The Journal of Thoracic and Cardiovascular Surgery, Vol 105, 120-131, Copyright © 1993 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
Left ventricular pressure overload during postnatal development. Effects on coronary vasodilator reserve and tolerance to hypothermic global ischemia
H Yamamoto and M Avkiran
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, England.
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.
