Effect of lidocaine on left ventricular pressure-volume curves during demand ischemia in pigs.
The diastolic pressure-volume curve shifts upward during demand ischemia, most likely because of changes in Ca2+ dynamics within the sarcomere. It is possible that agents that affect Na+/Ca2+ exchange, such as lidocaine, a class 1b-type Na+-channel blocker that decreases intracellular Na+, could affect the diastolic pressure-volume relationship because of indirect effects on intracellular Ca2+. Lidocaine is a drug widely used to treat arrhythmias in patients with myocardial ischemia. We studied the effects of lidocaine on diastolic dysfunction associated with demand ischemia. We compared diastolic (as represented by the shift in the diastolic pressure-volume relationship) and systolic function during demand ischemia before and after lidocaine injection. We created demand ischemia in pigs before and after administering lidocaine (5 mg/kg) in eight open-pericardium anesthetized pigs. Demand ischemia was induced by constricting the left anterior descending coronary artery and then pacing at 1.5-1.8 times the baseline heart rate for 1.5-3 min. Hemodynamics were recorded during baseline, demand ischemia, baseline after lidocaine injection, and demand ischemia after lidocaine. Lidocaine did not affect systolic function or the time constant of isovolumic relaxation, but it increased the upward shift of the diastolic pressure-volume curve during demand ischemia compared with the increase that occurred before lidocaine was administered. This result suggests that lidocaine could aggravate diastolic dysfunction in patients with ischemic heart disease.
Tayama
M
M
Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, California 94143-0124, USA.
Solomon
S B
SB
Glantz
S A
SA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D003971:Diastole / Q000187:drug effects; D005260:Female; D008012:Lidocaine / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013599:Systole / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
D002316:Cardiotonic Agents; D008012:Lidocaine