Abstract
“Those diseases that medicines do not cure are cured by the knife. Those that the knife does not cure are cured by fire. Those that fire does not cure, must be considered incurable.” Hippocrates in 370 BC made the first recorded mention of the use of heat as a therapeutic. To this day, the effect of temperature on the body is of interest to clinicians, athletes, researchers, and perhaps anyone that has lived through Georgia summers or Michigan winters. The body maintains temperature homeostasis by the process of thermoregulation. The body’s ability to thermoregulate is an important coping mechanism to withstand various physiological states, such as fever, and environmental exposures such as the weather. The cardiovascular (CV) system plays a vital role in thermoregulation because of its influence on heat transfer via forced convection and conduction by changes in blood distribution, blood velocity, and proximity of tissues. It remains unclear how the allocation of blood in various compartments (such as the innermost core, fat, muscle, and skin) changes with temperature. Challenges in measuring core vasculature have resulted in a lack of empirical information regarding how it might change with core temperature. Therefore, to fully understand the CV system’s role in thermoregulation, this thesis focuses on using murine models to study the effect of temperature on core vasculature. The overall purpose is to provide a novel and physiologically accurate approach to studying thermoregulation by incorporating structural and functional changes in the CV system occurring in the core. Using murine models and MRI, we noninvasively quantified structural and functional vascular response in core arteries and veins to increasing core body temperature. We also studied the effects of sex and age on the CV response to increasing temperature. Using a PID-controlled heater to blow hot air across the animals, core temperature was controlled from mild hypothermia (35 °C) to mild hyperthermia (38 °C). At each temperature, we imaged three to four locations of the body from head-to-toe, and quantified blood flow and velocity, vessel area, and
measured circumferential cyclic strain of the core vessels. Overall, we have shown: 1) that increases in flow occur in most arteries and veins, which is opposite to current hypotheses regarding the venous response; 2) that the magnitude of increased flow varies based on anatomical location; and, 3) that the increase in flow sometimes involves cross-sectional area and velocity and other times involves only one or the other. These vascular responses are also influenced by sex and age. It is important to incorporate the cardiovascular changes occurring in the core into future bioheat or computational fluid dynamics modeling because blood flow is critical in heat
generation and transfer in vivo. This research can help researchers, clinicians, and others interested in temperature’s effect to better model and predict cardiovascular outcomes.