March 1, 1990Journal of Cardiovascular Pharmacology
Profibrillatory Actions of Pinacidil in a Conscious Canine Model of Sudden Coronary Death
Why the study?
Does pinacidil increase the incidence of ventricular fibrillation in a postinfarcted canine model during acute ischemia?
Population
Conscious canine model of sudden coronary death, n=31.
Comparison
Pinacidil 0.3 mg/kg/h i.v. for 6 h vs Vehicle-treated control
Design
Preclinical
Follow-up
24 hours
Authors
Discussion
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Implication
Pinacidil may heighten VF risk during acute ischemia in postinfarct models; leaves open human relevance of KATP modulation.
Key Points
- To determine whether the potassium channel opener pinacidil alters cardiac electrophysiology and predisposes postinfarcted hearts to lethal ventricular tachyarrhythmias during subsequent acute ischemia.
- Conscious dogs with subacute anterior myocardial infarction uninducible by programmed electrical stimulation (PES) were infused with pinacidil (0.3 mg/kg/h i.v. for 6 h) or vehicle.
- Electrophysiological testing with PES was repeated, followed by induction of acute posterolateral ischemia at a site remote from the prior infarction.
- Electrophysiological parameters, incidence of ventricular fibrillation within 1 hour, and 24-hour cumulative mortality were recorded.
- Pinacidil did not increase inducibility by PES compared to control (nonsustained ventricular tachyarrhythmia in 2/15 pinacidil vs 1/16 control; p = 0.96).
- Acute remote ischemia caused ventricular fibrillation within 1 hour in 9/15 (60%) pinacidil-treated dogs versus 1/15 (6.7%) vehicle controls (p = 0.007), with 24-hour mortality reaching 13/15 (87%) versus 3/15 (20%; p = 0.001).
- Pinacidil increased heart rate from 124 ± 6 to 143 ± 10 beats/min (p < 0.05) and reduced refractory periods in normal myocardium (178 ± 2 to 166 ± 4 ms, p < 0.05) and peri-infarct regions (p < 0.01).
Structured PICO
Does pinacidil increase the incidence of ventricular fibrillation in a postinfarcted canine model during acute ischemia?
P
Population
Conscious canine model of sudden coronary death (postinfarcted dogs unresponsive to programmed electrical stimulation and at low risk of ventricular fibrillation in response to acute posterolateral ischemia), n=31 (15 pinacidil, 16 control).
I
Intervention
Pinacidil 0.3 mg/kg/h i.v. for 6 h
C
Comparator
Vehicle-treated control
O
Outcome
Incidence of ventricular fibrillation within 1 h from the onset of acute ischemiahard clinical
Pinacidil increases the potential for ventricular fibrillation and mortality during acute ischemia in a postinfarcted canine model, likely due to reduced ventricular refractory periods.
Cite This Study
Chi et al. (1990) studied this question.