Effect of calcium, Bay K 8644, and reduced perfusion on basic indices of myocardial function in isolated hearts from rats after prolonged exposure toethanol

Citation
Lj. Guppy et Jm. Littleton, Effect of calcium, Bay K 8644, and reduced perfusion on basic indices of myocardial function in isolated hearts from rats after prolonged exposure toethanol, J CARDIO PH, 34(4), 1999, pp. 480-487
Citations number
27
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
ISSN journal
01602446 → ACNP
Volume
34
Issue
4
Year of publication
1999
Pages
480 - 487
Database
ISI
SICI code
0160-2446(199910)34:4<480:EOCBK8>2.0.ZU;2-2
Abstract
We previously reported findings consistent with a marked upregulation in fu nctional L-type voltage-operated calcium channels (L-VOCCs) in hearts obtai ned from rats exposed over the long term to ethanol. These experiments were undertaken to establish whether detrimental effects on cardiac function we re associated with excess calcium entry into the myocardium in these hearts . Isolated hearts from adult male Sprague-Dawley rats received intoxicating concentrations of ethanol for 6-10 days by inhalation, were perfused with Krebs-Henseleit buffer by a modified Langendorff technique, and several fun ctional parameters were assessed continuously. In some experiments, the cal cium concentration in the perfusate was first reduced from the physiologic range (1.2 mM) to 0.15 mM and then increased in a step-wise fashion to 4 mM . In other experiments, hearts were exposed to buffer containing concentrat ions of the L-VOCC activator, (+/-)Bay K 8644, increasing from 10(-9) to 10 (-6) M. These perfusion protocols were repeated in hearts from treated anim als subject to reduced coronary flow because of induction of partial left v entricular ischemia. There were some close similarities in the effects of t hese different stimuli. When the calcium concentration in the perfusate exc eeded a physiologic level, there were signs of decreased function relative to controls in the hearts from ethanol-exposed rats. Thus R-wave amplitude and systolic pressure were lower, diastolic pressure also was reduced, but heart rate was elevated above that of controls. Similarly the presence of ( +/-)Bay K 8644 in the perfusate caused a decrease in systolic and diastolic pressure and an increase in heart rate in hearts from ethanol-exposed rats . When cardiac perfusion was reduced in vitro by inflation of a balloon in the left ventricle, some of the effects of excess calcium and (+/-)Bay K 86 44 were reproduced in control hearts. However, imposition of this "ischemic " stress did not appear to exacerbate the effects of prior exposure to etha nol. In general, in control hearts, indices of contractility were increased across the range of calcium concentration or by perfusing with (+/-)Bay K 8644. Hearts from ethanol-exposed rats, however, showed no further increase in these parameters once physiologic levels of calcium were exceeded, or s howed inhibition of contractility in the presence of (+/-)Bay K 8644. The r esults are consistent with calcium entry through L-VOCCs in hearts from eth anol-exposed animals having detrimental effects on cardiac function once ph ysiologic levels are exceeded. However, it is possible that these channels also may be involved in maintenance of cardiac function at hypocalcemic lev els.