title: Bidirectional effects of aminophylline on myocardial ischemia.
abstract: 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.
  
  
  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 alpha 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 alpha 1-adrenoceptor stimulation, which improves endomyocardial flow in the ischemic myocardium. The deleterious effect was attributable to the aminophylline-induced blockade of adenosine receptors.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Minamino
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
authors.forename: T
authors.initials: T
authors.lastname: Morioka
authors.forename: K
authors.initials: K
authors.lastname: Node
authors.forename: Y
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: M
authors.initials: M
authors.lastname: Chujo
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: H
authors.initials: H
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000628:Aminophylline / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D006321:Heart / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D015203:Reproducibility of Results; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D007773:Lactates; D058915:Purinergic P1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018047:Receptors, Purinergic P1; D000628:Aminophylline; D019344:Lactic Acid; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D011224:Prazosin