The effects of cigarette smoke and nicotine on platelet thrombus formation in stenosed dog coronary arteries: inhibition with phentolamine.
This study was undertaken to examine in vivo the effects of cigarette smoke on cyclic reductions in coronary flow due to platelet thrombus formation in the stenosed coronary arteries of anesthetized dogs. The circumflex coronary artery of 21 mongrel dogs was stenosed 60 - 80%, with blood flow measured with an electromagnetic flow probe. After the administration of cigarette smoke, plasma epinephrine was elevated nine times the control level (p less than 0.001) and peak mean blood pressure was elevated one and one-half times control (p less than 0.01). The hematocrit increased several percent (p less than 0.01) with cigarette smoke, although blood gases and pH remained unchanged. In all 21 dogs, spontaneous reductions in coronary blood flow were greatly exacerbated in the stenosed circumflex artery as evidenced by the number of flow reductions, the increased size of the reductions and the rate of flow reduction. Nicotine administered intravenously in doses comparable to those achieved through absorption of cigarette smoke by the lungs provoked similar responses of alpha-adrenergic stimulation and potentiation of the platelet thrombus formation. An alpha-adrenergic antagonist, phentolamine, was given (3 mg/kg) intravenously to inhibit the exacerbated platelet thrombus formation due to cigarette smoke or infused nicotine. In 18 of 21 dogs, an acute occlusive platelet thrombus was prevented 15 minutes after phentolamine and after phentolamine and after a cigarette smoke or nicotine challenge. This study confirms a link between cigarette smoking, platelet formation, and the potential for humans to develop an acute occlusive platelet thrombus in a diseased and stenotic coronary artery.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000139:chemically induced*; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005260:Female; D007263:Infusions, Parenteral; D008297:Male; D009538:Nicotine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010646:Phentolamine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D012907:Smoking
D009538:Nicotine; D004837:Epinephrine; D010646:Phentolamine