The hypertrophied heart is susceptible to functional depression by volatile anesthetics, and differentially affected by isoflurane compared to halothane and compared to the normal heart. The potential mechanisms of volatile anesthetics including halothane, isoflurane and sevoflurane on this contractile dysfunction relating to 1) alterations in intracellular calcium regulation, 2) sensitivity of the contractile apparatus to intracellular calcium and 3) kinetics of cross-bridge formation have not been investigated using specific techniques. The four specific aims of this proposal address the following hypotheses: 1) hypertrophy-induced changes in intracellular calcium precessing result in a predisposition to myocardial depression caused by volatile anesthetics, 2) volatile anesthetics decrease calcium sensitivity are of similar magnitude to normal tissue and do not contribute to anesthetic induced cardiodepression, 3) volatile anesthetic induced cardiodepression (contractility) is secondary to effects on calcium handling rather than to actual cross-bridge kinetics, and 4) the cardiodepression can be modeled using computer simulations.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Mayo Clinic, Rochester
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