ABSTRACT
BACKGROUND: Atrial natriuretic peptide (ANP), which is released by the heart in response to acute cardiac stretch, possesses cardiac electrophysiological properties that include modulation of ion channel function and repolarization. However, data regarding whether ANP can directly modulate electrical instability or arrhythmias are largely lacking. OBJECTIVE: This study sought to determine whether ANP modifies onset or electrophysiological characteristics of ventricular fibrillation (VF) induced by severe hypokalemia in an isolated heart model. METHODS: Langendorff-perfused rabbit hearts in the absence and presence of 10 nM ANP (n = 9 in each group) were subjected to a low potassium (K+) perfusate (1.2 mM K+). Left ventricular (LV) epicardial monophasic action potential (MAP) and pressure were monitored continuously. Incidence and time to onset of VF and dominant frequency during VF determined by spectral analysis were evaluated. RESULTS: ANP did not alter ventricular repolarization (MAP duration) or LV pressure during perfusion with physiologic, K+-containing solution. Within the first 30 s after low K+ perfusion, ANP accelerated the onset of beat-to-beat repolarization alternans (100% vs. 33% in ANP-treated vs. non-treated hearts, p < 0.01). During low K+ perfusion, the incidence of VF did not differ between ANP-treated and non-treated hearts (8 of 9 [89%] in each group). However, VF occurred sooner (3.75 ± 0.33 vs. 5.78 ± 0.70 min, P < 0.05) and immediately after VF onset, peak dominant frequency was higher (24.1 ± 7.3 vs. 14.2 ± 2.3 Hz, P = 0.01) in ANP-treated than in non-treated hearts. CONCLUSIONS: ANP accelerates initiation of VF and increases maximum dominant frequency during VF in isolated hearts subjected to severe hypokalemia.
