title: Activator calcium and myocardial contractility in fetal sheep exposed to long-term high-altitude hypoxia.
abstract: We studied myocardial contractility in fetal sheep from ewes exposed to approximately 112 days of hypoxia at high altitude (3,820 m). We measured the inotropic response to extracellular Ca2+ concentration ([Ca2+]o, 0.2-10 mM) and ryanodine (10(-10) to 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 shifted left, and the top plateaus were decreased by approximately 35% in both left and right ventricles. In normoxic and hypoxic fetuses, ryanodine (10(-4) M) reduced maximum active tension (Tmax) to approximately 25-40% of baseline values, indicating that the sarcoplasmic reticulum was the chief source of activator Ca2+ and that Ca2+ 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 maximum rate of rise in the left ventricle after treatment with ryanodine. DHPR number did not change, but RyR number and the RyR/DHPR in both ventricles were higher in hypoxic fetuses. We conclude that hypoxia decreases contractility, possibly by reducing the availability of activator Ca2+. Further studies are needed to directly measure the Ca2+ current and intracellular Ca2+ transient and to examine myofilament protein and adenosinetriphosphatase activity.
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, California 92350, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Browne
authors.forename: V M
authors.initials: VM
authors.lastname: Stiffel
authors.forename: W J
authors.initials: WJ
authors.lastname: Pearce
authors.forename: L D
authors.initials: LD
authors.lastname: Longo
authors.forename: R D
authors.initials: RD
authors.lastname: Gilbert
mesh_terms: D000531:Altitude; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D004558:Electric Stimulation; D005260:Female; D005318:Fetal Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D000860:Hypoxia; D066298:In Vitro Techniques; D017275:Isradipine / Q000378:metabolism; D009124:Muscle Proteins / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D012433:Ryanodine / Q000378:metabolism / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D012756:Sheep; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002118:Calcium; D017275:Isradipine