Beneficial Cardiac Effects of Cicletanine in Conscious Rabbits With Metabolic Syndrome

Drimba, László; Hegedűs, Csaba; Yin, Dong; Sári, Réka; Németh, József; Szilvássy, Zoltán; Peitl, Barna

doi:10.1097/fjc.0b013e31825c3c4c

Cited by 3 publications

(4 citation statements)

References 40 publications

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“…However, less time is required (8 to 12 weeks) to administer high-fat diets supplemented with cholesterol [38,49]. This is due to the greater sensitivity of rabbits to cholesterol and the rapid development of biochemical and vascular changes.…”

Section: Discussionmentioning

confidence: 99%

“…This monitoring can be carried out using restricted diets with an equal number of calories per day according to the weight of the animal. Another form of diet administration is to allow “ad libitum” water intake without restriction, which is self-regulated by the same animal according to the caloric density [14,19,23,36,38].…”

Section: Diet Regimesmentioning

confidence: 99%

“…In fact, studies using diets with 2% added cholesterol showed high plasma levels of LDL, HDL, and triglycerides. In addition, significant changes in cardiovascular function (blood pressure and heart rate) were shown, producing a proarrhythmic state [38].…”

Section: Diet Regimesmentioning

confidence: 99%

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Diet-Induced Rabbit Models for the Study of Metabolic Syndrome

Lozano

Arias-Mutis

Calvo

et al. 2019

Animals

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Obesity and metabolic syndrome (MetS) have become a growing problem for public health and clinical practice, given their increased prevalence due to the rise of sedentary lifestyles and excessive caloric intake from processed food rich in fat and sugar. There are several definitions of MetS, but most of them describe it as a cluster of cardiovascular and metabolic alterations such as abdominal obesity, reduced high-density lipoprotein (HDL) and elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides, glucose intolerance, and hypertension. Diagnosis requires three out of these five criteria to be present. Despite the increasing prevalence of MetS, the understanding of its pathophysiology and relationship with disease is still limited. Indeed, the pathological consequences of MetS components have been reported individually, but investigations that have studied the effect of the combination of MeS components on organ pathological remodeling are almost nonexistent. On the other hand, animal models are a powerful tool in understanding the mechanisms that underlie pathological processes such as MetS. In the first part of the review, we will briefly overview the advantages, disadvantages and pathological manifestations of MetS in porcine, canine, rodent, and rabbit diet-induced experimental models. Then, we will focus on the different dietary regimes that have been used in rabbits to induce MetS by means of high-fat, cholesterol, sucrose or fructose-enriched diets and their effects on physiological systems and organ remodeling. Finally, we will discuss the use of dietary regimes in different transgenic strains and special rabbit breeds.

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Section: Discussionmentioning

confidence: 99%

Section: Diet Regimesmentioning

confidence: 99%

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Diet-Induced Rabbit Models for the Study of Metabolic Syndrome

Lozano

Arias-Mutis

Calvo

et al. 2019

Animals

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“…The electrophysiological parameters calculated from the records were as follows: R‐R length (converted to heart rate [HR]), Q‐T end (from the onset of the Q wave to the end of the T wave), QT cb interval (calculated using Bazett's formula dividing the QT measurements by the square root of the RR interval) [Bazett, ]. Ventricular effective refractory period (VERP) was measured using programmed electrical stimulation as described [Drimba et al., ].…”

Section: Methodsmentioning

confidence: 99%

In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS‐7229

Drimba

Németh

Sári

et al. 2012

Drug Development Research

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Preclinical Research The basic hemodynamic, electrophysiological, and pharmacological effects of EGIS‐7229 (E‐7229) were evaluated and compared with those of a pure “Class III“ antiarrhythmic drug (GLG‐V‐13) in conscious rabbits. Both compounds decreased heart rate dose‐dependently. Mean arterial blood pressure was not influenced by E‐7229; however, GLG‐V‐13 produced a significant elevation on this parameter. Left ventricular end‐diastolic pressure was gradually increased by E‐7229, while GLG‐V‐13 induced more considerable elevation on that at intermediate doses. QT and QTcb were lengthened by both compounds; however, higher doses of E‐7229 resulted in shortening of the prolonged QT and QTcb. Ventricular effective refractory period (VERP) was significantly prolonged by either drug studied. Threshold doses to produce QT50%, QTmax, VERP50%, and VERPmax were significantly higher for E‐7229 compared with GLG‐V‐13. Significantly higher doses were required for E‐7229 to induce arrhythmias. The safety ratio was comparable for both of the compounds. E‐7229 can exert multiple actions on cardiac ion channels with minimal influence on hemodynamic parameters and reduced proarrhytmic profile in our preclinical model.

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The role of acute hyperinsulinemia in the development of cardiac arrhythmias

Drimba

Döbrönte

Hegedűs

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 ± 0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.

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Beneficial Cardiac Effects of Cicletanine in Conscious Rabbits With Metabolic Syndrome

Abstract: Cicletanine exerts beneficial cardiac effects in rabbits with symptoms of MS, which may be of influence with regard to the clinical application of the drug.

Cited by 3 publications

References 40 publications

Diet-Induced Rabbit Models for the Study of Metabolic Syndrome

Diet-Induced Rabbit Models for the Study of Metabolic Syndrome

In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS‐7229

The role of acute hyperinsulinemia in the development of cardiac arrhythmias

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