Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene

Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy stat us in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged m atched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each gr oup were examined with P-31 magnetic resonance spectroscopy to determine th e cardiac energy status. Transgenic mice had a significantly higher body we ight (BW), 53.2 +/- 2.4 us. 34.6 +/- 3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6 +/- 1.6 u s. 2.7 +/- 0.2 mg/g, P < 0.01. Several indexes of systolic function were de pressed in transgenic animals compared with controls mice such as shortenin g Fraction 25 +/- 3.0% us. 39.9 +/- 3.1%; ejection fraction, 57 +/- 9 us. 7 7 +/- 5; mean velocity of circumferential shortening, 4.5 +/- 0.8 us. 7.0 /- 1.1 circ/sec, p < 0.01. Creatine phosphate-to;ATP ratio was significantl y lower in bGH overexpressing mice (1.3 +/- 0.08 us. 2.1 +/- 0.23 in contro ls, P < 0.05). Ultrastructural examination of the hearts from transgenic mi ce revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deterio rating effects of long exposure to high level of GH on heart function.