Impaired right and left ventricular function and relaxation induced by pulmonary regurgitation are not reversed by tardive anti-fibrosis treatment

2021 ◽  
Author(s):  
Yohei Akazawa ◽  
Tao Fujioka ◽  
Haruki Ide ◽  
Kana Yazaki ◽  
Osami Honjo ◽  
...  
Keyword(s):  
Ventricular Dysfunction ◽  
Systolic Dysfunction ◽  
Pulmonary Regurgitation ◽  
Left Ventricular ◽  
Receptor Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Valve Implantation ◽  
Rv Function ◽  
Losartan Treatment

Pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) is associated with progressive right (RV) and left (LV) ventricular dysfunction and fibrosis. However, angiotensin Ⅱ receptor blockade therapy has shown mixed and often disappointing results. The aim of this study was to serially assess changes in biventricular remodeling, dysfunction and interactions in a rat model of isolated severe PR and to study the effects of angiotensin Ⅱ receptor blockade. PR was induced in Sprague-Dawley rats by leaflet laceration. Shams (n=6) were compared to PR (n=5) and PR+losartan treatment (n=6). In the treatment group, oral losartan (50mg/kg/day) was started 6-weeks after PR induction and continued for 6-weeks until the terminal experiment. In all groups serial echocardiography was performed every 2 weeks until the terminal experiment where biventricular myocardium was harvested and analyzed for fibrosis. PR and PR+losartan rats experienced early progressive RV dilatation by 2-weeks which then stabilized. RV systolic dysfunction occurred from 4-weeks after insult and gradually progressed. In PR rats, RV dilatation caused diastolic LV compression and impaired relaxation. PR rats developed increased RV fibrosis compared to shams. While losartan decreased RV fibrosis RV dilatation and dysfunction were not improved. This suggests that RV dilatation is an early consequence of PR and affects LV relaxation. RV dysfunction may progress independent of further remodeling, suggesting that late pulmonary valve implantation may not improve RV function. Reduced RV fibrosis was not associated with improved RV function and may not be a viable therapeutic target in rTOF with predominant RV volume-loading.

Right ventricular rather than left ventricular systolic dysfunction predicts outcome in patients undergoing transcatheter aortic valve implantation: insights from cardiac magnetic resonance imaging

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Koschutnik ◽  
C Nitsche ◽  
C Dona ◽  
V Dannenberg ◽  
A.A Kammerlander ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Prognostic Information ◽  
Transcatheter Aortic Valve ◽  
Kaplan Meier ◽  
Lv Volumes ◽  
Valve Implantation ◽  
Rv Function

Abstract Background Right ventricular (RV) function is strongly associated with outcome in heart failure. Whether it also adds important prognostic information in patients undergoing transcatheter aortic valve implantation (TAVI) is unknown. Methods We consecutively enrolled patients with severe aortic stenosis (AS) scheduled for TAVI and preprocedural cardiac magnetic resonance (CMR) imaging. Kaplan-Meier estimates and multivariate Cox regression analyses were used to identify factors associated with outcome. A composite of heart failure hospitalization and/or cardiovascular death was selected as primary study endpoint. Results 423 consecutive patients (80.7±7.3 years; 48% female) were prospectively included, 201 (48%) underwent CMR imaging. 55 (27%) patients presented with RV systolic dysfunction (RVSD) defined by RV ejection fraction (RVEF) <45%. RVSD was associated with male sex (69 vs. 40%; p<0.001), New York Heart Association (NYHA) functional status (NYHA ≥ III: 89 vs. 57%; p<0.001), NT-proBNP serum levels (9365 vs. 2715 pg/mL; p<0.001), and history of atrial fibrillation (AF: 51 vs. 30%; p=0.005). On CMR, RVSD was associated with left ventricular (LV) volumes (end-diastolic: 187 vs. 137 mL, end-systolic: 119 vs. 53 mL; p<0.001) and EF (39 vs. 64%; p<0.001). A total of 51 events (37 deaths, 14 hospitalizations for heart failure) occurred during follow-up (9.8±9 months). While LVSD (LVEF <50%) was not significantly associated with outcome (HR 0.83, 95% CI: 0.33 – 2.11; p=0.694), RVSD showed a strong and independent association with event-free survival by multivariate Cox regression analysis (HR 2.47, 95% CI: 1.07–5.73; p=0.035), which was adjusted for all relevant CMR parameters (LV volumes and EF), cardiovascular risk factors (sex, NYHA, AF, diabetes mellitus type II, use of diuretics), and routine biomarkers (NT-proBNP, creatinine). Conclusions RVSD rather than LVSD, as determined on CMR, is an important predictor of outcome in patients undergoing TAVI. RV function might thus add useful prognostic information on top of established risk factors. Figure 1. Kaplan-Meier survival curves Funding Acknowledgement Type of funding source: None

Right ventricular TNF resistance during endotoxemia: the differential effects on ventricular function

2007 ◽  
Vol 293 (5) ◽  
pp. R1893-R1897 ◽  
Author(s):  
Troy A. Markel ◽  
Paul R. Crisostomo ◽  
Meijing Wang ◽  
Jeremy L. Herrmann ◽  
Aaron M. Abarbanell ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Ventricular Function ◽  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Endotoxin Exposure ◽  
Sprague Dawley Rats ◽  
Developed Pressure ◽  
The Right ◽  
Rv Function

Right and left ventricular myocytes originate from different cellular progenitors; however, it is unknown whether these cells differ in their response to endotoxemia. We hypothesized that 1) the percentage of endotoxemic functional depression within the right ventricle (RV) would be smaller than that of the left ventricle; and 2) that better RV function would correlate with lower levels of right ventricular TNF production. Adult Sprague-Dawley rats were divided into right and left control and endotoxin groups. Controls received vehicle, while endotoxin groups received LPS at 20 mg/kg ip. Hearts were excised either 2 or 6 h after injection. Hearts excised at 2 h were assayed for TNF, IL-6, TNF receptor 1 (TNFR1), TNFR2, and via ELISA, while hearts excised at 6 h were assayed via the Langendorff model. The percentage of cardiac functional depression, exhibited as developed pressure, contractility, and rate of relaxation (expressed as a percentage of control) was significantly smaller in right ventricles compared with left ventricles following endotoxin exposure. Tissue levels of TNF were significantly elevated in both right and left ventricles 2 h after endotoxin exposure, and right ventricular endotoxin groups expressed higher levels of TNF compared with their left ventricular counterparts. No significant differences in IL-6, TNFR1, or TNFR2 levels were noted between endotoxin-exposed ventricles. This is the first study to demonstrate that right and left ventricular function differs after endotoxin exposure.

Intracellular EDEMA does not adversely affect the ability to cryopreserve intact hearts

1993 ◽  
Vol 51 ◽  
pp. 278-279
Author(s):  
CL Hastings ◽  
RD Carlton ◽  
FG Lightfoot ◽  
AF Tryka
Keyword(s):  
Cell Injury ◽  
Median Sternotomy ◽  
Left Ventricular ◽  
Ventricular Free Wall ◽  
Hypoxic Cell ◽  
Free Wall ◽  
Sprague Dawley ◽  
Left Ventricular Free Wall ◽  
Sprague Dawley Rats

The earliest ultrastructural manifestation of hypoxic cell injury is the presence of intracellular edema. Does this intracellular edema affect the ability to cryopreserve intact myocardium? To answer this guestion, a model for anoxia induced intracellular edema (IE) was designed based on clinical intraoperative myocardial preservation protocol. The aortas of 250 gm male Sprague-Dawley rats were cannulated and a retrograde flush of Plegisol at 8°C was infused over 90 sec. The hearts were excised and placed in a 28°C bath of Lactated Ringers for 1 h. The left ventricular free wall was then sliced and the myocardium was slam frozen. Control rats (C) were anesthetized, the hearts approached by median sternotomy, and the left ventricular free wall frozen in situ immediately after slicing. The slam frozen samples were obtained utilizing the DDK PS1000, which was precooled to -185°C in liguid nitrogen. The tissue was in contact with the metal mirror for a dwell time of 20 sec, and stored in liguid nitrogen until freeze dry processing (Lightfoot, 1990).

scholarly journals Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5006
Author(s):  
Pema Raj ◽  
Karen Sayfee ◽  
Mihir Parikh ◽  
Liping Yu ◽  
Jeffrey Wigle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Additive Effects ◽  
Sprague Dawley ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Sprague Dawley Rats ◽  
And Function ◽  
Neutrophil Gelatinase

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.

Dietary carbohydrates modify cardiac myosin isoenzyme profiles of semistarved rats

1989 ◽  
Vol 256 (4) ◽  
pp. R976-R981
Author(s):  
G. S. Morris ◽  
R. E. Herrick ◽  
K. M. Baldwin
Keyword(s):  
Food Restriction ◽  
Systemic Blood Pressure ◽  
Left Ventricular ◽  
Cardiac Myosin ◽  
Dietary Carbohydrates ◽  
Sprague Dawley ◽  
Myosin Isoenzyme ◽  
Sprague Dawley Rats ◽  
Serum T3

Although food restriction reduces the relative expression of the rodent cardiac myosin isoenzyme V1, the contribution of accompanying metabolic changes to the induction and maintenance of this isoenzyme shift remains unknown. Hence, this study was undertaken to determine the role of carbohydrate (CHO) utilization in the regulation of cardiac myosin isoenzyme distribution in food-restricted rats. Female Sprague-Dawley rats received either a mixed diet (55% of calories as CHO, M) or a high-carbohydrate diet (75% of calories as CHO, HC). Additional animals in each dietary group received daily injections of triiodothyronine (T3; 0.075 microgram/100 microM + T3, HC + T3). Three weeks of food restriction reduced left ventricular Ca2+-activated myofibrillar adenosinetriphosphatase activity by 24% and the relative amount of the myosin V1 isoenzyme by 57% in the M group relative to free-eating controls (P less than 0.05). In contrast, these measures were reduced by only 9 and 21%, respectively, in the HC group. Administration of T3 exerted no apparent effect on V1 expression, regardless of diet. Furthermore, the increased expression of V1 in both HC and HC + T3 groups occurred independently of changes in several measures of thyroid status including serum T3 levels, O2 consumption, heart rate, and systemic blood pressure. These results further suggest that metabolic factors, specifically those associated with CHO utilization, can influence cardiac myosin isoenzyme expression.

Captopril prevents vascular and fibrotic changes but not cardiac hypertrophy in aortic-banded rats

1996 ◽  
Vol 271 (3) ◽  
pp. H906-H913 ◽  
Author(s):  
C. P. Regan ◽  
P. G. Anderson ◽  
S. P. Bishop ◽  
K. H. Berecek
Keyword(s):  
Cardiac Hypertrophy ◽  
Coronary Vessels ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Vessel Morphology ◽  
Sprague Dawley Rats ◽  
Quantitative Image

To determine the role of the renin-angiotensin system (RAS) on cardiovascular remodeling in a pressure overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male, Sprague-Dawley rats. Rats were left untreated (AB) or given captopril (Cap, 400 mg/l) (AB-Cap). Sham-operated controls were either left untreated (S) or given Cap (S-Cap). After 4 wk, rats were catheterized, and carotid and femoral mean arterial pressures (CMAP and FMAP in mmHg, respectively) were recorded. Hearts were isolated, and minimal coronary resistance (MCR) was determined. Hearts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for vessel morphology. Changes in coronary artery medical thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Cap than S or S-Cap rats (P < 0.05). There was no difference in FMAP in AB vs. S rats, but AB-Cap and S-Cap had lower FMAP values than S rats. Total heart weight and left ventricular weight-to-body weight ratios were increased in AB and AB-Cap rats compared with S and S-Cap rats (P < 0.05). MCR of AB was greater than S and S-Cap rats. MCR of AB-Cap rats was significantly greater than S and S-Cap rats but was significantly less than AB rats. In coronary vessels, medial thickness was greatest in AB, whereas there was no difference among AB-Cap, S, and S-Cap rats. Similarly, the increase in perivascular fibrosis was greatest in AB rats, and there was no difference among AB-Cap, S, and S-Cap rats. These data suggest that the RAS, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure overload hypertrophy.

scholarly journals Rats are protected from the stress of chronic pressure overload compared with mice

2020 ◽  
Vol 318 (5) ◽  
pp. R894-R900 ◽  
Author(s):  
Koichi Nishimura ◽  
Marko Oydanich ◽  
Jie Zhang ◽  
Denis Babici ◽  
Diego Fraidenraich ◽  
...  
Keyword(s):  
Troponin I ◽  
Diastolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Pressure Gradients ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Systolic And Diastolic Function ◽  
Systolic Wall Stress

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats ( n = 7) and mice ( n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats ( n = 12) and mice ( n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats ( n = 6) than in mice ( n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC ( n = 4), but they were preserved in rats ( n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.

Sudden Cardiac Death and Heart Failure

2009 ◽  
Vol 20 (4) ◽  
pp. 356-365
Author(s):  
Brenda S. Thompson
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Left Ventricular Dysfunction ◽  
Cardiac Death ◽  
Ventricular Dysfunction ◽  
Treatment Guidelines ◽  
Systolic Dysfunction ◽  
The United States ◽  
Left Ventricular ◽  
Current Evidence

Ischemic heart disease and dilated cardiomyopathy are among the most common cardiovascular disease processes associated with heart failure that can lead to lethal arrhythmias and sudden cardiac death (SCD). With the increasing incidence of heart failure in the United States, many patients are now at risk for SCD. Nurses should understand the pathophysiology, current treatment guidelines, and the rationale for these therapies to effectively manage systolic dysfunction and to mitigate the risk of SCD. Nurses are more involved than ever with this patient population and play a key role as members of the heart failure disease management team. As a result, nurses are uniquely positioned to improve survival and reduce SCD in individuals diagnosed with left ventricular dysfunction. The purpose of this article is to increase the awareness of the risk of sudden death in patients with left ventricular dysfunction. Current evidence-based practice guidelines with rationale are reviewed.

Glibenclamide improves postischemic recovery of myocardial contractile function in trained and sedentary rats

2001 ◽  
Vol 91 (4) ◽  
pp. 1545-1554 ◽  
Author(s):  
Korinne N. Jew ◽  
Russell L. Moore
Keyword(s):  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Diastolic Stiffness ◽  
Pressure Development ◽  
Increased Sensitivity ◽  
Developed Pressure

In this study, we sought to determine whether there was any evidence for the idea that cardiac ATP-sensitive K+ (KATP) channels play a role in the training-induced increase in the resistance of the heart to ischemia-reperfusion (I/R) injury. To do so, the effects of training and an KATP channel blocker, glibenclamide (Glib), on the recovery of left ventricular (LV) contractile function after 45 min of ischemia and 45 min of reperfusion were examined. Female Sprague-Dawley rats were sedentary (Sed; n = 18) or were trained (Tr; n = 17) for >20 wk by treadmill running, and the hearts from these animals used in a Langendorff-perfused isovolumic LV preparation to assess contractile function. A significant increase in the amount of 72-kDa class of heat shock protein was observed in hearts isolated from Tr rats. The I/R protocol elicited significant and substantial decrements in LV developed pressure (LVDP), minimum pressure (MP), rate of pressure development, and rate of pressure decline and elevations in myocardial Ca2+ content in both Sed and Tr hearts. In addition, I/R elicited a significant increase in LV diastolic stiffness in Sed, but not Tr, hearts. When administered in the perfusate, Glib (1 μM) elicited a normalization of all indexes of LV contractile function and reductions in myocardial Ca2+content in both Sed and Tr hearts. Training increased the functional sensitivity of the heart to Glib because LVDP and MP values normalized more quickly with Glib treatment in the Tr than the Sed group. The increased sensitivity of Tr hearts to Glib is a novel finding that may implicate a role for cardiac KATP channels in the training-induced protection of the heart from I/R injury.

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