scholarly journals Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology

2020 ◽  
Vol 116 (13) ◽  
pp. 2081-2090 ◽  
Author(s):  
Erik S Dietrichs ◽  
Karen McGlynn ◽  
Andrew Allan ◽  
Adam Connolly ◽  
Martin Bishop ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Cardiac Electrophysiology ◽  
Relative Effect ◽  
Moderate Hypothermia ◽  
Conduction Time ◽  
Ventricular Fibrillation Threshold ◽  
Severe Hypothermia ◽  
Qt Intervals ◽  
Ventricular Activation

Abstract Aims Treatment of arrhythmias evoked by hypothermia/rewarming remains challenging, and the underlying mechanisms are unclear. This in vitro experimental study assessed cardiac electrophysiology in isolated rabbit hearts at temperatures occurring in therapeutic and accidental hypothermia. Methods and results Detailed ECG, surface electrogram, and panoramic optical mapping were performed in isolated rabbit hearts cooled to moderate (31°C) and severe (17°C) hypothermia. Ventricular activation was unchanged at 31°C while action potential duration (APD) was significantly prolonged (176.9 ± 4.2 ms vs. 241.0 ± 2.9 ms, P < 0.05), as was ventricular repolarization. At 17°C, there were proportionally similar delays in both activation and repolarization. These changes were reflected in the QRS and QT intervals of ECG recordings. Ventricular fibrillation threshold was significantly reduced at 31°C (16.3 ± 3.1 vs. 35 ± 3.5 mA, P < 0.05) but increased at 17°C (64.2 ± 9.9, P < 0.05). At 31°C, transverse conduction was relatively unchanged by cooling compared to longitudinal conduction, but at 17°C both transverse and longitudinal conduction were proportionately reduced to a similar extent. The gap junction uncoupler heptanol had a larger relative effect on transverse than longitudinal conduction and was able to restore the transverse/longitudinal conduction ratio, returning ventricular fibrillation threshold to baseline values (16.3 ± 3.1 vs. 36.3 ± 4.3 mA, P < 0.05) at 31°C. Rewarming to 37°C restored the majority of the electrophysiological parameters. Conclusions Moderate hypothermia does not significantly change ventricular conduction time but prolongs repolarization and is pro-arrhythmic. Further cooling to severe hypothermia causes parallel changes in ventricular activation and repolarization, changes which are anti-arrhythmic. Therefore, relative changes in QRS and QT intervals (QR/QTc) emerge as an ECG-biomarker of pro-arrhythmic activity. Risk for ventricular fibrillation appears to be linked to the relatively low temperature sensitivity of ventricular transmural conduction, a conclusion supported by the anti-arrhythmic effect of heptanol at 31°C.

Formulation of Oral Mucoadhesive Tablets using Mucilage Isolated from Buchanania lanzan spreng Seeds

2014 ◽  
Vol 7 (2) ◽  
pp. 2494-2503
Author(s):  
Sudarshan Singh ◽  
Ayaz Ahmad ◽  
Sunil Bothara B
Keyword(s):  
Drug Delivery ◽  
Guar Gum ◽  
Physical Property ◽  
Flow Property ◽  
Relative Effect ◽  
Losartan Potassium ◽  
In Vitro Dissolution ◽  
Wet Granulation ◽  
Microbial Count

The present study was taken to formulate and evaluate mucilage obtained from Buchanania lanzan spreng seeds (BL) belonging to family anacardiacea for oral mucoadhesive drug delivery system containing losartan potassium. Physiochemical characteristics of mucilage, such as swelling index, microbial count, viscosity, hydration capacity, flow property, and pH were studied. The mucilage was evaluated for its mucoadhesive properties in compressed tablet, containing losartan potassium. Granules were prepared by wet granulation process using polyvinylpyrrolidone as binding agent. Mucilage was used in four different concentrations i.e., 21, 42 and 55% w/w. The tablet were prepared and evaluated for its physical property. Further, in vitro dissolution and swelling index was determined. The property of bioadhesive strength of isolated mucilage was compared with Guar gum and HPMC E5LV, which was used as standard mucoadhesive agent concentration. Bioadhesive strength of the tablet was measured on the modified physical balance. Result revealed that tablets had good physiochemical properties, and drug release was retarded as concentration of mucilage was increased. The force of adhesion was obtained 0.1238N, 0.2822N, 0.5175N, 0.8679N and 0.3983N respectively for F1, F2, F3, F4 and F5. Formulations were subjected for study the effect of agitation at different rpm. Formulation showed relative effect on release of drug from formulation. All the formulations were subjected to stability studies for three months, all formulations showed stability with respect to release pattern. In conclusions, these results indicate that the seed mucilage of BL can be a suitable excipient for oral mucoadhesive drug delivery systems.  

scholarly journals Automated Framework for the Inclusion of a His–Purkinje System in Cardiac Digital Twins of Ventricular Electrophysiology

2021 ◽  
Author(s):  
Karli Gillette ◽  
Matthias A. F. Gsell ◽  
Julien Bouyssier ◽  
Anton J. Prassl ◽  
Aurel Neic ◽  
...  
Keyword(s):  
Cardiac Electrophysiology ◽  
Ventricular Myocardium ◽  
Activation Patterns ◽  
Purkinje System ◽  
Digital Twins ◽  
Emergent Features ◽  
Ventricular Activation ◽  
Endocardial Layer ◽  
Right Ventricular Apical Pacing ◽  
Electrocardiogram Ecg

AbstractPersonalized models of cardiac electrophysiology (EP) that match clinical observation with high fidelity, referred to as cardiac digital twins (CDTs), show promise as a tool for tailoring cardiac precision therapies. Building CDTs of cardiac EP relies on the ability of models to replicate the ventricular activation sequence under a broad range of conditions. Of pivotal importance is the His–Purkinje system (HPS) within the ventricles. Workflows for the generation and incorporation of HPS models are needed for use in cardiac digital twinning pipelines that aim to minimize the misfit between model predictions and clinical data such as the 12 lead electrocardiogram (ECG). We thus develop an automated two stage approach for HPS personalization. A fascicular-based model is first introduced that modulates the endocardial Purkinje network. Only emergent features of sites of earliest activation within the ventricular myocardium and a fast-conducting sub-endocardial layer are accounted for. It is then replaced by a topologically realistic Purkinje-based representation of the HPS. Feasibility of the approach is demonstrated. Equivalence between both HPS model representations is investigated by comparing activation patterns and 12 lead ECGs under both sinus rhythm and right-ventricular apical pacing. Predominant ECG morphology is preserved by both HPS models under sinus conditions, but elucidates differences during pacing.

Effects of physiological aging on cardiac electrophysiology in perfused Fischer 344 rat hearts

1992 ◽  
Vol 262 (1) ◽  
pp. H97-H105 ◽  
Author(s):  
O. Schmidlin ◽  
S. Bharati ◽  
M. Lev ◽  
J. B. Schwartz
Keyword(s):  
Heart Rate ◽  
Age Differences ◽  
Cardiac Electrophysiology ◽  
Histopathological Examination ◽  
Conduction Time ◽  
Fischer 344 Rats ◽  
Aging Effects ◽  
Middle Aged ◽  
Fischer 344 ◽  
Av Conduction

Aging effects on heart rate and atrioventricular (AV) conduction were studied in Langendorff-perfused hearts from 18 mature (4-6 mo), 12 middle-aged (12-14 mo), and 18 senescent (24-26 mo) Fischer 344 rats. Heart rate decreased with increasing age from 218 +/- 18 in mature to 196 +/- 27 (mean +/- SD) beats/min in middle-aged rats to 183 +/- 22 beats/min in senescent rats (analysis of variance, P less than 0.001). Spontaneous AV conduction time increased from 43 +/- 7 to 49 +/- 5 to 62 +/- 9 ms with aging (P less than 0.0001). Paced AV conduction time also lengthened with aging, and AV Wenckebach block cycle length increased from 122 +/- 10 to 133 +/- 9 to 152 +/- 16 ms (P less than 0.005). Intra-atrial conduction time was unaffected by age. Age differences in heart rate and AV conduction responses to isoproterenol (0.5 x 10(-9) to 1 x 10(-7) M) were noted with greater sensitivity at lower doses in hearts from younger rats. In separate experiments, 18 mature and 19 senescent Fischer 344 rats received reserpine (0.25 mg.kg-1.day-1 ip) for 6 days before study. Age differences in heart rate and AV conduction persisted (P less than 0.0001). Histopathological examination of AV nodal and His-bundle tissues in three hearts from each age group showed increased intercellular collagen with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Perinatal hyperoxia for 14 days increases nerve conduction time and the acute unitary response to hypoxia of rat carotid body chemoreceptors

2005 ◽  
Vol 99 (1) ◽  
pp. 114-119 ◽  
Author(s):  
David F. Donnelly ◽  
Insook Kim ◽  
Claire Carle ◽  
John L. Carroll
Keyword(s):  
Functional Impairment ◽  
Nerve Conduction ◽  
Single Unit ◽  
Acute Hypoxia ◽  
Adult Life ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Conduction Time ◽  
Activity Levels

Hyperoxia in the immediate perinatal period, but not in adult life, is associated with a life-long impairment of the ventilatory response to acute hypoxia. This effect is attributed to a functional impairment of peripheral chemoreceptors, including a reduction in the number of chemoreceptor afferent fibers and a reduction in “whole nerve” afferent activity. The purpose of the present study was to assess the activity levels of single chemoreceptor units in the immediate posthyperoxic period to determine whether functional impairment extended to single chemoreceptor units and whether the impairment was only induced by hyperoxia exposure in the immediate postnatal period. Two groups of rat pups were exposed to 60% inspired O2 fraction for 2 wk at ages 0–14 days and 14–28 days, at which time single-unit activities were isolated and recorded in vitro. Compared with control pups, hyperoxia-treated pups had a 10-fold reduction in baseline (normoxia) spiking activity. Peak unit responses to 12, 5, and 0% O2 were reduced and nerve conduction time was significantly slower in both hyperoxia-treated groups compared with control groups. We conclude that 1) hyperoxia greatly reduces single-unit chemoreceptor activities during normoxia and acute hypoxia, 2) the treatment effect is not limited to the immediate newborn period, and 3) at least part of the impairment may be due to changes in the afferent axonal excitability.

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