Ann Thorac Surg 2005;80:257-258
© 2005 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
Yuji Hiramatsu, MD, PhD
Department of Cardiac Surgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575 Japan
(Email: yuji3{at}md.tsukuba.ac.jp).
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Introduction
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This article by Kondo and colleagues is an important addition to the literature on our continuing struggle to achieve "platelet anesthesia" during cardiopulmonary bypass (CPB). Undoubtedly, FK633, a synthetic platelet glycoprotein (GP) IIb/IIIa inhibitor is one of the most promising platelet anesthetics available, because the drug has a relatively short half-life [1]. The authors’ pre-CPB dose strategy is aimed at shutting down the first and biggest burst of platelet activation, which occurs during the initial contact with the artificial surface and the initial exposure to tissue factor. This concept is quite attractive, and they previously demonstrated the successful inhibition of 
-granule release throughout in vitro CPB with such a single dose regimen. However, as the authors mention, the bolus regimen of FK633 before this in vivo CPB did not provide a complete restoration of platelet function at the time protamine was given. This could be explained by the fact that the platelet aggregability resumes too early in CPB, partly by recruiting new cells from their pools in vivo. The optimal protocol for platelet anesthesia would probably include the continuous administration of an ultra-short acting inhibitor, unless a mechanism to immediately reverse its action existed. Because currently available GP IIb/IIIa inhibitors are not very short-acting, the next important issue is deciding when and how to restore the function of deeply anesthetized platelets as promptly as possible just at the termination of CPB. For platelet anesthesia in cardiac operations, prompt and complete recovery of platelet inhibition is an absolute requirement.
Previous studies provide evidence for an inhibitory effect of platelet antagonists on the coagulation mechanisms leading to thrombin generation by the interaction between GP IIb/IIIa and prothrombin. However, this inhibitory mechanism on thrombin generation cannot be overestimated and was not actually reproduced by the studies in this article. A number of recent investigations suggest that the extrinsic coagulation pathway plays a more important role in thrombin generation than even the intrinsic pathway [2]. Although platelet anesthesia is an important and probably the most practical aspect of the concept "blood anesthesia," which envisions inhibiting the initial reaction of all blood elements to temporarily shut down the amplification cascade of clotting and inflammation during CPB [3], competent strategies to control the contact pathway, the extrinsic pathway, and the inflammatory cascade need to be thoroughly pursued. A number of multi-spectrum inhibitors such as nafamostat, aprotinin, and nitric oxide have been tested as potential blood anesthetics. However, none of them have been routinely used clinically or have overcome the efficacy of standard heparin by themselves.
When we truly reach the goal of platelet anesthesia, as a logical consequence we will face the dilemma that we need to develop novel anti-platelet protocols that protect grafts or prosthetics from disastrous thrombus formation by a larger quantity of fresh platelets immediately after cardiac surgery. However when that time comes we will be willing to accept such a dilemma as a reward for our continuing efforts.
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Southern Thoracic Surgical Association: Fifty-Second Annual Meeting
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The Fifty-Second Annual Meeting of the Southern Thoracic Surgical Association (STSA) will be held November 10–12, 2005, in Orlando, Florida.
The Postgraduate Course will be held the morning of Thursday, November 10, 2005, and will provide in-depth coverage of cardiothoracic surgical topics selected primarily as a means to enhance and broaden the knowledge of practicing thoracic and cardiac surgeons.
Manuscripts accepted for the Resident Competition must be submitted to the STSA headquarters office no later than September 16, 2005. The Resident Award will be based on abstract, presentation, and manuscript.
Applications for membership should be completed by September 15, 2005, and forwarded to Richard L. Prager, MD, Membership Committee Chairman, Southern Thoracic Surgical Association, 633 N Saint Clair St, Suite 2320, Chicago, IL 60611-3658.
| Please visit the STSA (http://www.stsa.org) or CTSNet (http://www.ctsnet.org) websites for detailed information on submitting abstracts. All abstracts must be submitted electronically for consideration.
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References
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- Tabata S, Yamaguchi H, Nagamine H, et al. Efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist on platelet preservation during and after cardiopulmonary bypass Eur J Cardiothorac Surg 2004;26:289-293.[Abstract/Free Full Text]
- De Somer F, Van Belleghem Y, Caes F, et al. Tissue factor as the main activator of the coagulation system during cardiopulmonary bypass J Thorac Cardiovasc Surg 2002;123:951-958.[Abstract/Free Full Text]
- Gorman III JH, Edmunds Jr LH. Blood anesthesia for cardiopulmonary bypass J Card Surg 1995;10:270-279.[Medline]
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Platelet Preservation With a Glycoprotein IIb/IIIa Inhibitor in a Porcine Cardiopulmonary Bypass Model
- Norihiro Kondo, Yasuyuki Suzuki, Fuminori Wakayama, Yoshiko Tamai, Kaiqiang Ji, Kozo Fukui, and Ikuo Fukuda
Ann. Thorac. Surg. 2005 80: 251-257.
[Abstract]
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Introduction
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