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 investigate the in vivo role of the ATP-sensitive potassium channel (KATP) in the coronary arteries, we examined the effects of intravenous (i.v.) glibenclamide (GLB, 0.3, 1.0, and 3.0 mg/kg), a specific KATP blocker, in chronically instrumented dogs. Epicardial coronary artery diameter (CoD) and coronary blood flow (CBF) were measured continuously. CoD and CBF oscillated in all 6 dogs after injection of 3 mg/kg GLB. CoD oscillated only slightly, with a decrease of 2.3 +/- 0.4%; CBF showed marked oscillation, with a peak flow rate of 21.9 +/- 2.7 ml/min (+26.6%) and a trough flow rate of 10.3 +/- 2.9 ml/min (-46.3%) (baseline flow rate was 17.8 +/- 2.4 ml/min). GLB 1 mg/kg produced a slight decrease in CBF without oscillation, and at 0.3 mg/kg had almost no effect. These oscillations were not associated with a decrease in myocardial blood flow as measured by the hydrogen gas clerance method. Nicorandil (0.2 mg/kg), cromakalim (20 micrograms/kg), and diltiazem (0.2 mg/kg) almost completely suppressed the GLB-induced oscillations, but nitroglycerin (NTG 15 micrograms/kg) did not. Thus, oscillation of large and small coronary arteries was induced by GLB and was independent of myocardial ischemia. In addition, these findings suggest that KATP has an important in vivo role in modulating large and small coronary artery tone through activation of the voltage-dependent Ca2+ channel.
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PMID:Glibenclamide-induced oscillation of canine coronary artery is independent of myocardial ischemia. 751 93

Organic nitrates are widely used in the treatment of ischemic heart disease. The magnitude and duration of their circulatory and ischemic effects are, however, rapidly reduced during continuous treatment. The specific mechanisms underlying this tolerance development are not clear. According to the most widely accepted theory, tolerance is due to an intracellular depletion of thiol compounds (GSH and/or cysteine) involved in the conversion of nitrates to vasoactive intermediates. This presentation deals with aspects of in vivo thiol/nitrate interactions in different experimental and clinical conditions. The major results and conclusions are: The acute hypotensive effect of NTG is decreased by lowering of intracellular GSH levels. This finding emphasizes that normal intracellular thiol levels are required for optimal conversion of nitrates. Thus, intracellular GSH plays a critical role in the metabolism of NTG. Despite development of tolerance to the hypotensive effect of NTG, arterial and venous thiol levels are similar in nitrate tolerant and non-tolerant animals, suggesting that depletion of vascular thiol compounds may not be the cause of nitrate tolerance in vivo. The effect of exogenous thiol administration on intravascular thiol levels are different in nitrate tolerant and non-tolerant conscious rats. Exogenous thiol compounds (e.g. NAC) augments the hypotensive effect of NTG by a tolerance nonspecific mechanism. This effect is most likely mediated by an extracellular and/or membrane-related nitrate/thiol interaction and formation of NO. N-acetylcysteine inhibits angiotensin converting enzyme and counteracts nitrate-induced stimulation of the renin angiotensin system in vivo. Therefore, in addition to an effect on nitrate metabolism, thiol compounds may modify tolerance development by attenuating nitrate-induced counter-regulatory mechanisms. In the clinical setting, co-administration of NAC and ISDN delays and partially prevents tolerance to the antianginal and antiischemic effects normally seen in patients with stable angina pectoris during treatment with ISDN. N-acetylcysteine treatment in humans, potentiates and preserves nitrate induced venodilation and augments the effect of nitrates on small resistance vessels without affecting the response to nitrates in larger sized arteries. Thus, administration of NAC may change the normal vasodilator profile of nitrates. In conclusion, changes in cellular thiol levels may modify the hemodynamic effect of organic nitrates and the cellular handling of thiols and/or thiol related enzymes is altered after development of nitrate tolerance. In addition, a tolerance unrelated thiol/nitrate interaction, potentiating the effect of nitrates, may occur after administration of exogenous thiol compounds. In the clinical setting administration of thiols results in a characteristic change in the vasodilator profile of nitrates and an attenuation of the nitrate-induced stimulation of the renin-angiotensin system. The combination of these effects probably contributes to the improvement in antianginal and antiischemic parameters which may be seen during continuous and prolonged treatment with nitrates and thiol compounds.
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PMID:Thiol compounds and organic nitrates. 874 3

The aims of this study were to investigate whether nicorandil (NIC), an ATP-sensitive potassium channel (KATP) opener and nitrate, has antiischemic effects during transient ischemia in pigs, and to investigate whether its effects are due to its KATP-opening action or nitrate action. Myocardial ischemia was induced by ligating the proximal portion of the left anterior descending coronary artery for 1 minute in anesthetized open-chest pigs, and was measured as the magnitude of ST-segment elevation on epicardial electrocardiogram (ECG). Epicardial ST-segment elevation during coronary occlusion was significantly reduced by pretreatment with NIC (3 mg, intracoronary [i.c.]), but not by pretreatment with nitroglycerin (NTG, 0.2 mg, i.c.). Pretreatment with glibenclamide (GLB, a KATP blocker, 6 mg, i.c.) significantly augmented the ST-segment elevation during coronary occlusion. The augmentation of ST-segment elevation by GLB was significantly reduced by subsequent administration of NIC, but not by that of NTG (0.2 mg, i.c.). There were no significant differences between hemodynamic variables immediately before coronary occlusion with and without pretreatment. The intracoronary administration of NIC (3 mg) significantly shortened the endocardial monophasic action potential durations at 50% (MAPD50) and 90% repolarization (MAPD90) by 28.3 +/- 6.9% and 17.0 +/- 4.7%, respectively. These results suggest that the intracoronary administration of NIC has antiischemic effects during transient ischemia via KATP activation in myocardium.
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PMID:Nicorandil improves ischemic changes in epicardial ECG during short-term coronary occlusion by opening ATP-sensitive potassium channels in pigs. 951 71

Molsidomine, coronary drug which acts similar to organic nitrates, belongs to the drug class of sydnones . SIN-1A metabolite of Molsidomine has pharmacologically active group of NO, which by increasing levels of cGMP, decreases levels of intracellular calcium ions in smooth muscle cells. This effect leads to relaxation of smooth muscle vasculature, inhibits platelets aggregation and has indirect antiproliferative effect. In clinical observations no effect of tolerance to the drug was observed. Experimental data show additional mechanism of action of the drug: SIN-1C metabolites protects the reoxygenated cardiomyocyte from post-reperfusion damage. Indications for use of Molsidomine are: ischaemic heart disease, chronic heart failure and pulmonary hypertension. Effects of Molsidomine use in acute myocardial infarction and unstable angina were compared in clinical trials to effects of nitroglycerin use. Both drugs were found equally potent, but authors underline the fact of better Molsidomine tolerability comparing NTG, but longer serum half-time of Molsidomin effects that control of the treatment is worse. In clinical trials it was suggested that intravenous use of Molsidomine metabolite SIN-1 during PTCA procedures is more effective than use of isosorbide dinitrate in the same procedures. In other clinical trials molsidomin was found to produce beneficial effects in patients with heart failure due to ischaemic cardiomyopathy, dilatative cardiomyopathy, in essential hypertension, pulmonary artery hypertension in COPD patients and in congestive heart failure.
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PMID:[Molsidomine: importance in treatment of circulation disorders]. 1022 68

Perioperative myocardial ischemic episodes are predictive of adverse cardiac outcomes after coronary artery bypass surgery. We compared the efficacy of continuous infusions of nicardipine (group NIC) and nitroglycerin (group NTG) in reducing the frequency and severity of myocardial ischemic episodes. Patients received either a nicardipine infusion, 0.7 to 1.4 microg/kg/min (n = 30), nitroglycerin infusion, 0.5 to 1 microg/kg/min (n = 30), or neither medication (group C; n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes were considered as ST segment depressions or elevations of 1 mm or greater from baseline, each at J + 60 milliseconds and lasting 1 minute or greater, using a two-channel Holter monitor. Only nicardipine significantly decreased the duration (3.2 +/- 1.2 min/h) and the area under the ST time curve (AUC; 5.7 +/- 15.7 AUC/h) of 1-mm or greater myocardial ischemic episodes compared with group C (17.2 +/- 5.6 min/h and 30.1 +/- 49 AUC/h, respectively) during the intraoperative postbypass period. A trend toward lower frequency, duration, and area under the ST time curve of myocardial ischemic episodes was observed in group NIC compared with group NTG. Cardiac indices and mixed venous oxygen saturations were significantly greater, whereas systemic pressures were less in group NIC compared with group NTG for the same period. These results suggest that nicardipine, but not nitroglycerin, decreased the duration and area under the ST time curve of myocardial ischemic episodes shortly after coronary revascularization. Larger studies are required to verify the efficacy of nicardipine in reducing the severity of myocardial ischemia during cardiac surgery.
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PMID:Effects of nicardipine and nitroglycerin on perioperative myocardial ischemia in patients undergoing coronary artery bypass surgery. 1037 52

Myocardial ischaemia and left ventricular dysfunction have been described in cocaine users. Whether nitric oxide (NO) inhibition may potentiate the effects of cocaine on coronary circulation and ventricular function is still unknown. In order to test this hypothesis, 38 pentobarbital-anaesthetized pigs were instrumented for systolic blood pressure, coronary blood flow, left ventricular dp/dt, cardiac output, left ventricular end-diastolic and end-systolic lengths and shortening fraction. The pigs were randomized into three groups: control group: i.v. saline (n = 5); group 1: i.v. cocaine, 10 mg kg-1 over 20 min (n = 17); group 2: the same doses of cocaine 30 min after i.c. L-NAME 20 microg/kg min-1 infusion (n = 16). In order to know whether the observed effects were specific of NO inhibition, in five pigs i.c. L-arginine was simultaneously infused with L-NAME, in five pigs i.c. NTG, an endothelial-independent vasodilator, was simultaneously infused with L-NAME before cocaine was administered, and in nine additional pigs the proximal left anterior descending (LAD) flow was reduced to around 20% of the basal value by means of a mechanical occluder before cocaine was administered. Cocaine i.v did not change the coronary blood flow, while it induced a significant reduction in cardiac output, left ventricular dp/dt and shortening fraction (15 +/- 4-8 +/- 4%, P < 0.05). When cocaine was administered after L-NAME infused i.c. during 30 min, a significantly more severe reduction of the shortening fraction (12 +/- 3-4 +/- 2%, P < 0.0001) was induced; this effect was abolished by simultaneous perfusion of L-arginine i.c. NTG. The results when cocaine was administered after the 20% LAD flow reduction by mechanical occluder did not differ from those of cocaine alone. NO inhibition intensifies the cocaine-induced left ventricular dysfunction.
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PMID:Nitric oxide inhibition intensifies the depressant effect of cocaine on the left ventricular function in anaesthetized pigs. 1111 57

Prior to anesthesia a 65-year-old patient received 8 mg dexamethasone to prevent postoperative nausea and vomiting (PONV). Instantly she reported tingling and burning followed by intense pain in the genital region spreading to the whole body. Shortly later she complained about shortness of breath and pre-cordial pain. Acute hypertension could only be lowered by NTG, beta-blockade and induction of anesthesia. The ECG showed ST-segment depressions and troponin-T was elevated (0.3 ng/ml). Coronary angiography revealed no significant stenosis and an abdominal CT scan showed no evidence of a pheochromocytoma. Urine metabolites of catecholamines were negative. Thus, the most likely diagnosis was stimulation of endogenous catecholamines by painful stress after dexamethasone injection with the consequence of myocardial ischemia. As a result we now routinely inject dexamethasone after anesthesia induction as prophylaxis for PONV.
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PMID:[Acute hypertension following dexamethasone. A critical incident during anesthesia]. 1662 58


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