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Vessel tone affects transmural distribution of coronary flow during hypoperfusion
1Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, Pennsylvania 15213.
Insights
Vessel tone independently impacts subendocardial blood flow and distribution during reduced coronary perfusion. Increasing vessel tone with endothelin-1 improved flow homogeneity compared to adenosine, even at low pressures.
Area of Science:
- Cardiovascular Physiology
- Myocardial Perfusion Dynamics
Background:
- Subendocardial blood flow is vulnerable during coronary hypoperfusion.
- Intramyocardial vessel compression and tone affect coronary flow oscillations.
- The independent role of vessel tone in subendocardial perfusion during hypoperfusion was unclear.
Purpose of the Study:
- To determine if vascular tone is an independent determinant of subendocardial perfusion during coronary hypoperfusion.
- To investigate the effects of endothelin-1 (ET-1) on coronary flow dynamics compared to adenosine.
Main Methods:
- Utilized an open-chest pig model with a carotid-to-coronary artery shunt.
- Manipulated coronary pressure during intracoronary infusion of ET-1 or adenosine.
- Employed microspheres to quantify myocardial layer blood flow at various pressures.
Main Results:
- Higher coronary resistance and lower subendocardial flow were observed with ET-1 versus adenosine at comparable coronary pressures.
- ET-1 resulted in more homogeneous transmural flow distribution than adenosine, even under hypoperfusion conditions.
- Homogeneous flow was maintained with ET-1 despite pressures causing lactate production and hypokinesis.
Conclusions:
- Vascular tone is an independent determinant of both absolute subendocardial flow and its distribution across the left ventricular wall during coronary hypoperfusion.
- Modulating vascular tone offers a potential strategy to improve subendocardial perfusion and homogeneity under ischemic conditions.
Abstract:
Subendocardial flow is selectively impaired during coronary hypoperfusion. Systolic compression of intramyocardial vessels not only stops capillary flow but empties vessels as well, leading to reversed flow in the arteries that penetrate the myocardium. The tone of these vessels influences the magnitude of flow oscillation during the cardiac cycle, but whether vessel tone is an independent determinant of subendocardial perfusion during coronary hypoperfusion has not been determined. The discovery of endothelin (ET-1) has made it possible to counteract metabolic vasodilation and increase vessel tone during hypoperfusion. A shunt from a carotid artery to the left anterior descending coronary artery was installed in open-chest pigs anesthetized with halothane. Arterial pressure and heart rate were held constant, and coronary pressure was reduced in stages by restricting shunt flow during intracoronary infusion of ET-1 (n = 7) or adenosine (n = 5). Microspheres were injected at each stage to determine layer flow. Coronary resistance was two- to three-fold higher and subendocardial flow was lower at similar coronary pressures in the animals receiving ET-1 than in those receiving adenosine. In contrast, flow distribution across the left ventricular wall was more homogeneous with ET-1 than with adenosine, even at coronary pressures low enough to cause lactate production and regional hypokinesis. These results demonstrate that vessel tone has an independent effect on absolute subendocardial flow as well as transmural flow distribution during coronary hypoperfusion.