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(Circulation. 1998;97:2279.)
© 1998 American Heart Association, Inc.

Correspondence

Adenosine Pretreatment of Human Myocardium and Ischemic Preconditioning

H. Thomas Lee, MD, PhD

Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY

To the Editor:

I congratulate Leesar et al¹ for their innovative research. Evidences are mounting to indicate that ischemic preconditioning (IPC) can be demonstrated in human myocardium,^{2 3 4} and this has stimulated interest in its potential clinical applicability. However, their study is not the first to demonstrate that adenosine (ADO) pretreatment can protect against myocardial reperfusion injury. In 1993, ADO was infused into the right ventricle of patients undergoing CABG operations.⁵ It has been conclusively demonstrated for the first time that ADO pretreatment before the initiation of cardiopulmonary bypass improves postbypass cardiac function and reduces postoperative CPK release.

Recently, IPC has been demonstrated to occur in organ systems other than myocardium. IPC has been demonstrated to occur in skeletal muscle of the rat and pig.⁶ Other organ systems such as liver,⁷ lung,⁸ brain,⁹ and spinal cord¹⁰ also would appear to benefit from the protective effects of IPC against ischemia/reperfusion injury.

References

1. Leesar MA, Stoddard M, Ahmed M, Broadbent J, Bolli R. Preconditioning of human myocardium with adenosine during coronary angioplasty. Circulation. 1997;95:2500–2507.[Abstract/Free Full Text]

2. Martin HB, Walter CL. Preconditioning: an endogenous defense against the insult of myocardial ischemia. Anesth Analg. 1996;83:639–645.[Medline] [Order article via Infotrieve]

3. Reimer KA, Jennings RB. Ischemic preconditioning: a brief review. Basic Res Cardiol. 1996;91:1–4.

4. Deutsch E, Berger M, Kussmaul WG, Hirshfield JW, Herrmann HC, Laskey WK. Adaptation to ischemia during percutaneous transluminal coronary angioplasty: clinical, hemodynamic, and metabolic features. Circulation. 1990;82:2044–2051.[Abstract/Free Full Text]

5. Lee HT, LaFaro RJ, Reed GE. Pretreatment of human myocardium with adenosine during open heart surgery. J Card Surg. 1995;10:665–676.[Medline] [Order article via Infotrieve]

6. Lee HT, Schroeder CA, Shah PM, Babu SC, Thompson CI, Bellini FL. Preconditioning with ischemia or adenosine protects skeletal muscle from ischemic tissue reperfusion injury. J Surg Res. 1996;63:29–34.[Medline] [Order article via Infotrieve]

7. Lloris-Carsi JM, Cejalvo D, Toledo-Pereyra LH, Calvo MA, Suzuki S. Preconditioning: effect upon lesion modulation in warm liver ischemia. Transplant Proc. 1993;25:3303–3304.[Medline] [Order article via Infotrieve]

8. Du ZY, Hicks M, Winlaw D, Spratt P, Macdonald P. Ischemic preconditioning enhances donor lung preservation in the rat. J Heart Lung Transplant. 1996;15:1258–1267.[Medline] [Order article via Infotrieve]

9. Heurteaux C, Lauritzen I, Widmann C, Lazdunski M. Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci USA. 1995;92:4666–4670.[Abstract/Free Full Text]

10. Matsuyama K, Chiba Y, Ihaya A, Kimura T, Tanigawa N, Muraoka R. Effect of spinal cord preconditioning on paraplegia during cross-clamping of the thoracic aorta. Ann Thorac Surg. 1997;63:1315–1320.[Abstract/Free Full Text]

Response

Roberto Bolli, MD

Professor of Medicine, Physiology, and Biophysics

Massoud A. Leesar, MD

Assistant Professor of Medicine, University of Louisville, Louisville, Ky

The study by Lee et al¹ purports to show that pretreatment with intravenous adenosine protects human myocardium during CABG. Unfortunately, there are several problems that make this conclusion untenable. First, the number of patients studied by Lee et al was small (7 control subjects and 7 adenosine-treated subjects). Second, infusion of adenosine caused significant hypotension (mean systolic arterial pressure fell by 30 mm Hg; in 2 of the 7 treated patients, systolic pressure fell below 70 mm Hg, requiring a decrease in the dose of adenosine). This hypotensive effect could have caused either global or regional (due to "coronary steal") myocardial . . . [Full Text of this Article]