The in-vivo effect of pyrrolidine dithiocarbamate on hepatic parenchymal microcirculation and oxygenation of the rat liver.
OBJECTIVE
Pyrrolidine dithiocarbamate has been shown to be a potent inducer of haemeoxygenase-1. This study investigated its in-vivo effects on systemic and hepatic microcirculatory perfusion.


METHODS
Male Sprague-Dawley rats (n=12) were administered intravenously with pyrrolidine dithiocarbamate (10, 20 and 50 mg/kg body weight) or vehicle (0.2 ml physiological saline) served as control. Systemic and hepatic haemodynamics including arterial oxygen saturation, heart rate, mean arterial blood pressure and portal blood flow were monitored. Microcirculation in skeletal muscle and liver was measured by laser Doppler flowmetry and intravital fluorescence microscopy, whereas hepatic tissue oxyhaemoglobin and cytochrome oxidase CuA redox state, which is an indicative of extracellular and intracellular oxygenation were measured by near infrared spectroscopy.


RESULTS
Pyrrolidine dithiocarbamate induced a dose-dependent increase in mean arterial blood pressure and skeletal muscle microcirculation. The hepatic parenchymal microcirculation was significantly improved and an increase in sinusoidal diameter and reduction in RBC velocity were observed. Pyrrolidine dithiocarbamate also showed beneficial effect on hepatic tissue oxygenation showed by an increase in oxyhaemoglobin and cytochrome oxidase CuA redox state as well.


CONCLUSIONS
Pyrrolidine dithiocarbamate improves hepatic parenchymal microcirculation and tissue oxygenation, suggesting that it may be used as a potential agent in pharmacological preconditioning in the liver.
Seifalian
Alexander M
AM
Gastrointestinal and Hepatobiliary Research Unit, UCL Division of Surgery and Interventional Science, University College London, London, UK. a.seifalian@ucl.ac.uk
Mallick
Ismail H
IH
Hajinasrollah
Esmaeil
E
Sogbodjor
Amaki L
AL
Gustafsson
Bengt I
BI
Delbro
Dick S
DS
Winslet
Marc C
MC
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000098:blood supply; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000098:blood supply; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid