Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA.
Commun Biol. 2022 Apr 6;5(1):319. doi: 10.1038/s42003-022-03279-y.
Investigation of the complex relationships and dependencies of multiple cellular processes that govern cardiac physiology and pathophysiology requires simultaneous dynamic assessment of multiple parameters. In this study, we introduce triple-parametric optical mapping to simultaneously image metabolism, electrical excitation, and calcium signaling from the same field of view and demonstrate its application in the field of drug testing and cardiovascular research. We applied this metabolism-excitation-contraction coupling (MECC) methodology to test the effects of blebbistatin, 4-aminopyridine and verapamil on cardiac physiology. While blebbistatin and 4-aminopyridine alter multiple aspects of cardiac function suggesting off-target effects, the effects of verapamil were on-target and it altered only one of ten tested parameters. Triple-parametric optical mapping was also applied during ischemia and reperfusion; and we identified that metabolic changes precede the effects of ischemia on cardiac electrophysiology.
研究控制心脏生理学和病理生理学的多个细胞过程的复杂关系和相互依存性需要同时动态评估多个参数。在本研究中，我们引入三重参数光学映射技术，从同一视场同时成像代谢、电兴奋和钙信号，并展示其在药物测试和心血管研究领域的应用。我们应用这种代谢-兴奋-收缩偶联（MECC）方法来测试 blebbistatin、4-氨基吡啶和维拉帕米对心脏生理学的影响。虽然 blebbistatin 和 4-氨基吡啶改变了心脏功能的多个方面，表明存在脱靶效应，但维拉帕米的作用是靶标相关的，它只改变了十个测试参数中的一个。三重参数光学映射也应用于缺血再灌注期间，我们发现代谢变化先于缺血对心脏电生理学的影响。
