Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts

Abstract

Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca²⁺ handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na⁺/Ca²⁺ exchanger blocker KB-R7943, propranolol, and the adenosine A₂ receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control ( n = 9), KB-R7943 (1 μM, n = 9), propranolol (1 μM, n = 9), and SCH-58261 (1 μM, n = 9). Both the Na⁺/Ca²⁺ exchanger blocker KB-R7943 and propranolol induced a significant reduction ( P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na⁺/Ca²⁺ exchanger blocker KB-R7943 and by propranolol but not by the adenosine A₂ receptor antagonist SCH-58261.