Absence of meal-induced insulin sensitization (AMIS) in aging rats is associated with cardiac dysfunction that is protected by antioxidants

2011 ◽  
Vol 111 (3) ◽  
pp. 704-714 ◽  
Author(s):  
Zhi Ming ◽  
Dallas J. Legare ◽  
W. Wayne Lautt
Keyword(s):  
Cardiac Dysfunction ◽  
Insulin Action ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Sprague Dawley ◽  
Antioxidant Treatment ◽  
Aging Rats ◽  
Progressive Development

We have previously demonstrated that progressive development of absence of meal-induced insulin sensitization (AMIS) leads to postprandial hyperglycemia, compensatory hyperinsulinemia, resultant hyperlipidemia, increased oxidative stress, and obesity, progressing to syndrome X in aging rats. The present study tested the hypothesis that progressive development of AMIS in aging rats further resulted in deterioration in cardiac performance. Anesthetized male Sprague-Dawley rats were tested at 9, 26, and 52 wk to determine their dynamic response to insulin and cardiac function. Dynamic insulin sensitivity was determined before and after atropine to quantitate hepatic insulin sensitizing substance (HISS)-dependent and -independent insulin action. Cardiac performance was evaluated using a Millar pressure-volume conductance catheter system. AMIS developed with age, as demonstrated by significant decrease in HISS-dependent insulin action, and this syndrome was increased by sucrose supplementation and inhibited by the antioxidant treatment. Associated with progressive development of AMIS, aging rats showed impaired cardiac performance, including the reduction in cardiac index, heart rate, dP/d tmax, dP/d tmin, ejection fraction and decreased slope of left ventricular end-systolic pressure-volume relationship, and increased relaxation time constant of left ventricular pressure as well as increased left ventricular end-diastolic pressure. Total peripheral vascular resistance also increased with age. Sucrose supplementation and antioxidant treatment, respectively, potentiated and attenuated cardiac dysfunction associated with age. In addition, poor cardiac performance correlated closely with the development of AMIS. These results indicate that AMIS is the first metabolic defect that leads to homeostatic disturbances and dysfunctions, including cardiovascular diseases.

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

scholarly journals Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats

2015 ◽  
Vol 37 (1) ◽  
pp. 94-104 ◽  
Author(s):  
Rong Zhang ◽  
Huifang Niu ◽  
Xiaohui Kang ◽  
Tao Ban ◽  
Hong Hong ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Mitogen Activated Protein Kinase ◽  
Elevated Plasma

Background/Aims: The purpose of the present study was to clarify whether chronically elevated plasma neuropeptide Y (NPY) might affect heart function and cardiac remodeling in rats. Methods: Male Wistar rats were administered NPY (85 μg for 30 days) by mini-osmotic pump subcutaneously implanted between the scapulae. Associated indices for heart function, cardiac remodeling and hypertrophy were evaluated. Results: Compared to the sham group, the baseline systolic blood pressure (SBP) in rats administered NPY was significantly increased; cardiac function was significantly decreased, as indicated by reduced ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (±dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed markedly increased expressions of β-myosin heavy chain (β-MHC), calcineurin (CaN) and phosphorylated p38 proteins, while no changes were found in the expressions of p38 total protein and the phosphorylations of JNK and ERK. Conclusion: This study reported for the first time that long-term elevated plasma concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and this phenomenon could, in part, be mediated by the Ca2+/CaM-dependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats.

Abstract 156: The Nitroxyl Donor Angeli's Salt Elicits Concomitant Concentration-Dependent Coronary Vasodilatory and Inotropic Actions in the Intact Rat Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Rebecca H Ritchie ◽  
Kai Yee Chin ◽  
Chengxue Qin ◽  
Nga Cao ◽  
Barbara K Kemp-Harper ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Soluble Guanylyl Cyclase ◽  
High Reactivity ◽  
Left Ventricular ◽  
Lv Function ◽  
Sprague Dawley ◽  
Response Curves ◽  
Ventricular Systolic Pressure ◽  
Angeli's Salt

Nitroxyl (HNO) is a novel redox sibling of NO• that elicits vasodilator, antihypertrophic and superoxide-suppressing actions. HNO is however resistant to scavenging by superoxide, and has high reactivity with thiols (enabling potent enhancement of LV function). In the present study, hearts from adult male Sprague-Dawley rats were Langendorff-perfused at constant pressure. Dose-response curves to the HNO donor Angeli’s salt were performed following preconstriction with U46619 to ∼50% of baseline coronary flow (CF). Angeli’s salt (10pmol-10µmol, n=6) elicited significant dose-dependent increases in left ventricular systolic pressure (LVSP), LV developed pressure (LVDP), LV end-diastolic pressure (LVEDP), LV±dP/dt, and CF. The effects of the highest dose of Angeli's salt studied on LV function are shown in the Table; these were significantly inhibited by co-administration of the HNO scavenger L-cysteine (4mM, n=6) or the soluble guanylyl cyclase inhibitor ODQ (10µM, n=5). The EC 50 for Angeli's salt-induced vasodilatation was increased from -8.6±0.3mol to -7.5±0.2mol (p<0.01) and -7.6±0.3mol (p<0.05) by L-cysteine and ODQ, respectively. Although CGRP is a putative mediator of HNO actions, both the inotropic and vasodilator actions of Angeli's salt were insensitive to the CGRP antagonist CGRP 8-37 (0.1µM, n=5). The vehicle for Angeli’s salt, 0.01M NaOH, had no effect on any of these parameters (n=3, results not shown). Our results demonstrate that the cardiac effects of Angeli’s salt are thiol-sensitive, and mediated by HNO and cGMP, but not CGRP. HNO donors represent potential therapy for the failing heart, alone or in addition to standard care.

scholarly journals Clinical value and role of microRNA-29c-3p in sepsis-induced inflammation and cardiac dysfunction

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Bingyu Zhang ◽  
Lin Yu ◽  
Ying Sheng
Keyword(s):  
Inflammatory Response ◽  
Roc Curve ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Diastolic Pressure ◽  
Cecal Ligation ◽  
Systolic Pressure ◽  
Diagnostic Value ◽  
Left Ventricular ◽  
Tnf Α

Abstract Background The goal of this study was to investigate the diagnostic value of miR-29c-3p in sepsis and its role in sepsis-induced inflammatory response and cardiac dysfunction. Methods Serum level of miR-29c-3p was detected by qRT-PCR. The ROC curve was used to evaluate the diagnostic value of miR-29c-3p for Sepsis. The cecal ligation and puncture method (CLP) was used to establish a rat sepsis model. To assess cardiac function, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax) in different experimental groups were detected, and the serum cardiac troponin I (cTnI), creative kinase isoenzyme MB (CK-MB) were measured by ELISA. Meanwhile, TNF-α, IL-1β, and IL-6 were detected by ELISA to assess the level of inflammatory response in animals. Results miR-29c-3p level was upregulated in sepsis patients. ROC curve revealed that miR-29c-3p had the ability to distinguish sepsis patients from healthy controls. Cardiac dysfunction and inflammation were observed in sepsis rat, which were characterized by the decrease of LVSP and + dp/dtmax, the increase of LVEDP, − dp/dtmax, cTnI, CK-MB, TNF-α, IL-1β, IL-6. All effects were reversed by the injection of miR-29c-3p antagomir. Logistics regression analysis manifested miR-29c-3p is an independent factor in the occurrence of cardiac dysfunction in sepsis patients. Conclusions miR-29c-3p has potential as a biomarker for the diagnosis of sepsis, and inhibition of miR-29c-3p expression in animal models reduced sepsis-induced cardiac dysfunction and inflammatory response.

scholarly journals d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats

2012 ◽  
Vol 90 (9) ◽  
pp. 1257-1268 ◽  
Author(s):  
Jay H. Kramer ◽  
Christopher F. Spurney ◽  
Micaela Iantorno ◽  
Constantine Tziros ◽  
Joanna J. Chmielinska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Mass ◽  
Cardiac Dysfunction ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Treated Group ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Cardiac Inflammation

d-Propranolol (d-Pro: 2–8 mg·(kg body mass)–1·day–1) protected against cardiac dysfunction and oxidative stress during 3–5 weeks of iron overload (2 mg Fe–dextran·(g body mass)–1·week–1) in Sprague–Dawley rats. At 3 weeks, hearts were perfused in working mode to obtain baseline function; red blood cell glutathione, plasma 8-isoprostane, neutrophil basal superoxide production, lysosomal-derived plasma N-acetyl-β-galactosaminidase (NAGA) activity, ventricular iron content, and cardiac iron deposition were assessed. Hearts from the Fe-treated group of rats exhibited lower cardiac work (26%) and output (CO, 24%); end-diastolic pressure rose 1.8-fold. Further, glutathione levels increased 2-fold, isoprostane levels increased 2.5-fold, neutrophil superoxide increased 3-fold, NAGA increased 4-fold, ventricular Fe increased 4.9-fold; and substantial atrial and ventricular Fe-deposition occurred. d-Pro (8 mg) restored heart function to the control levels, protected against oxidative stress, and decreased cardiac Fe levels. After 5 weeks of Fe treatment, echocardiography revealed that the following were depressed: percent fractional shortening (%FS, 31% lower); left ventricular (LV) ejection fraction (LVEF, 17%), CO (25%); and aortic pressure maximum (Pmax, 24%). Mitral valve E/A declined by 18%, indicating diastolic dysfunction. Cardiac CD11b+ infiltrates were elevated. Low d-Pro (2 mg) provided modest protection, whereas 4–8 mg greatly improved LVEF (54%–75%), %FS (51%–81%), CO (43%–78%), Pmax (56%–100%), and E/A >100%; 8 mg decreased cardiac inflammation. Since d-Pro is an antioxidant and reduces cardiac Fe uptake as well as inflammation, these properties may preserve cardiac function during Fe overload.

Interaction of interval-force relationship with aortic pressure and stroke volume

1976 ◽  
Vol 230 (4) ◽  
pp. 893-900 ◽  
Author(s):  
ER Powers ◽  
Foster ◽  
Powell WJ
Keyword(s):  
Heart Rate ◽  
Stroke Volume ◽  
Diastolic Pressure ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Right Heart ◽  
Anesthetized Dogs ◽  
Right Heart Bypass ◽  
Force Relationship

The modification by aortic pressure and stroke volume of the response in cardiac performance to increases in heart rate (interval-force relationship) has not been previously studied. To investigate this interaction, 30 adrenergically blocked anesthetized dogs on right heart bypass were studied. At constant low aortic pressure and stroke volume, increasing heart rate (over the entire range 60-180) is associated with a continuously increasing stroke power, decreasing systolic ejection period, and an unchanging left ventricular end-diastolic pressure and circumference. At increased aortic pressure or stroke volume at low rates (60-120), increases in heart rate were associated with an increased performance. However, at increased aortic pressure or stroke volume at high rates (120-180), increases in heart rate were associated with a leveling or decrease in performance. Thus, an increase in aortic pressure or stroke volume results in an accentuation of the improvement in cardiac performance observed with increases in heart rate, but this response is limited to a low heart rate range. Therefore, the hemodynamic response to given increases in heart rate is critically dependent on aortic pressure and stroke volume.

Effect of human urotensin-II infusion on hemodynamics and cardiac function

2003 ◽  
Vol 81 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Ghada S Hassan ◽  
Fazila Chouiali ◽  
Takayuki Saito ◽  
Fu Hu ◽  
Stephen A Douglas ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Urotensin Ii ◽  
Ventricular Systolic Pressure ◽  
Wide Range ◽  
Dose Dependent Decrease

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.

Severe diastolic dysfunction with preserved energy conversion efficiency after countershock

1997 ◽  
Vol 273 (2) ◽  
pp. H583-H592 ◽  
Author(s):  
S. Yasuda ◽  
T. Shishido ◽  
Y. Goto
Keyword(s):  
Diastolic Dysfunction ◽  
Mechanical Performance ◽  
Diastolic Pressure ◽  
Mechanical Energy ◽  
Systolic Pressure ◽  
Myocardial Edema ◽  
Energy Conversion Efficiency ◽  
Left Ventricular ◽  
Stunned Myocardium ◽  
Before And After

The left ventricular (LV) mechanical performance and the LV myocardial oxygen consumption (VO2)-to-pressure-volume area (PVA; LV total mechanical energy index) relationship were measured in isovolumic contraction of isolated blood-perfused dog hearts before and after direct current (DC) countershocks. At a constant LV volume, DC shocks increased LV end-diastolic pressure progressively and strikingly with the progression of myocardial edema and a marked prolongation of the time constant of LV pressure decay. In contrast, DC shocks changed neither the slope of the LV end-systolic pressure-volume relationship nor the contractile efficiency (the slope of the Vo2-PVA relationship). The oxygen cost of contractility (the slope of the relationship between PVA-independent VO2 and LV contractility) increased 27% after DC shocks. However, the magnitude of this change was considerably smaller than that previously reported in postischemic stunned myocardium (123%), suggesting that the adverse effect of DC shocks on the energy cost of excitation-contraction coupling is relatively minor. Thus, despite the severe diastolic dysfunction, DC shocks do not substantially impair either the efficiency of cross-bridge cycling or calcium cycling. Myocardial interstitial edema is more likely a potential mechanism of diastolic dysfunction after DC shocks.

scholarly journals A simulation study of left ventricular decompression using a double lumen arterial cannula prototype during a veno-arterial extracorporeal membrane oxygenation

2019 ◽  
Vol 42 (12) ◽  
pp. 748-756
Author(s):  
Filip Ježek ◽  
Svitlana Strunina ◽  
Brian E Carlson ◽  
Jiří Hozman
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Cardiogenic Shock ◽  
Cardiovascular System ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Double Lumen ◽  
Membrane Oxygenation ◽  
Arterial Cannula

Background: Veno-arterial extracorporeal membrane oxygenation can be vital to support patients in severe or rapidly progressing cardiogenic shock. In cases of left ventricular distension, left ventricular decompression during veno-arterial extracorporeal membrane oxygenation may be a crucial factor influencing the patient outcome. Application of a double lumen arterial cannula for a left ventricular unloading is an alternative, straightforward method for left ventricular decompression during extracorporeal membrane oxygenation in a veno-arterial configuration. Objectives: The purpose of this article is to use a mathematical model of the human adult cardiovascular system to analyze the left ventricular function of a patient in cardiogenic shock supported by veno-arterial extracorporeal membrane oxygenation with and without the application of left ventricular unloading using a novel double lumen arterial cannula. Methods: A lumped model of cardiovascular system hydraulics has been coupled with models of non-pulsatile veno-arterial extracorporeal membrane oxygenation, a standard venous cannula, and a drainage lumen of a double lumen arterial cannula. Cardiogenic shock has been induced by decreasing left ventricular contractility to 10% of baseline normal value. Results: The simulation results indicate that applying double lumen arterial cannula during veno-arterial extracorporeal membrane oxygenation is associated with reduction of left ventricular end-systolic volume, end-diastolic volume, end-systolic pressure, and end-diastolic pressure. Conclusions: A double lumen arterial cannula is a viable alternative less invasive method for left ventricular decompression during veno-arterial extracorporeal membrane oxygenation. However, to allow for satisfactory extracorporeal membrane oxygenation flow, the cannula design has to be revisited.

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

2002 ◽  
Vol 282 (4) ◽  
pp. H1197-H1205 ◽  
Author(s):  
Michael J. Cox ◽  
Harpreet S. Sood ◽  
Matthew J. Hunt ◽  
Derrick Chandler ◽  
Jeffrey R. Henegar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blot Analysis ◽  
Diastolic Pressure ◽  
Volume Overload ◽  
Left Ventricular ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Lung Weight ◽  
Cardiac Relaxation

The hypothesis is that chronic increases in left ventricular (LV) load induce oxidative stress and latent matrix metalloproteinase (MMP) is activated, allowing the heart to dilate in the absence of endothelial nitric oxide (NO) and thereby reduce filling pressure. To create volume overload, an arteriovenous (A-V) fistula was placed in male Sprague-Dawley rats. To decrease oxidative stress and apoptosis, 0.08 mg/ml nicotinamide (Nic) was administered in drinking water 2 days before surgery. The rats were divided into the following groups: 1) A-V fistula, 2) A-V fistula + Nic, 3) sham operated, 4) sham + Nic, and 5) control (unoperated); n = 6 rats/group. After 4 wk, hemodynamic parameters were measured in anesthetized rats. The heart was removed and weighed, and LV tissue homogeneates were prepared. A-V fistula caused an increase in heart weight, lung weight, and end-diastolic pressure compared with the sham group. The levels of malondialdehyde (MDA; a marker of oxidative stress) was 6.60 ± 0.23 ng/mg protein and NO was 6.87 ± 1.21 nmol/l in the LV of A-V fistula rats by spectrophometry. Nic treatment increased NO to 13.88 ± 2.5 nmol/l and decreased MDA to 3.54 ± 0.34 ng/mg protein ( P= 0.005). Zymographic levels of MMP-2 were increased, as were protein levels of nitrotyrosine and collagen fragments by Western blot analysis. The inhibition of oxidative stress by Nic decreased nitrotyrosine content and MMP activity. The levels of tissue inhibitor of metalloproteinase-4 mRNA were decreased in A-V fistula rats and increased in A-V fistula rats treated with Nic by Northern blot analysis. TdT-mediated dUTP nick-end labeling-positive cells were increased in A-V fistula rats and decreased in fistula rats treated with Nic. Acetylcholine and nitroprusside responses in cardiac rings prepared from the above groups of rats suggest impaired endothelial-dependent cardiac relaxation. Treatment with Nic improves cardiac relaxation. The results suggest that an increase in the oxidative stress and generation of nitrotyrosine are, in part, responsible for the activation of metalloproteinase and decreased endocardial endothelial function in chronic LV volume overload.

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