Role of adenosine receptors in late preconditioning against myocardial stunning in conscious rabbits
Role of adenosine receptors in late preconditioning against myocardial stunning in conscious rabbits
复制标题
DOI：
10.1152/ajpheart.1997.273.3.h1324
复制
发表时间：
1997-09-01
影响因子：
4.8
通讯作者：
Bolli, R
中科院分区：
文献类型：
--
作者：
Maldonado, C;Qiu, YM;Bolli, R
清醒家兔连续2天进行6次4分钟的冠状动脉闭塞，其间穿插4分钟的再灌注期（第一阶段第1天和第2天）; 2 wk后，进行相同的方案（第二阶段第1和第2天），但他们收到8-（对磺苯基）茶碱（SPT）在第1天（组I，n = 5）或2-氯-N-6-环戊基-腺苷（CCPA）在第1天的前一天（组II，n = 6）。在第I阶段第1天，I组和II组的收缩期室壁增厚（WTh）持续数小时显著降低，表明心肌顿抑;然而，在第2天，WTh的总赤字与第1天相比减少了50%（P < 0.01），表明针对心肌顿抑的晚期预处理（PC）的发展。尽管给予SPT，在I组中，II期WTh的缺损在第2天比第1天减少55%（P < 0.05）。在第1天接受PD-115199给药的其他3只家兔中获得了相似的结果。在第二组，预处理与CCPA在第二阶段未能减少赤字的WTh在第1天。本研究提出了一种新的清醒兔模型，用于研究心肌顿抑，相对便宜，技术要求较低，比大型动物模型。在该模型中，晚期PC对抗心肌顿抑的发展不被SPT或PD 115199非选择性阻断腺苷受体所阻断，也不被CCPA激活腺苷A（1）受体所诱导，表明腺苷受体不参与该现象的发病机制。
Conscious rabbits underwent six 4-min coronary occlusions interspersed with 4-min periods of reperfusion for 2 consecutive days (days 1 and 2 of stage I); 2 wk later, they underwent the same protocol (days 1 and 2 of stage II) except that they received either 8-(p-sulfophenyl)theophylline (SPT) on day 1 (group I, n = 5) or 2-chloro-N-6-cyclopentyl-adenosine (CCPA) on the day before day 1 (group II, n = 6). In both groups I and II, on day 1 of stage I, systolic wall thickening (WTh) remained significantly depressed for several hours, indicating myocardial stunning; on day 2, however, the total deficit of WTh was similar to 50% less than on day 1 (P < 0.01), indicating the development of late preconditioning (PC) against myocardial stunning. Despite administration of SPT, in group I the deficit of WTh during stage II was 55% less on day 2 than on day 1 (P < 0.05). Similar results were obtained in three other rabbits treated with PD-115199 on day 1. In group II, pretreatment with CCPA during stage II failed to decrease the deficit of WTh on day 1. This study presents a new conscious rabbit model for studying myocardial stunning that is relatively inexpensive and technically less demanding than larger animal models. In this model, the development of late PC against myocardial stunning is not blocked by nonselective blockade of adenosine receptors with either SPT or PD115199, nor is it induced by activation of adenosine A(1) receptors with CCPA, indicating that adenosine receptors are not involved in the pathogenesis of this phenomenon.