Metabolic markers of myocardium insulin resistance in dogs with heart failure

Background: Heart failure syndrome is an aspect of primary or secondary heart disease and is associated with decompensation, formation, and activation of pathological interactions between regulation systems. This results in myocardial energy metabolism alteration. This study was carried out to defy some metabolic aspects of myocardial tissue insulin resistance (IRM) development in canine heart failure.Aim: To investigate the myocardial tissue concentration of adenosine triphosphate (ATP), glucose transporters 1 and 4, pyruvate dehydrogenase (PDH), hexokinase 2, insulin receptor (InsR), and adropin (ADR) protein and to screen metabolic changes and IRM in canine myocardium with heart failure.Methods: We studied 28 dogs of different sexes, ages, and breeds. Groups were formed according to primary pathology: apparently healthy dogs (HD, n = 6); dogs with CDVD (CDVDD, n = 8); dogs with DCM (DCMD, n = 6); and dogs with doxorubicin chemotherapy and doxorubicin-induced cardiomyopathy (DoxCMD, n = 8). Animals in the study were diagnosed for primary disease by standard methods and algorithms. Animals were euthanized due to incurable neurological disease, refractory heart failure, or by owners will. The material was obtained immediately after death, fixed in liquid nitrogen, and stored in −80°C refrigerator. Studied proteins concentrations were analyzed in a specialized research laboratory, using ELISA kits, provided by Cloud-Clone Corp.Results: ATP, GLUT1, and GLUT4 concentrations in myocardial tissue from the valvular disease group did not differ from the HD group. In CDVD, we found depression of PDH, hexokinase II (HX2), and ADR concentrations in comparison to HD. InsR was significantly lower in the CDVD and DoxCMD groups in comparison to the HD group, but in the DCM group, it was twofold higher than in the HD group. In the DCMD and DoxCMD groups, all parameters were lower than in the HD group. ATP, HX2, ADR, GLUT1, and GLUT4 were higher in the CDVD group, than in the DCM and DoxCM groups. PDH in the CDVD and DoxCM groups did not differ. PDH was depleted in the DCM to CDVD and DoxCM groups. InsR did not differ between the CDVD and DoxCM groups, but was upregulated in the DCM to CDVD and DoxCM groups.Conclusion: Development of myocardial tissue IRM is a part of the structural, functional and metabolic remodeling in dogs with heart failure of different etiology. At the late stages, we found significant changes in energy supply availability and production in the myocardium.

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Metabolic Markers of Insulin Resistance in Feline Hypertrophied Myocardium. Insulin Resistance in Heart Failure

American Journal of Animal and Veterinary Sciences ◽

10.3844/ajavsp.2020.275.283 ◽

2020 ◽

Vol 15 (4) ◽

pp. 275-283

Author(s):

Oleinikov Dmitrii Arkadievich

Keyword(s):

Heart Failure ◽

Insulin Resistance ◽

Metabolic Markers ◽

Hypertrophied Myocardium

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Cardiac insulin resistance as a common feature of pressure overload- and myocardial infarction-induced heart failure

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0029-1246859 ◽

2010 ◽

Vol 58 (S 01) ◽

Author(s):

PA Amorim ◽

TD Nguyen ◽

A Schrepper ◽

A Köppen ◽

Y Shingu ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Insulin Resistance ◽

Pressure Overload

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Single patch repair of complete atrioventricular septal defect in neonates within the first three months of age suffering from therapy refractory heart failure. Is it feasible?

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0030-1269155 ◽

2011 ◽

Vol 59 (S 01) ◽

Author(s):

A Horke ◽

I Tzanavaros ◽

A Narr ◽

L Meschenmoser ◽

J Rein ◽

...

Keyword(s):

Heart Failure ◽

Septal Defect ◽

Atrioventricular Septal Defect ◽

Patch Repair ◽

Refractory Heart Failure ◽

Complete Atrioventricular Septal Defect ◽

Complete Atrioventricular

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Predictive Markers of Early Cardiovascular Impairment and Insulin Resistance in Obese Pediatric Patients

Diagnostics ◽

10.3390/diagnostics11040735 ◽

2021 ◽

Vol 11 (4) ◽

pp. 735

Author(s):

Laura Mihaela Trandafir ◽

Elena Cojocaru ◽

Mihaela Moscalu ◽

Maria Magdalena Leon Constantin ◽

Ingrith Miron ◽

...

Keyword(s):

Insulin Resistance ◽

Plasma Cortisol ◽

Predictive Power ◽

Pediatric Patients ◽

The Body ◽

Control Group ◽

Homa Index ◽

Obese Patients ◽

Metabolic Markers ◽

Markers Of Inflammation

Background: The increased prevalence of obesity among children determined the rising number of its comorbidities in children and adults, too. This study aimed to evaluate certain markers of inflammation and insulin resistance in obese pediatric patients, identifying those who are more likely to develop further complications. Methods: We included 115 obese pediatric patients: 85 overweight and obese patients in the study group and 30 normal-weight patients in the control group. We calculated the body mass index (BMI) and we evaluated markers (biological, inflammatory) and the hormones profile. Results: Low-threshold inflammation was assessed by measuring interleukin 6 IL-6 and Intercellular Adhesion Molecules (ICAM). The analysis showed that IL-6 is significantly correlated with glucose (p = 0.001) and BMI value (p = 0.031). ICAM correlates significantly with triglycerides (p = 0.001), glucose (p = 0.044) and BMI percentile (p = 0.037). For pediatric obese patients, endotoxemia has been significantly correlated only with BMI percentile (p = 0.001). Plasma cortisol did not show significant correlations with total cholesterol, triglycerides, glucose or BMI percentile. The results indicated a significant predictive power of BMI percentile on inflammatory markers: IL-6 (AUC = 0.803, p < 0.001), ICAM (AUC = 0.806, p < 0.001) and endotoxemia (AUC = 0.762, p = 0.019). Additionally, BMI percentile has a significant predictive power for metabolic markers of insulin resistance (insulin value: AUC = 0.72, p < 0.001 and HOMA index: AUC = 0.68, p = 0.003). Conclusions: The study highlighted the importance of early markers of cardiovascular risk in obese pediatric patients represented by IL-6, ICAM, endotoxemia and their correlation with metabolic markers of insulin resistance represented by insulinemia, HOMA index and plasma cortisol. It can clearly be considered that the BMI percentile has significant predictive power for metabolic markers of insulin resistance.

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Aetiology-dependent impairment of mitochondrial function in the failing human heart

European Heart Journal ◽

10.1093/ehjci/ehaa946.3606 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Borger ◽

D Scheiber ◽

P Horn ◽

D Pesta ◽

U Boeken ◽

...

Keyword(s):

Heart Failure ◽

Mitochondrial Function ◽

Human Study ◽

Left Ventricular ◽

Myocardial Tissue ◽

Funding Source ◽

Ros Production ◽

German Research Foundation ◽

Long Term Outcome ◽

Tissue Specimens

Abstract Background Alterations of mitochondrial function have been identified to play a role in Heart Failure (HF) pathophysiology. Oxidative phosphorylation (OXPHOS) capacity of the myocardium was shown to be reduced in the failing heart. Ineffective mitochondrial function promotes formation of reactive oxygen species (ROS) that may affect remodelling in ischemia. Thus far, human mitochondrial function comparing dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) resembling the main aetiologies of heart failure with reduced ejection fraction (HFrEF) has not been investigated. Purpose We hypothesised that 1. ROS production is elevated in left ventricular myocardial tissue specimens of ICM patients compared to DCM. 2. Mitochondrial OXPHOS capacity is higher in left ventricular myocardial tissue specimens of DCM compared to ICM patients. Methods Myocardial tissue was obtained from the left ventricular apex from 63 patients (38 ICM, 25 DCM) with advanced HFrEF requiring implantation of a Left Ventricular Assist Device (LVAD). We performed high-resolution respirometry (HRR, OROBOROS Oxygraph-2k) in saponine-permeabilised myocardial fibres and measured ROS production fluoroscopically via the Amplex Red method. Statistical analysis was conducted using GraphPad Prism 7 and IBM SPSS v26.0. Results Groups were of comparable age (61.5±1.2 vs. 59.3±2.4 years, p=n.s.), sex (87% vs 85% male, p=n.s.), diabetic status (32% vs 38.4% type 2 diabetes mellitus, p=n.s.), and body mass index (28.1±0.8 vs. 26.3±1.1 kg/m2, p=n.s.). We detected reduced myocardial mitochondrial OXPHOS capacity in ICM under state 3 conditions by about 15% (68.7±34.0 vs. 80.9±30.5 pmol/(s*mg), p<0.05), after addition of Glutamate by 25% (78.9±38.7 vs. 104.8±41.2 pmol/(s*mg), p<0.01) as well as after Succinate (115.5±65.5 vs. 155±62.0 pmol/(s*mg), p<0.01), uncoupling agent FCCP (114.1±56.8 vs. 150.5±47.3 pmol/(s*mg), p<0.01), and by about 40% after addition of Complex I inhibitor Rotenone (55.5±25.9 vs. 96.9±28.0 pmol/(s*mg), p<0.001). We detected no difference in ROS production between ICM and DCM (0.6±0.05 vs. 0.76±0.08 pmol/(s*ml), p=n.s.). Conclusion This is the first human study deciphering distinct alterations in mitochondrial function (OXPHOS capacity) in ventricular myocardium of HFrEF patients. Future studies may address how distinct metabolic patterns at the time of implantation may relate to long-term outcome of HFrEF in terms of remodelling and recovery. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): DFG (German Research Foundation)

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Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study

Journal of Clinical Monitoring and Computing ◽

10.1007/s10877-021-00717-w ◽

2021 ◽

Author(s):

Takuya Nishikawa ◽

Kazunori Uemura ◽

Yohsuke Hayama ◽

Toru Kawada ◽

Keita Saku ◽

...

Keyword(s):

Heart Failure ◽

Oxygen Consumption ◽

Myocardial Oxygen Consumption ◽

Atrial Pressure ◽

Right Atrial ◽

Canine Heart ◽

Circulatory Collapse ◽

Inotropic Effects ◽

Administration System ◽

Β Blocker

AbstractBeta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and PLA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean PLA were controlled within the acceptable ranges (AP within 5 mmHg below target; PLA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2–3.8)] and PLA [3.6% (2.2–5.7)]. The system decreased MVO2 and PLA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and PLA to avoid circulatory collapse, and reduced MVO2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted.

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Hypocalcemic cardiomyopathy after parathyroidectomy in a patient with uremia: A case report and literature review

Journal of International Medical Research ◽

10.1177/0300060520942115 ◽

2020 ◽

Vol 48 (7) ◽

pp. 030006052094211

Author(s):

Wei Zhang ◽

Feng Xue ◽

Quandong Bu ◽

Xuemei Liu

Keyword(s):

Heart Failure ◽

Case Report ◽

Secondary Hyperparathyroidism ◽

Calcium Supplementation ◽

Severe Heart Failure ◽

Cardiac Complications ◽

Refractory Heart Failure ◽

First Case ◽

Insight Into

Hypocalcemia is a rare, but reversible, cause of dilated cardiomyopathy. Although cardiomyopathy may cause severe heart failure, calcium supplementation can reverse heart failure. We report here a patient with uremia and secondary hyperparathyroidism, who was complicated by persistent hypocalcemia and refractory heart failure. The cardiac failure was refractory to treatment with digitalis and diuretics, but dramatically responded to calcium therapy and restoration of normocalcemia. As a result, the patient was eventually diagnosed with hypocalcemic cardiomyopathy. To the best of our knowledge, this is the first case of this disease to be reported in a patient with uremia. Findings from our case may help clinicians to better understand hypocalcemic cardiomyopathy. Our case might also provide new insight into long-term cardiac complications and prognoses of patients undergoing parathyroidectomy due to secondary hyperparathyroidism.

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Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure

The Egyptian Heart Journal ◽

10.1186/s43044-020-00099-5 ◽

2020 ◽

Vol 72 (1) ◽

Author(s):

Yasser Gaber Metwally ◽

Heba Kamal Sedrak ◽

Inass Fahiem Shaltout

Keyword(s):

Heart Failure ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

Ischemic Cardiomyopathy ◽

Diabetic Patients ◽

Promising Strategy ◽

Improve Insulin Resistance ◽

First Choice ◽

The Difference

Abstract Background Although B-blockers provide unequivocal benefits in heart failure (HF) management, some B-blockers worsen insulin resistance. It will be a promising strategy to recruit such a B blocker that did not worsen or can even improve insulin resistance (IR). So, this study aimed to assess the effect of two of the third-generation B-blockers (carvedilol versus nebivolol) on insulin sensitivity state in non-diabetic patients with non-ischemic cardiomyopathy with heart failure. Results Out of 43 patients enrolled, 58.1% represented the carvedilol group while 41.9% represented the nebivolol group. Nebivolol improves insulin resistance-related variables (fasting glucose, fasting insulin, and HOMA-IR; P < 0.001, 0.01, and 0.01 respectively). The percentage of change at homeostasis model of assessment (HOMA-IR), indicative of insulin sensitivity status, between baseline versus at 3-months follow-up level of intra-group comparison was increased by 4.58% in the carvedilol arm whereas it was decreased by 11.67% in the nebivolol arm, and the difference on the intragroup level of comparison was significant (P < 0.001 and 0.01 respectively). Conclusion Nebivolol improves insulin resistance-related variables .Nebivolol may be recommended as the B blocker of the first choice for those with non-ischemic cardiomyopathy heart failure with evident insulin resistance; however, larger scaled prospective multicenter randomized trials are needed for confirming our favorable results.

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