Biodesign of a skeletal muscle flap as a model for cardiac assistance

In using autologous muscles for cardiac assistance, it is crucial to reduce ischemia-reperfusion injury in the surgically traumatized skeletal muscle. In adult sheep, we developed a simple model of surgically designed 2 latis simus dorsi muscle leaflets by modifying the vascular supply to these leafl ets. Three pockets with graded injury were established, and muscle morpholo gy and vascular remodeling were monitored in 3 experimental groups: muscle leaflets without any treatment (Group 1, n = 6) that served as controls; mu scle leaflets integrated with a fibrin interlayer (Group 2, n = 6); and lea flets integrated with fibrin and entrapped pyrrolostatin (Group 3, n = 6). We applied the fibrinogen and thrombin solutions, which polymerize to form a three-dimensional meshwork joining the tissues, creating a provisional ma trix for angiogenesis, and acting as a delivery depot for agents aimed at m inimizing ischemia-reperfusion lesion formation. After 2 months, the muscle leaflets biointegrated with the fibrin interface showed none of the signs of necrosis or ischemia-reperfusion lesions seen in the controls. Although no angiogenic factors were incorporated, the fibrin interlayer rapidly (<2 weeks) became a densely vascularized tissue replete with a voluminous capil lary network. In contrast, controls showed poor bonding between the tissues , muscle fiber deterioration, and a compromised vascular network. Muscle st ructure was best preserved and angiogenesis was greatest when pyrrolostatin , a free radical scavenger, was added to the fibrin meshwork to reduce dama ge caused by overproduction of free radicals. This newly designed model wil l be useful to study many current approaches in cardiovascular biology, fro m pharmaceuticals to gene therapy, which might prove advantageous in muscle -designed cardiac assistance.