Weak Spots Inside the Myocardium of a Langendorff Rat Heart Observed by Nadh Videofluorometry

Abstract

Myocardial function is highly dependent on an aerobic metabolism and can only be maintained when the oxygen delivery is more than the oxygen demand. Dysoxia occurs when the demand of oxygen by the heart exceeds that being supplied through the myocardial vasculature. Hypoperfusion of the myocardium causes a marked heterogeneity of well and less well perfused areas. These areas have been shown to be anatomically defined by the properties of the myocardial microvasculature (King et al. 1985, Franzen et al. 1988, Ince et al. 1993, Rakusan et al. 1994, Duling 1994). The properties of these dysoxic areas under different physiological conditions have been most studied by NADH fluorescence imaging techniques (Barlow et al. 1976, Steenbergen et al. 1977, Ince et al. 1993, Vetterlein et al. 1995). The NADH fluorescence technique was introduced by Chance and makes use of the fluorescence properties of mitochondrial NADH for the measurement of mitochondrial energy state of tissue cells in situ (Chance et al. 1976). NADH is situated at the high-energy side of the respiratory chain and during dysoxia accumulates in concentration because less NADH is oxidised to NAD⁺. Episodes of high cardiac oxygen consumption, as occurs during high work rates, causes reduction of NADH levels (Osbakken 1994, Ashruf et al. 1995). The optical properties of NADH and NAD⁺ clearly differ. Upon excitation with UV-light (365 nm) NADH, unlike NAD⁺, fluoresces at the 460 nm light (blue). Under borderline hypoxic conditions imaging the distribution of NADH in the heart surface shows a heterogeneous distribution of well, and less well perfused areas. The less well perfused areas we have termed as cardiac “weak spots” since they are first to become dysoxic when the heart becomes comprised such as occurs during severe tachycardia (Ince et al. 1993) or during severe vasoconstriction as occurs during nitric oxide synthesis inhibition in endotoxemic hearts (Avontuur et al. 1995).