HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rudd, D. M. Articles by Dobson, G. P. Search for Related Content PubMed Articles by Rudd, D. M. Articles by Dobson, G. P. Related Collections Cardiac - physiology Coronary disease Myocardial protection Transplantation - heart

J Thorac Cardiovasc Surg 2009;137:198-207
© 2009 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Toward a new cold and warm nondepolarizing, normokalemic arrest paradigm for orthotopic heart transplantation

Heart Research Laboratory, Department of Physiology and Pharmacology, James Cook University, Townsville, Queensland, Australia

Received for publication February 23, 2008; revisions received May 21, 2008; accepted for publication June 15, 2008.

^_* Address for reprints: Geoffrey P. Dobson, PhD, Heart Research Laboratory, Department of Physiology and Pharmacology, James Cook University, Townsville, Queensland, Australia 4811. (Email: geoffrey.dobson{at}jcu.edu.au).

Objective: Currently, the safe human heart preservation time is limited to around 4 to 5 hours of cold ischemic storage. Longer arrest times can lead to donor heart damage, early graft dysfunction, and chronic rejection. The aim of this study was to examine a new nondepolarizing, normokalemic preservation solution with adenosine and lidocaine for as long as 6 hours of arrest at cold and warmer storage temperatures.

Methods: Isolated perfused rat hearts (n = 87) were switched from working to Langendorff (nonworking) mode and arrested at 37°C with 200-µmol/L adenosine and 500-µmol/L lidocaine in Krebs–Henseleit buffer (10-mmol/L glucose, pH 7.7, 37°C) or with Celsior (Sangstat Medical Corp, Fremont, CA). Hearts were removed and placed in static storage at 4°C for 2 and 6 hours or remained on the apparatus and were intermittently flushed at 37°C every 20 minutes for 2 minutes at 68 mm Hg (average arrest temperature 28°–30°C) for 2 and 6 hours. We further investigated the effect of the warmer adenosine–lidocaine solution supplemented with 1- or 5-mmol/L pyruvate.

Results: Adenosine–lidocaine solution arrested hearts in 16 ± 2 seconds (n = 32), whereas Celsior did so in 39 ± 4 seconds (n = 23). After 2 hours of cold static storage, there were no functional differences between the adenosine–lidocaine and Celsior groups, with approximately 70% return of cardiac output. In contrast, after 6 hours of 4°C storage, adenosine–lidocaine hearts had significantly higher functional recoveries (68% ± 5% cardiac output) than Celsior hearts (47% ± 14% cardiac output) during 60 minutes of reperfusion. In addition, Celsior hearts took 5 minutes longer to reanimate and showed early reperfusion arrhythmias. At warmer temperatures after 2 hours of arrest, adenosine–lidocaine and Celsior hearts were not significantly different, despite a 43% higher cardiac output in adenosine–lidocaine hearts (80% ± 3% vs 56% ± 12%). After 6 hours, adenosine–lidocaine hearts had recovered 55% ± 3% of prearrest cardiac output, which increased significantly to 75% ± 4% with addition of 1-mmol/L pyruvate. Adenosine–lidocaine with 1-mmol/L pyruvate hearts spontaneously recovered 106% heart rate, 93% to 105% developed pressures, 70% aortic flow, and 81% coronary flow. Coronary vascular resistance increased 1.7- to 1.9-fold during the 6-hour arrest. In contrast, Celsior hearts did not have return of aortic or coronary flow after 6 hours in these warmer conditions.

Conclusion: A new nondepolarizing, normokalemic adenosine–lidocaine arrest solution in Krebs–Henseleit buffer with 10-mmol/L glucose was versatile at both 4°C and 28°C to 30°C relative to Celsior, and the addition of 1-mmol/L pyruvate significantly improved cardiac output at warmer arrest temperatures. This new arrest paradigm may be useful in the harvest, storage, and implantation of donor hearts.