scholarly journals Hyperoxia-induced hypertrophy and ion channel remodeling in left ventricle

2013 ◽  
Vol 304 (12) ◽  
pp. H1651-H1661 ◽  
Author(s):  
Siva K. Panguluri ◽  
Jared Tur ◽  
Jutaro Fukumoto ◽  
Wei Deng ◽  
Kevin B. Sneed ◽  
...  

Ventricular arrhythmias account for high mortality in cardiopulmonary patients in intensive care units. Cardiovascular alterations and molecular-level changes in response to the commonly used oxygen treatment remains unknown. In the present study we investigated cardiac hypertrophy and cardiac complications in mice subjected to hyperoxia. Results demonstrate that there is a significant increase in average heart weight to tibia length (22%) in mice subjected to hyperoxia treatment vs. normoxia. Functional assessment was performed in mice subjected to hyperoxic treatment, and results demonstrate impaired cardiac function with decreased cardiac output and heart rate. Staining of transverse cardiac sections clearly demonstrates an increase in the cross-sectional area from hyperoxic hearts compared with control hearts. Quantitative real-time RT-PCR and Western blot analysis indicated differential mRNA and protein expression levels between hyperoxia-treated and control left ventricles for ion channels including Kv4.2 (−2 ± 0.08), Kv2.1 (2.54 ± 0.48), and Scn5a (1.4 ± 0.07); chaperone KChIP2 (−1.7 ± 0.06); transcriptional factors such as GATA4 (−1.5 ± 0.05), Irx5 (5.6 ± 1.74), NFκB1 (4.17 ± 0.43); hypertrophy markers including MHC-6 (2.17 ± 0.36) and MHC-7 (4.62 ± 0.76); gap junction protein Gja1 (4.4 ± 0.8); and microRNA processing enzyme Drosha (4.6 ± 0.58). Taken together, the data presented here clearly indicate that hyperoxia induces left ventricular remodeling and hypertrophy and alters the expression of Kv4.2 and MHC6/7 in the heart.

2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Bernard KP ◽  
Aliocha NN ◽  
Roger KZ ◽  
Annie NT ◽  
Emmanuel LB ◽  
...  

Diet is one of the mosaics of environmental factors that can affect heart health. This impact, positive or negative, could occur through left ventricular remodeling.


2021 ◽  
Vol 9 (2) ◽  
pp. 91-95
Author(s):  
Madhura AR ◽  
Gowda KMV ◽  
Jayachandra V

Background: Chronic heart failure (CHF) is characterized by sustained activation of neurohormonal and cytokine systems leading to a series of end-organ changes within the myocardium referred to as left ventricular remodeling. Renin-Angiotensin system activation leading to secondary hyperaldosteronism is accompanied by ionized hypocalcemia with secondary hyperparathyroidism which causes dyshomeostasis of extra and intracellular calcium leading to cardiomyocyte necrosis. Objectives: To study the levels of serum calcium in patients of heart failure and its association with severity and duration of chronic heart failure. Methods: The study was conducted on 50 patients with CHF after taking informed consent. All patients met inclusion and exclusion criteria and underwent blood sampling, urine examination and other relevant investigations. Serum calcium levels were correlated with the severity and duration of CHF statistically. Results: Among the patients studied, 96% with ejection fraction (EF)≤ 35%, 87.5% with EF between 35-40% and 44.4% with EF ≥ 40% had low serum calcium values ≤9 mg/dl (p-value <0.001). All patients with duration of heart failure ≥ 2 years and 70.4% patients with duration of heart failure 1-2 years had low serum calcium levels ≤ 9 mg/dl (p value =0.001). Conclusion: There is a significant positive correlation of serum calcium levels with severity of heart failure as measured by EF and significant negative correlation with duration of CHF and NYHA functional grades. The degree of hypocalcemia correlates with severity of cardiomyocyte injury and extent of the neurohormonal response, and accordingly the corresponding risk of adverse cardiovascular events.


2009 ◽  
Vol 297 (4) ◽  
pp. H1361-H1368 ◽  
Author(s):  
Stephen C. Kolwicz ◽  
Scott M. MacDonnell ◽  
Brian F. Renna ◽  
Patricia O. Reger ◽  
Rachid Seqqat ◽  
...  

We investigated how exercise training superimposed on chronic hypertension impacted left ventricular remodeling. Cardiomyocyte hypertrophy, apoptosis, and proliferation in hearts from female spontaneously hypertensive rats (SHRs) were examined. Four-month-old SHR animals were placed into a sedentary group (SHR-SED; n = 18) or a treadmill running group (SHR-TRD, 20 m/min, 1 h/day, 5 days/wk, 12 wk; n = 18). Age-matched, sedentary Wistar Kyoto (WKY) rats were controls ( n = 18). Heart weight was greater in SHR-TRD vs. both WKY ( P < 0.01) and SHR-SED ( P < 0.05). Morphometric-derived left ventricular anterior, posterior, and septal wall thickness were increased in SHR-SED relative to WKY and augmented in SHR-TRD. Cardiomyocyte surface area, length, and width were increased in SHR-SED relative to WKY and further increased in SHR-TRD. Calcineurin abundance was increased in SHR-SED vs. WKY ( P < 0.001) and attenuated in SHR-TRD relative to SHR-SED ( P < 0.05). Protein abundance and mRNA of Akt was not different among groups. The rate of apoptosis was increased in SHR-SED relative to WKY and mitigated in SHR-TRD. The abundance of Ki-67+ cells across groups was not statistically different across groups. The abundance of cardiac progenitor cells (c-Kit+ cells) was increased in SHR-TRD relative to WKY. These data suggest that exercise training superimposed on hypertension augmented cardiomyocyte hypertrophy, despite attenuating calcineurin abundance. Exercise training also mitigated apoptosis in hypertension and showed a tendency to enhance the abundance of cardiac progenitor cells, resulting in a more favorable cardiomyocyte number in the exercise-trained hypertensive heart.


Author(s):  
T.I. Nimtsovych ◽  
A.M. Kravchenko ◽  
O.Yu. Mishcheniuk ◽  
К.О. Mikhaliev ◽  
T.Ya. Chursina

Purpose: to study the association of blood pressure (BP) visit-to-visit variability (VVV) with non-valvular atrial fibrillation (AF) in rural dwellers with arterial hypertension (HTN). Material and methods. The cross-sectional study retrospectively analyzed complex data from consecutive 160 males with primary HTN (mean age 50 ± 6 years). Patients with major HTN complication were excluded. We analyzed the office systolic BP (SBP) and diastolic BP (DBP) levels, obtained at four consecutive doctor`s visits. As a metric of BP VVV, we used standard deviation (SD) and coefficient of variation (CV) values. The criteria for high BP VVV were Patients were ascertained to have high BP VVV in case of SD (SBP) ≥15 mm Hg and/or SD (DBP) ≥14 mm Hg. Totally, high BP VVV status was in 82 (51,3 %) patients. Paroxysmal AF was detected in 29 (18,1 %) patients. Results. HTN with AF group (vs. HTN alone) was characterized by higher average values of BB VVV metrics (median, interquartile range): SD (SBP) (16,7 (15,9-17,5) vs. 8,7 (4,6-15,2) mm Hg, respectively); SD (DBP) (11,5 (8,9-14,6) vs. 5,7 (3,9-8,9) mm Hg, respectively); CV (SBP) (10,1 (9,6-10,7) vs. 5,6 (2,9-9,2) %, respectively); and CV (DBP) (12,9 (9,3-15,5) vs. 6,3 (4,1-9,7) %, respectively) (р<0,001 in all the comparisons). Additionally, HTN with AF group associated with worse kidney filtration function (estimated glomerular filtration rate (eGFR): 57 (53-59) vs. 67 (62-77) ml/mim/1,73 m2, respectively) and more pronounced albuminuria (urine albumin/creatinine ratio (A/Cu): 36,1 (32,3-40,6) vs. 10,3 (6,5-26,9) mg/mmol, respectively) (р<0,001 in both comparisons). While integral assessment of eGFR and A/Cu values, we determined higher frequency of patients with high and very high cardiovascular and renal adverse events risk (AER) in HTN with AF group. Moreover, patients with HTN and AF presented with higher left atrial antero-posterior dimension (LAD) (4,3 (4,2-4,6) сm vs. 3,9 (3,6-4,1) cm, respectively; р<0,001), as well as with more advanced left ventricular remodeling. At multivariable analysis, SD (SBP) ≥15 mm Hg and SD (DBP) ≥14 mm Hg, along with AER and LAD, were the most significant factors independently associated with AF. Conclusion. In rural males with HTN, the presence of high BP VVV is one of the factors associated with non-valvular AF risk increase. High BP VVV could be proposed as an additional modified AF risk factor in patients with HTN.


2011 ◽  
Vol 209 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Priyanka De ◽  
Sreerupa Ghose Roy ◽  
Dipak Kar ◽  
Arun Bandyopadhyay

Ventricular dysfunction is one of the important side effects of the anti-inflammatory agent, glucocorticoid (GC). The present study was undertaken to examine whether abnormal calcium signaling is responsible for cardiac dysfunction due to an excess of GC hormone. The synthetic GC drug, dexamethasone (DEX), significantly (P<0.001, n=20) increased heart weight to body weight ratio, left ventricular remodeling, and fibrosis. The microarray analysis showed altered expression of several genes encoding calcium cycling/ion channel proteins in DEX-treated rat heart. The altered expression of some of the genes was validated by real-time PCR and western blotting analyses. The expression of the L-type calcium channels and calsequestrin was increased, whereas sarcoendoplasmic reticulum calcium transport ATPase 2a (SERCA2a) and junctin mRNAs were significantly reduced in DEX-treated rat left ventricular tissues. In neonatal rat ventricular cardiomyocytes, DEX also increased the level of mRNAs of atrial- and brain natriuretic peptides, L-type calcium channels, and calsequestrin after 24 h of treatment, which were mostly restored by mifepristone. The caffeine-induced calcium release was prolonged by DEX compared to the sharp release in control cardiomyocytes. Taken together, these data show that impaired calcium kinetics may be responsible for cardiac malfunction by DEX. The results are important in understanding the pathophysiology of the heart in patients treated with excess GC.


2013 ◽  
Vol 91 (12) ◽  
pp. 1044-1054 ◽  
Author(s):  
Yi Xin Hu ◽  
Hua Cui ◽  
Li Fan ◽  
Xiu Jie Pan ◽  
Ji Hua Wu ◽  
...  

The objective of this study was to investigate left cardiac damage and the cardioprotective effects of resveratrol in old rats with COPD. Rats 22 months old were divided into three groups: control (CTL), smoking and lipopolysaccharides (SM/LPS), and SM/LPS plus resveratrol (SM/LPS-Res). Cardiac function, pathology, oxidative stress, and apoptosis index were measured. Expression of myocardial SIRT1 was studied by real-time quantitative polymerase chain reaction (PCR) and Western blot detection. The heart weight – body weight ratio (LVW/BW) increased in the SM/LPS group compared with the CTL group. Both the LVW/BW and the area of fibrosis in the SM/LPS-Res group decreased compared with those in the SM/LPS group. 8-OHdG expression increased in cardiac tissue of rats in the SM/LPS group, which could be inhibited by resveratrol. Resveratrol significantly increased the activity of superoxide dismutase (SOD) and reduced the cardiac malonyldialdehyde (MDA) level in the SM/LPS-Res group. There was a significant decrease in the extent of cardiomyocyte apoptosis in the SM/LPS-Res group compared with the SM/LPS group. SIRT1 mRNA increased in the SM/LPS-Res group compared with the SM/LPS group. In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD).


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