INTEGRATIVE ASPECTS OF CARDIOVASCULAR FUNCTION

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DESCRIPTION (Adapted from the applicant's abstract): The overall goal of the projects proposed in this application is to further our understanding of the mechanisms producing the hemodynamic adjustments that accompany dynamic exercise. The studies will investigate how, and when, mechanical (or hydraulic) factors and reflex control mechanisms contribute to these adjustments. Knowledge of how bodily processes function in health is needed to understand disease. The overriding methodological approach is one whereby the components of the circulatory system can be studied in an integrative fashion with the other elements of the circulation regulated. AIM I: Rhythmic contraction and relaxation of skeletal muscle drives blood flow through the active muscles, termed the skeletal muscle pump. Although the muscle pump exerts a profound influence on cardiac output, right atrial pressure, and arterial blood pressure in exercise, relatively little is known about the mechanical properties of the muscle pump. This void will be filled by studying the isolated muscle pump. Hindlimb muscles of anesthetized animals will be made to perfuse themselves during brief periods of electrically induced contractions. This will be accomplished by shunting venous blood draining from the active muscles directly back into the arteries supplying the muscles. In essence, the active muscles will perfuse themselves by driving blood around a "short-circuit" that isolates the muscles from the remainder of the circulation; this is analogous to isolated heart-lung preparations that have greatly increased our understanding of the mechanical properties of the ventricular pumps. AIM II: The effects of changes in the mechanical activity of the heart on cardiac filling pressure will be assessed. The rise in heart rate that accompanies exercise must lead to a decrease in the time-averaged volume of blood "stored" in the heart chambers, owing to the reduction in time spent at end-diastolic volume. A fall in heart volume must cause a reciprocal increase in extra-cardiac blood volume and pressure. The ability of the heart to raise its own filling pressure when heart rate rises will be tested by making the heart pump the same cardiac output at a low heart rate and then again at a high heart rate. Cardiac filling pressure should be higher during fast pacing of the heart owing to transfer of blood volume from cardiac chambers to central veins. AIM III: The role of the venous system in making blood available to the heart will be examined by determining the effect on cardiac filling pressure of actively changing the distribution of cardiac output between compliant and non-compliant circulations. The approach is to control and manipulate cardiac output and hindlimb blood flow (a non-compliant circulation) by computer controlled ventricular pacing and vascular occluder cuffs. AIM IV: The influence of the muscle chemoreflex, stimulated by making contracting muscles ischemic, or arterial baroreflex stimulus-response curves will be investigated to see if the muscle chemoreflex "resets" the baroreflex to a higher operating point in exercise. AIM V: The ability of the muscle chemoreflex to raise cardiac filling pressure will be assessed.