INFLUENCE OF KETAMINE ON INOTROPIC AND CHRONOTROPIC RESPONSIVENESS OF HEART-MUSCLE

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 201  (1) , 171-183
Abstract
The influence of ketamine on the inotropic and chronotropic responsiveness of heart muscle was examined in spontaneously beating right atrial preparations and in electrically driven left atrial preparations of guinea pigs. Ketamine (2.63 .times. 10-5-4.2 .times. 10-4 M) decreased heart rate of right atria and decreased contractile tension and its maximum rate of increase in both right and left atrial preparations (right atria > left atria). Ketamine did not prevent the heart rate increase produced by norepinephrine [NE] (NE; 1 .times. 10-8-1 .times. 10-4 M) in right atria; however, the maximum heart rate was consistently lower in ketamine-treated than in control muscles even after exposure to NE. Although contractile tension was decreased by ketamine, the maximum inotropic response to NE was consistently greater in ketamine-treated atria than in control atria. An inhibitor of the slow Ca2+ current in heart muscle, D600 [.alpha.-isopropyl-.alpha.-[N-methyl-N-homoveratryl-.gamma.-aminopropyl]-3,4,5-trimethoxyphenylacetonitrile], depressed the contractile effects of NE but did not prevent the positive inotropic interaction of ketamine and NE. Ketamine similarly enhanced the inotropic responses to norepinephrine (1 .times. 10-6 M), epinephrine (1 .times. 10-6 M), isoproterenol (1 .times. 10-7 M) and dibutyryl cyclic AMP (4 .times. 10-3 M) in left atria electrically paced at a constant frequency of contraction of 1 Hz; however, ketamine inhibited the positive inotropic response to increased frequency of stimulation (0.1-3.0 Hz) and to ouabain (3 .times. 10-7 M). Ketamine can exert a selective positive inotropic influence in heart muscle independent of heart rate or direct or reflexogenic autonomic nervous system changes, and this activity could in some way by associated with an alteration of the intracellular disposition of cyclic AMP.

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