The electrophysiological and mechanical effects of 2,3-butane-dione monoxime and cytochalasin-D in the Langendorff perfused rabbit heart.
Procedures that reduce contraction are used to facilitate optical measurements of membrane potential, but it is unclear to what extent they affect the excitability of the heart. This study has examined the electrophysiological consequences of a range of extracellular [Ca2+] (0.7-2.5 mmol l(-1)), 2,3-butane-dione monoxime (BDM; 1-20 mmol l(-1)) and cytochalasin-D (Cyto-D; 1-5 micromol l(-1)).


METHODS
Monophasic action potentials (MAPs) were recorded from the basal epicardial surface of the left ventricle of isolated rabbit hearts. Conduction delay (CD) and time to 90% repolarisation of the monophasic action potential (MAPD90) were measured. The effects of BDM and Cyto-D on restitution were studied at a [Ca2+] of 1.9 mmol l(-1). Restitution curves for MAPD90 were generated using a standard S1-S2 protocol.


RESULTS
All manoeuvres decreased left ventricular developed pressure (LVDP): 0.7 mmol l(-1) Ca2+ to 74.0 +/- 6.1%, 20 mmol l(-1) BDM to 4.5 +/- 1.0%, and 5 micromol l(-1) Cyto-D to 12.8 +/- 3.5% of control value. CD decreased from a control value (33.3 +/- 1.0 ms, n= 16) to 93.0 +/- 2.2% in 0.7 mmol l(-1) Ca2+, but increased to 133.7 +/- 10.5% in 20 mmol l(-1) BDM and 127.4 +/- 10.6% in 5 micromol l(-1) Cyto-D. At 350 ms pacing cycle length, MAPD90 (control = 119.6 +/- 1.7 ms n= 16) was prolonged by reduced extracellular [Ca2+]. BDM had no effects on MAPD90 at control pacing rates. Cyto-D caused a significant prolongation (to 115.0 +/- 3.0% of control, n= 6) at the highest concentration studied (5 micromol l(-1)). Both BDM (20 mmol l(-1)) and Cyto-D (3 micromol l(-1)) flattened the restitution curves but neither agent altered maximum MAPD90.


CONCLUSIONS
Extracellular [Ca2+] of 1.9 mmol l(-1) in conjunction with a moderate dose of Cyto-D (3 micromol l(-1)) reduced contractility with minimal effects on action potential duration and conduction at a fixed pacing cycle length. However, both BDM and Cyto-D had pronounced effects on electrical restitution.
Kettlewell
S
S
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK.
Walker
N L
NL
Cobbe
S M
SM
Burton
F L
FL
Smith
G L
GL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009431:Neural Conduction / Q000187:drug effects; D055095:Optics and Photonics; D009994:Osmolar Concentration; D010477:Perfusion; D011312:Pressure; D011817:Rabbits; D011930:Reaction Time / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D004791:Enzyme Inhibitors; C004717:diacetylmonoxime; D015638:Cytochalasin D; D003931:Diacetyl; D002118:Calcium