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)

We studied the effects of carbocromene (4 mg/kg plus 40 micrograms/kg/min i.v.) and molsidomine (0.1 mg/kg plus 2 micrograms/kg/min i.v.) on arrhythmias occurring during 90-min occlusion and 30-min reperfusion of the left anterior descending coronary artery in anesthetized dogs. Both drugs reduced the incidence of left ventricular (LV) premature depolarization during ligation (39% after carbocromene and 33% after molsidomine vs. 80% in controls; both p less than 0.05) and tachycardia (44% after carbocromene and 38% after molsidomine vs. 85% in controls; p less than 0.05). During reperfusion, the incidence of LV fibrillation was reduced in the carbocromene- (6 vs. 38% in controls; p less than 0.05) and molsidomine-treated dogs (10 vs. 38% in controls; p less than 0.05). The high incidence of ectopic activity and the ST segment elevation occurring after coronary ligation in control animals were prevented by both drugs. The hemodynamic deterioration after coronary occlusion, i.e., increase in blood pressure, LV systolic and end-diastolic pressures, LV dP/dtmax, and tachycardia observed in controls, was prevented by carbocromene. Molsidomine reduced blood pressure and LV pressure by 18 and 27% (p less than 0.05), respectively, during coronary occlusion. During reperfusion, no hemodynamic alterations occurred in the drug-treated animals. We conclude that carbocromene reduced the electrophysiologic consequences of acute ischemia by hemodynamic and anti-ischemic effects on heart metabolism. Molsidomine protected the jeopardized heart by a similar attenuation of hemodynamic derangement after coronary occlusion and perhaps by influencing prostanoid release from the ischemic myocardium.
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PMID:Protection by carbocromene and molsidomine against arrhythmias occurring during coronary artery occlusion and reperfusion in dogs. 241 9

Platelet suppressive agents have been shown to improve the prognosis of coronary diseases such as myocardial infarction and unstable angina. Several markers of platelet activation during myocardial ischemia have been found to be increased. Platelet granule constituents (beta thromboglobulin or platelet factor 4) or thromboxane B2 have been reported to be enhanced and, in some studies, to be correlated with the ischemia. Molsidomine or its active metabolite SIN-1 have antithrombotic properties in experimental models. This effect seems to be at least partly related to their antiplatelet activities. SIN-1A inhibited platelet aggregation and release reaction. Specific investigations have demonstrated that SIN-1A acts at a early stage of platelet activation inhibiting calcium influx and phospholipase activity which lead to inhibition of thromboxane formation and fibrinogen binding. Antiplatelet properties were also observed after oral administration of molsidomine but the extent of inhibition appeared to vary with the subjects.
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PMID:[Role of molsidomine on platelet activation in coronary ischemia]. 296

The effect of molsidomine, a novel antianginal agent, on the epicardial electrographic changes induced by reduced perfusion of the left anterior descending coronary artery (LAD) was investigated in the anesthetized dog. The LAD was cannulated and perfused at a constant volume with blood taken from a carotid artery. The perfusion volume was than reduced by approximately 75%. The sum of the ST-segment changes obtained from six unipolar epicardial leads was taken as a measure of myocardial hypoxia. Simultaneously, heart rate, blood pressure, left ventricular end-diastolic pressure, pulmonary arterial pressure, and heart contractility were also recorded. In control animals, reduction of the perfusion volume of the LAD resulted in a dramatic elevation of the ST segments lasting more than 4 hr. Molsidomine administered after the induction of the ischemia at a dose of 0.05 mg/kg i.v. resulted within 40 min in a complete normalization of the electrographic changes. This effect was evident for over 4 hr in spite of the continuous reduced perfusion of the LAD. The beneficial effect of molsidomine on the electrical changes paralleled the reduction of the left ventricular end-diastolic pressure. It is suggested that the effect of molsidomine on the ischemic electrographic changes is brought about by a reduction of the preload, resulting in a better perfusion of the ischemic zones.
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PMID:Anti-ischemic effects of molsidomine in an experimental model of coronary artery stenosis. 668 48

Molsidomine is a derivative of the sydnonimines and is a long-acting vasodilator that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy and drug tolerance, eight men with stable angina pectoris performed a symptom-limited maximal exercise test on a computer-assisted treadmill. After ingesting either placebo or molsidomine administered in single blind fashion 90 min before the exercise test on the first day of treatment, molsidomine decreased the average systolic blood pressure response from 154 +/- 3 (SEM) to 135 +/- 4 mmHg (p less than 0.01). However it did not significantly change the average heart rate response (117 +/- 7 to 124 +/- 8 beats/min) and the rate-pressure product (18.1 +/- 1.2 X 10(3) to 16.8 +/- 1.1 X 10(3]. The average time up to the onset of ischemia at which significant ST-segment deviation (0.1 mV) first appeared was increased from 9.0 +/- 1.7 to 12.8 +/- 1.2 min (p less than 0.001) after molsidomine. At peak exercise after molsidomine, the mean value of ST-segment deviation in V5 or aVF was decreased (p less than 0.001). This result was obtained even though the average exercise duration was increased from 11.4 +/- 1.7 to 13.6 +/- 1.2 min (p less than 0.001). The treadmill score according to Hollenberg was also improved from -47 +/- 24 to 1 +/- 14 after molsidomine administration. After six weeks of continued therapy with molsidomine the favorable effect on exercise tolerance was significantly decreased in terms of exercise duration, the time up to the onset of ischemia, and the treadmill score.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of molsidomine on exercise tolerance in patients with exertional angina pectoris. 668 83

This paper is a synopsis on recent reports dealing with the pharmacological basis of molsidomine-induced circulatory effects. The therapy of coronary insufficiency by molsidomine is based on different pathophysiological and pharmacological mechanisms. The inactive compound molsidomine is metabolized--mainly in the liver--to form the vasoactive and antiaggregatory compound SIN-1 and SIN-1A. Due to the gradual conversion into the active compound, the peak effects are observed only after 15 min (intravenously) or 30 to 60 min (orally). The effects are long-lasting and can be observed up to four to six hours. The c-GMP mediated dilation of various vascular sites comprise mainly the venous system (both small and large veins), resulting in a significant preload reduction, a decrease in cardiac output, a decrease in heart size and circumferential wall stress, a decrease in myocardial oxygen consumption and a therapeutically important improvement of O2-delivery versus myocardial O2-consumption. This effect results in a significant improvement of myocardial ischemia (reducing frequency of anginal attacks, improvement of exercise tolerance and of exercise induced ST-depressions). In animal experiments molsidomine diminishes infarct size and suppresses reperfusion-induced ventricular fibrillation following ischemia. Molsidomine dilates, like nitroglycerin, the large coronary arteries. Therefore, in coronary heart disease, it may improve collateral flow in addition to beneficial effects on subendocardial perfusion resulting from the reduction of ventricular wall stress. In addition to direct dilating effects on collateral vessels an improvement in perfusion of asynergistically contracting ventricular sections has been observed. In contrast to nitroglycerin, effects on peripheral resistance appear only under extremely high dosages and reflex increases in heart rate are rarely observed. In general molsidomine-induced changes (increases) in heart rate, in stroke volume (decreases), and in cardiac output (decreases) are of small magnitude. Recently interesting findings on molsidomine-induced suppression of thrombocyte aggregation, of thromboxan-synthesis inhibition and of increased prostacyclin formation have been presented, which may be important in the improvement of myocardial (micro-) circulation under ischemic conditions.
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PMID:[Pharmacological basis of therapy with molsidomine]. 689 44

Aim of this experimental study is to verify the protective effect of molsidomine on the renal function and structural modifications in the ischemia-reperfusion rat kidney. Sixty-eight male Sprague-Dawley rats, which were right nephrectomized and occluded left renal artery for 60 minutes were used. Group I (n = 10) Sham-Operated animals, which only underwent right nephrectomy. Group II (n = 20) Untreated ischemic rats, which underwent left renal ischemia by occlusion of the renal artery for 60 minutes before blood flow was restored. Group III (n = 18) Molsidomine treated ischemic rats, Group IV (n = 20) L-NAME (N(G)-nitro-L-arginine methyl ester) treated ischemic rats. Serum creatinine and blood urea nitrogen (BUN) were measured daily and biopsies were obtained from the remaining left kidneys. At seventh day, 55% and 50% of the rats remained alive at the G-II and G-IV respectively. Molsidomine treated rats (G-III) were alive and healthy at day 7. The serum creatinine and BUN levels were significantly higher in G-II and G-IV when compared with the sham-operated group (G-I). G-III rats showed a rapid return to the normal serum creatinine and BUN values on postoperative days 1, 2, 3 and 4. The obtained values in G-II were significantly lower in comparison to the values of G-II and G-IV. The most severe damage (grade 3 to 4) was determined in the kidneys of rats from GII or GIV. The degree of renal tubular damage in GIII was evaluated as grade 1 or 2 tubular damage according to Jablonkski's scale. Our findings suggested that the administration of molsidomine may vanquish the pernicious effects of warm ischemia on kidney structure and function.
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PMID:The effects of the nitric oxide donor molsidomine prevent in warm ischemia-reperfusion injury of the rat renal--a functional and histophatological study. 1198 49

It is suggested that gastrointestinal mucosal blood flow depends on a balanced release of vasoactive substances from the endothelium. The present study investigated the effects of molsidomine on the small intestine after ischemia-reperfusion (I/R) injury in four groups of 10 rats each composed: (1) SO, sham operation; (2) untreated I/R; (3) ML, I/R plus molsidomine pretreatment; (4) L-NAME, I/R plus N-omega-nitro-L-arginine methyl ester pretreatment. Intestinal ischemia for 45 min and reperfusion for 60 min were applied. Ileum specimens were obtained to determine the tissue level of malondialdehyde (MDA) and histologic changes. Mean MDA levels in the SO, untreated I/R, ML, and L-NAME groups were 95.60 +/- 2.59, 136.90 +/- 4.35, 121.10 +/- 3.38, and 137.40 +/- 4.42 nmol/g wet tissue, respectively. Although the MDA level in the ML group was higher than in the SO group ( P < 0.0001), it was significantly lower compared to the untreated I/R and L-NAME groups ( P < 0.0001, P < 0.0001). Mucosal injury scores (MIS) in groups 1-4 were 0.2 +/- 0.42, 3.9 +/- 0.73, 1.5 +/- 0.70, and 4.1 +/- 0.56, respectively. In group 3 the MIS was significantly lower than in groups 2 and 4 ( P < 0.0001, P < 0.0001). Molsidomine plays a role in attenuating reperfusion injury of the small intestine by depression of tissue MDA levels and MIS and regulates post-ischemic intestinal perfusion while restoring the intestinal microcirculatory blood flow and histologic injury.
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PMID:The nitric oxide donor molsidomine prevents ischemia/reperfusion injury of the adult rat small intestine. 1278 56

Ischemia reperfusion (I-R)-induced renal damage is reduced by systemic administration of the NO-dependent vasodilator molsidomine. The aim of this study was to estimate the effect of direct intrarenal molsidomine administration on renal dysfunction and inflammatory reaction after experimental I-R in rats, in order to assess only renal NO effects and to obviate its systemic hemodynamic action. Ischemia was induced by renal pedicle ligation (60 min) followed by reperfusion and contralateral nephrectomy. Molsidomine (4 mg/kg) was infused into the renal artery 15 min before reperfusion and its effects were compared with those of the NO-independent vasodilator hydralazine (2 mg/kg). Survival rates after 7 days were 100% in the sham-operated group and 75% in the I-R rats. Molsidomine treatment almost completely prevented the I-R-induced renal dysfunction, and survival reached 100%. Molsidomine prevented an I-R-induced increase in superoxide anion and reduced plasma levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta and IFN-gamma), whereas it enhanced anti-inflammatory cytokines (IL-6 and IL-10). Inflammatory cell infiltration and cell-adhesion molecules (ICAM-1, PECAM-1, VCAM-1 and P-selectin) were lower in the molsidomine-treated kidneys than in the untreated animals. All these protective effects were not observed after hydralazine administration. In conclusion, intrarenal administration of molsidomine before reperfusion improved renal function and decreased inflammatory responses after I-R.
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PMID:Intrarenal administration of molsidomine, a molecule releasing nitric oxide, reduces renal ischemia-reperfusion injury in rats. 1536 15

Molsidomine is a well-known vasodilatating, antianginal drug. Despite earlier studies with its metabolites (3-morpholino-syndnonimine (SIN-1) and N-nitroso-N-morpholino-amino-acetonitrile (SIN-1A)), which indicated a potential favorable cardioprotective activity, a lot of controversy remains. The aim of our research was to compare molsidomine, SIN-1, SIN-1A, and lidocaine influence on arrhythmias and hemodynamic parameters in 2 experimental models in rats. In the Langendorff heart study, SIN-1A markedly elevated left ventricular systolic pressure, maximum rise and fall of the first pressure derivative, coronary flow, and myocardial oxygen consumption. In addition, SIN-1A more so than SIN-1 significantly lowered creatine kinase release. The antiarrhythmic action of SIN-1 was observed, while lidocaine significantly diminished ventricular arrhythmias duration in comparison with the control. In the ischemia-reperfusion-induced arrhythmias model, hypotensive action of molsidomine was observed as well as the reduction in pressure rate product. Molsidomine also prolonged ventricular tachycardia duration. On the other hand, no significant effects on hemodynamic parameters as well as on ventricular arrhythmias were found in any of the SIN-1 and SIN-1A groups. In conclusion, our research suggests a possible direct, cardioprotective action of SIN-1A. It seems worthwhile to further investigate molsidomine derivatives, especially SIN-1A, because of its potential use in invasive cardiology procedures such as percutaneous transluminal coronary angioplasty.
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PMID:New approach to molsidomine active metabolites coming from the results of 2 models of experimental cardiology. 2791 57