Negative inotropy of lidocaine: possible biochemical mechanisms

Abstract

Previous studies have shown that lidocaine has a negative inotropic effect on the myocardium. This effect could be mediated by a decrease in O2 supply and/or utilization, or abnormalities in intracellular Ca2+ 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 (4-16 mg.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 Ca2+ uptake rate. During lidocaine infusion, coronary blood flow increased (23%), while ATP, Ca2+ uptake by the SR and percentage segment length shortening decreased by 20%, 19% and 30% respectively. However, O2 consumption in the LADCA region did not differ before or during lidocaine infusion (102 +/- 20 and 104 +/- 29 ml.min-1, respectively). Hence, lidocaine in doses sufficient to depress regional myocardial function does not decrease O2 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 Ca2+ uptake by the SR may be related to the negative inotropic action of lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial O2consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O2delivery

“…Lidocaine might have had a slight effect. A higher dose directly into a coronary artery may results in an effect on wall motion and an increase in blood flow (49). We cannot exclude that the lidocaine somewhat contributed to slight coronary vasodilation.…”

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

“…They may involve Adeno's slowing of the sinoatrial node (negative chronotropy), slowing atrial contractility (negative inotropy) and delaying of A-V nodal impulse conduction (negative dromotropy) (15), and Lido's ability to downregulate voltage-dependent Na ϩ fast channels in cardiac myocytes and intercalated discs (52) and its negative inotropic effect via action potential shortening (39,66). Adenosine may also stabilize myocardial excitability by activating the A 1 receptor subtype (and perhaps A 3 ), blunt the stimulatory effects of catecholamines (inhibiting sarcolemmal Na ϩ /H ϩ and Na ϩ / Ca 2ϩ exchangers), and inhibit norepinephrine release from nerve terminals (15,18).…”

“…AL solution's protection may also relate to shortening of the action potential duration: Adeno by opening of the ATPsensitive K ϩ (K ATP ) channels (and possibly other K ϩ channels) through enhanced phase 3 repolarization (17,29,37,45), and Lido's effect through its interaction with cardiac sarcolemmal Ca 2ϩ channels (39,66). Because increased K ϩ channel activation and rapid action potential duration shortening are known to cause arrhythmias (9), the AL combination may "clamp" ischemic cells at more polarized potentials than either Adeno or Lido alone (12).…”

Effect of lignocaine in myocardial contusion: an experiment on rabbit isolated heart

“…and dP/dtm,,. Several phenomena have been advocated to explain this fall in contractility: alteration of Ca2" release by the sarcoplasmic reticulum (Lynch, 1986;Wilson et al, 1993) or impaired oxygen consumption (Lofstrom, 1992;Wilson et al, 1993 (Mazoit et al, 1990). Lignocaine markedly improved contractility rapidly after its infusion, and this effect persisted after the end of infusion as though lignocaine was able to break a vicious circle or to reestablish an impaired function.…”