Abstract 15180: Myeloid Differentiation Factor 2 Inhibitor Improves Left Ventricular Function And Heart Rate Variability Via Attenuating Cardiac Mitochondrial Dysfunction In Pre-diabetic Rats

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Natticha Sumneang ◽  
Thura Thun Oo ◽  
thidarat jaiwongkam ◽  
Busarin Arunsak ◽  
Nattayaporn Apaijai ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mitochondrial Dysfunction ◽  
Systemic Inflammation ◽  
Mitochondrial Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Myeloid Differentiation ◽  
Lv Function ◽  
Lv Dysfunction ◽  
Myeloid Differentiation Factor

Introduction: Systemic inflammation is known as a key mediator of left ventricular (LV) dysfunction in pre-diabetic models including obese-insulin resistance. In obese rats, lipopolysaccharide activates myeloid differentiation factor 2 (MD2)/toll-like receptor 4 complex, leading to systemic inflammation. Previously, MD2 inhibitor L6H21 (20 mg/kg) was shown to effectively reduce systemic inflammation in obese mice. However, its potential benefits on the heart and the underlying mechanisms in pre-diabetic obese-insulin resistant rats are unknown. Hypothesis: L6H21 exerts cardiometabolic protection in pre-diabetic rats by improving LV function and heart rate variability (HRV) via reducing cardiac mitochondrial dysfunction. Methods: Male Wistar rats were fed either a normal diet (n=8) or high-fat diet (HFD, n=40) for 12 weeks. In HFD group, rats were divided into 5 groups (n=8/group): 1) vehicle (1% Na-carboxymethyl cellulose), 2) metformin (300 mg/kg, positive control), 3-5) L6H21 at 10, 20, and 40 mg/kg. After 4 weeks of treatments, LV function and HRV were examined. Heart tissue was assessed for mitochondrial function. Results: Pre-diabetic rats had impaired glucose tolerance, depressed HRV, and decreased LV ejection fraction (LVEF), indicating cardiac autonomic imbalance and LV dysfunction. Cardiac mitochondrial dysfunction was also observed, shown by increased mitochondrial ROS levels, mitochondrial depolarization, and mitochondrial swelling. Although L6H21 at 20 and 40 mg/kg improved insulin sensitivity, cardiac autonomic balance, LV function, and mitochondrial function, L6H21 at 40 mg/kg exerted the highest cardioprotective effects, compared to metformin, in pre-diabetic rats by restoring LV function, HRV, and cardiac mitochondrial function (Fig) . Conclusions: L6H21 exerted cardiometabolic protection in pre-diabetic rats by improving insulin sensitivity and cardiac mitochondrial function, leading to restoring LV function.

scholarly journals Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats

2017 ◽  
Vol 232 (2) ◽  
pp. 189-204 ◽  
Author(s):  
Pongpan Tanajak ◽  
Hiranya Pintana ◽  
Natthaphat Siri-Angkul ◽  
Juthamas Khamseekaew ◽  
Nattayaporn Apaijai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Metabolic Regulation ◽  
Left Ventricular ◽  
Lv Function ◽  
Insulin Resistant

Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling pathway were determined. Rats on a HFD developed insulin and FGF21 resistance, oxidative stress, cardiac mitochondrial dysfunction and impaired LV function. Rats on CR alone showed both decreased body weight and visceral fat accumulation, whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative stress. However, vildagliptin improved heart rate variability (HRV), cardiac mitochondrial function and LV function better than the CR. Chronic HFD consumption leads to obese-insulin resistance and FGF21 resistance. Although CR is effective in improving metabolic regulation, vildagliptin provides greater efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21 signaling pathways and attenuating cardiac mitochondrial dysfunction in obese-insulin-resistant rats.

scholarly journals Necroptosis inhibitor directly reduced left ventricular dysfunction in obese-insulin resistant rats, independent of the metabolic status

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Apaijai ◽  
K Jinawong ◽  
K Singhanat ◽  
T Jaiwongkam ◽  
S Kerdphoo ◽  
...  
Keyword(s):  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Left Ventricular ◽  
Metabolic Parameters ◽  
Lv Function ◽  
Cardiac Diseases ◽  
Funding Source ◽  
Insulin Resistant ◽  
Lv Dysfunction

Abstract Background The number of obese people is increasing globally. Our previous studies showed that chronic high-fat diet (HFD) consumption led to obesity with peripheral insulin resistance, which was associated with left ventricular (LV) dysfunction. Mechanistically, cardiac mitochondrial dysfunction and cell death are proposed as an underlying mechanism for LV dysfunction in obese subjects. Recently, necroptosis was defined as a novel cell death pathway, which can be found in various types of cardiac diseases such as myocardial ischaemia and heart failure. Pharmacological inhibition of necroptosis by necrostatin 1 (nec-1) provided the favorable outcomes to those cardiac diseases. However, the roles of necroptosis and the effects of nec-1 on the heart of obese-insulin resistant rats have never been investigated. Purpose We hypothesized that nec-1 attenuates LV dysfunction by reducing cardiac mitochondrial dysfunction, necroptosis, and apoptosis in obese-insulin resistant rats. Methods Male rats (n=32) were fed with normal diet (ND) or HFD for 12 weeks to induce obese-insulin resistance. At weeks 13, HFD-fed rats were assigned into 3 interventional groups (n=8/group) as follows: 1) HFD-fed rats treated with saline, 2) HFD-fed rats treated with nec-1 (1.65 mg/kg/day, subcutaneous injection), 3) HFD-fed rats treated with metformin (300 mg/kg/day, oral gavage feeding, served as a positive control). ND rats were treated with saline. Rats received their assigned interventions for additional 7 weeks. Blood pressure (BP), cardiac sympathovagal balance, and LV function were determined. At the end, the heart was excised to determine cardiac mitochondrial function including mitochondrial respiration, reactive oxygen species (ROS) levels, membrane potential changes, swelling, as well as apoptosis and necroptosis protein levels. Results HFD-fed rats had increased body weight, visceral fat deposition, hyperinsulinemia with euglycemia, and dyslipidemia. Moreover, HFD-fed rats had increased systolic and diastolic BP, reduced cardiac sympathovagal balance, and %LV ejection fraction (LVEF) (Fig. 1A). For mitochondrial function, respiratory control ratio was decreased, ROS levels were increased, along with mitochondrial membrane depolarization and swelling (Fig. 1B). Both necroptosis and apoptosis were observed in HFD-fed rats. Treatment with nec-1 reduced systolic and diastolic BP, cardiac sympathovagal imbalance, and increased %LVEF (Fig. 1A). Necroptosis and apoptosis were reduced, and all mitochondrial function parameters were improved in nec-1 treated rats (Fig. 1B). However, the metabolic parameters were not modified by nec-1. Treatment with metformin had similar benefits as nec-1 (Fig. 1), with additional improvement in metabolic parameters in HFD-fed rats. Conclusion Nec-1 directly improves LV function in obese-insulin resistant rats via attenuating cardiac mitochondrial dysfunction and cell death, independent of metabolic parameters. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science and Technology Development Agency, Thailand Research Fund (TRF)

Hyperbaric oxygen therapy attenuates D-galactose-induced-age-related cardiac dysfunction through mitigating cardiac mitochondrial dysfunction in pre-diabetic rats

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Bo-Htay ◽  
T Shwe ◽  
S Palee ◽  
T Pattarasakulchai ◽  
K Shinlapawittayatorn ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
Normal Diet ◽  
Lv Function ◽  
High Fat ◽  
Insulin Resistant ◽  
Lv Dysfunction ◽  
Age Related ◽  
Mitochondrial Functions

Abstract Background D-galactose (D-gal) induced ageing has been shown to exacerbate left ventricular (LV) dysfunction via worsening of apoptosis and mitochondrial dysfunction in the heart of obese rats. Hyperbaric oxygen therapy (HBOT) has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in multiple neurological disorders. However, the cardioprotective effect of HBOT on inflammation, apoptosis, LV and mitochondrial functions in D-gal induced ageing rats in the presence of obese-insulin resistant condition has never been investigated. Purpose We sought to determine the effect of HBOT on inflammation, apoptosis, mitochondrial functions and LV function in pre-diabetic rats with D-gal induced ageing. We hypothesized that HBOT attenuates D-gal induced cardiac mitochondrial dysfunctions and reduces inflammation and apoptosis, leading to improved LV function in pre-diabetic rats. Methods Forty-eight male Wistar rats were fed with either normal diet or high-fat diet for 12 weeks. Then, rats were treated with either vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-gal groups (150 mg/kg/day, SC) for 8 weeks. At week 21, rats in each group were equally divided into 6 sub-groups: normal diet fed rats treated with vehicle (NDV) sham, normal diet fed rats treated with D-gal (NDDg) sham, high fat diet fed rats treated with D-gal (HFDg) sham, high fat diet fed rats treated with vehicle (HFV) + HBOT, NDDg + HBOT and HFDg + HBOT. Sham treated rats were given normal concentration of O2 (flow rate of 80 L/min, 1 ATA for 60 minutes), whereas HBOT treated rats were subjected to 100% O2 (flow rate of 250 L/min, 2 ATA for 60 minutes), given once daily for 2 weeks. Results Under obese-insulin resistant condition, D-gal-induced ageing aggravated LV dysfunction (Fig 1A) and impaired cardiac mitochondrial function, increased cardiac inflammatory and apoptotic markers (Fig 1B). HBOT markedly reduced cardiac TNF-α level and TUNEL positive apoptotic cells, and improved cardiac mitochondrial function as indicated by decreased mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling, resulting in the restoration of the normal LV function in HFV and NDDg rats, compared to sham NDDg rats. In addition, in HFDg treated rats, HBOT attenuated cardiac TNF-α level, TUNEL positive apoptotic cells and cardiac mitochondrial dysfunction, compared to sham HFDg rats, leading to improved cardiac function as indicated by increased %LV ejection fraction (LVEF) (Figure 1). Conclusion HBOT efficiently alleviates D-gal-induced-age-related LV dysfunction through mitigating inflammation, apoptosis and mitochondrial dysfunction in pre-diabetic rats. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand, 2. Thailand Research Fund Grants

scholarly journals Transmural differences in respiratory capacity across the rat left ventricle in health, aging, and streptozotocin-induced diabetes mellitus: evidence that mitochondrial dysfunction begins in the subepicardium

2011 ◽  
Vol 300 (2) ◽  
pp. C246-C255 ◽  
Author(s):  
J. R. MacDonald ◽  
M. Oellermann ◽  
S. Rynbeck ◽  
G. Chang ◽  
K. Ruggiero ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Streptozotocin Diabetes ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Rat Hearts ◽  
Myocardial Layers ◽  
Streptozotocin Induced Diabetes ◽  
Old Rats

In diabetic cardiomyopathy, ventricular dysfunction occurs in the absence of hypertension or atherosclerosis and is accompanied by altered myocardial substrate utilization and depressed mitochondrial respiration. It is not known if mitochondrial function differs across the left ventricular (LV) wall in diabetes. In the healthy heart, the inner subendocardial region demonstrates higher rates of blood flow, oxygen consumption, and ATP turnover compared with the outer subepicardial region, but published transmural respirometric measurements have not demonstrated differences. We aim to measure mitochondrial function in Wistar rat LV to determine the effects of age, streptozotocin-diabetes, and LV layer. High-resolution respirometry measured indexes of respiration in saponin-skinned fibers dissected from the LV subendocardium and subepicardium of 3-mo-old rats after 1 mo of streptozotocin-induced diabetes and 4-mo-old rats following 2 mo of diabetes. Heart rate and heartbeat duration were measured under isoflurane-anesthesia using a fetal-Doppler, and transmission electron microscopy was employed to observe ultrastructural differences. Heart rate decreased with age and diabetes, whereas heartbeat duration increased with diabetes. While there were no transmural respirational differences in young healthy rat hearts, both myocardial layers showed a respiratory depression with age (30–40%). In 1-mo diabetic rat hearts only subepicardial respiration was depressed, whereas after 2 mo diabetes, respiration in subendocardial and subepicardial layers was depressed and showed elevated leak (state 2) respiration. These data provide evidence that mitochondrial dysfunction is first detectable in the subepicardium of diabetic rat LV, whereas there are measureable changes in LV mitochondria after only 4 mo of aging.

Positive Inotropic and Lusitropic Effects of Triiodothyronine in Conscious Dogs with Pacing-induced Cardiomyopathy 

1997 ◽  
Vol 87 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Iyad N. Jamali ◽  
Paul S. Pagel ◽  
Douglas A. Hettrick ◽  
Dermot Lowe ◽  
Judy R. Kersten ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Contractility ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Segment Length ◽  
Lv Function ◽  
Baseline Heart Rate ◽  
Stroke Work ◽  
Lv Dysfunction

Background The effects of triiodothyronine (T3) on systemic hemodynamics, myocardial contractility (preload recruitable stroke work slope; Mw), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs. Methods Dogs (n = 8) were chronically instrumented for measurement of aortic and LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5 min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs were then continuously paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration of T3 was repeated. Results T3 produced immediate and sustained (24 h) increases (P < 0.05) in Mw and dP/dtmax in dogs before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3 caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs. Conclusions The findings indicate that T3 produces favorable alterations in hemodynamics and modest positive inotropic and lusitropic effects in conscious dogs with LV dysfunction produced by rapid LV pacing.

scholarly journals Metformin exerts cardioprotection via attenuating mitochondrial fission in cardiac ischaemia-reperfusion injury in rats

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Palee ◽  
L Higgins ◽  
T Leech ◽  
S.C Chattipakorn ◽  
N Chattipakorn
Keyword(s):  
Infarct Size ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Funding Source ◽  
Cardiac Ischaemia

Abstract Background Cardiac ischemia/reperfusion (I/R) injury following myocardial infarction reperfusion therapy is a phenomenon that results in further cardiomyocytes death and impaired cardiac contractility. Although metformin has been shown to exert cardioprotection in addition to glycemic control, its effect on cardiac I/R injury are still controversy, and the comparative doses of metformin in cardiac I/R injury have never been investigated. Purpose We hypothesized that metformin given acutely prior to cardiac ischaemia exerts cardioprotection in rats with cardiac I/R injury via attenuating cardiac mitochondrial dysfunction, leading to improved left ventricular (LV) function. Methods Forty Male Wistar rats were subjected to cardiac I/R injury. Four treatment groups were investigated. The first group received saline as a control group. The second to the fourth groups received metformin at 100, 200, and 400 mg/kg intravenously, respectively. During the I/R protocols, the LV function, arrhythmia score, and mortality rate were determined. At the end, the hearts were rapidly removed to determine infarct size, cardiac mitochondrial function, cardiac mitochondrial dynamics, and cardiac apoptosis. Results Metformin 200 mg/kg exerted the highest level of cardioprotection through the attenuated incidence of arrhythmia, decreased infarct size (Fig. 1), improved cardiac mitochondrial function, and decreased mitochondrial fission (Fig. 1) and cardiac apoptotic markers, leading to improved cardiac function during I/R injury. Although Metformin at all doses effectively decreased infarct size, improved cardiac mitochondrial function and LV function, Metformin at 200 mg/kg exerted the best efficacy (Fig. 1). Conclusions Metformin exerts cardioprotection by attenuating mitochondrial dysfunction and decreased mitochondrial fission, leading to decreased infarct size and ultimately improved LV function after acute cardiac I/R injury in rats. These findings also indicate the potential biphasic effects of metformin on infarct size which are dose-dependent. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science and Technology Development Agency Thailand (NC), and Thailand Research Fund (SCC)

Myeloid differentiation factor-88 contributes to TLR9-mediated modulation of acute coxsackievirus B3-induced myocarditis in vivo

2010 ◽  
Vol 298 (6) ◽  
pp. H2024-H2031 ◽  
Author(s):  
Alexander Riad ◽  
Dirk Westermann ◽  
Felicitas Escher ◽  
Peter M. Becher ◽  
Konstantinos Savvatis ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Coxsackievirus B3 ◽  
Left Ventricular ◽  
Myeloid Differentiation ◽  
Lv Function ◽  
Differentiation Factor ◽  
Tnf Α ◽  
Chronic Myocarditis ◽  
Cvb3 Infection ◽  
Myeloid Differentiation Factor

Toll-like receptor 9 (TLR9) is a member of the innate immune system and has been shown to influence myocardial function, but its role in myocarditis is hitherto unknown. We therefore investigated whether or not TLR9 plays a role in this disease in coxsackievirus B3 (CVB3)-induced myocarditis in mice. Left ventricular (LV) function, cardiac immune cell infiltration, virus mRNA, and components of the TLR9 downstream pathway were investigated in TLR9-deficient [knockout (KO)] and wild-type (WT) mice after infection with CVB3. Murine cardiac TLR9 expression was significantly increased in WT mice with acute CVB3 infection but not in WT mice with chronic myocarditis. Furthermore, in the acute phase of CVB3-induced myocarditis, CVB3-infected KO mice displayed improved LV function associated with reduced cardiac inflammation indexed by reduced amounts of immune cells compared with CVB3-infected WT mice. In contrast, in the chronic phase, LV function and inflammation were not seen to differ among the infected groups. The cardioprotective effects due to TLR9 deficiency were associated with suppression of the TLR9 downstream pathway as indexed by reduced cardiac levels of the adapter protein myeloid differentiation factor (MyD)-88 and the proinflammatory cytokine TNF-α. In addition, TLR9 deficiency led to an activation of the antiviral cytokine interferon-β in the heart as a result from viral infection. In conclusion, the MyD88/TNF-α axis due to TLR9 activation in the heart contributes the development of acute myocarditis but not of chronic myocarditis.

Abstract 15634: High-fat Diet Consumption Accelerates Cardiometabolic Impairment via Deteriorating Mitochondrial Function in Non-obese Spontaneously Type 2 Diabetic Rats

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wanpitak Pongkan ◽  
KEWARIN JINAWONG ◽  
Siriporn Chattipakorn ◽  
Nipon CHATTIPAKORN
Keyword(s):  
Mitochondrial Function ◽  
High Fat Diet ◽  
Time Course ◽  
Left Ventricular ◽  
Normal Diet ◽  
The Body ◽  
Lv Function ◽  
High Fat ◽  
Lv Dysfunction

Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disease which is related to genetic, environmental, and lifestyle factors. In genetically-induced T2DM rats, normal diet could induce spontaneous diabetes, and induce left ventricular (LV) dysfunction over time. However, the effect of high-fat diet (HFD) in these genetically-induced T2DM rats on the cardiometabolic changes, including LV function and cardiac mitochondrial function has rarely been investigated. Hypothesis: High-fat diet (HFD) consumption accelerates the development of T2DM and LV dysfunction by inducing mitochondrial dysfunction in genetically-induced non-obese T2DM-Spontaneously Diabetic Torii (SDT) rats. Methods: Male SDT rats (n=18/group) were divided into 2 groups to receive either normal diet (ND, 19.77% fat) or HFD (57.60% fat) for 4, 8 or 12 weeks. At each time course, cardiac function determined by echocardiography and the pressure-volume loop determined by invasive intracardiac catheterization were assessed. The heart was removed to study cardiac mitochondrial function at each time-course. Results: The body weight, food intake, and visceral fat were not different between ND and HFD rats at any times. Increased blood glucose was seen earlier at week 4 in HFD rats, but later at week 12 in ND rats. The development of LV contractile dysfunction and decreased stroke volume was observed earlier at week 8 in HFD rats, compared to ND rats and HFD rats at the baseline. Increased cardiac mitochondrial ROS production and decreased mitochondrial membrane potential (i.e. mitochondrial depolarization) was observed earlier at week 8 in HFD rats, compared to ND rats (Fig). Conclusions: High-fat diet accelerates cardiometabolic impairments via impaired cardiac mitochondrial function in genetically-induced non-obese T2DM rats.

scholarly journals Testosterone Deprivation Aggravates Left-Ventricular Dysfunction in Male Obese Insulin-Resistant Rats via Impairing Cardiac Mitochondrial Function and Dynamics Proteins

Gerontology ◽  
2018 ◽  
Vol 64 (4) ◽  
pp. 333-343 ◽  
Author(s):  
Nattayaporn Apaiajai ◽  
Titikorn Chunchai ◽  
Thidarat Jaiwongkam ◽  
Sasiwan  Kerdphoo ◽  
Siriporn C. Chattipakorn ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Left Ventricular ◽  
Normal Diet ◽  
Male Rats ◽  
Lv Function ◽  
Sham Operation ◽  
Insulin Resistant ◽  
Lv Dysfunction

Background: We have previously reported that testosterone deprivation at a very young age accelerated, but did not aggravate, left-ventricular (LV) dysfunction in obese insulin-resistant rats. However, the effects of testosterone deprivation during adulthood on LV function in obese insulin-resistant rats remains unclear. We hypothesized that testosterone deprivation aggravates LV dysfunction and cardiac autonomic imbalance via the impairment of cardiac mitochondrial function and dynamics proteins, a reduction in insulin receptor function, and an increase in apoptosis in obese insulin-resistant rats. Methods: Male rats were fed on either a normal diet (ND) or a high-fat diet (HFD) for 12 weeks. They were then subdivided into 2 groups: sham operation (NDS, HFS) and orchiectomy (NDO, HFO). Metabolic parameters, blood pressure, heart rate variability (HRV), and LV function were determined at baseline and before and after orchiectomy. Mitochondrial function and dynamics proteins, insulin signaling, and apoptosis were determined 12 weeks postoperatively. Results: HFS rats exhibited obese insulin resistance, depressed HRV, and LV dysfunction. In HFO rats, systolic blood pressure was increased with more excessive depression of HRV and increased LV dysfunction, compared with HFS rats. These adverse cardiac effects were consistent with markedly increased mitochondrial dysfunction, reduced mitochondrial complex I and III proteins, reduced mitochondrial fusion proteins, and increased apoptosis, compared with HFS rats. However, testosterone deprivation did not lead to any alteration in the insulin-resistant condition in HFO rats, compared with HFS rats. Conclusion: We concluded that testosterone deprivation during adulthood aggravated the impairment of mitochondrial function, mitochondrial respiratory complex, mitochondrial dynamics proteins, and apoptosis, leading to LV dysfunction in obese insulin-resistant rats.

Urine Albumin to Creatinine Ratio and Echocardiographic Left Ventricular Structure and Function in Patients with Essential Hypertension

2011 ◽  
Vol 9 (2) ◽  
pp. 90 ◽  
Author(s):  
Rohola Hemmati ◽  
Mojgan Gharipour ◽  
Hasan Shemirani ◽  
Alireza Khosravi ◽  
Elham Khosravi ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Peak Velocity ◽  
Left Ventricular ◽  
Lv Function ◽  
Creatinine Ratio ◽  
Uncomplicated Hypertension ◽  
Urine Albumin ◽  
Lv Dysfunction ◽  
Mitral Annulus Velocity ◽  
Lv Mass

Background:Appearance of microalbuminuria, particularly in patients with hypertension, might be associated with a higher prevalence of left ventricular (LV) dysfunction and geometric abnormalities. This study was undertaken to determine whether high urine albumin to creatinine ratio (UACR) as a sensitive marker for microalbuminuria can be associated with LV hypertrophy (LVH) and systolic and diastolic LV dysfunction.Methods:The study population consisted of 125 consecutive patients with essential uncomplicated hypertension. Urine albumin and creatinine concentration was determined by standard methods. LVH was defined as a LV mass index >100 g/m2 of body surface area in women and >130 g/m2 in men. Echocardiographic LV systolic and diastolic parameters were measured.Results:The prevalence of microalbuminuria in patients with essential hypertension was 5.6 %. UACR was significantly no different in patients with LVH than in patients with normal LV geometry (21.26 ± 31.55 versus 17.80 ± 24.52 mg/mmol). No significant correlation was found between UACR measurement and systolic and diastolic function parameters, including early to late diastolic peak velocity (E/A) ratio (R=-0.192, p=0.038), early diastolic peak velocity to early mitral annulus velocity (E/E') ratio (R=-0.025, p=0.794), LV ejection fraction (R=0.008, p=0.929), and LV mass (R=-0.132, p=0.154). According to the receiver operator characteristic (ROC) curve analysis, UACR measurement was not an acceptable indicator of LVH with areas under the ROC curves 0.514 (95 % confidence interval 0.394–0.634). The optimal cut-off value for UACR for predicting LVH was identified at 9.4, yielding a sensitivity of 51.6 % and a specificity of 48.3 %.Conclusion:In patients with uncomplicated essential hypertension, abnormal systolic and diastolic LV function and geometry cannot be effectively predicted by the appearance of microalbuminuria.

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