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Critical Volume of Human Myocardium Necessary to Maintain Ventricular Fibrillation.

ABSTRACT: Background: Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death because of ventricular fibrillation (VF). Consequently, Food and Drug Administration recommends testing all pharmacological agents for QT toxicity as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in cardiac tissue conductivity. Mines demonstrated in 1913 that cardiac wavelength (?) determines inducibility of reentrant arrhythmia, where both repolarization time or action potential duration and conduction velocity determine ?=action potential duration×conduction velocity. We aimed to determine the role of anisotropic wavelength in inducibility of VF in explanted human left ventricular preparations. We tested the hypothesis that 3-dimensional cardiac wavelength, which takes into account anisotropic cardiac tissue conductivity, can accurately predict VF sustainability.

Methods: We conducted panoramic optical mapping of coronary perfused human left ventricular wedge preparations subjected to pharmacologically induced shortening and prolongation of action potential duration, by I_K,ATP agonist pinacidil and antagonist glybenclamide, respectively. This measured action potential duration, conduction velocity, and thus determined pacing cycle length-dependent wavelengths in longitudinal (?_L), transverse (?_TV), and transmural (?_TM) directions using S1S1 pacing protocol, from which wavelength volume (V_?) was determined, as V_?=?_L×?_TV×?_TM, and compared with tissue volume_. We tested a hypothesis that tissue volume/V_? ratio can predict VF sustainability.

Results: At baseline, at pacing rate of 240 beats per minute, the wavelengths were ?_L=9.6±0.6 cm, ?_TV=4.2±0.3 cm, and ?_TM=5.8±0.2 cm, respectively (n=7), and thus V_?=246.4±42.1 cm³. Administration of pinacidil at escalating concentrations progressively decreased V_?, and VF became sustained, when tissue volume/V_? was above safety factor ?=4.4±0.6 (n=9) during rapid pacing. Treatment with glybenclamide decreased V_T/V_? below ? at any pacing rate and prevented VF sustainability.

Conclusions: Sustained VF was only sustained in ventricular volume exceeding critical V_?=?_L×?_TV×?_TM.

SUBMITTER: Aras KK

PROVIDER: S-EPMC7722395 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Critical Volume of Human Myocardium Necessary to Maintain Ventricular Fibrillation.

Aras Kedar K KK Faye Ndeye Rokhaya NR Cathey Brianna B Efimov Igor R IR

Circulation. Arrhythmia and electrophysiology 20181101 11

<h4>Background</h4>Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death because of ventricular fibrillation (VF). Consequently, Food and Drug Administration recommends testing all pharmacological agents for QT toxicity as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in ...[more]

PMID: 30376733

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Project description:PurposeTo determine whether left ventricular (LV) extracellular volume (ECV) expansion is associated with atrial fibrillation (AF) or AF-mediated LV systolic dysfunction (LVSD) while minimizing the influence of biologic and imaging methodologic confounders.Materials and methodsThis study examined the prevalence of LV ECV expansion in 137 patients with AF (mean age, 62 years ± 11 [standard deviation]; 92 male patients and 45 female patients; 83 paroxysmal and 54 persistent) who underwent preablation cardiovascular MRI. Biologic confounders were minimized by measuring the ECV fraction and excluding patients with severe LV hypertrophy, defined as wall thickness greater than 1.5 cm. Imaging confounders were minimized by using an arrhythmia-insensitive-rapid (AIR) cardiac T1 mapping pulse sequence. Other cardiac functional parameters, including LV ejection fraction (LVEF) and left atrial end-diastolic volume indexed to body surface area, were assessed using cine cardiovascular MRI. A substudy was conducted in 32 patients with no AF (mean age, 54 years ± 16) in sinus rhythm to establish control values and convert these values between the AIR sequence and literature-based modified Look-Locker inversion recovery (MOLLI) values.ResultsThe mean ECV was not significantly different (P > .05) between patients with AF with a normal LVEF (24.5% ± 2.8; n = 107), patients with AF with LVSD (24.5% ± 2.5; n = 30), and patients with no AF (24.4% ± 3.8; n = 32), but there was a significant interaction between ECV and CHA2DS2-VASc score (P = .045). Compared with the literature data obtained from healthy control patients scanned using MOLLI, 99.3% of patients with AF had ECV below the fibrosis cutoff point (32.8% when converted from MOLLI T1 mapping to AIR T1 mapping), including a subset of patients with AF (n = 28) with low CHA2DS2-VASc score (0/1 for men/women).ConclusionStudy results suggest that an LV ECV expansion is not associated with AF or AF-mediated LVSD. Supplemental material is available for this article. © RSNA, 2020See also the commentary by Stillman in this issue.

Project description:BackgroundHeart failure (HF) is associated with highly significant morbidity, mortality, and health care costs. Despite the significant advances in therapies and prevention, HF remains associated with poor clinical outcomes. Understanding the contractile force and kinetic changes at the level of cardiac muscle during end-stage HF in consideration of underlying etiology would be beneficial in developing targeted therapies that can help improve cardiac performance.ObjectiveInvestigate the impact of the primary etiology of HF (ischemic or non-ischemic) on left ventricular (LV) human myocardium force and kinetics of contraction and relaxation under near-physiological conditions.Methods and resultsContractile and kinetic parameters were assessed in LV intact trabeculae isolated from control non-failing (NF; n = 58) and end-stage failing ischemic (FI; n = 16) and non-ischemic (FNI; n = 38) human myocardium under baseline conditions, length-dependent activation, frequency-dependent activation, and response to the β-adrenergic stimulation. At baseline, there were no significant differences in contractile force between the three groups; however, kinetics were impaired in failing myocardium with significant slowing down of relaxation kinetics in FNI compared to NF myocardium. Length-dependent activation was preserved and virtually identical in all groups. Frequency-dependent activation was clearly seen in NF myocardium (positive force frequency relationship [FFR]), while significantly impaired in both FI and FNI myocardium (negative FFR). Likewise, β-adrenergic regulation of contraction was significantly impaired in both HF groups.ConclusionsEnd-stage failing myocardium exhibited impaired kinetics under baseline conditions as well as with the three contractile regulatory mechanisms. The pattern of these kinetic impairments in relation to NF myocardium was mainly impacted by etiology with a marked slowing down of kinetics in FNI myocardium. These findings suggest that not only force development, but also kinetics should be considered as a therapeutic target for improving cardiac performance and thus treatment of HF.

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Critical Volume of Human Myocardium Necessary to Maintain Ventricular Fibrillation.

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Critical Volume of Human Myocardium Necessary to Maintain Ventricular Fibrillation.

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