scholarly journals Effects of long-term nonylphenol exposure on myocardial fibrosis and cardiac function in rats

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Chao Liu ◽  
Chengyu Ni ◽  
Weichu Liu ◽  
Xiaolian Yang ◽  
Renyi Zhang ◽  
...  

Abstract Background Myocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases. Studies have found that myocardial fibrosis is closely associated with exposure to environmental estrogens such as nonylphenol (NP), as a representative of environmental estrogens. The aim of this study was to examine the effects of NP chronic exposure on myocardial fibrosis as well as cardiac structure and function. Forty Sprague–Dawley rats were randomly divided into four groups (n = 10): control group (C), low NP dose (0.4 mg/kg, L), medium NP dose (4 mg/kg, M), and high NP dose (40 mg/kg, H) groups. The NP dose groups were gavaged with NP for 180 days. Results The NP level in the heart of the NP groups was significantly higher than those in the control group (F = 43.658, P < 0.001). Serum aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isozyme (CK-MB), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) significantly increased in the NP groups compared with the control group (P < 0.05). Histopathological examination of the heart biopsy illustrates that in the medium and high NP groups, the fibrous connective tissue had a disordered and loose gridding shape, muscle fibers had fractured, and muscle fibers were loose with a widened gap. Extensive inflammatory cell infiltration and fibroblast proliferation in the myocardial interstitium were also found. With increasing NP dose, the degree of muscle fiber loosing and disorder became more significant in the NP-treatment groups, and the collagen volume fraction (CVF) was higher than that in the control group (P < 0.01). Compared with the control group, the expression of collagen I and collagen III increased significantly in the medium and high NP groups (P < 0.05). The values of the systolic thickness of the left ventricular anterior wall (LVAWs), the diastolic thickness of the left ventricular posterior wall (LVPWd), the systolic thickness of the left ventricular posterior wall (LVPWs), and the left ventricular anterior wall (LVAWd) in the NP groups are were slightly lower than those in of the control group. The values of left ventricular end systolic dimensions (LVIDs) in the NP groups increased compared with the control group. Conclusions Long-term NP exposure could lead to fibrosis in the rat myocardium, which is characterized by increased expressions of myocardial collagen I and collagen III, as well as elevated cardiac enzymes. In addition, the cardiac structure was affected and changes were observed in the thinner ventricular wall and as an enlarged ventricular cavity.

2021 ◽  
Author(s):  
Chao Liu ◽  
Chengyu Ni ◽  
Weichu Liu ◽  
Xiaolian Yang ◽  
Renyi Zhang ◽  
...  

Abstract Background: Myocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases. Studies have found that myocardial fibrosis is closely associated with exposure to environmental estrogens such as nonylphenol (NP), as a representative of environmental estrogens. The aim of this study was to examine the effects of NP chronic exposure on myocardial fibrosis as well as cardiac structure and function. Forty Sprague Dawley rats were randomly divided into four groups (n = 10): control group (C), low NP dose (0.4 mg/kg, L), medium NP dose (4 mg/kg, M), and high NP dose (40 mg/kg, H) groups. The NP dose groups were gavaged with NP for 180 days. Results: The NP level in the heart of the NP groups was significantly higher than those in the control group (F = 43.658, P < 0.001). Serum aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isozyme (CK-MB), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) significantly increased in the NP groups compared with the control group (). Histopathological examination of the heart biopsy illustrates that in the medium and high NP groups, the fibrous connective tissue had a disordered and loose gridding shape, muscle fibers had fractured, and muscle fibers were loose with a widened gap. Extensive inflammatory cell infiltration and fibroblast proliferation in the myocardial interstitium were also found. With increasing NP dose, the degree of muscle fiber loosing and disorder became more significant in the NP treatment groups, and the collagen volume fraction (CVF) was higher than that in the control group (P < 0.01). Compared with the control group, the expression of collagen I and collagen III increased significantly in the medium and high NP groups (P < 0.05). The values of the systolic thickness of the left ventricular anterior wall (LVAWs), the diastolic thickness of the left ventricular posterior wall (LVPWd), the systolic thickness of the left ventricular posterior wall (LVPWs), and the left ventricular anterior wall (LVAWd) in the NP groups are were slightly lower than those in of the control group. The values of left ventricular end systolic dimensions (LVIDs) in the NP groups increased compared with the control group. Conclusions: Long-term NP exposure could lead to fibrosis in the rat myocardium, which is characterized by increased expressions of myocardial collagen I and collagen III, as well as elevated cardiac enzymes. In addition, the cardiac structure was affected and changes were observed in the thinner ventricular wall and as an enlarged ventricular cavity.


2017 ◽  
Vol 45 (6) ◽  
pp. 1708-1719 ◽  
Author(s):  
S Gonzalez ◽  
JD Windram ◽  
T Sathyapalan ◽  
Z Javed ◽  
AL Clark ◽  
...  

Objective Epidemiological studies suggest that adult-onset growth hormone deficiency (AGHD) might increase the risk of death from cardiovascular causes. Methods This was a 6-month double-blind, placebo-controlled, randomised, cross-over trial followed by a 6-month open-label phase. Seventeen patients with AGHD received either recombinant human growth hormone (rGH) (0.4 mg injection daily) or placebo for 12 weeks, underwent washout for 2 weeks, and were then crossed over to the alternative treatment for a further 12 weeks. Cardiac magnetic resonance imaging, echocardiography, and cardiopulmonary exercise testing were performed at baseline, 12 weeks, 26 weeks, and the end of the open phase (12 months). The results were compared with those of 16 age- and sex-matched control subjects. Results At baseline, patients with AGHD had a significantly higher systolic blood pressure, ejection fraction, and left ventricular mass than the control group, even when corrected for body surface area. Treatment with rGH normalised the insulin-like growth factor 1 concentration without an effect on exercise capacity, cardiac structure, or cardiac function. Conclusion Administration of rGH therapy for 6 to 9 months failed to normalise the functional and structural cardiac differences observed in patients with AGHD when compared with a control group.


1996 ◽  
Vol 42 (2) ◽  
pp. 15-17
Author(s):  
Ye. I. Sokolov ◽  
A. P. Zayev ◽  
R. P. Olkha ◽  
T. P. Morozova ◽  
S. A. Zhizhina ◽  
...  

Echocardiographic parameters of the central and intracardiac hemodynamics were analyzed in 67 patients with compensated diabetes mellitus of types I and II of 2 to 6 years standing. The control group consisted of 30 subjects. The increase of the minute volume, stroke volume, specific power of the left ventricle, and reduction of total peripheral resistance were revealed in both groups of patients. These shifts are characteristic of a hyperkinetic type of central hemodynamics. The hyperdynamic syndrome was due to left-ventricular hypertrophy in patients with noninsulin-dependent diabetes and due to increased heart rate and the rate of circulatory shortening of myocardial fibers in patients with the insulin-dependent condition. Impaired diastolic function presenting as an increase of the end diastolic volume and a reduced rate of relaxation of the left-ventricular posterior wall myocardium were observed in all the patients, no matter what the type of the condition. The above shifts are predictors of a reduction of myocardial contractility, responsible for the grave and atypical course of coronary disease in diabetics.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nisha Plavelil ◽  
Mark C Haigney ◽  
Robert E Goldstein ◽  
Michael Klein ◽  
Matie Shou ◽  
...  

Introduction: Although frequently used in heart failure (HF), long-term furosemide exacerbates HF in a swine model. This paradoxical phenomenon may reflect furosemide-induced alterations in signaling proteins of the extracellular matrix (ECM) to increase fibrosis. Examination of the ECM may clarify how treatments like furosemide enhance the progression of HF. Hypothesis: The administration of furosemide increased inflammation and fibrosis of the heart, leading to accelerated HF deterioration in a swine model. Methods: After Institutional Animal Care and Use Committee (IACUC) approval, Yorkshire swine (N=10, 5 = furosemide, 5 = saline) were paced 3 to 5 weeks at 200 beats per minute to induce HF (left ventricular fractional shortening <16% on echocardiogram). Animals were treated with furosemide (1 mg/kg intramuscularly) or saline. Western Blot and histology with Masson’s trichrome stain were performed on transmural LV myocardium to quantify critical determinants of fibrosis. ANOVA with Tukey HSD correction and descriptive statistics were performed using SPSS with significance by α of 0.05; mean ± SEM. Results: The overall increase in ECM fibrosis in HF was clearly demonstrated on Masson’s trichrome histology associated with significant, uniform increase in signaling pathways leading to fibrosis associated with furosemide use. SMAD 2-HF Furosemide to Control (p<.05): HF Furosemide 0.266 ±.05, HF Saline 0.183±.02, Control 0.163±.01 ERK-all (p<.05): HF Furosemide 0.312±.02, HF Saline 0.209±.01,Control 0.149±.01 GDF-15-HF Furosemide to Control (p<.05): HF Furosemide 0.095 ±.00, HF Saline 0.073±.01, Control 0.062±.01 MMP-14-all (p<.05): HF Furosemide 0.451±.02, HF Saline 0.374±.03,Control 0.231±.02 TIMP-1-all (p<.05): HF Furosemide 0.184±.01, HF Saline 0.0135±.03,Control 0.033±.01 PAI-1-all (p<.05): HF Furosemide 0.105±.01, HF Saline 0.046±.01,Control 0.043±.00 Conclusions: Histologic and biochemical analysis showed worsening HF in furosemide-treated paced swine was associated with consistent increases in fibrosis and indices of adverse ECM remodeling. The diuretic intended to reduce water retention during HF appeared to enhance myocardial fibrosis, paradoxically accelerating pathological processes responsible for HF.


Author(s):  
Guglielmo Stefanelli ◽  
Fabrizio Pirro ◽  
Vincenzo Smorto ◽  
Alessandro Bellisario ◽  
Emilio Chiurlia ◽  
...  

Objective Stentless aortic valves have shown superior hemodynamic performance and faster left ventricular mass regression compared to stented bioprostheses. Yet, controversies exist concerning the durability of stentless valves. This case-matched study compared short- and long-term clinical outcomes of stentless LivaNova-Sorin Pericarbon Freedom™ (SPF) and stented Carpentier-Edwards Perimount (CEP) aortic prostheses. Methods From 2003 through 2006, 134 consecutive patients received aortic valve replacement with SPF at our institution. This cohort was matched, according to 20 preoperative clinical parameters, with a control group of 390 patients who received CEP prosthesis during the same time. The resulting 55 + 55 matched patients were analyzed for perioperative results and long-term clinical outcomes. Results Early mortality was 0% for both groups. Lower transvalvular gradients were found in the SPF group (10.6 ± 2.9 versus 15.7 ± 3.1 mmHg, P < 0.001). Overall late mortality (mean follow-up: 10.03 years) was similar for both groups (50.1% versus 42.8%, P = 0.96). Freedom from structural valve degeneration (SVD) at 13 years was similar for both groups (SPF = 92.3%, CEP = 73.9%, P = 0.06). Freedom from aortic valve reinterventions did not differ (SPF = 92.3%, CEP = 93.5%, P = 0.55). Gradients at 13-year follow-up remained significantly lower in SPF group (10.0 ± 4.5 versus 16.2 ± 9.5 mmHg, P < 0.001). Incidence of acute bacterial endocarditis (ABE) and major adverse cardiovascular and cerebrovascular events (MACCE) was similar. Conclusions SPF and CEP demonstrated comparable long-term outcomes related to late mortality, SVD, aortic valve reinterventions, and incidence of ABE and MACCE. Superior hemodynamic performance of SPF over time can make this valve a suitable choice in patients with small aortic root and large body surface area.


2020 ◽  
Vol 33 (4) ◽  
pp. 371-371
Author(s):  
Hong Ding ◽  
Ning-ying Li ◽  
Xiang Zhang ◽  
Pan-pan Zhang ◽  
Jing Yu

Abstract Objective To investigate the effects of valsartan on left ventricular mass, function, and oxidative stress in ovariectomized spontaneous hypertensive rats (SHR). Methods Twelve-week-old female SHRs were randomly divided into ovariectomy (OVX) control (n = 12), OVX + valsartan (n = 12), sham control (Sham, n = 13), and Sham + valsartan (n = 14) groups. Valsartan (30 mg/kg/day) or double-distilled water was given by oral gavage. After 12 weeks of valsartan or water treatment, left ventricular wall thickness and function, superoxide dismutase (SOD), glutathione peroxidase (GSH), and 8-hydroxydeoxyguanosine (8-OHdG) were assessed. Results There was a significant interaction between ovariectomy and valsartan on interventricular end-diastolic septum thickness (IVSTd), end-systolic interventricular septum thickness (IVSTs), left ventricular end-diastolic posterior wall thickness (LVPWTd), and left ventricular end diastolic diameter (LVEDD) (P &lt; 0.05). Valsartan treatment in OVX rats decreased IVSTd, IVSTs, LVPWTd, and LVPWTs compared to OVX control (P &lt; 0.05). Compared with Sham + control group, LVESP and ±dP/dt of LV were decreased while LVEDP was increased in OVX + control group (all P &lt; 0.05). After valsartan treatment, LVESP and ±dP/dt of LV were increased and LVEDP was decreased in ovariectomized rats (all P &lt; 0.05). Ovariectomy decreased GSH and SOD levels and increased 8-OHdG levels, which were reversed by valsartan treatment (all P &lt; 0.05). Conclusion Valsartan treatment decreases oxidative stress, reduces LV hypertrophy, and improves cardiac function in overiectomized SHR.


1993 ◽  
Vol 74 (5) ◽  
pp. 2469-2477 ◽  
Author(s):  
M. P. McDonald ◽  
A. J. Sanfilippo ◽  
G. K. Savard

Changes in arterial and cardiopulmonary baroreflex function and cardiac structure were followed throughout 10 wk of moderate endurance training [60 min of cycling, 3 days/wk, 60% maximal O2 uptake (VO2max)] in sedentary normotensive men (22–34 yr old). Subjects were randomly assigned to an exercise training group (ET; n = 9) or to a control group (UT; n = 4). Decreases in resting heart rate (8.9 +/- 2.6%, P < 0.01) and mean arterial pressure (7.0 +/- 2.3%, P < 0.05) and an increase in VO2max occurred after 10 wk in ET. An increase in the gain or slope of the spontaneous baroreflex response at rest was found after 10 wk in ET (50.1 +/- 6.3%, P < 0.01) but not in UT. An upward shift in the resting carotid-cardiac baroreflex response curve also occurred after 10 wk in ET, although the maximum range and gain of the response and the vagally mediated peak reflex sinus node responses were unchanged. Cardiopulmonary baroreflex function (reflex changes in forearm vascular conductance) and measured indexes of left ventricular structure were not altered in either ET or UT, although peak transmitral inflow velocity increased in ET (P < 0.05). These findings demonstrate that moderate exercise training results in an enhancement in the ability to reflexly adjust heart rate with spontaneous changes in arterial pressure within the operating range. This occurs independently of any changes in carotid-cardiac baroreflex function over the full response range in cardiopulmonary baroreflex function or in cardiac structure.


1991 ◽  
Vol 261 (5) ◽  
pp. H1570-H1577 ◽  
Author(s):  
M. A. Young ◽  
K. M. Mullane

The effects of repeated episodes of demand-induced ischemia on regional myocardial wall thickening, endocardial electrogram, and regional myocardial blood flow are not well delineated. We studied the cumulative effects of six periods of pacing-induced ischemia in 35 chloralose-anesthetized dogs with circumflex coronary stenosis. Repetitive ischemia of the posterior left ventricular free wall was induced with six 5-min pacing periods separated by 15-min recovery periods. The three groups of dogs studied were 1) saline control, 2) the purine precursor 5-aminoimidazole 4-carboxamide riboside (AICA-r), and 3) nitroglycerin (NTG). During the initial pacing period (before treatment), thickening of the posterior wall declined in the saline group (43 +/- 5% of control), the AICA-r group (47 +/- 8% of control), and the NTG group (55 +/- 3% of control), associated with endocardial S-T segment elevation and a decrease in subendocardial blood flow. Wall thickening continued to decrease in each group with each successive pacing episode. However, during the sixth pacing period wall thickening was significantly (P less than 0.05) less in the saline group (2 +/- 5% of control) than in the AICA-r (31 +/- 7% of control) or NTG (61 +/- 7% of control) group. The progressive decline in wall thickening was accompanied by a further decrease in subendocardial blood flow and a rise in S-T segment in the saline group but not in the AICA-r or NTG group (P less than 0.05). These results demonstrate that sequential periods of ischemia and reperfusion cause a progressive decline in regional wall motion, coincident with a progressive decrease in subendocardial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)


2003 ◽  
Vol 228 (6) ◽  
pp. 674-682 ◽  
Author(s):  
R. Golfetti ◽  
T. Rork ◽  
G. Merrill

Male and female Hartley strain guinea pigs weighing 280 ± 10 g were given acetaminophen-treated water ad libitum for 10 days. Sham-treated control animals were given similar quantities of untreated tap water (vehicle-treated control group). On Day 10, hearts were extracted, instrumented, and exposed to an ischemia (low-flow, 20 min)/reperfusion protocol. Our objective was to compare and contrast ventricular function, coronary circulation, and selected biochemical and histological indices in the two treatment groups. Left ventricular developed pressure in the early minutes of reperfusion was significantly greater in the presence of acetaminophen, e.g., at 1 min, 40 ± 4 vs 21 ± 3 mmHg ( P < 0.05). Coronary perfusion pressure was significantly less from 3 to 40 min of reperfusion in the presence of acetaminophen. Creatine kinase release in vehicle-treated hearts rose from 42 ± 14 (baseline) to 78 ± 25 units/liter by the end of ischemia. Corresponding values in acetaminophen-treated hearts were 36 ± 8 and 44 ± 14 units/liter. Acetaminophen significantly ( P < 0.05) attenuated release of creatine kinase. Chemiluminescence, an indicator of the in vitro production of peroxynitrite via the in vivo release of superoxide and nitric oxide, was also significantly attenuated by acetaminophen. Electron microscopy indicated a well-preserved myofibrillar ultrastructure in the postischemic myocardium of acetaminophen-treated hearts relative to vehicle-treated hearts (e.g., few signs of contraction bands, little or no evidence of swollen mitochondria, and well-defined light and dark bands in sarcomeres with acetaminophen; opposite with vehicle). We conclude that chronic administration of acetaminophen provides cardioprotection to the postischemic, reperfused rodent myocardium.


1981 ◽  
Vol 15 ◽  
pp. 464-464
Author(s):  
Stanley J Goldberg ◽  
Lawrence Z Stern ◽  
Linda Feldman ◽  
Suzana Horowitz ◽  
David J Sahn ◽  
...  

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