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CLINICAL STUDIES

Effects of naloxone on myocardial ischemic preconditioning in humans

Fabrizio Tomai, MD, FACC^*, Filippo Crea, MD, FACC, Achille Gaspardone, MD, FACC^*, Francesco Versaci, MD, FACC^*, Anna S. Ghini, MD^*, Claudio Ferri, MD, Giovambattista Desideri, MD, Luigi Chiariello, MD, FACC^* and Pier A. Gioffré, MD^*

^* Divisione di Cardiochirurgia, Università di Roma Tor Vergata, European Hospital, Rome, Italy
Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Rome, Italy
Cattedra di Clinica Medica I, Università La Sapienza, Rome, Italy

Manuscript received October 15, 1998; revised manuscript received January 25, 1999, accepted February 15, 1999.

Reprint requests and correspondence: Dr. Fabrizio Tomai, Divisione di Cardiochirurgia, Università di Roma Tor Vergata, European Hospital, via Portuense 700, 00149 Rome, Italy

OBJECTIVES

We attempted to establish whether naloxone, an opioid receptor antagonist, abolishes the adaptation to ischemia observed in humans during coronary angioplasty after repeated balloon inflations.

BACKGROUND

Experimental studies indicate that myocardial opioid receptors are involved in ischemic preconditioning.

METHODS

Twenty patients undergoing angioplasty for an isolated stenosis of a major epicardial coronary artery were randomized to receive intravenous infusion of naloxone or placebo during the procedure. Intracoronary electrocardiogram and cardiac pain (using a 100-mm visual analog scale) were determined at the end of the first two balloon inflations. Average peak velocity in the contralateral coronary artery during balloon occlusion, an index of collateral recruitment, was also assessed by using a Doppler guide wire in the six patients of each group with a stenosis on the left anterior descending coronary artery.

RESULTS

In naloxone-treated patients, ST-segment changes and cardiac pain severity during the second inflation were similar to those observed during the first inflation (12 ± 6 vs. 11 ± 7 mm, p = 0.3, and 58 ± 13 vs. 56 ± 12 mm, p = 0.3, respectively), whereas in placebo-treated patients, they were significantly less (6 ± 3 vs. 13 ± 6 mm, p = 0.002 and 31 ± 21 vs. 55 ± 22 mm, p = 0.008, respectively). In both naloxone- and placebo-treated patients, average peak velocity significantly increased from baseline to the end of the first inflation (p = 0.04 and p = 0.02, respectively), but it did not show any further increase during the second inflation.

CONCLUSIONS

The adaptation to ischemia observed in humans after two sequential coronary balloon inflations is abolished by naloxone and is independent of collateral recruitment. Thus, it is due to ischemic preconditioning and is, at least partially, mediated by opioid receptors, suggesting their presence in the human heart.

Abbreviations and Acronyms   ECG = electrocardiogram   KATP channel = adenosine triphosphate–sensitive K+ channel   PKC = protein kinase C

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