A. George Akingba

Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion

BACKGROUND Small conductance calcium-activated potassium (SK) channels are responsible for afterhyperpolarization that suppresses nerve discharges. OBJECTIVES To test the hypothesis that low-level vagus nerve stimulation (LL-VNS) leads to the upregulation of SK2 proteins in the left stellate ganglion. METHODS Six dogs (group 1) underwent 1-week LL-VNS of the left cervical vagus nerve. Five normal dogs (group 2) were used as controls. SK2 protein levels were examined by using Western blotting. The ratio between SK2 and glyceraldehydes-3-phosphate-dehydrogenase levels was used as an arbitrary unit (AU). RESULTS We found higher SK2 expression in group 1 (0.124 ± 0.049 AU) than in group 2 (0.085 ± 0.031 AU; P<.05). Immunostaining showed that the density of nerve structures stained with SK2 antibody was also higher in group 1 (11,546 ± 7,271 μm(2)/mm(2)) than in group 2 (5321 ± 3164 μm(2)/mm(2); P<.05). There were significantly more ganglion cells without immunoreactivity to tyrosine hydroxylase (TH) in group 1 (11.4%±2.3%) than in group 2 (4.9% ± 0.7%; P<.05). The TH-negative ganglion cells mostly stained positive for choline acetyltransferase (95.9% ± 2.8% in group 1 and 86.1% ± 4.4% in group 2; P = .10). Immunofluorescence confocal microscopy revealed a significant decrease in the SK2 staining in the cytosol but an increase in the SK2 staining on the membrane of the ganglion cells in group 1 compared to group 2. CONCLUSIONS Left LL-VNS results in the upregulation of SK2 proteins, increased SK2 protein expression in the cell membrane, and increased TH-negative (mostly choline acetyltransferase-positive) ganglion cells in the left stellate ganglion. These changes may underlie the antiarrhythmic efficacy of LL-VNS in ambulatory dogs.

Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.

Microcirculation (2010) 17, 3–20. doi: 10.1111/j.1549‐8719.2010.00008.x

Autonomic nerve activity and blood pressure in ambulatory dogs

BACKGROUND The relationship between cardiac autonomic nerve activity and blood pressure (BP) changes in ambulatory dogs is unclear. OBJECTIVE The purpose of this study was to test the hypotheses that simultaneous termination of stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) predisposes to spontaneous orthostatic hypotension and that specific β₂-adrenoceptor blockade prevents the hypotensive episodes. METHODS We used a radiotransmitter to record SGNA, VNA, and BP in eight ambulatory dogs. Video imaging was used to document postural changes. RESULTS Of these eight dogs, five showed simultaneous sympathovagal discharges in which the minute-by-minute integrated SGNA correlated with integrated VNA in a linear pattern (group 1). In these dogs, abrupt termination of simultaneous SGNA-VNA at the time of postural changes (as documented by video imaging) was followed by abrupt (>20 mm Hg over four beats) drops in BP. Dogs without simultaneous on/off firing (group 2) did not have drastic drops in pressure. ICI-118,551 (ICI, a specific β₂-blocker) infused at 3 µg/kg/h for 7 days significantly increased BP from 126 mm Hg (95% confidence interval 118-133) to 133 mm Hg (95% confidence interval 125-141; P = .0001). The duration of hypotension (mean systolic BP <100 mm Hg) during baseline accounted for 7.1% of the recording. The percentage was reduced by ICI to 1.3% (P = .01). CONCLUSION Abrupt simultaneous termination of SGNA-VNA was observed at the time of orthostatic hypotension in ambulatory dogs. Selective β₂-adrenoceptor blockade increased BP and reduced the duration of hypotension in this model.

Steady Flow Hemodynamic and Energy Loss Measurements in Normal and Simulated Calcified Tricuspid and Bicuspid Aortic Valves

The bicuspid aortic valve (BAV), which forms with two leaflets instead of three as in the normal tricuspid aortic valve (TAV), is associated with a spectrum of secondary valvulopathies and aortopathies potentially triggered by hemodynamic abnormalities. While studies have demonstrated an intrinsic degree of stenosis and the existence of a skewed orifice jet in the BAV, the impact of those abnormalities on BAV hemodynamic performance and energy loss has not been examined. This steady-flow study presents the comparative in vitro assessment of the flow field and energy loss in a TAV and type-I BAV under normal and simulated calcified states. Particle-image velocimetry (PIV) measurements were performed to quantify velocity, vorticity, viscous, and Reynolds shear stress fields in normal and simulated calcified porcine TAV and BAV models at six flow rates spanning the systolic phase. The BAV model was created by suturing the two coronary leaflets of a porcine TAV. Calcification was simulated via deposition of glue beads in the base of the leaflets. Valvular performance was characterized in terms of geometric orifice area (GOA), pressure drop, effective orifice area (EOA), energy loss (EL), and energy loss index (ELI). The BAV generated an elliptical orifice and a jet skewed toward the noncoronary leaflet. In contrast, the TAV featured a circular orifice and a jet aligned along the valve long axis. While the BAV exhibited an intrinsic degree of stenosis (18% increase in maximum jet velocity and 7% decrease in EOA relative to the TAV at the maximum flow rate), it generated only a 3% increase in EL and its average ELI (2.10 cm2/m2) remained above the clinical threshold characterizing severe aortic stenosis. The presence of simulated calcific lesions normalized the alignment of the BAV jet and resulted in the loss of jet axisymmetry in the TAV. It also amplified the degree of stenosis in the TAV and BAV, as indicated by the 342% and 404% increase in EL, 70% and 51% reduction in ELI and 48% and 51% decrease in EOA, respectively, relative to the nontreated valve models at the maximum flow rate. This study indicates the ability of the BAV to function as a TAV despite its intrinsic degree of stenosis and suggests the weak dependence of pressure drop on orifice area in calcified valves.

Management of vascular trauma from dog bites

BACKGROUND Vascular trauma from large-dog bites present with a combination of crush and lacerating injuries to the vessel, as well as significant adjacent soft tissue injury and a high potential for wound complications. This retrospective case series evaluates our 15 years of experience in managing this uncommonly seen injury into suggested treatment recommendations. METHODS From our database, 371 adult patients presented with dog bites between July 1997 and June 2012. Twenty (5.4%) of those patients had vascular injuries requiring surgical intervention. Patient demographics, anatomic location of injury, clinical presentation, imaging modality, method of repair, and complication rates were reviewed to assess efficacy in preserving limb function. Pediatric patients were managed at the regional childrens hospital and, therefore, not included in this study. RESULTS Among the 20 surgically treated vascular injuries, there were 13 arterial-only injuries, two venous-only injuries, and five combination arterial and venous injuries. Seventeen patients (85%) had upper extremity injuries; three patients had lower extremity injuries (15%). The axillobrachial artery was the most commonly injured single vessel (n = 9/20; 45%), followed by the radial artery (n = 4/20; 20%). Surgical repair of vascular injuries consisted of resection and primary anastomosis (four), interposition bypass of artery with autogenous vein (13), and ligation (two), with (one) being a combination of bypass and ligation. All patients had debridement of devitalized tissue combined with pulse lavage irrigation and perioperative antibiotics. Associated injuries requiring repair included muscle and skin (n = 10/20; 50%), bone (n = 1/20; 5%), nerve (n = 1/20; 5%), and combinations of the three (n = 5/20; 25%). Postoperative antibiotic therapy was administered for 14.7 ± 8.2 days in all 20 patients. Four patients (20%) developed postoperative wound infections, although this did not compromise their vascular repair. Of the patients compliant with postoperative surveillance, all limbs (100%) were viable at discharge and at 1-year follow-up. CONCLUSIONS Dog bite vascular injuries are an uncommon occurrence, where extremity pulse abnormalities are the most common presentation. These injuries are also associated with significant adjacent soft tissue trauma, which warrants aggressive debridement and perioperative antibiotic therapy. Despite vigilant management, nearly one-fifth of our patients sustained wound infections. All infections were successfully managed with broad-spectrum antibiotics, and all limbs were preserved 1-year postoperatively.

Nanoelectrode arrays for measuring Sympathetic Nervous Activity

This paper reports on the use of arrays of nanoelectrodes to measure activity of the Sympathetic Nervous System. Measurements of the Sympathetic Nervous Activity (SNA) have not been easy; primarily because of poor signal-to-noise ratio (SNR). We report improved SNR of SNA measurements achieved by the use of novel Planar Nanoelectrode Arrays (PNA). Nano scale features on the electrodes provide increased contact area with the host nerve reducing the limiting (Johnson) noise. These electrodes are fabricated using standard CMOS compatible fabrication techniques on a high resistivity silicon substrate and used to measure SNA in test animals. For comparison, traditional wire electrodes were used simultaneously to measure the same signal. The PNAs consistently exhibit significant improvement in the SNR of the measured SNA (35.71 dB vs. 25.08 dB for the wire electrode). Moreover, the PNAs are capable of recording events lost in the noise floor of the wire electrodes.

Computational Hemodynamic Assessment of a Novel Modular Anastomotic Valve Device for Improving Hemodialysis Vascular Access Patency

End-stage renal disease (ESRD) occurs as a result of any renal injury that chronically decreases renal excretory and regulatory function. ESRD patients are most commonly treated with hemodialysis (HD) to manage their renal failure while awaiting kidney transplant. Current practices for maintenance of HD vascular access consist of arteriovenous fistulas (AVFs) or grafts (AVGs), which are both fraught with problems that compromise the patency and use of these surgically created shunts. The major cause of shunt failure is thrombosis caused by occlusion of the outflow venous anastomosis and draining vein. Intimal hyperplasia (IH), which consists of the thickening of the innermost layer of the vessel wall, is the initial pathological event leading to shunt stenosis/thrombosis and has been associated with the presence of flow disturbances and abnormal wall shear stress (WSS) at the graft-vein anastomosis. Therefore, the improvement of HD via the enhancement of vascular access patency requires the development of a novel vascular access technology preserving the normal hemodynamics of the native vein.Copyright

Wireless measurement of Sympathetic Nervous activity using planar nanoelectrode arrays

This paper reports on the use of arrays of nanoelectrodes as implantable sensors to wirelessly measure the activity of the Sympathetic Nervous System - Sympathetic Nervous Activity (SNA). SNA can be measured as a train of electrical pulses. Traditionally, SNA has been measured with wire electrodes. These measurements have not been easy because of poor signal-to-noise ratio (SNR). In the current work, we have successfully demonstrated improved SNR of SNA measurements achieved by the use of novel Planar Nanoelectrode Arrays (PNAs) in a chronic setting. The PNAs are placed on the left stellate ganglion (SG) via a thoracotomy. Nano scale features on the electrodes provide increased contact area with the nerve of interest (in this case the SG) thereby reducing the limiting (Johnson) noise. The PNAs were fabricated using standard CMOS compatible fabrication techniques on a high resistivity silicon substrate. After suitable wire-bonding and packaging, the PNAs were placed on the left stellate ganglion of a canine test subject. For adequate comparison, a standard set of wire electrodes were embedded on the same nerve in close proximity of the PNAs. Both the sensors were connected to a wireless transmitter (Model No. TR 70BB) powered with a rechargeable battery also placed within the canine test subject. The thoracotomy incision was repaired and the canine test subject allowed to recover before beginning SNA measurements. Our results showed that the PNAs consistently exhibit superior SNR of the measured SNA. Measurements have been successfully made up to three months after implantation of the electrodes and the SNR of the PNA has been consistently better than the wire electrodes. After one month the SNR of the PNA was 48.54 ± 2.71 dB vs. 17.88 ± 4.49 dB for the wire electrode (p <; 0.001). At three months the SNR of the PNA was 48.57 ± 1.63 dB vs. 18.98 ± 2.38 dB for the wire electrode (p <; 0.001).