Standard whole skeletal muscle grafts up to 6 g in mass revascularize and reinnervate spontaneously. The revascularization follows the period of ischemia and during this period fibers degenerate and regenerate. Grafts larger than 6 g can only be grafted successfully if blood vessels are anastomosed. Compared to control muscles, all types of grafts show deficits. The most critical functional deficits observed for grafts are in maximum tetanic tension development ad resistance to fatigue. Deficits in maximum tetanic tension development for whole grafts result from regeneration of fewer fibers, or fibers with smaller cross-sectional areas. Increased fatigability of grafts is associated with decreased oxidative capacity and capillary density, and an inappropriate blood flow. In grafts, the number of fibers that regenerate is dependent on the degree of revascularization and reinnervation whereas the fiber area and types of fibers that regenerate are dependent on innervation and subsequent use. The overall goals is to compare in rabbits the functional deficits that occur in nerve-anastomosed standard and vascularized grafts transplanted into the site of the rectus femoris muscle when both types of grafts are initially equal in mass. Comparisons will be made after the maximum tetanic tension of each type of graft has stabilized.
The specific aims are to determine the causes of these deficits and design procedures to reduce the deficits. Portions of latissimus dorsi muscles 1, 4, 7, and 10 g in mass, but of equal length will be grafted. Vascularization of grafts will be varied by operative procedures that result in spontaneous revascularization (standard grafts) or reperfusion of grafts by vascular anastomoses (vascularized grafts). Postoperative procedures will include ablation of synergistic muscles and contractions of grafts with chronic 10 Hz stimulation for 8 hrs. per day. With control muscles and 100 mg grafts in rats, ablation of synergists results in increased maximum tension and chronic stimulation in increased oxidative capacity, capillarity, blood flow, and resistance to fatigue. The causes of functional deficits will be evaluated by histological, histochemical, biochemical, and physiological measurements of whole grafts and of single motor units in grafts. Blood flow will be assessed by intravital microscopy and radioactive microsphere techniques. The results should clarify the optimal operative and postoperative procedures for the effective transplantation of human skeletal muscles.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034164-04
Application #
3346833
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1985-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Brooks, S V; Faulkner, J A; McCubbrey, D A (1990) Power outputs of slow and fast skeletal muscles of mice. J Appl Physiol 68:1282-5
Faulkner, J A; Zerba, E; Brooks, S V (1990) Muscle temperature of mammals: cooling impairs most functional properties. Am J Physiol 259:R259-65
Burton, H W; Stevenson, T R; White, T P et al. (1989) Force deficit of vascularized skeletal muscle grafts in rabbits. J Appl Physiol 66:675-9
Claflin, D R; Faulkner, J A (1989) The force-velocity relationship at high shortening velocities in the soleus muscle of the rat. J Physiol 411:627-37
Sandercock, T G; Cote, C; Faulkner, J A (1989) Properties of motor units in nerve-intact autografts of cat extensor digitorum longus muscles. J Neurophysiol 62:231-8
Markley Jr, J M; Faulkner, J A; Cote, C (1989) Transplantation and transposition of skeletal muscles into the faces of monkeys. Plast Reconstr Surg 84:424-31;discussion 432-3
Ridings, J W; Barry, S R; Faulkner, J A (1989) Aminophylline enhances contractility of frog skeletal muscle: an effect dependent on extracellular calcium. J Appl Physiol 67:671-6
Cote, C; White, T P; Faulkner, J A (1988) Intramuscular substrate depletion and fatigability of soleus grafts in rats. Can J Physiol Pharmacol 66:829-32
Guelinckx, P J; Faulkner, J A; Essig, D A (1988) Neurovascular-anastomosed muscle grafts in rabbits: functional deficits result from tendon repair. Muscle Nerve 11:745-51
Burton, H W; Stevenson, T R; Dysko, R C et al. (1988) Total and regional blood flows in vascularized skeletal muscle grafts in rabbits. Am J Physiol 255:H1043-9

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