| Abstrakt: |
Previous studies have shown that lidocaine has a negative inotropic effect on the myocardium. This effect could be mediated by a decrease in O supply and/or utilization, or abnormalities in intracellular Ca handling by the myocardium. To investigate which of these mechanisms are involved we studied nine open-chest anaesthetized pigs, which received an infusion of lidocaine (4–16mg. min−1) in the left anterior descending coronary artery (LADCA), sufficient to induce a severe depression of the regional myocardial function. Biopsies for high energy phosphate levels were obtained from both the LADCA and control regions before and during the infusion. After measurements at peak lidocaine dose, the hearts were rapidly excised for harvesting of LADCA, and control region sarcoplasmic reticulum (SR) vesicles for in vitro measurements of Ca uptake rate. During lidocaine infusion, coronary blood flow increased (23%), while ATP, Ca uptake by the SR and percentage segment length shortening decreased by 20%, 19% and 30% respectively. However, O consumption in the LADCA region did not differ before or during lidocaine infusion (102 ± 20 and 104 ± 29 ml. min respectively). Hence, lidocaine in doses sufficient to depress regional myocardial function does not decrease O supply, but decreases the efficiency of oxygen utilization. Although we cannot entirely rule out the possibility that blockade of fast sodium channels is a contributory factor, the observed decrease in the tissue level of ATP and the rate of Ca uptake by the SR may be related to the negative inotropic action of lidocaine. However, the effects of lidocaine on SR membrane vesicles in vitro do not support the contribution of tile last mode of action, but lidocaine may indirectly suppress the SR in vivo. Thus both O, utilization and Ca handling appear to play roles in the in vivo negative inotropism of lidocaine. [ABSTRACT FROM PUBLISHER] |
