The Effect of Dobutamine on Susceptibility to Ischemia‐Induced Ventricular Fibrillation in the Isolated Rat Heart

Sudden cardiac death due to ventricular fibrillation (VF) continues to be a major cause of mortality, but the triggers of VF in ischemia remain poorly understood. Our hypothesis is that VF is triggered in myocardial ischemia as a result of ATP depletion, which causes ionic imbalance and electrical dysfunction that creates an arrhythmogenic substrate. The purpose of this study was to test this hypothesis by determining the effect of increasing cardiac ATP consumption on susceptibility to VF using a classical inotrope, dobutamine. Isolated rat hearts (n=12 per group) were perfused in the Langendorff mode with modified Krebs containing 3 mM K + . Dobutamine or vehicle was locally infused in a randomized and blinded manner to achieve a concentration of dobutamine of 3µM. After a further 15 min, regional ischemia was induced by coronary artery occlusion and maintained for 30 min. VF was determined from the ECG, and cardiac function was evaluated using an intraventricular balloon. Dobutamine increased heart rate and left ventricular developed pressure compared to controls as expected. The incidence of VF (75% vs 67%; P=NS) and time to onset of VF (892±68s vs 730±80s; P=NS) were similar in control and dobutamine groups respectively. Dobutamine reduced ischemic contracture, with end diastolic pressure 36±6 vs 15±3 mmHg after 25 min ischemia in control and dobutamine groups respectively (P<0.05). Thus, although β 1 stimulation by dobutamine increased cardiac work, it did not increase susceptibility to ischemic VF.