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Ann Thorac Surg 1995;60:310
© 1995 The Society of Thoracic Surgeons
DR SAFUH ATTAR (Baltimore, MD): I congratulate Bukhari and associates on this study, which is really complex. My comments are directed at the fact that we cannot really conclude, as they did in their report, that aprotinin is a risky drug to use and may enhance the production of myocardial infarction. I do not think the studies presented here can be applied to the human heart. I think they may apply to the sheep, but I do not think the findings justify the conclusion that have been made.
DR BUKHARI: In fact, the Cleveland Clinic group has demonstrated that when aprotinin is used clinically there is an increased incidence of operative myocardial infarction, but this was not statistically significant. This increased operative myocardial infarction rate has been demonstrated by other groups.
At the Riyadh Military Hospital, we also have studied the clinical application of aprotinin and have demonstrated an increased incidence of operative myocardial infarction from 3.5% to 7% (364 patients). This likewise approached statistical significance with a calculated p value of 0.09.
In this controlled study in sheep, we have demonstrated that aprotinin increases myocardial infarction, and this may have impact on the clinical application.
DR LUDWIG K. von SEGESSER (Zurich, Switzerland): One of the criticisms made of the Cleveland study was the heparinization regimen or the activated clotting time that was used. Can you tell us about how you handled the heparinization during your procedures?
DR BUKHARI: We believe that the sheep were heparinized adequately based on three points. First, we administered 300 units of heparin per kilogram body weight per hour. Second, Dave Royston and others have suggested from clinical studies that an activated clotting time of 750 seconds or greater is optimal. Our activated clotting time was much higher than that at 1,350 seconds. Third, Wang and associates reported that celite activation of the activated clotting time can give you a falsely high result in excess of 47% to 71%. Our data indicated that the activated clotting time was 90% higher than that normally measured. On these grounds we believe that the sheep were heparinized adequately.
DR SAMUEL V. LICHTENSTEIN (Vancouver, BC, Canada): Irrespective of the effect of aprotinin, certainly preconditioning seems to be a potent modality. Have you given any thought to how that might be applied clinically or how we might make use of preconditioning clinically?
DR BUKHARI: We recently have published a study indicating that cardiopulmonary bypass alone elicits the preconditioning response. These data were presented at the American Heart Association meeting in November 1994. Whether preconditioning elicited by bypass will be sufficient to neutralize any potential deleterious effects of aprotinin is not clear. This warrants further study.
Related Article
Ann. Thorac. Surg. 1995 60: 307-310.
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