Abstract 184: Exposure To Air Pollution In Utero Causes Persistent Cardiovascular Dysfunction

Exposure to air pollutants during pregnancy can have devastating effects on offspring, inducing intrauterine growth retardation and maturation deficits. These developmental insufficiencies can affect the formation and function of the adult heart. We hypothesized that exposure to air pollution in utero would induce abnormal cardiac function at adulthood. FVB mice were exposed (6h/day, 7d/wk) to environmentally relevant concentrations of ambient particulate matter (PM2.5) or filtered air (FA) beginning when animals were paired for breeding. After birth, both groups remained in FA. Cardiac echocardiography was performed at 10 weeks of age. Birth weight was reduced in pups exposed to PM2.5 during intrauterine development compared to FA exposed pups, and litter size did not differ significantly between groups. Echocardiography revealed reduced left ventricular fractional shortening with greater left ventricular end systolic diameter in PM2.5 exposed mice at 10 weeks of age. These results were similar to data from mice exposed perinatally (until weaning). This study supports the hypothesis that exposure to air pollution in utero can lead to heart dysfunction at adulthood.

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Abstract 411: In Utero Exposure to PM2.5 Causes Adult Cardiovascular Dysfunction and Reduced Exercise Capacity

Circulation Research ◽

10.1161/res.119.suppl_1.411 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Vineeta Tanwar ◽

Kristin I Stanford ◽

Loren E Wold

Keyword(s):

Exercise Training ◽

Cardiac Function ◽

Exercise Capacity ◽

Posterior Wall ◽

In Utero ◽

Exercise Group ◽

Left Ventricular ◽

Average Concentration ◽

Intrauterine Development ◽

Total Distance

Objective: Exposure to particulate matter 2.5 μm (PM2.5) during intrauterine development is associated with adverse cardiovascular outcomes at adulthood. Deteriorations in cardiac function are observed with increased myocardial demand in PM2.5-exposed individuals. The goal of this study was to determine the effects of in utero PM2.5exposure on exercise training capacity and cardiac function in adult mice. Methods: Female FVB mice were exposed either to filtered air (FA) or PM2.5at an average concentration of 73.61μg/m 3 for 6h/day, 7days/wk throughout pregnancy. 12wk old male offspring from exposed dams were assigned to in utero FA (n=5) or PM2.5 (n=5) exposed groups which underwent exercise training for 3 weeks (housed with running wheels for 3 weeks). We measured total distance travelled and performed echocardiography at baseline, 1, 2 and 3 weeks. Results: There was a progressive decrease in total distance travelled each week in the in utero PM2.5 exposed mice (Week 1: 12.2±3.46 Km FA, 5.32±2.06 Km PM2.5; Week 2: 41.4±9.62 Km FA, 17.28±6.60 Km PM2.5; Week 3: 61.8±16.59 Km FA, 25.92.±8.62 Km PM2.5) compared to the in utero FA exposed mice. When comparing to their respective sedentary counterparts, the FA exercise group showed increased fractional shortening (%FS), left ventricular end systolic (LVESd) and diastolic (LVEDd) diameters, suggesting eccentric hypertrophy. There was a modest decrease in %FS and marked increase in posterior wall thickness during diastole (PWTd) in the PM2.5 exercise group suggesting concentric hypertrophy. Comparison of in utero FA vs PM2.5 exercise groups after 3 weeks of exercise training showed reduced %FS and marked decrease in LVEDd in the PM2.5 exercise group compared to the FA exercise group. Furthermore, a decrease in PWTs and increased PWTd was also observed in the PM2.5 group compared to FA controls. Conclusions: In utero PM2.5exposure reduced exercise capacity at adulthood and the development of both systolic and diastolic dysfunction. Thus, our study showed that individuals residing in high pollution areas are predisposed to develop cardiac dysfunction under conditions of increased myocardial demand.

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Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00224.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. R1232-R1241 ◽

Cited By ~ 8

Author(s):

Loren P. Thompson ◽

Ling Chen ◽

Brian M. Polster ◽

Gerard Pinkas ◽

Hong Song

Keyword(s):

Heart Function ◽

Left Ventricular ◽

Complex Iv ◽

In Vivo Measurement ◽

End Diastolic Volume ◽

Consumption Rates ◽

Ventricular Wall Thickness ◽

And Function ◽

Fractional Shortening

Adverse intrauterine conditions cause fetal growth restriction and increase the risk of adult cardiovascular disease. We hypothesize that intrauterine hypoxia impairs fetal heart function, is sustained after birth, and manifests as both cardiac and mitochondrial dysfunction in offspring guinea pigs (GPs). Pregnant GPs were exposed to 10.5% O2 (HPX) at 50 days of gestation (full term = 65 days) or normoxia (NMX) for the duration of the pregnancy. Pups were allowed to deliver vaginally and raised in a NMX environment. At 90 days of age, mean arterial pressure (MAP) was measured in anesthetized GPs. NMX and prenatally HPX offspring underwent echocardiographic imaging for in vivo measurement of left ventricular cardiac morphology and function, and O2 consumption rates and complex IV enzyme activity were measured from isolated cardiomyocytes and mitochondria, respectively. Prenatal HPX increased ( P < 0.01) MAP (52.3 ± 1.3 and 58.4 ± 1.1 mmHg in NMX and HPX, respectively) and decreased ( P < 0.05) stroke volume (439.8 ± 54.5 and 289.4 ± 15.8 μl in NMX and HPX, respectively), cardiac output (94.4 ± 11.2 and 67.3 ± 3.8 ml/min in NMX and HPX, respectively), ejection fraction, and fractional shortening in male, but not female, GPs. HPX had no effect on left ventricular wall thickness or end-diastolic volume in either sex. HPX reduced mitochondrial maximal respiration and respiratory reserve capacity and complex IV activity rates in hearts of male, but not female, GPs. Prenatal HPX is a programming stimulus that increases MAP and decreases cardiac and mitochondrial function in male offspring. Sex-related differences in the contractile and mitochondrial responses suggest that female GPs are protected from cardiovascular programming of prenatal HPX.

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Progressive feline pressure-overload: noninvasive assessment correlates with abnormalities in single cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.4.h1307 ◽

1993 ◽

Vol 264 (4) ◽

pp. H1307-H1314 ◽

Cited By ~ 1

Author(s):

P. S. Pollack ◽

B. A. Bailey ◽

R. Budjak ◽

E. Fernandez ◽

S. R. Houser

Keyword(s):

Myocardial Dysfunction ◽

Single Cells ◽

Pressure Overload ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Septal Wall ◽

Septal Wall Thickness ◽

Feline Model ◽

And Function ◽

Fractional Shortening

Serial echocardiography and Doppler were used to monitor the progression of pressure-overload produced by banding the ascending aortas of young cats. The peak Doppler gradient across the band increased (as the animals grew in size) from 42 +/- 4.2 mmHg at 1 wk to 78 +/- 4.5 mmHg at 2-3 mos. Echocardiographic measurements of septal wall thickness increased significantly at 1 wk. Global ventricular function was unaltered in banded cats versus shams at each time point. However, in the subgroup of animals with an aortic-constricted area of < 0.025 cm2 at 1 wk, fractional shortening decreased by 40% at 2-3 mos. Contractile abnormalities were present in isolated myocytes from hypertrophied hearts. Mechanical function was more profoundly depressed in cells from hearts with echocardiographic evidence of ventricular decompensation. Echocardiographic and Doppler studies assessed cardiac size and function and identified indexes predictive of global and cellular myocardial dysfunction. The use of noninvasive techniques as a predictor of failure makes the feline model of progressive left ventricular pressure-overload useful for studies of cellular and molecular factors regulating not only the development of cardiac hypertrophy but also the transition from compensated hypertrophy to myocardial failure.

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The Impact of Woodsmoke, Point Sources and Traffic-Related Air Pollution on Intrauterine Growth Retardation (IUGR)

Epidemiology ◽

10.1097/01.ede.0000289016.50964.35 ◽

2007 ◽

Vol 18 (Suppl) ◽

pp. S197

Author(s):

M Brauer ◽

C Lencar ◽

L Tamburic ◽

J Marshall ◽

C Karr ◽

...

Keyword(s):

Air Pollution ◽

Growth Retardation ◽

Intrauterine Growth Retardation ◽

Point Sources ◽

Intrauterine Growth ◽

The Impact

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Cardiac left heart morphology and function in newborns with intrauterine growth restriction: relevance for long-term assessment

Medical Ultrasonography ◽

10.11152/mu-1667 ◽

2019 ◽

Vol 21 (1) ◽

pp. 62

Author(s):

Gabriela Corina Zaharie ◽

Monica Hasmasanu ◽

Ligia Blaga ◽

Melinda Matyas ◽

Daniel Muresan ◽

...

Keyword(s):

Intrauterine Growth Restriction ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Growth Restriction ◽

Control Group ◽

Left Heart ◽

Functional Changes ◽

Intrauterine Growth ◽

Cardiac Adaptation ◽

And Function

Aim: To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction (IUGR) pregnancies.Material and method: A cohort of IUGR infants were evaluated by serial echocardiographies at delivery and at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the control group according to gestational age (AGA).Results: Left heart measurements were significantly lower in IUGR newborns compared to AGA babies. Left ventricular size increased at follow-up inthe IUGR group (p<0.05). Systolic dysfunction (the myocardial performance index (MPI)> 0.47) was identified in 40% of the neonates in the IUGR group (16/40), respectively 4.76% in the control group. IUGR neonates had a significantly increased proportion of systolic malfunction (p=0.004).Conclusion: IUGR patients had reduced left ventricle dimensions compared to AGA babies. The MPI stands out as a marker of leftheart function in newborns. Systolic dysfunction was a hallmark of the cardiac adaptation in IUGR neonates.

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Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00940.2003 ◽

2004 ◽

Vol 286 (3) ◽

pp. H1070-H1075 ◽

Cited By ~ 86

Author(s):

Fumito Ichinose ◽

Kenneth D. Bloch ◽

Justina C. Wu ◽

Ryuji Hataishi ◽

H. Thomas Aretz ◽

...

Keyword(s):

Wall Thickness ◽

Maximum Rate ◽

Pressure Overload ◽

Posterior Wall ◽

Left Ventricular ◽

Mouse Strains ◽

Term Administration ◽

And Function ◽

The Impact ◽

Fractional Shortening

To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3–/–) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3–/– mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3–/– than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3–/– than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3–/– than in WT mice at 28 days after TAC. Mortality was greater in NOS3–/– than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3–/– mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload.

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Low-Circulating Homoarginine is Associated with Dilatation and Decreased Function of the Left Ventricle in the General Population

Biomolecules ◽

10.3390/biom8030063 ◽

2018 ◽

Vol 8 (3) ◽

pp. 63 ◽

Cited By ~ 2

Author(s):

Martin Bahls ◽

Dorothee Atzler ◽

Marcello Markus ◽

Nele Friedrich ◽

Rainer Böger ◽

...

Keyword(s):

Population Based ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Linear Regression Models ◽

Population Based Study ◽

Ventricular Ejection Fraction ◽

Liquid Chromatography Tandem Mass ◽

And Function ◽

Independent Marker ◽

Fractional Shortening

Low homoarginine is an independent marker of mortality in heart failure patients and incident cardiovascular events. Whether homoarginine is related with healthier cardiac structure and function is currently unclear. We used data of the population-based “Study of Health in Pomerania” (SHIP-Trend) to assess this relation. Homoarginine was measured in serum using liquid chromatography-tandem mass spectrometry. Linear regression models assessed the relation between homoarginine and several structural as well as functional parameters and N-terminal pro B-type natriuretic peptide (NTproBNP). All models were adjusted for age, sex, body mass index, and renal function. A total of 3113 subjects (median age 48 (25th percentile 37 to 75th percentile 60) years, 46% male) were included. A standard deviation decrease in homoarginine was associated with a larger left ventricular diastolic diameter (0.3; 95%-confidence interval (CI): 0.2 to 0.5 mm; p < 0.001), left ventricular systolic diameter (0.38; 95%-CI: −0.22 to 0.54 mm; p < 0.001) as well as a less relative wall thickness (–0.003 95%-CI: −0.006 to −0.0008; p = 0.01), left ventricular ejection fraction (–0.47; 95%-CI: –0.79 to −0.15%; p < 0.01) and fractional shortening (−0.35; 95%-CI: −0.62 to 0.07%; p = 0.01). Low homoarginine was also related to higher NTproBNP (−0.02 95%-CI: −0.034 to −0.009 log pg/mL; p < 0.01). Lower serum homoarginine is associated with dilatation of the heart and decreased function. Prospective clinical studies should assess if homoarginine supplementation improves cardiac health in subjects with low serum concentrations.

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Leptin induces elongation of cardiac myocytes and causes eccentric left ventricular dilatation with compensation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00579.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. H2387-H2396 ◽

Cited By ~ 65

Author(s):

Yukiko Abe ◽

Koh Ono ◽

Teruhisa Kawamura ◽

Hiromichi Wada ◽

Toru Kita ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Myocytes ◽

Systolic Function ◽

Left Ventricular ◽

Leptin Receptors ◽

Jak2 Inhibitor ◽

Axis Length ◽

And Function ◽

Plasma Leptin ◽

Fractional Shortening

One of the major manifestations of obesity is an increased production of the adipocyte-derived 16-kDa peptide leptin, which acts mainly on hypothalamic leptin receptors. Leptin receptors are widely distributed in various tissues, including the heart. Whereas increased plasma leptin levels have been reported in patients with congestive heart failure, systemic alterations induced by obesity can affect cardiac hypertrophy, and the direct effects of leptin on cardiac structure and function still remain to be determined. We first exposed primary cardiac myocytes from neonatal rats to leptin for 48 h. This resulted in a significant increase in myocyte long-axis length ( P < 0.05 at 50 ng/ml) but not in the short-axis width. Leptin induced the rapid phosphorylation of STAT3 and its DNA binding in cardiac myocytes. Administration of a JAK2 inhibitor, AG-490, completely inhibited all of these effects by leptin. Furthermore, we examined the effect of continuous infusion of leptin for 4 wk following myocardial infarction in mice. Echocardiography demonstrated that left ventricular fractional shortening in the leptin-infused group (28.4 ± 2.8%) was significantly higher than that in the PBS-infused group (18.4 ± 2.2%) following myocardial infarction. Interestingly, left ventricular diastolic dimension in the leptin-infused group (4.56 ± 0.12 mm) was also higher than that in the PBS-infused group (4.13 ± 0.09 mm). These results demonstrate that leptin induces the elongation of cardiac myocytes via a JAK/STAT pathway and chronic leptin infusion causes eccentric dilatation with augmented systolic function after myocardial infarction.

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Impact of Dialysis Adequacy on Cardiac Function in Pediatric CAPD Patients

Peritoneal Dialysis International ◽

10.1177/089686080102100411 ◽

2001 ◽

Vol 21 (4) ◽

pp. 395-400 ◽

Cited By ~ 13

Author(s):

Sevcan A. Bakkaloąlu ◽

Mesiha Ekim ◽

Gülendam Koçak ◽

Semra Atalay ◽

Necmiye Tümer

Keyword(s):

Peritoneal Dialysis ◽

Ejection Fraction ◽

Beneficial Effect ◽

Left Ventricular ◽

Structure And Function ◽

Cardiac Structure ◽

Dialysis Adequacy ◽

Cardiac Structure And Function ◽

And Function ◽

Fractional Shortening

Background Left ventricular hypertrophy is a major cause of morbidity and mortality among patients with chronic renal failure. Uremia-related risk factors play a fundamental role in its occurrence, thus better prognosis and prolonged survival can be attained by successful dialytic therapies. Objective To investigate whether dialysis adequacy has a beneficial effect on cardiac structure and function in children receiving continuous ambulatory peritoneal dialysis (CAPD). Design Cross-sectional study in the Pediatric Peritoneal Dialysis Unit of a university hospital. Patients Eighteen children, aged 13.3 ± 2.8 years, being treated with CAPD, and 20 healthy age- and sex-matched control subjects were enrolled in this study. Main Outcome Measures Echocardiographic evaluation was performed in all subjects. Dialysis adequacy indices [weekly urea (Kt/V) and creatinine clearance (TCCr)] were calculated in the dialysis group. Results Interventricular septal thickness, left ventricular (LV) posterior wall thickness, LV mass index (LVMI), and LV end systolic and diastolic dimensions were all found to be significantly higher in the CAPD group compared to the control subjects ( p < 0.01). Ejection fraction and fractional shortening of the LV were not significantly different between the two groups. Mean Kt/V was 2.02 ± 0.71 and mean TCCr was 58 ± 33 L/wk/1.73 m2. There were significant negative correlations between dialysis adequacy indices and LV end systolic and diastolic dimensions ( p < 0.05 and p < 0.001). Ejection fraction and fractional shortening were positively correlated with Kt/V ( p < 0.01). Systolic and diastolic blood pressures were positively correlated with LVMI ( r = 0.501 and r = 0.523). Significant inverse correlations between mean arterial pressure and both Kt/V and TCCr ( r = -0.555 and r = -0.520) were detected. Conclusion These data clearly document that cardiac structure and function are remarkably influenced by the uremic state and dialysis therapy in pediatric CAPD patients. The close relationships between echocardiographic findings and dialysis adequacy indices suggest that adequate dialysis has a beneficial effect on cardiac function via effective removal of toxic substances.

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