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Ischemia-reperfusion impairs endothelium-dependent relaxation of coronary microvessels but does not affect large
J E Quillen1, F W Sellke, L A Brooks
1University of Iowa, Cardiovascular Center, Iowa City.
Insights
Ischemia with reperfusion significantly impairs coronary microvascular relaxation, while large coronary arteries remain largely unaffected. This selective damage highlights the vulnerability of smaller vessels to reperfusion injury.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Ischemia-Reperfusion Injury
Background:
- Coronary artery disease involves ischemia and reperfusion.
- Understanding vascular responses to these events is crucial for treatment.
- Both large conduit and small resistance arteries may be affected differently.
Purpose of the Study:
- To investigate the impact of ischemia and reperfusion on coronary artery relaxation.
- To differentiate effects on endothelium-dependent vs. -independent pathways.
- To compare responses in conduit vs. resistance coronary arteries.
Main Methods:
- Canine model of coronary artery occlusion (1 hour) with/without reperfusion (1 hour).
- Organ chamber studies for conduit artery relaxation.
- In vitro microvessel imaging for pressurized resistance artery relaxation.
- Assessment of relaxation to various stimuli (acetylcholine, ADP, calcium ionophore, nitroglycerin).
Main Results:
- Conduit coronary artery function was unaffected by ischemia or reperfusion.
- Ischemia alone caused mild impairment of endothelium-dependent microvascular relaxation.
- Ischemia with reperfusion markedly reduced endothelium-dependent relaxation in microvessels.
- Nitroglycerin-induced relaxation in microvessels remained unaltered.
Conclusions:
- Large epicardial coronary arteries are resistant to ischemia/reperfusion effects on relaxation.
- Coronary microcirculation shows impaired endothelium-dependent relaxation after ischemia/reperfusion.
- Reperfusion injury selectively damages microvascular endothelium-dependent function.
Abstract:
We examined the effects of ischemia with and without reperfusion on endothelium-dependent and -independent vascular relaxation in both conduit and resistance coronary arteries. Studies were performed on dogs under control conditions (n = 13) or after 1 hour of circumflex coronary artery occlusion with (n = 10) or without (n = 8) 1 hour of reperfusion. Rings of obtuse marginal branches of the left circumflex coronary artery (conduit arteries) were studied in organ chambers. Coronary microvessels (110-220-microns diameter) were studied in a pressurized state with an in vitro microvessel imaging apparatus. Relaxation was evaluated after preconstriction with prostaglandin F2 alpha and U46619 (a thromboxane A2 analogue) in conduit and resistance vessels, respectively. Conduit vessel function was not altered by ischemia with or without reperfusion. Endothelium-dependent microvascular relaxation was depressed in response to acetylcholine, ADP, and calcium ionophore A23187 after ischemia with reperfusion compared with control relaxation (ED50 as -log[M]: 6.0 +/- 0.2 [p less than 0.05], 5.1 +/- 0.4 [p less than 0.05], and 5.8 +/- 0.1 versus 6.8 +/- 0.2, 6.8 +/- 0.2, and 6.6 +/- 0.2, respectively). Ischemia without reperfusion modestly altered microvascular endothelium-dependent relaxation. Microvascular relaxation to nitroglycerin was not altered by ischemia with reperfusion. We conclude that 1) endothelium-dependent relaxation in large epicardial coronary arteries is relatively refractory to ischemia with or without reperfusion, 2) ischemia alone produces mild alterations of coronary microvascular reactivity, 3) ischemia followed by reperfusion produces a marked and selective impairment of endothelium-dependent responses in the coronary microcirculation.