Asimakis G K, Inners-McBride K, Conti V R
University of Texas Medical Branch, Galveston 77555-0528.
Cardiovasc Res. 1993 Aug;27(8):1522-30. doi: 10.1093/cvr/27.8.1522.
The aim was to test the hypothesis that adenosine mediates the cardioprotective effects of ischaemic preconditioning in the isolated rat heart.
Transient exposure of the hearts to adenosine and the A1 selective agonist, PIA, were tested for the ability to mimic the cardioprotective effects of ischaemic preconditioning in hearts that underwent 40 min normothermic ischaemic followed by 30 min reperfusion. Treated hearts were perfused with 10 or 50 microM adenosine or 10(-7) M R-phenylisopropyladenosine (PIA) for 5 min followed by a 5 min washout period. Preconditioned hearts underwent 5 min of ischaemia and 5 min of reflow prior to the 40 min ischaemic period. The ability of the adenosine receptor antagonist, BW A1433U, to inhibit the cardioprotective effects of ischaemic preconditioning was also tested. The effects of these treatments on metabolite levels and postischaemic haemodynamic function were assessed.
Adenosine (50 microM), but not PIA, resulted in enhanced accumulation of lactate after 40 min ischaemia: 122(SEM 8) v 96(5) nmol.mg-1 protein in control hearts (p < 0.002). Adenosine and PIA treatments did not significantly affect myocardial acidosis during ischaemia. Postischaemic contractile function (as assessed by percent recovery of the heart rate x developed pressure) was lower in 50 microM, but not 10 microM, adenosine treated hearts [8.8(2.2)] and PIA treated hearts [11.9(2.5)] than in control hearts [20.4(3.6)] (p < 0.01). Ischaemic preconditioning (1) lowered glycogen levels prior to the 40 min ischaemic period [57(6) v 110(18) nmol glucosyl units.mg-1 protein; p < 0.01]; (2) lowered lactate levels at the end of the 40 min ischaemic period [61(4) v 104(5) nmol.mg-1 protein]; (3) preserved myocardial pH during ischaemia [6.69(0.07) v 6.40(0.07); p < 0.01]; and (4) enhanced recovery of postischaemic contractile function [42.3(4.4)% v 19.7(6.0)%; p < 0.02]. BW A1433U did not prevent these effects of ischaemic preconditioning.
The cardioprotective effects of ischaemic preconditioning are not mediated by adenosine released during the preconditioning period in the isolated rat heart. Also, transient treatment of the heart with A1 adenosine receptor agonists can exacerbate postischaemic contractile dysfunction.
旨在验证腺苷介导缺血预处理对离体大鼠心脏的心脏保护作用这一假说。
检测心脏短暂暴露于腺苷及A1选择性激动剂PIA时，模拟缺血预处理对经历40分钟常温缺血及30分钟再灌注心脏的心脏保护作用的能力。将处理过的心脏用10或50微摩尔/升腺苷或10⁻⁷摩尔/升R-苯异丙基腺苷（PIA）灌注5分钟，随后冲洗5分钟。预处理的心脏在40分钟缺血期之前先经历5分钟缺血和5分钟再灌注。还检测了腺苷受体拮抗剂BW A1433U抑制缺血预处理心脏保护作用的能力。评估这些处理对代谢物水平及缺血后血流动力学功能的影响。
腺苷（50微摩尔/升）而非PIA，导致40分钟缺血后乳酸积累增加：对照心脏中为122（标准误8）对96（5）纳摩尔/毫克蛋白质（p < 0.002）。腺苷和PIA处理在缺血期间对心肌酸中毒无显著影响。缺血后收缩功能（通过心率×收缩压恢复百分比评估）在50微摩尔/升但非10微摩尔/升腺苷处理的心脏[8.8（2.2）]和PIA处理的心脏[11.9（2.5）]中低于对照心脏[20.4（3.6）]（p < 0.01）。缺血预处理（1）在40分钟缺血期之前降低糖原水平[57（6）对11
