bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of Green Tea in experimental myocardial infarction
Authors: Lustosa Beatriz , Batista Diego , Polegato Bertha , Minicucci Marcos , Pereira Elenize , Okoshi Katashi , Matsubara Luiz , Zornoff Leonardo , Paiva Sergio , Gonçalves andrea , azevedo Paula
Published: June 2021

The objective of this study is to evaluate whether green tea attenuates cardiac remodeling after acute myocardial infarction.

Methods

Wistar rats were allocated in 4 groups: C (control); GT (diet with green tea 0,25%); MI (infarcted group) IGT (infarcted group with green tea 0,25%). After 3 months, animals were submitted to echocardiography and isolated heart study. Two way anova and Holm Sidak tests were performed.

Results

Both infarcted groups showed the same infarction size(p=0,7). Echocardiographic data without interaction:Left atrium/weight (with MI 14,4±0,5; without MI 10,7±0,6)(p<0,001)(with GT 13,0±0,5; without GT 12,1±0,6)(p=0,2); end diastolic ventricle diameter/weight (with MI 21,2±0,6; without MI 17,4±0,7)(p<0,001)(with GT 19,1±0,6; without GT 19,7±0,7)(p=0,5). Systolic function: Fractional area change (with MI 41,2±1,8; without MI 70,8±2) (p<0,001)(with GT 56,1±1,8; without GT 55,8±2)(p=0,9). Data with interaction (p=0,04) E wave deceleration time (EDT)(C 48,5±2,9; GT 45±2,6; MI 35,3±2,5; MIGT 43±2,4). Isolated heart study: Maximum systolic pressure (with MI 143±12; without MI 104±24)(p<0,001)(with GT 133±28; without GT 114±24)(p=0,03).

Conclusion

green tea improved systolic and diastolic function in isolated heart study, increasing EDT. Supported by FAPESP.
RENAL ISCHEMIA/REPERFUSION INDUCED CARDIAC HYPERTROPHY IN MICE: CONTRIBUTION OF APOPTOTIC PROCESS
Authors: Trentin-Sonoda Mayra , Cirino-Silva Rogério , Carneiro-Ramos Marcela Sorelli
Published: June 2021

Objectives

Nowadays, some studies has emphasize the apoptosis plays a decisive role in cardiac hypertrophy. The aim of this study was to investigate if apoptotic factors were altered in heart after renal ischemia/reperfusion.

Methods

C57bl/6J mice were subjected to unilateral 60 min kidney ischemia, followed by reperfusion of 5, 8, 12, 15 and 20 days. Levels of urea were measured to confirm renal failure and gene expression were analyzed by real time PCR.

Results

Urea levels were increased in groups 5, 15 and 20 days (P<0.05). The group 15 days showed a significant increase in heart weight/body weight ratio when compared to sham group. The AIF was increased at 8 and 12 days groups (P<0.05), whereas the anti‐apoptotic Bcl‐2 mRNA levels were increased after 8 days (P<0.05). The Caspase 3 and 9 mRNA levels were increased only after 15 days of reperfusion (p<0.05).

Conclusion

First, the results indicate that renal ischemia/reperfusion model is able to induce a transient cardiac hypertrophy in mice. Levels of mRNA analysis suggests that pro‐apoptotic AIF, Bid, Caspase 3 and 9 might be involved to modulation of cardiac hypertrophy, since we observed an increase in major pro‐apoptotic factors at the same time we observed an increase in cardiac mass.
Impact of High‐Fructose Consumption on Gene Expression and the Cardiovascular System through NO‐Superoxide Interaction
Authors: Kertowidjojo Elizabeth , Song Su , Ojaimi Caroline , Hintze Thomas H
Published: June 2021

Fructose consumption (FC) has caused much concern due to its prominence in today's diet and its link to cardiovascular disease. We hypothesized that the effects of FC are mediated by overactivation of NADPH oxidase (Nox), which increases superoxide (O2−) production, reducing NO bioavailability. SD rats were fed either a normal or a 60% fructose diet for 21 days. FC animals showed increases in blood pressure and plasma insulin (3.1 ± 0.4 to 5.4 ± 0.4 ng/mL). In pregnancy, fetal weights of FC rats were significantly lower (5.84 ± .06 to 4.71 ± .06 g, ~20%). Furthermore, the reduction of myocardial O2 consumption (MVO2) ex vivo by bradykinin was impaired in FC (28 ± 2% to 17 ± 2%), an effect reversed by apocynin or tiron, a Nox inhibitor and O2− scavenger, respectively. Finally, microarray of mRNA revealed significant changes in 237 genes (p < .05, fold change > ± 1.5), including upregulation of cholesterol transporter caveolin 1 and endothelin receptor B, and repression of mitochondrial protein Mrpl12, and mitochondrial ATP synthase subunit Atp5S. Analysis of miRs showed repression of miRs associated with upregulated genes and vice versa, including trends seen in heart failure: upregulation of miR126, a regulator of angiogenesis, and miR21. In conclusion, FC triggers gene expression changes in the heart with involvement of miRs, which leads to the lowering of NO bioavailability through the generation of O2−. Supported by PO43023.
Role of PI3K/Akt in the biphasic inotropic effects of ethanol on the heart
Authors: Cousins Valerie , Sankavaram Kavitha , El-Rubaiee Mustafa , Allard Joanne S , Kinfemichael Bezawit , Haddad Georges E
Published: June 2021

Studies have shown that low alcohol is associated with beneficial cardiovascular effects, while high alcohol is proven to be harmful. Previously we have shown that the survival pathway, PI3K, is essential for cardiac inotropy. Therefore, we hypothesized that ethanol may mediate its inotropic effects partially via PI3K pathway. Contractility and [Ca2+]i measurements were performed on adult rat myocytes exposed to low (LA: 5 mM) and high (HA: 100 mM) doses of ethanol (2hr) in the presence or absence of PI3K inhibitor (LY 294002; 1 uM) or PI3K agonist, IGF‐1 (10 uM). LA increased cellular and sarcomeric contraction associated with increase in the velocity of contraction. Relaxation and calcium sequestration was also improved by LA. Inhibition of PI3K negated the contractile effects of LA, but enhanced the relaxation ones. HA decreased the strength of contraction and increased speed of relaxation and calcium sequestration. IGF‐1 reduced the negative contractile effects of HA. On the molecular level, HA increased Akt mRNA expression, however, no changes in protein levels were observed. Our results suggest that the regulation of PI3K activity is crucial for the positive LA‐as well as the negative HA‐induced inotropic effects. Furthermore, the translation of PI3K downstream target, Akt, is decreased with HA, which partly explains the detrimental inotropic effect of alcohol on the heart. Funded by NIH/NIAAA and NIH/NIGMS.
MnSOD reduction causes mtDNA damage in HAEC under Oscillatory Shear Stress
Authors: Quigley Katherine , Fang Karen , Jen Nelson , Li Rongsong , Hsiai Tzung
Published: June 2021

Fluid shear stress is intimately involved in vascular reactive oxygen species (ROS) production and inflammatory responses. While atheroprotective flow up‐regulates the expression of manganese superoxide dismutase (Mn‐SOD), atherogenic flow; namely, oscillatory shear stress (OSS) down‐regulates MnSOD. We hypothesize that OSS promotes mitochondrial DNA (mtDNA) via the down‐regulation of MnSOD. To simulate oscillatory shear stress at an arterial bifurcation, we exposed human aortic endothelial cells (HAEC) to a well‐defined flow profile (OSS at +/− 3 dynes/cm2) for 4 hours in a dynamic parallel flow system. MtDNA damage levels were quantified through amplification via PCR of the common 4,997‐bp deletion previously used as a DNA damage biomarker. Under these conditions, OSS increased mtDNA damage (p< 0.05, n=6). By the addition of an MnSOD mimetic, MnTMPγP, mitochondrial DNA damage was attenuated twofold (p<0.05, n=3). Further, in the presence of an MnSOD adenovirus, OSS‐induced mtDNA damage was also attenuated. Taken together, these results suggest that OSS induces vascular mtDNA damage via a reduction in MnSOD expression.
Intracoronary vs Intravenous Delivery of Adeno‐associated Virus for Cardiac Gene Transfer in Mice
Authors: Fang Hongfei , Lai Ngai Chin , Tang Eric , Roth David M. , Gao Mei Hua , Hammond H. Kirk
Published: June 2021

Adeno‐associated virus (AAV) is a useful vector for cardiac gene transfer, but the optimal delivery route has not been established. We examined the relative efficacy of three AAV serotypes (AAV5, AAV6, AAV9) and two delivery methods: indirect intracoronary (IC) vs intravenous (IV) in mice. AAV5.EGFP, AAV6.EGFP, and AAV9.EGFP (5 × 1011 genome copies) were delivered by IV and IC injection. Three weeks later left ventricular samples were assessed for EGFP expression using fluorescent microscopy. IC delivery was superior to IV delivery for all serotypes in EGFP fluorescence analysis (Figure), findings that were confirmed by similiar increases in immunoblotting and qPCR (data not shown).

Conclusion

IC was superior to IV delivery for all three AAV serotypes tested, and AAV9 was superior to AAV6 and AAV5. In settings where maximum cardiac gene transfer is desired, IC delivery should be used.
Regulation of Lipoma Preferred Partner in the heart
Authors: Boateng Samuel , Hooper Charlotte
Published: June 2021

Adaptor proteins play an important role in signalling pathways by providing a platform on which many proteins interact. Malfunction or mislocalisation of these proteins play a role in the development of disease. Lipoma preferred partner (LPP) is a nucleocytoplasmic shuttling adaptor protein. Previous work show that LPP plays a role in the function of smooth muscle cells and in atherosclerosis. In this study we wanted to determine whether LPP has a role in the myocardium. LPP expression increased by 56% in hearts from pressure overload aortic banded rats (p<0.05 n=4), but not after myocardial infarction, suggesting mechanical regulation of its expression. In vitro, LPP expression was 87% higher in cardiac fibroblasts than myocytes (P<0.05 n=3). LPP expression was down‐regulated in the absence of the actin cytoskeleton but not when microtubules were disassembled. We mechanically stretched cardiac fibroblasts using the Flexcell 4000 for 48h (1Hz, 5% maximum strain), which decreased total LPP expression by 35% and membrane localization in subcellular fractions (P<0.05, n=5). LNAME, an inhibitor of NO synthase upregulated LPP expression but not smooth muscle actin. These findings suggest that LPP is regulated by a complex interplay between NO and mechanical cues and may play a role in heart failure induced by mechanical stress.
Protective effect of fasting in hearts and arteries of Pparα−/− mice
Authors: Silswal Neerupma , Green Troy , Badr Mostafa , Wacker Michael J. , Andresen Jon
Published: June 2021

Peroxisome proliferator activated receptors (PPARs), of which there are three subtypes, are important determinants of cardiovascular health. Generally, following stimulation by fatty acids, PPARs alter the expression of metabolic genes that regulate energy homeostasis. In the present study, we examined the effect of fasting on cardiac and vascular function in wild‐type (WT) and PPARα‐deficient (Pparα−/−) mice. In isolated aortas from mice fed normal chow, relaxation to acetylcholine (ACh), but not sodium nitroprusside, was impaired by 25% in Pparα−/− mice. Additionally, we found that eNOS mRNA expression was reduced 2.4‐fold in aortas of fed Pparα−/− mice. Interestingly, fasting for 36 hours restored relaxation to ACh in Pparα−/− mice without altering the response in WT mice. Ex vivo cardiac contractility demonstrated that hearts from fed Pparα−/− mice were 37% weaker than WT hearts. Similar to the aorta, fasting for 36 hours improved cardiac contractility by 46% in Pparα−/− mice. Thus, fasting improves endothelial function and cardiac contractility in Pparα−/− mice, suggesting that PPARα is normally protective in the cardiovascular system. This work was supported by AHA SDGs 0735053N (Dr. Andresen), 11SDG5330016 (Dr. Wacker), AHA Postdoctoral grant 7650044 (Dr. Silswal), and a NIH‐NIAMS grant RC2 AR058962 (Drs. Andresen and Wacker).
Reversible cardiac remodeling after renin‐angiotensin system stimulation in CYP1A1‐Ren2 transgenic rats
Authors: Janssen Ben , Heijnen Bart , Pelkmans Leonie , Danser Jan , Garrelds Ingrid , Mullins John , De Mey Jo , Struijker-Boudier Harry
Published: June 2021

In transgenic inducible Cyp1a1‐Ren2 hypertensive rats (IHR) (pro)renin levels and blood pressure (BP) can be dose‐dependently titrated by administration of indole‐3‐carbinol (I3C). We examined if activation of (pro)renin to levels that cause severe hypertension (HT) would provoke hypertrophic cardiomyopathy or heart failure (HF). Echocardiographic studies in young and adult IHR revealed that stimulation of (pro)renin for 4 weeks (SBP>200mmHg) did not result in HF but incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness and decreased LV volume. Hypertrophic gene expression was upregulated, whereas activation of matricellular, inflammatory and fibrotic responses were absent. We tested also if this cardiac remodeling process could be reversed by de‐activation of the (pro)renin system. Four weeks after withdrawal of I3C, (pro)renin levels were normalized young and adult IHR. While in adult IHR BP returned to normal, HT was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin induced severe HT in IHR causes an age‐independent fully reversible myocardial concentric hypertrophic remodeling. In addition, de‐activation of the renin‐angiotensin system was sufficient for the reversion of cardiac hypertrophy, despite the presence of elevated BP.
Abnormal heart rate control in SCN5A‐[Delta]KPQ Mice
Authors: Wu Maddalena Alessandra , Bari Vlasta , Calvillo Laura , Crotti Lia , Schwartz Peter J , Porta Alberto , Montano Nicola
Published: June 2021

Patients with mutations on the sodium channel gene SCN5A (LQT3) are at highest risk for cardiac arrest/sudden death during sleep or rest. The availability of knock‐in mice, heterozygous for the highly malignant SCN5A‐[Delta]KPQ mutation, is a precious translational tool. We assessed the cardiac phenotypic characterization of the [Delta]KPQ mice in the attempt of identifying predictors of risk.

Heart rate (HR), body temperature and the locomotor activity signals were continuously recorded by a telemetric system for 3 consecutive days, in 6 wild type (WT) and 6 transgenic LQT3 mice (LQT). Animals were kept in a temperature‐controlled room at 20–24°C, with constant light/dark cycle. Circadian rhythm variation analysis was performed through the averaging of each 5 min for the whole 24 hours. The 24‐hours were divided in two 12‐hours periods, LIGHT (the quiet/sleep cycle) and DARK (the activity/wake cycle).

In the LQT group HR was lower during LIGHT than during DARK (497±70 vs 535±51 bpm; p<0.05). WT group behaved similarly (545±23 vs 571±40 bpm; p<0.05). The HR variability was larger in the LQT group than in the WT one both during DARK (5453±781 vs 4185±1427 bpm2; p<0.05) and LIGHT (5266±388 vs 4189±966 bpm2; p<0.05).

LQT and WT mice showed a preserved HR circadian behavior. In addition, in the LQT mice HR variations were unusually large, thus suggesting an abnormal cardiac regulation. Telethon Grant
Cardiac amyloidosis and its suppression in a Huntington's disease model in the Drosophila heart
Authors: Melkani Girish C. , Bodmer Rolf , Ocorr Karen , Bernstein Sanford I.
Published: June 2021

Cardiac failure is one of the major causes of mortality in Huntington's disease (HD) patients, apparently as a result of toxic amyloid buildup due to oxidative stress and/or protein misfolding. We explored cardiac defects linked with HD‐causing amyloid protein by expressing mutant Huntingtin (Htt) with short (UAS‐Httex1‐PolyQ25) and disease causing expanded (UAS‐Httex1‐PolyQ72) PolyQ in the Drosophila heart using a cardiac specific driver. Expression of disease causing Poly‐Q in 1 and 3 week old fly hearts resulted in severe cardiac defects as evidenced by a significantly increased incidence of arrhythmias, extreme cardiac dilation and reduced cardiac performance. Structural analysis revealed severe myofibrillar disorganization and the presence of amyloid aggregates. No such physiological and structural defects were seen upon expression of short PolyQ. To further explore the mechanism underlying the PolyQ‐induced cardiac defect, we co‐expressed expanded PolyQ with either the antioxidant enzyme superoxide dismutase (SOD) or a chaperone protein UNC‐45. Our results suggest that cardiac dilation, arrhythmias and amyloid aggregates are reduced and cardiac performance is enhanced upon co‐expression of SOD or UNC‐45. This novel Drosophila disease model allows us to explore the role of oxidative stress and/or protein misfolding in cardiac defects associated with the accumulation of HD‐causing amyloid.
Stepwise Ischemic Preconditioning Mitigates Prolonged Ischemia/Reperfusion injury
Authors: Yamakawa Kentaro , Zhou Wei , Mahajan Aman
Published: June 2021

The current cardiac ischemic preconditioning (IPC) protocol may not be clinically beneficial due to its deleterious effects on myocardium. This study attempted to assess the effects of a novel stepwise IPC on cardiac performance, infarct size and arrhythmia in a rabbit model of prolonged I/R. Anesthetized open chest rabbits were subjected to 60 min occlusion of the first left antero‐lateral coronary branch followed by 180 min reperfusion. Animals were divided into five groups (n=6 each). All animals except for control group were subjected to four IPC groups as follows: 1) short IPC group (three cycles of 2min I/R); 2) standard IPC group (three cycles of 5 min I/R); 3) prolonged IPC group (three cycles of 10 min I/R); 4) stepwise IPC group (2, 5, 10 min I/R). Compared to control group, short, standard, and prolonged IPC decreased arrhythmia score by 16%, 67% and 33%, respectively; while stepwise IPC resulted in a 78% reduction of arrhythmias. The stepwise IPC showed the most marked reduction of LV infarct size, compared to the short, standard and prolonged IPC (8.6% vs. 22%, 10.3% and 15.7%). These results suggest that the stepwise IPC has better cardioprotective effects against prolonged I/R injury and may serve as an acceptable approach to heart surgeries such as angioplasty on a beating heart.
Protective Mechanism of PPAR‐delta‐HIF1 signaling in the Ischemic Diabetic Heart
Authors: Nanayakkara Gayani K. , Wyble Johnathon , Quindry John , Amin Rajesh H.
Published: June 2021

Diabetes associated heart disease is at epidemic proportions often manifesting as ischemic heart disease. Therapies which improve myocardial energy availability mitigate the development of myocardial infarction. We observed that Peroxisomal Proliferator Activated Receptor‐delta (PPARδ) activation induces Hypoxia Inducible Factor‐1 (HIF1) expression and nuclear localization in diabetic (db/db) mouse hearts. HIF1 regulates genes associated with protection against ischemic stress and increase energy availability. Adiponectin is among HIF1 inducible genes and increases fatty acid oxidation. We hypothesize
that PPARδ mediated increase in HIF‐1 protects cardiomyocytes against ischemic injury by stimulating heart specific adiponectin production.

Results

(1) Db/db hearts expresses attenuated levels of HIF1 and adiponectin. (2) PPARδ activation (GW0742, 10 mg/kg, 7 days) in db/db mice increases HIF1 expression and nuclear localization. Promoter activity assays (luciferase) in HEK293 cells reveal that PPARδ transcriptionally regulates HIF‐1. (3) PPARδ activation increases heart specific expression of adiponectin. (4) PPARδ activation significantly protects the diabetic heart from Ischemia Reperfusion injury compared to control db/db hearts.

Conclusion

PPAR‐δ mediated protection against IR injury in the diabetic heart involves HIF1. Funding: Auburn University Internal Grant Program
Apocynin exerts cardioprotection in ischemia/reperfusion (I/R) by inhibiting superoxide release from NADPH oxidase
Authors: Bartol Kyle D , Habtamu Tsion , Tolson Jasmine , Koko Deima , Diaz Brian , Murphy Ryan , Chen Qian , Young Lindon
Published: June 2021

I/R results in a marked cardiac contractile dysfunction. Inhibiting superoxide (SO) release via NADPH oxidase may preserve cardiac contractile function following I/R. Apocynin (MW= 166) inhibits NADPH oxidase by blocking the translocation of p47phox to the membrane. We studied isolated rat hearts following ischemia (30 min) and reperfusion (45 min). Control I/R hearts (n=5) recovered to 41 ± 8% and 30 ± 6% of baseline values for left ventricular developed pressure (LVDP) and the rate of LVDP (+dP/dtmax) respectively at the end of reperfusion. Apocynin (400μM, n=3) given at reperfusion significantly restored LVDP (p<0.05) and +dP/dt max (p<0.01) by 81 ± 5% and 80 ±3%, respectively, at 45 minutes post reperfusion compared to I/R hearts. Phorbol 12‐myristate 13‐acetate (PMA, 100nM, n=12) and N‐formyl‐L‐methionyl‐ L‐phenylalanine (fMLP, 1μM, n=27) stimulated neutrophil SO release was measured spectrophotometrically. Apocynin dose dependently attenuated fMLP and PMA stimulated neutrophil SO release by 63 ± 8% (400μM, n=11, p<0.01), 81 ± 9% (1mM, n=10, p<0.01), and 29 ± 5% (400μM, n=10, p<0.05), 47 ± 6% (1mM, n=10, p<0.01), respectively. These results suggest that apocynin attenuates post I/R cardiac contractile dysfunction by inhibiting the release of SO from NADPH oxidase in post reperfused tissues.
Metabolic Profiles of the second and third windows of ischemic preconditioning
Authors: Bravo Claudio Andres , Kudej Raymond K , Vatner Stephen F , Vatner Dorothy E , Yan Lin
Published: June 2021

There have been numerous studies on the differences between the first window of ischemic preconditioning (IPC) and late IPC, i.e. the second window of IPC.

Recently our group has shown the presence of a third window of IPC, which is induced by 6 episodes of non lethal ischemia over 3 days. This model differs from classical second window IPC, induced by 1 or 2 episodes of non lethal ischemia, followed 24 hr. later by a longer period of ischemia. The underlying molecular mechanisms mediating the second and third windows of IPC are very different, but both paradigms of IPC appear to affect myocardial metabolism. The goal of this study was to provide a global analysis of the metabolic profile of these two late IPC models, using a metabolomic approach based on liquid chromatography‐mass spectrometry (LC‐MS) and gas chromatography‐mass spectrometry (GC‐MS) techniques. Myocardial samples from the ischemic section of porcine hearts subjected to second and third window IPC were compared against sham controls. Out of 287 assessed metabolites, there were more changes in metabolic pathways noted in third window (119 metabolites) than second (24 metabolites), but surprisingly only 7 metabolites were common to both models. The results of this study confirm the importance of metabolic pathways mediating late IPC, and again illustrate major differences between the third and second windows of IPC.
Mitochondrial DNA Fragmentation Impairs Endothelial Function In Zucker Lean Rats
Authors: Pung Yuh Fen , Kolz Christopher , Shokolenko Inna , Wilson Glenn L , Chilian William M
Published: June 2021

Mitochondrial (mt) oxidative stress is implicated in vascular dysfunction in the metabolic syndrome (MS), a risk factor for ischemic heart disease. We observed increased mt‐oxidative stress in aortae of Zucker Obese Fatty rats (model of human MS), and endothelial dysfunction in microvessels. Because mt‐oxidative stress is associated with excessive production of mt‐ROS and these species can induce mtDNA fragmentation, we tested the hypotheses that mt‐DNA fragmentation is responsible for endothelial dysfunction and that a manifestation of mt‐DNA fragmentation is decreased energy supply in the vascular wall. Accordingly, mitochondrial‐targeted exonuclease III (Mt‐tat‐ ExoIII) was utilized to fragment mt‐DNA in lean rats treated with Mt‐tat‐ExoIII (80 μg/day, iv for 3 days). This treatment produced endothelial dysfunction (impaired endothelial relaxation to acetylcholine) and increased mt‐ROS levels (mitoSox fluorescence). Dilation to nitroprusside was not impaired suggesting smooth muscle function was not altered. In endothelial cell cultures, mt‐tat‐ExoIII increased O2 consumption. This increase appeared to be uncoupled to energy production because phosphorylation of the energy senor, AMP‐kinase was elevated, suggesting decreased ATP levels. Taken together, our study demonstrates the importance mitochondrial DNA integrity in modulating mitochondrial function and bioenergetics.
Gamma‐tocopherol nebulization attenuates acute lung injury with burn and smoke inhalation in the ovine model
Authors: Sousse Linda Elias , Yamamoto Yusuke , Enkhbaatar Perenlei , Kraft Ed R , Wright Charlotte L , Taylor Alan , Cox Robert A , Hawkins Hal K , Traber Lillian D , Traber Maret G , Szabo Csaba , Herndon David N , Traber Daniel L
Published: June 2021

We hypothesize that nebulization of gamma‐tocopherol (g‐T) in the airway of our ovine model of acute respiratory distress syndrome (ARDS) will effectively improve pulmonary function following burn and smoke inhalation after 96 hrs. Adult ewes (n=14) were subjected to 40% total body surface burn and were insufflated with 48 breaths of smoke under deep anesthesia, in a double‐blind comparative study. A customized aerosolization device continuously delivered g‐T in ethanol from 3 to 48 hrs after injury (g‐T group, n=6), while the control group (n=5) was nebulized with only ethanol. All animals were sacrificed after 96 hrs. Lung g‐T concentration and PaO2/FiO2 ratio significantly increased after g‐T nebulization compared to the control group (p<0.05). The following clinical parameters were significantly improved with g‐T treatment (p<0.05): pulmonary shunt, peak and pause pressures, lung bloodless wet‐to‐dry weight ratios, and obstruction. Delivery of g‐T into the lungs may be a safe, novel, and efficient approach for patients who have sustained oxidative damage to the airway. SUPPORT: GM66312‐01 and GM60668, and SHC 8630, 8520, 8954, 84060, 8450.
Effects of Coffee Consumption on NASH‐Induced Oxidative Stress in Rat Heart
Authors: Cheng Hsin-Yao , Tsai Shiow-Chwen , Huang Wei-Chih , Yang Ai-Lun , Chan Che-Chang
Published: June 2021

OBJECTIVE

To investigate whether coffee consumption improved NASH induced oxidative stress in heart.

METHODS

8‐week‐old male rats were randomly divided into 3 groups: control, methionine‐choline‐deficient (MCD) and MCD combined with coffee (MCD+Co); feeding with coffee (1.5 ml/day) for 4 weeks until sacrifice. The production of lipid peroxidation and the activities of antioxidant enzymes in left ventricular (LV) tissues were measured by commercial kits. All of the data were presented at Mean ± S.E.M., p <0.05 regard as significantly difference.

RESULTS

Rat fed with the MCD diet showed a rapid loss of body weight and heart weight, but not altered the ratio of LV and body weight. The production of lipid peroxidation was increased in MCD, but not in MCD+Co compared with MCD0. The activity of SOD were significantly increased 3 fold in MCD+Co (p<0.0001) and increased 1.5 fold in MCD (p=0.004) compared with control group. Compared with MCD0, the activity of catalase were enhanced by MCD+Co significantly (p=0.018). Coffee consumption improved the maintenance of glutathione peroxidase (GPx) during the feeding of MCD diet.

CONCLUSION

Coffee inhibit the production of lipid peroxidation through enhancing the activity of catalase and GPx in LV.
Evaluation of lung damage related to extra‐vehicular activity (EVA) during space exploration using a novel murine and cell model of repeated double‐hit low‐level radiation and hyperoxia exposure
Authors: Christofidou-Solomidou Melpo , Pietrofesa Ralph A , Dukes Floyd , Tyagi Sonia , Solomides Pantelis , Arguiri Evguenia , Solomides Charalambos C
Published: June 2021

Extra‐vehicular activities (EVA) during spaceflight missions expose crew members to challenges, such as hyperoxia and low levels of cosmic/galactic radiation that may present a threat to their health. Our objectives were to develop and characterize in vivo/in vitro models of similar double‐hit challenges. Mouse cohorts (n=10/group) were exposed to: a) normoxia; b) >95% O2 (O2); c) 0.25Gy gamma radiation (RAD); or d) a combination of O2 and RAD (O2+RAD). Challenge (O2 or RAD) was given 3X weekly for 1, 2 or 4 wks; 8‐hour hyperoxia was spanned by normoxic intervals. Lungs were evaluated for oxidative damage, inflammation, injury and fibrosis. In addition, mouse lung epithelial cells, exposed to similar O2 or RAD conditions were evaluated for apoptosis, DNA fragmentation and survival. After just 1 wk, all treatments resulted in significant mouse lung injury (p<0.05) evidenced by increased bronchoalveolar lavage protein levels and significant inflammation (p<0.003). O2 and O2+RADexposed mice had higher oxidative tissue damage (p<0.01) by 2 wks. Elevated lung tissue fibrosis was detected (p<0.04) as early as 1 wk. Epithelial cells exposed to all conditions had marked increases in apoptosis and DNA damage, and reduced survival. In conclusion, we have developed and characterized an EVA‐related in vivo/in vitro model of repeated low‐level radiation and hyperoxia. Funded by: NIH/NCI, NASA (MCS)
Physical training promotes different cardiac autonomic adaptations after premature and physiological ovarian failure in aged rats
Authors: Tezini Geisa Cristina Singolani Vaccari , Dias Daniel Penteado Martins , Souza Hugo Celso Dutra
Published: June 2021

We investigated the effects of physical training on cardiac autonomic control in rats subjected to premature and physiological ovarian failure by means of different approaches: double autonomic blockade (methylatropine and propranolol, iv) and pulse interval (PI) variability analysis in the frequency domain. Sixty female rats were assigned into six groups: sham sedentary young, sham trained young, sham sedentary aged, sham trained aged, ovariectomized (OVX) sedentary aged and OVX trained aged. Sham young sedentary rats showed vagal predominance on HR control, whereas sedentary aged groups, sham and OVX, showed a sympathetic predominance. Physical training increased vagal tone in sham young group and leaded to an inversion of predominance in sham aged group. PI variability analysis showed that sedentary aged groups, sham and OVX, showed a reduction in variance and in the power of low (LF, 0.25–0.75 Hz) and high frequency (HF, 0.75–3.00 Hz) bands of the PI spectrum. Physical training in sham groups, young and aged, decreased LF power and augmented HF power of the PI spectrum and no changes were observed in PI variability of OVX aged rats. In conclusion, aging associated with premature or physiological ovarian failure, had negative effects on cardiac autonomic control. Nevertheless, physical training had positive effects on cardiac autonomic control only in rats with physiological ovarian failure.
Exercise alone limits reductions in intimal smooth muscle K+ current in a swine model of coronary artery disease
Authors: Tharp Darla L. , Ivey Jan R. , Bowles Doug K.
Published: June 2021

We previously demonstrated in Rapacz familial hypercholesterolemic (FH) swine with coronary artery disease that exercise (EX) combined with a low fat diet attenuated reductions in intimal coronary smooth muscle (iCSM) whole cell K+ current. The goal of the present study was to determine if EX alone is sufficient in attenuating these reductions and to identify the K+ channels responsible. FH swine were placed on a high fat diet at 14 months of age and then were treadmill trained (EX; n=5) or remained sedentary (SED; n=6) from 20 to 24 months of age. iCSM whole cell K+ current was measured in the presence and absence of blockers for voltage‐gated (Kv; 4‐AP, 2mM), large‐conductance (BK; Iberiotoxin, IBTX, 100nM) and intermediate‐conductance Ca2+ activated K+ (IK; TRAM‐34, 100nM) channels from −70 to +100 mV. Compared to weight matched non‐FH control swine (84.3 ± 9.3 pA/pF, n=20), FH SED had reduced peak (+100 mV) whole cell K+ current (14.3 ± 2.1, n=33), which was attenuated by EX (32.3 ± 4.6, n=42; p<0.001). SED (0.10 ± 0.29, n=30) had reduced Kv current compared to EX (1.72 ± 0.74, n=20; +30 mV; p=0.02). BK current was not different between groups [SED (6.0 ± 1.6, n=24) vs. EX (12.5 ± 5.4, n=17); p=0.19]. Neither SED nor EX had measurable IK current. In conclusion, EX alone attenuated reductions in iCSM K+ current in FH swine, in part via the maintenance of Kv current. NIH HL52490
Effects of acute exercise on circulating endothelial progenitor cells and endothelial function in patients with increased cardiometabolic risk
Authors: Rocha Natalia G , Sales Allan R K , Silva Mayra S , Miranda Renan L , Carvalho Sara B , Silva Jemima R F , Silva Bruno M , Santos Aline A , Nóbrega Antonio C L
Published: June 2021

Endothelial progenitor cells (EPC) play a critical role in vascular repair and its depletion is usually associated with endothelial dysfunction. In addition, regular moderate‐intensity aerobic exercise increases EPC mobilization from bone marrow to peripheral blood and, consequently, improves endothelial function. Therefore, this is a potential mechanism by which exercise reduces the risk of atherosclerosis in patients with cardiometabolic risk (CMR). However, it is unclear whether exercise‐induced EPC mobilization is preserved in patients with CMR and whether EPC mobilization is associated with endothelial function in this population. Accordingly, healthy subjects (CT group; n=3) and patients with CMR (CMR group; n=7) were studied. Circulating EPC were evaluated quantitatively (flow cytometry) and qualitatively (immunofluorescence) before and 20 min after a 40‐ min bout of cycling exercise. Endothelial function was evaluated by flow‐mediated dilation (FMD, Doppler). The CMR group had a significant reduction in CD34 cells (P=0.02) and a trend of reduction in CD34/VEGFR2 cells (P=0.09) after exercise. Moreover, there was a marginal correlation between mobilization of CD34/VEGFR2 cells and FMD (r=0.55; P=0.10). These preliminary results suggest that a bout of aerobic exercise reduced circulating EPC in patients with CMR and EPC mobilization tended to be associated with endothelial function.

Supported by CNPq, FAPERJ, FINEP and CAPES.
Effect of aerobic training on the deposition of collagen fibers and glomerular proteoglycans in hypertensive rats
Authors: Batista Álvaro Martins , Alves Tatiana Pereira , El Chaar Laiali Jurdy , Souza-Oliveira Thais Cristina , Rabechi Nara Baptistella , Piva Camila Jesus , Jordão Maria Tereza , Viegas Katia Aparecida , Michelini Lisete Compagno , Lacchini Silvia
Published: June 2021

This study evaluated if aerobic training (AT) improves glomerular morphology in hypertensive (SHR) and normotensive (WKY) rats. We used SHR and WKY male rats 10weeks‐age submitted or not to AT (1hr, 5 times/week) for 1, 2, 4, 8 and 12 weeks or kept sedentary for 0 and 12 weeks (n=8/each). Mean arterial pressure (MAP) and heart rate (HR) were recorded, and kidneys harvested for Bowmanˈs capsule (BC) evaluation. Results were compared by ANOVA, using p=0.05 as significant. Both WKY and SHR improved physical performance after 6 and 12 weeks of AT(S0:1.02±0.3 vs 1.62±0.4, T6:1.32±0.2 vs 2.09±0.3, T12:1.92±0.4 vs 2.40±0.4km/h). SHR decreased MAP and HR (179±10 vs 163±6mmHg, 394±18 vs 363±3bpm; on S0 vs T12). BC thickness showed greater deposition of collagen fibers in SHR compared to WKY (3.72±1.35 vs 1.98±0.25?m; on sedentary), and reduction after AT in SHR (1.79±0.24μm). Proteoglycan analysis showed an increased deposition induced by hypertension (1.34±0.41 vs 0.90±0.09μm; sedentary SHR vs WKY), and AT decreased this in both(SHR:1.34±0.41 vs 0.75±0.09μm, WKY:0.90±0.09 vs 0.65±0.02μm; S0 vs T12). We also observed that the time of hypertension increases deposition of proteoglycans (1.34±0.41 vs 1.64±0.48μm; S0 vs S12). The data suggest that AT induces glomerular remodeling, reducing glomerular fibrosis and glomerulosclerosis in SHR, and may be associated with the observed fall in MAP.

Grant Funding Source : FAPESP
The role of exercise on oxidative stress and inflammation in macrophages involved in atherosclerosis
Authors: Chirico Erica N , Patsouris David , Geloen Alain , Rieusset Jennifer , Pialoux Vincent , Canet-Soulas Emmanuelle
Published: June 2021

Atherosclerosis is a chronic inflammatory disease that is overwhelmed by oxidative stress, with macrophages being main actors in this process. Exercise training has been shown to reduce oxidative stress and inflammation, providing protection in many diseases. We hypothesize that exercise training could improve the macrophage activation, oxidative stress, and inflammation in ApoE−/− mice. Young (8 weeks) and old (66 weeks) ApoE−/− mice on high fat/cholesterol diet were trained or kept sedentary for 12 weeks. Bone marrow derived macrophages (BMDM) were extracted in order to assess the direct effects of exercise on macrophage polarization. Exercise decreases oxidative stress (AOPP) and inflammation (TNFα, IL‐1β) regardless of age. The positive correlation between AOPP in plasma with TNFα confirms the interaction between oxidative stress and inflammation in atherosclerosis. Our results confirm a peak of inflammation in atherosclerotic plaque at 20 weeks, as demonstrated by magnetic resonance imaging and higher level of plasma TNFα, NF‐κB and IL‐1β compared to old mice. Stimulation of oxidative stress in BMDM increased inflammatory markers, while addition of antioxidants inhibited this response. In conclusion, these results suggest that the decrease in oxidative stress through exercise training could improve systemic inflammation and macrophage polarization in this animal model of atherosclerosis.
Glutathione Protects Against Exercise‐Induced Oxidative Stress In Mature db/db Mice Hearts
Authors: GHOSH SANJOY , HALDER SWAGAT , BEAM JULIANNE , BAHNIWAL RUPINDER
Published: June 2021

Low‐intensity exercise improves cardiac antioxidants in young animals irrespective of metabolic changes in type 2 diabetes (T2D). As diabetes and aging synergistically can decrease antioxidants, if exercises can increase antioxidants in mature T2D hearts, is unknown. 8‐month old db/db and wild‐type (WT) mice were moderately exercised for 3 weeks, and cardiac redox regulation was evaluated. Without altering metabolic status, exercise increased cardiac antioxidants and attenuated stress in mature WT mice. In contrast, exercise in db/db mice worsened oxidative damage, which was not explained by superoxide dismutase or catalase activities. Instead, loss of the antioxidant, glutathione (GSH) was noted. Further, GSH biosynthesis [γ‐glutamylcysteine synthase] and recycling [NADPH/NADP, glutathione reductase] were impaired while GSH‐dependent stress (GPX, 4‐hydroxynonenal, TGF‐β) was increased in these hearts. To validate the causal role for GSH, exercising db/db mice were administered exogenous GSH, which attenuated cardiac damage. This study shows that unlike younger animals, short‐term exercise may induce oxidative stress in mature animals and GSH supplementation can inhibit such stress in these hearts. Therefore, recent assertions of detrimental impact of antioxidants during exercise in healthy individuals should be extrapolated with caution in mature T2D patients undergoing exercise.
Differential Effects on Regional Pulse Wave Velocity & Augmentation Index Following Maximal Exercise in Healthy Young Men
Authors: New Karl James , Morgan Ashley , Harris Trevor , Fall Lewis , Brugniaux Julien , Bailey Damian M
Published: June 2021

Nine young normotensive healthy males (24.6± 3.7 years; 75.4± 10.2 kg) MAP = 91 ± 6 mmHg were studied for 1‐hour following an incremental ramp protocol to VO2peak (56.2± 10.5 ml/kg/min) on an electronically braked cycle ergometer. Blood pressure was assessed via an automated blood pressure monitor (Datex‐Ohmeda, Finland). Regional limb pulse wave velocity (PWV) was determined simultaneously in the left arm and leg by oscillometry (QVL P84, UK) whilst contemporaneously determining central aortic stiffness (AIx) via aplannation tonometry (Sphygmocor, Atcor Medical, Australia). The operator index, which is an estimate of quality of the SphygmoCor derived waveforms, was above the recommended level with an average index of >80%. Following mathematical confirmation of distribution normality using the Shapiro‐Wilks test data were analysed with a repeated measures ANOVA and post‐hoc Bonferroni‐corrected paired samples T‐tests.

During exercise there was an intensity‐related increase in MAP, heart rate and pulse pressure (P<0.01). Exercise decreased both systolic blood pressure across the 60‐minute recovery period (P<0.01) and MAP in the initial recovery from exercise (P<0.05). Upper limb PWV was reduced following exercise (P<0.05) whilst lower limb PWV was unchanged. AIx was elevated at the termination of exercise (P<0.05) but did not decrease below resting levels in the recovery period.

These results indicate that in active healthy individuals acute exercise induces a systemic hypotension and increased arterial compliance in the upper limb vascular bed but not the lower limb vascular bed. Furthermore, estimated aortic stiffness and central pressure appears to remain un‐modified in the recovery from exercise. Hence there are clear differential responses in central and peripheral large artery haemodynamic recovery from exercise.
Effects of physical exercise and high fructose diet on cardiac autonomic control in rats
Authors: Farah Daniela , Nunes Jonas Pereira , Bechara Ana Carolina Carneiro , Yokota Rodrigo , Sartori Michelle , Irigoyen Maria Claudia , De Angelis Katia , Fiorino Patricia , Farah Vera
Published: June 2021

The aim of this study was to evaluate the cardiovascular autonomic control in trained youth male rats fed with high fructose diet. Weaned male Wistar rats (21 days) fed with fructose in drinking water (10%, 8wks) were randomized into sedentary (FS, n=5) and trained (FT, n=8), treadmill running,5 days/w, 60 min/d, during 8 wks) groups. Insulin resistance was evaluated by Glucose Tolerance Test. Arterial pressure signals were recorded using a data acquisition system (Windaq, 2KHz) in conscious and freely animals. Vagal and sympathetic tonus were measured by pharmacological blockade. The FT group had higher exercise capacity and lower insulin resistance compared to the FS group. Mean arterial pressure was similar between groups (FS: 124 ± 6 vs. FT: 125 ± 3 mmHg), however, the FT group presented resting bradycardia (339 ± 10 bpm) compared to the FS group (366 ± 13bpm). The sympathetic tone was lower in the FT group (41 ± 13bpm) compared to the FS (80 ± 6 bpm), however vagal tone was similar between groups. Thus, our results suggest that physical training during lifespan can be effective in attenuating the autonomic dysfunction resulting from high fructose consumption.
Posterior cerebral artery blood flow response to visual stimulation during exercise
Authors: Yamaguchi Yuji , Ikemura Tsukasa , Kashima Hideaki , Hayashi Naoyuki
Published: June 2021

Neurovascular coupling (NVC) in the posterior cerebral artery (PCA) with visual stimulation during aerobic exercise at 70% of the maximal heart rate was reported to be maintained (Willie et al., 2011), but the effect of exercise intensity on NVC is still unknown. To investigate this effect, we measured the blood flow velocity in the PCA (PCAv) by transcranial Doppler ultrasound flowmetry during rest and exercise while fourteen healthy males performed a leg‐cycle exercise under mild, moderate, and heavy intensity conditions (120, 140, and 160 bpm of the heart rate, respectively). We estimated the NVC as the relative change in PCAv from eye‐closing to each two types of 40‐s visual stimuli such as eye‐opening and looking at a reversed checkerboard. Under the three exercise conditions, PCAv significantly increased from the baseline. Both visual stimuli significantly increased PCAv compared with eye‐closing at all conditions. The relative change in PCAv on reversed checkerboard stimulation was significantly lower under the moderate than the other intensity conditions. It was suggested that NVC in PCA in response to visual stimulation is affected by the exercise intensity.
Maternal exercise during pregnancy alters vascular smooth muscle relaxation in offspring
Authors: Bahls Martin , Sheldon Ryan D , Taheripour Pardis , Clifford Kerry A , Foust Kallie B , Cabot Ryan A , Newcomer Sean C
Published: June 2021

The intrauterine environment is influenced by maternal behavior and known to effect lifelong atherosclerotic disease susceptibility in offspring. The purpose of this investigation was to test the hypothesis that maternal exercise during pregnancy increases endothelial function in offspring. A total of 8 pubertal gilts, six months of age were randomly assigned to an exercise (n=4) or sedentary (n=4) group throughout pregnancy. Exercise consisted of treadmill running for 20–45 minutes, five times per week, for all but the last week of gestation. Dose‐dependent endothelium‐dependent (bradykinin (BK); 10−10–10−6 M) and –independent (sodium nitroprusside (SNP); 10−10–10−4 M) vascular relaxation was assessed in femoral arteries of offspring at 3, 5, and 9 months of age using wire‐myography. Exercise had no effect on litter characteristics. No main effects were observed for BK relaxation. However, exercise during pregnancy had a main effect on SNP relaxation (p=0.01). Specifically, decreased SNP relaxation was observed in the offspring of the exercise compared to the sedentary sows at 3 (p<0.01) and 9 (p<0.01) months of age. These results demonstrate that exercise for the finite duration of pregnancy has long lasting functional effects on the vasculature. Future studies will need to determine whether the observed reductions in vascular smooth muscle function affect atherosclerotic disease susceptibility.
Acute Oral Ingestion of Ascorbic Acid Improves Muscle Blood Flow and Oxygen Consumption During Exercise In Older Healthy Humans
Authors: Richards Jennifer C. , Crecelius Anne R. , Kirby Brett S. , Garcia Leora J. , Larson Dennis , Luckasen Gary J. , Dinenno Frank A.
Published: June 2021

Intra‐arterial infusion of ascorbic acid (AA) reverses the age associated blood flow impairment during mild handgrip exercise by improving endothelium‐derived nitric oxide bioavailability. We tested the hypothesis that acute oral AA would improve forearm blood flow (FBF) and oxygen consumption (VO2) during graded rhythmic handgrip exercise among older men (n=8; 65 ± 3 years). Subjects performed two bouts (15 minutes each) of graded rhythmic handgrip exercise (5, 15, 25% of maximum voluntary contraction (MVC)). Following trial 1 (control), participants ingested 2 g of AA and rested comfortably for 2 hours and repeated the exercise bout (trial 2). At rest and during exercise, we measured FBF (Doppler ultrasound) and calculated VO2 using deep venous blood samples. Compared to control, there was no influence of AA at rest or during 5% MVC exercise. AA significantly increased FBF (199 ± 13 vs. 248 ± 16 ml/min and 343 ± 24 vs. 403 ± 33 ml/min (P< 0.05)) and VO2 (262 ± 20 vs. 337 ± 28 ml/min and 433 ± 42 vs. 504 ± 58 ml/min (P< 0.05)) at both 15% and 25% MVC exercise, respectively. On a separate study day, participants repeated the protocol with a placebo pill (n = 4); there were no differences in any variable between trials 1 and 2 at rest or during exercise. We conclude that acute oral AA is capable of increasing FBF and VO2 during moderate intensity handgrip exercise in older healthy humans.

Supported by HL095573