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Allopurinol and lodoxamide in complement-induced hepatic ischemia
W J Schirmer1, J M Schirmer, G B Naff
1Department of Surgery, Veterans Administration Medical Center, Case Western Reserve University Hospitals, Cleveland, Ohio 44106.
The Journal of Surgical Research
|July 1, 1988
Summary
Complement activation impairs liver blood flow. This study found that inhibiting xanthine oxidase or mast cell release did not prevent this reduction in hepatic blood flow in rats. Further research is needed to understand the mechanisms involved.
Area of Science:
- Physiology
- Immunology
- Pharmacology
Background:
- Intravascular complement activation, triggered by substances like zymosan or cobra venom factor (CVF), is known to reduce hepatic blood flow.
- Oxygen radical scavengers can mitigate this ischemia, but the source of these radicals (complement-stimulated phagocytes or reperfused cells) remains unclear.
Purpose of the Study:
- To investigate the role of xanthine oxidase-derived oxygen radicals in CVF-induced hepatic hypoperfusion.
- To determine if mast cell mediators contribute to the reduction in hepatic blood flow during complement activation.
Main Methods:
- Rats were pretreated with allopurinol (a xanthine oxidase inhibitor) or lodoxamide tromethamine (a mast cell inhibitor) before CVF challenge.
- Effective hepatic blood flow (EHBF) was measured using galactose clearance.
- Systemic hemodynamics and hematocrit were monitored.
Main Results:
- CVF challenge significantly reduced EHBF by 25% in vehicle-pretreated rats compared to controls.
- Neither allopurinol nor lodoxamide tromethamine pretreatment significantly improved EHBF following CVF challenge.
- Systemic hemodynamics and hematocrit remained largely unaffected.
Conclusions:
- The study suggests that xanthine oxidase-derived radicals or mast cell mediators are not the primary contributors to the observed reduction in hepatic blood flow after CVF-induced complement activation.
- The exact mechanisms causing CVF-induced hepatic hypoperfusion require further investigation.