Report on workshop on the microcirculatory approach to peripheral vascular function.

Abstract As might be anticipated, no single preparation was ideal. Each had attractive features not present to the same degree in other models. What emerged was the need for a set of standards which could be applied both in a local and in a systemic context to make certain that the preparation was as close to physiologic norm as possible, and, if certain sacrifices had to be made, that their implications were clearly spelled out. Included should be central manifestations of the state of the animal as a whole, the depth of anesthesia, its response to surgical intervention, its ability to maintain core temperature, etc. On the local level, criteria for viability could include spontaneous vasomotor activity, the ability of arterioles and venules to react to chemical stimuli, the absence of leukocyte sticking, the relative diameter of paired arterioles and venules, and the presence of an intermittent circulation in the various capillaries of the network. In autoperfused preparations, deteriorization of the animal as a whole is a critical factor. Tissue preparations tend to change with time, but here again no criteria have been adopted to document in the protocol the extent of the deteriorization. On the whole, clinically oriented workers or physiologists, accustomed to working with the circulatory system as an entity, were more critical of the failure to monitor conventional indices, such as pO 2 , pCO 2 , levels of anesthesia, etc. Microcirculationists, on the other hand, tended to emphasize local control of the tissue environment—temperature and bathing fluid composition. Despite the desirability of setting up criteria for establishing the effects of particular factors such as temperature on the reactivity of a particular vascular bed, it was concluded that the answer depended on the function being considered. Reactivity to drugs requires careful control of temperature; whereas the response to nervous stimuli seemed to permit a wider range of tolerance. Frequently neglected features are the gas content of solutions suffusing exposed tissues and adequate buffering. Anesthesia presents a difficult problem in terms of management in small animals—airway obstruction is a frequent hazard. Pentobarbital, the agent most commonly used to immobilize experimental animals, has undesirable effects on respiration and nervous regulation. The resulting effects on pO 2 , pCO 2 , and pH, in turn, influence vascular behavior in an unpredictable way. Of the preparations available for microscopic analysis, only a limited number do not require surgery or general anesthesia. These include the transparent chamber in the ear or skin, the bat wing, or the conjunctiva of the eye. A number of attempts have been made to provide artificial access to tissues such as the cheek pouch of the hamster so they could be studied without surgery or anesthesia. The small size of the mouse or bat has made it difficult to acquire important systemic measurements such as blood pressure or repeated blood samples for analysis. This latter contingency has led many investigators to concentrate on the maintenance of the viability of the tissue without equal concern for the status of the animal as a whole. For the most part, factors such as anesthetic management and adequate blood oxygenation, have not been properly routinized; some structures, such as the bat wing and the hamster cheek pouch, have atypical features which may not be directly applicable to the circulation in other areas. The transparent ear chamber in the rabbit is a structure which bypasses problems of anesthesia and surgery. The tissue is totally physiologic and provides a fine example of circulation in subcutaneous areolar connective tissue. Access to the enclosed tissue is however limited, except perhaps by way of laser beam irradiation. Workers who wish to examine the behavior of the microcirculation directly are confronted with two basic choices and must weight the pros and cons of this irony—either their needs can be met with simple viewing and photographic recording, or they must artificially set up conditions which may detract from the physiological status of the preparation so as to have direct access to the vessels.