Effect of Fetal Hypoxia on Heart Susceptibility to Ischemia and Reperfusion Injury in the Adult Rat

Abstract

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 (10.5% oxygen from day 15 to 21) gbroups. Hearts of 6-month-old male progeny were studied using Langendorff preparation and were subjected to two protocols of I-R: 10 minutes of ischemia and 3 hours of reperfusion (I-R₁₀) or 25 minutes of ischemia and 3 hours of reperfusion (I-R₂₅).

Results: Prenatal hypoxia did not change basal left ventricular (LV) function. I-R₁₀ produced myocardial stunning and a transient decrease in LV function in control hearts but caused myocardial infarction and a persistent decrease in postischemic recovery of LV function in hypoxic hearts. I-R₂₅ caused myocardial infarction in both control and hypoxic hearts, which was significantly higher in hypoxic hearts. The postischemic recovery of LV function was significantly reduced in hypoxic hearts. I-R₂₅-induced activation of caspase-3 and apoptosis in the left ventricle were significantly higher in hypoxic than control hearts. there was a significant decrease in LV heat shock protein 70 and endothelial nitric oxice synthase levels in hypoxic hearts. Prenatal hypoxia did not change β₁-adrenoreceptor levels but significantly increased β₂-adrenoreceptor in the left ventricle. In addition, it increased G_sα but decreased G_iα.

Conclusion: Prenatal chronic hypoxia increases the susceptibility of adult heart to I-R injury. Several possible mechanisms may be involved, including an increase in β₂-adrenoreceptor and theG_sα/G_iα ratio, and a decrease in heat shock protein 70 and endothelial nitric oxide synthase in the left ventricle.

Keywords

Fetus chronic hypoxia heart ischemia-reperfusion injury apoptosis

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