Hypoxic Region of Guinea Pig and Ferret Papillary Muscles

Papillary muscles were mounted in a three-compartment bath. The tip of the muscle was exposed to hypoxic and glucose-free solution. The other parts of the preparation were superfused with Tyrode's solution, building a free-flow border between hypoxic and normoxic superfusates. The normoxic part of the bath was subdivided by a rubber membrane so that current pulses could be applied between segments of the preparation. Signs of electrotonic interaction between nonnoxic and hypoxic parts were observed a few minutes after the onset of hypoxia. Transmembrane action potentials in the normoxic part retained their plateau, but progressively shortened. Those in the hypoxic tip showed an early phase of rapid repolarizan'on followed by a plateau phase near the resting potential. Terminal repolarization in the two parts coincided for many minutes. After 35 minutes, fast propagated activity ceased in the tip and was replaced first by conducted slow responses, then by decremental conduction. At 50 minutes, cells near the borderline had resting potentials of either —76 ± 7 mV (SD, n = 9) in normoxic tissue or —16 ± 3 mV (SD, n = 9) in hypoxic tissue. Concurrently, subthreshold potentials no longer appeared to spread into the tip. Unipolar electrograms remained diphasic over the normoxic part but lost their negative deflection near the borderline, implying the absence of axial current flow into the hypoxic part. Furthermore, electrotonic potentials generated by current flow across the rubber membrane did not spread beyond a line of demarcation. Reduced nicotinamide adenine dinucleotide fluorescence increased in the hypoxic part, and appeared to correlate with the development of electrical decoupling. It is concluded that decoupling progresses gradually, but eventually results in a sharp borderline between regions of normoxic and hypoxic superfusion. (Circ Res 56: 876883, 1985)