More in vivo experimentation is needed in cardiovascular physiology.

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IN THIS PERSPECTIVE, I present the view that cardiovascular physiologists may do well to reinvent some of our old in vivo experiments to gain a deeper and more useful understanding of physiology and disease. Certainly, many physiological and pathophysiological phenomena were discovered through classic in vivo experiments on cardiovascular function (exemplified particularly by the work of A. C. Guyton and his colleagues in the 1970s), but methodological limitations at that time precluded the elucidation of the underlying molecular mechanisms. During the ensuing four decades, new methodologies and the extensive use of isolated tissues, isolated cells, and cell lines led to the discovery of a myriad of molecular mechanisms that undoubtedly contribute to cardiovascular regulation. Nevertheless, such studies do not necessarily inform us about the relative contributions of these mechanisms in vivo. A case in point: in clinical trials (perhaps the ultimate in vivo experiment) the approval success rate for new cardiovascular drugs is only 8.7% (3). One frequent reason for the poor success is unanticipated complexity of the intact organism. Thus a new, more insightful, in vivo experimental approach is needed for cardiovascular physiologists to elucidate normal physiological and pathophysiological mechanisms. Many new approaches are now possible, but one with exceptional potential in my opinion is the visualization and quantification of signal transduction within cells in the living, and even conscious, animal. This could be considered a reinvention of classic intravital imaging, extended to the molecular