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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six hours of coronary occlusion has been thought to produce extensive and irreversible transmural damage and no possibility of salvage by reperfusion. This has been based on findings of adenosine triphosphate depletion and histochemical (triphenyltetrazolium chloride nonstaining) and ultrastructural changes (conventional preparatory techniques). This study tests the hypothesis that, in contrast to conventional wisdom, considerable structural and mitochondrial functional integrity remains in cardiac muscle subjected to 6 hours of regional ischemia. Twenty open-chest anesthetized dogs underwent isolation of the left anterior descending coronary artery and were observed for 6 hours. Eight of the 20 did not undergo ischemia and served as controls. Twelve underwent 6 hours of proximal ligation of the left anterior descending coronary artery (30% +/- 2% area at risk). Transmural biopsy specimens were analyzed. Coronary occlusion reduced regional blood flow (radioactive microspheres) to less than 10 ml/100 gm/min (p less than 0.05) and dyskinesia persisted in the area at risk for 6 hours. High-energy phosphates (adenosine triphosphate and creatine phosphate) declined to negligible levels and histochemical damage occurred (49% +/- 12% triphenyltetrazolium chloride non-staining). Mitochondrial ultrastructural changes (low protein denaturation embedding technique) were mild (the integrity of the inner and outer mitochondrial surface membranes and crystal membranes was maintained and myofibrillar degeneration did not occur). Mitochondrial oxidative phosphorylation rate remained at 63% of control levels, respiratory control index remained at 77%, and adenosine diphosphate/oxygen ratio was maintained at 96%. Mitochondrial Ca++ increased with lanthanum (from 26 to 46 nmol/mg protein, p less than 0.05), but irreversible calcium precipitation did not occur; calcium could be mobilized to normal levels (i.e., 13 nmol/mg protein) by ethylenediaminetetraacetic acid chelation. These data support our inference that necrosis does not occur after 6 hours of coronary occlusion and suggest that muscle salvage by reperfusion is possible after at least 6 hours of regional myocardial ischemia.
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PMID:Studies on prolonged acute regional ischemia. I. Evidence for preserved cellular viability after 6 hours of coronary occlusion. 281 16

Platelets are involved in the progression of coronary atherosclerosis as well as in the development of the acute precipitating event. Recently, it has been shown that normal subjects present increased platelet aggregation between 6.00 a.m. and 9.00 a.m.; epidemiological studies have shown a higher incidence of myocardial infarction between these times. This study evaluated, by an impedence method using whole blood, platelet aggregation induced by ADP (3 microM) and collagen (2 microM/ml). Measurements were made at 6.00 a.m., 9.00 a.m. and 12.00 noon, the day before and the day after evening administration of 200 mg indobufen, a platelet aggregation inhibitor, in 12 patients with ischaemic heart disease. Patients showed a significant increase of platelet aggregation between 6.00 a.m. and 9.00 a.m. which was inhibited by the prior evening administration of indobufen.
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PMID:Effect of indobufen on whole blood platelet aggregation recorded in the morning in patients with ischaemic heart disease. 279 57

Under effects of myocardial ischemia (30 min), the activities of the intermembrane enzymes of rabbit heart mitochondria, i.e., adenylate kinase and creatine kinase, are inhibited by 20% and 23%, respectively. Consequently, the creatine- and AMP-activated respiration of mitochondria diminishes by 52% and 39%, respectively. An inhibitory analysis of ADP-, AMP- and creatine-activated mitochondrial respiration performed in the presence of atractyloside has demonstrated that ischemia (30 min), adriblastin (0.688 mM) and succinate (10 mM) cause alterations in the functional coupling of adenylate kinase and creatine kinase with the adenine nucleotide translocator. These alterations lead to the diminution of the rate and efficiency of energy transfer from mitochondria to hexokinase, as an arbitrary site of energy consumption. An addition of cytochrome c to ischemic heart mitochondria results in an increase in the rate of ATP synthesis; however, the efficiency of this process is lowered. The toxic effect of the anticancer drug--adriblastin on heart mitochondria respiration is enhanced in the presence of creatine in the bathing solution.
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PMID:[Functional changes in the mitochondrial site of adenylate kinase and creatine kinase systems of energy transport induced by myocardial ischemia and adriablastin]. 284 Jan 29

The effects of beta-blocking and class I antiarrhythmic agents on free radical-mediated sarcolemmal lipid peroxidation were examined. Highly purified canine myocytic sarcolemmal membranes were pretreated with 10-800 microM of selected beta-blocking (propranolol, pindolol, metoprolol, atenolol, or sotalol) and class I (quinidine, lidocaine, procainamide, or diphenylhydantoin) antiarrhythmic agents at 37 degrees C for 10 minutes. Subsequently, a superoxide radical (derived from dihydroxyfumarate) driven, Fe3+-ADP catalyzed free radical generating system was added and incubated for up to 45 minutes. Lipid peroxidation of sarcolemma was determined by malondialdehyde formation. Pretreatment of the membranes with the five beta-blockers resulted in various degrees (20-95%) of inhibition of sarcolemmal peroxidation in a concentration- and time-dependent manner. All the class I agents were less effective (less than 20% inhibition). The order of potency of the beta-blockers was propranolol greater than pindolol greater than metoprolol greater than atenolol greater than sotalol and appeared to relate to their degree of lipophilicity. Propranolol, the most potent agent, achieved half-maximal inhibition of peroxidation at about 100 microM and achieved significance (p less than 0.01) at 20 microM. At pH 6.0, the efficacy of pindolol, metoprolol, atenolol, and sotalol diminished by 30-50% compared to pH 7.2, but the potency of propranolol remained unchanged. Since increased free radical production may occur during myocardial ischemia/reperfusion injury, the above findings suggest that the lipophilic beta-blockers may provide additional antiperoxidative protection of ischemic tissue.
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PMID:Protection by beta-blocking agents against free radical-mediated sarcolemmal lipid peroxidation. 289 7

The aim of this study was to elucidate the role of platelet aggregation as a risk factor for ischemic heart disease (IHD) and the relationship between fatty acids and platelet function. Platelet aggregation upon adenosine diphosphate (ADP), adrenaline and thrombin were measured in middle aged men in east and west, two regions of Finland with a nearly twofold difference in IHD mortality. Platelet aggregation results were correlated with the fatty acid compositions of plasma lipid fractions, adipose tissue triglycerides and platelet phospholipids. There was no significant east-west difference in platelet reactivity to ADP, adrenaline and thrombin. ADP-induced platelet aggregation showed significant negative correlations with all the platelet C20-C22 n-3 polyunsaturated fatty acids (PUFA), but significant positive correlations with the percentage of 18:2n-6 in adipose tissue and plasma cholesterol esters (CE) and triglycerides (TG). Adrenaline-induced aggregation correlated negatively with the percentage of 20:5n-3 in plasma CE and TG, and positively with the total percentage of saturated fatty acids in platelets. Aggregation upon thrombin had a negative correlation with the 20:3n-6/20: 4n-6 ratio in plasma CE and a positive correlation with 18:2n-6 in adipose tissue. The percentages of the major PUFA in platelets correlated significantly with the same fatty acids in plasma CE and phospholipids PL. Platelet 20: 5n-3 had a highly significant negative correlation with the percentage of 18: 2n-6 in plasma and adipose tissue lipids. Platelet 20: 4n-6 was unrelated to its precursors in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary fats and platelet function among Finnish men. 292 2

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Systemic and transcardiac platelet activity in acute myocardial infarction in man: resistance to prostacyclin. 293 81

Serum lipoproteins, fatty acids in plasma lipid esters and in platelet phospholipids were assessed in 64 patients with ischaemic heart disease (IHD) and in 67 controls. Hyperlipoproteinemia (HLP) (VLDL triglycerides greater than 1.4 mmol/l and/or LDL cholesterol greater than 5.2 mmol/l) was found in 64% of the patients. In the plasma lipid esters the relative concentrations of saturated and monounsaturated fatty acids as well as dihomo-gammalinolenic acid were higher in the IHD patients whereas the linoleic acid concentrations were lower. The altered fatty acid pattern was apparent both in patients with and without HLP. In the platelet phospholipids there was a relative increase of oleic acid and a decrease of stearic acid. The relative content of eicosapentaenoic acid was slightly reduced whereas the linoleic acid concentrations were unchanged compared to the controls. Platelet aggregation induced by ADP and collagen was enhanced in the IHD patients. The lowest threshold value for ADP-induced aggregation was found in the normolipidemic patients. Since there were almost no differences in the relative contents of the long-chain polyunsaturated fatty acids in the platelet phospholipids between patients and controls it is concluded that mechanisms other than the prostaglandin-mediated pathway may contribute to the increased platelet aggregation in IHD patients.
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PMID:Fatty acid composition of platelets and of plasma lipid esters in relation to platelet function in patients with ischaemic heart disease. 293 56

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore, an understanding of factors which impact on platelet performance is important. The present study was undertaken 1. to characterize during evolving myocardial infarction (MI) platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and 2. to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving MI were studied. 22 patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 minutes. In 15 of these patients, who had an anterior MI, transcardiac platelet function and response to PGI2 were studied. The results are as follows: Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, are elevated three and ten fold. 6-keto-prostaglandin F1 alpha, the stable end product of PGI2, is less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets, circulating during evolving MI ("ischemic platelets") are hyperaggregable in response to adenosine diphosphate and relatively resistent to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic adenosine monophosphate and the cAMP response to PGI2 are diminished. The platelet hyper-reactivity is most intense early during infarct evolution and decreases with time. Transcardiac measurements indicate that thromboxane is produced across the ischemic/infarcting compartment in ten of 15 patients with anterior MI. The antiplatelet effect of PGI2 is greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving MI characterized by a pro-aggregatory environment, heightened platelet re-activity, both in the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequence of the data are that the infarct patient in the acute phase may benefit from platelet function suppression and requires significantly greater doses of prostacyclin than normal subjects. The data also suggest future directions for therapeutic manipulation of platelet hyper-reactivity in the setting of acute myocardial ischemia.
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PMID:Platelet hyperactivity in acute myocardial infarction in man--effects of prostacyclin. 293 12

The abnormalities in regional function produced by myocardial ischemia persist after the ischemic episode resolves. Since a close functional coupling exists between myofibrillar creatine kinase and myosin ATPase, a disruption of this coupling could adversely influence myocardial function and might provide a mechanism for the myocardial dysfunction observed. The purpose of the present study was to determine if an alteration in the activity of creatine kinase associated with the myofibril occurs in the postischemic period. Anesthetized open-chest dogs (n = 6) underwent coronary occlusion for 15 minutes, followed by reperfusion for 15 minutes. In reperfused myocardium, adenine nucleotide content was decreased (72 +/- 10% of nonischemic myocardium, p less than 0.05), documenting the presence of previous ischemia. The creatine phosphate content of reperfused myocardium returned to normal, indicating resumption of myocardial energy production. The creatine kinase activity of purified myofibrils isolated from reperfused myocardium was decreased by 17 +/- 7% compared to that of nonischemic myofibrils (p less than 0.03). In addition, the free adenosine diphosphate concentration in reperfused myocardium was calculated to be 96 microM and was less than the Km of adenosine diphosphate determined for myofibrillar creatine kinase (105 microM). The results suggest two putative mechanisms for disruption of energy use in postischemic myocardium: decreased creatine kinase activity associated with the myofibril, and limitation of substrate necessary for maximal creatine kinase activity.
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PMID:Disruption of myofibrillar energy use: dual mechanisms that may contribute to postischemic dysfunction in stunned myocardium. 295 65

Unstable coronary artery disease (CAD) might be related to obstructions of coronary blood flow by platelet aggregates. In 121 men and 43 women admitted to the coronary care unit with suspected unstable CAD, blood samples for tests of platelet function were obtained within 24 hours after admission. Platelet reactivity was tested in vitro in platelet rich plasma as the aggregability towards ADP 1 microM and collagen 1 mg/ml and as the sensitivity to prostacyclin (PSP). The levels of beta-thromboglobulin and platelet factor 4 were determined ex vivo in platelet poor plasma. Patients who developed a nontransmural myocardial infarction (n = 39) or had signs of myocardial ischemia at an exercise test performed within a week (n = 39) were considered to have unstable CAD while patients without signs of ischemia constituted the control group. In the acute phase the PSP was reduced in patients with unstable CAD without any difference between genders. The aggregability towards ADP was higher in women than men but otherwise there were no differences between groups or sexes in any other test in the acute phase. After 12 months there were no differences in PSP between the groups but women had a lower PSP than men. Thus, in the acute phase of unstable CAD, the platelet sensitivity to the inhibitory effects of prostacyclin was reduced which might contribute to the risk for further platelet aggregation, coronary occlusion and myocardial infarction.
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PMID:Platelet reactivity in unstable coronary artery disease. 295 54


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