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(Circulation. 1995;92:1254-1260.)
© 1995 American Heart Association, Inc.

Articles

Bidirectional Effects of Aminophylline on Myocardial Ischemia

Tetsuo Minamino, MD; Masafumi Kitakaze, MD; Toshikazu Morioka, MD; Koichi Node, MD; Yoshiro Shinozaki BE; Mitsuaki Chujo, MSC; Hidezo Mori, MD; Hiroshi Takeda, MD; Michitoshi Inoue, MD; Masatsugu Hori, MD; Takenobu Kamada, MD

From the First Department of Medicine, Osaka University School of Medicine, Osaka; Second Department of Physiology, Tokai University School of Medicine, Isehara (Y.S., M.C., H.M.); and Department of Information Science, Osaka (Japan) University Hospital (T. Minamino, H.T., M.I.).

Correspondence to Masafumi Kitakaze, MD, The First Department of Medicine, Osaka University School of Medicine, 2-2, Yamadaoka, Suita 565, Japan.

Background Aminophylline blocks adenosine receptors and increases levels of plasma catecholamines. We investigated the effect of aminophylline on myocardial ischemia by varying its severity and attempted to identify the mechanism by which aminophylline modulates myocardial ischemia in the canine model.

Methods and Results In 41 open-chest dogs, the left anterior descending coronary artery was cannulated and perfused with blood through a bypass tube from the left carotid artery. When coronary blood flow (CBF) was reduced to 80% of the control, aminophylline increased fractional shortening (FS) from 11.0±0.4% to 18.5±1.7% (P<.05) and lactate extraction ratio (LER) from 7.5±0.1% to 13.6±1.0% (P<.01). The endocardial to epicardial flow ratio (Endo/Epi ratio) of regional myocardium was also increased. Release of adenosine was increased compared with the nonischemic condition (7±3 versus 28±5 pmol/mL). Prazosin, an ₁-adrenoceptor antagonist, blunted the aminophylline-induced improvement in contractile and metabolic function. Administration of 8-phenyltheophylline, a selective antagonist of adenosine receptors, did not increase FS, LER, or the Endo/Epi ratio when CBF was reduced to 80% of control. When CBF was reduced to 60% of control, aminophylline did not change the metabolic and contractile function. In contrast, when CBF was reduced to 33% of control, release of adenosine was increased markedly (243±19 pmol/mL) and aminophylline induced decreases in FS, LER, and Endo/Epi ratio similar to those observed with 8-phenyltheophylline.

Conclusions Aminophylline had opposite effects on the ischemic myocardium depending on the severity of ischemia. It improved mild ischemia but worsened severe ischemia. The beneficial effect of aminophylline was attributable to ₁-adrenoceptor stimulation, which improves endomyocardial flow in the ischemic myocardium. The deleterious effect was attributable to the aminophylline-induced blockade of adenosine receptors.

Key Words: catecholamines • vasoconstriction • adenosine

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