This research focuses on the characterization of the dimensions and function of the microvessels in regenerated skeletal muscle. The model to be used is the grafted retractor muscle in the hamster. The muscle is removed, placed in a myotoxic solution and grafted into its original position. All of the original fibers, blood vessels and nerves are destroyed by this process. The muscle fibers regenerate and the graft is revascularized by the ingrowth of vessels from the surrounding tissue. The microvasculature of the muscle graft will be observed at different times between 30 and 270 days, by the use of in vivo video-microscopy. The muscle graft is isolated, exposed and superfused with a bicarbonate buffered physiological salt solution. Responses of the microvessels to various topically applied or infused substances are taped and replayed for direct measurement from a television monitor. The study is divided into 3 parts: 1. The description of the microvascular dimensions (arteriole, capillary and venule length and diameters) and the orientation of capillaries; 2. The response (change in diameter) of arterioles to vasoactive substances that a) act on the smooth muscle and are either receptor mediated (norepinephrine, adenosine, and prostaglandin E1) or non-receptor mediated (verapamil, potassium), or b) are dependent upon an intact endothelium for their actions (acetlycholine, Calcium ionophore A23187, and Substance P); 3. The measurement of the relative permeability of post-capillary venules to selected substances that are either receptor mediated (histamine and bradykinin), non-receptor mediated (phospholipase A2 and Calcium ionophore A 23187) or somehow alter the macromolecular organization of the endothelial cell surface (protamine sulfate and Evans blue dye). This research will elucidate some of the mechanisms that underlie the alterations in microvessel function and blood flow characteristics that accompany skeletal muscle degeneration and regeneration following injury. This will lead to a better understanding of performance and fatigability of skeletal muscle that has been damaged and repaired and may help in the development of intervention and/or rehabilitation strategies of injuries associated with ischemia, trauma, disease, myotoxic agents and strenuous exercise.
| Burton, H W; Walker, J A (1994) Delayed recovery of endothelium-dependent vasodilation in regenerating arterioles of skeletal muscle autografts. Microvasc Res 48:85-95 |
