scholarly journals Effects of genetic background, sex, and age on murine atrial electrophysiology

EP Europace ◽  
2021 ◽  
Author(s):  
Julius Obergassel ◽  
Molly O’Reilly ◽  
Laura C Sommerfeld ◽  
S Nashitha Kabir ◽  
Christopher O’Shea ◽  
...  
Keyword(s):  
Genetic Background ◽  
Monophasic Action Potential ◽  
Atrial Arrhythmias ◽  
Activation Time ◽  
Factors Influencing ◽  
Normal Ranges ◽  
Atrial Electrophysiology ◽  
Cycle Lengths ◽  
Perfused Hearts ◽  
Atrial Effective Refractory Period

Abstract Aims Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized. Methods and results We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107 male) from 2.5 to 17.7 months (mean 7 months) with different genetic backgrounds (C57BL/6, FVB/N, MF1, 129/Sv, Swiss agouti). Left atrial monophasic action potential duration (LA-APD), interatrial activation time (IA-AT), and atrial effective refractory period (ERP) were summarized at different pacing cycle lengths (PCLs). Factors influencing atrial electrophysiology including genetic background, sex, and age were determined. LA-APD70 was 18 ± 0.5 ms, atrial ERP was 27 ± 0.8 ms, and IA-AT was 17 ± 0.5 ms at 100 ms PCL. LA-APD was longer with longer PCL (+17% from 80 to 120 ms PCL for APD70), while IA-AT decreased (−7% from 80 to 120 ms PCL). Female sex was associated with longer ERP (+14% vs. males). Genetic background influenced atrial electrophysiology: LA-APD70 (−20% vs. average) and atrial ERP (−25% vs. average) were shorter in Swiss agouti background compared to others. LA-APD70 (+25% vs. average) and IA-AT (+44% vs. average) were longer in 129/Sv mice. Atrial ERP was longer in FVB/N (+34% vs. average) and in younger experimental groups below 6 months of age. Conclusion This work defines normal ranges for murine atrial EP parameters. Genetic background has a profound effect on these parameters, at least of the magnitude as those of sex and age. These results can inform the experimental design and interpretation of murine atrial electrophysiology.

Effects of sterile pericarditis on connexins 40 and 43 in the atria: correlation with abnormal conduction and atrial arrhythmias

2007 ◽  
Vol 293 (2) ◽  
pp. H1231-H1241 ◽  
Author(s):  
Kyungmoo Ryu ◽  
Li Li ◽  
Celeen M. Khrestian ◽  
Naomichi Matsumoto ◽  
Jayakumar Sahadevan ◽  
...  
Keyword(s):  
Volume Fraction ◽  
Immunoblot Analysis ◽  
Atrial Arrhythmias ◽  
Fibroblast Proliferation ◽  
Activation Time ◽  
Vimentin Expression ◽  
Cycle Lengths ◽  
Rapid Pacing ◽  
The Right ◽  
Transmural Gradient

The canine sterile pericarditis model is characterized by impaired conduction and atrial arrhythmia vulnerability. Electrical and structural remodeling processes caused by the inflammatory response likely promote these abnormalities. In the present study, we tested the hypothesis that altered distribution of atrial connexins is associated with markedly abnormal atrial conduction, thereby contributing to vulnerability to atrial flutter (AFL) and atrial fibrillation (AF) induction and maintenance. During rapid pacing and induced, sustained AFL or AF in five sterile pericarditis (SP) and five normal (NL) dogs, epicardial atrial electrograms were recorded simultaneously from both atria (380 electrodes) or from the right atrium (RA) and Bachmann's bundle (212 electrodes). Tissues from RA sites were subjected to immunostaining and immunoblotting to assess connexin (Cx) 40 and Cx43 distribution and expression. Transmural myocyte (α-actinin) and fibroblast (vimentin) volume were also assessed by immunostaining. RA pacing maps showed markedly abnormal conduction in SP, with uniform conduction in NL. Total RA activation time was significantly prolonged in SP vs. NL at 300-ms and 200-ms pacing-cycle lengths. Sustained arrhythmias were only inducible in SP [total: 4/5 (AFL: 3/5; AF: 1/5)]. In NL, Cx40, Cx43, α-actinin, and vimentin were homogeneously distributed transmurally. In SP, Cx40, Cx43, and α-actinin were absent epicardially, decreased midmyocardially, and normal endocardially. SP increased epicardial vimentin expression, suggesting fibroblast proliferation. Immunoblot analysis confirmed reduced expression of Cx40 and Cx43 in SP. The transmural gradient in the volume fraction of Cx40 and Cx43 in SP is associated with markedly abnormal atrial conduction and is likely an important factor in the vulnerability to induction and maintenance of AFL/AF in SP.

scholarly journals Diurnal variations of the dominant cycle length of chronic atrial fibrillation

2001 ◽  
Vol 280 (1) ◽  
pp. H401-H406 ◽  
Author(s):  
Carl J. Meurling ◽  
Johan E. P. Waktare ◽  
Fredrik Holmqvist ◽  
Antti Hedman ◽  
A. John Camm ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cycle Length ◽  
Vagal Tone ◽  
Chronic Atrial Fibrillation ◽  
Frequency Domain Analysis ◽  
Diurnal Variations ◽  
Diurnal Fluctuation ◽  
Cycle Lengths ◽  
Parasympathetic Influences ◽  
Atrial Effective Refractory Period

High-resolution digital Holter recording was carried out in 21 patients (15 men, 64 ± 12 yr) with chronic atrial fibrillation. Dominating atrial cycle length (DACL) was derived by frequency domain analysis of QRST-reduced electrocardiograms. Daytime mean DACL was 150 ± 17 ms, and nighttime mean was 157 ± 22 ms ( P = 0.0002). Diurnal fluctuation in DACL differed among patients: it tended to be virtually absent in those with a short mean DACL, but in those with longer DACL the night-day difference was as much as 23 ms ( R = 0.72, P < 0.001, correlation of mean DACL to night-day difference). Mean DACL also correlated with ventricular cycle length ( R = 0.40, P < 0.001), particularly at night ( r = 0.49). The shorter cycle lengths found in this study during the day are consistent with sympathetic and/or other physiological modulation, but since increased vagal tone shortens atrial refractoriness in most models, parasympathetic influences are not likely to play a major role. Alternatively, atrial effective refractory period may not be the sole determinant of atrial cycle length during atrial fibrillation.

1272Effect of age, genetic background and experimental conditions on left atrial monophasic action potential duration, effective refractory period and activation time in Langendorff-perfused murine hearts

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
J Obergassel ◽  
S N Kabir ◽  
M O"reilly ◽  
L C Sommerfeld ◽  
C O"shea ◽  
...  
Keyword(s):  
Body Weight ◽  
Action Potential ◽  
Genetic Background ◽  
Left Atrial ◽  
Coronary Flow ◽  
Weight Ratio ◽  
Monophasic Action Potential ◽  
Heart Weight ◽  
Body Weight Ratio ◽  
Experimental Conditions

Abstract Funding Acknowledgements Supported by EU [CATCH ME] 633196, British Heart Foundation FS/13/43/30324, AA/18/2/34218 LF, PK, DFG FA413 LF, Studienstiftung to JO. Background Studying cardiac electrophysiology in isolated perfused beating murine hearts is a well-established method. The range of normal values for left atrial action potential durations (LA-APD), activation times (LA-AT) and effective refractory periods (atrial ERP) in murine wildtype (WT) is not well known. Purpose This study aimed to establish reference values for LA-APD, LA-AT and atrial ERP and to identify factors that influence these electrophysiological parameters in wildtype (WT) mice. Method We combined results from isolated beating heart Langendorff experiments carried out in WT between 2005 and 2019 using an octopolar catheter inserted into the right atrium and a monophasic action potential electrode recording from the LA epicardium. Electrophysiological parameters (LA-APD at 50%, 70%, 90% repolarization (APD50, APD70, APD90), LA-AT and atrial ERP) at different pacing cycle lengths (PCL) were summarized. We analyzed effects of PCL, genetic background, age, gender, heart weight to body weight ratio (HW/BW), LA weight to body weight ratio (LAW/BW) as well as coronary flow and temperature as experimental conditions. Results Electrophysiological parameters from 222 isolated hearts (114 female, mean age 6.6 ± 0.25 months, range 2.47-17.7 months) of different backgrounds (77 C57BL/6, 23 FVB/N, 33 MF1, 69 129/Sv and 20 Swiss agouti) were combined. Coronary flow rate, flow temperature and start of isolation to cannulation time were constant experimental conditions over the timespan of experiments. LA-APD was longer while LA-AT decreased with longer PCL throughout all genetic backgrounds (Figure 1A). Genetic background showed strong effects on all electrophysiological parameters. LA activation was delayed in 129/Sv compared to other backgrounds (Figure 1D). LA-APD70 and atrial ERP were significantly shorter in Swiss agouti background compared to others. LA-APD70 was also significantly prolonged in 129/Sv background compared to MF1 (Figure 1C). Atrial ERP was longer in FVB/N compared to other backgrounds. Age effects were compared in groups. Atrial ERP was significantly longer in mice ≤ 3 months compared to all older mice. Atrial ERP was also significantly prolonged (+ 3.4ms, + 13.5%) in female mice compared to males (Figure 1B). Conclusion This dataset summarizes left atrial electrophysiological parameters in the beating mouse heart and can serve as a reference for design and interpretation of electrophysiological experiments in murine models of commonly used genetic backgrounds. We confirm that cycle length, genetic background, age and gender affect atrial electrophysiological parameters. Awareness of these will support successful experimental design. Abstract Figure 1

Cardiac electrophysiological variables in blood-perfused and buffer-perfused, isolated, working rabbit heart

1996 ◽  
Vol 271 (2) ◽  
pp. H784-H789 ◽  
Author(s):  
A. M. Gillis ◽  
E. Kulisz ◽  
H. J. Mathison
Keyword(s):  
Ventricular Fibrillation ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
High Cardiac Output ◽  
Ventricular Afterload ◽  
Cardiac Hemodynamics ◽  
Perfused Hearts ◽  
Krebs Henseleit Buffer

Effects of crystalloid buffer and blood-buffer perfusates on cardiac electrophysiological parameters were compared in four groups of isolated, working rabbit hearts. Hearts were perfused with Krebs-Henseleit buffer or blood plus Krebs-Henseleit buffer (10% hematocrit) over a range of left ventricular afterload (30-100 cmH2O) and cardiac outputs (30-180 ml/min). Left ventricular monophasic action potential duration (APD) was significantly shorter at low afterload and high cardiac output in buffer-perfused (114 +/- 35 ms) compared with blood-perfused hearts (177 +/- 23 ms, P < 0.001). APD shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05), and APD was similar in blood-perfused (151 +/- 19 ms) compared with buffer-perfused hearts (142 +/- 24 ms, P = NS). Ventricular effective refractory period (VERP) was significantly shorter at low afterload in buffer-perfused (154 +/- 32 ms) compared with blood-perfused hearts (227 +/- 17 ms, P < 0.001). VERP shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05) and was similar in blood-perfused (166 +/- 26 ms) compared with buffer-perfused hearts (151 +/- 37 ms, P = NS). Determination of VERP was associated with induction of ventricular fibrillation in 10 of 15 buffer-perfused hearts, whereas ventricular fibrillation was not observed in blood-perfused hearts (P < 0.001). Thus significant differences in ventricular repolarization and cardiac hemodynamics are observed in working rabbit hearts perfused with a blood-buffer perfusate compared with a crystalloid buffer. Blood-perfused working hearts are electrophysiologically more stable.

Abstract 16295: Human Epicardial Bipolar Electrograms Prolong and Reduce in Amplitude Prior to Induction of Peri-Operative Atrial Fibrillation and Are Related to Sites of High Electrogram Dominant Frequency in Sinus Rhythm

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Junaid Zaman ◽  
Leanne Harling ◽  
Thanos Athanasiou ◽  
Nicholas S Peters
Keyword(s):  
Sinus Rhythm ◽  
Artery Bypass ◽  
Dominant Frequency ◽  
Bypass Grafting ◽  
Activation Time ◽  
Frequency Domains ◽  
Cycle Lengths ◽  
Electrophysiological Findings ◽  
Atrial Activation ◽  
Right Atria

Background: The exact trigger/substrate interactions leading to post-operative AF are unknown. Sites of high DF in sinus rhythm are proposed to harbor ‘fibrillar myocardium’ or ‘AF nests’. We studied AF inducibility related to putative upstream substrate changes by characterising epicardial electrograms (EGM) in both time and frequency domains. Method: AF naïve patients (n=14) undergoing coronary artery bypass grafting (CABG) had bipolar electrograms recorded from the lateral right atria (RA) wall with a high density spiral catheter, sampled at 1kHz. RA burst pacing at cycle lengths (CL) of 200, 500 and 1000ms was performed with any episodes of AF > 30s recorded. Electrograms were analysed using an average of 5 consecutive beats for duration, peak to peak amplitude, dominant frequency (DF) and activation time at all bipole pairs during every pacing drive train (total EGMs analysed 3430). Results: Bipolar EGM duration was significantly longer during AF (mean = 76.64ms, SD = 29.35ms) than all other CLs or NSR (p<0.0001). There was no difference between CLs but a trend to longer EGM at 200ms CL. EGM amplitude was significantly smaller during AF (mean = 0.85mV, SD = 0.51mv) vs. 500ms CL and NSR (p<0.0001) and at 200ms vs. 500ms CL (p<0.05) and NSR (p<0.0001). The EGM DF was significantly lower in AF (mean = 75.87Hz, SD = 23.63Hz) vs NSR (mean = 89.33Hz, SD = 25.99Hz) (p<0.05) but not vs. pacing CLs. Activation time was significantly prolonged at 200ms CL (mean = 29.41ms, SD = 16.23ms) vs AF and NSR (p<0.001 and 0.05 respectively). Conclusions: Human bipolar EGMs prolong and reduce in amplitude in induced peri-operative AF than in NSR or pacing. Atrial activation slows at 200ms CL, prior to initiation of AF. These changes are accompanied by high DF sites in NSR which may reveal underlying ‘AF nests’ even in non-remodelled atria. These novel peri-operative electrophysiological findings suggest upstream substrate changes which may predispose patients to post-operative AF.

Cellular and environmental factors influencing biofilm formation and colonization of plant tissue by a beneficial strain of bacteria, Pseudomonas donghuensis P482.

2020 ◽  
Author(s):  
Magdalena Rajewska ◽  
Marta Matuszewska ◽  
Sylwia Jafra
Keyword(s):  
Antimicrobial Activity ◽  
Environmental Factors ◽  
Biofilm Formation ◽  
Genetic Background ◽  
Plant Pathogens ◽  
Knock Out ◽  
Factors Influencing ◽  
Fungal Plant Pathogens ◽  
Artificial Surfaces ◽  
Strain Type

&lt;p&gt;The ability to colonize different environmental niches by bacteria is most&amp;#160;often determined by the ability to form biofilms - complex, multicellular&amp;#160;communities. This, in turn, depends on both cellular and extracellular&amp;#160;factors such as genetic background of the strain, type of surface (biotic&amp;#160;or abiotic) to which bacteria attach, availability of nutrients,&amp;#160;temperature, &lt;em&gt;etc&lt;/em&gt;. &lt;em&gt;Pseudomonas donghuensis&lt;/em&gt; P482 strain is a little-known&amp;#160;isolate from tomato rhizosphere, exhibiting antimicrobial activity towards&amp;#160;bacterial and fungal plant pathogens. Studies have shown that it&amp;#160;efficiently colonizes plant rhizosphere and forms biofilm on artificial&amp;#160;surfaces. Which genetic or environmental factors underlie the mechanism of&amp;#160;biofilm formation were yet to be elucidated. The presented research aimed&amp;#160;at identifying those factors. Basing on the analysis of genome, knock-out&amp;#160;mutants of the P482 strain were constructed in the genes potentially&amp;#160;involved in biofilm formation and further analyzed for motility, colony&amp;#160;morphology, attachment to artificial surfaces in different culture&amp;#160;conditions, and colonization of maize and tomato rhizosphere.&lt;/p&gt;

scholarly journals Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

2011 ◽  
Vol 300 (6) ◽  
pp. H2230-H2237 ◽  
Author(s):  
David Benoist ◽  
Rachel Stones ◽  
Mark Drinkhill ◽  
Olivier Bernus ◽  
Ed White
Keyword(s):  
Action Potential ◽  
Right Ventricular ◽  
Action Potential Duration ◽  
Ventricular Hypertrophy ◽  
Pulmonary Artery Hypertension ◽  
Monophasic Action Potential ◽  
Rt Pcr ◽  
Arrhythmogenic Substrate ◽  
Ventricular Tachycardias ◽  
Perfused Hearts

Mechanisms associated with right ventricular (RV) hypertension and arrhythmias are less understood than those in the left ventricle (LV). The aim of our study was to investigate whether and by what mechanisms a proarrhythmic substrate exists in a rat model of RV hypertension and hypertrophy. Rats were injected with monocrotaline (MCT; 60 mg/kg) to induce pulmonary artery hypertension or with saline (CON). Myocardial levels of mRNA for genes expressing ion channels were measured by real-time RT-PCR. Monophasic action potential duration (MAPD) was recorded in isolated Langendorff-perfused hearts. MAPD restitution was measured, and arrhythmias were induced by burst stimulation. Twenty-two to twenty-six days after treatment, MCT animals had RV hypertension, hypertrophy, and decreased ejection fractions compared with CON. A greater proportion of MCT hearts developed sustained ventricular tachycardias/fibrillation (0.83 MCT vs. 0.14 CON). MAPD was prolonged in RV and less so in the LV of MCT hearts. There were decreased levels of mRNA for K+ channels. Restitution curves of MCT RV were steeper than CON RV or either LV. Dispersion of MAPD was greater in MCT hearts and was dependent on stimulation frequency. Computer simulations based on ion channel gene expression closely predicted experimental changes in MAPD and restitution. We have identified a proarrhythmic substrate in the hearts of MCT-treated rats. We conclude that steeper RV electrical restitution and rate-dependant RV-LV action potential duration dispersion may be contributing mechanisms and be implicated in the generation of arrhythmias associated with in RV hypertension and hypertrophy.

Effects of Thoracic Epidural Anesthesia with and without Autonomic Nervous System Blockade on Cardiac Monophasic Action Potentials and Effective Refractoriness in Awake Dogs

2001 ◽  
Vol 95 (1) ◽  
pp. 132-138 ◽  
Author(s):  
Andreas Meissner ◽  
Lars Eckardt ◽  
Paulus Kirchhof ◽  
Thomas Weber ◽  
Norbert Rolf ◽  
...  
Keyword(s):  
Action Potential ◽  
Epidural Anesthesia ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Monophasic Action Potential ◽  
Thoracic Epidural Anesthesia ◽  
Thoracic Epidural ◽  
Monophasic Action Potentials ◽  
Cycle Lengths

Background The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization. Methods The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters. Results Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected. Conclusions This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.

Abstract 14317: Kvβ2 Mediates Cardiac Repolarization and Injury: Role of Pyridine Nucleotides

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kalyan C Chapalamadugu ◽  
Jared Tur ◽  
Javier Cuevas ◽  
Chris Katnik ◽  
Srinivas M Tipparaju
Keyword(s):  
Ex Vivo ◽  
Pyridine Nucleotide ◽  
Heart Tissue ◽  
Monophasic Action Potential ◽  
Cardiac Repolarization ◽  
Qtc Interval ◽  
Pyridine Nucleotides ◽  
Kv Channel ◽  
Perfused Hearts

Background: Voltage-gated potassium channel (Kv) β2 subunits (Kvβ2) belong to the aldoketo-reductase superfamily and associate with the Kv channel modulating its function. Also, Kvβ2 binds pyridine nucleotides (NAD[P] + /NAD[P]H) with high affinity altering Kv channel gating. However, the physiological relevance of Kvβ2 in cardiac health and disease is unknown. Hypothesis: We tested the hypothesis that Kvβ2 is essential to both basal and pyridine nucleotide mediated regulation of cardiac repolarization. Methods and Results: Kvβ2 knockout (KO) and wild type (Wt) mice were utilized for this study. ECG analysis showed prolonged QTc interval (74.7± 3.7 vs. 65.6 ± 3, n=3 , p<0.05 ) in KO mice when compared to Wt. Monophasic action potential (MAP) data also showed prolonged duration (ms) at 50% repolarization level in KO mouse hearts vs. Wt (MAPD50; 13.2 ± 0.3 vs. 9.7 ± 0.6, n=5-6 , p<0.05 ). To test the obligatory role of Kvβ2 in pyridine nucleotide modulation of cardiac repolarization, we exposed ex vivo perfused hearts or isolated cardiomyocytes to higher lactate levels. These data revealed that acute lactate exposure leads to significant but similar raise in NADH concentration [NADH] i in both KO and Wt heart tissue. However, marked repolarization deficits appeared only in Wt group when tested utilizing ex vivo perfused hearts (MAPD50 - Wt:11.5 ± 0.7 vs. 8.3 ± 0.5, p<0.05 ; KO:12.6 ± 0.7 vs. 12± 0.5, p=0.5 , ms) or isolated myocytes (ΔAPD50 – Wt: 4.7±1.6 ms, p<0.05 ; KO:1.5 ± 0.7 ms, p=0.1 ). Perfusion with high pyruvate levels returned both [NADH] i and MAPD50 to basal levels in Wt mouse hearts. Similarly, we observed that a 14 day isoproterenol treatment also leads to significant increase in cardiac [NADH] i , but only the Wt mouse hearts showed significant repolarization deficits; ex-MAPD50 (5.5 ± 1.6, p< 0.01 ), when compared to no changes in KO (1.9 ± 0.9, p< 0.1) . Conclusions: Our results suggest that Kvβ2 regulates cardiac repolarization. Further, the differential repolarization changes despite similar increases in cardiac [NADH] i indicates an obligatory role of Kvβ2 in the pyridine nucleotide modulation of cardiac repolarization.

Monophasic action potential recordings in response to graded hyperkalemia in dogs

1989 ◽  
Vol 256 (4) ◽  
pp. H956-H961
Author(s):  
P. M. Sutton ◽  
P. Taggart ◽  
D. W. Spear ◽  
H. F. Drake ◽  
R. H. Swanton ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Regional Differences ◽  
Monophasic Action Potential ◽  
Extracellular Potassium ◽  
Activation Time ◽  
Biphasic Response ◽  
The Difference ◽  
Alpha Chloralose

Recent interest in sudden cardiac death during exercise in normal healthy people has highlighted the possible role of swings of extracellular potassium in arrhythmogenesis in conditions other than ischemia. Regional differences in action potential duration and conduction may be important. We have recorded monophasic action potentials (MAPs) from the endocardium and epicardium in nine open-chest dogs during graded intravenous infusion of potassium up to a plasma level of 9 mM. The animals were anesthetized with alpha-chloralose and urethan. Continuous, online arterial potassium monitoring was employed. MAP duration showed a biphasic response with initial shortening up to 7 mM, which tended to be more obvious on the epicardium. Regional activation time was measured as the difference between the onset of depolarization of the endocardial and epicardial MAP. Regional activation time also showed a biphasic response with initial shortening and subsequent delay. The QRS width of the scalar lead II electrocardiogram also showed biphasic changes, and the T wave amplitude progressively decreased. Our results suggest that regional differences in repolarization time may develop in the nonischemic myocardium in response to increased extracellular potassium levels mainly as a result of local changes in regional activation time rather than as a result of a direct effect on action potential duration.

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