Pulmonary platelet sequestration is increased following monocrotaline pyrrole treatment of rats.
111In-labeled platelets were used to study the localization and survival of circulating platelets at various times after a single, intravenous administration of 3.5 mg/kg monocrotaline pyrrole (MCTP) to rats. Lung injury, assessed from elevated lung weight, lavage fluid total protein and albumin concentrations, and lactate dehydrogenase activity, was evident at Days 8 and 14. In addition, right ventricular hypertrophy was manifested by 14 days after MCTP administration. Pulmonary sequestration of 111In-labeled platelets was also elevated by Days 8 and 14, while circulating blood platelet number remained unchanged. Concomitantly, the hemoglobin concentration and total hemoglobin content of the lung homogenate supernatant in MCTP-treated rats on these days was decreased when compared to those in controls. A decrease in splenic platelet sequestration on Day 14 was accompanied by an increase in the combined radioactivity of the heart and kidneys. Platelet half-life and mean life span were increased only on Day 14. A higher dose of MCTP (35 mg/kg) caused moderate lung injury at 6 hr. However, this treatment did not result in increased platelet sequestration in the lungs, although a trend was observed. Data from this study support the hypothesis that platelets are involved in the development of the pulmonary hypertensive response following MCTP-induced lung injury.
White
S M
SM
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Roth
R A
RA
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D006332:Cardiomegaly / Q000139:chemically induced; D002470:Cell Survival / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D008168:Lung / Q000187:drug effects*; D008297:Male; D016686:Monocrotaline / Q000031:analogs & derivatives*; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D006454:Hemoglobins; D011763:Pyrrolizidine Alkaloids; C014114:monocrotaline pyrrole; D016686:Monocrotaline