Diaphragm fatigue properties restored by growth hormone after chronic undernutrition

We have observed previously that fatigue induced with isometric contractioas results in higher resistance to force loss in undernourished (UN) rat diaphragm muscle, and that maximum velocity of shortening was further depressed than controls (Amcndes, B.Am. J.Repir. Crit. Care Med. 151:A156,1995). However, since the diaphragm normally shortens during breathing, fatigue characteristics were further tested with repeated isotonic contractions (30%P_o). Also, growth hormone (GH) was administered during refeeding (RF) after UN, to determine if the mechanical performance changes were reversible by an anabolic hormone. Shortening (S) properties of diaphragm muscle bundles were measured in vitro (37°C), during fatigue induced by repetitive electrical stimulation (0.2ms pulses, 250ms trains, 1train/2s, 2 min. trial). The fatigue resistance index (FRI) was assessed as the ratio of S at specific times divided by initial S (S_x/S_i). UN resulted in maintenance of repeated shortening throughout the trial, whereas the others ceased shortening before the end. At 1 min., UN FRI=0.54, as compared to FRI of controls (0, p<0.05), RF(0.28), and RF + GH (0.11, p<0.05) diaphragms. Myosin heavy chain (MHC) analysis indicated relative decreases in percentage of type IIB (-30%) and IIX MHC (-20%), and increases in type I (+20%) and IIA (+50%)MHC with UN, which was reversed with RF+GH. These data are consistent with the idea that GH treatment acts to reverse the effects of chronic UN on the diaphragm muscle through re-establishment of the type IIB and IIX MHC profile, and subsequent restoration of mechanical and fatigue properties.