Publications by authors named "Raymond D Gilbert"

Objective: The purpose of this study was to investigate the mechanisms of tension and intracellular calcium regulation following stimulation with the thromboxane A(2) receptor agonist U46619 in the left anterior descending coronary artery of fetal sheep exposed to long-term hypoxia. We hypothesized that there would be a reduction in intracellular calcium responses in long-term hypoxic left anterior descending coronary artery accompanied by an increase in calcium sensitivity of the contractile mechanism.

Methods: Pregnant sheep were kept at altitude (3820 m) from day 30 of gestation until day 140.

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Objectives: We have previously shown that after exposure to long-term hypoxia, fetal coronary flow is maintained at control levels despite a 25% reduction in cardiac output. We also demonstrated that coronary vascular rings isolated from the long-term hypoxic fetuses and studied in well-oxygenated bath system displayed significantly reduced depolarization-induced contraction strength in response to KCl. To study the mechanism of reduced fetal coronary vascular responses to KCl-induced contractions following exposure to long-term hypoxia, we measured tension and intracellular calcium simultaneously, as well as L-type Ca2+ channel density and sensitivity.

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The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia-reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg(-1)) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups.

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Objective: We studied the effects of long-term high-altitude hypoxia and protein kinase A (PKA) phosphorylation on calcium (Ca2+) responses of skinned cardiac papillary muscles from fetal and adult sheep.

Methods: Fetal and nonpregnant adult sheep were exposed to high-altitude (3820 m), long-term (approximately 110 days) hypoxia. Papillary muscles were isolated and mounted in well-oxygenated, temperature-controlled baths.

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In response to high altitude long-term hypoxemia, the heart of fetal sheep shows a decrease in cardiac output that is secondary to a decrease in myocardial cell contractile function. The intracellular mechanisms responsible for these reductions might include reduced myofibrillar Mg(2+)-activated ATPase. There is also a decrease in beta(1)-adrenergic receptor stimulated augmentation of myocardial contraction.

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Objective: Epidemiologic studies showed an association between adverse intrauterine environment and ischemic heart disease in the adult. We tested the hypothesis that prenatal hypoxia increased the susceptibility of adult heart to ischemia-reperfusion (I-R) injury.

Methods: Time-dated pregnant rats were divided between normoxic and hypoxic (10.

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Article Synopsis
  • Fetal sheep exposed to long-term hypoxia showed a decreased ability to enhance heart contractility via beta-adrenergic receptor stimulation, despite increased cAMP production compared to normoxic sheep.
  • The study measured protein kinase A (PKA) activity and troponin I (TnI) isoforms in fetal and adult sheep at high altitude, using specific methods to assess their responses.
  • Results indicated that while fetal hearts had higher resting PKA activity in hypoxia, there were no significant differences in overall PKA activity or TnI isoform composition between normoxic and hypoxic groups, suggesting these factors did not explain the observed reduction in cardiac responsiveness.
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Objective: We studied the effect of long-term, high-altitude hypoxia on cardiac myosin, actin, and troponin T (TnT) isoforms and Ca(2+)- and Mg(2+)-activated myofibrillar adenosine triphosphatase (ATPase) activities in fetal and adult sheep.

Methods: We exposed pregnant (beginning at day 30 of gestation) and nonpregnant sheep to high altitude (3820 m) for 110 days. Myosin, actin, and TnT isoforms were analyzed by Western analysis.

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