EVALUATION OF THE PLATELET PROTECTING EFFECTS OF NITRIC OXIDE (NO) AND APROTININ DURING CARDIOPULMONARY BYPASS

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671771
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: TEIKYO UNIVERSITY SCHOOL OF MEDICINE
• Principal Investigator: MORITA Shigeho TEIKYO UNIVERSITY,SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (60143476)
• Co-Investigator(Kenkyū-buntansha): OSAKA Shinichi TEIKYO UNIVERSITY,SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (40160832) ; ICHINOSE Fumito TEIKYO UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (40276712)
• Project Period (FY): 1996 – 1997
• Keywords: cardiopulmonary bypass / nitric oxide / coronary artery bypass grafting / platelet function / postoperative bleeding / flow cytometry / aprotinin / monoclonal antibody

Research Abstract

We have undertaken these studies to examine whether NO gas can reduce platelet activation and blood loss in patients who had elective coronary artery bypass grafting (CABG) with CPB.We also compared the effects of NO gas to aprotinin. The data from remaining 20 patients were subsequently analyzed.
CPB was performed at a minimal temperature of 28ﾟC with a nonpulsatile flow of 2.4 L/min/kg. Chest tube draignage was recorded hourly until removal of drains. In patietnts who received aprotinin, 500,000 KIU of aprotinin was slowly given after the induction of anesthesia and before the start of CPB,and another 500,000 KIU aprotinin was added to pump priming solution. NO gas was mixed into the sweep gas flow of the membrane oxygenator, with a specially made flow meter. Concentration of oxygen, NO,NO2 were measured immediately before and after the oxygenator, and NO gas flow was adjusted so that 100 ppm NO gas was mixed into the oxygenator sweep gas. Platelet activation is quantified based on th e increased surface expression of P-selectin (CD62). The decreased surface expression of GPlb (CD42b) was also regarded as alteration of platelet function caused by CPB,and quantified. Anslysis of list mode data files was performed using CELLQuest software (Beckton Dickinson Immunocytometry Systems).
In control and NO treated patients, activated platelets, indicated by increased events positive for CD62PE,significantly increased during and after CPB.In aprotinin-treated patients, platelet activation was modestly attenuated during CPB.There was a tendency that blood loss during the first 24 hrs after operation was modestly decreased by aprotinin treatment, but statistical significance was not achieved at this point. No difference was found between, control and the NO-treated group in 24 hr blood loss.
Since currently we do not have enough number of patients in our study, we cannot make any conclusion at this point. However, preliminary results from out study showed that giving NO at 100 ppm to the membrane oxygenator sweep gas does not reduce platelet activation due to the synthetic surfaces of CPB.The amount of blood loss during the first 24 hrs after the operation was also not altered by NO gas infusion. On the other hand, low dose aprotinin employed in our study attenuated platelet activation as previously reported with higher doses of aprotinin. There was a tendency that aprotinin decreased postoperative blood loss in the first 24 hours, but statistical significance was not achieved at this point. We will increase number of patients and also try to examine the effects of NO gas plus aprotinin on platelet activation during CPB.