Negative inotropy of lidocaine: possible biochemical mechanisms.
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)
Wilson
R A
RA
Laboratory for Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Soei
L K
LK
Bezstarosti
K
K
Lamers
J M
JM
Verdouw
P D
PD
D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003864:Depression, Chemical; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D000099211:Phospholamban
D000227:Adenine Nucleotides; D002118:Calcium; D002135:Calcium-Binding Proteins; D008012:Lidocaine; D000099211:Phospholamban