Hepatic and renal blood flow responses to a clinical dose of intravenous cyclosporine in the pig.
The immunosuppressant Cyclosporine A (CsA) is considered to induce nephrotoxicity in part by causing vasoconstriction of the glomerular afferent arterioles. Although CsA is widely used in hepatic transplantation, little is known concerning its effects on hepatic blood flow. We used ultrasonic flow probes in an anesthetized swine model to measure the effects of a single 60 min infusion of a clinically comparable dose of CsA (5 mg/kg per h) on hepatic, renal, and supraceliac descending aortic blood flows (n = 7 swine). To account for any change in systemic output or systemic vascular resistance during the 60 min CsA infusion that may non-specifically affect hepatic and renal blood flows, the total hepatic (portal vein plus hepatic artery) and renal blood flows were reported relative to the supraceliac descending aortic blood flow (termed 'fractional' total hepatic and renal blood flows). The fractional total hepatic blood flow decreased significantly (p < 0.05) by 40 min of CsA infusion vs baseline, and continued to decrease throughout the infusion (baseline = 0.38 +/- 0.03 units vs 0.28 +2- 0.05 units by 60 min of CsA infusion). During the recovery period, the fractional total hepatic blood flow increased to a value which was not different from baseline (recovery = 0.38 +2- 0.03 units). Fractional right renal artery blood flow did not change significantly from baseline at any time during the CsA infusion or during the recovery period. We conclude that a single, clinically comparable dose of CsA results in a significant decrease in total hepatic blood flow, and that this decrease is greater than that seen in renal blood flow.
Andreoni
K A
KA
Department of Surgery and Anesthesiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21215.
O'Donnell
C P
CP
Burdick
J F
JF
Robotham
J L
JL
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D003714:Denervation; D005260:Female; D006499:Hepatic Artery / Q000294:innervation; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects*; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D013552:Swine
D014677:Pharmaceutical Vehicles; C022131:cremophor; D011092:Polyethylene Glycols; D016572:Cyclosporine