Oxygen Dose-Response Curve of Cardiac Papillary Muscle From Fetal and Nonpregnant Adult Sheep Exposed to Long-Term,High-Altitude Hypoxemia

Abstract

Objective: We tested the hypothesis that hearts of fetal and nonpregnant adult sheep exposed to long-term hypoxemia would be able to sustain higher contractile function during exposure to acute hypoxia than hearts from normoxic animals.

Methods: Pregnant and nonpregnant sheep were exposed to high altitude (3820 m) for 100 days. Right and left ventricular papillary muscle strips were obtained from fetuses and nonpregnant adults, mounted in an isolated bath system, stimulated electrically and subjected to acute hypoxia in a dose response manner. Measurements were made of maximum tension production (T_max), maximum rate of tension development (+dT/dt_max), maximum rate of relaxation (-dT/dt_max), time to peak tension, and duration of contraction. Results were compared to papillary muscle from a normoxic group of animals.

Results: Baseline values (95% O₂ + 5% CO₂ bubbled in the bath) of T_max and ±dT/dt_max for each ventricle were greater in adults than fetuses in both normoxic and long-term hypoxemic groups. During hypoxia (at 40 and 20% O₂) T_max and ±dT/dt_max were all maintained at significantly higher values in papillary muscle from long-term hypoxemic fetuses than in papillary muscle from normoxic fetuses. Duration of contraction and time to peak tension did not differ between the normoxic and hypoxemic groups. In both ventricles of the long-term hypoxemic adult, T_max and ±dT/dt_max, as well as duration and time to peak tension, were significantly higher than in normoxic adults, but only at the lowest level of hypoxia (20% O₂).

Conclusions: Contrary to the original hypothesis, heart muscle from both fetal and adult sheep that had been exposed to long-term hypoxemia could maintain contractile function better during acute hypoxia. The responsible mechanisms are not clearly understood.