Haemodynamic and haematologic effects of Acanthaster planci venom in dogs.
This study was designed to examine haemodynamic and haematologic effects of the crown-of-thorns starfish venom (Acanthaster planci venom: APV) in dogs. Severe systemic hypotension, thrombocytopenia and leukopenia were induced by APV (1.0 mg protein/kg i.v.), followed by gradual return to the baseline level within 60 min. Hypotension was presumably caused by two factors: an early decrease in systemic vascular resistance and the large reduction in cardiac output due to reduced ventricular filling. Indomethacin, a cyclooxygenase inhibitor, remarkably suppressed systemic hypotension induced by APV. The peak reduction in systemic pressure was associated with concomitant rise of plasma 6-keto-PGF1 alpha, a major stable metabolite of prostacyclin. Thus, the hypotensive effect of APV may be caused primarily by prostacyclin and/or some vasodilating prostaglandins. In contrast, thrombocytopenia and leukopenia were not affected by cyclooxygenase inhibitor, 5-lipoxygenase inhibitor or platelet activating factor (PAF) receptor antagonist. When APV was administered repeatedly, tachyphylaxis was developed in haemodynamic effects, but not in haematologic effects. These findings suggest that APV-induced hypotensive effects may occur mainly through endogenous production of vasodilating prostaglandins including prostacyclin, although APV-induced thrombocytopenia and leukopenia may be caused by other mechanism(s) unrelated to arachidonate metabolites and/or PAF.
Shiroma
N
N
Department of Pharmacology, School of Medicine, University of the Ryukyus, Okinawa, Japan.
Noguchi
K
K
Matsuzaki
T
T
Ojiri
Y
Y
Hirayama
K
K
Sakanashi
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D016859:Lipoxygenase Inhibitors; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D013215:Starfish; D013618:Tachyphylaxis; D013921:Thrombocytopenia / Q000139:chemically induced; D014655:Vascular Resistance / Q000187:drug effects; D014688:Venoms / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D014688:Venoms; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin