Cardiopulmonary dysfunctions caused by ADP-induced platelet aggregation.
Intravenous (i.v.) injection of 0.1 mg/kg of ADP within one second in 13 rats caused a prompt drop in platelet count to 55.1 plus or minus 3.2% of the preinjection value with a statistical significance (p less than 0.01) at 30 seconds after the injection. At that time, mean arterial pressure and arterial PO2 decreased, while central venous pressure increased. Heart rate decreased with an appearance of sinus bradycardia and variable A-V block. Various respiratory effects such as shallow or slow respiration or apnea appeared. Such changes showed a tendency to recovery within 3 minutes. Splenectomy did not prevent these changes in 6 rats. In 6 thrombocytopenic and leukopenic rats treated with busulfan, these changes did not appear. Intra-arterial injection of the same amount of ADP induced almost no response. When ADP was injected twice 20 seconds apart in 10 rats, the second injection resulted in no effects or slight responses. In contrast, when 10 rats were injected twice 180 seconds apart, both the first and second injections showed the same effects on platelets and cardiopulmonary functions. The results suggests that the effects observed following I.V. ADP are probably due to transient obstruction of coronary and pulmonary microvessels by platelet aggregates. Reduced response following two successive injections may be due either to the reduced platelet count or to a refractory state induced by the first injection. ADP is probably rapidly metabolized in systemic microvascular beds.
D000244:Adenosine Diphosphate / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001772:Blood Cell Count; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced; D002066:Busulfan / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D010100:Oxygen / Q000097:blood; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D012119:Respiration / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000139:chemically induced*; D012848:Sinoatrial Block / Q000139:chemically induced; D013154:Spleen / Q000502:physiology; D013156:Splenectomy; D013997:Time Factors
D000244:Adenosine Diphosphate; D002066:Busulfan; D010100:Oxygen