Browsing by Author "Shelton, Richard"

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Estimating Sympathetic Tone by Recording Subcutaneous Nerve Activity in Ambulatory Dogs
(2015-01-01)
Robinson, Eric A.
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Rhee, Kyoung-Suk
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Doytchinova, Anisiia
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Kumar, Mohineesh
;
Shelton, Richard
Subcutaneous Nerve Activity IntroductionWe tested the hypothesis that subcutaneous nerve activity (SCNA) of the thorax correlates with the stellate ganglion nerve activity (SGNA) and can be used to estimate the sympathetic tone. Methods and ResultsWe implanted radio transmitters in 11 ambulatory dogs to record left SGNA, left thoracic vagal nerve activity (VNA), and left thoracic SCNA, including 3 with simultaneous video monitoring and nerve recording. Two additional dogs were studied under general anesthesia with apamin injected into the right stellate ganglion while the right SGNA and the right SCNA were recorded. There was a significant positive correlation between integrated SGNA (iSGNA) and integrated SCNA (iSCNA) in the first 7 ambulatory dogs, with correlation coefficient of 0.70 (95% confidence interval [CI] 0.61-0.84, P < 0.05 for each dog). Tachycardia episodes (heart rate exceeding 150 bpm for 3 seconds) were invariably preceded by SGNA and SCNA. There was circadian variation of both SCNA and SGNA. Crosstalk was ruled out because SGNA, VNA, and SCNA bursts had different timing and activation patterns. In an eighth dog, closely spaced bipolar subcutaneous electrodes also recorded SCNA, but with reduced signal to noise ratio. Video monitoring in additional 3 dogs showed that movement was not a cause of high frequency SCNA. The right SGNA correlated strongly with right SCNA and heart rate in 2 anesthetized dogs after apamin injection into the right stellate ganglion. ConclusionsSCNA recorded by bipolar subcutaneous electrodes correlates with the SGNA and can be used to estimate the sympathetic tone.
Small Conductance Calcium-Activated Potassium Current Is Important in Transmural Repolarization of Failing Human Ventricles
(2015-06-01)
Yu, Chih-Chieh
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Corr, Christopher
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Shen, Changyu
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Shelton, Richard
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Yadava, Mrinal
Background The transmural distribution of apamin-sensitive small conductance Ca2+-activated K+ (SK) current (I-KAS) in failing human ventricles remains unclear. Methods and Results We optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (APD) before and after 100 nmol/L apamin administration in all wedges and after sequential administration of apamin, chromanol, and E4031 in 4 wedges. Apamin prolonged APD from 363 ms (95% confidence interval [CI], 341-385) to 409 (95% CI, 385-434; P<0.001) in all hearts, and reduced the transmural conduction velocity from 36 cm/s (95% CI, 30-42) to 32 cm/s (95% CI, 27-37; P=0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL). The percent APD prolongation is negatively correlated with baseline APD and positively correlated with PCL. Only 1 wedge had M-cell islands. The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after apamin, chromanol, and E4031 were 9.1% (95% CI, 3.9-14.2), 17.3% (95% CI, 3.1-31.5), and 35.9% (95% CI, 15.7-56.1), respectively. Immunohistochemical staining of subtype 2 of SK protein showed increased expression in intercalated discs of myocytes. Conclusions SK current is important in the transmural repolarization in failing human ventricles. The magnitude of I-KAS is positively correlated with the PCL, but negatively correlated with APD when PCL is fixed. There is abundant subtype 2 of SK protein in the intercalated discs of myocytes.