Dihydrocyclosporin D in sheep: haemodynamic and renal effects

1. This study was designed to test the haemodynamic and renal effects in sheep of dihydrocyclosporin D (dCyD), an immunosuppressant agent derived from the fungus Tolypocladium inflatum Gams. 2. dCyD was infused for 5 days at 12 mg/kg per day. Mean arterial pressure (MAP) was elevated after 24 h, but thereafter returned to control levels. Heart rate was significantly elevated throughout the infusion and was still high 24 h postinfusion. Cardiac output rose after 5 days, but total peripheral resistance was unchanged during the infusion. 3. Glomerular filtration rate, renal blood flow and effective renal plasma flow remained unchanged, although urine sodium excretion rose for the first 48 h. 4. Infusion of the castor oil-based vehicle for cyclosporin, Cremaphore EL, for 5 days in four sheep did not produce any sustained changes in any of the parameters measured.