Microvascular Shunts, Intracranial Pressure, and the Impact of Drag-Reducing Polymers.

In the 50 years of my membership in ISOTT, I, Edwin M Nemoto, have enjoyed the application of many of the technologies developed in our society including microelectrodes for pH, PO, and near-infrared spectroscopy (NIRS) in the measurement of tissue oxygenation and metabolism. The greatest joy has been the number of great scientists I have had the pleasure of knowing and exchanging scientific ideas with across the United States, Europe, and Asia. This will be the enduring legacy of ISOTT for me personally as we continue beyond our half-century existence.Every organ in our body, including the tegmentum, is endowed with microvascular shunts (MVS), which may be involved in physiological regulation, i.e. temperature regulation or pathophysiological responses to tissue injury and oedema. MVS that open in response to increased capillary resistance and tissue oedema in the brain, heart, kidneys, liver, and muscles conduct neither nutrient nor gas exchange with tissue promoting tissue oedema in a vicious cycle. Pharmacologic arteriolar vasodilation cannot correct the MVS flow as may occur after a stroke or traumatic brain injury because pan arteriolar vasodilation would shunt flow to the normal tissue and away from the injured brain in a "reverse" steal or a "Robin Hood" phenomenon. A high molecular weight (4000 kDa) drag-reducing polymer (DRP) of polyethylene oxide or Lamiflo enhances blood flow by altering the physical dynamics of red blood cells (RBC) and blood flow, increasing the shear rate in the microvasculature and capillaries where shear rate is highest as it is inversely proportional to the 3rd power of blood vessel diameter. The shear rate sensed on the endothelium through the glycocalyx exerts precise control of endothelial function, including endothelial water permeability, nitric oxide synthase activity, lymphocyte adhesion to and transport across the endothelium, and microglial activation, all in response to low endothelial shear rate. DRP has proven effective in reversing MVS flow and increasing capillary flow in haemorrhagic shock, myocardial ischaemia, stroke, renal ischaemia, traumatic brain injury, stroke, sepsis, and Alzheimer's Disease. Our aim is to establish the universality of MVS in the pathogenesis of vascular disease and in taking DRP to clinical treatment of vascular diseases.