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)

Experiments were carried out to provide evidence of the effect of L-arginine (L-Arg), its analogue NG-monomethyl-L-arginine (MeArg) and of some nitrovasodilators (sodium nitroprusside, NaNP; 3-morpholino-sydnonimine, SIN-1) which spontaneously release nitric oxide (NO) on ischemia-reperfusion injury, histamine release and mast cell degranulation, occurring after multiple ligature and release of the left anterior descending (LAD) coronary artery in isolated perfused guinea-pig hearts. The reopening of the LAD coronary artery leads to a release of histamine related to a decrease in microdensitometry of cardiac mast cells and to calcium overload. The perfusion of the heart with NO-donors significantly reduces either the release of histamine, the loss of mast cell metachromasia and the overload of calcium. These effects were potentiated by SOD. The results suggest that the endogenous formation of NO and molecules able to generate NO have a role in the prevention of post-ischemic tissue injury.
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PMID:The effect of nitric oxide generators on ischemia reperfusion injury and histamine release in isolated perfused guinea-pig heart. 171 36

The effect of ischemia-reperfusion on endothelium-dependent relaxations and reactivity of vascular smooth-muscle cells was studied in rings of basilar arteries obtained from six dogs exposed to 12 min of complete global cerebral ischemia followed by 100 min of reperfusion. Three sham-operated control dogs served as controls. Ischemia was induced either by an increase in intracranial pressure or by aortic occlusion. The rings were suspended for isometric tension recording in physiological salt solution. Ischemia-reperfusion did not affect endothelium-dependent relaxations to vasopressin and bradykinin. In rings without endothelium relaxations to sodium nitroprusside, molsidomine (SIN-1), and papaverine as well as contractions to 5-hydroxytryptamine and KCl were preserved. These results demonstrate that in large canine cerebral arteries, ischemia-reperfusion of these durations does not affect relaxations mediated by activation of endothelium or direct relaxations and contractions of vascular smooth-muscle cells.
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PMID:Ischemia-reperfusion does not affect reactivity of isolated canine basilar artery. 187 14

The effects of the molsidomine metabolite SIN-I (0.5 mg) on tolerance to ischemia were studied in twelve patients during coronary angioplasty of the LAD. SIN-I resulted in a significant prolongation of time to ST-segment alteration one, five and ten minutes after intracoronary injection. Beside hemodynamic reasons the effects of SIN-I on circulating blood cells and collateral perfusion are discussed as mechanisms of action. The effects of molsidomine (2 X 8 mg/d) on restenosis rate after initially successful coronary angioplasty were studied in 393 patients in a prospective, randomized and controlled trial. 29% of patients treated with molsidomine experienced restenosis at control coronary angiography at six months. The control group receiving nifedipine (3 X 20 mg/d) and acetylsalicylic acid (1 X 500 mg/d) showed a restenosis in 33% of patients. Therefore, molsidomine seems as effective as nifedipine and acetylsalicylic acid in treating patients after coronary angioplasty.
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PMID:[Acute and chronic effects of molsidomine in therapeutic coronary angioplasty]. 218 4

To monitor free radical scavenging properties of drugs, the 'stable' radical 2,2,6,6-tetramethylpiperidino-1-oxyl (TEMPO) was used. The sydnonimine molsidomine (SIN-1) effectively reduced the ESR signal whereas the nitrate isosorbidemononitrate (ISMN) did not. Thiol reagents like 2-mercaptopropionylglycine (MPG) or glutathione (GSH) only were effective in the presence of Fe2+ or Fe3+. Protein-bound iron in hemoglobin proved about four times more effective in reducing ESR signal height by thiols. It is suggested that the decrease in thiol content adds to the lack in protein bound iron of hemoglobin to induce the burst of free radicals in hypoxia (ischemia) and reperfusion.
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PMID:Free radical scavenging drugs, assessed by ESR studies: influence of hemoglobin. 285 30

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

In six anesthetized dogs with myocardium partially damaged by ischemia (LAD occlusion), the effect of an i.v. bolus injection of 0.05 mg molsidomine/kg body weight followed by a 6-h i.v. infusion of 0.5 micrograms molsidomine/kg/min on the volume of myocardial ischemia, the relative remaining blood flow in the ischemic area, and the dynamics of the left ventricle were examined by means of computer tomography. The extent of the ischemic volume in the group treated with molsidomine was by far lower than in the control group; this difference was significant if one takes into account the individual heart size. The relative remaining blood flow in the ischemic region was not influenced by molsidomine. The reduction of preload and afterload resulted in corresponding changes in left ventricular areas, segments of these areas, the long axis, thickness of myocardium, ejection fraction and stroke volume. Aortic pressure was lowered insignificantly, heart rate remained nearly unchanged. Plasma analyses of molsidomine. SIN 1 and SIN 1C show that the applied dosage was sufficient to reach a constant concentration over the whole period of observation in the dog.
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PMID:The influence of molsidomine on myocardial ischemia and ventricular dynamics. An in-vivo study in anesthetized dogs by means of computer tomography. 341 34

The long-acting antianginal drug molsidomine has been shown experimentally to reduce myocardial infarct size when administered prior to or after cardiac insult. This is due to several drug actions. Dilation of postcapillary capacitance vessels diminishes venous return, preload, heart dimensions, and myocardial oxygen consumption. Relaxation of stenosed conductive coronary arteries increases the perfusion of myocardial areas at risk of infarction due to enhanced collateral circulation. Increased regional blood supply nourishes predominantly subendocardial cardiac muscles as a result of reduction of extravascular coronary pressure, and resistance. The stable heart rate and cardiac contractility favor improved heart performance. The inhibition of platelet aggregation in vivo by molsidomine or its active metabolites, SIN-1 and SIN-1A, is linked to the stimulation of prostacyclin synthesis, inhibition of thromboxane release with induction of thrombosis and vasoconstriction, and enhanced concentrations of cyclic guanosine monophosphate. Dilation of coronary arteries after intracoronary administration of SIN-1, with inhibition of platelet aggregation by restrained release of adenosine diphosphate and stabilization of platelet membranes, facilitates the recanalization of stenosed arteries and reduces coronary muscle tone at the site of thrombosis. Activation of the human fibrinolytic system and drug-induced release of a plasminogen activator favor dysaggregatory effects. The drug's inhibiting actions on lipoxygenase products of arachidonate (e.g., 12-hydroperoxy-eicosatetraenoic acid and leukotrienes) may shift prostaglandin catabolism to cyclooxygenase products (e.g., prostacyclin) that protect against the expansion of ischemia and the induction of coronary spasm. Experimentally, the hemodynamic effectiveness of molsidomine can be antagonized by catecholamines (afterload effects) and dihydroergotamine (preload and afterload effects) respectively. Further clinical investigations will clarify the application of these mechanisms for the therapeutic success of the drug in human myocardial infarction.
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PMID:Molsidomine: alternative approaches to treat myocardial ischemia. 355 58

In 28 patients with unstable angina pectoris biplane coronary angiography was performed in the acute stage. Arteriography of the ischemia-related vessel was subsequently repeated in 14 patients after intracoronary infusion of 0.2 mg nifedipine and ten minutes later after 10 mg sublingual nifedipine (group I) and in 14 patients after intracoronary infusion of 0.4 mg 3-N-morpholinosyndnonimine (SIN-1) (group II). 17 patients were on intravenous nitroglycerin and 11 patients on high-dose oral isosorbide dinitrate therapy at the time of angiography. Pre- and postintervention, the degree of coronary stenosis of the ischemia-related vessel was determined by three morphometric methods: rmin, minimal diameter of the stenosis, Amin, planimetered area under the stenosis and minimal diameter ratio (min diam ratio), ratio of the minimal diameter of the stenosis and the pre- and poststenotic diameter. An increase in lumen was considered to be significant when two of the three parameters increased by more than 5%. Nifedipine application resulted in an increase in lumen in 13 patients of group I. After i.c. nifedipine the lumen increased by 16% and after s.l. nifedipine by an additional 9%. Combined i.c. and s.l. nifedipine increased the lumen of the critical stenosis by 24 +/- 6.8%. In 10 patients of group II, SIN-1 application was successful and resulted in a luminal increase of 28 +/- 2.6%. In more than 80% of our patients with unstable angina pectoris application of nifedipine and SIN-1 resulted in an increase of the lumen. Thus, coronary vasoconstriction seems to be the predominant mechanism next to organic stenosis in unstable angina.
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PMID:[Dynamics of critical stenosis in patients with unstable angina pectoris]. 643 35

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

Langendorff-perfused rabbit hearts were subjected to 2 h of global, low-flow ischemia followed by 30 min of reperfusion. This resulted in a marked increase of left ventricular enddiastolic pressure and a loss in left ventricular creatine phosphokinase activity. NO formation was significantly reduced in early reperfusion. In the presence of superoxide dismutase (20 U/ml), NO release (oxyhemoglobin technique) was completely normalized, indicating inactivation of NO by superoxide radicals. Treatment with glyceryl trinitrate (GTN; 30 microM) prevented ischemia-induced myocardial tissue injury. SIN-1 (0.3 microM) was ineffective. These data demonstrate a protective effect of GTN but not SIN-1 in myocardial ischemia. It is concluded that the site of NO generation may play an important role in determining the biological activity of NO donating substances.
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PMID:Glyceryl trinitrate but not spontaneous NO donors preserve myocardial function and cell integrity in ischemic rabbit hearts. 771 78


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