The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload. NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions.

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The results suggest both genders can perform effective ECCs during simulated hypogravity. Women, however, cannot perform effective ECCs during microgravity simulation. These findings suggest that there is a gender difference when performing the Evetts-Russomano method.

Sympathetic control of regional cardiac function occurs through post-ganglionic innervation from stellate ganglia and thoracic sympathetic chain. While norepinephrine (NE) is their primary neurotransmitter, neuropeptide Y (NPY) is an abundant cardiac co-transmitter. NPY plays a vital role in homeostatic processes including angiogenesis, vasoconstriction, and cardiac remodeling. Elevated sympathetic stress, resulting in increased NE and NPY release, has been implicated in the pathogenesis of several cardiovascular disorders including hypertension, myocardial infarction, heart failure and arrhythmias, which may result in sudden cardiac death. Current methods for the detection of NPY in myocardium are limited in their spatial and temporal resolution and take days to weeks to provide results. (e.g. interstitial microdialysis with subsequent analysis by enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC) or mass spectrometry). In this study, we report a novel approach for measurement of interstitial and intravascular NPY using a minimally invasive capacitive immunoprobe (C.I. probe). The first high spatial- and temporal-resolution, multi-channel measurements of NPY release in vivo are provided in both myocardium and transcardiac vascular space in a beating porcine heart. We provide NPY responses evoked by sympathetic stimulation and ectopic ventricular pacing and compare these to NE release and hemodynamic responses. We extend this approach to measure both NPY and vasoactive intestinal peptide (VIP) and show differential release profiles under sympathetic stimulation. Our data demonstrate rapid and local changes in neurotransmitter profiles in response to sympathetic cardiac stressors. Future implementations include real-time intra-operative determination of cardiac neuropeptides and deployment as a minimally invasive catheter.

Introduction: Embedded accelerometers offer a novel method of measuring physical activity levels in the pacemaker population. In an initial cohort of 96 subjects with pacemakers, we previously showed sedentary behavior significantly correlates with decreased survival. We hypothesize that physical activity of < 2 hours/day correlates with mortality independently of the traditional cardiovascular risk factors in an expanded cohort. Methods: Records of 273 individuals with de novo Medtronic pacemaker implantation at a single center between January 1, 2005 and December 31, 2012 were reviewed. An accelerometer embedded in these devices measures activity level as above or below a 70 steps/minute threshold and reports the average hours/day of activity exceeding this threshold. Activity levels abstracted from pacemaker interrogations were averaged over a 1 year period following a 6-month blanking period after implantation. Among this cohort, 48.7% were categorized as having failed to reach the activity threshold for ≥2 hours/day (n=140). Survival was compared between groups by Kaplan-Meier estimate and Cox proportional hazards models. Multivariable logistic regression examined predictors of survival. Results: The average age of the study cohort was 71±13 years with CAD prevalent in 34.1% of subjects. Average follow-up time was 3.67±2.43 years. Death occurred in 40 subjects (14.7%). In unadjusted analysis, death was nearly 5 times more likely in the inactive group than the active group [OR 4.81, 95% CI (2.13-10.88), P<0.001]. A multivariate model revealed that < 2 hours of daily activity remained an independent predictor of death [OR 4.39, 95% CI (1.90-10.12), P=0.001] along with age [OR 1.04, 95% CI (1.01-1.08), P=0.02] while sex [OR 0.09, P=0.74] and CAD [OR 0.54, P=0.08] were not predictors. Conclusion: Sedentary behavior as measured by an implanted pacemaker correlates with increased mortality independently of traditional cardiovascular risk factors.

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