The Problem with Fashion

A continuing focus on subcellular processes could result in neglect of the framework through which these small processes are integrated. This focus could be particularly problematic in the cardiovascular system in which a patient’s clinical condition depends on the function of the whole system, specifically the pumping of blood and its distribution. These are currently less fashionable areas of research. However, the ability to characterize the intact system, for example during and after pharmacological or genetic perturbation, must be retained to realize the potential of molecular biology. Paradoxically, and unusually in medicine, the integrating processes within the circulation may be best understood by adopting a reductionist approach. Such an approach involves breaking down blood flow into its constituent elements. In this short editorial, we outline recent work on wavefronts, mathematically derived elemental forces in arterial flow that appear to provide a new perspective on the integrated system for clinicians and basic scientists alike. Although clinical applications remain to be elucidated, we speculate on likely areas of interest. The problem for intact system research is that elements are interdependent and are not easily held constant. There are many examples, e.g., cardiac output depends on the heart and the arteries but they are linked through afterload, coronary flow depends on aortic pressure and ventricular contraction and they interact, etc. In a system of tubes, the challenge frequently is how to resolve the directional basis of a perturbation, does it originate upstream or downstream, or both? How can interaction between constituent parts be considered as an interchange of energy? In the circulation, how do arteries serve as cables or transmission lines? It has long been recognized that the answers may be found in the mechanics of arterial wave travel (41), an area that has been mathematically redefined during the last few years (26). A wave-intensity analysis of forward and backward wave travel has the potential to quantify the amplitude and direction of energy transfer in the systemic (11, 12), pulmonary (9), or coronary arterial systems (32). This theoretical approach also has practical implications, because there is increasing evidence that upstream-downstream cardiovascular interactions have real prognostic (1) and therapeutic significance (24) for cardiology patients in the clinic. The disadvantageous development of left ventricular hypertrophy in hypertension and the advantageous use of vasodilators in heart failure serve as testimony to the importance of ventriculoarterial interaction.