Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model

Introduction We examined the acute effects of neutral endopeptidase inhibitor on the hemodynamics and electrical properties of dogs subjected to rapid atrial pacing. Methods Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration. Before and after the 6 hours rapid atrial pacing from the right atrial appendage, the hemodynamics, atrial effective refractory period, and monophasic action potential duration of the right atrial appendage were measured and blood samples were collected. Atrial tissue was also excised after the experiment. Results Candoxatril significantly increased plasma ANP levels (Control: 88.4 ± 50.25 vs. Candoxatril: 197.1 ± 32.09 pg/ml, p = 0.004) and prevented reductions in atrial effective refractory period and monophasic action potential duration. We further demonstrated that the treated animals exhibited significantly higher levels of atrial tissue cyclic GMP (Control: 28.1 ± 1.60 fmol/mg vs. Candoxatril: 44.5 ± 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 ± 5.5 vs. Candoxatril: 42 ± 7.1 pg/ml, p = 0.028). Conclusion Candoxatril suppressed the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model. As plasma ANP and the atrial tissue levels of cyclic GMP were higher in the Candoxatril group than the control, this effect was considered to appear through the reduction of calcium overload caused by ANP and cyclic GMP

Effect of nifekalant on life-threatening ventricular arrhythmias in patients with cardiopulmonary resuscitation or during the perioperative state

Background: Nifekalant is a unique class III anti-arrhythmic agent with a strong effect on prolonging the myocardial refractoriness, but its clinical effect is still unclear. In this study, we evaluated the effect of nifekalant on life-threatening ventricular arrhythmias and compared the clinical background between the effective and non-effective patients in order to clarify the clinical factors which may have an influence on the efficacy of nifekalant. Methods: The study population consisted of 47 consecutive patients who underwent nifekalant administration for life-threatening ventricular arrhythmias (VT/VF). Their clinical characteristics and ECG parameters were retrospectively compared between patients with and without an effective result with the nifekalant administration. Results: Nifekalant was effective for refractory VT/VF in 26/47 patients. There was no significant difference in the age, gender or left ventricular ejection fraction, but the incidence of ischemic heart disease was higher in the effective group (17/26) than non-effective group (9/21, p = 0.004). The incidence of in-hospital events was higher in the effective group than non-effective group (20/26 vs 10/21, p = 0.037). A significant prolongation in the QTc interval was observed in all patients and the degree of QTc prolongation was greater in the effective group than in the non-effective group (0.46 ± 0.04 vs 0.43 ± 0.02 sec1/2, p = 0.026). Conclusion: Nifekalant was effective in 55% of the patients for refractory VT/VF. It was considered that nifekalant was more effective for patients with ischemic heart disease, during the perioperative period or in those experiencing in-hospital events. The prolongation of the QTc interval might also be useful as an index for the efficacy of nifekelant administration

Morphological Properties of Atrial Fibrillation Waves in Patients with Left Ventricular Dysfunction—Spectral Analysis of Atrial Fibrillation Waves in Dilated Cardiomyopathy—

AbstractIntroduction: Although the atrial fibrillation cycle length (FCL) is considered to shorten in persistent atrial fibrillation (AF) as a result of electrical remodeling, whether a long-term change remains in FCL in patients with left ventricular (LV) dysfunction is uncertain. Morphological properties of AF waves were analyzed in patients with dilated cardiomyopathy (DCM). Methods and Results: The study population consisted of 43 patients with persistent AF, and they were divided into a DCM group (n = 14) and a control group (n = 29). Fibrillation waves from surface ECG lead V1 were purified by subtracting the QRS-T complex template. Power spectral analysis was performed by Fast Fourier Transformation, and the mean FCL was determined by the peak power frequency in 20 epochs at each recording. The LV ejection fraction was lower in the DCM group (50 ± 18%) than the control (63 ± 8%, p = 0.001). The mean FCL was shorter in the DCM group (132 ± 14 ms) than the control (151 ± 23 ms, p = 0.007) and there was a significant correlation between the FCL and LV dimensions (p = 0.03). Conclusion: In patients with persistent AF and LV dysfunction, FCL was shorter in comparison with the control, and seemed to be influenced by LV dimensions