(Circulation. 1998;97:2279.)
© 1998 American Heart Association, Inc.
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 ischemia, so that the
protective effects observed after surgery could have been secondary to
ischemic preconditioning rather than adenosine
preconditioning. Third, since the hemodynamic
parameters measured by Lee et al (cardiac index, stroke
volume index, left ventricular stroke work index, etc) are
highly dependent on the loading conditions, changes in these
variables are difficult to interpret. Postoperative administration
of vasoactive or inotropic agents could also have had a substantial
impact on the results. Fourth, the decrease in the release of creatine
kinase (CK) in adenosine-treated patients cannot be construed
as evidence of protection against ischemia/reperfusion injury,
since total CK (rather than MB-CK) was reported; the release of total
CK during surgery reflects mainly the trauma to skeletal and cardiac
muscle. Finally, the legend to Figure 5 in the article by Lee et al
shows that CK release during the first 24 hours postoperatively was
significantly greater versus prebypass in controls but not in
adenosine-treated patients; the significance of this comparison
is unclear. In summary, the findings of Lee et al cannot be construed
as evidence that adenosine preconditions human
myocardium against ischemia.
References
1.
Lee HT, LaFaro RJ, Reed GE. Pretreatment of human
myocardium with adenosine during open heart
surgery. J Card Surg. 1995;10:665–676.
