Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents

Cheng, Jianhua

doi:10.1016/s0008-6363(99)00061-9

Cited by 123 publications

(89 citation statements)

References 41 publications

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“…14 The activation-deactivation kinetics of I Kr (chromanol 293B-resistant component) and I Ks (chromanol 293B-sensitive component) in control rabbits were similar to those in our previous reports, 14,19 in which I Kr and I Ks were estimated as E-4031-sensitive and -insensitive components, respectively. Unlike other animal species, activation-deactivation kinetics of I Kr and I Ks in rabbits are similar (Table 2).…”

Section: Short-term Effects Of Amiodarone On I Kr and I Kssupporting

confidence: 88%

Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K ⁺ Current

et al. 2001

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Background-Amiodarone is the most promising drug for the treatment of life-threatening tachyarrhythmias in patients with structural heart disease. The pharmacological effects of amiodarone on cardiac ion channels are complex and may differ for short-term and long-term administration. Methods and Results-The delayed rectifier K ϩ current (I K ) of ventricular myocytes isolated from rabbit hearts was recorded with the whole-cell voltage-clamp technique. I K was separated into 2 components by use of specific blockers for either I Ks (chromanol 293B, 30 mol/L) or I Kr (E-4031, 10 mol/L). Short-term application of amiodarone caused a concentration-dependent decrease in I Kr with an IC 50 of 2.8 mol/L (nϭ8) but only a minimal reduction in I Ks . The short-term effects of amiodarone were also determined in Xenopus oocytes expressing the cloned human channels that conduct I Kr and I Ks (HERG and KvLQT1/minK). HERG current in oocytes was reduced by amiodarone (IC 50 ϭ38 mol/L), whereas KvLQT1/minK current was unaffected by 300 mol/L amiodarone. To study the effects of long-term drug administration, rabbits were treated for 4 weeks with oral amiodarone (100 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ) before cell isolation. Long-term administration of amiodarone decreased I K to 55% (nϭ10) in control rabbits and altered the relative density of I Kr and I Ks . The majority (92%) of current was I Kr . mRNA levels of rabbit ERG, KVLQT1, and minK in left ventricular myocardium did not differ between control and long-term amiodarone. Conclusions-Amiodarone has differential effects on the 2 components of I K , depending on the application period;short-term treatment inhibits primarily I Kr , whereas long-term treatment reduces I Ks .

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Section: Short-term Effects Of Amiodarone On I Kr and I Kssupporting

confidence: 88%

Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K ⁺ Current

et al. 2001

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“…The reasons for this include liability to development of QT interval prolongation and occurrence of TdP during sinus rhythm rather than during tachycardia, owing to its reverse use-dependent blocking effect. 18 Nevertheless, unlike AMD, NIF has a prompt onset of effect with little influence on hemodynamic status and, pharmacologically, has a much greater inhibitory effect than LID on re-entry, the mechanism of sustained arrhythmias. 19 NIF might thus become a drug of first choice for the control of sustained VT/VF associated with ACS if an appropriate method of administration, with emphasis laid on safety, can be established.…”

Section: Discussionmentioning

confidence: 99%

Effects of Intravenous Nifekalant as a Lifesaving Drug for Severe Ventricular Tachyarrhythmias Complicating Acute Coronary Syndrome

Yusu

Ikeda

Mera

et al. 2009

Circ J

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Background: Intravenous amiodarone (AMD) has been used for the treatment of ventricular tachycardia/fibrillation (VT/VF) in emergency care medicine. However, AMD acts slowly and is occasionally accompanied by hypotension and bradycardia. The antiarrhythmic effect of intravenous nifekalant (NIF) was assessed in patients with VT/VF complicating acute coronary syndrome (ACS) according to our study protocol. Methods and Results: Among a series of 1,143 ACS patients, 41 patients who suffered sustained VT/VF were enrolled; 19 failed to respond to a preceding lidocaine (LID) injection. NIF was given first as an intravenous bolus injection (0.2 mg/kg) and then as a continuous intravenous infusion at a relatively low dose level (0.2 mg · kg -1 · h -1 ). Sustained VT/VF was successfully inhibited by NIF in 34 patients (83%). In subgroup analysis, NIF achieved VT/VF inhibition in 79% of patients who received preceding LID and in 86% of patients who received direct NIF. There were no significant changes in systolic blood pressure or heart rate following NIF therapy. A corrected QT interval was significantly prolonged (P<0.01), whereas torsade de pointes developed in only 1 patient (2%). Conclusions: An intravenous bolus injection and subsequent continuous infusion of NIF at a relatively low dosage were effective in treating severe ventricular tachyarrhythmias complicating ACS, reducing the potential risk of proarrhythmia. (Circ J 2009; 73: 2021 -2028

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“…Diazoxide evolved first as an antihypertensive agent with vasodilatory action on peripheral arterioles. It was later found to inhibit insulin secretion from pancreatic b cells and reduce stimulation-evoked catecholamine release by opening ATP-sensitive K + channels, with the inhibition of insulin leading to increased glucose output from the liver [4][5][6][7][8]. Here we report a rare case of nesidioblastosis in an adult patient who was successfully treated with diazoxide.…”

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confidence: 89%

A Rare Case of Adult-onset Nesidioblastosis Treated Successfully with Diazoxide

et al. 2006

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Abstract.A 54-year-old man was admitted to our hospital for evaluation of hypoglycemia. He had frequent episodes of loss of concentration before dinner. The ratio of IRI to plasma glucose (PG) was 0.8-1.0. Abdominal CT revealed no pancreatic tumor, and angiography of splenic artery showed no definite tumor stain within the pancreas. Based on the results of selective arterial calcium stimulation and hepatic venous sampling (ASVS), the provisional diagnosis was a small insulinoma in the pancreatic body. The patient underwent subtotal distal pancreatectomy. However, histopathological and immunohistochemical examinations of the resected tissue showed hypertrophy of islets of Langerhans islands and b cells around pancreatic ducts. The final diagnosis was adult-onset nesidioblastosis. Postoperatively, the patient continued to exhibit hyperinsulinemia and nighttime hypoglycemia. Octreotide, voglibose and diet therapies failed to improve the nocturnal hypoglycemia. However, treatment with diazoxide at a starting dose of 200 mg/day resulted in immediate amelioration of nocturnal hypoglycemia. This is the first Japanese adult case of nesidioblastosis treated successfully with diazoxide. This case report suggests that diazoxide may be effective for adult-onset nesidioblastosis in a manner similar to that described for pediatric cases.

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Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents

Cited by 123 publications

References 41 publications

Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K ⁺ Current

Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K ⁺ Current

Effects of Intravenous Nifekalant as a Lifesaving Drug for Severe Ventricular Tachyarrhythmias Complicating Acute Coronary Syndrome

A Rare Case of Adult-onset Nesidioblastosis Treated Successfully with Diazoxide

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Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents

Cited by 123 publications

References 41 publications

Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K + Current

Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K + Current

Effects of Intravenous Nifekalant as a Lifesaving Drug for Severe Ventricular Tachyarrhythmias Complicating Acute Coronary Syndrome

A Rare Case of Adult-onset Nesidioblastosis Treated Successfully with Diazoxide

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Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K ⁺ Current

Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K ⁺ Current