Browsing by Author "Kamp, Nicholas J."

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Effects of ondansetron on apamin-sensitive small conductance calcium-activated potassium currents in pacing-induced failing rabbit hearts
(2020-02-01)
Yin, Dechun
;
Yang, Na
;
Tian, Zhipeng
;
Wu, Adonis Z.
;
Xu, Dongzhu
BACKGROUND Ondansetron, a widely prescribed antiemetic, has been implicated in drug-induced long QT syndrome. Recent patch clamp experiments have shown that ondansetron inhibits the apamin-sensitive small conductance calcium-activated potassium current (I-KAS). OBJECTIVE The purpose of this study was to determine whether ondansetron causes action potential duration (APD) prolongation by I-KAS inhibition. METHODS Optical mapping was performed in rabbit hearts with pacing-induced heart failure (HF) and in normal hearts before and after ondansetron (100 nM) infusion. APD at 80% repolarization (APD(80)) and arrhythmia inducibility were determined. Additional studies with ondansetron were performed in normal hearts perfused with hypokalemic Tyrode's (2.4 mM) solution before or after apamin administration. RESULTS The corrected QT interval in HF was 326 ms (95% confidence interval [CI] 306-347 ms) at baseline and 364 ms (95% CI 351-378 ms) after ondansetron infusion (P < .001). Ondansetron significantly prolonged APD(80) in the HF group and promoted early afterdepolarizations, steepened the APD restitution curve, and increased ventricular vulnerability. Ventricular fibrillation was not inducible in HF ventricles at baseline, but after ondansetron infusion, ventricular fibrillation was induced in 5 of the 7 ventricles (P = .021). In hypokalemia, apamin prolonged APD(80) from 163 ms (95% CI 146-180 ms) to 180 ms (95% CI 156-204 ms) (P = .018). Subsequent administration of ondansetron failed to further prolong APD(80) (180 ms [95% CI 156-204 ms] vs 179 ms [95% CI 165-194 ms]; P = .789). The results were similar when ondansetron was administered first, followed by apamin. CONCLUSION Ondansetron is a specific I-KAS blocker at therapeutic concentrations. Ondansetron may prolong the QT interval in HF by inhibiting small conductance calcium-activated potassium channels, which increases the vulnerability to ventricular arrhythmias.
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.
Using skin sympathetic nerve activity to estimate stellate ganglion nerve activity in dogs
(2015-06-01)
Jiang, Zhaolei
;
Zhao, Ye
;
Doytchinova, Anisiia
;
Kamp, Nicholas J.
;
Tsai, Wei-Chung
BACKGROUND Stellate ganglion nerve activity (SGNA) is important in cardiac arrhythmogenesis. However, direct recording of SGNA requires access to the thoracic cavity. Skin of upper thorax is innervated by sympathetic nerve fibers originating from the stellate ganglia and is easily accessible. OBJECTIVE The purpose of this study was to test the hypothesis that thoracic skin nerve activity (SKNA) can be used to estimate SGNA. METHODS We recorded SGNA and SKNAs using surface electrocardiogram leads in 5 anesthetized and 4 ambulatory dogs. Apamin injected into the right stellate ganglion abruptly increased both right SGNA and SKNA in 5 anesthetized dogs. We integrated nerve activities and averaged heart rate in each 1-minure window over 10 minutes, We implanted a radiotransmitter to record Left SGNA in 4 ambulatory dogs (2 normal, 1 with myocardial infarction, 1 with intermittent rapid atrial pacing). After 2 weeks of recovery, we simultaneously recorded the SKNA and Left SGNA continuously for 30 minutes when the dogs were ambulatory. RESULTS There was a positive correlation [average r = 0.877, 95% confidence interval (CI) 0.732-1.000, P<.05 for each dog] between integrated skin nerve activity (iSKNA) and SGNA (iSGNA) and between iSKNA and heart rate (average r = 0.837, 95% CI 0.752-0.923, P<.05). Similar to that found in the anesthetized dogs, there was a positive correlation (average r = 0.746, 95% CI 0.527-0.964, P<.05) between iSKNA and iSGNA and between iSKNA and heart rate (average r = 0.706, 95% CI 0.484-0.927, P<.05). CONCLUSION SKNAs can be used to estimate SGNA in dogs.