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.