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)

Despite the use of cold blood potassium (CBK) cardioplegia, the severely impaired myocardium and/or long ischemia time continue to be a challenge. Because of the association of Ca++ with cell injury and death, the use of Ca++ entry blockers is logical. Investigation of cold blood diltiazem (CBD) revealed no advantages over CBK cardioplegia. The combination of potassium and diltiazem is appropriate because of their different mechanisms of action. Ten dogs had 1 hour of myocardial ischemia with topical ice (temperature 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing potassium (30 mEq/L) and diltiazem (400 micrograms/kg). Eight dogs had 2 hours of ischemia after perfusion with 200 ml of cold blood containing potassium (30 mEq/L) and diltiazem (200 micrograms/kg) and reperfusion every 30 minutes with 100 ml of cold blood containing KCl (30 mEq/L) and diltiazem (100 micrograms/kg). Six dogs received the same treatment as the previous group except that diltiazem was increased to 1,600 micrograms/kg for all four perfusions. Baseline studies were repeated after 60 minutes of reperfusion without the use of Ca++ or inotropic agents. Heart rate, peak systolic pressure, velocity of the contractile element (Vce), maximum velocity of contractile element (Vmax), peak +dp/dt, peak -dp/dt, dp/dt over common peak isovolumic pressure, left ventricular compliance, stiffness and elasticity, and heart water were unchanged from control. Coronary vascular resistance was unchanged in Groups 1 and 2 but declined in Group 3. Creatine phosphate was preserved during ischemia; adenosine triphosphate (ATP) declined. With reperfusion there was continued fall in ATP, ADP, and the adenosine pool. Ultrastructure was well preserved. In 16 of 24 dogs defibrillation was not required, whereas all 48 dogs with CBK and all 13 with CBD required defibrillation. These data suggest that the addition of diltiazem to CBK provides more effective cardioplegia (preservation of creatine phosphate), although ATP and the adenosine pool continued to decline with reperfusion.
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PMID:Cold blood potassium diltiazem cardioplegia. 669 11

The effect of alcohol ingestion on primary hemostasis was investigated in fasting healthy humans. Primary hemostasis was measured with the template bleeding time and platelet aggregation assayed with the turbidometric method. Blood was collected to study coagulation and fibrinolysis. 1 h after ingestion of 2 ml/kg body weight of 40% alcohol the plasma alcohol concentration was 19.3 +/- 1.6 mmol/l. At this time there was a significant prolongation of the bleeding time accompanied by an impairment of platelet responsiveness to both collagen and ADP. A prolongation of the bleeding time and impairment of platelet function was also found 2 h after alcohol ingestion. Ingestion of this amount of alcohol did not affect parameters of coagulation or fibrinolysis. The data indicate that primary hemostasis is impaired in man after ingestion of moderate amounts of alcohol. This may explain the favorable effect of moderate alcohol consumption on ischemic heart disease but indicates an increased risk for patients with bleeding.
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PMID:Impairment of primary hemostasis and platelet function after alcohol ingestion in man. 673 79

The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.
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PMID:Effects of ischemia and reperfusion on pyruvate dehydrogenase activity in isolated rat hearts. 687 85

In 20 patients with ischaemic heart disease (IHD), platelet sensitivity to ADP-aggregation, plasma von Willebrand factor (vWF) and plasma beta-thromoboglobulin (beta-TG) were measured before and after isometric exercise. Effect of dipyridamole on these determinants was studied in a crossover fashion. To assess plasma vWF level, a new simple method was employed which has the advantage of not requiring an optical aggregometer and was proved to be reproducible. No significant difference was seen in platelet sensitivity to ADP-aggregation, vWF and beta-TG among healthy controls, IHD patients on placebo and on dipyridamole at rest. After exercise, platelet sensitivity to aggregation, plasma vWF and beta-TG increased significantly in IHD patients on placebo. In healthy controls, no significant changes were seen. On dipyridamole, above changes seen in IHD patients were not seen. The results suggests that isometric exercise may induce platelet release reaction in vivo and may produce hypercoagulable state in IHD patients. These phenomena may be prevented by pretreatment with dipyridamole.
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PMID:Platelet release reaction in vivo in patients with ischaemic heart disease after isometric exercise and its prevention with dipyridamole. 696 82

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood-potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing diltiazem, 400 micrograms per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 micrograms/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 micrograms/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used. Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak - dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p less than 0.025) and compliance decreased (p less than 0.02). In both groups, coronary vascular resistance declined (p less than 0.001) and recovery of adenosine triphosphate (p less than 0.001), adenosine diphosphate (p less than 0.025), and the adenosine pool (p less than 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2. Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.
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PMID:Cold blood-diltiazem cardioplegia. 706 65

During the induction of myocardial infarction in the rat by isoproterenol, a decrease in the voltage of the T wave in the electrocardiogram is produced, which reflects myocardial ischemia through a previous infusion of a KCl solution; while the perfusion of NaCl increases the voltage of such wave and therefore cardiac ischemia. The values of free Pi in the myocardium increase significantly with the administration of isoproterenol. If KCl has been perfused previously, the figures of free Pi are superior in 155% of those obtained with the perfusion of NaCl. The values of all the energetic phosphates, AMP, ADP and ATP decrease inversely and in a significant way with isoproterenol and the perfusion of NaCl and KCl. The activity of creatine-phosphokinase in the myocardium decreases with isoproterenol, specially with the previous perfusion of KCl Similarly, the activity of the isoenzimes of lactic dehydrogenase L1 and L2 (alpha-HBDH), decreases, which intensifies with previous perfusion of NaCl, but diminishes with KCl. The activity of malicodehydrogenase (MDH) in the myocardium decreases with isoproterenol, even with the previous perfusion of NaCl, but in lesser degree than with KCl.
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PMID:[Effect of sodium and potassium on cardiac infarct in rats]. 721 55

Aspirin, as an inhibitor of platelet aggregation, may be of benefit in ischemic heart disease. However, aspirin blocks not only platelet aggregation but also synthesis of prostacyclin, a vasodilator and platelet deaggregator. The relative sensitivity of prostaglandin-mediated coronary vasodilatation and platelet aggregation to inhibition by aspirin remains uncertain. We therefore investigated the relative dose-response relationship of aspirin on arachidonic acid-induced increments in coronary blood flow and on ADP-induced aggregation of platelets. In 11 open-chest dogs, intracoronary arachidonic acid, 0.1-3.0 mg, produced dose-related increases in coronary blood flow that were inhibited progressively by i.v. aspirin over the dose range 0.3-3.0 mg/kg. Aspirin at 3 mg/kg almost completely obliterated the response to 3 mg of arachidonic acid. Similarly, aspirin doses of 0.3-3.0 mg/kg progressively raised the minimal concentration of ADP necessary for platelet aggregation. The threshold concentration of ADP that produced aggregation of platelets from 10 control dogs ranged from 2.3 x 10(-6) M to 1.2 x 10(-5) M. Aspirin at 3 mg/kg completely inhibited aggregation of platelets from 11 of 12 dogs, even with ADP at 2.3 x 10(-4) M concentration, the maximum tested. Aspirin at 0.1 mg/kg failed to inhibit either ADP-induced platelet aggregation or arachidonic acid-induced increments in coronary blood flow. Thus, the two test systems showed similar sensitivity to inhibition by aspirin with respect to threshold dose and maximal effect. These results show that very low doses of aspirin inhibit arachidonic acid-induced coronary vasodilatation and that aspirin at low doses does not appear to selectively inhibit platelet activity relative to coronary vasodilatation.
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PMID:Relative effects of aspirin on platelet aggregation and prostaglandin-mediated coronary vasodilatation in the dog. 743 58

The effects of nitroglycerin (NTG) on platelet aggregation are controversial. Most in vitro investigations suggest that NTG suppresses platelet aggregation only at suprapharmacologic concentrations. We investigated various aspects of the antiaggregating effects of NTG in both normal individuals and in patients with stable angina pectoris not treated with nitrates. Platelets from patients exhibited hyperresponsiveness to ADP as an inductor of aggregation. Sublingual administration to patients of NTG (300 micrograms) decreased platelet aggregability; ADP concentrations inducing 50% aggregation were 3.3 +/- 0.3 microM after NTG versus 2.1 +/- 0.1 microM before NTG (p < 0.01). Consistent with previous findings, NTG was a weak inhibitor of platelet aggregation in vitro when added before induction of aggregation. When added after the beginning of aggregation, however, NTG induced both inhibition of developing aggregation and marked disaggregation at concentrations > or = 10(-8) M NTG; concentration associated with 50% reversal of aggregation was 1.4 +/- 0.3 x 10(-6) M. Therefore, antiplatelet effects of NTG in vitro are demonstrable in low, clinically achievable concentrations; previously reported effects of NTG have been underestimated owing to suboptimum experimental conditions. Platelets from patients with angina pectoris were 100-fold less responsive to the cyclic GMP-increasing and disaggregating effects of NTG in vitro, which, together with increased aggregability, could imply reduced platelet sensitivity to endogenous sources of nitric oxide (NO) in vivo. The observed antiplatelet effects of NTG raise the question of its potential utility to reduce the risk of thrombotic complications in patients with ischemic heart disease.
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PMID:Antiplatelet effects of nitroglycerin in healthy subjects and in patients with stable angina pectoris. 768 98

To identify any differences in inhibitory G protein (Gi) attributable to species or the cause of heart failure, we studied the changes in this protein in different animal models of heart failure: 1) different species; rats vs. hamsters (F1B) with cardiomyopathy induced by adriamycin (ADR) and 2) different etiologies; rats with ischemic heart failure (IHD) due to coronary artery ligation vs. rats with cardiomyopathy induced by ADR and F1B (20-week-old) hamsters with cardiomyopathy induced by ADR vs Syrian hamsters BIO 14.6 (40-week-old) with genetic cardiomyopathy, using Western blotting methods and ADP-ribosylation. We also sought to determine whether changes in the amount of Gi protein reflected the regulation of adenylate cyclase. The amount of immunodetectable Gi rose by 35% (p < 0.05) in ADR rats, 25% (p < 0.05) in ADR hamsters, 15% (p < 0.05) in IHD rats, and 28% (p < 0.05) in BIO 14.6 hamsters, as compared with control rats, F1B (20-week-old) hamsters, sham-operated control rats, and F1B (40-week-old) hamsters, respectively. Assessment of Gi by pertussis toxin-catalyzed ADP-ribosylation revealed increases in Gi of 24% (p < 0.05) in ADR rats and of 44% (p < 0.05) in BIO 14.6 hamsters, as compared with their respective controls. Gi function, as assayed by the acetylcholine-induced inhibition of adenylate cyclase, also increased. Thus, Gi protein appears to contribute to the changes in signal transduction in myocardium with heart failure.
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PMID:Increased levels of inhibitory G protein in myocardium with heart failure. 769 38

The photochemical reaction between rose bengal and light (540 nm) produces thrombotic occlusion in rat coronary artery. We have now developed an experimental myocardial infarction (MI) model by photochemically induced thrombosis (PIT) in rats and investigated the mechanisms responsible for the induction of MI. PIT in the coronary artery induced myocardial ischemia, which was determined by tissue oxygen tension (tpO2), and resulted in MI. Pretreatment with a thromboxane (TX) A2-receptor antagonist, vapiprost, prevented a decrease in myocardial tpO2 and markedly reduced the MI area, although vapiprost inhibited collagen-induced platelet aggregation by 30% ex vivo. An ADP-induced platelet aggregation inhibitor, clopidogrel, also reduced the MI area. In contrast to vapiprost, clopidogrel inhibited collagen-induced platelet aggregation by 90% ex vivo. Pretreatment with a 5-HT2-receptor antagonist, ketanserin, which did not inhibit collagen-induced platelet aggregation ex vivo, prevented the decrease in myocardial tpO2 and reduced the MI area. These results suggest that TXA2, 5-HT and ADP play a role in the induction of MI and that platelet aggregation and other factors induce ischemia in this model.
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PMID:An experimental myocardial infarction model in the rat and its properties. 774 45


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