An Increase in Coronary Blood Flow is not Associated with Increased Cardiac Function During Ex Situ Heart Perfusion
Supervisor / Principle Investigator:
Dr. Darren Freed
MD Class of 2021
Ex situ heart perfusion (ESHP) permits the preservation and assessment of donated hearts in a normothermic, functioning state. Optimization of this technology requires an understanding of cardiac physiology ex situ. In vivo, coronary artery blood flow (CBF) matches myocardial oxygen demands via coronary autoregulation (CAR), ensuring adequate oxidative metabolism for cardiac function. We sought to determine if CAR remains intact during ESHP by perfusing hearts procured from pigs using a working mode (WM: n=4) and non-working mode (NWM: n=4) perfusion method for 12 hours. Factors related to CAR (coronary vascular resistance, CBF, MVO2, % oxygen extraction and cardiac index) were recorded at 1, 5, and 11, hours of perfusion with hearts in WM. Myocardial ATP content was determined between in vivo myocardial samples (n=5) and myocardium perfused ex situ (n=5). CBF comparably increased during perfusion in WM and NWM, while % oxygen extraction, and coronary vascular resistance declined (p values<0.05). Cardiac index also decreased over time but was better preserved in WM (p values<0.05). Linear regression analysis revealed a negative relationship between CBF and cardiac index during perfusion (R2=0.203, p=0.027). CBF increased in NWM hearts during each transition into WM (p values<0.05). No difference in ATP content was observed. Overall CAR is impaired ex situ, indicated by the increasing CBF but declining cardiac index over time, and that different losses of cardiac index between NWM and WM occur at similar CBF’s. The correlation between these parameters is also poor. However, CAR is not entirely impaired as NWM to WM transitions are met with increases in CBF. Naturally, declines in cardiac index occur with declines in oxygen extraction, but this may be explained by a diminished oxygen delivery capacity in red blood cells warranting further investigation.