Application of optical mapping techniques and fluorescent dyes to image membrane potential and other modalities requires a relatively immobile preparation. Pharmacological interventions that reduce motion artifact may also affect electrophysiology. The effect of 2,3-butanedione monoxime (BDM) (1, 5 and 20 mM) and cytochalasin-D (cyto-D) (1, 3 and 5 mM) on electrophysiology and contractility were assessed in Langendorff-perfused rabbit hearts (n = 4).
NZ White rabbits (1.5-2 kg) were killed by I.V. administration of sodium pentobarbitone (100 mg kg-1) with 1000 IU heparin. Monophasic action potentials (MAPs) were recorded from the basal epicardial surface of the left ventricle. MAP duration was measured at 90 % repolarisation (MAPD90). Conduction delay (CD) was measured as the time between right ventricular basal stimulus artifact and the MAP upstroke. Left ventricular developed pressure (LVDP) was expressed as a percentage of the control value. The effect of 20 mM BDM (n = 3) and 3 mM cyto-D (n = 4) on restitution was assessed with 16 S1 stimuli at 350 ms intervals followed by an extra stimulus S2. S1-S2 was increased incrementally from 70 to 600 ms. An exponential curve was fitted to a graph of MAPD90 against preceding diastolic interval.
BDM increased CD in a dose-dependent manner; cyto-D had a smaller but significant effect. MAPD90 was unaffected by BDM, but at 5 mM cyto-D caused a significant prolongation (Table 1). Both agents increased the time constant. Maximum MAPD90 was decreased in 20 mM BDM and increased in 3 mM cyto-D (Table 2).
Both BDM and cyto-D have substantial negative inotropic effects. Any flattening of the restitution curve by such agents may have anti-arrhythmic consequences.
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