The general hypothesis to be tested is that the general anesthetics produce a depression of the cardiovascular system by both end-organ depression of the heart and vascular smooth muscle, and a depression of the sympathetic nervous system. Furthermore, clinically important slow channel antagonists may differentially potentiate the direct negative inotropic and chronotropic effects of inhalational anesthetics. The primary goals are to provide information on the effects of inhalational anesthetics and calcium antagonists on cardiac electrophysiology and cardiac muscle contraction in order to evaluate abnormalities of impulse generation, conduction, excitation-contraction coupling and muscle contraction. In addition, since the peripheral sympathetic nervous system offers additional sites at which inhalational anesthetics can act to attenuate cardiac function through sympathetic efferent nerve activity, effects of these agents on ganglionic transmission will also be studied.
The specific aims are: a) To compare impulse generation and intracellular free calcium changed (calcium transients) in the guinea pit sine-atrial node in vitro during introduction of inhalational anesthetics and calcium antagonists. b) To compare the sensitivity and slow inward current of Purkinje fibers and contractility of ventricular muscle cells during simultaneous exposure to inhalational anesthetics and calcium antagonists. c) To determine the actions of calcium antagonists following prolonged administration on cardiovascular response of the autonomic nervous system in vivo and on cardiac electrophysiology in vitro. d) To study the effects of inhalational anesthetic agents on synaptic, presynaptic, postsynaptic and axonal neurophsiologic events. The long term goals are to describe myocardial and smooth muscle cellular mechanisms affected by general anesthetics and by acute and chronic treatment with calcium antagonists, since it is anticipated that several distinct mechanisms could be involved due to their structural diversity and pharmacologic properties.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL001901-05
Application #
3074159
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1991-07-12
Budget End
1992-06-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Stekiel, T A; Stekiel, W J; Tominaga, M et al. (1996) Effect of halothane and isoflurane on in situ diameter responses of small mesenteric veins to acute graded hypercapnia. Anesth Analg 82:349-57
Tudoric, N; Coon, R L; Kampine, J P et al. (1995) Effects of halothane and isoflurane on antigen- and leukotriene-D4-induced constriction of guinea pig trachea. Acta Anaesthesiol Scand 39:1111-6
Tudoric, N; Coon, R L; Bosnjak, Z J (1994) Inhibition of neutral endopeptidase potentiates compound 48/80-induced constriction of guinea-pig tracheal smooth muscle. Pulm Pharmacol 7:343-7
Buljubasic, N; Marijic, J; Bosnjak, Z J (1994) Potassium channel current and coronary vasodilatation by volatile anesthetics. Adv Pharmacol 31:235-52
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
Tudoric, N; Coon, R L; Bosnjak, Z J (1994) Phosphoramidon modulates effects of the 5-lipoxygenase inhibition on anaphylactic contraction of the guinea pig trachea. Int Arch Allergy Immunol 103:293-7
Stekiel, T A; Bell, L B; Bosnjak, Z J et al. (1994) Effects of isoflurane on regulation of capacitance vessels under normotensive and chronically hypertensive conditions. Adv Pharmacol 31:409-30
Tudoric, N; Coon, R L; Bosnjak, Z J (1994) Phosphoramidon augments contraction of guinea pig tracheal smooth muscle induced by histamine and leukotriene-D4. Int Arch Allergy Immunol 103:286-92
Buljubasic, N; Marijic, J; Kampine, J P et al. (1994) Calcium-sensitive potassium current in isolated canine coronary smooth muscle cells. Can J Physiol Pharmacol 72:189-98
Sprung, J; Stowe, D F; Kampine, J P et al. (1994) Hypothermia modifies anesthetic effect on contractile force and Ca2+ transients in cardiac Purkinje fibers. Am J Physiol 267:H725-33

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