No abstract

Background-Abnormal intercellular communication caused by connexin dysfunction may be involved in atrial fibrillation (AF). The present study assessed the effect of the gap junctional conduction-enhancing peptide rotigaptide on AF maintenance in substrates that result from congestive heart failure induced by 2-week ventricular tachypacing (240 bpm), atrial tachypacing (ATP; 400 bpm for 3 to 6 weeks), and isolated atrial myocardial ischemia. Methods and Results-Electrophysiological study and epicardial mapping were performed before and after rotigaptide administration in dogs with ATP and congestive heart failure, as well as in similarly instrumented sham dogs that were not tachypaced. For atrial myocardial ischemia, dogs administered rotigaptide before myocardial ischemia were compared with no-drug myocardial ischemia controls. ATP significantly shortened the atrial effective refractory period (Pϭ0.003) and increased AF duration (Pϭ0.008), with AF lasting Ͼ3 hours in all 6-week ATP animals. Rotigaptide increased conduction velocity in ATP dogs slightly but significantly (Pϭ0.04) and did not affect the effective refractory period, AF duration, or atrial vulnerability. In dogs with congestive heart failure, rotigaptide also slightly increased conduction velocity (Pϭ0.046) but failed to prevent AF promotion. Rotigaptide had no statistically significant effects in sham dogs. Myocardial ischemia alone increased AF duration and impaired conduction (based on conduction velocity across the ischemic border and indices of conduction heterogeneity). Rotigaptide prevented myocardial ischemiainduced conduction slowing and AF duration increases. Conclusions-Rotigaptide improves conduction in various AF models but suppresses AF only for the acute ischemia substrate. These results define the atrial antiarrhythmic profile of a mechanistically novel antiarrhythmic drug and suggest that gap junction dysfunction may be more important in ischemic AF than in ATP remodeling or congestive heart failure substrates. (Circulation. 2007;115:310-318.)

The antiarrhythmic and cardioprotective effect of increasing gap junction intercellular communication during ischemia/ reperfusion injury has not been studied.

Five weeks after common bile duct ligation (CBL), Wistar rats had histologically verified liver cirrhosis with sodium retention but without ascites. Plasma concentrations of vasopressin and aldosterone were normal. Glomerular filtration rate was unchanged, although renal plasma flow was increased. A test dose of furosemide (7.5 mg/kg body wt iv) produced significantly greater diuretic (+59%) and natriuretic (+66%) responses in Wistar CBL rats than in sham-operated controls. Stereological examination of kidneys demonstrated a 47% increase in the volume of the inner stripe of the outer medulla, with a 55% increase in the volume of thick ascending limb of Henle's loop (TALH) epithelium in cirrhotic Wistar rats relative to controls. CBL produced a similar degree of liver cirrhosis in vasopressin-deficient Brattleboro rats. However, both functional and structural renal changes observed in cirrhotic Wistar rats were absent in vasopressin-deficient cirrhotic Brattleboro rats. These results suggest a permissive action of vasopressin for the adaptive changes in TALH in rats with experimental liver cirrhosis. Our results are consistent with the hypothesis that increased sodium chloride reabsorption in the TALH may contribute to the early sodium retention that precedes ascites formation in rats with secondary biliary liver cirrhosis.

ZP123 has no effects on atrial conduction during physiological conditions, but it selectively prevents atrial conduction slowing during metabolic stress.

No abstract

No abstract

Aims We aimed to investigate whether left atrial (LA) markers from cardiovascular magnetic resonance (CMR) were able to predict atrial fibrillation (AF) in elderly patients with risk factors for stroke. Methods and results At baseline, 203 participants with stroke risk factors but without history of AF underwent advanced CMR and received an implantable loop recorder. During a median of 40 (37–42) months of continuous monitoring, incident AF was detected in 79 patients (39%). With regards to CMR markers, a steep increase in incidence rate of AF was seen with LA maximum volume (LAmax) above 55 mL/m2, LA minimum volume (LAmin) above 30 mL/m2, LA total emptying fraction (LA TEF) below 45%, LA active emptying fraction (LA AEF) below 37%, LA strain S below 25%, LA strain A below 17%, and LA strain rate A above −1.7 s−1. After multivariate adjustment, the above-mentioned CMR markers remained associated with AF incidence: hazard ratio (95% confidence interval) 1.25 (1.06–1.48) and 1.51 (1.22–1.87) per 10 mL/m2 increase of LAmax and LAmin, respectively, 1.49 (1.26–1.76) and 1.46 CI (1.25–1.71) per 5% decrease in LA TEF and LA AEF, respectively, 1.23 (1.05–1.44) and 1.56 (1.18–2.06) per 5% decrease in LA strain S and A, respectively, and 2.06 (1.31–3.23) per s−1 increase in LA strain rate A. In prediction analyses, LA functional indices increased area under the receiver operating characteristic curve significantly. Conclusion The risk of AF, including asymptomatic AF, increases significantly with increasing LA volumes and worsening LA function.