Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057891-03
Application #
6180781
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Cole, Alison E
Project Start
1998-08-01
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$186,954
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Dworschak, Martin; Breukelmann, Dirk; Hannon, James D (2006) The effect of isoflurane during reoxygenation on the sarcoplasmic reticulum and cellular injury in isolated ventricular myocytes. Life Sci 78:888-93
Vandenboom, Rene; Weihe, Elizabeth K; Hannon, James D (2005) Dynamics of crossbridge-mediated activation in the heart. J Muscle Res Cell Motil 26:247-57
Dworschak, Martin; d'Uscio, Livius V; Breukelmann, Dirk et al. (2005) Increased tolerance to hypoxic metabolic inhibition and reoxygenation of cardiomyocytes from apolipoprotein E-deficient mice. Am J Physiol Heart Circ Physiol 289:H160-7
Dworschak, M; Breukelmann, D; Hannon, J D (2004) Isoflurane applied during ischemia enhances intracellular calcium accumulation in ventricular myocytes in part by reactive oxygen species. Acta Anaesthesiol Scand 48:716-21
Dworschak, Martin; Breukelmann, Dirk; Hannon, James D (2004) The impact of isoflurane during simulated ischemia/reoxygenation on intracellular calcium, contractile function, and arrhythmia in ventricular myocytes. Anesth Analg 99:1302-7; table of contents
Hannon, James D; Cody, Mark J; Sun, David X et al. (2004) Effects of isoflurane and sevoflurane on intracellular calcium and contractility in pressure-overload hypertrophy. Anesthesiology 101:675-86
Hannon, James D; Cody, Mark J (2002) Effects of volatile anesthetics on sarcolemmal calcium transport and sarcoplasmic reticulum calcium content in isolated myocytes. Anesthesiology 96:1457-64
Hannon, J D; Cody, M J; Housmans, P R (2001) Effects of isoflurane on intracellular calcium and myocardial crossbridge kinetics in tetanized papillary muscles. Anesthesiology 94:856-61
Prakash, Y S; Cody, M J; Hannon, J D et al. (2000) Comparison of volatile anesthetic effects on actin-myosin cross-bridge cycling in neonatal versus adult cardiac muscle. Anesthesiology 92:1114-25
Prakash, Y S; Cody, M J; Housmans, P R et al. (1999) Comparison of cross-bridge cycling kinetics in neonatal vs. adult rat ventricular muscle. J Muscle Res Cell Motil 20:717-23