Catecholamine-induced cardiac necroses: protective effect of leucocytopenia, influence of an S2 antagonist, thromboxanesynthetase inhibitor and prostacycline analogue.
The influence of various drugs and leucocytopenia (induced by cyclosphamid) on isoproterenol(40 mg/kg, s.c.)-induced cardiac necroses was investigated in female SPF Sprague Dawley rats. The influence of fibrinogen reduction was investigated in spontaneously hypertensive rats (SHR). 8-15% of the area of 15 cross-sections were evaluated with a computer-aided morphometric device allowing classification of number and area of necroses. The reduction of number and area of necroses amounted to approximately: 50% by prostacyclin analogue, 25% by S2 inhibition (ketanserin). Inhibition of thromboxane synthesis and fibrinogen reduction from elevated values (200 mg/dl) below the limit of detection by infusion of 35 U/kg Ancrod in SHR had no significant effects, where in SHR only 10 mg/kg isoproterenol were tolerated with a higher extent of necrosis formation. Leucocytopenia caused a reduction of necroses of over 90%. The condition of mismatch of oxygen consumption and supply induced by high doses of isoproterenol can be considered a model of angina pectoris. The effect of leucocytopenia indicates an essential role of leucocytes in necrosis formation in both situations.
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Institut für Physiologie, Medizinische Fakultät, RWTH Aachen, FRG.
Michalsky
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Kammermeier
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H
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology*; D007970:Leukopenia / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D002395:Catecholamines; D012702:Serotonin Antagonists; D007650:Ketanserin; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D007545:Isoproterenol