Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiarrhythmic effect of alpha 1-adrenoceptor antagonists during myocardial ischemia and reperfusion remains controversial. The potential antiarrhythmic properties of indoramin, an alpha 1-antagonist, were assessed in the isolated perfused rat heart during regional ischemia and during sustained reperfusion. Coronary artery ligation (CAL) decreased the ventricular fibrillation threshold (VFT) of control hearts from 9.1 +/- 1.3 (pre-CAL, mean +/- SEM) to 2.1 +/- 0.5 mA 15 min post-CAL (p less than 0.0001). Perfusion with indoramin 10(-8) M (alpha 1-receptor antagonistic concentration) started 5 min prior to CAL did not prevent the fall in VFT after CAL. Indoramin 10(-6) M prevented the fall in VFT after CAL relative to the control group. Indoramin 10(-5) M markedly increased the VFT before CAL from 9.9 +/- 1.0 to 28.6 +/- 2.9 mA (p less than 0.0001) and prevented the fall in VFT after CAL. During reperfusion, indoramin 10(-5) M decreased the incidence of spontaneous ventricular fibrillation (VF) to 1 of 6 vs. 6 of 6 in the control group (p less than 0.02). Indoramin 10(-5) M preserved adenosine triphosphate in the reperfused myocardium: 2.82 +/- 0.06 vs. 2.16 +/- 0.21 mumol/g in the control group (p less than 0.05). Specific alpha 1-antagonist properties of indoramin did not appear to be involved in the antiarrhythmic effects.
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PMID:Antiarrhythmic and metabolic effects of indoramin during acute regional ischemia and reperfusion in isolated rat heart. 169 64

Indoramin was administered as a single 50 mg oral tablet to 5 elderly (aged 68-71 years) and 6 middle-aged (aged 46-55 years) healthy female volunteers. The mean half life of indoramin in elderly subjects (14.7 +/- 4.8 h, mean +/- SEM) was statistically significantly longer than that seen in middle-aged subjects (5.1 +/- 1.0 h). The mean plasma concentrations of indoramin and mean area under the plasma concentration/time curve were also greater in elderly than in middle-aged subjects, although this did not achieve statistical significance. In many elderly patients, therefore, a reduction in dosage may be required due to the apparent reduction in clearance of indoramin. However, because of the wide inter-subject variability observed in the oral pharmacokinetics of indoramin, individual titration of indoramin dosage in all patients may be desirable.
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PMID:Pharmacokinetics of oral indoramin in elderly and middle-aged female volunteers. 649 5