Hypotension and cardiac arrest have been observed in patients anesthetized with the anesthetics halothane, enflurane, and isoflurane. These volatile anesthetics (VA's) are in wide clinical use today. Preliminary evidence suggests that the VA's might decrease the available of Ca2+ required for cardiac contraction. This project is designed to study the effect of the above mentioned anesthetics on structures in the myocardial cell that regulate Ca2+ flux and control the intensity of contraction. The elements that will be studied are: the sarolemma (SL), the outer membrane of the muscle cell; the sarcoplasmic reticulum (SR), a membranous network that controls the amount of myoplasmic Ca2+; the mitochondrion, the energy generating organelle which also serves to control tonic Ca2+ availability, and troponin (Tn), a protein that responds to Ca2+ binding by changing its shape and initiating the contractile process. Experiments will also be performed on isolated papillary muscles and myocytes to integrate the results found with the isolated subcellular structures with systems of more physiological complexity. Present evidence suggests that the SR and SL are affected by anesthetics and may be the major sites of alteration of contractility. The studies outlined will examine the interaction of halothane, enflurane, and isoflurane with the subcellular structures to observe alterations in Ca2+ response. The results will quantify the relative effect of each anesthetic on each structure and a possible mechanism of action will be postulated. The data obtained will help in formulating pharmacologic interventions to prevent anesthetic-induced cardiac depression in the operating room.
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