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In this prospective, randomized, double-blind, placebo-controUed study, the clinical, biochemical, and hemodynamic effects of xanthine oxidase inhibition in patients undergoing coronary artery bypass grafting were assessed. AUopurinol pretreatment significantly reduced the use of inotropic support after the operation (5 of 25 patients versus 13 of 25 patients, p < 0.01) and increased the rate of peripheral warming (11.4 ± 0.85 hours versus 14.4 ± 1 hours, p < 0.02). Twenty patients (9 in the aUopurinol group and 11 in the placebo group) underwent invasive hemodynamic monitoring and intraoperative coronary sinus cannulation. The cardiac indexes of both groups were similar before the operation and for the first postoperative hour; thereafter, the cardiac index increased significantly in only the active treatment group (F = 3.33 and df= 5,90, p < 0.004). Products of lipid peroxidation (thiobarbituric acid reactive substances) increased significantly in only the placebo group, with increases being evident both in the systemic circulation (9.5 ± 3.2 nmol/gm albumin, p < 0.007, and 24 ± 5 nmoljgm albumin, p < 0.001, at 30 seconds and 2 minutes of reperfusion, respectively) and the coronary sinus (19.4 ± 5.8 nmol/gm albumin, p < 0.004, and 28 ± 4 nmol/gm albumin, p < 0.001, at 2 and 5 minutes of reperfusion, respectively. No significant difference was evident between the groups with respect to cardiac enzyme or vitamin E release. It is proposed that xanthine oxidase inhibition exerts its beneficial effects by reducing the level of free radical activity associated with reperfusion during coronary artery bypass grafting.

1 Adenosine-5'-triphosphate (ATP) is a potent coronary vasodilator. Because of the e cient hydrolysis of ATP, adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) by ectonucleotidases located in the coronary endothelium ATP-induced vasodilation may be mediated via both P1 (AMP and adenosine) and P2Y (ATP and ADP) receptors. We have used the change in total coronary resistance (TCR) induced by intravascular ATP in the isolated working rat heart to determine both the component of the vasodilation mediated via P2Y receptors and the identity of the subclass of receptor involved. 2 The dose response for ATP revealed a half maximal e ect at an apparent ATP concentration of 0.08+0.009 mM. The response was saturated at apparent ATP concentrations greater than 0.23 mM. Contrary to much of the current literature, the perfusion of a 0.25 mM concentration of adenosine resulted in the identical response to an equimolar concentration of ATP suggesting a signi®cant role for adenosine in coronary vasodilation. 3 The non-selective P1 receptor antagonist 8-(p-Sulfophenyl)theophylline (8-SPT) was used to show that the response to ATP was mediated via both P1 and P2Y receptors. Whilst 8-SPT abolished the e ect of adenosine it reduced the e ect of ATP by only 50%. Thus, at a saturating concentration of ATP, P1 and P2Y receptors were shown to contribute equally to the observed vasodilation. 4 Uridine-5'-triphosphate (UTP), ADP and adenosine-5'-O-thiotriphosphate (ATPgS) were used to characterize the component of coronary vasodilation that was mediated via P2Y receptors. UTP at 0.25 mM was ine ective and did not induce vasodilation. Perfusion with 0.25 mM ADP resulted in a vasodilation that was identical to 0.25 mM ATP. In the absence of 8-SPT the perfusion of 0.25 mM ATPgS produced a vasodilation that was signi®cantly (P50.05) less than ATP. However, the vasodilation due to ATPgS, like that of adenosine, but unlike that of both ATP and ADP, was abolished in the presence of 8-SPT. The ability of ADP to induce vasodilation combined with both the lack of response to UTP and the ability of 8-SPT to abolish the vasodilation induced by ATPgS suggested very strongly that the component of ATP-induced coronary vasodilation in the isolated working rat heart that was mediated via P2Y receptors was achieved by the action of ADP (and not ATP) at P2Y 1 receptors. 5 These results suggest that the vasodilatory action of intravascular ATP in the coronary circulation should be attributed to the dual and equal activities of adenosine and ADP acting at P1 and P2Y 1 receptors respectively.

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T'he brains of dogs subjected to total cardiac bypass were examined for early signs of ischaemic nerve cell changes. Diffuse nerve cell changes were found immediately following two-and threehour non-pulsatile perfusions but not following pulsatile perfusions of the same durations. The nerve cell changes found in the brains were acute cell swelling and early isohaemic cell change. Acute cell swelling was found only in the cerebellar Purkinje cells. Ischaemic cell change was found in several regions of the brain but the cerebral cortex and cerebellar Purkinje cells were most frequently affected. Diffuse nerve cell changes are attributed to non-pulsatile blood flow but some complicating factors are recognized.Focal lesions found in three brains may have been due to embolism by blood cell aggregates and/or gas microbubbles.Roller pumps are currently in general use for the production of extracorporeal circulation during open-heart surgery. Their remarkable efficiency and easy control have been a hindrance to the development of alternative types of pump. However, an increasing volume of evidence supports the view that pumps producing pulsatile blood -flow would provide more efficient tissue perfusion than roller pumps producing ripple (non-pulsatile) blood flow. We have performed experiments to test this view using brain damage as a criterion for assessing tissue perfusion. MATERIALS AND METHODSGeneral anaesthesia was induced in 20 beagle and harrier dogs, 6-5-20-0 kg body weight, by intravenous injection of 0 25-0 5 g of sodium thiopentone (Intraval (DeBakey, 1934) or the MortonKeele prototype pulsatile pump (Sanderson et al.) with Harvard remote diaphragm heads. The circuit tubing was 6-0 mm internal 'diameter polyvinyl chloride (PVC). The reservoirs were also PVC and each reservoir had a capacity of 300 ml. The heat exchanger consisted of four stainless steel tubes each 15 m in length and with an internal diameter of 6-0 mm mounted in a copper water jacket. The heat exchanger was placed in the left atrial return instead of being in the delivery line from the left pump. This translocation was introduced to reduce damping of the pulse delivered by the pulsatile pump.All of the cannulae were made of stainless steel.The atria were drained through 6&0 mm internal diameter fenestrated cannulae. The internal diameters of the arterial cannulae were 4-0 or 5-0 mm for the pulmonary artery, 2 5, 3 0 or 3-5 mm for the femoral artery, and 4 0, 5 0 or 6-0 mm for the proximal aorta, depending upon the diameter of the lumen of the artery.The extracorporeal circuit was primed with 1,300 ml dog blood; 10 ml 10% low molecular weight dextran in 0-9% sodium chloride (Rheomacrodex) and 4 ml 10% mannitol/kg of body weight; plus 4 ml 20% sodium bicarbonate, 2,500 international units heparin, and 3 ml 20% calcium chloride/ 500 ml priming fluid.Using clean surgical techniques, a median sternotomy was performed to permit cannulation of the right and left atria and the pulmonary artery. For non-pulsatile flow, the aorta was retrogradely per...