• Sieck, Gary C (PI)

Project: Research project

Project Details


During early postnatal development, the contractile, fatigue and metabolic
properties of the diaphragm may be different than those in the adult muscle
due to the pattern of polyneuronal innervation of muscle fibers. Thus, the
diaphragm in younger animals may be more susceptible to respiratory
stresses. If either a diminished motor responsiveness or an abnormal
development resulted in diaphragm fatigue, respiratory failure might result
and contribute in conditions such as respiratory distress syndrome and
sudden infant death syndrome. The objectives of the proposed research are
to determine the developmental changes in: 1) The contractile and fatigue
properties of the diaphragm; 2) the metabolic properties of diaphragm
muscle fibers; and 3) the correlation between physiological and metabolic
properties. The proposed studies will examine the control of the diaphragm
of kittens during the first 3 weeks of postnatal development. This period
corresponds with the disappearance of polyneuronal innervation in the
diaphragm. The contractile and fatigue properties of the whole diaphragm
will be studied using an in vitro muscle strip preparation. In an in vivo
preparation, single diaphragm motor units will be isolated in anesthetized
kittens by stimulation of dissected ventral root filaments of the phrenic
nerve. In both preparations, the contractile properties to be studied will
include: 1) Contraction time; 2) Half relaxation time; and 3)
Force/frequency relationships. Fatigue will be assessed using a standard
fatigue test. The metabolic properties of individual muscle fibers in the
diaphragm will be determined by quantifying the histochemical reactions
for: 1) Succinate dehydrogenase (SDH), and oxidative enzyme; 2)
Alpha-Glycerophosphate dehydrogenase (GPD), a glycolytic enzyme; and 3)
Myosin adenosine triphophatase (ATPase), an enzyme involved in the
hydrolysis of ATP. This quantitative analysis of histochemical reactions
will utilize a photometric technique implemented on a computer-based image
processing system. In population studies, the mean SDH, GPD and ATPase
activities will be compared statistically with contractile and fatigue
properties of the whole muscle at different ages. In motor unit studies,
the constituent muscle fibers of a unit will be identified using the method
of glycogen depletion, where motor unit fibers are depleted of glycogen by
repeated activation. The SDH, GPD and myosin ATPase activities of these
unit fibers will then be compared with those of fibers not belonging to the
unit. The correlations between motor unit contractile and fatigue
properties and the metabolic properties of muscle fibers belonging to the
motor unit will be determined.
Effective start/end date7/1/863/31/03


  • Medicine(all)