Activator calcium and myocardial contractility in fetal sheep
exposed to long-term high-altitude hypoxia.
Browne, Vaughn A., Virginia M. Stiffel, William J. Pearce, Lawrence D.
Longo, and Raymond D. Gilbert.
Center for Perinatal Biology, Departments of Physiology and
Obstetrics and Gynecology, Loma Linda University School of Medicine,
Loma Linda, CA 92350
APStracts 3:0470H, 1996.
We studied myocardial contractility in fetal sheep from ewes exposed
to 112 days of hypoxia at high-altitude (3,820_m). We measured the
inotropic response to extracellular calcium [Ca2&]o (0.2-10_mM)
and ryanodine (10-10-10-4_M) in isometrically contracting papillary
muscles, and quantified dihydropyridine (DHPR) and ryanodine (RyR)
receptors. In hypoxic fetuses, curves describing the force
-[Ca2&]o relationship were left-shifted, and the top plateaus were
decreased by 35% in both left and right ventricles. In normoxic and
hypoxic fetuses, ryanodine (10-4_M) reduced maximum active tension
(Tmax) to 25-40% of baseline values, indicating that the sarcoplasmic
reticulum was the chief source of activator calcium, and that calcium
influx alone was not sufficient to activate a contraction of normal
amplitude. Hypoxia resulted in a lower Tmax in the right ventricle
and a lower +/-dT/dtmax in the left ventricle following treatment
with ryanodine. DHPR number did not change, but RyR number and the
RyR:DHPR ratios in both ventricles were higher in hypoxic fetuses. We
conclude that hypoxia decreases contractility, possibly by reducing
the availability of activator calcium. Further studies are needed to
directly measure the calcium current and intracellular calcium
transient, and to examine myofilament protein and ATPase activity.
Received 25 January 1996; accepted in final form 21 August 1996.
APS Manuscript Number H75-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996