Central beta-adrenergic mechanisms may modulate ischemic ventricular fibrillation in pigs.
A central noradrenergic process may permit expression of the stress-related increase in cardiac vulnerability to ventricular fibrillation (VF). Thus, the effect of central beta-adrenergic receptor blockade with L-propranolol (0.01 and 0.05 mg/kg) on ischemia-induced VF vulnerability was evaluated in the psychologically stressed pig model and compared with Ringer's solution and D-propranolol (0.05 mg/kg). The ischemia of a maximum 15-minute left anterior descending coronary artery occlusion was used since we previously determined that pigs surviving 15 minutes usually do not fibrillate. Time to the onset of VF was analyzed by time-to-event analysis and ranged from 0.75 to 13.8 minutes in vulnerable pigs. Intracerebroventricular administration of L-propranolol (0.05 mg/kg) prolonged the time to VF compared with Ringer's solution and D-propranolol (p less than 0.05). The high dose of L-propranolol also reduced the incidence of VF (7/15 fibrillated) compared with Ringer's solution (12/12 fibrillated) and D-propranolol (6/7 fibrillated). The lower dose of L-propranolol was without effect on VF vulnerability (7/9) fibrillated). The plasma concentration resulting from central administration of 0.05 mg/kg L-propranolol was found to be 9.05 +/- 3.25 ng/ml, which is significantly below therapeutic antiarrhythmic blood levels. We conclude that the reduced vulnerability to ischemia-induced VF after intracerebroventricular administration of propranolol is due to alteration of a central beta-adrenergic receptor-mediated phenomenon as opposed to an effect on the heart directly or to nonspecific membrane stabilization.
Parker
G W
GW
Departments of Medicine, Baylor College of Medicine, Houston, TX 77030.
Michael
L H
LH
Hartley
C J
CJ
Skinner
J E
JE
Entman
M L
ML
D000222:Adaptation, Physiological; D000818:Animals; D001696:Biomechanical Phenomena; D001921:Brain / Q000502:physiology*; D003327:Coronary Disease / Q000150:complications* / Q000503:physiopathology; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D007276:Injections, Intraventricular; D011433:Propranolol / Q000493:pharmacokinetics / Q000494:pharmacology; D011930:Reaction Time; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology
D011943:Receptors, Adrenergic, beta; D011433:Propranolol