Abstract 19223: Injection of Nanoformulated CaCl2 into Intrinsic Cardiac Ganglionic Plexi Suppresses Ganglionic Nerve Activity and Postoperative Atrial Fibrillation

    loading  Checking for direct PDF access through Ovid


Background: Postoperative atrial fibrillation (POAF), a complication of cardiac surgery, causes significant morbidity. Sympathetic surge promotes remodeling, leading to POAF. Intracellular Ca++ overload induces neural apoptosis. We hypothesize that injection of sustained release nanoformulated CaCl2 (nCaCl2) into cardiac ganglionic plexi (GP) will reduce cardiac autonomic nerve activity (NA) and prevent POAF.

Methods: We implanted radiotelemetry devices in 7 canines to record ambulatory heart rate (HR), extrinsic cardiac sympathetic (ECSNA), vagus (ECVNA) and intrinsic cardiac NA (ICNA) for 4 wks. 3 wks postop (PO) we injected nCaCl2 into the left superior and left inferior GP. Atrial effective refractory period (AERP) and AF inducibility (AFI) were measured at baseline, 3 wks PO, 1hr post nCaCl2, 1wk post nCaCl2 and 1hr post right sided GP nCaCl2, for 3 left atrial (LA) sites: LA appendage (LAA), posterior LA (PLA) and anterior LA (ALA). AFI was scored for ease of inducibility, arrhythmia duration and number of arrhythmias per site.

Results: AERP decreased from baseline to 3 wks PO at LAA (125±6 to 115±6 ms p=0.02), PLA (130±4 to 97±11 ms p<0.01) and ALA (132±8 to 102±11 ms p<0.05). AERP increased 1hr post nCaCl2 for PLA (118±8 ms p<0.05) and 1wk post nCaCl2 for LAA (130±3 ms p<0.01), PLA (128±2 ms p<0.02) and ALA (120±4 ms P<0.05). AFI decreased 1hr post nCaCl2 for LAA (7.43±3.10 to 0), PLA (7.71±2.78 to 2.57±2.26) and ALA (9±4.7 to 5.14±3.23), p<0.05. AFI reduction persisted for 1wk in LAA (1.33±0.88 p=0.05) and PLA (2.5±1.20 p<0.05). ECSNA increased (282.79±51.43 to 451.09±103.08 μV-s p<0.02) post nCaCl2 in ambulatory animals where ECVNA and ICNA were unchanged. ECSNA was unchanged during treadmill exercise (ETT), but ECVNA (260.00±60.55 to 221.29±44.11 μV-s p<0.05) and ICNA (1180.54±178.92 to 960.14±98.22 μV-s p<0.02) decreased post nCaCl2. HR decreased at rest (92±6 to 79±4 bpm p<0.01) and during 9-minute ETT (147±7 to 130±3 bpm p<0.01) post nCaCl2. Histologic sections showed neuronal apoptosis and confirmed nCaCl2 location in GP but not myocardium.

Conclusions: Increased CaCl2 concentration in GP is selectively neurotoxic, suppressing ICNA and ECVNA, increasing AERP and protecting against ECSNA surge. These changes cause prolonged POAF suppression.

Related Topics

    loading  Loading Related Articles