Long-term impairment of endothelium-dependent relaxations to aggregating platelets after reperfusion injury in canine coronary arteries.
Experiments were designed and performed to determine whether endothelial function remained chronically impaired after coronary artery reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (12 weeks). Rings (3-4 mm wide) of the reperfused artery and of normal left circumflex (control) coronary artery segments were suspended in organ chambers containing physiological saline solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurement. Endothelium-independent contractions to KCl or prostaglandin F2 alpha and endothelium-independent relaxations to nitric oxide or isoproterenol were comparable in control and chronically reperfused arteries. However, chronically reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to aggregating platelets. In addition, the reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to the platelet-derived compounds adenosine diphosphate, serotonin, and thrombin. However, the endothelium-dependent relaxations to acetylcholine were comparable between control and reperfused arteries. Thus, after 12 weeks of reperfusion, previously occluded coronary arteries exhibited a selective impairment of endothelium-dependent relaxation evoked by aggregating platelets. In vivo, this phenomenon could favor platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle and thus facilitate ischemic events such as vasospasm and coronary thrombosis.
Pearson
P J
PJ
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
Schaff
H V
HV
Vanhoutte
P M
PM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010974:Platelet Aggregation / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D011460:Prostaglandins F; D012701:Serotonin; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D013917:Thrombin