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The present study was designed to examine whether clenbuterol (CLEN) could reduce dexamethasone (DEX)-induced diaphragm dysfunction. We studied four groups of New Zealand white (NZW) rabbits, each receiving one of the following daily injections subcutaneously for 2 wk: saline (control), DEX 3 mg/kg, DEX 3 mg/kg + CLEN 2 mg/kg, and CLEN 2 mg/kg. Diaphragm fiber cross-sectional areas (CSA) were measured. Twitch transdiaphragmatic pressure (Pdi) and tetanic Pdi were measured during bilateral phrenic stimulation both before and after 60 min of inspiratory resistive loading (IRL). DEX produced a marked atrophy of type IIa and type IIb diaphragm fibers. This diaphragm atrophy was prevented by CLEN in the DEX plus CLEN group. CLEN alone increased CSAs of all three types of diaphragm fibers. Significant reductions in twitch Pdi and tetanic Pdi at all stimulation frequencies both before and after IRL were observed similarly in the DEX group as well as in the DEX plus CLEN group compared with the control animals. We conclude that DEX produces significant diaphragm atrophy and decreases diaphragmatic contractility. CLEN produces hypertrophy of the diaphragm and minimizes diaphragm atrophy induced by DEX, but it has no demonstrable protective effect on DEX-induced diaphragm dysfunction.

The neural activation of the diaphragm during quiet and vigorously stimulated breathing has been hypothesized to be submaximal. In this study, we measured phrenic motoneuron firing rates during brief progressively increasing inspiratory resistive loads in anesthetized rabbits. We recorded activity in 68 phrenic motoneurons in 17 rabbits. We found that 40 of these axons were active during quiet breathing. Twenty-seven axons were silent during quiet breathing but began to fire as inspiratory loading progressed. The level of drive reflected by transdiaphragmatic pressure where silent phrenic motoneurons were recruited ranged from 5 to 45 cmH2O. Silent motoneurons showed significantly higher average rates of firing and significantly greater increases in firing rate as loading progressed (P < 0.01). The firing rate of both active and silent axons tended to plateau as rates approached 70-80 Hz. All motoneurons except for one, which may have been an afferent, were activated by inspiratory resistive loading. Inspiratory resistive loading activated phrenic motoneurons at high rates, and our results did not support the presence of significant numbers of unrecruited motoneurons.