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Polymorphonuclear leucocytes induce endothelium-dependent contraction of rabbit aorta
43
JMRKASE 111 [‘=I] -III-l BIHDIIIG SIlTI DEWSIm RI -ES FRC# RAT m PgllpllsBD WIPB PlRllg SOBSTRAn MID m OXID&%. JianJun Liu, Scott Britnell, David J.Casley, Winifred G.Hayler. Departrant of Nedicine University of Kelbourne Austin liospital, Heidelberg, VIC, 3084, A&xalia. Endothelin-l(tZ-1) is a newly discovered potent vasownstxictor peptide secxeted by endotbelial cells and In ani-, injection of ET-1 cause6 sudden death. In thought to be associated with cardiovascular disease. humans plasma ET levels are increased in lyocaxdial infarction, cardicqenic shock and subarachnoid w. Our previous studies have shown that specific ET-1 binding site density (B-) increases af’tex >20 rin ischaeria Lither hypoxia, acidosis nor intenittent ischaenia incxeases the L. and further increases upon reperfusion. The present studies were and&&en to However, reoxygenation enhanced the B, and decreased the affinity. detenine whether free radicals could be responsible for the effect of iscbaetia and repexfusion. To generate free radicals rat hearts were perfused with buffer containing 2.3 I purine and 0.01 units@ xanthine ox&se for 15 lin. This resulted in a 93.3; + 4.2 loss (P
Theserwults resemblethosecausedby ischaeniaandreperfusion.
44 POLYMORPHONUCLEAR ;E~~~;~;lIN~L"
END&';3IUM-DEPENDENT EONTRACTION OF RABBIT AORTA. . . , A.G. Stewart , G.J. , . . Dusting', Departments of lPhy&oloay and zPhhrmacoloqy, University of Melbourne, Parkville, Australia. We have investigated whether PMNs might contribute to the altered vascular reactivity following ischaemia and reperfueion. Rabbit aortic rings with (EI) or without (-EX) endothelium w&e mounted in 5 ml organ baths at 37OC with a resting tension of 2 Q. Addition to the bath of rabbit autoloqous PMNs (10 '~3x10b/ml), which had been incubated for 20 min at 37OC, had no effect on EX rings, nor on EI rings at resting tension. However in EI rings precontracted (to 70% of maximum) with serotonin (5-HT) or phenylephrine, PUNS produced concentrationdependent contractions, or produced transient contraction followed by relaxation. The supernatant of PMNs simply contracted EI rings, but had no effect on EX rings. Haemoqlobin (10 @4) and N-nitro-L-arqinine prevented contractions subsequent (30 pM) addition of PMN -to supernatant (P c 0.05). Superoxide dismutase (30 u/ml) had no effect on supernatant-induced contractions indicating that superoxide anions do not cause this response. These results suggest rabbit PMNs release a substance which produces endothelium-dependent contraction of rabbit aorta by blocking the release or action of nitric oxide.
45
LOW-FLOW PERFUSION WITH L-ASPARTATE ENRICHED CARDIOPLEGIA IMPROVES LONG-TERM MYCCARDIAL PRESERVATION. Y.S.Choong and J.B. Gavin. Department of Pathology, University of Auckland, Auckland, New Zealand. The potential of continuous low flow (1.5ml/min) perfusion to improve the preservation of explanted hearts subjected to hypothermic cardioplegia in St Thomas’ Hospital No. 2 cardioplegic solution (STH) was investigated in isolated working rat hearts. Hearts (n = E/group) were aerobically perfused (20 min) with Krebs-Henseleiti buffer (20 min) prior to cardioplegic arrest (3 min, 4’C) with oxygenated STH either alone or enriched with glucose , aspartate or both (20mM each) and then stored (4°C) for 20 hr while being continuously perfused with one of these solutions. Hearts were then reperfused (10 min Langendorff, 20 min working) and the post-ischaemic functionql recovery was measured. Whereas control hearts (STH f glucose) showed poor recovery of mean aortic flow (17.7 + 8.6% and 21.6 f. 7.8% of pre-arrest values), those treated with aspartate or aspartate plus glucose showed significant (p < 0.001) improvements in both the rate and extent of recovered aortic flow (89.8 t 5.2% and 85.0 f 6.2X, respectively). These improvements were associated with enhanced ATP, CP and GTP resynthesis and prevention of Ca” and Nat uptake on reperfusion. These results demonstrate improved cardioplegic protection when L-aspartate is added to STH during prolonged ischaemic cardiac arrest. (Supported by the National Heart Foundation of New Zealand). xv
JMRKASE 111 [‘=I] -III-l BIHDIIIG SIlTI DEWSIm RI -ES FRC# RAT m PgllpllsBD WIPB PlRllg SOBSTRAn MID m OXID&%. JianJun Liu, Scott Britnell, David J.Casley, Winifred G.Hayler. Departrant of Nedicine University of Kelbourne Austin liospital, Heidelberg, VIC, 3084, A&xalia. Endothelin-l(tZ-1) is a newly discovered potent vasownstxictor peptide secxeted by endotbelial cells and In ani-, injection of ET-1 cause6 sudden death. In thought to be associated with cardiovascular disease. humans plasma ET levels are increased in lyocaxdial infarction, cardicqenic shock and subarachnoid w. Our previous studies have shown that specific ET-1 binding site density (B-) increases af’tex >20 rin ischaeria Lither hypoxia, acidosis nor intenittent ischaenia incxeases the L. and further increases upon reperfusion. The present studies were and&&en to However, reoxygenation enhanced the B, and decreased the affinity. detenine whether free radicals could be responsible for the effect of iscbaetia and repexfusion. To generate free radicals rat hearts were perfused with buffer containing 2.3 I purine and 0.01 units@ xanthine ox&se for 15 lin. This resulted in a 93.3; + 4.2 loss (P
Theserwults resemblethosecausedby ischaeniaandreperfusion.
44 POLYMORPHONUCLEAR ;E~~~;~;lIN~L"
END&';3IUM-DEPENDENT EONTRACTION OF RABBIT AORTA. . . , A.G. Stewart , G.J. , . . Dusting', Departments of lPhy&oloay and zPhhrmacoloqy, University of Melbourne, Parkville, Australia. We have investigated whether PMNs might contribute to the altered vascular reactivity following ischaemia and reperfueion. Rabbit aortic rings with (EI) or without (-EX) endothelium w&e mounted in 5 ml organ baths at 37OC with a resting tension of 2 Q. Addition to the bath of rabbit autoloqous PMNs (10 '~3x10b/ml), which had been incubated for 20 min at 37OC, had no effect on EX rings, nor on EI rings at resting tension. However in EI rings precontracted (to 70% of maximum) with serotonin (5-HT) or phenylephrine, PUNS produced concentrationdependent contractions, or produced transient contraction followed by relaxation. The supernatant of PMNs simply contracted EI rings, but had no effect on EX rings. Haemoqlobin (10 @4) and N-nitro-L-arqinine prevented contractions subsequent (30 pM) addition of PMN -to supernatant (P c 0.05). Superoxide dismutase (30 u/ml) had no effect on supernatant-induced contractions indicating that superoxide anions do not cause this response. These results suggest rabbit PMNs release a substance which produces endothelium-dependent contraction of rabbit aorta by blocking the release or action of nitric oxide.
45
LOW-FLOW PERFUSION WITH L-ASPARTATE ENRICHED CARDIOPLEGIA IMPROVES LONG-TERM MYCCARDIAL PRESERVATION. Y.S.Choong and J.B. Gavin. Department of Pathology, University of Auckland, Auckland, New Zealand. The potential of continuous low flow (1.5ml/min) perfusion to improve the preservation of explanted hearts subjected to hypothermic cardioplegia in St Thomas’ Hospital No. 2 cardioplegic solution (STH) was investigated in isolated working rat hearts. Hearts (n = E/group) were aerobically perfused (20 min) with Krebs-Henseleiti buffer (20 min) prior to cardioplegic arrest (3 min, 4’C) with oxygenated STH either alone or enriched with glucose , aspartate or both (20mM each) and then stored (4°C) for 20 hr while being continuously perfused with one of these solutions. Hearts were then reperfused (10 min Langendorff, 20 min working) and the post-ischaemic functionql recovery was measured. Whereas control hearts (STH f glucose) showed poor recovery of mean aortic flow (17.7 + 8.6% and 21.6 f. 7.8% of pre-arrest values), those treated with aspartate or aspartate plus glucose showed significant (p < 0.001) improvements in both the rate and extent of recovered aortic flow (89.8 t 5.2% and 85.0 f 6.2X, respectively). These improvements were associated with enhanced ATP, CP and GTP resynthesis and prevention of Ca” and Nat uptake on reperfusion. These results demonstrate improved cardioplegic protection when L-aspartate is added to STH during prolonged ischaemic cardiac arrest. (Supported by the National Heart Foundation of New Zealand). xv