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Constriction of canine coronary arteries by platelet activating factor after brief ischemia
Y D Kim1, R M Danchak, K F Heim
1Department of Anesthesia, Georgetown University Medical Center, Washington, D.C. 20007.
Insights
Platelet activating factor (PAF) causes vasodilation in healthy coronary arteries but vasoconstriction after ischemia-induced endothelial damage. This suggests endothelial function modulates PAF
Area of Science:
- Cardiovascular Physiology
- Endothelial Function
- Myocardial Ischemia Research
Background:
- Platelet activating factor (PAF) is implicated in coronary spasm and myocardial ischemia.
- PAF exhibits variable vasodilator or vasoconstrictor effects in different reports.
- Endothelial integrity is crucial for regulating vascular tone.
Purpose of the Study:
- To investigate if endothelial dysfunction modulates the vascular effects of PAF.
- To determine the role of endothelium in PAF-mediated coronary responses during ischemia.
Main Methods:
- Infusion of PAF into the left anterior descending coronary artery (LAD) in dogs.
- Measurement of coronary blood flow (CBF) using a Doppler flow probe.
- Assessment of responses to acetylcholine (ACh) before and after LAD ligation/reperfusion.
Main Results:
- Before ligation, PAF increased CBF by 28.4% and decreased coronary vascular resistance (CVR) by 21.5%.
- After ligation and reperfusion, PAF decreased CBF by 10.2% and increased CVR by 27.8%.
- Ischemia blunted the vasodilator response to ACh, indicating endothelial dysfunction.
Conclusions:
- Coronary vascular response to PAF is dependent on endothelial functional integrity.
- Endothelial damage due to ischemia transforms PAF's effect from vasodilation to vasoconstriction.
Abstract:
Platelet activating factor (PAF) has been suggested as a mediator of coronary spasm and acute myocardial ischemia. However, PAF can have either vasodilator or vasoconstrictor activities according to various reports. Because of the importance of endothelium in regulating vascular tone, we hypothesized that changes in endothelial function could modulate some of the observed differences in the activities of PAF. To test this hypothesis, PAF was infused directly into the left anterior descending coronary artery (LAD) of dogs at a rate of 0.3 microgram/min before and after 20 min of LAD ligation followed by reperfusion. Coronary blood flow (CBF) was measured continuously via a Doppler flow probe. Likewise, responses to the endothelium dependent vasodilator, acetylcholine (ACh) were measured before and after the LAD ligation. Before ligation, PAF produced a vasodilatory response in the LAD, resulting in 28.4 +/- 11.0% increase in CBF and a 21.5 +/- 5.8% decrease in coronary vascular resistance (CVR). However, after ligation and subsequent reperfusion, 0.3 microgram/min PAF produced vasoconstriction, resulting in a 10.2 +/- 8.7% decrease in CBF (p < 0.01 compared to pre-infusion change in (CBF), and a 27.8 +/- 23.2% increase in CVR (p = 0.05) compared to pre-infusion change in CVR). The vasodilator response to ACh was markedly blunted by ischemia. These results suggest that the coronary vascular response to PAF may depend upon the functional integrity of the endothelium, with endothelial damage resulting in constrictor responses to PAF.(ABSTRACT TRUNCATED AT 250 WORDS)