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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% O(2)/5% CO(2)) Krebs-Heinseleit solution at 37 degrees 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 EC(50) value of 2.0+/-0.1x10(-8) M and RA with an EC(50) value of 1. 9+/-0.1x10(8) 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 BC(50) 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 EC(50) values of 1.6+/-0.1x10(-7) M (LIMA) and 1.8+/-0.1x10(-7) M (RA). Presence of L-NAME (300 microM) 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.

Glibenclamide has been shown to inhibit prostanoid-induced contraction in a number of blood vessel types. In this study, the effects of glibenclamide on the contraction of human peripheral arteries in response to both prostanoid and non-prostanoid agonists were compared and possible mechanisms of action were investigated. Segments of left internal mammary artery (LIMA) and radial artery, taken from patients undergoing coronary artery bypass graft (CABG) surgery, were mounted in organ baths containing physiological saline solution aerated with 95% O2/5% CO2 at 37 degrees C. Contractions were obtained by either the use of a thromboxane analogue (U46619), L-phenylephrine, KCl or CaCl2. The effects of glibenclamide on these contractions were observed and pEC50 values were determined after manipulation of a logistic curve-fitting equation. Concentration-dependent relaxation of U46619-contracted LIMA and radial artery was observed in the presence of glibenclamide, with calculated pEC50 values of 4.2+/-0.17 (n = 7) for LIMA and 3.26+/-0.48 (n = 5) for radial artery. Incubation of both LIMA and radial artery with glibenclamide (50 microM) caused the concentration-response curves for U46619 and L-phenylephrine to shift significantly to the right. Similarly the KCl tension relationship was caused to shift to the right. Finally, glibenclamide (100 microM) also had an inhibitory effect on Ca2+-induced tension in radial artery. These results show that the inhibitory effects of glibenclamide on human peripheral blood vessels are not restricted to prostanoid-induced contractions. Furthermore, evidence has been provided to suggest that these effects might be mediated through an interaction with voltage-sensitive Ca2+ channels.

Unlabelled: Brain dysfunction after cardiopulmonary bypass (CPB) is common, and it has been hypothesized that this injury might be due partly to activation of inflammatory processes in the brain. We measured juguloarterial gradients for interleukin-1beta, interleukin-6, and interleukin-8 (IL-8) as indices of local proinflammatory cytokine production in the brain and studied the effect of temperature during CPB on these changes. Twelve patients undergoing coronary artery bypass graft surgery (normothermic CPB n = 6, hypothermic CPB n = 6) were studied. Cytokine levels were measured in paired arterial and jugular bulb samples obtained before, during, and after CPB. Although systemic levels of all three cytokines increased during and after CPB, increases in juguloarterial cytokine gradients were observed only for IL-8. Juguloarterial IL-8 gradients started to increase 1 h post-CPB and were significantly elevated 6 h post-CPB (P < 0.05). At this time point, the median (interquartile range) juguloarterial IL-8 gradients were significantly larger in the normothermic CPB group (25.81 [24.49-39.51] pg/mL) compared with the hypothermic CPB group (6.69 [-0.04 to 15.47] pg/mL; P < 0.05). These data imply specific and significant IL-8 production in the cerebrovascular bed during CPB and suggest that these changes may be suppressed by hypothermia during CPB., Implications: Using juguloarterial gradients to measure cerebrovascular cytokine production is novel in the setting of cardiopulmonary bypass and implicates the cerebral activation of inflammatory processes, which may contribute to brain dysfunction. Hypothermia during cardiopulmonary bypass may significantly attenuate this response.