Comparison of an <i>in vivo</i> Model with an <i>in vitro</i> Model Based on the Electrical Potential Decrease in the Myocardium or Myocardial Cells by an Extracellular Photosensitization Reaction

Abstract

In vivo 動物心筋モデルにおける talaporfin sodium を用いた細胞外光増感反応による電位減少を調査するために，酸 素環境を改善した in vitro 心筋細胞モデルを設定し，共通に使用できる評価基準を用いて比較した．電位計測は，in vivo モデルではイヌの薄い心房筋を対象とし，電極カテーテルを用いて行った．In vitro モデルでは膜電位感受性色素 を用いて細胞の膜電位計測を行った．In vitro モデルの酸素供給改善のため流路を作製し，反応領域中の溶液を 1 秒間 に約 3 回入れ替えた．In vivo および in vitro モデルにおいて，初期電位値の 1/e までの減少に必要な投入エネルギーの オーダーが一致したため， 本 in vitro 心筋細胞モデルは光増感反応による in vivo 心筋の電位減少の調査に有用と考える． キーワード：in vitro モデル，光増感反応，電気生理学，酸素供給の改善 Abstract To evaluate the electrical potential decrease in an in vivo animal myocardial model by oxidation induced by an extracellular photosensitization reaction using talaporfin sodium, the authors studied an in vitro myocardial cell model that has an irrigation system that improves the oxygen supply. To perform this evaluation, the authors compared the in vivo and in vitro models using a new metric to measure the electrophysiological effect on the myocardium/myocardial cells by a photosensitization reaction. The electrical potential in the myocardium on the inside surface of a canine superior vena cava of the in vivo model was measured by a multielectrode ring catheter. In the in vitro model, the spontaneous action potential waveforms were measured using a voltagesensitive dye. The model used a flowing talaporfin sodium solution-at a rate of approximately three replacements per secondto improve the oxygen supply in the area of the photosensitization reaction. A new metric-the radiant exposure required to decrease the electrophysiological signal to 1/e of its initial value-was used to compare the electrophysiological effects on