Invasive and Noninvasive Assessment of Exercise-induced Ischemic Diastolic Response Using Pressure Transducers

Manolas, Jan

doi:10.2174/1573403x10666140704111537

Cited by 4 publications

(4 citation statements)

References 40 publications

(108 reference statements)

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“…It is widely believed that diastolic dysfunction occurs independently or preceding a systolic dysfunction (Cazzaniga et al, 2007 ; Fontes-Carvalho et al, 2015 ; Manolas, 2015 ), we herein, found that the Nrf2 −/− mice with systolic dysfunction exhibited a higher degree of diastolic dysfunction after CEE in relation to WT mice. Previously, a co-occurrence of systolic and diastolic dysfunction has been noted in pathophysiological process of heart failure (Zile and Brutsaert, 2002 ; Patten and Hall-Porter, 2009 ; Maharaj, 2012 ) supporting that the loss of Nrf2 could be associated with both systolic and diastolic dysfunction and accelerate heart failure.…”

Section: Discussionsupporting

confidence: 62%

Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged Mice with Impaired Nrf2 Signaling

et al. 2017

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Nuclear factor erythroid 2 related factor 2 (Nrf2) signaling maintains the redox homeostasis and its activation is shown to suppress cardiac maladaptation. Earlier we reported that acute endurance exercise (2 days) evoked antioxidant cytoprotection in young WT animals but not in aged WT animals. However, the effect of repeated endurance exercise during biologic aging (WT) characterized by an inherent deterioration in Nrf2 signaling and pathological aging (pronounced oxidative susceptibility—Nrf2 absence) in the myocardium remains elusive. Thus, the purpose of our study was to determine the effect of chronic endurance exercise-induced cardiac adaptation in aged mice with and without Nrf2. Age-matched WT and Nrf2-null mice (Nrf2−/−) (>22 months) were subjected to 6 weeks chronic endurance exercise (25 meter/min, 12% grade). The myocardial redox status was assessed by expression of antioxidant defense genes and proteins along with immunochemical detection of DMPO-radical adduct, GSH-NEM, and total ubiquitination. Cardiac functions were assessed by echocardiography and electrocardiogram. At sedentary state, loss of Nrf2 resulted in significant downregulation of antioxidant gene expression (Nqo1, Ho1, Gclm, Cat, and Gst-α) with decreased GSH-NEM immuno-fluorescence signals. While Nrf2−/− mice subjected to CEE showed an either similar or more pronounced reduction in the transcript levels of Gclc, Nqo1, Gsr, and Gst-α in relation to WT littermates. In addition, the hearts of Nrf2−/− on CEE showed a substantial reduction in specific antioxidant proteins, G6PD and CAT along with decreased GSH, a pronounced increase in DMPO-adduct and the total ubiquitination levels. Further, CEE resulted in a significant upregulation of hypertrophy genes (Anf, Bnf, and β-Mhc) (p < 0.05) in the Nrf2−/− hearts in relation to WT mice. Moreover, the aged Nrf2−/− mice exhibited a higher degree of cardiac remodeling in association with a significant decrease in fractional shortening, pronounced ST segment, and J wave elevation upon CEE compared to age-matched WT littermates. In conclusion, our findings indicate that while the aged WT and Nrf2 knockout animals both exhibit hypertrophy after CEE, the older Nrf2 knockouts showed ventricular remodeling coupled with profound cardiac functional abnormalities and diastolic dysfunction.

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Section: Discussionsupporting

confidence: 62%

Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged Mice with Impaired Nrf2 Signaling

et al. 2017

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“…The results illustrated in Figure 3(a) show that such decrease in TCV would cause an increase of IVCD from 60 to 71 ms and a slight reduction of ðdP V /dtÞ max from 1780 to 1750 mmHg/s. For comparison, Figure 3(a) includes also two clinically measured normal pressure traces (digitized from literature [18,19]) which demonstrate a good agreement between our FE model and clinical observations. Besides the changes in values of the parameters derived from the pressure traces, an increased wall stress was detected in the endocardial and midmyocardial layers of the LV at the end of IVC (Figure 3(b)).…”

Section: Impact Of Decreased Transmural Conduction Velocity On the Fumentioning

confidence: 63%

“…dt) max = 1780 mmHg/s IVC time = 60 ms (dP/dt) max = 1750 mmHg/s IVC time = 71 ms (a) Effect of a 50% decrease of TCV on pressure rise in the LV during IVC. Pressure development obtained in the control simulation is compared with two normal pressure traces (in grey) digitized from literature[18,19]. (b) Effect of a 50% decrease of TCV on distribution of stresses (in the direction of myofibres) across the LV wall (from endocardium-0% to epicardium-100%) in the end of IVC.…”

mentioning

confidence: 99%

Impact of Decreased Transmural Conduction Velocity on the Function of the Human Left Ventricle: A Simulation Study

Vaverka

Moudr

Lokaj

et al. 2020

BioMed Research International

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This study investigates the impact of reduced transmural conduction velocity (TCV) on output parameters of the human heart. In a healthy heart, the TCV contributes to synchronization of the onset of contraction in individual layers of the left ventricle (LV). However, it is unclear whether the clinically observed decrease of TCV contributes significantly to a reduction of LV contractility. The applied three-dimensional finite element model of isovolumic contraction of the human LV incorporates transmural gradients in electromechanical delay and myocyte shortening velocity and evaluates the impact of TCV reduction on pressure rise (namely, dP/dtmax) and on isovolumic contraction duration (IVCD) in a healthy LV. The model outputs are further exploited in the lumped “Windkessel” model of the human cardiovascular system (based on electrohydrodynamic analogy of respective differential equations) to simulate the impact of changes of dP/dtmax and IVCD on chosen systemic parameters (ejection fraction, LV power, cardiac output, and blood pressure). The simulations have shown that a 50% decrease in TCV prolongs substantially the isovolumic contraction, decelerates slightly the LV pressure rise, increases the LV energy consumption, and reduces the LV power. These negative effects increase progressively with further reduction of TCV. In conclusion, these results suggest that the pumping efficacy of the human LV decreases with lower TCV due to a higher energy consumption and lower LV power. Although the changes induced by the clinically relevant reduction of TCV are not critical for a healthy heart, they may represent an important factor limiting the heart function under disease conditions.

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“… Time course of intraventricular pressure rise during IVC and the underlying increase of tension in LV wall under control conditions. (a) Simulated rise of intraventricular pressure and its comparison with digitalized experimental records published by Curtiss et al [ 14 ], Manolas [ 15 ], and Kern et al [ 16 ]. Note that the duration of IVK (∼60 ms) and dp / dt max⁡ (1780 mm Hg/s) agrees with clinically measured values (61 ms, 63 ms, 61 ms, and 1790 mm Hg/s, 1730 mm Hg/s, and 2130 mm Hg/s, resp.).…”

Section: Figurementioning

confidence: 99%

Effect of Transmural Differences in Excitation-Contraction Delay and Contraction Velocity on Left Ventricle Isovolumic Contraction: A Simulation Study

Vaverka¹,

Burša²,

Sumbera

et al. 2018

BioMed Research International

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Recent studies have shown that left ventricle (LV) exhibits considerable transmural differences in active mechanical properties induced by transmural differences in electrical activity, excitation-contraction coupling, and contractile properties of individual myocytes. It was shown that the time between electrical and mechanical activation of myocytes (electromechanical delay: EMD) decreases from subendocardium to subepicardium and, on the contrary, the myocyte shortening velocity (MSV) increases in the same direction. To investigate the physiological importance of this inhomogeneity, we developed a new finite element model of LV incorporating the observed transmural gradients in EMD and MSV. Comparative simulations with the model showed that when EMD or MSV or both were set constant across the LV wall, the LV contractility during isovolumic contraction (IVC) decreased significantly ((dp/dt)max⁡ was reduced by 2 to 38% and IVC was prolonged by 18 to 73%). This was accompanied by an increase of transmural differences in wall stress. These results suggest that the transmural differences in EMD and MSV play an important role in physiological contractility of LV by synchronising the contraction of individual layers of ventricular wall during the systole. Reduction or enhancement of these differences may therefore impair the function of LV and contribute to heart failure.

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Invasive and Noninvasive Assessment of Exercise-induced Ischemic Diastolic Response Using Pressure Transducers

Cited by 4 publications

References 40 publications

Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged Mice with Impaired Nrf2 Signaling

Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged Mice with Impaired Nrf2 Signaling

Impact of Decreased Transmural Conduction Velocity on the Function of the Human Left Ventricle: A Simulation Study

Effect of Transmural Differences in Excitation-Contraction Delay and Contraction Velocity on Left Ventricle Isovolumic Contraction: A Simulation Study

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