Effect of prenatal nicotine exposure on heart susceptibility to ischemia/reperfusion injury in adult male and female offspring

Abstract

Recent epidemiological studies have demonstrated that in utero exposure to maternal cigarette smoking is associated with cardiovascular diseases in offspring later in life. The present study tested the hypothesis that fetal and neonatal nicotine exposure increased heart susceptibility to ischemia/reperfusion (I/R) injury in adult offspring. Nicotine (2.1mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-min of ischemia followed by 60-min of reperfusion in a Langendorff preparation. Cardiac functional parameters: heart rate, left ventricular developed pressure and end diastolic pressure, dP/dtmax, dP/dtmin, and left ventricular infarct size were measured. Pre-ischemic values of cardiac function were not significantly different between the control and nicotine-treated hearts in either male or female offspring. Prenatal nicotine exposure significantly increased I/R-induced infarct size in left ventricles, and significantly attenuated postischemic recovery of left ventricular function in both male and female offspring. However, the effect of nicotine was significantly more pronounced in females than males. The findings suggest that prenatal nicotine exposure causes a reprogramming of cardiac function resulting in an increase in heart susceptibility to I/R injury in adult offspring. In addition, the effect of nicotine shows a gender dichotomy with females being more susceptible than males. (Supported in part by NIH grant S06GM073842 and TRDRP Award # 14FT-0075)