Left ventricular pressure overload during postnatal development: Effects on coronary vasodilator reserve and tolerance to hypothermic global ischemia

Abstract

The effect of pressure overload during postnatal development on (1) coronary reserve and (2) tolerance to cardioplegic arrest and hypothermic ischemia was investigated. Left ventricular pressure overload was induced in 1-week-old rats by aortic constriction (group AC), with control rats (group C) undergoing sham operation. Relative to group C rats, left ventricular weight/body weight ratio in group AC increased by 50% to 80% at 3 weeks of age and by 100% to 120% at 6 weeks of age. At these ages, hearts were isolated from group C and AC rats and Langendorff-perfused with bicarbonate buffer at perfusion pressures of 75 and 110 mm Hg, respectively. In the first study, minimal coronary vascular resistance was assessed during perfusion with adenosine (10 mumol/L). There was no difference in total minimal coronary vascular resistance between groups C and AC at 3 weeks of age. Total minimal coronary vascular resistance decreased with increasing cardiac mass between 3 and 6 weeks of age in group C (from 6.9 +/- 0.4 to 4.5 +/- 0.2 mm Hg/ml/min, p < 0.05), but not in group AC. Between these ages, minimal coronary vascular resistance per unit heart weight increased to a greater extent in group AC (from 2.9 +/- 0.2 to 7.0 +/- 0.3 mm Hg/ml/min/gm, p < 0.05) than in group C (from 1.8 +/- 0.0 to 2.7 +/- 0.1 mm Hg/ml/min/gm, p < 0.05). In the second study, hearts were arrested with St. Thomas' Hospital cardioplegic solution (15 degrees C) and subjected to hypothermic (15 degrees C) global ischemia (210 minutes at 3 weeks and 180 minutes at 6 weeks) followed by 65 minutes of reperfusion. At 3 weeks of age, coronary resistance profiles, changes in left ventricular end-diastolic pressure, and recoveries of left ventricular developed pressure during reperfusion were similar in groups C and AC. At 6 weeks of age, however, group AC had greater coronary resistance during reperfusion, a greater increase in left ventricular end-diastolic pressure (28 +/- 5 versus 1 +/- 1 mm Hg, p < 0.05), and consequently a reduced recovery of left ventricular developed pressure (50.7% +/- 3.6% versus 75.9% +/- 4.0%, p < 0.05) relative to group C. Thus 2 weeks of left ventricular pressure overload during neonatal development in the rat has little effect on coronary reserve and ischemic tolerance. Prolonged (5 weeks) pressure overload, however, results in postischemic diastolic dysfunction, which may be due to perfusion abnormalities during reperfusion.