| Abstrakt: |
Objective: Myocardial ischaemia can provoke a rise in cytosolic calcium which may in turn trigger malignant ventricular arrhythmias. Recently, inhibition of calcium entry has been shown to prevent these lethal arrhythmias. However, the contributions of calcium release from cytosolic stores to these disruptions in cardiac rhythm have not been investigated. This study examines the role of calcium release from the sarcoplasmic reticulum in the initiation of lethal ventricular arrhythmias. Methods: Mongrel dogs were chronically instrumented to measure left ventricular pressure, coronary blood flow, and cardiac electrical activity (ventricular electrocardiogram). The left anterior descending coronary artery was ligated during the surgery to produce a myocardial infarction. In addition, a hydraulic occluder was placed around the left circumflex artery. The susceptibility to ventricular fibrillation was then evaluated by the combination of acute myocardial ischaemia and exercise. Results: Ventricular fibrillation was induced in 10 animals during the exercise plus ischaemia test. On a subsequent day the exercise plus ischaemia test was repeated after pretreatment with ryanodine (10 μg·kg−1, n = 10), a drug which impairs calcium efflux from the sarcoplasmic reticulum. Ryanodine failed to prevent ventricular fibrillation induced by ischaemia. Ryanodine significantly (p<0.01) increased heart rate [control 115.3(SEM 6.3) v ryanodine 156.4(14.7) beats·min−1] but reduced left ventricular systolic pressure [control 141.8(4.9) v ryanodine 111.1(12.7) mm Hg] and positive left ventricular dP/dt [3312.9(217.4) v ryanodine 1462.9(226.3) mm Hg·s−1] both at rest and during exercise. In contrast, this drug abolished ventricular tachycardia induced by ouabain toxicity (n = 10, 40 μg·kg−1 bolus followed by 0.076 μg·kg−1·min−1 for 1 h, then 20 μg·kg−1 bolus, intravenously). Conclusions: These data suggest that calcium release from ryanodine sensitive channels in the sarcoplasmic reticulum may contribute significantly to the arrhythmias induced by ouabain toxicity but not to ventricular fibrillation provoked by ischaemia.Cardiovascular Research 1993;27:2152-2159 [ABSTRACT FROM PUBLISHER] |
