PURPOSE: In rats, controlled mechanical ventilation (CMV) induced a profound reduction in diaphragm (DIA) muscle force-generating capacity as early as 24h, whereas in rabbits a similar decline was observed after 48h. Conflicting responses in rats and rabbits were extended to high-dose of methylprednisolone (MP). In rats, high-dose MP had a protective effect on CMV-induced DIA dysfunction (Respir Research 2010), whereas in rabbits had a deleterious effect (Muscle Nerve 2011). This study aimed to determine DIA force-generating capacity in animal model of critical-illness myopathy in which both cisatracurium (NM) and high-dose MP were administered in rats and rabbits receiving CMV for 48 h.
METHODS: Fifteen Sprague Dawley rats and 16 New Zealand White rabbits were randomized into receiving 48 h of CMV and NM with either saline (n=4 rats, n=6 rabbits) or MP (30 mg/kg/d i.v.; n=5 rats or rabbits), or control (n=6 rats, n=5 rabbits) groups. At the end of the experiment, in vitro isometric DIA force was measured. The data were expressed as percentage of the average value of controls of the respective species. Data of rats and rabbits were compared using the unpaired t-test.
RESULTS: After 48h of CMV-NM alone, maximum tetanic force (Po) was 71.6±2.8% and 69.8±4.1% (mean±SE; p>0.05) in rats and rabbits, respectively. Po with the combined CMV-NM and high-dose MP was 66.8±3.3% and 58.0±1.7% (p< 0.05), in rats and rabbits, respectively.
CONCLUSIONS: Animal species had no influence on the rate of decline of DIA force-generating capacity when experiments were conducted within the same laboratory. High-dose MP had deleterious effects on DIA muscle function in both rats and rabbits, although the effects in rats were less than in rabbits.
CLINICAL IMPLICATIONS: Diaphragm muscle function is impaired with CMV-induced diaphragm muscle disuse. High-dose MP combined with CMV and NM is deleterious to diaphragm muscle function.
DISCLOSURE: The following authors have nothing to disclose: Catherine Sassoon, Ercheng Zhu, Liwei Fang, Daniel Wang
The study is a basic science animal research.