Related Experiment Video
Updated: Oct 26, 2026
Surgical Porcine Model of Chronic Myocardial Ischemia Treated by Exosome-laden Collagen Patch and Off-pump Coronary Artery Bypass Graft
Published on: September 15, 2023
Ischemic preconditioning attenuates postischemic coronary artery endothelial dysfunction in a model of minimally
V H Thourani1, M Nakamura, I G Duarte
1Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine, Carlyle Fraser Heart Center-Cardiothoracic Research Laboratory, Crawford Long Hospital, Atlanta, GA 30365-2225, USA.
Insights
Ischemic preconditioning protects coronary vessels from endothelial dysfunction during minimally invasive direct coronary artery bypass grafting. This protective effect preserves endothelial function and reduces neutrophil adhesion post-reperfusion.
Area of Science:
- Cardiovascular Surgery
- Vascular Biology
- Myocardial Protection
Background:
- Minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardioplegia can lead to endothelial dysfunction and myocardial injury.
- Polymorphonuclear neutrophils contribute to post-ischemic myocardial damage.
Purpose of the Study:
- To test if ischemic preconditioning can attenuate endothelial dysfunction in coronary vessels during MIDCAB.
- To evaluate the impact of ischemic preconditioning on endothelial function and neutrophil-mediated injury.
Main Methods:
- The study utilized an anesthetized dog model of MIDCAB.
- The left anterior descending coronary artery was subjected to 30 minutes of occlusion and 3 hours of reperfusion.
- Endothelial function was assessed by measuring relaxation responses to nitric oxide synthase stimulators, and neutrophil adherence was quantified.
Main Results:
- Ischemic preconditioning significantly improved endothelial-dependent relaxation in response to acetylcholine in the left anterior descending artery.
- Endothelial dysfunction, indicated by reduced acetylcholine-induced relaxation and increased neutrophil adherence, was attenuated by ischemic preconditioning.
- No differences in smooth muscle relaxation to sodium nitroprusside were observed, confirming endothelial-specific effects.
Conclusions:
- Ischemic preconditioning effectively attenuates both stimulated and basal endothelial dysfunction following ischemia-reperfusion in a MIDCAB model.
- This protective effect may reduce the risk of polymorphonuclear neutrophil-mediated myocardial injury during MIDCAB procedures.
Objective:
Unmodified reperfusion without cardioplegia in minimally invasive direct coronary artery bypass grafting procedures causes endothelial dysfunction that may predispose to polymorphonuclear neutrophil-mediated myocardial injury. This study tested the hypothesis that ischemic preconditioning in a minimally invasive direct coronary artery bypass grafting model attenuates postischemic endothelial dysfunction in coronary vessels.
Methods:
In anesthetized dogs, the left anterior descending coronary artery was occluded for 30 minutes and reperfused for 3 hours without ischemic preconditioning (no-ischemic preconditioning; n = 7); in 7 dogs, the left anterior descending occlusion was preceded by 5 minutes occlusion followed by 5 minutes of reperfusion. Relaxation responses to stimulators of nitric oxide synthase were used to evaluate endothelial function in arteries from the ischemic-reperfused (left anterior descending) and nonischemic (left circumflex coronary artery) zones.
Results:
Stimulated endothelial-dependent relaxation of epicardial left anterior descending artery to incremental concentrations of acetylcholine in the no-ischemic preconditioning animals was shifted to the right, and maximal relaxation was attenuated compared with the nonischemic left circumflex coronary artery (117% +/- 4% vs 138% +/- 5%). In contrast, acetylcholine-induced maximal relaxation was comparable in the left anterior descending artery versus left circumflex coronary artery in the ischemic preconditioning group (130% +/- 6% vs 135% +/- 5%). In 150- to 200- microm left anterior descending microvessels, 50% relaxation occurred with a lower concentration (log[M]) of acetylcholine in ischemic preconditioning versus no-ischemic preconditioning (-8.0 +/- 0.4 vs -7.0 +/- 0.1) with no group differences in smooth muscle relaxation to sodium nitroprusside, suggesting endothelial-specific damage. Adherence of fluorescent labeled polymorphonuclear neutrophils to epicardial coronary artery endothelium, used as an index of basal (unstimulated) anti-polymorphonuclear neutrophil function, was significantly attenuated by ischemic preconditioning versus no-ischemic preconditioning (293 +/- 25 polymorphonuclear neutrophils/mm2 vs 528 +/- 29 polymorphonuclear neutrophils/mm2).
Conclusion:
In this minimally invasive direct coronary artery bypass grafting model, both agonist-stimulated and basal postischemic endothelial dysfunction were attenuated by ischemic preconditioning.
