Am. J. Respir. Crit. Care Med., Volume 157, Number 4, April 1998, 1277-1282

Peritonitis Causes Diaphragm Weakness in Rats

KEVIN M. KRAUSE, MELANIE R. MOODY, FRANCISCO H. ANDRADE, ADDISON A. TAYLOR, CHARLES C. MILLER III, LESTER KOBZIK, and MICHAEL B. REID

Departments of Medicine and Surgery, Baylor College of Medicine, Houston, Texas; and Physiology Program, Harvard School of Public Health, Boston, Massachusetts

Respiratory failure is a common and often lethal complication of severe peritonitis. Because this inflammatory process develops in the abdomen, adjacent to the diaphragm, we hypothesized that peritonitis might directly compromise diaphragm function. We tested this hypothesis using male Sprague-Dawley rats. We injected oyster glycogen into the rats' peritoneum, and 16 h later the peritoneum was lavaged for leukocyte analysis and muscle samples were excised. Contractile properties of diaphragm fiber bundles were measured in vitro. We found that neutrophils and macrophages were concentrated in peritoneal lavage fluid of experimental animals (p < 0.01) and were adherent to the abdominal surface of the diaphragm. Immunohistochemistry showed increases in inducible nitric oxide synthase in microvessels of the diaphragm and limb skeletal muscles but not in heart or spleen. Peritonitis decreased maximal force production by the diaphragm (23.6 ± 0.6 versus 21.2 ± 0.6 N/cm²; p < 0.05) and decreased the absolute forces developed at physiologic stimulus frequencies (> 30 Hz; p < 0.01), depressing the overall force-frequency relationship (p < 0.001). Peritonitis had little effect on acute muscular fatigue. These data demonstrate that peritonitis weakens the diaphragm in rats and suggest that humans with peritonitis may be predisposed to respiratory muscle dysfunction.

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