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.