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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The known benefits of hypothermic pharmacological cardioplegia in protecting the ischemic adult heart may not extend to children. Protection of the ischemic immature rabbit heart with hypothermic Krebs-Henseleit bicarbonate buffer is better than with hypothermic St. Thomas' II cardioplegic solution. We investigated whether the availability of oxygen in the preischemic perfusate is responsible for the increased tolerance to ischemia of immature (7- to 10-day-old) hearts perfused with Krebs buffer in comparison with St. Thomas' II solution immediately before ischemia. After obtaining preischemic control data in the "working" mode, we perfused hearts (n = 8 per group) for 3 minutes with hypothermic (14 degrees C) Krebs buffer or hypothermic St. Thomas' II solution saturated with 0%, 25%, or 95% oxygen. This was followed by 2 hours of global ischemia at 14 degrees C. Hearts were reperfused for 15 minutes in the Langendorff mode and 35 minutes in the working mode, and recovery of function was measured. For preischemic oxygen concentrations of 0%, 25%, and 95%, recovery of aortic flow in hearts protected by hypothermia alone during ischemia was 74% +/- 9%, 82% +/- 4%, and 99% +/- 2% of preischemic values, respectively. In hearts protected by hypothermia plus cardioplegia, the values were 69% +/- 6%, 72% +/- 3%, and 86% +/- 5%, respectively. Thus, at equal oxygen concentrations, recovery of postischemic function was better in hearts protected by hypothermia alone compared with hypothermia plus cardioplegia. We conclude that factors other than oxygen availability are responsible for the damaging effect of St. Thomas' II solution on the ischemic immature rabbit heart.
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PMID:Cardioplegia-induced damage to ischemic immature myocardium is independent of oxygen availability. 224 86

It has been suggested that oxygen-derived free radicals may contribute to the myocardial injury associated with ischemia and reperfusion. As the presence of enhanced free radical generation is a prerequisite for such damage, several techniques have been used to provide evidence of increased oxygen free radical production during reperfusion; however, all such techniques have substantial limitations. In this study, we used enhanced chemiluminescence to evaluate oxygen free radical generation during ischemia and reperfusion in the isolated Langendorff-perfused rat heart. The chemiluminescent technique, which has high sensitivity and can monitor radical generation continuously, avoids some of the limitations of earlier methods. Chemiluminescence (expressed as counts per second) decreased from 219 +/- 11 at baseline to 142 +/- 9 during ischemia and markedly increased to a peak of 476 +/- 36 during the first 3-5 minutes of reperfusion. This was followed by a slow decline over 11-16 minutes to a steady-state level of 253 +/- 14 (each sequential change in chemiluminescence was highly significant; p less than 0.001). Superoxide dismutase (2,000 units/min) significantly decreased peak reperfusion chemiluminescence to 316 +/- 17 (p less than 0.01). Hearts subjected to a second period of ischemia and reperfusion had a higher peak chemiluminescence (626 +/- 62), which also was significantly attenuated by 1,000 units/min superoxide dismutase (398 +/- 16; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced chemiluminescence as a measure of oxygen-derived free radical generation during ischemia and reperfusion. 224 5

Effects of diltiazem upon mitochondrial ultrastructure and distribution of calcium were studied following ischemia (27 minutes) and reperfusion (30 minutes). Hearts receiving no drug recovered low contractile function, while mitochondria nearly doubled in cross-sectional area (0.98 vs 0.56 micron 2) and were structurally damaged (1.88 vs 0.17 score). Mitochondria contained fine calcium deposits (0.029-micron diam) in mildly damaged cells, larger deposits in moderately damaged cells, and a large deposit (0.17-0.29-micron diam) in severely injured cells. Glycocalyx Ca2+ stain, observed in nonischemic hearts, was reduced in moderately and severely damaged cells. Increased mitochondrial Ca2+ may be associated with loss of glycocalyx Ca2+. Diltiazem (7.5 microns), added before ischemia, improved recovery of contractile function and prevented mitochondrial swelling, structural grade change, and increase in mitochondrial Ca2+. Reduction in mitochondrial Ca2+ stain by diltiazem was associated with the maintenance of normal glycocalyx Ca2+.
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PMID:Shifts in calcium in ischemic and reperfused rat hearts: a cytochemical and morphometric study of the effects of diltiazem. 226 88

Alterations in energy substrate utilization during reperfusion of ischemic hearts can influence the functional recovery of the myocardium. Energy substrate preference by the reperfused myocardium, however, has received limited attention. Therefore, we measured oxidation rates of glucose and palmitate during reperfusion of ischemic hearts. Isolated working rat hearts were perfused with 1.2 mM palmitate and 11 mM [14C]glucose, 1.2 mM [14C]palmitate and 11 mM glucose, or 11 mM [14C]glucose alone, at an 11.5 mm Hg preload and 80 mm Hg afterload. Hearts were subjected to 60-minute aerobic perfusion or 25-minute global ischemia followed by 60-minute aerobic reperfusion. Steady-state oxidative rates of glucose or palmitate were determined by measuring 14CO2 production. In hearts perfused with glucose alone, oxidative rates during reperfusion were not significantly different than nonischemic hearts (1,008 +/- 335 vs. 1,372 +/- 117 nmol [14C]glucose oxidized/min/g dry wt, respectively). In the presence of palmitate, glucose oxidation was markedly reduced in reperfused and nonischemic hearts (81 +/- 11 and 101 +/- 15 nmol [14C]glucose oxidized/min/g dry wt, respectively). Palmitate oxidation rates were not significantly different in reperfused compared with nonischemic hearts (369 +/- 55 and 455 +/- 50 nmol [14C]palmitate oxidized/min/g dry wt, respectively). [14C]Palmitate was incorporated into myocardial triglycerides to a greater extent in reperfused ischemic hearts than in nonischemic hearts (26.0 and 13.8 mumol/g dry wt, respectively). Under the perfusion conditions used, palmitate provided over 90% of the ATP produced from exogenous substrates. Addition of the carnitine palmitoyltransferase I inhibitor, ethyl 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir, 10(-6) M), during reperfusion stimulated glucose oxidation and improved mechanical recovery of ischemic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. 229 17

There are conflicting reports of the detrimental or beneficial effects of hypothermic cardioplegia in the immature heart. We therefore investigated the temperature-dependence of myocardial protection and the ability of single-dose and multidose infusions of cardioplegic solution to protect the immature heart during hypothermic ischemia. Isolated, working hearts (n = 6 per group) from neonatal rabbits (aged 7 to 10 days) were perfused aerobically (37.0 degrees C) for 20 minutes before infusion (2 minutes) with either perfusion fluid (noncardioplegia control) or St. Thomas' Hospital cardioplegic solution and ischemic arrest (for 4, 6, and 18 hours) at various temperatures between 10.0 degrees and 30.0 degrees C. Hearts arrested with cardioplegic solution received either one preischemic infusion only (single-dose cardioplegia) or repeated infusions at intervals of 60 or 180 minutes (multidose cardioplegia). Ischemic arrest with single-dose cardioplegia for 4 hours at 10.0 degrees, 20.0 degrees, 22.5 degrees, 25.0 degrees, 27.5 degrees, and 30.0 degrees C resulted in 96.0% +/- 4.3%, 96.6 +/- 2.5%, 87.0% +/- 3.8%, 71.8% +/- 10.0% (p less than 0.05 versus 10.0 degrees C group), 35.1% +/- 10.3% (p less than 0.01 versus 10.0 degrees C group), and 3.0% +/- 1.9% (p less than 0.04 versus 10.0 degrees C group) recovery of preischemic cardiac output, respectively. With 6 hours of ischemia at 20.0 degrees C, single-dose cardioplegia significantly (p less than 0.01) increased the recovery of cardiac output from 20.9% +/- 13.1% (control) to 76.4% +/- 4.4%, whereas multidose cardioplegia (infusion every 60 minutes) further increased recovery to 97.8% +/- 3.8% (p less than 0.01 versus control and single-dose cardioplegia). In contrast, after 6 hours of ischemia at 10.0 degrees C, cardiac output recovered to 93.4% +/- 1.2% (control) and 92.3% +/- 3.1% (single-dose cardioplegia), whereas multidose cardioplegia reduced recovery to 76.9% +/- 2.2% (p less than 0.01 versus both groups). This effect was confirmed after 18 hours of ischemia at 10.0 degrees C; single-dose cardioplegia significantly increased the recovery of cardiac output from 24.5% +/- 10.9% (control) to 62.9% +/- 13.3% (p less than 0.05), whereas multidose cardioplegia reduced recovery to 0.8% +/- 0.4% (p less than 0.01 versus single-dose cardioplegia) and elevated coronary vascular resistance from 8.90 +/- 0.56 mm Hg.min/ml (control) to 47.83 +/- 9.85 mm Hg.min/ml (p less than 0.01). This effect was not reduced by lowering the infusion frequency (from every 60 to every 180 minutes).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protection of the immature heart. Temperature-dependent beneficial or detrimental effects of multidose crystalloid cardioplegia in the neonatal rabbit heart. 229 64

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children, resulting in poor postischemic recovery of function and increased mortality. The relative susceptibilities to ischemia modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused neonatal (3- to 4-day-old) rabbit and pig hearts. Hearts were perfused aerobically with Krebs buffer solution in the working mode for 30 minutes and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2 followed by hypothermic (14 degrees C) global ischemia (rabbits 2, 4, and 6 hours; pigs 2 and 4 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic aortic flow was measured. Hypothermia alone provided excellent protection of the ischemic neonatal rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 91% +/- 4% and 87% +/- 5% (mean +/- standard deviation) of its preischemic value. Recovery after 6 hours of ischemia was depressed to 58% +/- 9% of its preischemic value. Ischemic neonatal pig hearts protected with hypothermia alone recovered 94% +/- 3% of preischemic aortic flow after 2 hours; none was able to generate flow after 4 hours. St. Thomas' Hospital solution No. 2 decreased postischemic aortic flow after 4 hours of ischemia in rabbit hearts from 87% +/- 5% to 70% +/- 7% (p less than 0.05, hypothermia alone versus hypothermia plus cardioplegia) but improved postischemic recovery of aortic flow in pig hearts after 4 hours of ischemia from 0 to 73% +/- 13% (p less than 0.0001, hypothermia alone versus hypothermia plus cardioplegia). This effect was dose related in both species. We conclude that the neonatal pig heart is more susceptible to ischemia modified by hypothermia alone than the neonatal rabbit and that St. Thomas' Hospital solution No. 2 improves postischemic recovery of function in the neonatal pig but decreases it in the neonatal rabbit. This species-dependent protection of the neonatal heart may be related to differences in the extent of myocardial maturity at the time of study.
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PMID:Is protection of ischemic neonatal myocardium by cardioplegia species dependent? 229 65

We have shown previously that preconditioning myocardium with four 5-minute episodes of ischemia and reperfusion dramatically limited the size of infarcts caused by a subsequent 40-minute episode of sustained ischemia. The current study was undertaken to assess whether the same preconditioning protocol slowed the loss of high energy phosphates, limited catabolite accumulation, and/or delayed ultrastructural damage during a sustained ischemic episode. Myocardial metabolites and ultrastructure in the severely ischemic subendocardial regions were compared between control and preconditioned canine hearts. Hearts (four to 10 per group) were excised after 0, 5, 10, 20, or 40 minutes of sustained ischemia. All groups had comparable collateral blood flow. Preconditioned hearts developed ultrastructural injury more slowly than controls; evidence of irreversible injury was observed after 20 minutes in controls but not until 40 minutes in preconditioned hearts. Furthermore, after 40 minutes of ischemia, irreversible injury was homogeneous in controls but only focal in preconditioned myocardium. Preconditioning reduced starting levels of ATP by 29%. Nevertheless, it also slowed the rate of ATP depletion during the episode of sustained ischemia, so that after 10 minutes of ischemia, preconditioned hearts had more ATP than controls. However, after 40 minutes, ATP contents were not significantly different between groups. Preservation of ATP resulted from reduced ATP utilization and was not due to increased ATP production. Accumulation of purine nucleosides and bases (products of adenine nucleotide degradation) was limited in preconditioned myocardium. Accumulation of glucose-1-phosphate, glucose-6-phosphate, and lactate also was reduced markedly by preconditioning, due to reduced rates of glycogen breakdown and and anaerobic glycolysis. We propose that preconditioning reduces myocardial energy demand during ischemia, which results in a reduced rate of high energy phosphate utilization and a reduced rate of anaerobic glycolysis. Either preservation of ATP or reduction of the cellular load of catabolites may be responsible for delaying ischemic cell death.
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PMID:Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. 231 95

To determine whether venting the left ventricle during coronary reperfusion limits myocardial infarct size, we studied paced (200 beats/min) Langendorff rabbit hearts, perfused with blood from a support rabbit. A left coronary artery was occluded for 60 minutes, followed by 2 hours of reperfusion. Four experimental conditions, as follows, were used: In group 1 (control), the hearts contracted isovolumetrically on a fluid-filled balloon in the left ventricle during both occlusion and reperfusion. In group 2, the balloon was present only during occlusion, and the heart was vented during reperfusion. Hearts in group 3 were vented during occlusion and developed pressure during reperfusion. In group 4, the left ventricle was vented during occlusion and reperfusion. Perfusion pressure (91.2 +/- 0.9 mm Hg) and coronary flow (0.88 +/- 0.03 ml/min/g) were not different between groups. Left ventricular pressures (mean of all groups) were 87.3 +/- 1.5 mm Hg systolic and 6.5 +/- 0.6 mm Hg diastolic. Infarcted myocardium was assessed by triphenyl tetrazolium staining and expressed as a percentage of the area at risk, as measured by fluorescent particles. Venting during both ischemia and reperfusion (n = 10) did result in significantly smaller infarcts than in the unvented controls (n = 10), that is, 13 +/- 5% vs. 41 +/- 6%, respectively. Venting only during reperfusion (n = 10) or occlusion (n = 11) did not significantly limit infarct size (57 +/- 6% and 32 +/- 5%, respectively), as compared with controls. Thus, the clinically feasible intervention of left ventricular venting during reperfusion was not cardioprotective.
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PMID:Left ventricular unloading during reperfusion does not limit myocardial infarct size. 240 Oct 87

Considerable evidence suggests that free radicals engendered by redox-active metals, particularly iron and copper, are causative agents in reperfusion injury following ischemia. This study demonstrates that perfusion of the isolated rat heart with a buffer containing zinc, a non-redox active metal similar to copper in its coordination chemistry, inhibits the development of ventricular arrhythmias during reperfusion. Zinc was employed as the bishistidine complex, Zn--His2, to maintain solubility and permeability. Zn--His2 exerted an antiarrhythmic activity as hearts spent a longer time in normal sinus rhythm and a shorter time in ventricular fibrillation during reperfusion following 10 min of regional ischemia. However, Zn--His2 also produced a negative inotropic and chronotropic effect, evident during equilibration and ischemia. In the course of experiments which began in Israel and continued in the U.S. it was necessary to use two different sources of rats. Hearts from the two sources manifested different sensitivities to the concentrations of Zn--His2, although their physiological effects were similar. Differential activity responses were noted for antiarrhythmic activity, negative inotropic and chronotropic properties, and toxicity. In both groups of untreated hearts the incidence of ventricular fibrillation after ischemia was 100%. Ventricular fibrillation was reduced to 17% at 37.5 microM Zn--His2 in the U.S.-bred rat hearts and to 9% at 200 microM Zn--His2 in those from Israel. These changes in Zn--His2 treated animals were accompanied by a decrease in lactate dehydrogenase release from the myocardium during reperfusion. None of the protective effects was due to histidine alone. These results indicate that zinc prevents ventricular arrhythmias during reperfusion following regional ischemia and may prevent membrane damage, possibly, by reduction of free radical formation.
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PMID:The effect of zinc on reperfusion arrhythmias in the isolated perfused rat heart. 232 82

The purpose of this study was to determine if the cardioprotective effect of adenosine on the ischemic myocardium is mediated by interaction with specific adenosine receptor subtypes. Isolated rat hearts perfused at constant flow were subjected to global normothermic (37 degrees C) ischemia and the time to onset of ischemic contracture (TOIC) was used as a marker of myocardial ischemic injury. Hearts treated with adenosine and R-phenylisopropyladenosine (PIA), an adenosine A1 receptor agonist, exhibited a significantly greater TOIC than control hearts (18.60 +/- 0.40 and 16.64 +/- 1.15 min, respectively vs 9.12 +/- 0.66 min), whereas phenylaminoadenosine, an adenosine A2 receptor agonist, had no effect on TOIC (11.73 +/- 0.87 min). BW A1433U, an adenosine receptor antagonist, blocked the effects of adenosine and PIA on ischemic contracture time, and BW A1433U did not alter the ability of nifedipine or propranolol to delay the onset of ischemic contracture, thus indicating the specificity of this compound for the adenosine receptor. PIA-treated hearts exhibited significantly greater ATP levels throughout the ischemic period compared to control hearts, whereas hearts treated with BW A1433U showed a rapid decline in ATP content. These results suggest that the beneficial effects of adenosine on the ischemic myocardium are mediated by interaction with adenosine A1 receptors, and that endogenously formed adenosine plays a role in attenuating myocardial ischemic damage.
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PMID:Adenosine A1 receptor mediated protection of the globally ischemic isolated rat heart. 232 32


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