Fukunami M, Yellon D M, Kudoh Y, Maxwell M P, Wyse R K, Hearse D J
Can J Cardiol. 1987 Mar;3(2):94-103.
To characterize the temporal and spatial characteristics of transmural gradients of flow, ATP and CP, dogs (n = 17) were subjected to coronary artery ligation for either 30 minutes or 24 hours. Different radioactive microspheres were given at the onset and end of the ischemic period. Simultaneous multiple transmural biopsies (up to 20 per heart) were obtained (in situ freezing) from central ischemic and surrounding normal tissue after either 30 minutes or 24 hours of elapsed ischemia. After lyophilization each biopsy was divided into up to 6 transmural sub-fragments, each of which was analysed for flow, ATP and CP. At the onset of ischemia flow declined to less than 15% throughout the ischemic zone and there was a slight transmural gradient of flow from epi- to endocardium (12.4 +/- 1.6, 13.5 +/- 2.0, 11.0 +/- 1.8, 10.3 +/- 1.7, 8.5 +/- 1.9 and 8.3 +/- 3.1% of non-ischemic tissue). After 30 minutes of ischemia, collateral flow to the epicardial tissue had increased substantially but endocardial flow remained unchanged, the epi- to endo- gradient was 20.8 +/- 2.5, 18.9 +/- 2.4, 13.7 +/- 2.1, 10.8 +/- 1.5, 8.5 +/- 1.2, 7.6 +/- 1.7. After 24 hours there were further increases in the epi- and mid- myocardial regions but the endocardial flow remained severely depressed, the epi- to endo- gradient was 23.9 +/- 3.2, 24.5 +/- 3.0, 23.6 +/- 4.8, 16.4 +/- 3.3, 9.8 +/- 2.9, 5.8 +/- 2.9%. ATP and CP were severely depressed after 30 minutes of ischemia and reflected flow closely with sharp linear epi- to endo- gradients (17.5 to 10.9 muMol/g dry wt for ATP and 7.4 to 3.1 muMol/g dry wt for CP). After 24 hours, the decline in ATP had been slowed and there was a striking recovery of CP in the epi- and mid- myocardial regions which had experienced increasing collateral flow. CP in the endocardium remained severely depressed. Progressive supplementation of collateral flow early and throughout a 24 hour period of regional myocardial ischemia and the selective delivery of this flow to subepi- and mid- myocardial tissue accounts in part for the natural salvage of this tissue and the deterioration of the endocardium to necrosis. Gradients of flow and metabolism further influence these events and account for the "wave front" of cell death.
为了描述血流、三磷酸腺苷(ATP)和磷酸肌酸(CP)跨壁梯度的时空特征,对17只犬进行冠状动脉结扎,时长分别为30分钟或24小时。在缺血期开始和结束时给予不同的放射性微球。在缺血30分钟或24小时后,从中央缺血组织和周围正常组织获取同步多次跨壁活检标本(每颗心脏最多20个)(原位冷冻)。冻干后,每个活检标本被分成多达6个跨壁亚片段,分别分析其血流、ATP和CP。缺血开始时,整个缺血区血流降至不足15%,并且存在从心外膜到心内膜的轻微跨壁血流梯度(分别为非缺血组织的12.4±1.6%、13.5±2.0%、11.0±1.8%、10.3±1.7%、8.5±1.9%和8.3±3.1%)。缺血30分钟后,流向心外膜组织的侧支血流显著增加,但心内膜血流保持不变,心外膜到心内膜的梯度为20.8±2.5%、18.9±2.4%、13.7±2.1%、10.8±1.5%、8.5±1.2%、7.6±1.7%。24小时后,心外膜和心肌中层区域的血流进一步增加,但心内膜血流仍严重降低,心外膜到心内膜的梯度为23.9±3.2%、24.5±3.0%、23.6±4.8%、16.4±3.3%、9.8±2.9%、5.8±2.9%。缺血30分钟后,ATP和CP严重降低,并与血流密切相关,呈现出从心外膜到心内膜的陡峭线性梯度(ATP为17.5至10.9微摩尔/克干重,CP为7.4至3.1微摩尔/克干重)。24小时后,ATP的下降减缓,并且在经历侧支血流增加的心外膜和心肌中层区域CP有显著恢复。心内膜中的CP仍严重降低。在区域性心肌缺血的24小时期间早期及整个过程中,侧支血流逐渐增加,并选择性地流向心外膜下和心肌中层组织,这在一定程度上解释了该组织的自然挽救以及心内膜恶化至坏死的原因。血流和代谢梯度进一步影响这些事件,并解释了细胞死亡的“波阵面”。