Stress-Specific Influences of Opioids on Cardiac Electrical Stability

Opioids and Arrhythmias. Evidence is provided indicating that the action of opioids on cardiac electrical stability is contingent on the nature of the stress that impinges on the myocardium. This concept is illustrated by the studies of three clinically relevant conditions, namely, acute behavioral stress, hemorrhage, and myocardial ischemia. During aversive conditioning in dogs, morphine sulfate has been found to prevent the stress-induced reduction in cardiac electrical stability. This protective effect is significantly blunted by administration of atropine, indicating that enhanced vagal activity plays a major role. However, there is a remaining component of morphine's action, which is probably due to reduced perception of the aversive stress. In the context of hemorrhage, the mu-selective agonist fentanyl substantially reduces the profibrillatory effect of this physiological stress. The main mechanism involved in this condition is amplification of baroreceptor sensitivity leading to inhibition of cardiac sympathetic drive. Full activation of mu receptors with fentanyl is also effective in reducing vulnerability to fibrillation during acute coronary artery occlusion. This effect was due to vagal efferent activation and not to enhanced baroreceptor responsiveness as in the case of hemorrhage. Administration of the partial mu-agonist buprenorphine does not exert an antifibrillatory action. Collectively, these results not only demonstrate the potent stabilizing influence of opioids on cardiac rhythm but also the stress specificity of the intermediary mechanisms.