Abstract 465: Medical Device Materials and Blood Pressure Alterations in Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Rafael Jaimes ◽  
Meredith Sherman ◽  
Adam Swiercz ◽  
Narine Muselimyan ◽  
Paul Marvar ◽  
...  

Di-2-ethylhexyl phthalate (DEHP) is a plasticizer that is used to impart flexibility to polyvinyl chloride products. Patients have an increased exposure to phthalates through contact with DEHP-containing medical devices, including: storage bags containing blood, plasma, intravenous fluids, total parenteral nutrition, tubing associated with their administration, nasogastric tubes, enteral feeding tubes, catheters, extracorporeal membrane oxygenation (ECMO) circuits, hemodialysis tubing, respiratory masks and endotracheal tubes. Human health concerns pertaining to DEHP exposure are linked to its endocrine-disrupting properties. Accordingly, increased exposure has been associated with cancer, metabolic disturbances, reproductive and neurological disorders, and cardiovascular disease. As an example, epidemiological studies have shown a link between DEHP exposure and elevated systolic blood pressure in adolescents. Despite bans and restrictions on the use of DEHP-containing medical devices in other countries, there is currently no mandate from the Food & Drug Administration for the use of DEHP-free devices and storage containers. The objective of this study was to quantify the impact of in vivo DEHP exposure on cardiovascular function; thereby, providing additional information for regulatory decisions by the scientific, medical and regulatory community. Healthy C57BL/6 male mice were implanted with radiotelemetry transmitters; briefly, the transmitter catheter was placed in the carotid artery and biopotential leads were routed subcutaneously to collect electrocardiogram (ECG) signals. After surgical recovery, pre-exposure data was collected, and thereafter, animals were exposed to 0.2 mg/g DEHP or control diet. We observed a significant increase in systolic pressure in DEHP-treated (145 + 3 mmHg) vs control animals (136 + 1 mmHg). We also detected an increase in diastolic and mean arterial pressure in DEHP-treated (119 + 5 and 132 + 3 mmHg, respectively) vs control animals (107 + 2 and 121 + 2 mmHg). Our previous reports have shown that DEHP diminishes cardiac contractility, which suggests that these effects on blood pressure are likely attributed to alterations in sympathetic tone and/or an increase in vascular resistance.

2003 ◽  
Vol 81 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Ghada S Hassan ◽  
Fazila Chouiali ◽  
Takayuki Saito ◽  
Fu Hu ◽  
Stephen A Douglas ◽  
...  

Recent studies have shown that the vasoactive peptide urotensin-II (U-II) exerts a wide range of action on the cardiovascular system of various species. In the present study, we determined the in vivo effects of U-II on basal hemodynamics and cardiac function in the anesthetized intact rat. Intravenous bolus injection of human U-II resulted in a dose-dependent decrease in mean arterial pressure and left ventricular systolic pressure. Cardiac contractility represented by ±dP/dt was decreased after injection of U-II. However, there was no significant change in heart rate or diastolic pressure. The present study suggests that upregulation of myocardial U-II may contribute to impaired myocardial function in disease conditions such as congestive heart failure.Key words: urotensin-II, rat, infusion, heart.


2019 ◽  
Author(s):  
Amour B U Patel ◽  
Gareth L Ackland

Inotropes and vasopressors play a key role in the management of shock. The goal of therapy is to restore end-organ perfusion by augmenting cardiac output (CO) and vascular tone. Clinical trial data have thus far failed to identify precise hemodynamic end points associated with better outcomes; in any event, such end points are highly likely to be determined on an individualized basis, reflecting patients’ chronic arterial blood pressure, baseline cardiac function, and other pathophysiologic factors (e.g., end-stage renal failure, cardiac ischemia).1 Inotropes enhance cardiac contractility and CO; vasopressors raise blood pressure. The impact of these drugs in restoring hemodynamic parameters to “normal” values has principally been used to evaluate their effectiveness, with clinical practice guided by extrapolation from animal studies and pharmacologic trials.2 However, these drugs have important extra-cardiovascular effects on metabolic, neurohormonal, and autonomic regulation that are also injurious. This review discusses the mechanisms and evidence base for inotropes and vasopressors in various types of shock. This review contains 3 figures, and 39 references. Keywords: inotropes, vasopressors, catecholamines, monitoring, shock states, cardiogenic, hemorrhagic, septic, neurogenic


1975 ◽  
Vol 229 (2) ◽  
pp. 501-505 ◽  
Author(s):  
T Nivatpumin ◽  
T Yipintsoi ◽  
S Penpargkul ◽  
J Scheuer

To study the effects of acute uremia on the inotropic state of the rat heart, we subjected rats to bilateral nephrectomy and studied their hearts in the open chest 24 h later. Uremic rats had significantly higher systolic blood pressure than sham-operated animals. Left ventricular systolic pressure and maximum dP/dt, both during ejection and isovolumic contrations, were higher for any given end-diastolic pressure in hearts of uremic rats than in sham-operated animals. This difference in performance charcteristics was not abolished by doses of propranolol that blocked the heart rate response to isoproterenol. The administration of phenoxybenzamine during the 24 h of uremia abolished the blood pressure rise in uremic rats, but the increased contractile state persisted. Treatment of sham-operated animals with methoxamine to produce the same course of blood pressure as observed in uremic rats was also associated with an increased inotropic state. These results indicate that in the rat, acute uremia is associated with an increased inotropic state that is not mediated by beta-adrenergic mechanisms. The systolic hypertension of acute uremia is not the major cause of the increased contractility, although systolic hypertension without uremia can mimic the performance characteristics found in hearts of uremic rats.


2008 ◽  
Vol 11 (12) ◽  
pp. 1397-1406 ◽  
Author(s):  
Karen E Charlton ◽  
Krisela Steyn ◽  
Naomi S Levitt ◽  
Nasheeta Peer ◽  
Deborah Jonathan ◽  
...  

AbstractObjectiveTo assess the impact of a food-based intervention on blood pressure (BP) in free-living South African men and women aged 50–75 years, with drug-treated mild-to-moderate hypertension.MethodsA double-blind controlled trial was undertaken in eighty drug-treated mild-to-moderate hypertensive subjects randomised to an intervention (n40) or control (n40) arm. The intervention was 8-week provision of six food items with a modified cation content (salt replacement (SOLO™), bread, margarine, stock cubes, soup mix and a flavour enhancer) and 500 ml of maas (fermented milk)/d. The control diet provided the same quantities of the targeted foods but of standard commercial composition and 500 ml/d of artificially sweetened cooldrink.FindingsThe intervention effect estimated as the contrast of the within-diet group changes in BP from baseline to post-intervention was a significant reduction of 6·2 mmHg (95 % CI 0·9, 11·4) for systolic BP. The largest intervention effect in 24 h BP was for wake systolic BP with a reduction of 5·1 mmHg (95 % CI 0·4, 9·9). For wake diastolic BP the reduction was 2·7 mmHg (95 % CI −0·2, 5·6).ConclusionsModification of the cation content of a limited number of commonly consumed foods lowers BP by a clinically significant magnitude in treated South African hypertensive patients of low socio-economic status. The magnitude of BP reduction provides motivation for a public health strategy that could be adopted through lobbying of the food industry by consumer and health agencies.


2007 ◽  
Vol 35 (03) ◽  
pp. 487-496 ◽  
Author(s):  
Jun-Rong Du ◽  
Yan Yu ◽  
Yao Yao ◽  
Bo Bai ◽  
Xu Zong ◽  
...  

Radix Angelica sinensis, known as Danggui in Chinese, has been used to treat cardiovascular diseases in traditional Chinese medicine for a long time. Experimental evidence showed that the essential oil of Danggui could reduce blood pressure in rabbits, cats or hypertensive dogs when given intravenously. In this study, we investigated the effects of Z-ligustilide, the main lipophilic component of the essential oil of Danggui on aortic tension induced by phenylephrine, an alpha-adrenergic agonist, in vitro and the systolic blood pressure in SHR rats. We demonstrated for the first time that ligustilide can significantly reduce the phenylephrine-induced aortic tension in vitro with IC50 about 64 μg/ml, but has no in vivo effect on systolic blood pressure in SHR rats when administrated orally. The data on transport of ligustilide across Caco-2 monolayer suggested an efficient intestinal absorption of ligustilide in vivo, implying that the non-effectiveness of ligustilide in vivo is not due to the poor absorption in the gastrointestinal tract. Further studies on whether ligustilide is one of the main anti-hypertensive components of the essential oil are needed.


Author(s):  
Wei Feng ◽  
Wei Ji ◽  
Yong Wang ◽  
Qinghai Gong ◽  
Sixuan Li ◽  
...  

Background: We aimed to analyse the impact of elevated systolic blood pressure (SBP) levels on mortality and life expectancy among ≥25 yr adults in the municipality of Ningbo, China. Methods: The death cause data were collected from the Internet-based Comprehensive Chronic Disease Surveillance System in Zhejiang Province in 2015, and SBP level data were obtained from the Ningbo Adult Chronic Disease Surveillance survey. According to the comparative risk assessment theory, the population attributable fraction (PAF) of elevated SBP levels by gender and urban-rural regions has been calculated. The deaths and life expectancy loss due to elevated SBP levels were estimated. Results: In 2015, the average SBP level among ≥25 yr adults in Ningbo was 129.01 ± 17.73 mmHg, which was higher in men (131.67 ± 16.89 mmHg) than in women (126.24 ± 18.15 mmHg) and was higher among adults in rural regions (130.55 ± 18.75 mmHg) than among adults in urban regions (127.15 ± 16.19 mmHg). A total of 6181 deaths were attributed to elevated SBP levels among adults in Ningbo. The PAF of deaths caused by elevated SBP levels among adults was 16.14%, which was higher in women (18.73%) than in men (14.31%). The overall loss of life expectancy caused by elevated SBP levels among adults was 1.76 yr, which was higher in women (1.99 yr) than in men (1.53 yr) and was higher in rural regions (1.91 yr) than in urban regions (1.49 yr). Conclusion: Elevated SBP levels had a serious impact on the death and life expectancy loss of residents in Ningbo.


2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
J Santos ◽  
P Braz ◽  
A Costa ◽  
L Costa ◽  
M Santos ◽  
...  

Abstract Issue Health Impact Assessment (HIA) is a methodology that aims at assessing the impact of policies in health. A pilot HIA is in progress to kick off the implementation of this methodology in Portugal with the support of the World Health Organization (WHO). In this context, the impact of a nation-wide policy that intends to achieve a maximum of 1 g of salt/100 gr in bread is under assessment. Description of the issue In 2017, Portugal approved a protocol between the industry and other stakeholders to gradually decrease the amount of salt in bread, as this is the main source of salt intake. The purpose of this study was to assess the impact in blood pressure from current (1.4 gr) to 1 g (29% reduction) of salt in bread. Data from two different surveys regarding blood pressure and salt intake was gathered. We estimated the decrease in blood pressure with respect to current average values according to sex, age, education and region. Results It is expected that a reduction of 29% in salt intake through bread contributes to a general decrease in systolic pressure for normotensive people (from 120.4mmHg to 120.0mmHg, p = 0.85) and hypertensive people (from 151.0mmHg to 150.1mmHg, p = 0.68), although not statistically significant. Older hypertensive individuals (65 to 75 years) are the group with the largest benefit (152.8mmHg to 152.0mmHg) but no statistical difference was found. Disaggregation by sex, region and education also didn’t show any statistical difference. Lessons The impact in blood pressure from a 29% reduction in salt intake from bread seems very small. We found no statistical significance between the current and expected values in blood pressure either for total or group stratification. The absence of statistical effect might be due to sample size as our sources only allowed us to work with aggregated data. Key messages Quality and access to data is needed to assess impact of policies. to increase effects in blood pressure either salt reduction from bread must be larger or a wider range of products should be considered.


2007 ◽  
Vol 293 (3) ◽  
pp. H1689-H1695 ◽  
Author(s):  
Sándor Bátkai ◽  
Partha Mukhopadhyay ◽  
Judith Harvey-White ◽  
Raouf Kechrid ◽  
Pál Pacher ◽  
...  

Advanced liver cirrhosis is associated with hyperdynamic circulation consisting of systemic hypotension, decreased peripheral resistance, and cardiac dysfunction, termed cirrhotic cardiomyopathy. Previous studies have revealed the role of endocannabinoids and vascular CB1receptors in the development of generalized hypotension and mesenteric vasodilation in animal models of liver cirrhosis, and CB1receptors have also been implicated in the decreased β-adrenergic responsiveness of isolated heart tissue from cirrhotic rats. Here we document the cardiac contractile dysfunction in vivo in liver cirrhosis and explore the role of the endocannabinoid system in its development. Rats with CCl4-induced cirrhosis developed decreased cardiac contractility, as documented through the use of the Millar pressure-volume microcatheter system, low blood pressure, and tachycardia. Bolus intravenous injection of the CB1antagonist AM251 (3 mg/kg) acutely increased mean blood pressure, as well as both load-dependent and -independent indexes of systolic function, whereas no such changes were elicited by AM251 in control rats. Furthermore, tissue levels of the endocannabinoid anandamide increased 2.7-fold in the heart of cirrhotic compared with control rats, without any change in 2-arachidonoylglycerol levels, whereas, in the cirrhotic liver, both 2-arachidonoylglycerol (6-fold) and anandamide (3.5-fold) were markedly increased. CB1-receptor expression in the heart was unaffected by cirrhosis, as verified by Western blotting. Activation of cardiac CB1receptors by endogenous anandamide contributes to the reduced cardiac contractility in liver cirrhosis, and CB1-receptor antagonists may be used to improve contractile function in cirrhotic cardiomyopathy and, possibly, in other forms of heart failure.


2017 ◽  
Vol 313 (5) ◽  
pp. H1044-H1053 ◽  
Author(s):  
Rafael Jaimes ◽  
Adam Swiercz ◽  
Meredith Sherman ◽  
Narine Muselimyan ◽  
Paul J. Marvar ◽  
...  

Plastics have revolutionized medical device technology, transformed hematological care, and facilitated modern cardiology procedures. Despite these advances, studies have shown that phthalate chemicals migrate out of plastic products and that these chemicals are bioactive. Recent epidemiological and research studies have suggested that phthalate exposure adversely affects cardiovascular function. Our objective was to assess the safety and biocompatibility of phthalate chemicals and resolve the impact on cardiovascular and autonomic physiology. Adult mice were implanted with radiofrequency transmitters to monitor heart rate variability, blood pressure, and autonomic regulation in response to di-2-ethylhexyl-phthalate (DEHP) exposure. DEHP-treated animals displayed a decrease in heart rate variability (−17% SD of normal beat-to-beat intervals and −36% high-frequency power) and an exaggerated mean arterial pressure response to ganglionic blockade (31.5% via chlorisondamine). In response to a conditioned stressor, DEHP-treated animals displayed enhanced cardiovascular reactivity (−56% SD major axis Poincarè plot) and prolonged blood pressure recovery. Alterations in cardiac gene expression of endothelin-1, angiotensin-converting enzyme, and nitric oxide synthase may partly explain these cardiovascular alterations. This is the first study to show an association between phthalate chemicals that are used in medical devices with alterations in autonomic regulation, heart rate variability, and cardiovascular reactivity. Because changes in autonomic balance often precede clinical manifestations of hypertension, atherosclerosis, and conduction abnormalities, future studies are warranted to assess the downstream impact of plastic chemical exposure on end-organ function in sensitive patient populations. This study also highlights the importance of adopting safer biomaterials, chemicals, and/or surface coatings for use in medical devices.NEW & NOTEWORTHY Phthalates are widely used in the manufacturing of consumer and medical products. In the present study, di-2-ethylhexyl-phthalate exposure was associated with alterations in heart rate variability and cardiovascular reactivity. This highlights the importance of investigating the impact of phthalates on health and identifying suitable alternatives for medical device manufacturing.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jason W. Arnold ◽  
Jeffery Roach ◽  
Salvador Fabela ◽  
Emily Moorfield ◽  
Shengli Ding ◽  
...  

Abstract Background Prebiotic galacto-oligosaccharides (GOS) have an extensively demonstrated beneficial impact on intestinal health. In this study, we determined the impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects (“leaky gut”). We also evaluated if short-term GOS feeding influenced how the aging gut responded to antibiotic challenges in a mouse model of Clostridioides difficile infection. Finally, we assessed if colonic organoids could reproduce the GOS responder—non-responder phenotypes observed in vivo. Results Old animals had a distinct microbiome characterized by increased ratios of non-saccharolytic versus saccharolytic bacteria and, correspondingly, a lower abundance of β-galactosidases compared to young animals. GOS reduced the overall diversity, increased the abundance of specific saccharolytic bacteria (species of Bacteroides and Lactobacillus), increased the abundance of β-galactosidases in young and old animals, and increased the non-saccharolytic organisms; however, a robust, homogeneous bifidogenic effect was not observed. GOS reduced age-associated increased intestinal permeability and increased MUC2 expression and mucus thickness in old mice. Clyndamicin reduced the abundance Bifidobacterium while increasing Akkermansia, Clostridium, Coprococcus, Bacillus, Bacteroides, and Ruminococcus in old mice. The antibiotics were more impactful than GOS on modulating serum markers of inflammation. Higher serum levels of IL-17 and IL-6 were observed in control and GOS diets in the antibiotic groups, and within those groups, levels of IL-6 were higher in the GOS groups, regardless of age, and higher in the old compared to young animals in the control diet groups. RTqPCR revealed significantly increased gene expression of TNFα in distal colon tissue of old mice, which was decreased by the GOS diet. Colon transcriptomics analysis of mice fed GOS showed increased expression of genes involved in small-molecule metabolic processes and specifically the respirasome in old animals, which could indicate an increased oxidative metabolism and energetic efficiency. In young mice, GOS induced the expression of binding-related genes. The galectin gene Lgals1, a β-galactosyl-binding lectin that bridges molecules by their sugar moieties and is an important modulator of the immune response, and the PI3K-Akt and ECM-receptor interaction pathways were also induced in young mice. Stools from mice exhibiting variable bifidogenic response to GOS injected into colon organoids in the presence of prebiotics reproduced the response and non-response phenotypes observed in vivo suggesting that the composition and functionality of the microbiota are the main contributors to the phenotype. Conclusions Dietary GOS modulated homeostasis of the aging gut by promoting changes in microbiome composition and host gene expression, which was translated into decreased intestinal permeability and increased mucus production. Age was a determining factor on how prebiotics impacted the microbiome and expression of intestinal epithelial cells, especially apparent from the induction of galectin-1 in young but not old mice.


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