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Pre-clinical Model of Cardiac Donation after Circulatory Death

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Ischaemic endothelial dysfunction after single or multidose cardioplegia.

P S Mankad¹, A H Chester, M H Yacoub

¹National Heart and Lung Institute, London, U.K.

European Heart Journal

|July 1, 1992

Summary

St Thomas

Area of Science:

Cardiovascular Science
Physiology
Pharmacology

Background:

Cardiac surgery often involves ischemia, potentially damaging the coronary endothelium.
Endothelial dysfunction impairs coronary vasodilation, affecting blood flow.
St Thomas' Hospital cardioplegia solution (ST) is used to protect the heart during surgery.

Purpose of the Study:

To investigate the impact of ischemia and ST cardioplegia on endothelial function.
To assess the protective effects of single and multidose ST infusions against ischemia-induced endothelial dysfunction.
To compare the effects of ST on endothelium-dependent (5-Hydroxytryptamine, 5-HT) and endothelium-independent (nitroglycerine, GTN) vasodilation.

Main Methods:

Isolated rat hearts were perfused using a Langendorff preparation.

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Hearts were subjected to varying durations of ischemia (30, 60, or 90 minutes), with or without ST cardioplegia.

Coronary vasodilation was measured in response to 5-HT and GTN before and after ischemic periods.

Main Results:

Unprotected ischemia abolished 5-HT-induced vasodilation but preserved GTN response.
Single-dose ST infusion offered partial protection against ischemia-induced endothelial dysfunction.
Multidose ST infusions (two or more) effectively preserved 5-HT-induced vasodilation during prolonged ischemia (90 minutes).

Conclusions:

Coronary vascular endothelium is highly susceptible to ischemic damage, leading to early loss of function.
Multidose ST cardioplegia significantly protects endothelial function during prolonged cardiac ischemia compared to single-dose.
These findings highlight the importance of multidose cardioplegia for preserving coronary endothelial health in cardiac surgery.