Antioxidant and oxidative stress changes in experimental cor pulmonale

Although right heart failure (RHF) contributes to 20% of all cardiovascular complications, most of the information available on RHF in general is based on the experiences with left heart failure. This study on RHF investigates changes in antioxidants and oxidative stress which are suggested to play a role in the transition from hypertrophy to failure. RHF subsequent to pulmonary hypertension was produced in rats by a single injection of monocrotaline (MCT, 60 mg/kg, i.p.). Based on hemodynamic, clinical and histopathologic observations, the animals were grouped in three functional stages at 1-, 2- and 6-week post-injection periods. In the 1-week group, RV pressure overload and hypertrophy, and a mild increase in antioxidant enzymes was seen. In the 2-week group, compensated HF, a significant increase in antioxidant enzymes, an increase in septal (IVS) wall thickness and leftward displacement of IVS without change in LV free wall were seen. In the 6-week group, lung and liver congestion, RVF and dilation, a decrease in antioxidant enzyme activities, increase in lipid peroxidation and severe bulging of the IVS into the left ventricle were seen. These changes in the hemodynamic, biochemical and histopathologic characteristics suggest that in early stages of MCT-induced pulmonary hypertension at 1 and 2 weeks, RV hypertrophy was accompanied by sustained hemodynamic function and an increase in antioxidant reserve. In the later stage at 6 weeks, clinical RHF was associated with abnormalities of the right heart systolic and diastolic function along with a decrease in antioxidant reserve. These biphasic changes in RV antioxidant enzymes, i.e. an increase during hypertrophy and a decrease in failure may suggest a role of oxidative stress in the pathogenesis of right ventricular dysfunction.     

Role of nitric oxide in the induction of apoptosis by smokeless tobacco extract

The suggested role of oxidative stress in the pathogenesis of heart failure is largely based on utilizing left heart failure models. The present study on rats evaluated changes in antioxidants as well as oxidative stress in relation to hemodynamic function subsequent to the right heart failure induced by monocrotaline (50 mg/kg, i.p.). During the post-injection period, monocrotaline (MCT)-treated rats demonstrated a persistent growth depression. Two to three weeks after the injection, MCT-treated rats showed signs of fatigue, peripheral cyanosis and dyspnea. In these rats, right heart hypertrophy was confirmed by a significant increase in right ventricular weight as well as right ventricle to body weight ratio. In MCT-treated rats, there was also a significant increase in right ventricular systolic as well as end diastolic pressures. No change in lung and liver wet/dry weight ratios between MCT-treated and control animals was observed. Based on the hemodynamic data as well as other clinical observations, the functional stage achieved was compensated heart failure. Myocardial antioxidant enzymes, catalase, glutathione peroxidase and superoxide dismutase, in the MCT-treated rats were not different compared to control rats. Vitamin E levels were significantly depressed in the RV and there was no change in retinol levels. There was a significant increase in lipid hydroperoxide concentrations in MCT-treated rats as compared to the control group. These data provide evidence that right heart failure is associated with an increase in oxidative stress.     

Oxidative stress and heart failure

Various abnormalities have been implicated in the transition of hypertrophy to heart failure but the exact mechanism is still unknown. Thus heart failure subsequent to hypertrophy remains a major clinical problem. Recently, oxidative stress has been suggested to play a critical role in the pathogenesis of heart failure. Here we describe antioxidant changes as well as their significance during hypertrophy and heart failure stages. Heart hypertrophy in rats and guinea pigs, in response to pressure over-load, is associated with an increase in antioxidant reserve and a decrease in oxidative stress. Hypertrophied rat hearts show increased tolerance for different oxidative stress conditions such as those imposed by free radicals, hypoxia-reoxygenation and ischemia-reperfusion. On the other hand, heart failure under acute as well as chronic conditions is associated with reduced antioxidant reserve and increased oxidative stress. The latter may have a causal role as suggested by the protection seen with antioxidant treatment in acute as well as in chronic heart failure. It is becoming increasingly apparent that, anytime the available antioxidant reserve in the cell becomes inadequate, myocardial dysfunction is imminent.     

Persistent pulmonary hypertension results in reduced tetralinoleoyl-cardiolipin and mitochondrial complex II + III during the development of right ventricular hypertrophy in the neonatal pig heart

Persistent pulmonary hypertension of the newborn (PPHN) results in right ventricular (RV) hypertrophy followed by right heart failure and an associated mitochondrial dysfunction. The phospholipid cardiolipin plays a key role in maintaining mitochondrial respiratory and cardiac function via modulation of the activities of enzymes involved in oxidative phosphorylation. In this study, changes in cardiolipin and cardiolipin metabolism were investigated during the development of right heart failure. Newborn piglets (<24 h old) were exposed to a hypoxic (10% O(2)) environment for 3 days, resulting in the induction of PPHN. Two sets of control piglets were used: 1) newborn or 2) exposed to a normoxic (21% O(2)) environment for 3 days. Cardiolipin biosynthetic and remodeling enzymes, mitochondrial complex II + III activity, incorporation of [1-(14)C]linoleoyl-CoA into cardiolipin precursors, and the tetralinoleoyl-cardiolipin pool size were determined in both the RV and left ventricle (LV). PPHN resulted in an increased heart-to-body weight ratio, RV-to-LV plus septum weight ratio, and expression of brain naturetic peptide in RV. In addition, PPHN reduced cardiolipin biosynthesis and remodeling in the RV and LV, which resulted in decreased tetralinoleoyl-cardiolipin levels and reduced complex II + III activity and protein levels of mitochondrial complexes II, III, and IV in the RV. This is the first study to examine the pattern of cardiolipin metabolism during the early development of both the RV and LV of the newborn piglet and to demonstrate that PPHN-induced alterations in cardiolipin biosynthetic and remodeling enzymes contribute to reduced tetralinoleoyl-cardiolipin and mitochondrial respiratory chain function during the development of RV hypertrophy. These defects in cardiolipin may play an important role in the rapid development of RV dysfunction and right heart failure in PPHN.     

Right and left ventricular function after chronic pulmonary artery banding in rats assessed with biventricular pressure-volume loops

In many patients with congenital heart disease, the right ventricle (RV) is subjected to abnormal loading conditions. To better understand the state of compensated RV hypertrophy, which could eventually progress to decompensation, we studied the effects of RV pressure overload in rats. In the present study, we report the biventricular adaptation to 6 wk of pulmonary artery banding (PAB). PAB resulted in an RV pressure overload to approximately 60% of systemic level and a twofold increase in RV mass (P < 0.01). Systemic hemodynamic parameters were not altered, and overt signs of heart failure were absent. Load-independent measures of ventricular function (end-systolic pressure-volume relation, preload recruitable stroke work relation, maximum first time derivative of pressure divided by end-diastolic volume), assessed by means of pressure-volume (PV) loops, demonstrated a two- to threefold increase in RV contractility under baseline conditions in PAB rats. RV contractility increased in response to dobutamine stimulation (2.5 microg.kg(-1).min(-1)) both in PAB and sham-operated rats in a similar fashion, indicating preserved RV contractile reserve in PAB rats. Left ventricular (LV) contractility at baseline was unaffected in PAB rats, although LV volume in PAB rats was slightly decreased. LV contractility increased in response to dobutamine (2.5 microg.kg(-1).min(-1)), both in PAB and sham rats, whereas the response to a higher dose of dobutamine (5 microg.kg(-1).min(-1)) was blunted in PAB rats. RV pressure overload (6 wk) in rats resulted in a state of compensated RV hypertrophy with preserved RV contractile reserve, whereas LV contractile state at baseline was not affected. Furthermore, this study demonstrates the feasibility of performing biventricular PV-loop measurements in rats.     

Characterization of a rat model of right-sided heart failure induced by pulmonary trunk banding

Animal models of disease are essential for cardiovascular research. However, animal models of right-sided heart failure are few and remain poorly characterized. The aim with this study was to establish a rat model of right-sided heart failure (HF) using pulmonary trunk banding (PTB) and subsequently to characterize the systemic and cardiac changes in this model, including protein expression of SERCA2 and -sarcomeric actin. Rats underwent banding or sham operation. To evaluate the development of HF over time three groups were included in this study. They were killed 2–3, 5–7 or 16–17 weeks after operation, respectively. PTB rats showed marked hypertrophy of the right ventricle (RV). Catheterization of the RV showed a three- to four-fold increase in right ventricular systolic and diastolic pressures as well as increased dP/dT max and dP/dT min. Plasma analyses revealed increased liver enzymes in most PTB groups and post mortem examination revealed congestion of the liver as well as formation of ascites and hydrothorax in many PTB rats. Immunoblotting of the RV revealed no changes in SERCA2 or -sarcomeric actin. In conclusion, PTB was an effective method to induce right-sided HF. The presence of HF was confirmed by severe signs of backward failure in conjunction with markedly elevated RV pressures and reduced RV ejection fraction (EF).     

Induction of heat shock protein 72 in the failing heart is attenuated after an exposure to heat shock

Induction of heat shock protein (Hsp) 72 in the right ventricular muscle of the rat with heart failure following acute myocardial infarction (AMI) was examined. AMI was induced by the left coronary artery ligation (CAL). The animals at the 8th, but not 2nd, week after CAL revealed a decrease in cardiac output index (COI), suggesting that heart failure had developed by 8 weeks after CAL. Increases in the right ventricular developed pressure and the ratios of right ventricle/body weight and lung/body weight at the 2nd and 8th weeks showed the development of the right ventricular hypertrophy. After measurement of hemodynamic parameters, the hearts isolated from animals at the 2nd and 8th weeks after CAL (2w- and 8w-CAL hearts, respectively) were perfused and subjected to heat shock (at 42 degrees C, for 15 min) followed by 6-h perfusion. At the end of perfusion, Hsp72 content in the left ventricle without infarct area (viable LV) and the right ventricle (RV) was determined by the Western immunoblotting method. The production of myocardial Hsp72 in the viable LV and RV of the 2w-CAL heart increased after an exposure to heat shock. In contrast, induction of Hsp72 in the viable LV and RV of the 8w-CAL heart was blunted. The results suggest that the development of heart failure following AMI may result in a decrease in the ability for Hsp72 induction not only in the viable LV but also in the RV, leading to contractile dysfunction of the heart.     

曲美他嗪对肺动脉栓塞所致右心衰竭的保护作用

目的：评价曲美他嗪（TrimetazidineTMZ）对肺动脉栓塞所致右心衰竭的保护作用,及其对MMP-2,MMP-9和TIMP-1mRNA在右心室中表达的影响。方法：雄性wistar大鼠随机分为三组：右心衰竭组（RHF）左侧股静脉注射1％玻球微粒3mV100g;等量生理盐水注射为对照组（CON）;曲美他嗪治疗组（TMZ）为肺动脉栓塞后给TMZl0mg／kg／天。6周后各组大鼠首先进行经胸超声评价右心功能后取材进行病理学检测,以及RT—PCR检测右心室MMP-2,MMP-9,TIMP-1mRNA表达水平。结果：RHF组大鼠超声检测发现右心室内径扩大并伴有三尖瓣反流,三尖瓣环收缩期峰值位移下降（TAPSE）;Masson染色显示右心室纤维化增加;RTPCR结果显示MMP-2,MMP-9和TIMP-1mRNA表达水平明显升高;经TMZ治疗组大鼠右心室内径减小,TAPSE增加,而MMP-2,MMP-9和TIMP-1mRNA表达水平下降。结论：曲美他嗪能够抑制右心室纤维化,改善右心功能,可能与调节MMP-2,MMP-9和TIMP-1表达水平有关。     

Importance of antioxidant and antiapoptotic effects of beta-receptor blockers in heart failure therapy

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its beta-adrenergic blocking, antioxidant, and/or alpha-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2'-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension (r = -0.678, P < 0.0001), fractional shortening (r = 0.706, P < 0.0001), and apoptotic myocytes (r = -0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of beta-receptors in the treatment of CHF.     

Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat

We characterized hemodynamics and systolic and diastolic right ventricular (RV) function in relation to structural changes in the rat model of monocrotaline (MCT)-induced pulmonary hypertension. Rats were treated with MCT at 30 mg/kg body wt (MCT30, n = 15) and 80 mg/kg body wt (MCT80, n = 16) to induce compensated RV hypertrophy and RV failure, respectively. Saline-treated rats served as control (Cont, n = 13). After 4 wk, a pressure-conductance catheter was introduced into the RV to assess pressure-volume relations. Subsequently, rats were killed, hearts and lungs were rapidly dissected, and RV, left ventricle (LV), and interventricular septum (IVS) were weighed and analyzed histochemically. RV-to-(LV + IVS) weight ratio was 0.29 +/- 0.05 in Cont, 0.35 +/- 0.05 in MCT30, and 0.49 +/- 0.10 in MCT80 (P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 +/- 6% in Cont, 40 +/- 12% in MCT30 (P < 0.05 vs. Cont), and 26 +/- 6% in MCT80 (P < 0.05 vs. Cont and MCT30) rats. In MCT30 rats, cardiac output was maintained, but RV volumes and filling pressures were significantly increased compared with Cont (all P < 0.05), indicating RV remodeling. In MCT80 rats, RV systolic pressure, volumes, and peak wall stress were further increased, and cardiac output was significantly decreased (all P < 0.05). However, RV end-systolic and end-diastolic stiffness were unchanged, consistent with the absence of interstitial fibrosis. MCT-induced pressure overload was associated with a dose-dependent development of RV hypertrophy. The most pronounced response to MCT was an overload-dependent increase of RV end-systolic and end-diastolic volumes, even under nonfailing conditions.     

Antioxidant enzyme gene expression in congestive heart failure following mycardial infarction

Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time.     

Myocardial infarct in rats: right ventricular hypertrophy as a criterion of postinfarct left ventricular heart failure

The course of experimental myocardial infarction was accompanied by the growth response of the right ventricle (RV) in some rats. Rats with RV hypertrophy unlike ones without RV hypertrophy had depressed cardiac contraction force and velocity at rest as well as a minimal capacity to respond to functional stress. Dibunol (butylhydroxytoluene, 30 mg/kg) prevented the depression of cardiac contractility and RV growth. RV hypertrophy in the rats following left coronary artery ligation is the consequence of the left ventricle pump failure and resultant pulmonary hypertension. RV hypertrophy may be proposed as an index of postinfarct heart failure and its reduction as an index of the cardioprotective effect of various pharmacological interventions.     

Alteration of collagenous protein profile in congestive heart failure secondary to myocardial infarction

The rat model of myocardial infarction is characterized by progressive cardiac hypertrophy and failure. Rats with infarcts greater than 30% of the left ventricle exhibited early and moderate, stages of heart failure 4 and 8 weeks after the occlusion of the left coronary artery, respectively. As heart failure is usually associated with remodeling of the extracellular matrix, a histological and biochemical study of cardiac collagenous proteins was carried out using failing hearts. Total collagen content in the right ventricle increased at 2, 4, and 8 weeks following occlusion of the left coronary artery whereas such a change in viable left ventricle was seen after 4 and 8 weeks. Total cardiac hydroxyproline concentration was increased in both right and left ventricular samples from the infarcted animals when compared to those of control; this increase was due to elevation of pepsin-insoluble collagen fraction. The myocardial noncollagenous/collagenous protein ratio was decreased in experimental right and left ventricular samples when compared to control samples. These findings suggest that an increase in cross-linking of cardiac collagen as well as disparate synthesis of collagenous and noncollagenous proteins occurs in this model of congestive heart, failure.     

Changes in antioxidant status of myocardium during oxidative stress under the influence of coenzyme Q<Subscript>10</Subscript>

Changes in myocardium were studied during oxidative stress induced by infusion of hydrogen peroxide in the coronary vessels of isolated rat heart. Moderate concentrations of H2O2 increased the heart rate but decreased the contractile force, whereas higher concentrations of H2O2 decreased both parameters and increased the end diastolic pressure. The effect of H2O2 was stable, cumulative, and was associated with disturbance in respiration of mitochondria, increased production of ROS in them, and decrease in activities of antioxidant enzymes in the myocardium. Changes in the antioxidant status of the myocardium induced by long-term addition of coenzyme Q(10) into food was accompanied by decrease in the negative inotropic effect of H2O2, whereas the levels of superoxide dismutase and glutathione peroxidase after oxidative stress were virtually unchanged. The activities of these enzymes displayed a high positive correlation with the cardiac function. The findings suggest that coenzyme Q(10) should increase resistance of the myocardium to oxidative stress not only by a direct antioxidant mechanism but also indirectly, due to increased protection of antioxidant enzymes.     

Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure

In pathological conditions, the balance between reactive oxygen species (ROS) and antioxidants may shift toward a relative increase of ROS, resulting in oxidative stress. Conflicting data are available on antioxidant defenses in human failing heart and they are limited to the left ventricle. Thus, we aimed to investigate and compare the source of oxidant and antioxidant enzyme activities in the right (RV) and left (LV) ventricles of human failing hearts. We found a significant increase in superoxide production only by NADPH oxidase in both failing ventricles, more marked in RV. Despite unchanged mRNA or protein expression, catalase (CAT) and glutathione peroxidase (GPx) activities were increased, and their increases reflected the levels of Tyr phosphorylation of the respective enzyme. Manganese superoxide dismutase (Mn-SOD) activity appeared unchanged. The increase in NADPH oxidase-dependent superoxide production positively correlated with the activation of both CAT and GPx. However, the slope of the linear correlation (m) was steeper in LV than in RV for GPx (LV: m = 2.416; RV: m = 1.485) and CAT (LV: m = 1.007; RV: m = 0.354). Accordingly, malondialdehyde levels, an indirect index of oxidative stress, were significantly higher in the RV than LV. We conclude that in human failing RV and LV, oxidative stress is associated with activation of antioxidant enzyme activity. This activation is likely due to post-translational modifications and more evident in LV. Overall, these findings suggest a reduced protection of RV against oxidative stress and its potential contribution to the progression toward overt heart failure.     

Protection of Rat Myocardium by Coenzyme Q during Oxidative Stress Induced by Hydrogen Peroxide

Ubiquinone Q(10) (coenzyme Q) is an important component of the mitochondrial electron transport chain and an antioxidant. The purpose of this work was to find out whether an increase in the level of coenzyme Q in the heart changes its maximal working capacity and resistance to oxidative stress. Male Wistar rats were treated with coenzyme Q (10 mg/kg body weight per day) for six weeks, and this increased its content in the myocardium by 63%. The myocardial content of malonic dialdehyde and activities of key antioxidant enzymes were unchanged, except nearly 2.5-fold decrease in the activity of superoxide dismutase. The maximal working capacity of the isolated isovolumic heart did not change, but under conditions of oxidative stress induced by 45-min infusion of hydrogen peroxide (70 micro M) into coronary vessels the contractile function of these hearts decreased significantly more slowly. This was associated with less pronounced lesions in the ultrastructure of cardiomyocytes and lesser disorders in the oxidative metabolism of mitochondria that suggested increased antioxidant protection of the myocardium.     

Downregulation of vitamin C transporter SVCT-2 in doxorubicin-induced cardiomyocyte injury

Vitamin C (Vit C) has been shown to be protective against doxorubicin (Dox)-induced cardiotoxicity. However, Vit C uptake into cardiomyocytes is poorly understood. Furthermore, whether the antioxidant enzyme reserve is enhanced by Vit C is also not known. The present study investigated an influence of Dox on Vit C transporters, expression of endogenous antioxidant reserve as well as enzymes, oxidative stress, and apoptosis in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were exposed to control (culture medium 199 alone), Dox (10 μM), Vit C (25 μM), and Vit C + Dox for 24 h. Vit C transporter expression and localization, oxidative stress, antioxidant enzymes, and apoptosis were studied. Expression and localization of sodium-dependent vitamin C transporter-2 (SVCT-2) in the sarcolemma was reduced by Dox, but Vit C supplementation was able to blunt this change. There was a decrease in the expression of antioxidant enzymes glutathione peroxidase (GPx), catalase, and Cu/Zn superoxide dismutase (SOD) due to Dox, but only GPx expression was completely prevented and Cu/Zn SOD was partially rescued by Vit C. Dox-induced decrease in antioxidant reserve and increase in oxidative stress were partially mitigated by Vit C. Dox-induced apoptosis was ameliorated by Vit C. It is suggested that cardioprotection offered by Vit C in Dox-induced cardiomyopathy may involve an upregulation of SVCT-2 transporter followed by a reduction in oxidative stress as well as blunting of cardiomyocyte injury.     

Structural-metabolic changes in the ventricular myocardium in massive experimental pulmonary embolism]

A comparative study of hemodynamic and structural-metabolic changes in myocardium of right (RV) and left (LV) ventricles by compensative massive pulmonary embolism (MPE) and decompensated MPE was made in 29 mongrel dogs. By decompensated MPE the histoenzymological and ultrastructural methods reveal changes in RV which are not adequate to its high hemodynamic load: the catabolic enzymes activity decreases, the numeral density of mitochondrial profiles decreases too, the fraction of damaged mitochondria increases. By decompensated MPE the myocardial metabolism shifts from catabolic to biosynthetic processes, the activity of NADP.H-D and G-6-PDG increase in both ventricles.     

Phenotyping of Left and Right Ventricular Function in Mouse Models of Compensated Hypertrophy and Heart Failure with Cardiac MRI

Background

Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure.

Methods

MRI was used to quantify RV and LV function and morphology in healthy (n = 4) and sham operated (n = 3) C57BL/6 mice, and animals with a mild (n = 5) and a severe aortic constriction (n = 10).

Results

Mice subjected to a mild constriction showed increased LV mass (P<0.01) and depressed LV ejection fraction (EF) (P<0.05) as compared to controls, but had similar RVEF (P>0.05). Animals with a severe constriction progressively developed LV hypertrophy (P<0.001), depressed LVEF (P<0.001), followed by a declining RVEF (P<0.001) and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05).

Conclusions

Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence.