Submitted on November 25, 2003
Accepted on April 21, 2004
ADVERSE EFFECTS OF MYASTHENIA GRAVIS ON RAT PHRENIC-DIAPHRAGM CONTRACTILE PERFORMANCE
Erik van Lunteren1*, Michelle Moyer2, and Henry J Kaminski3
1 Department of Medicine(Pulmonary), Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Cleveland VA Medical Center, Cleveland, OH, USA; Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA
2 Department of Medicine, Cleveland VA Medical Center, Cleveland, OH, USA
3 Department of Neurology, Case Western Reserve University, Cleveland, OH, USA; Department of Neurology, Cleveland VA Medical Center, Cleveland, OH, USA; Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA
* To whom correspondence should be addressed. E-mail: exv4{at}po.cwru.edu.
Myasthenia gravis has variable effects on the respiratory system, ranging from no abnormalities in mild cases to life-threatening respiratory failure in severe cases. The present study characterized diaphragm muscle contractile performance in rats with autoimmune myasthenia gravis. Rats were injected with a monoclonal antibody which recognizes acetylcholine receptor determinants (or an inactive antibody), and three days later phrenic nerve and diaphragm were studied in vitro. Myasthenic rats segregated into two groups, those with normal versus impaired limb muscle function when tested in the intact animal ("mild" and "severe" myasthenic). Baseline diaphragm twitch force was reduced for both severe (P < 0.01) and mild (P < 0.05) myasthenic compared with control animals (twitch force normal 1352 ± 140, mild myasthenic 672 ± 99, severe myasthenic 687 ± 74 g/cm2). However, only severe myasthenic diaphragm had impaired diaphragm endurance, based on significantly (P < 0.05) accelerated rate of peak force decline during the initial period of stimulation (0.02 ± 0.02% per pulse for normal, 0.03 ± 0.01% per pulse for mild myasthenic, and 0.09 ± 0.01% per pulse for severe myasthenic during continous stimulation) and intra-train fatigue (up to 30.5 ± 7.4% intra-train force drop in severe myasthenic versus none in normal and mild myasthenic, P < 0.01). Furthermore, when compared with continuous stimulation, an intermittent stimulation pattern had a protective effect on force of severe myasthenic diaphragm (force after 2000 pulses was 31.4 ± 2.0% of initial during intermittent stimulation versus 13.0 ± 2.1% of initial during continuous stimulation, P < 0.01) but not on normal diaphragm. These data indicate that baseline force and fatigue may be affected to different extents by varying severity of myasthenia gravis, and furthermore provide a mechanism by which alterations in breathing pattern may worsen respiratory muscle function in neuromuscular diseases.
