scholarly journals Early postnatal rat ventricle resection leads to long-term preserved cardiac function despite tissue hypoperfusion

2014 ◽  
Vol 2 (8) ◽  
pp. e12115 ◽  
Author(s):  
Camila Zogbi ◽  
Ana E. T. Saturi de Carvalho ◽  
Juliana S. Nakamuta ◽  
Viviane de M. Caceres ◽  
Silvana Prando ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Tissue Hypoperfusion ◽  
Rat Ventricle

Exercise cardiac MRI unmasks cardiac dysfunction in childhood and adolescent cancer survivors with reduced cardiopulmonary fitness

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Foulkes ◽  
B Costello ◽  
E.J Howden ◽  
K Janssens ◽  
H Dillon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Cancer Survivors ◽  
Pediatric Cancer ◽  
Cardiac Dysfunction ◽  
Cardiopulmonary Fitness ◽  
Cardiac Reserve ◽  
Pediatric Cancer Survivors ◽  
Increased Risk

Abstract Background Young cancer survivors are at increased risk of impaired cardiopulmonary fitness (VO2peak) and heart failure. Assessment of exercise cardiac reserve may reveal sub-clinical abnormalities that better explain impairments in fitness and long term heart failure risk. Purpose To investigate the presence of impaired VO2peak in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac reserve Methods Twenty pediatric cancer survivors (aged 8–24 years) treated with anthracycline chemotherapy underwent cardiopulmonary exercise testing to quantify VO2peak, with a value <85% of predicted defined as impaired VO2peak. Resting cardiac function was assessed using 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate (HR), stroke volume index (SVi) and cardiac index (CI) using exercise cardiac magnetic resonance imaging. Results 12 of 20 survivors (60%) had impaired VO2peak (97±14% vs. 70±16% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired VO2peak. However, those with reduced VO2peak had diminished cardiac reserve, with a lesser increase in CI (Fig. 1A) and SVi (Fig. 1B) during exercise (Interaction P=0.001 for both), whilst the HR response was similar (Fig. 1C; P=0.71). Conclusions Resting measures of cardiac function are insensitive to significant cardiac dysfunction amongst pediatric cancer survivors with reduced VO2peak. Measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation

scholarly journals Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life

2021 ◽  
Author(s):  
Kendrick Lee ◽  
Steven R. Laviolette ◽  
Daniel B. Hardy
Keyword(s):  
Body Weight ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Cardiac Remodelling ◽  
Long Term Effects ◽  
Catch Up ◽  
First Time ◽  
Impaired Cardiac Function ◽  
In Pregnancy

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.

Long-term levosimendan treatment improves systolic function and myocardial relaxation in mice with cardiomyocyte-specific disruption of the Serca2 gene

2013 ◽  
Vol 115 (10) ◽  
pp. 1572-1580 ◽  
Author(s):  
Vigdis Hillestad ◽  
Frank Kramer ◽  
Stefan Golz ◽  
Andreas Knorr ◽  
Kristin B. Andersson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Cytosolic Calcium ◽  
Left Ventricular ◽  
Pressure Measurements ◽  
Human Heart Failure

In human heart failure (HF), reduced cardiac function has, at least partly, been ascribed to altered calcium homeostasis in cardiomyocytes. The effects of the calcium sensitizer levosimendan on diastolic dysfunction caused by reduced removal of calcium from cytosol in early diastole are not well known. In this study, we investigated the effect of long-term levosimendan treatment in a murine model of HF where the sarco(endo)plasmatic reticulum ATPase ( Serca) gene is specifically disrupted in the cardiomyocytes, leading to reduced removal of cytosolic calcium. After induction of Serca2 gene disruption, these mice develop marked diastolic dysfunction as well as impaired contractility. SERCA2 knockout (SERCA2KO) mice were treated with levosimendan or vehicle from the time of KO induction. At the 7-wk end point, cardiac function was assessed by echocardiography and pressure measurements. Vehicle-treated SERCA2KO mice showed significantly diminished left-ventricular (LV) contractility, as shown by decreased ejection fraction, stroke volume, and cardiac output. LV pressure measurements revealed a marked increase in the time constant (τ) of isovolumetric pressure decay, showing impaired relaxation. Levosimendan treatment significantly improved all three systolic parameters. Moreover, a significant reduction in τ toward normalization indicated improved relaxation. Gene-expression analysis, however, revealed an increase in genes related to production of the ECM in animals treated with levosimendan. In conclusion, long-term levosimendan treatment improves both contractility and relaxation in a heart-failure model with marked diastolic dysfunction due to reduced calcium transients. However, altered gene expression related to fibrosis was observed.

Abstract 12153: Impact of a Hybrid Nurse-Led Intervention for the Prevention of Progressive Cardiac Dysfunction in High Risk Individuals: Results From a Pragmatic, Randomized Trial (the NIL-CHF Study)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Simon Stewart ◽  
Melinda Carrington ◽  
Yih Kai Chan ◽  
Garry Jennings ◽  
Chiew Wong ◽  
...  
Keyword(s):  
High Risk ◽  
Cardiac Function ◽  
Diastolic Dysfunction ◽  
Cardiac Dysfunction ◽  
Systolic Dysfunction ◽  
Cardiac Abnormality ◽  
Coronary Syndrome ◽  
History Of ◽  
Hybrid Program

Background: The natural history of chronic heart failure (CHF) is characterized by initial cardiac insult and/or stressors over time that leaves affected individuals at high risk for progressive cardiac dysfunction and eventual development of the syndrome. Methods: Of a total of 624 subjects at high risk of developing CHF randomized into the NIL-CHF Study comparing a hybrid program of home and clinic-based follow-up (NIL-CHF group) to Standard Care, 454 (73%) underwent serial echocardiography at 1 month post index cardiac hospitalization and at 3 years. At both time points (nil signs/symptoms of CHF at baseline), these were blindly classified as follows: 1) no cardiac abnormality, 2) systolic dysfunction/HFrEF - LVEF ≤ 45% ), 3) diastolic dysfunction/HFpEF as defined by any moderate diastolic dysfunction (with pseudonormalization pattern) or E/E prime ratio ≥ 15, 4) combination of 2 & 3 and 5) other cardiac abnormality (including LVH). Pre-specified criteria were used to determine - i) no change, ii) improvement or iii) deterioration in cardiac function from baseline to 3 years. Results: Mean age was 66±11 years, 71% were male, 70% were hospitalized with an acute coronary syndrome and 62% and 26%, respectively, were being treated for hypertension and diabetes. At baseline 25.2% vs. 28.4% (p=ns), 15.1% vs. 9.1% (p<0.05), 35.1% vs. 32.4% (p=ns) and 34.3% vs. 39.6% had normal cardiac function, HFrEF, HFpEF (13% both HFrEF and HFpEF overall) and LVH (the predominant “other” cardiac abnormality), respectively. At 3 years the proportion of subjects with reversal of pre-existing HFrEF or HFpEF was lower in the NIL-CHF group (23% vs. 16%; p=0.063). Moreover, significantly more NIL-CHF subjects demonstrated any form of cardiac recovery/reversal on echocardiography (39% vs. 25%, p=0.011, 95% CI 1.35, 95% CI 1.04, 1.76). They also demonstrated significantly greater regression to normal LV structure (36% vs. 25%; p=0.047) among those with LVH at baseline. Conclusions: These pre-specified analyses (secondary endpoint) of the recently completed NIL-CHF Study suggests a cardio-protective effect conferred by a long-term, nurse-led, home and clinic-based intervention targeting hospitalized individuals at high risk for developing CHF.

Abstract 381: Prolonged Renal Failure Leads to Reduced Number of Active Cardiac Mitochondria in a Rat Model for Long Term Chronic Kidney Disease

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Einat A Hertzberg-Bigelman ◽  
Michal Entin-Meer ◽  
Genya Aharon-Hananel ◽  
Ann Saada ◽  
Ran Levy ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Mitochondrial Dna ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Rat Model ◽  
Dna Content ◽  
Cardiac Mitochondria ◽  
Mitochondrial Content ◽  
Mitochondrial Dna Content

Objectives - Cardiorenal syndrome type 4 is characterized by primary chronic kidney disease (CKD) leading to an impairment of cardiac function. We recently showed a reduced expression of several cardiac mitochondrial genes in short-term CKD rat model. We aimed to evaluate whether cardiac mitochondrial structure and function is modified in long-term CKD and if so, to characterize the potential associated mechanisms. Methods - Lewis rats underwent 5/6 nephrectomy for induction of CKD. Upon necroscopy, eight months later, cardiac sections were analyzed by histology and electron microscopy (EM). Mitochondrial DNA content was determined by the mitochondrial gene, cytochrome B. Mitochondrial content was assessed by citrate synthase (CS) activity in tissue homogenate and respiratory chain function was determined by the activity of complexes I-IV in isolated mitochondria. The levels of PGC1a, a transcription factor for mitochondrial biogenesis, Angiotensin II type 1 receptor and cytosolic cytochrome C were assayed by western blot. Cytokine serum profile was determined by microarray. Results - Long-term CKD leads to cardiac hypertrophy and increased interstitial fibrosis. EM analysis revealed a massive spatial disarrangement accompanied by a considerably increased volume of swollen-damaged mitochondria in CKD hearts (32±3%, n=5, 48±6%, n=4; respectively; p<0.05). Total mitochondrial DNA content was decreased in cardiac tissue of CKD rats. Concomitantly, active mitochondrial content was significantly reduced. Conversely, no differences were observed in respiratory chain enzymes’ functions (complexes I-IV) in isolated active mitochondria. Moreover, inflammatory response and activation of Renin-Angiotensin-Aldosterone-System (RAAS) were detected in the CKD setting. Conclusion - CKD results in a marked reduction of active mitochondria in the heart. Inflammatory cytokines and RAAS, may set a deleterious environment to cardiac mitochondria, as suggested in non-CKD models. The data may represent a significant milestone in the personalized medicine strategy for treating CKD patients who present with normal cardiac function accompanied by positive biomarkers for cardiac mitochondria damage.

scholarly journals Oral delivery of xenon for cardiovascular protection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xing Yin ◽  
Melanie R. Moody ◽  
Valeria Hebert ◽  
Melvin E. Klegerman ◽  
Yong-Jian Geng ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Oral Delivery ◽  
Noble Gas ◽  
Left Ventricular ◽  
Beneficial Effects ◽  
Normal Left Ventricular ◽  
Term Administration ◽  
Apoe Knockout Mice

Abstract Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an orally deliverable, effective Xe formulation for long-term administration. We employed 2-hydroxypropyl)-β-cyclodextrin (HPCD), which was dissolved in water to increase the Xe concentration in solution. The beneficial effects of long-term oral administration of Xe-enriched solutions on cardiovascular function were evaluated in vivo. HPCD increased Xe solubility from 0.22 mM to 0.67 mM (3.8-fold). Aged ApoE knockout mice fed high-fat diet for 6 weeks developed hypertension, and myocardial hypertrophy with impaired cardiac function. Oral Xe prevented this ischemic damage, preserving normal blood pressure, while maintaining normal left ventricular mass and wall thickness. This novel formulation allows for gastrointestinal delivery and cardiovascular stabilization.

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