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)

We examined the effects of the heparin ion-pair complex ITF 1300 on ventricular fibrillation (VF) and other arrhythmias elicited by regional ischemia and by reperfusion in isolated rat hearts (n = 12 per group). During 30-min ischemia, 1, 3, and 10 mg/L ITF 1300 reduced the incidence of VF concentration dependently, with complete abolition of VF at the highest concentration (p < 0.05). Similar but weaker effects were observed for other arrhythmias [ventricular tachycardia (VT) and salvos]. Reperfusion-induced arrhythmias (elicited after 10- or 30-min regional ischemia) were affected similarly, with complete abolition of VF at the highest drug concentration (p < 0.05). Coronary blood flow (CBF), recovery of CBF during reperfusion, and occluded zone sizes were little affected (p = NS). ITF 1300 caused concentration-dependent bradycardia, PR interval widening, and QT widening. In further studies, we examined the roles of these changes in mediating the antiarrhythmic effects. Left atrial pacing at a rate close to control rate (300 beats/min) abolished the antiarrhythmic effects of ITF 1300 and the QT widening, indicating that bradycardia and QT widening were important in mediating the antiarrhythmic effects. Doubling the calcium concentration in the perfusion solution prevented ITF 1300-induced PR widening, indicating that calcium antagonist activity probably mediated the drug's effects on this variable. However, the antiarrhythmic effect of ITF 1300 was not affected by high calcium perfusion. ITF 1300 is an effective antiarrhythmic agent in a model of ischemic heart disease. Its effects are mediated primarily by heart rate-dependent QT widening and were not related to possible calcium antagonist activity.
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PMID:Protection by ITF 1300, a heparin ion-pair complex, against arrhythmias induced by regional ischemia and reperfusion in the isolated rat heart: possible mechanism of action. 759 34

The actions of ITF 296 and isosorbide dinitrate (ISDN), 20, 70, and 200 g/kg/min, on myocardial transmural blood flow distribution during acute thrombotic occlusion of the left circumflex coronary artery (LCX) have been evaluated in seven and three anesthetized open-chest dogs, respectively, and compared with four animals receiving vehicle. Occlusion of LCX was achieved in 14 +/- 2 min by the insertion of a copper coil. This caused transmural myocardial ischemia in the LCX area, while leaving blood flow in the left anterior descending coronary artery (control area) unaffected. Infusion of ITF 296 (200 g/kg/min) increased transmural coronary flow in the border zone and in the control area without affecting blood flow in the central ischemic area. ISDN, given in the same dose, reduced systemic blood pressure but did not affect LCX blood flow. In three dogs with residual perfusion in the LCX central area ITF 296 also increased blood flow. These results confirm that ITF 296 promotes an increase of flow to the border zone, thus possibly reducing the area of myocardial infarction.
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PMID:The new nitroderivative ITF 296 improves collateral blood flow in a canine model of coronary thrombosis. 883 24

The activity of ITF 296 against methacholine-induced myocardial ischemia was investigated in anesthetized rats in comparison with the organic nitrates nitroglycerin (NTG) and isosorbide dinitrate (ISDN), the K(+)-channel openers nicorandil and cromakalim, the Ca(2+)-channel blocker amlodipine, and the vasodilator dipyridamole. Given as i.v. boluses, ITF 296 (0.1-100 micrograms/kg) dose-dependently prevented methacholine-induced ST-segment elevation without affecting mean arterial blood pressure or heart rate to a significant extent. In this situation, ITF 296 was 10- to 30-fold more potent than the other coronary vasodilators tested. The protective effect of ITF 296 and ISDN against myocardial ischemia was also observed after oral administration, demonstrating good absorption and a limited first-pass metabolism of the two drugs. The anti-ischemic action of ITF 296 at 1 and 10 micrograms/kg/min was well maintained during 2 h of continuous i.v. infusion, whereas the effect of NTG and ISDN was attenuated or abolished by the end of the infusion. The new nitrate ester ITF 296 has a potent and long-lasting cardioprotective action in the anesthetized rat. The anti-ischemic effect displayed by this compound is probably mediated by an improvement of myocardial blood supply caused by pronounced coronary dilatation, whereas the contribution of systemic vasodilation is not important. Moreover, the maintenance of the anti-ischemic action during continuous i.v. infusion suggests a reduced "tolerance" development for ITF 296 compared with other nitrovasodilators.
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PMID:Protective effect of the nitrate ester ITF 296 against methacholine-induced myocardial ischemia in the anesthetized rat. 883 25