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Coronary artery endothelial dysfunction after global ischemia, blood cardioplegia, and reperfusion
K Nakanishi1, Z Q Zhao, J Vinten-Johansen
1Department of Cardiothoracic Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1096.
Insights
Blood cardioplegia (BCP) does not prevent endothelial dysfunction caused by reperfusion injury after cardiac surgery. Reperfusion, with or without BCP, leads to endothelial damage, impacting nitric oxide pathways.
Area of Science:
- Cardiovascular Surgery
- Cardioplegia Research
- Endothelial Function Studies
Background:
- Global normothermic ischemia, cardioplegic arrest, and reperfusion are critical phases in cardiac surgery.
- Endothelial dysfunction, particularly related to nitric oxide, is a significant concern post-cardiac procedures.
- Blood cardioplegia (BCP) is used to protect the heart during arrest, but its effect on endothelial integrity needs clarification.
Purpose of the Study:
- To test if blood cardioplegia (BCP) attenuates endothelial dysfunction after normothermic ischemia, cardioplegic arrest, and reperfusion.
- To identify the specific time point and conditions leading to endothelial injury in a canine model.
- To evaluate the impact of BCP on nitric oxide-mediated vascular responses post-ischemia and reperfusion.
Main Methods:
- Anesthetized open-chest dogs on cardiopulmonary bypass were subjected to normothermic ischemia.
- Five groups were established: control, ischemia only, ischemia with reperfusion, ischemia with BCP without reperfusion, and ischemia with BCP and reperfusion.
- In vitro coronary vascular relaxation to acetylcholine, A23187, and NaNO2 was measured; electron microscopy assessed endothelial morphology.
Main Results:
- Impaired coronary vascular relaxation to acetylcholine (endothelium-dependent) was observed in groups subjected to reperfusion (with or without BCP).
- Electron microscopy confirmed significant endothelial damage in reperfused groups, while groups without reperfusion showed intact endothelium.
- Responses to A23187 and NaNO2 were not significantly altered, suggesting damage primarily affects receptor-dependent nitric oxide pathways.
Conclusions:
- Morphologic and functional endothelial damage occurs following blood reperfusion, irrespective of whether blood cardioplegia (BCP) was administered.
- The study indicates that 1-hour hypothermic BCP arrest following normothermic ischemia does not exacerbate endothelial damage.
- Reperfusion injury, rather than BCP itself, is the primary cause of endothelial dysfunction in this model.
Abstract:
This study tests the hypothesis that blood cardioplegia (BCP) attenuates endothelial dysfunction related to nitric oxide after global normothermic ischemia, cardioplegic arrest, and reperfusion in anesthetized open-chest dogs placed on cardiopulmonary bypass. The dogs were divided into five groups to identify the time when endothelial injury occurred: group 1 = control without ischemia; group 2 = 45 minutes of normothermic ischemia only; group 3 = 45 minutes of normothermic ischemia plus unmodified reperfusion; group 4 = 45 minutes of ischemia plus intermittent BCP without reperfusion; and group 5 = ischemia plus BCP and reperfusion. In vitro coronary vascular relaxation responses to the nitric oxide stimulator acetylcholine (endothelium-dependent, receptor-dependent), the calcium ionophore A23187 (endothelium-dependent, receptor-independent), and acidified NaNO2 (endothelium-independent) were measured at the end of the protocol. Maximum in vitro coronary vascular responses to acetylcholine were similar among groups 1, 2, and 4, indicating an absence of endothelial injury. In contrast, significantly impaired relaxations to acetylcholine were demonstrated in the two reperfused groups (groups 3 and 5). Relaxation responses to A23187 and NaNO2 were not altered markedly in any group. Electron microscopy showed intact endothelium in groups 1, 2, and 4. However, moderately severe endothelium damage was seen in groups 3 and 5. We conclude that morphologic and functional endothelial damage occurs after blood reperfusion with or without BCP, and 1-hour hypothermic BCP arrest after normothermic ischemia is not associated with extension of endothelial damage.