Development of methods to evaluate myocardial phosphoinositide turnover using positron emitter labeled compounds

我们推测蛋白激酶C（PKC）在大鼠心肌梗死后左室重构中被激活。我们用[H-3]佛波醇12，13-二丁酸酯（PDBu）体外放射自显影法测定了大鼠心肌局部膜蛋白激酶C（PKC）。使用成像板和计算机辅助图像处理系统（参考文献1）。分别于结扎左冠状动脉后1、3、7、21、10个月取出心脏。我们发现，[H-3] PDBu结合在梗死区比非梗死区术后7天增加，并保持高于非梗死区，直到21天后。组织学检查显示，大量的成纤维细胞样细胞存在于[H-3] PDBu结合增加的部位。此外，我们研究了[C-11]或[F-18]甘油二酯是否能在注射后30分钟追踪大鼠心肌磷脂酰肌醇转换（PI转换），这与PKC激活密切相关。 关于我们 n.在注射[C-11]二酰甘油的大鼠心肌中，掺入PI转换中间体的放射性占主导地位。在注射[F-18]二酰基甘油的大鼠中，PI周转的中间体不是主要代谢产物。最后，我们还进行了体内放射自显影大鼠注射[C-11]甘油二酯7天后，冠状动脉结扎。梗塞区放射自显影强度较非梗塞区有增高趋势。这些结果表明，PI周转和PKC在梗死区被激活，成纤维细胞样细胞可能是负责这些增加的活动。我们已经使用正电子发射断层扫描证明心肌病患者存在心肌代谢异常（参考文献2）。我们的研究结果还表明，正电子发射体标记的化合物和正电子发射断层扫描有一个潜在的作用，在可视化的异常区域信号转导以及代谢异常的各种心脏病患者。少

We hypothesized that protein kinase C (PKC) is activated in left ventricular remodeling after myocardial infarction in rats. We measured the regional myocardial membranous PKC using in vitro autoradiography with [H-3] phorbol 12,13-dibutyrate (PDBu) in rats. Imaging plates and a computer-assisted image processing system were used (Ref. 1). The heart was removed 1,3,7,21 days, and 10 months after left coronary artery ligation. We found that [H-3] PDBu binding was increased in the infarcted region compared with the non-infarcted region 7 days after operation and remained higher than the non-infarcted region until 21 days after. Histological examination revealed that abundant fibroblast-like cells were present at the sites with the increased [H-3] PDBu binding. Furthermone, we investigated whether [C-11] diacylglycerol or [F-18] diacylglycerols could trace the myocardial phosphoinositide turnover (PI turnover), which closely relates to PKC activation, in rats 30 minutes after the injectio … More n. The radioactivity incorporated into the intermediates of PI turnover was predominant in the myocardium of rats injected with [C-11] diacylglycerol. In rats injected with [F-18] diacylglycerols, the intermediates of PI turnover were not the main metabolites. Finally, we also performed in vivo autoradiography in rats injected with [C-11] diacylglycerol 7 days after coronary artery ligation. The autoradiographic intensity at the infarcted regions tended to increase compared with that in the non-infarcted region. These results suggest that PI turnover and PKC was activated at the infarcted region, and that fibroblast-like cell may be responsible for these increased activity. We have shown that myocardial metabolic abnormality in patients with cardiomyopathy using positron emission tomography (Ref. 2). Our results also suggest that positron emitter labeled compounds and positron emission tomography have a potential role in visualizing the abnormalities of regional signal transduction as well as metabolic abnormalities in various heart disease patients. Less