| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1999;67:1539-1540
© 1999 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, University of Southern California and Childrens Hospital Los Angeles, 1510 San Pablo St, Los Angeles, CA 90033, USA
e-mail: mbarr{at}surgery.usc.edu
To the Editor
We appreciate Dr Wittwer and associates’ interest in our recent publication [1]. Their question regarding the utility of adding serine protease inhibitors to either Celsior or Perfadex preservation solutions is valid and can only be answered by evaluating those specific solutions using a dose titration of aprotinin or recombinant Kunitz protease inhibitor after a sufficient period of ischemic storage.
Doctor Wittwer and associates’ negative findings were with two extracellular-type solutions (neither of which are available for routine human use in the US), whereas our experiments involved two intracellular type solutions, which are the most commonly used clinical pulmonary preservation solutions in the US. Our finding of a beneficial effect of adding aprotinin to Euro-Collins or University of Wisconsin solutions involved significantly longer ischemic times (6 and 12 h). The 4-h ischemic time evaluated by Wittwer and associates is particularly short in a small animal model, especially when extracellular solutions like Celsior and Perfadex are used, in which longer ischemic times are well tolerated [2, 3]. After 24 h of ischemic storage, Nagahiro and associates [4] showed a beneficial effect of adding recombinant Kunitz protease inhibitor to low-potassium dextran-1% glucose solution (which is a similar solution to the Perfadex solution used by Dr Wittwer with opposite findings). The dose of aprotinin used by Dr Wittwer is 50% higher than we used in our study. While we found that 150 KIU/mL resulted in optimal in vitro endothelial cell viability, the optimal dose to reduce the capillary filtration coefficient in the isolated, blood-perfused lung model was only 100 KIU/mL, and that dose was used for the subsequent experiments we reported. The importance of the specific serine protease inhibitor dose/concentration added to a particular preservation solution was also documented by Nagahiro and associates [4]. They showed that recombinant Kunitz protease inhibitor added to low-potassium dextran-glucose in both the flush and recipient negated the beneficial effect of adding it to the flush solution alone.
To answer the question posed regarding whether addition of aprotinin to Celsior or Perfadex is worthwhile, we would recommend that those solutions be evaluated using longer ischemic storage times (as small animal models are more resistant to ischemia-reperfusion injury than in large animal models or human experiments, ischemic times of 6, 12, or 24 h in a rodent model might yield more clinically relevant results), and after a dose titration of aprotinin or recombinant Kunitz protease inhibitor is performed to determine the optimal dose of each agent for each solution. Anecdotally, using Euro-Collins and University of Wisconsin solutions, two centers in the US have administered 100 KIU/mL of aprotinin to the lung donor and/or flush, and used aprotinin as usual for hemostasis in the recipients, with excellent pulmonary preservation in several patients after 4- to 8-h storage periods.
Taking Dr Wittwer and associates’ conclusion further, we strongly agree with the concept of evaluating any additives to any organ preservation solution on a solution-by-solution basis, and optimally validating the results in a large animal orthotopic transplant model before entering the clinical setting. We also feel, based on several small and large animal experimental studies, that low-potassium, extracellular-type solutions such as Celsior and Perfadex (even without any additives) are superior to intracellular-type solutions for preventing pulmonary ischemia-reperfusion injury and will hopefully be routinely used in the US for lung preservation when they become available.
References
Related Article
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
