicle.
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PMID:Effects of intracoronary verapamil administration in a sheep model of acute myocardial ischemia and reperfusion. 338 62

In cells, hyperthermia induces synthesis of heat-shock proteins and the acquisition of thermotolerance. Thermotolerant cells are resistant to subsequent oxidative stress. In this study, heat-shocked hearts were examined for evidence of protection during ischemia and reperfusion. Rats were exposed to 15 minutes of 42 degrees C hyperthermia. Twenty-four hours later their hearts were isolated and perfused and the contractility examined during and after ischemic perfusion. No protection was observed during ischemic perfusion. However, upon reperfusion heat-shocked hearts had recovery of contractility within 5 minutes of reperfusion, while control hearts showed no contractility at this time. Throughout 30 minutes of reperfusion heat-shocked hearts had significantly improved recovery of contractile force, rate of contraction and rate of relaxation. Creatine kinase release, associated with reperfusion injury, was significantly reduced from a high of 386.8 +/- 78.9 mU/min/g heart wt for controls to 123.7 +/- 82.9 mU/min/g heart wt for heat-shocked hearts at 5 minutes of reperfusion. Following 30 minutes of reperfusion, ultrastructural examination revealed less damage of mitochondrial membranes in the heat-shocked hearts. Further biochemical investigations revealed that the antioxidative enzyme, catalase, was significantly increased to 137 +/- 12.7 U/mg protein in the heat-shocked hearts while the control value was 64.8 +/- 8.3 U/mg protein. Hyperthermic treatment, which induces the heat-shock response, may be therapeutic for salvaging ischemic myocardium during reperfusion, through a mechanism involving increased levels of myocardial catalase.
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PMID:Heat-shock response is associated with enhanced postischemic ventricular recovery. 340 86


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