Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the action of aspirin upon the myocardium per se, independent of thrombosis, coronary occlusion with a balloon catheter was induced in 53 anesthetized dogs divided into two groups. One group (N = 20) was treated daily with aspirin (600 mg/dog) for seven days and another (N = 33) was untreated. Left ventricular hemodynamics and precordial ECG mapping were used to assess the influence of myocardial ischemia over a four hour period. There were no significant differences in left ventricular function or extent of injury as judged by ECG mapping between the two groups. However, there was a significant decrease in the incidence of ventricular fibrillation in the treated dogs (5% vs 39%). Serial plasma samples for free fatty acid determination showed a significant rise in the untreated group. Aspirin blocked the FFA increment in the treated animals. Tissue samples from the ischemic area of left ventricle exhibited a significant reduction of the sodium and water increments, as well as a lesser potassium loss in the treated animals compared to the controls and may have been the basis for the lower incidence of arrhythmias. Since infusion of 51Cr labelled platelets showed no myocardial accumulation of platelets in either group, microthrombi did not appear to contribute to the observed differences.
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PMID:Antiarrhythmic effects of aspirin during nonthrombotic coronary occlusion. 63 Jun 76

To evaluate the influence of glucose infusate administered with insulin and potassium on left ventricular function during 4 h of ischemia, as well as mechanism of action, four groups of intact anesthetized dogs were studied. Acute regional ischemia was induced with a balloon tip catheter in the left anterior descending artery and infusates were begun after 20 min of ischemia. A threefold increase of plasma glucose concentration was associated with improved left ventricular function during ischemia, compared to animals receiving isovolumic saline. There was a significant decline of left ventricular end-diastolic pressure associated with elevation of stroke volume and ejection fraction to control levels, as determined by indicator dilution. In a separate subgroup studied by cineangiography, shortening of the ischemic anterior wall, after an initial decline, was increased in response to glucose but there was no evidence of extension of injury. Ischemic tissue exhibited a smaller gain of water as well as Na+ per gram dry weight as compared to ischemic controls. On precordial electrocardiogram mapping there was a significant decrease in the sigmaST (sum of ST elevation) as well as NST (number of ST segment elevations), but the reduction of R wave amplitude was not different from controls. To further evaluate long-term effects, eight controls and six treated animals underwent myocardial ischemia and were sacrificed after 4 mo. Calculated area and weight of scar, as well as degree of wall thinning, were similar in both groups. The glucose-treated animals had a significant decrease of plasma FFA in contrast to controls which manifested a significant rise. To examine the postulate that the decrease in FFA was important to therapeutic action, a third group was infused with Intralipid (Cutter Laboratories, Inc., Berkeley, Calif.) and heparin, simultaneously with the glucose infusate, to effect an elevation of plasma FFA during ischemia. Changes in myocardial function and electrolyte composition, as well as precordial electrocardiogram mapping, were similar to that of animals receiving glucose alone. Because serum osmolality was increased approximately 40 mosmol during the glucose infusion, the potential role of hyperosmolality was assessed by infusion of 20% mannitol during acute ischemia in a fourth group. After a transient small increase, there was a moderate decline in function by 4 h, suggesting that the response to glucose is not dependent upon extracellular osmolality. Thus, it is concluded that during the initial hours after the onset of myocardial ischemia the glucose infusate improves ventricular performance without evidence of arrhythmia induction or intensification of ischemic injury. Evolution of irreversible necrosis appears to be delayed rather than prevented under the circumstances of this study.
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PMID:Sustained effect of glucose-insulin-potassium on myocardial performance during regional ischemia. Role of free fatty acid and osmolality. 65 87

To assess the protective effects of L-carnitine (LC) infusion on ischemic heart disease, 30 patients who had angina and ischemic ECG changes during exercise were evaluated by bicycle ergometry. They were categorized in LC and non-treatment (NT) groups. There were no significant differences in age and sex between the 2 groups. Before exercise, 15 patients (9 males and 6 females) received 60 mg/kg LC and the results including hemodynamics, coronary circulation, and cardiac metabolism at rest and during exercise were compared with those of the NT group studied in the same protocol (50 watts x to cycle, 15 min). At the end of 30 min LC drip infusion, the arterial carnitine content (LC (a)) reached 1,980 +/- 257.3 microM and then was maintained at 1,212.7 +/- 136.2 microM during exercise. There was no correlation of LC (a) with the coronary arterio-venous difference nor with myocardial uptake of LC. Although there was no significant difference in coronary blood flow (CBF: mliters/100 g/min) between the LC and NT groups at rest (LC: 92.1 +/- 29.0 vs NT: 88.0 +/- 26.5), CBF during exercise increased significantly in the LC group compared with the NT group (LC: 230.4 +/- 113.8 vs NT: 139.1 +/- 52.7; p < 0.05). In the NT group, there was no significant change in coronary arterio-venous oxygen difference ((a-cs) O2: vol %) during exercise, but in the LC group (a-cs) O2 increased significantly from 10.2 +/- 1.3 to 11.5 +/- 1.9 (p < 0.01). Furthermore, although there was no significant difference in myocardial oxygen consumption (MVO2: mliters/100 g/min) at rest between the 2 groups (LC: 9.30 +/- 2.96 vs NT: 9.71 +/- 3.09), it increased significantly in the LC group compared with the NT group during exercise (LC: 25.11 +/- 9.98 vs NT: 15.55 +/- 6.09). MVO2/LVWI (LVWI = left ventricular work index) and MVO2MT (MT = myocardial tension) did not significantly differ at rest between the 2 groups. However, these 2 indices decreased significantly during exercise (p < 0.05) in the NT group, and remained unchanged in the LC group, showing a significant difference between the 2 groups (both p < 0.05). In myocardial energy substrates, the myocardial uptake ((a-cs) x CBF) of free fatty acid (FFA: muEq/100 g/min) increased significantly in the LC group compared with that of the NT group (LC: 10.16 +/- 13.26-->31.88 +/- 27.58* vs NT: 16.02 +/- 27.92-->18.11 +/- 31.00;* = p < 0.05, LC vs NT).
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PMID:[Effect of L-carnitine in patients with ischemic heart disease]. 184 35

Glucose-insulin-potassium (GIK) given during myocardial ischemia or anoxemia results in improved myocardial function and augments energy reserves of myocardial glycogen (MG). Because many patients with heart disease also have myocardial hypertrophy, our purpose was to examine whether similar elevations in MG can occur in hypertrophic hearts with GIK administration and to study the effect of hypovolemic shock on those MG levels. Mongrel dogs (n = 5) with myocardial hypertrophy underwent serial myocardial biopsies of the left (LV) and right (RV) ventricles, and blood samples were followed by GIK infusion (14.5 ml/kg/hr) for 2 hr. after which the dogs were subjected to 2 hr of hypovolemic shock (mean arterial pressure = 40 mmHg). It was found that after GIK infusion MG was consistently elevated in both RV (.43 +/- .02 to .60 +/- .04 g%) and LV (.63 +/- .07 to .71 +/- .01 g%) and FFA declined (.20 +/- .05 to .05-.01 mEq/liter). The MG responded to hypovolemia by further significant elevations (RV 1.16 +/- .33; LV .82 +/- .17), as did FFA (.38 +/- .21). These results indicate that hypertrophic hearts can indeed respond to GIK infusion by increasing MG in both the RV and LV, as do normal hearts. These hearts then submitted to hypovolemic shock showed a further elevation of MG. The elevated insulin levels post-GIK resulted in suppression of FFA. Thus GIK administration may have a sparing effect on energy stores of the heart during hypovolemic shock, which could have clinical implications in the treatment of patients with hypertrophic myocardia.
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PMID:Response of hypertrophic heart myocardial glycogen to GIK and hypovolemic shock. 294 28

Twenty-six patients on chronic (greater than 3 months) beta-receptor blocking therapy due to ischaemic heart disease and/or hypertension were randomly distributed to a 4-day gradual withdrawal (n = 13) or a continuation of ordinary therapy until a planned cholecystectomy under neurolept anaesthesia (n = 13). Plasma-adrenaline, -noradrenaline, -potassium, -glycerol, -FFA, -insulin and b-glucose were determined perioperatively. The metabolic response to surgery was as expected with hyperglycaemia and depressed insulin levels, which did not differ significantly between the two groups of patients. Plasma-catecholamines showed the highest mean values during emergence from anaesthesia. Plasma-adrenaline and -potassium were constantly highest in the beta-receptor-blocked patients, who also showed indices of a relatively depressed lipolysis compared to patients in whom beta-receptor blockers had been withdrawn. These discrepancies between withdrawal versus continuation of preoperative beta-receptor blockade seemed to be of small clinical importance and did not oppose the present view that beta-receptor blockers should generally be continued during surgery. However, findings in individual patients suggest that beta-receptor blockade may maintain hypoglycaemia in catabolic patients.
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PMID:Long-term beta-receptor blockade--adrenergic and metabolic response to surgery and neurolept anaesthesia. 613 Jun 65

The fatty acid compositions of 4 serum lipid fractions were analysed from 244 randomly selected 30-59-year-old Finnish men from 4 areas involved in a population survey ('Mini-Finland') in 1979-80. Men in eastern Finland had significantly lower mean percentages of linoleate (18:2) in CE, TG, FFA and PL (45.1, 10.3, 9.3 and 18.8%, respectively) than men in the western part of the country (48.4, 12.5, 10.6 and 20.2%, respectively). Very low values of 18:2 were encountered in the North Karelian community of Ilomantsi, especially in men aged 50-59 (40.9, 8.0, 7.5 and 16.8%, respectively). The percentage of alpha-linolenate tended also to be lower and those of saturated and monounsaturated fatty acids higher in the east, but there were no or only inconsistent differences in the contents of the prostaglandin precursors dihomo-gamma-linolenate, arachidonate and eicosapentaenoate. Eighteen men were studied in November and the following April. Only minor changes in the mean composition of serum fatty acids took place during this period and the correlation coefficients between the percentages of 18:2 recorded at the two time points ranged from 0.70 to 0.81. The low concentrations of 18:2 in serum lipids in Finnish men obviously reflect a low dietary P/S ratio and may contribute to the high prevalence of IHD in Finland and to its regional differences.
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PMID:Serum fatty acids in Finnish men. 666 77

In acute experiments on open chest pigs 15 min occlusions of the left anterior descending coronary artery were performed, each occlusion followed by 45 min reperfusion. Myocardial ischaemia was defined by epicardial electrogram recorded from the border of the ischaemic area. Myocardial extraction of lactate and glucose as well as the extraction of FFA were measured before and at the 15th min of occlusion. Inosine (5 mg/kg/min) or 0.9% NaCl infusion was administered i.v. throughout the occlusion period. Inosine significantly diminished the number of ischaemic points and reduced an increase in R-wave voltage induced by coronary occlusion. Myocardial extraction of measured substrates was not significantly influenced by inosine administration. In conclusion, inosine decreases the area of ischaemic injury induced by acute coronary occlusion in the pig.
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PMID:The influence of inosine on the size of myocardial ischaemia and myocardial metabolism in the pig. 688 39

The influence of an acute myocardial ischemia on lipoprotein lipase (LPL) activity in the myocardium was studied in open chest dogs. Myocardial ischemia was induced by occlusion of a branch of left descending coronary artery and biopsies were taken from non-ischemic and ischemic myocardium. After 60 min of myocardial ischemia a significantly lower LPL activity was found in full wall biopsies of ischemic than of non-ischemic left ventricular myocardium. The ischemia-induced reduction in LPL activity was most pronounced in the endocardial half of the myocardium. Reduction of LPL activity in the ischemic zone might contribute to limitation of the ischemic injury through reduction of FFA extraction from plasma triglycerides.
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PMID:Myocardial lipoproteins lipase activity during acute myocardial ischemia in dogs. 706 1

Insulin resistance is an important issue in the understanding of the metabolic syndrome. Clinical insulin resistance is usually defined by reduced insulin-mediated uptake of glucose in skeletal muscle. However, new studies have shown that liver and fat cells may also develop insulin resistance in subjects with the metabolic syndrome, specifically when these subjects are hyperglycaemic. New investigations also indicate that the endothelial cell itself can be insulin-resistant, reduced blood flow and increased peripheral resistance as the outcome. Insulin resistance may not only induce hyperglycaemia, but also dyslipidaemia (increased plasma levels of free fatty acids and triglyceride, and reduced plasma HDL levels) and arterial hypertension. All these variables may provoke arteriosclerosis and ischaemic heart disease. Specifically, abdominal adiposity seems to be responsible for insulin resistance in subjects with the metabolic syndrome. The mechanism could be intracellular accumulation of acyl CoA and triglyceride. However, an increased production of peptides from the adipose tissue, such as TNF alpha and reduced production of adiponectine may also play a role. The mechanism by which FFA and triglyceride, together with the peptides mentioned, may induce insulin resistance at a cellular level, resulting in reduced glucose transport and intracellular glucose processing, is still being discussed. A change in the insulin signalling cascade is one possibility, but the results so far have been contradictory. Another possibility is, of course, that the cellular accumulation of acyl CoA itself intervenes with gene expression and with phosphorylation of proteins.
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PMID:[Insulin resistance: organ manifestations and cellular mechanisms]. 1198 54

Diabetic patients with ischaemic heart disease have a greater amount of myocardial ischaemia, often silent, and an increased incidence of heart failure compared to nondiabetic patients. This is the result of altered myocardial metabolism and accelerated atherogenesis with involvement of peripheral coronary segments causing chronic hypoperfusion and diffuse hybernation. In patients with diabetes mellitus and myocardial ischaemia, the metabolic changes occurring as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the diabetic metabolic changes. An important metabolic alteration of diabetes is the increase in free fatty acid concentrations and increased muscular and myocardial free fatty acid uptake and oxidation. This increased uptake and utilization of free fatty acid during stress and ischaemia is responsible for the increased susceptibility of the diabetic heart to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared to nondiabetic hearts. Given the metabolic alterations of the diabetic heart at rest and during episodes of myocardial ischaemia, a therapeutic approach aimed at an improvement of cardiac metabolism through manipulations of the utilization of metabolic substrates should result in an improvement of myocardial ischaemia and of left ventricular function. Modulation of myocardial free fatty acid metabolism should be the key target for metabolic interventions in patients with coronary artery disease with and without diabetes. In diabetic patients, the effects of modulation of free fatty acid metabolism should be even greater than those observed in patients without diabetes. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, decreases cardiac ischaemia and therefore prevents the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischaemia. Because of its effect on cardiac metabolism at rest, its effects on myocardial ischaemia and left ventricular function trimetazidine should always be considered for the treatment of diabetic patients with ischaemic heart disease with or without left ventricular dysfunction.
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PMID:Metabolic therapy for the diabetic patients with ischaemic heart disease. 1634 Mar 99


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