Bretylium: Relations between plasma concentrations and pharmacologic actions in high-frequency ventricular arrhythmias

OBJECTIVE: To evaluate the pharmacodynamics of intravenous lidocaine in patients with acute-onset and chronic ventricular arrhythmias. DESIGN: Open-label, pharmacodynamic evaluation. SETTING: Private, university-affiliated, hospital coronary-care unit. PATIENTS: Twenty cardiac patients with acute-onset ventricular ectopy and 20 with chronic ventricular ectopy. INTERVENTIONS: Intravenous lidocaine was administered to all patients as a 1-mg/kg bolus, a 0.5-mg/kg bolus, and a 2.8-mg/min constant infusion for 48 hours. MAIN OUTCOME MEASURES: Changes in ventricular premature beat (VPB) frequency against total treatment period frequency and by an hour-to-hour assessment of changes in VPB frequency compared with total baseline frequencies. Response was defined as ≥80 percent total VPB reduction, ≥90 percent paired VPB reduction, and total abolition of nonsustained ventricular tachycardia events. RESULTS: A statistically significant difference in the pharmacodynamic effects of lidocaine were observed during the first eight hours of treatment in patients with acute-onset and chronic VPBs. The number of patients with acute-onset VPBs who responded to lidocaine in the first hour of treatment did not change significantly over the remaining hours of treatment. Response to lidocaine was less in patients with chronic VPBs than in patients with acute-onset VPBs. The response rate to lidocaine was significantly less during the first eight hours in patients with chronic VPBs than in patients with acute-onset VPBs. Following eight hours of treatment, the response rates between acute-onset and chronic VPB patients were not significantly different. Mean lidocaine plasma concentrations were not different between the groups. In addition, there were no significant differences in the incidence of adverse effects between the two groups. CONCLUSIONS: The onset of antiarrhythmic effect as measured by suppression of ventricular ectopy is delayed in patients with chronic VPBs compared with patients with acute-onset VPBs. Decisions about lidocaine response in patients with chronic VPBs cannot be made accurately in the first eight hours of therapy.

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Plasma concentrations of lidocaine during bronchoscopy under high-frequency jet ventilation

Journal of Cardiothoracic Anesthesia ◽

10.1016/0888-6296(89)90026-4 ◽

1989 ◽

Vol 3 (1) ◽

pp. 127

Keyword(s):

High Frequency ◽

Plasma Concentrations ◽

Jet Ventilation ◽

High Frequency Jet Ventilation

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Antiarrhythmic Plasma Concentrations of Cibenzoline on Canine Ventricular Arrhythmias

Journal of Cardiovascular Pharmacology ◽

10.1097/00005344-198702000-00004 ◽

1987 ◽

Vol 9 (2) ◽

pp. 148-153 ◽

Cited By ~ 14

Author(s):

Keitaro Hashimoto ◽

Kentaro Akiyama ◽

Harumi Mitsuhashi

Keyword(s):

Ventricular Arrhythmias ◽

Plasma Concentrations

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Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

Frontiers in Physiology ◽

10.3389/fphys.2021.713717 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuki Kuwabara ◽

Siamak Salavatian ◽

Kimberly Howard-Quijano ◽

Tomoki Yamaguchi ◽

Eevanna Lundquist ◽

...

Keyword(s):

Dorsal Root Ganglion ◽

High Frequency ◽

Dorsal Root ◽

Ventricular Arrhythmias ◽

Low Frequency ◽

Electrode Array ◽

Sympathetic Hyperactivity ◽

Electrophysiological Recordings ◽

Before And After ◽

Yorkshire Pigs

Introduction: Sympathetic hyperactivity is strongly associated with ventricular arrhythmias and sudden cardiac death. Neuromodulation provides therapeutic options for ventricular arrhythmias by modulating cardiospinal reflexes and reducing sympathetic output at the level of the spinal cord. Dorsal root ganglion stimulation (DRGS) is a recent neuromodulatory approach; however, its role in reducing ventricular arrhythmias has not been evaluated. The aim of this study was to determine if DRGS can reduce cardiac sympathoexcitation and the indices for ventricular arrhythmogenicity induced by programmed ventricular extrastimulation. We evaluated the efficacy of thoracic DRGS at both low (20 Hz) and high (1 kHz) stimulation frequencies.Methods: Cardiac sympathoexcitation was induced in Yorkshire pigs (n = 8) with ventricular extrastimulation (S1/S2 pacing), before and after DRGS. A DRG-stimulating catheter was placed at the left T2 spinal level, and animals were randomized to receive low-frequency (20 Hz and 0.4 ms) or high-frequency (1 kHz and 0.03 ms) DRGS for 30 min. High-fidelity cardiac electrophysiological recordings were performed with an epicardial electrode array measuring the indices of ventricular arrhythmogenicity—activation recovery intervals (ARIs), electrical restitution curve (Smax), and Tpeak–Tend interval (Tp-Te interval).Results: Dorsal root ganglion stimulation, at both 20 Hz and 1 kHz, decreased S1/S2 pacing-induced ARI shortening (20 Hz DRGS −21±7 ms, Control −50±9 ms, P = 0.007; 1 kHz DRGS −13 ± 2 ms, Control −46 ± 8 ms, P = 0.001). DRGS also reduced arrhythmogenicity as measured by a decrease in Smax (20 Hz DRGS 0.5 ± 0.07, Control 0.7 ± 0.04, P = 0.006; 1 kHz DRGS 0.5 ± 0.04, Control 0.7 ± 0.03, P = 0.007), and a decrease in Tp-Te interval/QTc (20 Hz DRGS 2.7 ± 0.13, Control 3.3 ± 0.12, P = 0.001; 1 kHz DRGS 2.8 ± 0.08, Control; 3.1 ± 0.03, P = 0.007).Conclusions: In a porcine model, we show that thoracic DRGS decreased cardiac sympathoexcitation and indices associated with ventricular arrhythmogenicity during programmed ventricular extrastimulation. In addition, we demonstrate that both low-frequency and high-frequency DRGS can be effective neuromodulatory approaches for reducing cardiac excitability during sympathetic hyperactivity.

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Poisoning with Over-the-Counter Doxylamine Preparations: An Evaluation of 109 Cases

Human Toxicology ◽

10.1177/096032718700600503 ◽

1987 ◽

Vol 6 (5) ◽

pp. 355-359 ◽

Cited By ~ 38

Author(s):

C. Köppel ◽

J. Tenczer ◽

K. Ibe

Keyword(s):

Plasma Level ◽

High Frequency ◽

Therapeutic Dose ◽

Plasma Concentrations ◽

Age Distribution ◽

Gastric Lavage ◽

Maximum Plasma ◽

Impaired Consciousness ◽

Over The Counter ◽

Clinical Symptomatology

One hundred and nine cases of monointoxication with doxylamine were evaluated with respect to age distribution, amount ingested, plasma level, and clinical symptomatology. The age of 60% of the patients ranged between 16 and 30 years. In about 60% of the cases 10 to 40 times a single therapeutic dose (25 mg) was ingested. Doxylamine plasma concentrations exceeded the maximum plasma level after a therapeutic dose by a factor of 10 to 40 in two-thirds of cases. The most frequent symptoms included impaired consciousness, seizures, tachycardia, mydriasis and a 'psychosis' similar to that in catatonic stupor. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. No symptoms were observed in 39% of the patients. No correlation was found between the amount ingested or doxylamine plasma level and the clinical symptomatology. Primary detoxication included gastric lavage, administration of activated charcoal and sodium sulfate. Regarding the high frequency of doxylamine overdose and its possible complications the question arises as to whether doxylamine-containing preparations should be subjected to prescription.

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Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00173.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. H1923-H1929 ◽

Cited By ~ 60

Author(s):

Arvinder K. Dhalla ◽

Wei-Qun Wang ◽

Joan Dow ◽

John C. Shryock ◽

Luiz Belardinelli ◽

...

Keyword(s):

Blood Pressure ◽

Ventricular Arrhythmias ◽

Left Coronary Artery ◽

Blood Pressure Monitoring ◽

Ischemia Reperfusion ◽

Plasma Concentrations ◽

Median Number ◽

Vehicle Group ◽

Pressure Monitoring ◽

Antianginal Agent

We tested the effect of the antianginal agent ranolazine on ventricular arrhythmias in an ischemic model using two protocols. In protocol 1, anesthetized rats received either vehicle or ranolazine (10 mg/kg, iv bolus) and were subjected to 5 min of left coronary artery (LCA) occlusion and 5 min of reperfusion with electrocardiogram and blood pressure monitoring. In p rotocol 2, rats received either vehicle or three doses of ranolazine (iv bolus followed by infusion) and 20 min of LCA occlusion. With protocol 1, ventricular tachycardia (VT) occurred in 9/12 (75%) vehicle-treated rats and 1/11 (9%) ranolazine-treated rats during reperfusion ( P = 0.003). Sustained VT occurred in 5/12 (42%) vehicle-treated but 0/11 in ranolazine-treated rats ( P = 0.037). The median number of episodes of VT during reperfusion in vehicle and ranolazine groups was 5.5 and 0, respectively ( P = 0.0006); median duration of VT was 22.2 and 0 s in vehicle and ranolazine rats, respectively ( P = 0.0006). With p rotocol 2, mortality in the vehicle group was 42 vs. 17% ( P = 0.371), 10% ( P = 0.162) and 0% ( P = 0.0373) with ranolazine at plasma concentrations of 2, 4, and 8 μM, respectively. Ranolazine significantly reduced the incidence of ventricular fibrillation [67% in controls vs. 42% ( P = 0.414), 30% ( P = 0.198) and 8% ( P = 0.0094) in ranolazine at 2, 4, and 8 μM, respectively]. Median number (2.5 vs. 0; P = 0.0431) of sustained VT episodes, incidence of sustained VT (83 vs. 33%, P = 0.0361), and the duration of VT per animal (159 vs. 19 s; P = 0.0410) were also significantly reduced by ranolazine at 8 μM. Ranolazine markedly reduced ischemia-reperfusion induced ventricular arrhythmias. Ranolazine demonstrated promising anti-arrhythmic properties that warrant further investigation.

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