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 effect of diltiazem on the development of infarcts was investigated in porcine hearts. The left anterior descending coronary artery was occluded in each of 32 anesthetized pigs for 75 min and was reperfused for 4 hr. Diltiazem (15 micrograms/kg X min) was infused in 11 pigs for 30 min before occlusion (therapy A) and in another eight pigs before reperfusion (therapy B). Eleven pigs served as controls. Tissue concentrations of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD) were determined in transmural needle biopsy samples taken from the ischemic apex after 70 min of ischemia. The infarct size, expressed as the ratio of the infarcted tissue over the area at risk of necrosis multiplied by 100, amounted to 79 +/- 20% in the control group. Although there was no significant difference between hemodynamics in the control and the treated groups, pretreatment with diltiazem significantly reduced infarct size (53 +/- 26%; p = .025). Reduction of infarct size by therapy B did not reach the required level of significance (66 +/- 33%). The ischemic loss of ATP and NAD was significantly lower in the pretreated group, which further indicates that the beneficial effect of diltiazem was exerted primarily during ischemia and not during reperfusion.
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PMID:The effect of two different diltiazem treatments on infarct size in ischemic, reperfused porcine hearts. 670 55

Experiments on albino rats have shown that kidney ischemia and its simulation by the anaerobic incubation of postmitochondrial kidney homogenate fraction without a substrate induce a considerable damage of the glycolytic system at the stage of the glucoso-6-phosphate transformation into fructoso-1.6-diphosphate and a less pronounced damage in the fructoso-1.6-diphosphate transformation into lactate. Administration of adenosine diphosphate (ADP) and nicotinamide adenine dinucleotide (NAD) to rats before kidney vessel occlusion or their addition to the postmitochondrial fraction before the anaerobic incubation without a substrate decreased a degree of the glycolytic system damage. The damage of the glycolytic system and protective action of NAD are also detected under simulation of liver ischemia. Possible mechanisms of the ischemic damage in the glycolytic liver and kidney tissue system are discussed.
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PMID:[Effect of NAD and ADP on glycolysis in the kidneys and liver of rats during ischemia]. 671 Jun 14

The effects of reperfusion on ischemic myocardium generally depend on the severity of the preceding ischemic injury. Reperfusion of myocardium, irreversibly injured by ischemia, produces further progression of myocardial necrosis that is accompanied by simultaneously occurring stimulation of interstitial cell proliferation resulting in scar formation. Reperfusion of reversibly injured myocardium leads to structural improvement and reorganization. Thus, it may be stated from the ultrastructural part of this study that reperfusion of ischemic myocardium induces 1) slow structural recuperation after reversible injury, and 2) accelerated cellular destruction and symptoms of scar formation after irreversible ischemic injury. We observed that the reduced tissue content of nicotinamide adenine dinucleotide (NAD), rather than reduced dehydrogenase activity, is the basis of histochemical reactions employing tetrazolium salts. Directly measured NAD tissue content in ischemic tissue correlated well with the degree of ultrastructural injury and with macroscopic differential staining. Occlusion of two small coronary arteries in the same heart followed by reperfusion of only one artery (identical occlusion times for both arteries) showed identical infarct sizes for reperfused and nonreperfused myocardium for occlusion times of 3 and 6 hours. When the effects of occlusion times of less than 3 hours are studied with tetrazolium salts, a difficult technical problem arises: during that time, tissue-NAD concentrations have not decreased enough to enable differential staining. Reperfusion leads to washout of NAD, thus producing differential staining; this may be a harmful effect of reperfusion. However, because early reperfusion leads to significant structural and functional recovery and to small infarcts, reperfusion injury is unlikely to occur. Both ultrastructural and histochemical evidence suggest that reperfusion is beneficial for reversibly injured tissue but accelerates the decay of irreversibly injured tissue.
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PMID:Reperfusion of ischemic myocardium: ultrastructural and histochemical aspects. 683 43

We evaluated the consequences of platelet activation within the coronary circulation and determined the contribution of released thromboxanes, the most potent vasoconstrictors known, to the ensuing cardiac ischemia. Human platelets were isolated by sepharose column chromatography from blood of normal donors and added to the crystalloid perfusate of a Langendorff rabbit heart (platelet counts greater than or equal to 10,000/microliters). Following thrombin-induced (1 U/ml) platelet activation, the coronary flow decreased by 30 +/- 10% (mean +/- SEM, P less than 0.02), the mean concentration of thromboxane B2 in the coronary sinus effluent rose to 62 +/- 25 pmol/ml, and immediate, often irreversible cardiac ischemia as monitored by nicotinamide adenine dehydrogenase autofluorescence photography, ensued. However, with high concentrations of the platelet inhibitor and vasodilator, prostaglandin E1 (1.0 mM), the coronary flow increased by 50 +/-= 15%, and the epicardial fluorescence remained unchanged despite a small (10 +/- 3 pmol/ml) increase in coronary sinus thromboxanes. Platelets isolated from donors who ingested aspirin were incapable of thromboxane synthesis (less than 5 pmol/ml) but remained normally responsive to thrombin-induced activation. When these platelets were challenged by thrombin during cardiac perfusion, however, coronary flow and epicardial fluorescence remained unchanged. We conclude that platelet activation within the coronary circulation can induce irreversible cardiac ischemia, which, however, can be prevented by appropriate pharmacologic inhibition of platelet function. Furthermore, the fact that cardiac perfusion was preserved during a thrombin challenge of platelets from aspirin-treated donors establishes a fundamental role for the products of cyclooxygenase activity (e.g., thromboxanes) in the genesis of this form of myocardial ischemia.
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PMID:Mediation of cardiac ischemia by thromboxanes released from human platelets. 704 97

Purine and pyrimidine nucleotides are essential energy sources for basic metabolic reactions and play important roles in protein, glycogen, and nucleic acid synthesis, cyclic nucleotide metabolism, and energy transfer reactions. Brief coronary occlusions (12 min) were produced in seven open-chest dogs, and repetitive myocardial samples were taken in order to determine the response of the nucleotide pool to ischemia and reperfusion. During ischemia adenosine 5'-triphosphate (ATP) decreased to 57% of control, and similar decreases occurred in the guanosine 5'-triphosphate (GTP), cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP), and nicotinamide adenine dinucleotide (NAD+) pools. The decrease in nucleotides was accompanied by an increase in nucleosides and bases. After 60 min of reperfusion the content of all nucleotides had increased but was still significantly less than nonischemic values. The content of nucleosides and bases decreased immediately upon reperfusion. In contrast, creatine phosphate (CP) fell to 10% of control during ischemia but rebounded to above control values immediately upon reperfusion. Thus depletion of all nucleotide pools occurs during ischemia, and with reperfusion nucleotide content is restored only slowly. Delayed repletion is not caused by a defect in mitochondrial synthesis of ATP because CP content is restored rapidly. The slow repletion of nucleotides may be secondary to loss of nucleotide precursors during reperfusion and may result in widespread alterations in myocardial metabolism.
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PMID:Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog. 708 54

Studies were undertaken to determine the effects of lidocaine on ischemic myocardium, which was induced by coronary artery constriction in open-chested dogs. A real-time epicardial fluorescent technique to detect in vivo-reduced nicotinamide adenine dinucleotide (NADH) during 60 seconds of ischemia was used. Blood flow of ischemic myocardium was measured by using radioactive microspheres of 9 +/- 1 micrometers (mean +/- SE) and was compared with that of normal myocardium, shown by injection of alpha-zurine blue dye. Lidocaine effectively reduced peak NADH fluorescence by 18.6%, from 93.9 +/- 7.2 to 76.4 +/-4.1 mV (p less than 0.005). Lidocaine delayed the onset of fluorescence (2.2 +/- 0.2 versus 1.3 +/- 0.1 s p less than 0.002) and facilitated the recovery from ischemia (38.4 +/- 2.9 versus 54.8 +/- 2.9 s p less than 0.001). Increase in NADH concentration during ischemia correlated (r=0.76, p less than 0.006) with ischemic fluorescence. These findings were independent of altered hemodynamics or change in myocardial blood flow. Results indicate that lidocaine provides myocardial cellular protection during transient ischemia; there is an altered NADH fluorescent response to coronary artery occlusion.
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PMID:Protective effect of lidocaine during regional myocardial ischemia: an altered pathophysiologic response assessed by NADH fluorescence. 708 50

Regional changes in myocardial function and oxidative metabolism during acute coronary artery occlusion were recorded spectrophotometrically by incorporating fiber optics in the isolated rat heart perfused by Langendorff's procedure. Oxygen saturation of myoglobin, reduction of cytochrome aa3, and the dynamic wall thickness of the left ventricle were continuously and concurrently measured from absorbancy increments at 581-592 nm, 605-630 nm, and 568-592 nm, respectively. In contrast to a gradual decrease in the extent of systolic wall thickening in anoxia, observed decreases in both the extent and the duration of systolic wall thickening and the appearance of a late systolic bulge occurred within 5 s after the onset of regional ischemia. After 10 s of both anoxia and regional ischemia, oxygen saturation of myoglobin decreased by 50%, but fluorescence of nicotinamide adenine dinucleotide remained at aerobic level which indicated that mitochondrial oxidative energy production might still be maintained. Thus early and pronounced dysfunction of the ischemic region appeared to precede a substantial loss of ATP production.
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PMID:Regional myocardial function and metabolism during acute coronary artery occlusion. 709 58

The value of three agents in reducing the area of myocardial ischemia in rabbit hearts perfused with crystalloid solution was examined. Ten hearts received crystalloid solution with methylprednisolone (M), 0.25 mg/ml; 18 with hyaluronidase (H), 4 U/ml; and 10 with propranolol (P), 1 microgram/ml. Thirty-six hearts served as controls. The mitral valves were excised, the hearts were paced at 240 beats/min and a coronary artery was ligated. The ischemic area was evaluated by nicotinamide adenine dinucleotide autofluorescence photography, an intrinsic, high-resolution display of anoxic tissue. The ischemic area was determined by computer from standardized photographs. Myocardial oxygen consumption (MVO2) was determined and photographs were taken before and at 10-minute intervals after ligation. At 60 minutes, each heart was perfused with rhodamine dye and quick-frozen. In hearts treated with M and H, coronary blood flow increased by 151% (51.7 +/- 3 to 77.9 +/- 3 ml/min) and 150% (48.3 +/- 2 to 72.3 +/- 2 ml/min), respectively (p less than 0.001), whereas in hearts treated with U and P, coronary flow decreased at 60 minutes. In the control hearts, the ischemic area did not change between 5 and 40 minutes of ischemia. The ischemic area of H-treated hearts decreased from 136 +/- 4 mm2 to 110 +/- 9 mm2 between the postligation control and the end of the experiment (p less than 0.01). The ischemic area of M-treated hearts decreased from 131 +/- 5 mm2 to 113 +/- 5 mm2 (p less than 0.05). P produced no change in ischemic area (p greater than 0.4). There was no change in the oxygen-diffusion zone of P-treated or control hearts (439 +/- 13 vs 383 +/- 12 mu, p greater than 0.1). The oxygen-diffusion zone between perfused and anoxic tissue in the M and H hearts increased from 383 +/- 12 mu to 861 +/- 76 mu and 681 +/- 62 mu, respectively (p less than 0.001). We conclude that significant volumes of myocardium remain normoxic within nonperfused areas of M-, P- and H-treated hearts.
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PMID:Pharmacologic modification of myocardial ischemia. 709 66

The cellular levels of adenine nucleotides and their metabolites in ischemic rat liver were assayed by high pressure liquid chromatography with high theoretical plate numbers. The method was sensitive enough to measure all the metabolites in about 1 mg of tissue, and to examine changes in their levels in a single liver in ischemia. In ischemia the cellular level of ATP decreased rapidly. Concomitantly there was a transitory increase in AMP, followed by its degradation to allantoin via adenosine with accumulation of all species of purine catabolites. NAD was also degraded gradually with concomitant accumulation of nicotinamide. Thus, the level of total adenine nucleotides decreased during ischemia and the amount of this decrease ws equal to the sum of the amounts of catabolites produced. The ATP level was rapidly restored on recirculation after an ischemic period of less than 15 min. However, recovery of the ATP level was depressed by prolonged ischemia and was not observed after an ischemic period of 2 h. Intermediate purine catabolites that accumulated in ischemia were also cleared during recirculation either by their removal in the blood flow or by further oxidative degradation, but they were not salvaged for reuse until the cellular level of ATP was restored. Administration of allopurinol resulted in marked accumulation of hypoxanthine in ischemic liver, but neither this drug nor chlorpromazine had any appreciable effect on recovery of the ATP level during recirculation.
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PMID:Changes in cellular levels of ATP and its catabolites in ischemic rat liver. 709 91

The influence of hyaluronidase (H) on subacute experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial nicotinamide adenine dinucleotide (NADH) fluorescence photography, an intrinsic high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. Hyaluronidase was begun 20 minutes after coronary artery occlusion at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-minute intervals up to 60 minutes of ischemia. Coronary sinus oxygen tension (PcsO2), myocardial oxygen consumption (MVO2), and coronary flow were determined. After 70 minutes, the hearts were perfused with rhodamine solution to identify areas of myocardial perfusion. In 13 H-treated hearts 54.3% +/- 3.7% (mean +/- SEM) of the nonperfused area (rhodamine stained) was ischemic (NADH fluorescent). In 14 untreated hearts 79.8% +/- 3.2% of the nonperfused area was ischemic (p less than 0.0001) and the ischemic areas were uniform. The distance between perfused and ischemic tissue was 952 +/- 78 micrometers in the H hearts and 504 +/- 35 micrometers in the untreated heart (p less than 0.0001). In the H hearts PcsO2 increased to 155% of the post-ligation control while it decreased to 79% in the untreated hearts (p less than 0.0001). MVO2 decreased in the H-treated hearts to 62%; the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 146% of the post-ligation control while it fell to 91% in the untreated group (p less than 0.0001). We conclude that H increases coronary flow while decreasing MVO2 during subacute ischemia. In H-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas, and may potentially be salvaged after prolonged myocardial ischemia.
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PMID:Mechanism of action of hyaluronidase in decreasing myocardial ischemia post coronary occlusion in the isolated perfused rabbit heart. 711 92


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