The evaluation of constant coronary artery flow versus constant coronary perfusion pressure during normothermic ex situ heart perfusion

https://doi.org/10.1016/j.healun.2022.08.009Get rights and content
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Background

Evidence suggests that hearts that are perfused under ex-situ conditions lose normal coronary vasomotor tone and experience contractile failure over a few hours. We aimed to evaluate the effect of different coronary perfusion strategies during ex situ heart perfusion on cardiac function and coronary vascular tone.

Methods

Porcine hearts (n = 6 each group) were perfused in working mode for 6 hours with either constant aortic diastolic pressure (40 mmHg) or constant coronary flow rate (500 mL/min). Functional and metabolic parameters, cytokine profiles, cardiac and vascular injury, coronary artery function and oxidative stress were compared between groups.

Results

Constant coronary flow perfusion demonstrated better functional preservation and less edema formation (Cardiac index: flow control = 8.33 vs pressure control = 6.46 mL·min−1·g−1, p = 0.016; edema formation: 7.92% vs 19.80%, p < 0.0001). Pro-inflammatory cytokines, platelet activation as well as endothelial activation were lower in the flow control group. Similarly, less cardiac and endothelial injury was observed in the constant coronary flow group. Evaluation of coronary artery function showed there was loss of coronary autoregulation in both groups. Oxidative stress was induced in the coronary arteries and was relatively lower in the flow control group.

Conclusions

A strategy of controlled coronary flow during ex situ heart perfusion provides superior functional preservation and less edema formation, together with less myocardial damage, leukocyte, platelet, endothelial activation, and oxidative stress. There was loss of coronary autoregulation and decrease of coronary vascular resistance during ESHP irrespective of coronary flow control strategy. Inflammation and oxidative stress state in the coronary vasculature may play a role.

KEYWORDS

ex situ heart perfusion
coronary artery flow
coronary autoregulation
leukocyte activation
oxidative stress

Abbreviation

ESHP
Ex Situ Heart Perfusion
dP/dt max
Maximum rates of pressure change
dP/dt min
Minimum rates of pressure change
CVR
Coronary vascular resistance
LVSW
Left ventricle stroke work
CBF
Coronary blood flow
IL-6
Interleukin-6
IL-1α
Interleukin-1α
IL-1β
Interleukin-1β
IL-10
Interleukin-10
TNF-α
Tumor necrosis factor-α
β-TG
β-Thromboglobulin
sCD-40L
Soluble CD-40 ligand
ELISA
Enzyme-linked immunosorbent assay
MPO
Myeloperoxidase
cTnI
Cardiac troponin I
VCAM-1
Vascular cell adhesion molecule 1
vWF
Von Willebrand factor
ETAR
Endothelin A receptor
ETBR
Endothelin B receptor
oxLDL
Oxidized low-density lipoprotein
MDA
Malondialdehyde
ROS
Reactive oxygen species
RNS
Reactive nitrogen species
DAMP
Damage associate molecular pattern

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