Complement mediates attenuation of endothelium-dependent relaxations in canine coronary arteries after porcine serum exposure: A mechanism for vascular thrombosis in xenograft hyperacute rejection

David G. Cable, Kunikazu Hisamochi, Hartzell V. Schaff

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background: Evidence for complement activation in xenograft hyperacute rejection includes prolongation of graft survival after complement inactivation as well as component deposition and consumption during hyperacute rejection. The current investigations examined the endothelial production of vasoactive substances during heterologous serum exposure. Methods: Segments of canine coronary artery were exposed to either autologous canine serum for 90 minutes or heterologous porcine serum for 30, 60, or 90 minutes. After replacement of the serum with buffered saline, segments were contracted with phenylephrine (10-6 mol/L) in the presence of indomethacin (10-5 mol/L). Results: Compared with responses of vessels exposed to autologous canine serum, receptor-dependent relaxation to acetylcholine was impaired in arteries after 60 or 90 minutes of exposure to porcine serum. Receptor-independent relaxation to calcium ionophore A23187 was not significantly impaired at any length of porcine serum exposure. Endothelial- independent relaxation to sodium nitroprusside was not impaired with either canine or porcine serum exposure. Oxyhemoglobin (10-6 mol/L) abolished acetylcholine-mediated relaxation, indicating that nitric oxide was the predominant mediator of the impaired pathway. Basal release of nitric oxide after a 60-minute porcine serum exposure was reduced by half compared with coronary arteries exposed to autologous canine serum. Serum pretreated by either heat inactivation of complement or immunoadsorption with anti-C3 antibodies failed to depress endothelial-dependent relaxation on 60 minutes of exposure to canine coronary arteries. Scanning electron microscopy revealed an intact endothelial layer in coronary arteries exposed to either porcine or canine serum for 60 minutes. Conclusions: Hyperacute xenograft rejection impairs receptor-dependent relaxation of canine coronary arteries at 60 and 90 minutes. These data strongly suggest that impairment of endothelial production of nitric oxide during acute xenograft rejection is mediated by complement activation.

Original languageEnglish (US)
Pages (from-to)II58-II64
JournalCirculation
Volume96
Issue number9 SUPPL.
StatePublished - Nov 4 1997

Keywords

  • Cardiac transplantation
  • Complement
  • Endothelium
  • Nitric oxide
  • Nitricoxide
  • Organ chamber
  • Xenotransplant

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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