Weaning of newborn infants from mechanical ventilation is a major clinical problem. This has been attributed to the premise that premature infants have respiratory muscles which fatigue easily. Recent data from premature baboon diaphragm show that while enzyme histochemistry of this muscle's fibers is predominantly oxidative, they are surprisingly resistant to fatigue. We hypothesize that postnatal events, not prenatal development, cause alteration in the diaphragm muscle of premature baboon and human infants thus predisposing them to muscle fatigue. Specifically, we therorize that: 1. inadequate nutrition retards growth, differentiation, and performance of the diaphragm muscle; and 2. modes of mechanical ventilation which limit active diaphragm contraction cause greater diaphragm muscle atrophy and increased fatigability as compared to techniques which allow muscle contractions. To test this hypothesis we will utilize a previously validated model of prematurity and hyaline membrane disease in the 140/day baboon. Forty baboon infants delivered by hysteromy at 80% of gestation will be randomized into four treatment groups. Groups 1 and 2 will be ventilated with intermittent mandatory ventiliation (IMV). Group 1 will be noursihed with protein sparing calories only, while group 2 will be fully nourished using a balanced hyperalimentation solution. Animals in groups 3 and 4 will be fully nourished and assigned to either controlled positive pressure ventilation (IMV with pharmacologic paralysis) or high frequency oscillatory ventilation for the duration of the experiment. Nutritional status will be assessed using weight, caloric intake, and measures of nitrogen balance, respiratory quotient, and oxygen consumption. All animals will be maintained with routine nursery tehniques and sacrificed at 10 days. Samples of diaphragm muscle will be collected at necropsy and coded so as to blind analyses to treatment group. Diaphragm musccle fiber type distribution, mean fiber area, and mean fiber cross-sectional area will be determined and compared with extensive developmental data derived in our laboratories. Force-frequency relationships will be plotted for all samples. Additional functional studies will be: twitch tension, maximal isometric tetanic tension, twitch to tetanus ratio, time to peak tension, one-half relaxation time, and maximum rate of tension development. Isotonic contractile measures of maximum velocity of shortening and maximum velocity of unloaded shortening will be determined using standard techniques.
| Kasper, C E (1999) Recovery of plantaris muscle from impaired physical mobility. Biol Res Nurs 1:4-11 |
| Maxwell, L C; Enwemeka, C S; Fernandes, G (1992) Effects of exercise and food restriction on rat skeletal muscles. Tissue Cell 24:491-8 |
| Kasper, C E; White, T P; Maxwell, L C (1990) Running during recovery from hindlimb suspension induces transient muscle injury. J Appl Physiol 68:533-9 |
| Delemos, J; Dryer, G; Gerstmann, D et al. (1989) Oliguria in the premature baboon with hyaline membrane disease: a manifestation of multisystem immaturity? J Perinatol 9:19-25 |
| Maxwell, L C; Kuehl, T J; McCarter, R J et al. (1989) Regional distribution of fiber types in developing baboon diaphragm muscles. Anat Rec 224:66-78 |
