Autonomic control of heart rate in dogs treated chronically with morphine

The vagotonic effect of chronic morphine on the parasympathetic control of the heart was examined in dogs treated with morphine for 2 wk. Because norm al vagal function is critical to myocardial stability. the study was conduc ted to evaluate for potential impairments following chronic vagal stimulati on. The hypothesis that persistent vagal outflow would result in a loss of vagal reserve and reduced vagal control of heart rate was tested. Heart rat e and the high-frequency variation in heart rate (power spectral analysis) declined shortly after initiation of subcutaneous morphine infusion. A prog ressive bradycardia correlated well with the rising plasma morphine. The re sting bradycardia (57 beats/min) was maintained through day 2 and was accom panied by a significant parallel increase in vagal effect and a decline in the intrinsic heart rate (160 vs. 182 beats/min). A compensatory increase i n the ambient sympathetic control of heart rate was evident on day 2 and wa s supported by an increase in circulating catecholamines. The lowered intri nsic heart rate and elevated sympathetic activity were maintained through d ay 10 despite a return of the resting heart rate and plasma catecholamines to pretreatment values. These observations suggested that chronic morphine alters either the intrinsic function of the sinoatrial node or reduces the postvagal tachycardia normally attributed to nonadrenergic, noncholinergic agents. Both acute and chronic morphine depressed the rate of development o f bradycardia during direct vagal nerve stimulation without altering the ra te of recovery afterward. This last observation suggests that acute morphin e reduces the rate of acetylcholine release. Results provide insight into t he mechanisms that maintain vagal responsiveness. The results are also rele vant clinically because opiates are increasingly prescribed for chronic pai n and opiate abuse is currently in resurgence.