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Influence of activated polymorphonuclear leukocytes on myocardial microcirculation
J Mol Cell Cardiol 24 (Supplement I) (1992)
3-17-l
REDIRECTION ANTIPLATELET
OF PROSTAGLANDIN ENDOPEROXIDE SYNTHESIS EXERTS ADDITIVE EFFECTS IN THE PRESENCE OF THROMBOXANE A, RECEPTOR BLOCKADE.
Paolo Golino, Giuseppe Ambrosia;Massimo Ragni,Enrico RussoIiUo,ImmacolataPascucci,GiovanBattista Leproux, MassimoChiarielIo. Divisionof Cardiology,2ndSchoolofMedicine,UniversityofNaples andSamilSpA,Rome.Italy To assesswhether pmstagIandin (PG) endoperoxides play a role in modulating platelet reactivity in the setting of thromboxane A, (TxAd blockade, cyclic flow reductions (CFRs), due to recurrent platelet aggregation, were initiated instenotic.endothelially-injuredcamtidarteriesof39rabbits. After30minofCFRs,theanimalsreceived: 1)dazoxiben (D; 5 mg/kg bolus + 5 mg&& n=13), a TxA, synthaseinhibitor, 2) SQ29548 (SQ: 0.6 mg/kg bolus + 0.6 mg@fhr, n=13), a TxA,/PGH, receptor antagonist; 3) picotamide (P: 20 mglkg b&s + 20 mglkgfhr, n=13), a drug with simultaneous TxA, synthaseand receptor blocking properties. CFRswere abolished in 7 of 13.6 of 13, and 12 of 13 animals treated with D, SQ, and P, respectively(p
O-17-2 THROMBOXANE SYNTHETASE INHIBITOR (TXSI) REDUCED REPERFUSION ARRHYTHMIAS BUT FAILED TO LIMIT SIZE OF MYOCARDIAL INFARCTION AFTER CORONARY ARTERY OCCLUSION (CAO) AND REPERFUSION (CAR) IN DOGS Naoki Sate, Takao Endo, Haruo Kaneko, Kaname Kiuchi, Chikao Ibuki, Yoshifumi Tomita, Jun Nejima, Hirokazu Hayakawa. First Dept of Internal Medicine, Nippon Medical School, Tokyo, Japan It is well documented that TXSIs reduce infarct size (IS) and arrhythmias after CA0 without CAR. However, their effects on reperfusion injury are controversial. We examined effects of a new TXSI, Y20811, on IS and arrhythmias after 90 min CA0 and 6 h CAR in anesthetized dogs. Thirty min before CAO, Y-2081 1 (1 mglkg) was iv given, which decreased serum TXF$ formation by 98% 30 min later and by 72% at 6 h after CAR. Ventricular fibrillation developed in 1115 in control (C) vs 3110 in treated (T) during CA0 (p=NS), whereas after CAR it occurred in 7/14 in C vs 017 in T (p-20.05). The number of arrhythmic beats during the first one hour of CAR was reduced in T (134&-74 beats/min in C vs 14*4 in T, p < 0.05). Hemodynamics, area at risk (AR), and epicardial collateral flow after CA0 were similar for two groups. IS/AR {2&O&10.0% (n=7) in C vs 27.6k6.296 (n=7) in T), its relation to collateral flow, and degree of neutrophil accumulation did not differ in two groups. Thus, Y-2081 1 at the dose given reduced reperfusion arrhythmias but failed to limit IS and neutrophil infiltrate after CAO/CAR in dogs.
o-1 7-3 INFLUENCE OF ACTIVATEDPOLYMORPHONUCLEARLEUKOCYTES
ONMYOCARDIALMICROCIR-
CULATION.
Peter R Hansen, Jesper H Svendsen, Soren Hoier, Arsalan Kharazmi, Stig Hauns.0. Rigshospitalet, University of Copenhagen, Denmark. Activated polymorphonuclear leukocytes (PMN) may contribute to myocardial microvascular injury after ischemia and reperfusion by production of toxic mediators (e.g. oxygen free radicals and phospholipase products) and mechanical capillary plugging. To examine these effects in open-chest anesthetized dogs, isolated PMN (5x106-5x10’ cells) were injected into the distal left anterior descending artery, before and after ex vivo activation with N-formyl-Meth-Leu-Phe (FMLP) (n=2, human PMN) or PMA (n=4, autologous PMN). The regional myocardial plasma flow and the capillary extraction (E) and capillary permeabilitysurface area (PS) product of wmDTPA were determined by the single injection, residue detection method before, and 5 and 30 minutes after injection of non-activated PMN, and activated PMN, respectively, with each dog serving as its own control. The microcirculatory parameters were not significantly altered by injection of PMN, and we conclude that during normal perfusion pressure, PMN-activation per se is insufficient to result in microvascular damage. s.99
3-17-l
REDIRECTION ANTIPLATELET
OF PROSTAGLANDIN ENDOPEROXIDE SYNTHESIS EXERTS ADDITIVE EFFECTS IN THE PRESENCE OF THROMBOXANE A, RECEPTOR BLOCKADE.
Paolo Golino, Giuseppe Ambrosia;Massimo Ragni,Enrico RussoIiUo,ImmacolataPascucci,GiovanBattista Leproux, MassimoChiarielIo. Divisionof Cardiology,2ndSchoolofMedicine,UniversityofNaples andSamilSpA,Rome.Italy To assesswhether pmstagIandin (PG) endoperoxides play a role in modulating platelet reactivity in the setting of thromboxane A, (TxAd blockade, cyclic flow reductions (CFRs), due to recurrent platelet aggregation, were initiated instenotic.endothelially-injuredcamtidarteriesof39rabbits. After30minofCFRs,theanimalsreceived: 1)dazoxiben (D; 5 mg/kg bolus + 5 mg&& n=13), a TxA, synthaseinhibitor, 2) SQ29548 (SQ: 0.6 mg/kg bolus + 0.6 mg@fhr, n=13), a TxA,/PGH, receptor antagonist; 3) picotamide (P: 20 mglkg b&s + 20 mglkgfhr, n=13), a drug with simultaneous TxA, synthaseand receptor blocking properties. CFRswere abolished in 7 of 13.6 of 13, and 12 of 13 animals treated with D, SQ, and P, respectively(p
O-17-2 THROMBOXANE SYNTHETASE INHIBITOR (TXSI) REDUCED REPERFUSION ARRHYTHMIAS BUT FAILED TO LIMIT SIZE OF MYOCARDIAL INFARCTION AFTER CORONARY ARTERY OCCLUSION (CAO) AND REPERFUSION (CAR) IN DOGS Naoki Sate, Takao Endo, Haruo Kaneko, Kaname Kiuchi, Chikao Ibuki, Yoshifumi Tomita, Jun Nejima, Hirokazu Hayakawa. First Dept of Internal Medicine, Nippon Medical School, Tokyo, Japan It is well documented that TXSIs reduce infarct size (IS) and arrhythmias after CA0 without CAR. However, their effects on reperfusion injury are controversial. We examined effects of a new TXSI, Y20811, on IS and arrhythmias after 90 min CA0 and 6 h CAR in anesthetized dogs. Thirty min before CAO, Y-2081 1 (1 mglkg) was iv given, which decreased serum TXF$ formation by 98% 30 min later and by 72% at 6 h after CAR. Ventricular fibrillation developed in 1115 in control (C) vs 3110 in treated (T) during CA0 (p=NS), whereas after CAR it occurred in 7/14 in C vs 017 in T (p-20.05). The number of arrhythmic beats during the first one hour of CAR was reduced in T (134&-74 beats/min in C vs 14*4 in T, p < 0.05). Hemodynamics, area at risk (AR), and epicardial collateral flow after CA0 were similar for two groups. IS/AR {2&O&10.0% (n=7) in C vs 27.6k6.296 (n=7) in T), its relation to collateral flow, and degree of neutrophil accumulation did not differ in two groups. Thus, Y-2081 1 at the dose given reduced reperfusion arrhythmias but failed to limit IS and neutrophil infiltrate after CAO/CAR in dogs.
o-1 7-3 INFLUENCE OF ACTIVATEDPOLYMORPHONUCLEARLEUKOCYTES
ONMYOCARDIALMICROCIR-
CULATION.
Peter R Hansen, Jesper H Svendsen, Soren Hoier, Arsalan Kharazmi, Stig Hauns.0. Rigshospitalet, University of Copenhagen, Denmark. Activated polymorphonuclear leukocytes (PMN) may contribute to myocardial microvascular injury after ischemia and reperfusion by production of toxic mediators (e.g. oxygen free radicals and phospholipase products) and mechanical capillary plugging. To examine these effects in open-chest anesthetized dogs, isolated PMN (5x106-5x10’ cells) were injected into the distal left anterior descending artery, before and after ex vivo activation with N-formyl-Meth-Leu-Phe (FMLP) (n=2, human PMN) or PMA (n=4, autologous PMN). The regional myocardial plasma flow and the capillary extraction (E) and capillary permeabilitysurface area (PS) product of wmDTPA were determined by the single injection, residue detection method before, and 5 and 30 minutes after injection of non-activated PMN, and activated PMN, respectively, with each dog serving as its own control. The microcirculatory parameters were not significantly altered by injection of PMN, and we conclude that during normal perfusion pressure, PMN-activation per se is insufficient to result in microvascular damage. s.99