The purpose of this protocol is to provide a mechanism f

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Patients in the operating room or intensive care unit frequently need medications to improve the pumping ability of their hearts and their circulatory function. Commonly used medications for these purposes stimulate receptors in the cardiovascular system to achieve these results. These receptors are known as adrenergic receptors and have two major types - alpha and beta. Alpha receptor stimulation causes arteries to constrict and thereby increases blood pressure. Beta receptor stimulation increases heart rate and pumping force and also dilates arterial blood vessels. Patients in the operating room and intensive care unit also receive narcotic medications like fentanyl as part of their anesthesia or for the treatment of pain. Fentanyl by itself has very little, if any, depressant effect on the heart except to decrease the heart rate. While this lack of cardiac effects has been described in the scientific literature, no studies have investigated whether fentanyl could decrease the effect of alpha- or beta-adrenergic stimulants on the cardiovascular system. In this study, we have shown in dogs that fentanyl diminishes the effectiveness of isoproterenol on cardiac function primarily through heart rate. We have also shown that the interaction between fentanyl and alpha and beta receptors are mediated by G-proteins. Studies are presently being performed to determine the neural role of this interaction. Additional studies investigating the role of heart rate by knocking out the sino-atrial node and controlling heart rate via pacing is also being investigated. Further understanding whether narcotics interact with cardiac stimulatory drugs within the heart could lead to better management of patients with shock or cardiac disease in the operating room or intensive care unit, and thereby improve outcome and potentially save lives.