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Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP‐induced cardiac damage. Thirty‐six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin‐I, Creatine kinase‐myocardial band (CK‐MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP‐ribose) polymerase‐1 (PARP‐1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme‐linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein‐1 (FSP1), transforming growth factor‐beta‐ 1 (TGF‐β1) and α‐smooth muscle actin (α‐SMA) expressions were determined in heart tissue. The CYP group's troponin‐I, total cholesterol, triglyceride, CK‐MB, ROS, PARP‐1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP‐induced pathological damage, TRPM2, FSP1, TGF‐β1 and α‐SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF‐β1, FSP1 and α‐SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP‐induced cardiac damage. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) has been linked to congenital heart disease and fetal alcohol syndrome. The heart primarily relies on mitochondria to generate energy, so impaired mitochondrial function due to alcohol exposure can significantly affect cardiac development and function. Our study aimed to investigate the impact of PAE on myocardial and mitochondrial functions in offspring mice. Methods: We administered 30% alcohol (3 g/kg) to pregnant C57BL/6 mice during the second trimester. We assessed cardiac function by transthoracic echocardiography, observed myocardial structure and fibrosis through staining tests and electron transmission microscopy, and detected cardiomyocyte apoptosis with dUTP nick end labeling assay and real‐time quantitative PCR. Additionally, we measured the reactive oxygen species content, ATP level, and mitochondrial DNA copy number in myocardial mitochondria. Mitochondrial damage was evaluated by assessing the level of mitochondrial membrane potential and the opening degree of mitochondrial permeability transition pores. Results: Our findings revealed that PAE caused cardiac systolic dysfunction, ventricular enlargement, thinned ventricular wall, cardiac fibrosis in the myocardium, scattered loss of cardiomyocytes, and disordered arrangement of myocardial myotomes in the offspring. Furthermore, we observed a significant increase in mitochondrial reactive oxygen species content, a decrease in mitochondrial membrane potential, ATP level, and mitochondrial DNA copy number, and sustained opening of mitochondrial permeability transition pores in the heart tissues of the offspring. Conclusions: These results indicated that PAE had adverse effects on the cardiac structure and function of the newborn mice and could trigger oxidative stress in their myocardia and contribute to mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Background and Purpose: Complement activation may drive hypertension through its effects on immunity and tissue integrity. Experimental Approach: We examined expression of C3, the central protein of the complement cascade, in hypertension. Key Results: Increased C3 expression was found in kidney biopsies and micro‐dissected glomeruli of patients with hypertensive nephropathy. Renal single cell RNA sequence data from normotensive and hypertensive patients confirmed expression of C3 in different cellular compartments of the kidney. In angiotensin II (Ang II) induced hypertension renal C3 expression was up‐regulated. C3−/− mice revealed a significant lower albuminuria in the early phase of hypertension. However, no difference was found for blood pressure, renal injury (histology, glomerular filtration rate, inflammation) and cardiac injury (fibrosis, weight, gene expression) between C3−/− and wildtype mice after Ang II infusion. Also, in deoxycorticosterone acetate (DOCA) salt hypertension, a significantly lower albuminuria was found in the first weeks of hypertension in C3 deficient mice but no significant difference in renal and cardiac injury. Down‐regulation of C3 by C3 targeting GalNAc (n‐acetylgalactosamine) small interfering RNA (siRNA) conjugate decreased C3 in the liver by 96% and lowered albuminuria in the early phase but showed no effect on blood pressure and end‐organ damage. Inhibition of complement C5 by siRNA showed no effect on albuminuria. Conclusion and Implications: Increased C3 expression is found in the kidneys of hypertensive mice and men. Genetic and therapeutic knockdown of C3 improved albuminuria in the early phase of hypertension but did not ameliorate arterial blood pressure nor renal and cardiac injury. [ABSTRACT FROM AUTHOR]

Abemaciclib (ABE) is a cyclin‐dependent kinase inhibitor used in combination with an antiestrogen in the treatment of breast cancer. In addition to the important therapeutic properties of this drug, its side effects are not fully known. In this study, we aimed to investigate the protective effect of curcumin (CUR) on cardiac damage caused by ABE administration. Forty rats were equally divided into control, dimethyl sulfoxide (150 µL), CUR (30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CUR (26 mg/kg/day ABE and 30mg/kg/day CUR) groups (n = 8). Injections were administered daily for 28 days. Troponin‐I, total cholesterol, and creatine kinase myocardial band (CK‐MB) levels and cardiac fibrosis were higher in the ABE group than in the control group (p < 0.05), and were lower in the ABE + CUR group than in the ABE group (p < 0.05). The results showed that ABE administration can cause cardiac damage and increase cardiac fibrosis. However, they showed that coadministration of CUR with ABE could suppress increases in CK‐MB, troponin‐I, and total cholesterol levels and also cardiac fibrosis associated with cardiac damage. Therefore, we can infer that the subsequent administration of CUR ABE treatment can be used as a therapeutic strategy for preventing cardiac damage. [ABSTRACT FROM AUTHOR]

Anthracyclines are standard‐of‐care chemotherapy for the treatment of triple‐negative breast cancer (TNBC). However, high anthracyclines cumulative doses increase heart failure risk. Designing therapeutic strategies that ameliorate cardiac toxicities without compromising oncologic efficacy are important to improve TNBC outcomes and survivorship. The purpose of this study was to determine the impact of diet on TNBC chemotherapeutic responsiveness and development of chemotherapy‐induced cardiac damage. Female BALB/c mice fed a control, Western, Mediterranean, or Western + fish oil diet were injected with 1 × 106 4T1‐luciferase TNBC into the mammary fat pad. Tumors grew for 21 days before surgical tumor resection, then mice were treated with 3.3 mg/kg i.v. doxorubicin for 3 weeks. Vevo (R) cardiac ultrasound was performed. Female nu/nu mice were placed on diets before 1 × 105 MDA‐MB‐231‐luciferase TNBC were injected via the tail vein to induce the development of lung metastases. Mice were treated with saline or 3.3 mg/kg i.v. doxorubicin for 3 weeks, and the development of metastases visualized by IVIS (R). Consumption of a high‐fat diet increased TNBC growth regardless of dietary pattern. Western diet‐fed mice developed lung metastases sooner and displayed increased lung metastatic lesion formation, which was not observed in Mediterranean diet‐fed mice. Western diet‐fed animals displayed worse cardiac function when compared with Mediterranean diet‐fed animals. Hearts from Western diet‐fed animals displayed increased fibrosis. Diet represents a modifiable component directly impacting tumor growth, antitumor chemotherapy efficacy, and cardiac toxicities. Our data suggest that the Mediterranean diet may reduce lung metastatic lesions formation and prevent the development of cardiac toxicities. [ABSTRACT FROM AUTHOR]

This study investigated the potential mechanism(s) and the signaling pathway(s) underlying the prophylactic effect of proanthocyanidin extract (PE) against doxorubicin (DOX)‐induced cardiotoxicity in rats. A total of 32 male albino rats were randomly allocated into four groups. Control rats were orally administrated normal saline. Rats in the second group were orally administrated PE (50 mg/kg bw/once daily) for 4 weeks. Rats in the third group were intraperitoneally injected with DOX (10 mg/kg on Days 3, 9, 15, and 21 of the experiment). Rats in the fourth group were injected with DOX and PE simultaneously for 4 weeks. DOX significantly augmented the levels of serum heart damage biomarkers. In addition, histopathology indicated that DOX‐induced cardiac tissue injury upregulated the expression of fibrogenic factors, alpha smooth muscle actin (α‐SMA), transforming growth factor β1 (TGF‐ β1), and p16INK4A. Downregulation of cell proliferation markers, cyclin‐dependent kinase‐4 (CDK4), and retinoblastoma (Rb) was also observed. Furthermore, DOX‐induced oxidative and inflammatory stress resulted in increased cardiac malondialdehyde (MDA), protein carbonyl (PC), interleukin‐2 (IL‐2), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α). Decreased cardiac glutathione (GSH) levels and enzyme activity of catalase (CAT), superoxide dismutase (SOD), and glutathione S‐transferase (GST) were observed. Treatment of DOX‐induced rat cardiotoxicity with PE normalized serum parameters for the aforementioned parameters and alleviated cardiac tissue structure. Furthermore, reduced cardiac tissue α‐SMA and TGF‐β1, and increased CDK4 and Rb protein expression, along with the amelioration of oxidative and inflammatory effects were observed. PE attenuates DOX‐induced cardiomyocyte inflammation possibly by attenuating the nuclear factor kappa‐B (NF‐ kB) signaling pathway. These results indicate that PE may be useful as a preventative agent against DOX‐induced cardiac toxicity. [ABSTRACT FROM AUTHOR]

Although emerging data demonstrated mortality of young COVID‐19 patients, no data have reported the risk factors of mortality for these young patients, and whether obesity is a risk for young COVID‐19 patients remains unknown. We conducted a retrospective study including 13 young patients who died of COVID‐19 and 40 matched survivors. Logistic regression was employed to characterize the risk factors of mortality in young obese COVID‐19 patients. Most of the young deceased COVID‐19 patients were mild cases at the time of admission, but the disease progressed rapidly featured by a higher severity of patchy shadows (100.00% vs 48.70%; P =.006), pleural thickening (61.50% vs 12.80%; P =.012), and mild pericardial effusion (76.90% vs 0.00%; P <.001). Most importantly, the deceased patients manifested higher body mass index (odds ratio [OR] = 1.354; 95% confidence interval [CI] = 1.075‐1.704; P =.010), inflammation‐related index C‐reactive protein (OR = 1.014; 95% CI = 1.003‐1.025; P =.014), cardiac injury biomarker hs‐cTnI (OR = 1.420; 95% CI = 1.112‐1.814; P =.005), and increased coagulation activity biomarker D‐dimer (OR = 418.7; P =.047), as compared with that of survivors. Our data support that obesity could be a risk factor associated with high mortality in young COVID‐19 patients, whereas aggravated inflammatory response, enhanced cardiac injury, and increased coagulation activity are likely to be the mechanisms contributing to the high mortality. [ABSTRACT FROM AUTHOR]

The nocturnal blood pressure (BP) has been identified as a prognostic factor for cardiovascular events. This study aimed to investigate the association between different patterns of nocturnal masked hypertension (MH) and the echocardiographic parameters in the untreated nocturnal MH patients. A total of 721 untreated MH patients (309 females and 412 males, mean age = 56.59 ± 15.20 years) from June 2006 and June 2016 were included and divided into nocturnal systolic MH (n = 77), nocturnal diastolic MH (n = 232), and nocturnal systolic/diastolic MH (n = 412) groups according to the ambulatory blood pressure monitoring. Baseline characteristics, office BP values, ambulatory BP monitoring parameters, and echocardiographic parameters were compared among the three groups. The independent factors associated with echocardiographic parameters were analyzed by multivariate linear regression. The nocturnal systolic group had the highest ratio of males, mean age, and office systolic BP (SBP), and the lowest office, 24-hour, daytime, nocturnal diastolic BP and heart rate among the three groups. The nocturnal diastolic group had the lowest interventricular septum (IVS) thickness, left atrium (LA) dimension, and left ventricular (LV) mass among the three groups. Multivariate linear regression analysis revealed that 24-hour, daytime, and nocturnal SBPs were all positively associated with LA dimension, IVS thickness, and LV mass (all B were positive and P < .050). Pearson's correlation analysis showed that nocturnal SBP was positively correlated with LA dimension, IVS thickness, and LV mass. These results suggested that different patterns of nocturnal MH had different echocardiographic outcomes. Nocturnal SBP was the independent factor associated with the echocardiographic parameters. [ABSTRACT FROM AUTHOR]

Hypertension is associated with cognitive deficits, probably caused by cerebral small vessel disease. The authors examined whether additional presence of cardiac and renal organ damages, and their combined presence, are associated with future cognitive performance. In 78 patients with essential hypertension (mean age 51.2 ± 12.0 years), brain damage was determined by MRI features, cardiac damage by left ventricular mass index (LVMI), and renal damage by estimated glomerular filtration rate (eGFR) and albuminuria. At 9-year follow-up, neuropsychological assessment was performed. LVMI was associated with future lower cognition (P = 0.032), independent of age, sex, premorbid cognition, and brain damage, but eGFR and albuminuria were not. The presence of 2 or 3 types of organ damage compared to none was associated with future lower cognition. Increasing number of hypertensive organ damages, and cardiac damage independently of brain damage, might indicate a more severe hypertensive disease burden and could help to identify patients at risk of cognitive problems. [ABSTRACT FROM AUTHOR]

Cardiac biomarker release after exercise is well documented in endurance sports, but neither the impact of intermittent high-intensity exercise nor the reproducibility has yet been established. Floorball, a popular sport in Scandinavia, involves intermittent periods of high-intensity exercise. This study aimed to determine the prevalence and reproducibility of elevated cardiac marker levels among elite floorball players after two games. Twenty-three healthy male elite floorball players of median age 19 years (range 16-34 years) participated in two standard games. Blood was drawn at three time points: pregame, immediately after, and 2 h after the game. Creatine kinase MB ( CK- MB), myoglobin, and high-sensitivity cardiac troponin T (hs- cTnT) were measured. The results showed significantly elevated median postgame values in all markers. In both games, hs- cTnT exceeded the cutoff for myocardial damage (≥ 14 ng/L) 2 h postgame in the same six players. The major findings were that postgame cardiac hs- cTnT values among elite floorball players were significantly elevated and reproducible. The findings imply that extended investigations should incorporate evaluation of myocardial function and myocardial perfusion during exercise to seek the clinical significance and underlying mechanisms of elevated cardiac troponin after high-intensity exercise. [ABSTRACT FROM AUTHOR]

Objectives Our aim was to examine the predictive value of preoperative stress echocardiography regarding early myocardial ischemia and late cardiac events after carotid endarterectomy ( CEA). Methods Patients with coronary artery disease undergoing CEA were prospectively included in this study. All patients (n = 162) were classified into low, medium, and high cardiac risk group, according to preoperative stress echocardiography. Classification was based on the criteria of the American Society of Echocardiography. For all patients, cTnI was measured before surgery and on postoperative days 1, 3, and 7. Postoperative cTnI values ranging from 0.05 to 0.5 ng/mL were classified as myocardial ischemia; values >0.5 ng/mL were classified as myocardial infarction. Cardiac damage was defined as either myocardial ischemia or infarction. Results No deaths, strokes, or symptomatic coronary events were observed during the early postoperative period. There were 112 low cardiac risk patients, 42 medium-risk patients, and 8 high-risk patients, according to stress echocardiography findings. Overall, there were 22 patients (14%) that increased their cTnI values postoperatively (12 of low cardiac risk and 10 of medium cardiac risk), and all of them were asymptomatic. None of the high-risk patients showed any troponin increase. Late cardiac events were associated with cTnI increase, although no high-risk patients showed any late event. Conclusions Preoperative stress echocardiography does not seem to independently recognize patients in high risk for asymptomatic cardiac damage after CEA. Postoperative troponin elevation seems to be more predictive for late adverse cardiac events than preoperative stress echocardiography. [ABSTRACT FROM AUTHOR]

Swimming stamina, measured as time-to-fatigue, was reduced by approximately two-thirds in rainbow trout experimentally infected with Ichthyophonus. Intensity of Ichthyophonus infection was most severe in cardiac muscle but multiple organs were infected to a lesser extent. The mean heart weight of infected fish was 40% greater than that of uninfected fish, the result of parasite biomass, infiltration of immune cells and fibrotic (granuloma) tissue surrounding the parasite. Diminished swimming stamina is hypothesized to be due to cardiac failure resulting from the combination of parasite-damaged heart muscle and low myocardial oxygen supply during sustained aerobic exercise. Loss of stamina in Ichthyophonus-infected salmonids could explain the poor performance previously reported for wild Chinook and sockeye salmon stocks during their spawning migration. [ABSTRACT FROM AUTHOR]

Presents several studies about metabolic syndrome. "Risk for Coronary Heart Disease in Young to Middle-Aged Adults With Metabolic Syndrome Compared to Coronary Heart Disease Equivalent," by Kwame O. Akosah et al; "Lisigama in the Treatment of Hypertensive Patients With Metabolic Syndrome and Microalbuminuria," by Ilgar G. Alizade et al; "The Effects of Weight Reduction on the Hemodynamic, Metabolic and Neuroendocrine Profiles of Grade 1 Obese Subjects," by Kelly B. G. Barbato et al.

Background: Sepsis patients with cardiac dysfunction have significantly higher mortality. Although several pathways are associated with myocardial damage in sepsis, the precise cause(s) remains unclear and treatment options are limited. This study was designed to develop a new model to investigate the early events of cardiac damage during sepsis progression., Methods and Results: Francisella tularensis subspecies novicida (Ft.n) is a Gram-negative intracellular pathogen causing severe sepsis syndrome in mice. BALB/c mice (N=12) were sham treated or infected with Ft.n through the intranasal route. Serial electrocardiograms were recorded at multiple time points until 96 hours. Hearts were then harvested for histology and gene expression studies. Similar to septic patients, we illustrate both cardiac electrical and structural phenotypes in our murine Ft.n infection model, including prominent R' wave formation, prolonged QRS intervals, and significant left ventricular dysfunction. Notably, in infected animals, we detected numerous microlesions in the myocardium, previously observed following nosocomial Streptococcus infection and in sepsis patients. We show that Ft.n-mediated microlesions are attributed to cardiomyocyte apoptosis, increased immune cell infiltration, and expression of inflammatory mediators (tumor necrosis factor, interleukin [IL]-1β, IL-8, and superoxide dismutase 2). Finally, we identify increased expression of microRNA-155 and rapid degradation of heat shock factor 1 following cardiac Ft.n infection as a primary cause of myocardial inflammation and apoptosis., Conclusions: We have developed and characterized an Ft.n infection model to understand the pathogenesis of cardiac dysregulation in sepsis. Our findings illustrate novel in vivo phenotypes underlying cardiac dysfunction during Ft.n infection with significant translational impact on our understanding of sepsis pathophysiology., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)