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