Dual optical mapping of the innervated Langendorff-perfused heart reveals novel insights into acute electrophysiological responses to sympathetic stimulation

Background: Sympathetic activation of the cardiac tissue has been recognized as one of the key adaptive mechanisms in the mammalian heart. However, few studies have looked at the dynamic effects of physiological sympathetic nerve activation on cardiac action potentials (AP) and intracellular Ca2+ transients (CaT). Methods and Results: The heart and posterior thoracic cavity from rabbits (NZW, N=9) and mice (C57Bl6, N=8) were dissected and perfused through the descending aorta for dual optical mapping of transmembrane potential (Vm) and intracellular Ca2+ to study the effects of direct sympathetic nerve stimulation (SNS). SNS was achieved through spinal cord stimulation at T1-T3. Our results show that acute SNS (60 sec, 5-10Hz) increased heart rate (HR) and CaT amplitude in both species. The maximum HR (144±15 to 254±23 BPM in the rabbit and 368±33 to 506±45 BPM in the mouse) and CaT amplitude (increased 9.3±1.6% in the rabbit and 5.9±2.7% in the mouse) were reached after 20sec of SNS. The CaT amplitude increase was more prominent at the base than at the apex (12.3±4.6% vs. 6.3±1.5%, p<0.05 in the rabbit and 11.3±5.3% vs. 1.0±5.8%, p<0.05 in the mouse), consistent with the anatomical distribution pattern of the sympathetic nerves in the heart. While AP duration (APD) and CaT duration (CaTD) monotonically decreased during SNS in the rabbit, the mouse APD showed a biphasic response, with an initial phase of APD prolongation. The maximum APD prolongation (50.9±5.1 to 60.6±4.1ms) occurred after 20sec of SNS. In addition, rabbit hearts displayed a complete reversal of the direction of repolarization, whereas mouse hearts did not. Conclusions: These data demonstrate that the mouse heart possesses not only unique AP and intracellular CaT morphologies, but also has a significantly different response to physiological sympathetic activation. These important differences should be considered when selecting species for translational cardiac electrophysiology investigations.