Fetal myocardial responses to long-term hypoxemia.
In fetal sheep subjected to high altitude hypoxemia for 110 days beginning on day 30 of gestation, cardiac output was decreased 24% compared to normoxic control fetuses. This decrease was due to a 33% reduction in right ventricular output, with only a 14% reduction in left ventricular output. There were no changes in preload or heart rate, but approximately 7% of the reduction in cardiac output could be explained by an increase in arterial blood pressure (afterload). In papillary muscle isolated from long-term hypoxemic fetal hearts, maximum developed tension in response to increasing concentrations of calcium was reduced in both the right and left ventricles, but sensitivity to calcium was increased in both. This finding suggests alterations in the calcium pathway for excitation-contraction coupling in the hypoxemic fetal hearts may be responsible for the reduction in contractility. The mechanism for the decrease in contractility could not be explained by changes in sarcolemmal L-type calcium channel number or sarcoplasmic reticulum calcium release channel number. In addition, there were no changes in the calcium-induced calcium release mechanism involving the sarcoplasmic reticulum, which could explain the reduced contractility. We speculate that the decreased calcium response may be due to other factors, such as the amount of calcium stored in the sarcoplasmic reticulum, myofilament calcium sensitivity, or cellular content of myofilaments.
Center for Perinatal Biology, Loma Linda University School of Medicine, California 92350, USA. rgilbert@ccmail.llu.edu
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D000064:Acclimatization; D000222:Adaptation, Physiological; D000531:Altitude; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002302:Cardiac Output; D005260:Female; D005318:Fetal Heart / Q000378:metabolism / Q000503:physiopathology*; D005311:Fetal Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep; D013997:Time Factors
D002118:Calcium