Anesthesia and surgery in the presence of recent myocardial infarction entails increased risk of mortality but is occasionally required for life threatening disease. The proposed study will examine the interaction between the commonly employed volatile anesthetics halothane, enflurane and isoflurane and the pathologic properties of ischemic Purkinje fibers associated with the generation of potentially lethal arrhythmias. The one-day-old canine infarction model to be employed is widely utilized in investigations of the effects of the antiarrhythmic drugs on ischemic cardiac tissues. Our preliminary studies indicate that halothane inhibits automaticity and triggered activity in this model, by decreasing the spontaneous rate, while simultaneously facilitating the generation of re-entrant antiarrhythmic drugs on ischemic cardiac triggered activity in this model, by decreasing the spontaneous rate, while simultaneously facilitating the generation of re-entrant arrhythmias. The hypothesis to be tested is that the volatile anesthetics influence the occurrence of ischemia related arrhythmias by their differential actions on the transmembrane currents associated with generation of the action potential in nonischemic and ischemic Purkinje fibers. The specific objectives are: 1) To determine in vitro the electrophysiologic properties of subendocardial Purkinje fibers in the one-day-old infarcted canine heart associated with the occurrence of dysrhythmias due to abnormal impulse generation and conduction. 2) To compare in vitro the actions of the volatile anesthetics on the action potential and refractory characteristics of Purkinje fibers in noninfarcted and infarcted canine hearts and to correlate these actions with their effects on the spontaneous ventricular arrhythmias observed in infarcted animals in vivo. 3) To directly measure the changes in the transsarcolemmal membrane currents and intracellular free calcium transient associated with exposure of nonischemic and ischemic Purkinje fibers to the anesthetic agents utilizing single Purkinje fiber voltage clamping techniques and intracellularly injected bioluminescent protein aequorin. The anesthetic management of patients with ischemia related perioperative arrhythmias is at present entirely empirical. The proposed study is designed to fill a gap in our knowledge regarding the interaction of the modern volatile anesthetics and the mechanisms known to underlie the generation of ischemia related arrhythmias.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Medical College of Wisconsin
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Kulier, A H; Turner, L A; Vodanovic, S et al. (2000) Multiple agents potentiate alpha1-adrenoceptor-induced conduction depression in canine cardiac purkinje fibers. Anesthesiology 92:1713-21
Vodanovic, S; Turner, L A; Hoffmann, R G et al. (1997) Actions of phenylephrine, isoproterenol, and epinephrine with halothane on endocardial conduction and activation in canine left ventricular papillary muscles. Anesthesiology 87:117-26
Kulier, A H; Woehlck, H J; Hogan, Q H et al. (1996) Epinephrine dysrhythmogenicity is not enhanced by subtoxic bupivacaine in dogs. Anesth Analg 83:62-7
Turner, L A; Vodanovic, S; Hoffmann, R G et al. (1995) A subtype of alpha 1 adrenoceptor mediates depression of conduction in Purkinje fibers exposed to halothane. Anesthesiology 82:1438-46
Sprung, J; Laszlo, A; Turner, L A et al. (1995) Effects of hypothermia, potassium , and verapamil on the action potential characteristics of canine cardiac Purkinje fibers. Anesthesiology 82:713-22
Stowe, D F; Sprung, J; Turner, L A et al. (1994) Differential effects of halothane and isoflurane on contractile force and calcium transients in cardiac Purkinje fibers. Anesthesiology 80:1360-8
Liao, R; Helm, P A; Hajjar, R J et al. (1994) [Ca2+]i in human heart failure: a review and discussion of current areas of controversy. Yale J Biol Med 67:247-64
Turner, L A; Polic, S; Hoffmann, R G et al. (1993) Actions of halothane and isoflurane on Purkinje fibers in the infarcted canine heart: conduction, regional refractoriness, and reentry. Anesth Analg 76:718-25
Vodanovic, S; Turner, L A; Hoffmann, R G et al. (1993) Transient negative dromotropic effects of catecholamines on canine Purkinje fibers exposed to halothane and isoflurane. Anesth Analg 76:592-7
Turner, L A; Polic, S; Hoffmann, R G et al. (1993) Actions of volatile anesthetics on ischemic and nonischemic Purkinje fibers in the canine heart: regional action potential characteristics. Anesth Analg 76:726-33

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