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Eur J Cardiothorac Surg 2000;18:241-245
© 2000 Elsevier Science NL

The action of diaspirin cross-linked haemoglobin blood substitute on human arterial bypass conduits

^a Department of Cardiothoracic Surgery, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, UK
^b Department of Anaesthesia, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, UK
^c Department of Pharmacology, University of Cambridge, Cambridge, UK

Received 11 October 1999; received in revised form 1 March 2000; accepted 7 March 2000.

Corresponding author. Tel.: +44-1480-364406; fax: +44-1480-831143
e-mail: alain.vuylsteke{at}which.net

Background: Immediately available blood substitutes could transform medicine. In coronary artery surgery, vasoconstriction induced by some of these agents could have serious implications. We have examined some of the vasoactive effects of one of these blood substitute, diaspirin cross-linked haemoglobin (DCLHb), on isolated rings of human arterial conduits. Methods: Sections of human left internal mammary artery (LIMA) and radial artery (RA) were cut into 3-mm rings, mounted in individual organ baths containing aerated (95% O₂/5% CO₂) Krebs–Heinseleit solution at 37°C and attached to isometric strain gauge for measurements of tension. All rings were tested for the presence of endothelium by addition of carbachol to rings pre-contracted with phenylephrine. The relative importance of nitric oxide (NO) in contraction mediated by the addition of DCLHb was studied. Results: Carbachol relaxed phenylephrine precontracted LIMA by 72.3±1.7% and RA by 97±0.7% confirming the presence of a functional endothelium. Sodium nitroprusside (SNP) caused complete relaxation of LIMA with an EC₅₀ value of 2.0±0.1x10^-8 M and RA with an EC₅₀ value of 1.9±0.1x10⁸ M. In the presence of DCLHb (10^-7 M), carbachol-induced relaxation was significantly reduced to 46.3±0.7% (P<0.01) and the BC₅₀ value for SNP relaxation increased to 1.2±0.1x10^-7 M (P<0.01). DCLHb caused rings to contract in the absence of phenylephrine with EC₅₀ values of 1.6±0.1x10^-7 M (LIMA) and 1.8±0.1x10^-7 M (RA). Presence of L-NAME (300 µM) caused no alteration in DCLHb-induced contraction. Conclusion: In this study of isolated rings of human vessels, DCLHb causes a significant reduction in relaxation mediated by carbachol and SNP, which is likely to be due to its ability to bind NO. However, it is possible that other mechanisms might contribute to the vasoconstrictor effects of DCLHb and these might be amenable to anti-vasospastic strategies.

Key Words: Blood substitute • Coronary artery surgery • Internal mammary artery • Radial artery

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