Systolic ventricular dysfunction causes selective diaphragm atrophy in rats

In order to examine the relative impairment of the diaphragm and other skel etal muscles in systolic ventricular dysfunction (VD), their structure and function were compared between rats with VD induced by left coronary artery ligation (n = 17) and sham-operated rats (Co, n = 10). In addition, in an attempt to unravel the mechanism of the observed impairment, we examined al terations in insulin-like growth factor-I (IGF-I) serum levels and IGF-I ex pression in the liver, diaphragm, and gastrocnemius. In a second series of rats (VD, n = 5 and Co, n = 5) hemodynamic measurements were performed. All measurements were performed 3 mo after the operation. Infarct size average d 32 +/- 10 and 44 +/- 20% in the two series, respectively (NS). Hemodynami c measurements revealed a decrease in left ventricular peak systolic pressu re of 19% (p < 0.05). Significant diaphragm atrophy (weight: 622 +/- 52 mg in VD versus 750 +/- 54 mg in Co, p < 0.0005), without alterations in diaph ragm contractile properties was present in VD animals. For all animals comb ined, the reduction in diaphragm weight was related to infarct size (r = -0 .74, p < 0.001). No alterations were observed in the other inspiratory and peripheral muscles. ATPase staining of the diaphragm showed atrophy of type I and type IIx/b fibers, their cross-sectional area (CSA) being reduced by 13 and 16%, respectively (p < 0.05). There were no signs of myopathic alte rations. IGF-I expression was increased by 55% in the diaphragm of rats wit h VD (p < 0.05). ICF-I expression in the liver and gastrocnemius and serum IGF-I levels were unaltered. These data suggest the presence of compensator y mechanisms aimed at minimizing diaphragmatic fiber atrophy. We conclude t hat systolic VD caused: (1) selective diaphragm atrophy, which was related to infarct size; (2) a decrease in diaphragm type I and IIx/b CSA not assoc iated with myopathic changes; (3) an increase in the IGF-I mRNA content of the diaphragm. The selective diaphragm involvement in the present study may be related to the moderate degree of ventricular dysfunction induced.