AJP - Heart and Circulatory Physiology, Vol 252, Issue 6 1235-H1242, Copyright © 1987 by American Physiological Society
Inducers of adenylate cyclase reverse the effect of leukotriene D4 in isolated working guinea pig heart
O. G. Bjornsson, K. Kobayashi and J. R. Williamson
The recovery of coronary flow and cardiac work was studied in isolated
guinea pig hearts (working-heart preparation) after successive bolus
injections of leukotriene D4 (LTD4) at increasing doses (0.01-1,000 ng).
LTD4 caused an immediate (within 1 min) reduction in coronary flow and
cardiac work and an increase in myocardial NADH fluorescence. There was
limited spontaneous recovery at any dose and at the end of the cumulative
LTD4 study, coronary flow recovered only from 41.4 +/- (SE) 3.5 (n = 10) to
53.5 +/- 4.7% of initial values, and cardiac work recovered from 21.2 +/-
4.1 to 33.1 +/- 5.6% (P less than 0.05). Adenosine (1 X 10(-6) M) or
iloprost (1 X 10(-7) M) restored coronary flow but not cardiac work after
LTD4 injections, in contrast to full recovery of cardiac work observed in
hearts subjected to a similar degree of ischemia induced by reducing the
coronary flow by a peristaltic pump, or hypoxia caused by reducing PO2 of
the perfusion fluid. Adenosine (1 X 10(-6) M) and forskolin (1 X 10(-6) M)
in combination, or iloprost (1 X 10(-7) M) and isoproterenol (1 X 10(-8) M)
in combination, restored both coronary flow and cardiac work to control
levels. Myocardial NADH levels, which increased immediately after LTD4
injections, returned to normal after perfusion with adenosine or iloprost.
The data suggest that LTD4 has a prolonged vasoconstrictive effect on the
heart. Reversal of this effect by compounds that stimulate adenylate
cyclase of the vascular tissue (adenosine, prostacyclin) revealed a direct
suppressive effect on the myocardium independent of the vascular effect and
myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
