ADVERSE INFLUENCE OF SYSTEMIC VASCULAR STIFFENING ON CARDIAC DYSFUNCTION AND ADAPTATION TO ACUTE CORONARY-OCCLUSION

Background Age is an independent risk factor for increased mortality f rom ischemic heart disease. Arterial stiffening with widening of the p ulse pressure may contribute to this risk by exacerbating cardiac dysf unction after total coronary artery occlusion. Methods and Results To test the above hypothesis, 14 open-chest dogs underwent surgery in whi ch the intrathoracic aorta was bypassed with a stiff plastic tube. Dir ecting ventricular outflow through the bypass widened the arterial pul se pressure from 41 to 115 mm Hg at similar mean pressure and flow. He arts ejecting into the native aorta (NA) exhibited only modest dysfunc tion after 2 minutes of mid-left anterior descending coronary artery o cclusion. However, the same occlusion applied during ejection into the bypass tube (BT) induced far more severe cardiodepression (ie, systol ic pressure fell by -41+/-10 mm Hg for BT versus -15+/-3 mm Hg for NA, and end-systolic volume rose by 15+/-3 versus 6+/-2 mL), with a three fold greater decline in ejection fraction. This disparity was not due to higher baseline work loads because total pressure-volume area was s imilar in both cases. Furthermore, marked increases in basal work load and wall stress induced by angiotensin II infusion (in four additiona l studies) did not reproduce this behavior. Although peak systolic cha mber stress was greater with the BT, this did not increase systolic dy skinesis as measured in the central ischemic zone. However, the total mass of myocardium that was rendered severely ischemic (ie, flow reduc ed by greater than or equal to 80%) was twice as large with BT ejectio n, likely expanding the region of dyskinesis. This disparity may relat e to altered phasic coronary flow during BT ejection, which displays m arked enhancement of systolic flow and renders the heart more vulnerab le to diminished mean and systolic perfusion pressures. Conclusions Ca rdiac election into a stiff systemic vasculature augments cardiac dysf unction and ischemia due to coronary occlusion by tightening the link between cardiac systolic performance and myocardial perfusion. This ma y contribute to the higher mortality risk from ischemic heart disease due to age.