Circulation, Vol 55, 200-205, Copyright © 1977 by American Heart Association
CF Wu, B Haider, SS Ahmed, HA Oldewurtel, MM Lyons and TJ Regan
The effects of chronic tolbutamide treatment were examined in a diabetic
animal model in which abnormal myocardial function and composition have
previously been demonstrated. Eight diabetic dogs were given tolbutamide
250 mg/day orally and compared with seven untreated diabetics, five healthy
dogs receiving tolbutamide, and eight normal controls. After one year,
resting hemodynamic studies in the intact anesthetized state showed that
treated diabetic dogs had a significantly higher left ventricular
end-diastolic pressure of 12.1+/- 1.3 mm Hg associated with normal
end-diastolic volume, compared to 6.1+/-0.8 mm Hg in untreated diabetics (P
less than 0.01) and 6.3+/-0.5 in normals. Stroke work and ejection fraction
were similar to normals. Acute volume expansion revealed a larger rise of
left ventricular end- diastolic pressure in treated and untreated diabetics
than normals, without a significant stroke volume response in treated
diabetics. Enhanced stiffness of myocardium appeared to be related to
interstitial accumulation of periodic acid-Schiff staining material,
further intensified in treated diabetics by triglyceride accumulation
observed on electron microscopy and by chemical analysis. Thus treatment of
diabetes with tolbutamide, despite improved glucose tolerance, effected
further reduction of left ventricular function and altered morphology of
myocardium.
ARTICLES
The effects of tolbutamide on the myocardium in experimental diabetes
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