Fetal exposure to a maternal low-protein diet is associated with altered left ventricular pressure response to ischaemia–reperfusion injury

Abstract

Rats exposed to protein restriction as fetuses develop hypertension as adults. Hypertension increases the risk of myocardial ischaemia and infarction. We investigated whether rats exposed to low-protein diets in utero are more susceptible to myocardial ischaemia-reperfusion (IR) injury. Pregnant Wistar rats were fed control or low-protein (MLP) diets throughout pregnancy. At 4 and 8 weeks postnatal age systolic blood pressure was determined in the offspring using tail-cuff plethysmography. At 6 months of age, rats were treated with saline or N-acetylcysteine (NAC) for 48 h. Rapidly excised hearts were retro-perfused (Langendorff) to assess isolated cardiac function before (baseline), during 30 min ischaemia (no coronary perfusion) and for 60 min after reinstating coronary perfusion (reperfusion). Hearts were then harvested and treated appropriately for analysis of infarct size. Exposure to the MLP diet in utero significantly increased systolic blood pressure at 4 and 8 weeks of age (6-13 mmHg increase; P < 0.001) and significantly impaired recovery of left ventricular developed pressure after ischaemia at 6 months of age in male offspring only (P < 0.003). Pre-treatment with NAC prevented this impairment of recovery in MLP male offspring and improved recovery in all females. Myocardial infarct size was not different between dietary groups after IR, but NAC pre-treatment significantly reduced the degree of infarction (P < 0.001). In conclusion, an MLP diet throughout gestation significantly impairs recovery of the 6-month-old adult rat heart to IR-induced injury in a sex-specific manner. Undernutrition during development may increase susceptibility to CHD by impairing recovery from coronary events.