Experience with tissues subjected to trauma and prolonged or repeated ischemia, as in cases of multiple anastomotic revisions, led to recognition of the "no-reflow phenomenon" as a microsurgical complication.10 This phenomenon had been reported earlier in ischemic organ transplants. Functionally, the no-reflow phenomenon is a state in which the microcirculation distal to a microvascular arterial anastamosis no longer functions as a patent bed. Venous return does not appear, the resistance of the microcirculation progressively increases, and arterial thrombosis occurs because of stasis. If the loss of microcirculatory patency is irreversible, the tissue is lost. The "no-reflow phenomenon" is initiated by ischemic tissue injury, and specific processes of cellular edema, capillary obstruction and constriction, microthrombosis, acidosis, impaired fibrinolysis, and the intracellular biochemical disorders of shock play roles in its progression and climax. 10,46-49 Investigators exploring ways to prevent or reverse these interlocking processes have pursued further nuances of anticoagulation 41,50 and "pharmacologic delay";16,51,52 and have begun to explore prostaglandin biology29,53,54 and components of intracellular biochemistry, including free radical scavengers13 and substrate reinforcement.55-57

None of these specific physiologic problems - vasospasm, early and late clotting, and the tissue responses to acute and prolonged ischemia - exist in isolation from the others, but most pharmacologic agents are used with the purpose of specifically modifying one process. Commonly used multiple-agent therapies, such as aspirin, dextran, and chlorpromazine,33,58 are empiric attempts to ensure additionally against possible ill effects from multiple physiologic processes. Clearly valid experimental models or prospective clinical trials establishing the relative importance of these recognize physiologic complications or the efficacy of any pharmacologic agent have not been reported, however.

Classification of Pharmacologic Agents

Rohrich, Cherry, and Spira59 proposed a definition of the ideal microsurgical pharmacologic adjunct and included the characteristics of safety, availability, reliability, known mechanism of action, and demonstrable efficacy. Despite the great number of drugs investigated experimentally and used clinically, no reported agent meets these criteria. Organization and review of the published work on microsurgical pharmacology therefore require generation of tentative conclusions based on empiric reports and a complicated and controversial body of experimental data.

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