Procainamide and lidocaine produce dissimilar changes in ventricular repolarization and arrhythmogenicity in guinea-pig

2013 ◽  
Vol 28 (4) ◽  
pp. 382-393 ◽  
Author(s):  
Oleg E. Osadchii
Keyword(s):  
Guinea Pig ◽  
Ventricular Repolarization

Quinidine elicits proarrhythmic changes in ventricular repolarization and refractoriness in guinea-pig

2013 ◽  
Vol 91 (4) ◽  
pp. 306-315 ◽  
Author(s):  
Oleg E. Osadchii
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Left Ventricular ◽  
Ventricular Repolarization ◽  
Monophasic Action Potential ◽  
Delayed Rectifier ◽  
Rate Dependent ◽  
Delayed Rectifier Current ◽  
Left Ventricular Chamber ◽  
The Right

Quinidine is a class Ia Na+ channel blocker that prolongs cardiac repolarization owing to the inhibition of IKr, the rapid component of the delayed rectifier current. Although quinidine may induce proarrhythmia, the contributing mechanisms remain incompletely understood. This study examined whether quinidine may set proarrhythmic substrate by inducing spatiotemporal abnormalities in repolarization and refractoriness. The monophasic action potential duration (APD), effective refractory periods (ERPs), and volume-conducted electrocardiograms (ECGs) were assessed in perfused guinea-pig hearts. Quinidine was found to produce the reverse rate-dependent prolongation of ventricular repolarization, which contributed to increased steepness of APD restitution. Throughout the epicardium, quinidine elicited a greater APD increase in the left ventricular chamber compared with the right ventricle, thereby enhancing spatial repolarization heterogeneities. Quinidine prolonged APD to a greater extent than ERP, thus extending the vulnerable window for ventricular re-excitation. This change was attributed to increased triangulation of epicardial action potential because of greater APD lengthening at 90% repolarization than at 30% repolarization. Over the transmural plane, quinidine evoked a greater ERP prolongation at endocardium than epicardium and increased dispersion of refractoriness. Premature ectopic beats and monomorphic ventricular tachycardia were observed in 50% of quinidine-treated heart preparations. In summary, abnormal changes in repolarization and refractoriness contribute greatly to proarrhythmic substrate upon quinidine infusion.

scholarly journals Accurate detection of drug-induced delayed ventricular repolarization with a suitable correction formula in Langendorff guinea pig heart

2010 ◽  
Vol 35 (5) ◽  
pp. 687-698 ◽  
Author(s):  
Mitsuyasu Tabo ◽  
Ryuichi Komatsu ◽  
Takehito Isobe ◽  
Masaki Honda ◽  
Yuichiro Yamada ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Ventricular Repolarization ◽  
Drug Induced ◽  
Guinea Pig Heart ◽  
Correction Formula ◽  
Accurate Detection

scholarly journals Effects of the Fluoroquinolone Antibacterial Drug Ciprofloxacin on Ventricular Repolarization in the Halothane-Anesthetized Guinea Pig

2013 ◽  
Vol 122 (3) ◽  
pp. 205-212 ◽  
Author(s):  
Kazuhiro Matsuo ◽  
Kaori Fujiwara ◽  
Naoki Omuro ◽  
Itsuki Kimura ◽  
Kazuko Kobayashi ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Ventricular Repolarization ◽  
Antibacterial Drug

Ionic Basis of the Differential Effects of Intravenous Anesthetics on Erythromycin-induced Prolongation of Ventricular Repolarization in the Guinea Pig Heart 

1997 ◽  
Vol 87 (5) ◽  
pp. 1172-1181 ◽  
Author(s):  
Timothy E. Morey ◽  
Anatoly E. Martynyuk ◽  
Charles A. Napolitano ◽  
M. J. Pekka Raatikainen ◽  
Thomas S. Guyton ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Guinea Pig ◽  
Long Qt Syndrome ◽  
Ventricular Repolarization ◽  
Long Qt ◽  
Whole Cell ◽  
Intravenous Anesthetics ◽  
Cell Patch Clamp ◽  
Whole Cell Patch Clamp ◽  
Qt Syndrome

Background Dysrhythmias and death occur in patients with acquired long QT syndrome (LQTS). Little information exists regarding interactions between anesthetics and drugs that prolong ventricular repolarization. Therefore the effects of three commonly used intravenous anesthetics on ventricular repolarization were investigated in the setting of drug-induced, long QT syndrome. Methods The effects of increasing concentrations (0, 10, 25, and 50 microM) of propofol, ketamine, and thiopental on ventricular repolarization were evaluated by measuring the monophasic action potential duration at 90% repolarization (MAPD90) in guinea pig Langendorff-perfused hearts in the absence or presence of erythromycin (100 microM). If an anesthetic enhanced erythromycin-induced prolongation of MAPD90, its effects on the delayed rectifier (I[K]) and inward rectifier (I[Kl]) potassium currents were measured using the whole-cell patch-clamp technique. Results At clinically relevant concentrations, only thiopental significantly modulated erythromycin's effect on MAPD90. Thiopental at 10, 25, and 50 microM prolonged MAPD90 from a control of 163 +/- 6 ms by 18 +/- 4, 30 +/- 3, and 31 +/- 4 ms, respectively. In a separate group, erythromycin prolonged MAPD90 from 155 +/- 2 ms to 171 +/- 2 ms (n = 21, P < 0.001). In the presence of erythromycin, thiopental at 10, 25, and 50 microM caused significantly greater prolongation from a control of 171 +/- 2 ms by 39 +/- 2, 58 +/- 3, and 72 +/- 6 ms, respectively. Whole-cell patch-clamp experiments indicated that thiopental inhibited I(K) and I(Kl). Conclusions Intravenous anesthetics caused markedly different effects on ventricular repolarization. Thiopental, unlike propofol and ketamine, potentiated the effects of erythromycin on ventricular repolarization by inhibiting I(K) and I(Kl).

Utility of the JT Peak Interval and the JT Area in Determining the Proarrhythmic Potential of QT-Shortening Agents

2018 ◽  
Vol 24 (2) ◽  
pp. 160-171 ◽  
Author(s):  
Bo Qiu ◽  
Yuhong Wang ◽  
Congxin Li ◽  
Huicai Guo ◽  
Yanfang Xu
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Potassium Channel ◽  
Early Phase ◽  
Characteristic Curve ◽  
Ventricular Tachyarrhythmia ◽  
Ventricular Repolarization ◽  
Dependent Manner ◽  
Potassium Channel Openers ◽  
Concentration Dependent Manner

Drug-induced long QT increases the risk of ventricular tachyarrhythmia known as torsades de pointes (TdP). Many biomarkers have been used to predict TdP. At present, however, there are few biomarkers for arrhythmias induced by QT-shortening drugs. The objective of the present study was to identify the best biomarkers for predicting arrhythmias caused by the 4 potassium channel openers ICA-105574, NS-1643, R-L3, and pinacidil. Our results showed that, at higher concentrations, all 4 potassium channel openers induced ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts, but not in rabbit hearts. The electrocardiography parameters were measured including QT/QTc, JT peak, Tp-e interval, JT area, short-term beat-to-beat QT interval variability (STV), and index of cardiac electrophysiological balance (iCEB). We found that the potassium channel openers at test concentrations shortened the QT/QTc and the JT peak interval and increased the JT area. Nevertheless, even at proarrhythmic concentrations, they did not always change STV, Tp-e, or iCEB. Receiver operating characteristic curve analysis showed that the JT peak interval representing the early repolarization phase and the JT area reflecting the dispersion of ventricular repolarization were the best predictors of VT/VF. Action potential recordings in guinea pig papillary muscle revealed that except for pinacidil, the potassium channel openers shortened APD30 in a concentration-dependent manner. They also evoked early or delayed afterdepolarizations at fast pacing rates. Patch-clamp recordings in guinea pig ventricular cardiomyocytes showed that the potassium channel openers enhanced the total outward currents during the early phase of action potential repolarization, especially at proarrhythmic concentrations. We concluded that the JT peak interval and the JT area are surrogate biomarkers identifying the risk of proarrhythmia associated with the administration of QT-shortening agents. The acceleration of early-phase repolarization and the increased dispersion of ventricular repolarization may contribute to the occurrence of arrhythmias.

Clobutinol Delays Ventricular Repolarization in the Guinea Pig Heart: Comparison With Cardiac Effects of hERG K+ Channel Inhibitor E-4031

2009 ◽  
Vol 54 (6) ◽  
pp. 552-559 ◽  
Author(s):  
Akira Takahara ◽  
Rieko Sasaki ◽  
Mariko Nakamura ◽  
Akiko Sendo ◽  
Yukiko Sakurai ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Ventricular Repolarization ◽  
K Channel ◽  
Guinea Pig Heart ◽  
Cardiac Effects

Effect of Contraceptive Steroids on the Endometrium of Guinea Pig: SEM study

1977 ◽  
Vol 35 ◽  
pp. 668-669
Author(s):  
Mai M. Said ◽  
Ramesh K. Nayak ◽  
Randall E. McCoy
Keyword(s):  
Guinea Pig ◽  
Reproductive Tract ◽  
Three Dimensional ◽  
Female Reproductive Tract ◽  
Human Female ◽  
Surface Ultrastructure ◽  
Transmission Electron ◽  
Sem Study ◽  
Uterine Mucosa ◽  
Group 1

Burgos and Wislocki described changes in the mucosa of the guinea pig uterus, cervix and vagina during the estrous cycle investigated by transmission electron microscopy. More recently, Moghissi and Reame reported the effects of progestational agents on the human female reproductive tract. They found drooping and shortening of cilia in norgestrel and norethindrone- treated endometria. To the best of our knowledge, no studies concerning the effects of mestranol and norethindrone given concurrently on the three-dimensional surface features on the uterine mucosa of the guinea pig have been reported. The purpose of this study was to determine the effect of mestranol and norethindrone on surface ultrastructure of guinea pig uterus by SEM.Seventy eight animals were used in this study. They were allocated into two groups. Group 1 (20 animals) was injected intramuscularly 0.1 ml vegetable oil and served as controls.

Ultrastructure and Drug Metabolism in the Developing Guinea Pig

1973 ◽  
Vol 31 ◽  
pp. 538-539
Author(s):  
W. Kuenzig ◽  
M. Boublik ◽  
J.J. Kamm ◽  
J.J. Burns
Keyword(s):  
Guinea Pig ◽  
Metabolic Activity ◽  
Animal Species ◽  
Adult Animal ◽  
Smooth Endoplasmic Reticulum ◽  
Fetal Life ◽  
Mixed Function Oxidase ◽  
Cytochrome P 450 ◽  
Microsomal Mixed Function Oxidase ◽  
Mixed Function Oxidase Activity

Unlike a variety of other animal species, such as the rabbit, mouse or rat, the guinea pig has a relatively long gestation period and is a more fully developed animal at birth. Kuenzig et al. reported that drug metabolic activity which increases very slowly during fetal life, increases rapidly after birth. Hepatocytes of a 3-day old neonate metabolize drugs and reduce cytochrome P-450 at a rate comparable to that observed in the adult animal. Moreover the administration of drugs like phenobarbital to pregnant guinea pigs increases the microsomal mixed function oxidase activity already in the fetus.Drug metabolic activity is, generally, localized within the smooth endoplasmic reticulum (SER) of the hepatocyte.

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