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BACKGROUND Coordinated interactions within central and peripheral neural networks determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation in response to ischemia is a major contributor to sudden cardiac death. OBJECTIVE To define fundamental aspects of cardiac-related autonomic neural network interactions within the thoracic cord, and those specifically related to modulating sympathetic preganglionic (SPN) neural activity during cardiovascular stress. METHODS Adult, anesthetized Yorkshire pigs (n=10) were implanted with penetrating high-density microarrays (64 electrodes) at the T2level of the thoracic spinal cord to record extracellular potentials concurrently from left-sided dorsal horn (DH) and SPN neurons. Electrical stimulation of the T2paravertebral chain allowed for antidromic identification of SPNs located in the intermediolateral cell column (57 of total 1,703 recorded neurons). Cardiac stressors included epicardial touch, occlusion of great vessels to transiently alter preload/afterload and transient occlusion of the left anterior descending (LAD) coronary artery. Spatial/temporal assessment of network interactions was characterized by cross-correlation analysis. RESULTS While some DH neurons responded solely to changes in preload/afterload (8.5±1.9%) or ischemic stress (10.5±3.9%), the majority of cardiovascular-related DH neurons were multimodal (30.2±4.7%) with ischemia sensitivity being one of the modalities (26.1±4.7%). The sympathoexcitation associated with transient LAD occlusion was associated with increased correlations from baseline within DH neurons (2.43±0.61 to 7.30 ±1.84%, p=0.04) and between SPN to DH neurons (1.32±0.78 to 7.24±1.84%, p=0.02). DH to SPN network correlations were reduced during great vessel occlusion. CONCLUSION Increased intra-segmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation.Patients with peripheral arterial disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity is unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Eleven PAD patients and 11 age, and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2 to 12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure (BP), femoral blood flow velocity (FBV), and muscle oxygen saturation (SmO2) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the BP tracings. Ruboxistaurin chemical structure Mean arterial blood pressure and TPR were significantly augmented in PAD compared to control during PF. FBF increased during exercise to an equal extent in both groups. However, SmO2 of the exercising limb remained significantly lower in PAD compared to control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared to controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD.This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure (P = 0.59), dP/dtmax (P = 0.26), or dP/dtmin (P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% (P less then 0.01), which was accompanied by a significant increase in coronary blood flow (P less then 0.05) and reductions in left ventricular end-diastolic volume and stroke volume (P less then 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow Background Surgical treatment of basal joint arthritis commonly consists of trapeziectomy followed by various suspensionplasty techniques to provide stability to the thumb ray. Our study goal was to assess the motion and stability of the thumb ray after trapeziectomy and placement of a suture button (Mini TightRope®, Arthrex, Naples, Florida) in a high- or low-angle trajectory. We hypothesized that a low-angle trajectory would yield the greatest stability while providing maximal motion of the thumb. Methods Eleven fresh-frozen cadaver arms were imaged fluoroscopically in anterior-posterior and lateral views before and after trapeziectomy, and after placement of low- and high-angle suture buttons. The intermetacarpal angle between the thumb and index metacarpals was measured after application of a standard force. Radial abduction, opposition, subsidence, palmar abduction, adduction, and subsidence were measured. Results Compared to posttrapeziectomy constructs, low- and high-angle TightRope constructs demonstrated less subsidence, low-angle TightRopes had less palmar abduction, and high-angle TightRope constructs had less radial abduction and adduction. High-angle TightRopes allowed more palmar abduction than low-angle constructs. The high-angle TightRopes trended toward more subsidence than low-angle constructs, although it was not significant. Conclusions Both TightRope constructs provided improved axial stability after trapeziectomy while not excessively limiting any one motion of the thumb. Compared to the high-angle trajectory, the low-angle TightRope placement provided a more stable construct with respect to subsidence and angular motion. Given the concern for excessive motion of the first metacarpal base with the high-angle construct, we recommend a low-angle trajectory TightRope placement.

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