In Reply:—

We thank Drs. Geissler, Mehlhorn, Laine, and Allen for commenting positively on our recent article. 1We agree that the authors have contributed significantly over the past 10 yr to demonstrating the safety and efficacy of intracoronary β-adrenergic receptor (β-AR) antagonists as an alternative to cardioplegia in the setting of coronary artery bypass grafting surgery. In contrast, our study does not compare or contrast methods for administration of β-ARs during coronary artery bypass grafting surgery, but, rather, the mechanisms by which protection might occur. As such, our comments on “the paucity of data” in the area of β-AR antagonists during cardiac surgery refers to both a lack of mechanistic data demonstrating the rationale for beneficial effects and a lack of large-scale, randomized, clinical trials.

To support this claim, we cited recent American College of Cardiology and American Heart Association concerns, 2as well as American College of Cardiology and American Heart Association guidelines that state that, at this time, “there is no universally applicable myocardial protection technique” for reducing the risk of perioperative myocardial dysfunction. 3Geissler et al.  further comment that the use of intravenous esmolol as an adjunct to cold crystalloid cardioplegia (e.g. , rather than intracoronary esmolol) makes “no sense from a cardiac surgeon's point of view.” However, the model used in our study was based on the common practice in the United States of intravenous β-blockade during cardiopulmonary bypass, a strategy that has recently been shown to have benefit in terms of neuroprotection in humans. 4 

Our study 1also clearly demonstrates prevention of acute myocardial β-AR desensitization in a canine model with use of this approach. Crystalloid cardioplegia has been supplemented with many agents over the years in the quest for better myocardial protection; Geissler et al.  have contributed in very positive ways to alternative thinking in this regard in their use of esmolol as a sole “cardioplegic” agent. Our study does not purport to answer this controversial question. Rather, our quest for understanding the mechanisms by which stress affects the myocardium, in this case via β-ARs, is based on the hope that such insight may lead to novel approaches for protecting the heart during cardiac surgery in the future.

Booth JV, Spahn DR, McRae RL, Chesnut LC, El-Moalem H, Atwell DM, Leone BJ, Schwinn DA: Esmolol improves left ventricular function via enhanced β-adrenergic receptor signaling in a canine model of coronary revascularization. A nesthesiology 2002; 97: 162–9
Ryan TJ, Antman EM, Brooks NH, Califf RM, Hillis LD, Hiratzka LF, Rapaport E, Riegel B, Russell RO, Smith EE 3rd, Weaver WD, Gibbons RJ, Alpert JS, Eagle KA, Gardner TJ, Garson A Jr, Gregoratos G, Smith SC Jr: 1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1999; 34: 890–911
Eagle KA, Guyton RA, Davidoff R, Ewy GA, Fonger J, Gardner TJ, Gott JP, Herrmann HC, Marlow RA, Nugent W, O'Connor GT, Orszulak TA, Rieselbach RE, Winters WL, Yusuf S, Gibbons RJ, Alpert JS, Garson A Jr, Gregoratos G, Russell RO, Ryan TJ, Smith SC Jr: ACC/AHA guidelines for coronary artery bypass graft surgery: Executive summary and recommendations: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1991 guidelines for coronary artery bypass graft surgery). Circulation 1999; 100: 1464–80
Amory DW, Grigore A, Amory JK, Gerhardt MA, White WD, Smith PK, Reves JG, Schwinn DA, Newman MF: Neuroprotection is associated with β-adrenergic receptor antagonists during cardiac surgery: Suggestive evidence from 2,575 patients. J Cardiothorac Vasc Anesth 2002; 16: 270–7