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The Journal of Thoracic and Cardiovascular Surgery, Vol 93, 741-754, Copyright © 1987 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
KG Warner, SF Khuri, RA Kloner, M Josa, KM Dalecki-Chipperfield, MD Butler, SN Assousa, SS Lee, EM Barsamian and M Seiler
To characterize the ultrastructural and metabolic changes occurring in the
hypertrophied ventricle during cardiac operations in man, we studied 36
patients with valvular heart disease undergoing valve replacement, during
which multiple doses of cold potassium cardioplegic solution were
administered (Group I). Each patient had substantial ventricular
hypertrophy according to measurements made of left ventricular mass, with a
mean of 232.1 +/- 19.8 gm/m2 (normal: 92 +/- 16 gm/m2). Serial biopsy
specimens were obtained from the left ventricular apex at the initiation of
bypass, during the cross-clamp interval, and during reperfusion. Each
specimen was scored from 0 to 4 according to ischemic changes in nuclear
chromatin, mitochondrial swelling, myofibrillar edema, glycogen depletion,
and overall cell morphology. Myocardial pH and temperature were measured
continuously in the left ventricular free wall. During the cross-clamp
period, ischemic injury was evidenced by changes in nuclear chromatin (0.38
+/- 0.10 to 1.25 +/- 0.21, p less than 0.0001), intracellular edema (0.43
+/- 0.06 to 0.97 +/- 0.14, p less than 0.002), overall cell morphology
(0.37 +/- 0.06 to 0.97 +/- 0.14, p less than 0.001), and mitochondria (0.10
+/- 0.05 to 0.19 +/- 0.07, p less than 0.0001). During reperfusion,
mitochondrial swelling increased further (0.19 +/- 0.07 to 0.35 +/- 0.08, p
less than 0.0001) and glycogen stores were depleted (0.63 +/- 0.13 to 0.96
+/- 0.17, p less than 0.02), while the other structures remained unchanged.
Myocardial pH declined during ischemic arrest from 6.89 +/- 0.04 to 6.40
+/- 0.04 (p less than 0.001). The changes in myocardial pH in Group I were
compared to changes in myocardial pH in 10 patients (Group II) with no left
ventricular hypertrophy undergoing isolated coronary bypass graft
operations with the same protective techniques. In contrast to Group I,
myocardial pH did not fall in Group II during ischemic arrest (6.98 +/-
0.06 to 6.94 +/- 0.05, p = not significant). Thus, with the use of current
myocardial protective techniques, ultrastructural and metabolic changes
indicative of ischemia are produced in the hypertrophied myocardium. The
structural alterations consist of changes in nuclear chromatin and
intracellular edema during the ischemic phase and by mitochondrial swelling
during reperfusion.
ARTICLES
Structural and metabolic correlates of cell injury in the hypertrophied myocardium during valve replacement
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