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J Am Coll Cardiol, 1999; 34:2111-2119 © 1999 by the American College of Cardiology Foundation |
a Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
Manuscript received September 7, 1998; revised manuscript received June 18, 1999, accepted August 23, 1999.
Reprint requests and correspondence: Dr. Pamela S. Douglas, Beth Israel Deaconess Medical Center, Cardiovascular Division, East Campus, 330 Brookline Avenue, Boston, Massachusetts 02215
pdouglas{at}caregroup.harvard.edu
OBJECTIVES
We sought to evaluate in vivo and in vitro left ventricular (LV) geometry and function in streptozotocin-induced diabetic rats and the possible role of the nitric oxide (NO) pathway.
BACKGROUND
Diabetes results in cardiac dysfunction; however, the specific abnormalities are unknown. Because decreased NO contributes to abnormal vascular function in diabetics, we hypothesized that NO pathway abnormalities may contribute to diabetic cardiomyopathy.
METHODS
Control rats and those with non–insulin-dependent diabetes mellitus (NIDDM) underwent echocardiography, hemodynamic assessment, isolated heart perfusion and measurement of exhaled NO and LV endothelial constitutive nitric oxide synthase (ecNOS).
RESULTS
Diabetic rats had increased LV mass (3.3 ± 0.6 vs. 2.6 ± 0.3 g/g body weight [BW], p < 0.001) and cavity dimensions (diastolic 2.0 ± 0.1 vs. 1.8 ± 0.2 cm/cm tibial length [TL], p < 0.05). Diabetic rats had prolonged isovolumic relaxation time (IVRT) (40 ± 8 vs. 26 ± 6 ms, p < 0.0001), increased atrial contribution to diastolic filling (0.47 ± 0.09 vs. 0.30 ± 0.08 m/s, p < 0.0001), and elevated in vivo LV end-diastolic pressure (7 ± 6 vs. 2 ± 1 mm Hg, p = 0.04). Diabetic rats had increased chamber stiffness. Shortening was similar in both groups, despite reduced meridional wall stress in diabetics, suggesting impaired systolic contractility. Exhaled NO was lower in diabetic rats (1.8 ± 0.2 vs. 3.3 ± 0.3 parts per billion, p < 0.01) and correlated with Doppler LV filling. The ecNOS was similar between the groups.
CONCLUSIONS
Diabetic cardiomyopathy is characterized by LV systolic and diastolic dysfunction, the latter correlating with decreased exhaled NO. The NO pathway is intact, suggesting impaired availability of NO as contributor to cardiomyopathy.
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