Manthei S A, Reiling C M, Van Wylen D G
Department of Biology, St. Olaf College, Northfield, MN, USA.
Cardiovasc Res. 1998 Jan;37(1):171-8. doi: 10.1016/s0008-6363(97)00213-7.
The purpose of this study was: 1) to evaluate a dual microdialysis technique coupled with local drug administration in the regionally ischemic rabbit heart, and; 2) to assess the ischemia-induced changes in interstitial fluid (ISF) adenosine during inhibition of adenosine deaminase or adenosine kinase.
Two microdialysis probes were implanted parallel to each other and separated by 5 mm in myocardium perfused by a branch of the left coronary artery. Probes were used to sample myocardial ISF and to deliver drugs locally to the myocardium; purine metabolite concentrations in the collected dialysate were used as indices of ISF levels. Three groups of pentobarbital-anesthetized rabbits were studied. In a control group (n = 6), both probes were perfused with Krebs-Henseleit buffer. In the second and third groups, one probe was perfused with buffer, whereas the other probe was perfused with buffer containing 1 mM erythro-2-(2-hydroxy-3-nonyl)adenine (EHNA) (n = 5), an adenosine deaminase inhibitor, or 10 microM iodotubercidin (n = 9), an adenosine kinase inhibitor. All animals were exposed to 30 min of regional myocardial ischemia followed by 60 min of reperfusion.
In the control group, similar increases in dialysate purine metabolites during ischemia were observed in both probes. Locally administered EHNA increased dialysate adenosine prior to ischemia and decreased dialysate inosine and hypoxanthine. During ischemia, the increase in dialysate adenosine in the EHNA-perfused probe was markedly augmented, while the increases in inosine and hypoxanthine were attenuated. In contrast, local infusion of iodotubercidin did not alter dialysate purine metabolites before ischemia, but there was a modest augmentation of adenosine during ischemia. These data illustrate the feasibility of dual microdialysis for assessing the effect of locally administered compounds on interstitial metabolite concentration in the regionally ischemic rabbit heart. Furthermore, adenosine deaminase inhibition has a more profound adenosine augmenting effect than adenosine kinase inhibition in the rabbit heart.
本研究的目的是：1）评估在局部缺血兔心脏中结合局部给药的双微透析技术；2）评估在抑制腺苷脱氨酶或腺苷激酶期间缺血诱导的间质液（ISF）腺苷变化。
在由左冠状动脉分支灌注的心肌中，将两个微透析探针彼此平行植入，相距5毫米。探针用于采集心肌ISF并将药物局部递送至心肌；收集的透析液中嘌呤代谢物浓度用作ISF水平的指标。研究了三组戊巴比妥麻醉的兔子。在对照组（n = 6）中，两个探针均用Krebs-Henseleit缓冲液灌注。在第二组和第三组中，一个探针用缓冲液灌注，而另一个探针用含有1 mM 赤藓红-2-（2-羟基-3-壬基）腺嘌呤（EHNA）（n = 5）的缓冲液灌注，EHNA是一种腺苷脱氨酶抑制剂，或用10 μM碘结核菌素（n = 9）灌注，碘结核菌素是一种腺苷激酶抑制剂。所有动物均经历30分钟的局部心肌缺血，随后再灌注60分钟。
在对照组中，两个探针在缺血期间透析液嘌呤代谢物均有相似的增加。局部施用的EHNA在缺血前增加了透析液腺苷，并降低了透析液肌苷和次黄嘌呤。在缺血期间，用EHNA灌注的探针中透析液腺苷的增加明显增强，而肌苷和次黄嘌呤的增加则减弱。相比之下，局部输注碘结核菌素在缺血前未改变透析液嘌呤代谢物，但在缺血期间腺苷有适度增加。这些数据说明了双微透析用于评估局部给药化合物对局部缺血兔心脏中间质代谢物浓度影响的可行性。此外，在兔心脏中，抑制腺苷脱氨酶比抑制腺苷激酶对腺苷的增强作用更显著。
