BAXTER, GF and YELLON, DM (1993) ATTENUATION OF REPERFUSION-INDUCED VENTRICULAR-FIBRILLATION IN THE RAT ISOLATED HYPERTROPHIED HEART BY PREISCHEMIC DILTIAZEM TREATMENT. CARDIOVASC DRUG THER , 7 (2) 225 - 231.
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The ability of the calcium antagonist diltiazem to protect against reperfusion-induced arrhythmias in hypertrophied myocardium was studied. Hearts from normotensive and DOCA-salt hypertensive rats were Langendorff perfused and subjected to 10 minutes of stabilization, 10 minutes of left coronary artery occlusion, and 5 minutes of reperfusion. The incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion were determined and the effects of diltiazem or vehicle (given as a single bolus 3 minutes before coronary artery occlusion) were assessed in hypertrophied and normal hearts. In vehicle-treated (control) hypertrophied hearts, VF incidence was 91% compared with 67% in normal hearts, and the median duration of VF was 272 seconds (mean 207.4 +/- 32.3) compared with 27 seconds (mean 110.6 +/- 36.6; p < 0.05), respectively, suggesting that reperfusion VF is more severe in hypertrophied hearts. In normal hearts, diltiazem 18 mug reduced VT incidence from 92% to 55%, reduced VF from 67% to 27%, and sustained VF from 42% to 9%. In hypertrophied hearts, 18 mug diltiazem reduced the VT incidence from 100% to 58%, reduced VF from 91% to 25% (p < 0.01), and sustained VF from 82% to 8% (p < 0.01). Median VF duration in this group was reduced to 0 seconds (p < 0.05; mean 24.7 +/- 22.6). Diltiazem did not significantly affect heart rate or coronary flow rate decreases during ischemia. However, developed tension, at the onset of ischemia, was lower in diltiazem-treated groups than in the control groups. We suggest that the attenuation by diltiazem of reperfusion-induced arrhythmias observed in this model was related to an energy-sparing effect during ischemia. This study shows that diltiazem administered acutely before the onset of ischemia attenuates reperfusion-induced arrhythmias in the hypertrophied myocardium, despite its greater susceptibility to reperfusion-induced arrhythmias.
|Title:||ATTENUATION OF REPERFUSION-INDUCED VENTRICULAR-FIBRILLATION IN THE RAT ISOLATED HYPERTROPHIED HEART BY PREISCHEMIC DILTIAZEM TREATMENT|
|Keywords:||LEFT VENTRICULAR HYPERTROPHY, ISCHEMIA-REPERFUSION, REPERFUSION ARRHYTHMIAS, VENTRICULAR FIBRILLATION, DILTIAZEM, INDUCED ARRHYTHMIAS, ISCHEMIC-INJURY, GLOBAL-ISCHEMIA, IMPROVEMENT, CONDUCTION, REDUCTION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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