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

Background: Immediately available blood substitutes could transform medicin e. In coronary artery surgery, vasoconstriction induced by some of these ag ents could have serious implications. We have examined some of the vasoacti ve effects of one of these blood substitute, diaspirin cross-linked haemogl obin (DCLHb), on isolated rings of human arterial conduits. Methods: Sectio ns 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% O-2/5% CO2) Krebs-Heinseleit solution at 37 degrees C and attached to isometric strain gauge for measurements of tension. All rings were tested f or the presence of endothelium by addition of carbachol to rings pre-contra cted with phenylephrine. The relative importance of nitric oxide (NO) in co ntraction 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 nitroprus side (SNP) caused complete relaxation of LIMA with an EC50 value of 2.0 +/- 0.1 x 10(-8) M and RA with an EC50 value of 1.9 +/- 0.1 x 10(8) M, In the presence of DCLHb (10(-7) M), carbachol-induced relaxation was significantl y reduced to 46.3 +/- 0.7% (P < 0.01) and the BC50 value for SNP relaxation increased to 1.2 +/- 0.1 x 10(-7) M (P < 0.01). DCLHb caused rings to cont ract in the absence of phenylephrine with EC50 values of 1.6 +/- 0.1 x 10(- 7) M (LIMA) and 1.8 +/- 0.1 x 10(-7) M (RA). Presence of L-NAME (300 mu M) caused no alteration in DCLHb-induced contraction. Conclusion: In this stud y 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 i ts ability to bind NO. However, it is possible that other mechanisms might contribute to the vasoconstrictor effects of DCLHb and these might be amena ble to anti-vasospastic strategies. (C) 2000 Elsevier Science B.V. All righ ts reserved.