The long-term objective of the proposed research is to describe the postnatal changes in contractile, fatigue and metabolic properties of the diaphragm muscle. Postnatal changes in diaphragm fatigue resistance are especially important, since fatigue of this vital muscle could result in ventilatory failure and sudden death.
The specific aims of the proposed research are to examine the postnatal changes in: 1) the relationships between diaphragm contractile and fatigue properties, and extent of polyneuronal innervation, the expression of different myosin heavy chains, fiber oxidative capacity (rate of SDH activity), and fiber energy utilization (rate of ATPase activity); 2) the contractile and fatigue properties of diaphragm motor units, and unit fiber type composition; and 3) the forces generated by the diaphragm during normal ventilation. The isometric contractile and fatigue properties of the neonatal rate and rabbit diaphragm will be determined using an in vitro preparation. The extent of polyneuronal innervation will be estimated by: Tension summation; End-plate potential increments; and Histological identification of nerve terminals. In serial sections of the same fibers, the expression of slow, neonatal, and adult fast myosin heavy chains will be identified immunohistochemically. Fibers will also be classified as type I, IIA, IIB, or IIC using standard histochemistry. Microphotometric procedures will be used to quantify fiber SDH and ATPase activities. Diaphragm motor units will be isolated in vitro by microdissection of cervical ventral rots. Unit contractile and fatigue properties will be characterized, and unit fibers will be identified by glycogen depletion. The myosin heavy chain composition, SDH and ATPase activities of unit fibers will be determined. The transdiaphgragmatic pressures (Pdi), generated during normal ventilation will be compared to the maximum Pdi's generated during bilateral phrenic nerve stimulation. The effects of the following experimental manipulations will also be examined: 1) Prolonged diaphragm inactivation (TTX) block of the phrenic nerve); 2) Partial (c4) denervation; and 3) Prenatal undernutrition.
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