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J Thorac Cardiovasc Surg 1997;113:617
© 1997 Mosby, Inc.

LETTERS TO THE EDITOR

Relation of cyclic guanosine monophosphate and cyclic adenosine monophosphate in reducing the toxic effects of protamine administration

S. Fehmi Katirciolu, MD, Ouz Tademir, MD, Kemal Bayazit, MD

Department of Cardiovascular Surgery
Turkiye Yüksek htisas Hastanesi
Ankara, Turkey

To the Editor:

We read with great interest the article by Raikar and associates ¹ regarding nitric oxide inhibition to relieve the adverse effects of protamine on blood pressure. They declared that hypotension caused by protamine administration can be blocked by nitrous oxide inhibition. We would like to add our experience to their information.

Adverse effects of protamine administration on various organ systems have been known for a long time. These changes were attributed to the increased complement levels associated with an increase in thromboxane and leukotriene levels. These mediators may impair the function of organs such as the heart and lungs, although these changes are mostly clinically insignificant. We ² documented that leukotriene and thromboxane levels increased after heparin reversal with protamine. These changes, which were associated with an increase in cyclic guanosine monophosphate (cGMP) levels and a reduction in cyclic adenosine monophosphate (cAMP) levels, adversely affected myocardial function. Monitoring cardiac output with a fast-response thermistor allowed us to calculate the ejection fraction changes in the right ventricle. After protamine administration, while right ventricular end-diastolic volume became stable, right ventricular end-systolic volume increased significantly, indicating the same degree of impairment in myocardial contractility. However, we did not observe any significant change in pulmonary artery pressure. These pressure changes were associated with a temporary defect in myocardial oxidative metabolism, as indicated by the changes in myocardial oxygen consumption and myocardial lactate extraction. Prostacyclin usage reduced the toxic mediator release and improved myocardial function. After protamine administration, we observed that protamine use decreased the cGMP level in the blood and increased the cAMP level in the blood. ², ³ In light of this study, we hypothesized that a fall in cAMP level and a rise in cGMP level are responsible for the toxic manifestations of heparin reversal with protamine, similar to our observation during ischemic reperfusion. ⁴ On the basis of this information, we used aminophylline, a phosphodiesterase inhibitor, to increase the cAMP level and observed that aminophylline use reduced the toxic mediator release and preserved myocardial function. ⁵ Finally, adverse effects of protamine on myocardial function can be controlled with agents that increase the cAMP level.

12/8/78748

References

1. Raikar GV, Hisamochi K, Raikar BL, Schaff HV. Nitric oxide inhibition attenuates systemic hypotension producecd by protamine. J Thorac Cardiovasc Surg 1996;111;1240-7
   
2. Katirciolu SF, Küçükaksu DS, Bozdayi M, et al. Effects of prostacyclin on heparin reversal with protamine. Vascular Surgery 1992;8:464-472.
   
3. Katirciolu SF, Küçükaksu DS, Tademir O, et al. Arachidonic acid metabolism after heparin reversal with protamine. Ann Thorac Surg 1995;59:550-1.[Free Full Text]
   
4. Katirciolu SF, Küçükaksu DS, Bozdayi M, et al. Beneficial effects prostacyclin treatment on reperfusion of the myocardium. Cardiovasc Surg 1995;3:405-408.[Medline]
   
5. Katirciolu SF, Küçükaksu DS, Bozdayi M, et al. Benefical effects of aminophylline administration on heparin reversal with protamine. Jpn J Surg 1994;24:99-102.
   

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Oguz Tasdemir Kemal Bayazit Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Katircioglu, S. F. Articles by Bayazit, K. Search for Related Content PubMed PubMed Citation Articles by Katircioglu, S. F. Articles by Bayazit, K.