title: A proposed mechanism for cardiac sensitisation: electrophysiological study of effects of difluorodichloromethane and adrenaline on different types of cardiac preparations isolated from sheep hearts.
abstract: Difluorodichloromethane (FC12) inhaled at high concentrations sensitises, as do numerous other volatile organic compounds, mammalian heart to adrenaline induced arrhythmias. In this study three types of cardiac tissue (spontaneously beating sinusal and Purkinje preparations and stimulated Purkinje fibres) were isolated from sheep hearts and perfused for electrophysiological recording to examine the effect of FC 12. Preparations were perfused alternately with a control solution of physiological fluid and a trial solution with dissolved FC 12, the partial pressure of oxygen remaining identical. Sensitisation to adrenaline was studied by injecting adrenaline at a dose causing a notable effect without producing arrhythmias in the control preparations. Examination of transmembrane potential recordings confirmed that FC 12 inhibits sinus node pacemaker stimulation by adrenaline. Conversely, the adrenaline induced acceleration of latent pacemakers in certain types of Purkinje fibres appeared to be potentialised by FC 12. The various types of arrhythmia observed in vitro were explained by the effect of FC 12 on cell membranes, an affect which can oppose or favour that of adrenaline. These phenomena explain the arrhythmias observed in isolated hearts or whole animal preparations and permit a better understanding of the mechanism involved in cardiac sensitisation to adrenaline induced arrhythmia, a mechanism in which variability in time and location is the essential factor in the FC 12 effect.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000335:Aerosol Propellants / Q000009:adverse effects* / Q000494:pharmacology; D000336:Aerosols / Q000009:adverse effects*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002462:Cell Membrane / Q000187:drug effects; D005617:Chlorofluorocarbons, Methane / Q000009:adverse effects* / Q000494:pharmacology; D004562:Electrocardiography; D004837:Epinephrine / Q000009:adverse effects* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D011690:Purkinje Fibers / Q000187:drug effects; D012756:Sheep
chemical_list: D000335:Aerosol Propellants; D000336:Aerosols; D005617:Chlorofluorocarbons, Methane; C007782:dichlorodifluoromethane; D004837:Epinephrine