Bertolet B D, Belardinelli L, Avasarala K, Calhoun W B, Franco E A, Nichols W W, Kerensky R A, Hill J A
Department of Medicine, University of Florida Health Sciences Center, Gainesvilla 32610-0277, USA.
Cardiovasc Res. 1996 Nov;32(5):839-45.
To determine the relative sensitivity of cardiac A1- and A2-adenosine receptor-mediated effects to antagonism by theophylline in man.
Baseline measurements of the A-H interval (A1-adenosine receptor-mediated effect) and coronary blood flow (A2-adenosine receptor-mediated effect) were made in 10 patients with angiographically normal coronary arteries. Adenosine was then administered as a continuous intravenous infusion followed by a rapid intravenous bolus, and measurements repeated. Theophylline (5 mg/kg i.v.) was then administered, and the adenosine infusion repeated. To corroborate the results found in man, the cardiac A1- and A2-adenosine receptor-mediated effects were measured in guinea pig isolated hearts exposed to increasing concentrations of adenosine, in the absence and presence of theophylline (60 microM).
Compared to baseline, adenosine infusion and bolus caused significant prolongation of the A-H interval (109 +/- 41 vs. 116 +/- 44 vs. 168 +/- 57 ms, respectively), and increase in coronary blood flow (46 +/- 37 vs. 86 +/- 71 vs. 172 +/- 98 ml/min, respectively). Theophylline abolished the prolongation of the A-H interval during adenosine infusion and bolus (99 +/- 36 and 107 +/- 44 ms, respectively), yet had minimal effect on the increase in coronary blood flow (63 +/- 51 and 136 +/- 121 ml/min, respectively). In guinea pig isolated hearts, theophylline was shown to significantly antagonize the A2-adenosine receptor-mediated effects only when the concentrations of adenosine were < or = 1.0 microM.
In man, theophylline completely antagonizes the A1-adenosine receptor-mediated prolongation of the A-H interval, but has minimal effect on the A2-receptor-mediated coronary vasodilation, particularly when adenosine concentrations exceed 1.0 microM.
确定在人体中心脏A1和A2腺苷受体介导的效应对于茶碱拮抗作用的相对敏感性。
对10例冠状动脉造影正常的患者进行A - H间期（A1腺苷受体介导的效应）和冠状动脉血流量（A2腺苷受体介导的效应）的基线测量。然后持续静脉输注腺苷，随后快速静脉推注，之后重复测量。接着静脉注射茶碱（5mg/kg），再重复腺苷输注。为证实人体研究结果，在豚鼠离体心脏中，测量在有无茶碱（60μM）存在的情况下，暴露于浓度递增的腺苷时心脏A1和A2腺苷受体介导的效应。
与基线相比，腺苷输注和推注导致A - H间期显著延长（分别为109±41、116±44和168±57毫秒），冠状动脉血流量增加（分别为46±37、86±71和172±98毫升/分钟）。茶碱消除了腺苷输注和推注期间A - H间期的延长（分别为99±36和107±44毫秒），但对冠状动脉血流量增加的影响极小（分别为63±51和136±121毫升/分钟）。在豚鼠离体心脏中，仅当腺苷浓度≤1.0μM时，茶碱才显示出显著拮抗A2腺苷受体介导的效应。
在人体中，茶碱完全拮抗A1腺苷受体介导的A - H间期延长，但对A2受体介导的冠状动脉血管舒张影响极小，尤其是当腺苷浓度超过1.0μM时。
