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      Global myocardial hypertrophy in conscious dogs with chronic elevation of plasma norepinephrine levels.

      Journal of Molecular and Cellular Cardiology
      Animals, Cardiomegaly, etiology, pathology, physiopathology, Disease Models, Animal, Dogs, Hemodynamics, Infusion Pumps, Myocardium, Norepinephrine, administration & dosage, blood, Organ Size

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          Abstract

          Chronically elevated plasma norepinephrine is associated with many disease states in which myocardial hypertrophy is also found, yet whether the hypertrophy results from the hemodynamic actions of catecholamines or a trophic effect is still unknown. The goal of our study was to determine the extent of hypertrophy following 28 days of norepinephrine infusion and the role of altered hemodynamics as the stimulus for the hypertrophy in conscious dogs. In a retrospective study gross cardiac weights were examined in 25 control instrumented dogs (controls) and in 41 instrumented dogs with elevated norepinephrine (NE). In the NE dogs LV (94 +/- 2.8 g), septum (33 +/- 1.5 g) and total heart weights (172 +/- 4.5 g) were greater than in controls (85 +/- 5.0, 31 +/- 1.9, and 158 +/- 9.0 g, respectively). The LV (3.95 +/- 0.10 g/kg), RV (1.91 +/- 0.06), septum (1.38 +/- 0.06) and total weight (7.23 +/- 0.15) to body weight ratios were also significantly greater (3.32 +/- 0.12, 1.73 +/- 0.08, 1.24 +/- 0.06, and 6.28 +/- 0.23 g/kg). The dry/wet weight ratios were not different in the two groups. After cutting the hearts into 1 cm rings, the planimetered area of each ring showed that the wall thickness increased at all levels, e.g. at the base by 25 +/- 3.2%. The chamber internal diameter was significantly increased only near the apex in the NE dogs making the heart more cylindrical in shape. There was no obvious sign of fibrosis in any layer of the myocardium. In physiologic studies, no index of contractility was altered including: LV dP/dt, LV dD/dt, shortening, LV dWT/dt and there was also no change in preload. Heart rate was significantly reduced throughout the 28 days of study. Cardiac output was reduced and there were no significant changes in cardiac work. Thus in these dogs NE caused a 19% and 10% increase in LV and RV to body weight ratios, respectively, without any obvious hemodynamic stimulus.

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