{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Filgueiras-Rama D"],"funding":["NHLBI NIH HHS"],"pagination":["561-70"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3380168"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(3)"],"pubmed_abstract":["<h4>Background</h4>Blockade of inward-rectifier K+ channels by chloroquine terminates reentry in cholinergic atrial fibrillation (AF). However, it is unknown whether inward-rectifier K+ channels and reentry are also important in maintaining stretch-induced AF (SAF). We surmised that reentry underlies SAF, and that abolishing reentry with chloroquine terminates SAF more effectively than traditional Na+-channel blockade by flecainide.<h4>Methods and results</h4>Thirty Langendorff-perfused sheep hearts were exposed to acute and continuous atrial stretch, and mapped optically and electrically. AF dynamics were studied under control and during perfusion of either chloroquine (4 µmol/L, n=7) or flecainide (2-4 µmol/L, n=5). Chloroquine increased rotor core size and decreased reentry frequency from 10.6±0.7 Hz in control to 6.3±0.7 Hz (P<0.005) just before restoring sinus rhythm (7/7). Flecainide had lesser effects on core size and reentry frequency than chloroquine and did not restore sinus rhythm (0/5). Specific IKr blockade by E-4031 (n=7) did not terminate AF when frequency values were >8 Hz. During pacing (n=11), flecainide reversibly reduced conduction velocity (≈30% at cycle length 300, 250, and 200 ms; P<0.05) to a larger extent than chloroquine (11% to 19%; cycle length, 300, 250, and 200 ms; P<0.05). Significant action potential duration prolongation was demonstrable only for chloroquine at cycle length 300 (12%) and cycle length 250 ms (9%) (P<0.05).<h4>Conclusions</h4>Chloroquine is more effective than flecainide in terminating SAF in isolated sheep hearts by significantly increasing core size and decreasing reentry frequency. Chloroquine's effectiveness may be explained by its inward-rectifier K+ channel blockade profile and suggest that reentry is important to maintain acute SAF."],"journal":["Circulation. Arrhythmia and electrophysiology"],"pubmed_title":["Chloroquine terminates stretch-induced atrial fibrillation more effectively than flecainide in the sheep heart."],"pmcid":["PMC3380168"],"funding_grant_id":["P01-HL039707","P01-HL087226","R01 HL087055","R01 HL080159","P01 HL039707","K99HL105574","P01 HL087226","K99 HL105574"],"pubmed_authors":["Ennis SR","Berenfeld O","Yamazaki M","Calvo CJ","Filgueiras-Rama D","Martins RP","Jalife J","Mironov S","Noujaim SF","Bandaru K","Kalifa J"],"additional_accession":[]},"is_claimable":false,"name":"Chloroquine terminates stretch-induced atrial fibrillation more effectively than flecainide in the sheep heart.","description":"<h4>Background</h4>Blockade of inward-rectifier K+ channels by chloroquine terminates reentry in cholinergic atrial fibrillation (AF). However, it is unknown whether inward-rectifier K+ channels and reentry are also important in maintaining stretch-induced AF (SAF). We surmised that reentry underlies SAF, and that abolishing reentry with chloroquine terminates SAF more effectively than traditional Na+-channel blockade by flecainide.<h4>Methods and results</h4>Thirty Langendorff-perfused sheep hearts were exposed to acute and continuous atrial stretch, and mapped optically and electrically. AF dynamics were studied under control and during perfusion of either chloroquine (4 µmol/L, n=7) or flecainide (2-4 µmol/L, n=5). Chloroquine increased rotor core size and decreased reentry frequency from 10.6±0.7 Hz in control to 6.3±0.7 Hz (P<0.005) just before restoring sinus rhythm (7/7). Flecainide had lesser effects on core size and reentry frequency than chloroquine and did not restore sinus rhythm (0/5). Specific IKr blockade by E-4031 (n=7) did not terminate AF when frequency values were >8 Hz. During pacing (n=11), flecainide reversibly reduced conduction velocity (≈30% at cycle length 300, 250, and 200 ms; P<0.05) to a larger extent than chloroquine (11% to 19%; cycle length, 300, 250, and 200 ms; P<0.05). Significant action potential duration prolongation was demonstrable only for chloroquine at cycle length 300 (12%) and cycle length 250 ms (9%) (P<0.05).<h4>Conclusions</h4>Chloroquine is more effective than flecainide in terminating SAF in isolated sheep hearts by significantly increasing core size and decreasing reentry frequency. Chloroquine's effectiveness may be explained by its inward-rectifier K+ channel blockade profile and suggest that reentry is important to maintain acute SAF.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Jun","modification":"2024-11-09T00:10:49.459Z","creation":"2019-03-26T23:49:24Z"},"accession":"S-EPMC3380168","cross_references":{"pubmed":["22467674"],"doi":["10.1161/circep.111.966820","10.1161/CIRCEP.111.966820"]}}