Left Ventricular Chamber Diameter Research Articles

Brazil nuts potential: effects on lipid peroxidation and heart health in nephrectomized rats.

To investigate the effects of a Brazil nut-enriched diet on the wall thickness and the left ventricular chamber diameter of the heart, and lipid peroxidation in a CKD-induced model. Male Wistar rats at 12weeks of age were divided into two groups (n=16/group): the Nx group, which underwent 5/6 nephrectomy, and the Sham group, as a control. After 5weeks, the groups were subdivided according to diet (n=8/group): the Nx and Sham groups received a control diet; the Nx5% and Sham5% groups received a diet enriched with 5 % Brazil nuts for 8weeks. The left ventricular thickening and chamber diameter were determined. Plasma biochemical parameters were evaluated. Analysis of thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity was performed in the plasma and the left ventricle (LV). LV mRNA expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by reverse transcription-polymerase chain reaction. The Nx5% group showed a remodeled LV wall with decreased thickness compared to the Nx group (p=0.016). Furthermore, LV TBARS concentration was reduced in the Nx5% group (p=0.0064). In addition, the Nx5% group showed an increase in plasma GPx activity (p=0.0431). No significant results were found concerning the LV mRNA expression of NF-κB and Nrf2 genes. A Brazil nut-enriched diet decreased LV thickness and LV TBARS concentration and increased GPx activity in a 5/6 nephrectomy experimental model, making it a promising adjuvant therapy to improve antioxidant status and cardiovascular outcomes in chronic kidney disease.

Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities.

Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked on a functional and genetic level. Most work has investigated CHD‐related neurodevelopmental abnormalities. Cardiac abnormalities in ASD have been less studied. We investigated the prevalence of cardiac comorbidities relative to ASD genetic contributors. Using high frequency ultrasound imaging, we screened 9 ASD‐related genetic mouse models (Arid1b (+/−), Chd8 (+/−), 16p11.2 (deletion), Sgsh (+/−), Sgsh (−/−), Shank3 Δexon 4–9 (+/−), Shank3 Δexon 4–9 (−/−), Fmr1 (−/−), Vps13b (+/−)), and pooled wild‐type littermates (WTs). We measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left‐ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, mitral inflow Peak E and A velocity ratio, ascending aorta velocity time integral (VTI). Mutant groups presented small‐scale alterations in cardiac structure and function compared to WTs (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in structural measures (LV chamber diameter and anterior wall thickness, HR, AoD). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmr1 (−/−), Arid1b (+/−). The mutant groups with most differences from other mutant groups were 16p11.2 (deletion), Sgsh (+/−), Fmr1 (−/−). Our results recapitulate the associated clinical findings. The characteristic ASD heterogeneity was recapitulated in the cardiac phenotype. The type of abnormal measures (morphological, functional) can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non‐lethal abnormalities impact normal development.Lay SummaryAutism spectrum disorder (ASD) and congenital heart disease (CHD) are linked functionally and genetically. ASD cardiac phenotyping is limited. We assessed the cardiac phenotype of 9 ASD‐related mouse models. We found subtle heterogenous cardiac abnormalities compared to controls, with more differences within ASD than between ASD and controls, mirroring clinical findings. Clinically, knowing the cardiac abnormalities in ASD is vital as even non‐lethal cardiac abnormalities can impact development.

Differential cardiac geometry during pregnancy in lean versus obese mice.

Pregnancy is a sensitive window where factors adversely affecting maternal cardiac health may leave women vulnerable to cardiovascular disease (CVD) later in life. However, it is not clear how cardiac changes during pregnancy influence long-term cardiovascular health. Obesity, an independent risk factor for CVD, promotes adverse cardiac remodeling. Effects of obesity-mediated cardiac remodeling concurrent with physiologic cardiac hypertrophy of pregnancy are not well-studied. Female C57BL/6J mice (8 weeks old) were fed a high fat (HF; 60% kcal from fat) or a control low fat (LF; 10% kcal from fat) diet for 8 weeks, then were crossed with male mice to become pregnant (P) or remained non-pregnant (NP) controls. After 18 days, cardiac morphology and function was quantified by echocardiography in LF and HF P and NP mice. Lean mice had increased left ventricular (LV) mass and LV end-diastolic diameter with pregnancy. In contrast, although LV mass was greater with obesity, it was not augmented with pregnancy in obese mice. Further, pregnant obese mice had decreased LV chamber diameter and increased relative wall thickness compared to lean mice. We report a differential cardiac geometry during pregnancy in lean versus obese mice in a mouse model of diet-induced obesity. These data suggest obesity during pregnancy promotes concentric remodeling, versus eccentric remodeling in lean mice. Adverse effects of obesity on cardiac remodeling during pregnancy may be an important contributor to subsequent maternal cardiovascular risk.

Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice

BackgroundOver a third of reproductive-age women in the USA are obese, and the prevalence of cardiovascular disease (CVD) is rising in premenopausal women. Cardiac hypertrophy is an independent predictor of CVD. In contrast to pregnancy, where transiently increased left ventricular (LV) mass is not associated with cardiac damage, obesity-mediated cardiac hypertrophy is pathological. There is a paucity of data describing the effect of obesity during pregnancy on maternal cardiovascular health. The purpose of this study was to determine the long-term effect of obesity during pregnancy on cardiac function and structure in mice.MethodsFemale C57BL/6 J mice were fed a high-fat (HF) or a low-fat (LF) diet for 20 weeks. After 4 weeks, LF- and HF-fed female mice were either crossed with males to become pregnant or remained non-pregnant controls. Following delivery, pups were euthanized, and females maintained on respective diets. After 20 weeks of diet feeding, cardiac function was quantified by echocardiography, and plasma leptin and adiponectin concentrations quantified in LF- and HF-fed postpartum and nulliparous females. mRNA abundance of genes regulating cardiac hypertrophy and remodeling was quantified from left ventricles using the NanoString nCounter Analysis System. Cardiac fibrosis was assessed from picrosirius red staining of left ventricles.ResultsHF-fed postpartum mice had markedly greater weight gain and fat mass expansion with obesity, associated with significantly increased LV mass, cardiac output, and stroke volume compared with HF-fed nulliparous mice. Plasma leptin, but not adiponectin, concentrations were correlated with LV mass in HF-fed females. HF feeding increased LV posterior wall thickness; however, LV chamber diameter was only increased in HF-fed postpartum females. Despite the marked increase in LV mass in HF-fed postpartum mice, mRNA abundance of genes regulating fibrosis and interstitial collagen content was similar between HF-fed nulliparous and postpartum mice. In contrast, only HF-fed postpartum mice exhibited altered expression of genes regulating the extracellular matrix.ConclusionsThese results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.

Long-term intake of phenolic compounds attenuates age-related cardiac remodeling.

With the onset of advanced age, cardiac‐associated pathologies have increased in prevalence. The hallmarks of cardiac aging include cardiomyocyte senescence, fibroblast proliferation, inflammation, and hypertrophy. The imbalance between levels of reactive oxygen species (ROS) and antioxidant enzymes is greatly enhanced in aging cells, promoting cardiac remodeling. In this work, we studied the long‐term impact of phenolic compounds (PC) on age‐associated cardiac remodeling. Three‐month‐old Wistar rats were treated for 14 months till middle‐age with either 2.5, 5, 10, or 20 mg kg−1 day−1 of PC. PC treatment showed a dose‐dependent preservation of cardiac ejection fraction and fractional shortening as well as decreased hypertrophy reflected by left ventricular chamber diameter and posterior wall thickness as compared to untreated middle‐aged control animals. Analyses of proteins from cardiac tissue showed that PC attenuated several hypertrophic pathways including calcineurin/nuclear factor of activated T cells (NFATc3), calcium/calmodulin‐dependent kinase II (CAMKII), extracellular regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase 3ß (GSK 3ß). PC‐treated groups exhibited reduced plasma inflammatory and fibrotic markers and revealed as well ameliorated extracellular matrix remodeling and interstitial inflammation by a downregulated p38 pathway. Myocardia from PC‐treated middle‐aged rats presented less fibrosis with suppression of profibrotic transforming growth factor‐ß1 (TGF‐ß1) Smad pathway. Additionally, reduction of apoptosis and oxidative damage in the PC‐treated groups was reflected by elevated antioxidant enzymes and reduced RNA/DNA damage markers. Our findings pinpoint that a daily consumption of phenolic compounds could preserve the heart from the detrimental effects of aging storm.

Structural and functional cardiovascular changes and their consequences following interventional patent ductus arteriosus occlusion in dogs: 24 cases (2000–2006)

To investigate cardiovascular changes and survival times following complete interventional device occlusion of uncomplicated left-to-right shunting patent ductus arteriosus in dogs. Retrospective cohort study. 24 dogs with uncomplicated patent ductus arteriosus that was fully occluded and reevaluated within 24 hours, approximately 3 months, and 1 year after the procedure. Information on medical history, diagnostic imaging findings, treatment received, and survival times were obtained from medical records. Patients were allocated into 2 groups on the basis of age (< 1 year [n = 14] and ≥ 1 year [10]) at the time of the procedure. Additional follow-up information was obtained through interviews of owners and referral veterinarians. Following ductal occlusion, decreases were detected in vertebral heart scale size, left ventricular chamber diameter in diastole and in systole, left atrial dimension, fractional shortening, aortic velocity, and ventricular wall thickness. There were no differences between age groups for postocclusion changes except vertebral heart scale size. Systolic dysfunction was detected in 14 (58%) patients on the final visit. Median survival time for all dogs after ductal occlusion was > 11.5 years. Complete ductal occlusion resulted in immediate removal of the volume overload state and eventual return of cardiac chamber dimensions to reference range, suggesting regression of eccentric hypertrophy. Systolic dysfunction persisted in some dogs but appeared to be clinically unimportant. Most cardiovascular changes were independent of patient age at the time of the procedure.

In vivo and in vitro cardiac responses to beta-adrenergic stimulation in volume-overload heart failure

Hearts in volume overload (VO) undergo progressive ventricular hypertrophy resulting in chronic heart failure that is unresponsive to β-adrenergic agonists. This study compared left ventricular (LV) and isolated cardiomyocyte contractility and β-adrenergic responsiveness in rats with end-stage VO heart failure (HF). Adult male Sprague-Dawley rats were studied 21weeks after aortocaval fistula (ACF) or sham surgery. Echocardiography revealed decreased fractional shortening accompanied by increased LV chamber diameter and decreased eccentric dilatation index at end-stage ACF compared to sham. Hemodynamic measurements showed a decrease in the slope of end-systolic pressure–volume relationship, indicating systolic dysfunction. Isolated LV myocytes from ACF exhibited decreased peak sarcomere shortening and kinetics. Both Ca2+ transient amplitude and kinetics were increased in ACF myocytes, with no change under the integrated Ca2+ curves relating to contraction and relaxation phases. Increases in ryanodine receptor and phospholamban phosphorylation, along with a decrease in SERCA2 levels, were observed in ACF. These changes were associated with decreased expression of β-myosin heavy chain, cardiac troponin I and cardiac myosin binding protein-C. In vivo inotropic responses to β-adrenergic stimulation were attenuated in ACF. Interestingly, ACF myocytes exhibited a similar peak shortening to those of sham in response to a β-adrenergic agonist. The protein expression of the gap junction protein connexin-43 was decreased, although its phosphorylation at Ser-368 increased. These changes were associated with alterations in Src and ZO-1. In summary, these data suggest that the disconnect in β-adrenergic responsiveness between in vivo and in vitro conditions may be associated with altered myofilament Ca2+ sensitivity and connexin-43 degradation.

Cardiomyocyte size estimated from noninvasive measurements of left ventricular wall thickness and chamber diameter

Noninvasive measurements of left ventricular wall thickness (LVT) and left ventricular chamber diameter (LVD) allow calculation of expected left ventricular weight (LVW), but not of myocyte breadth (MyB), so that specification of left ventricular hypertrophy (LVH) is not optimal. Hypertrophied hearts, excluding coronary heart disease, and comparison specimens without hypertrophy were compiled into a series of 78 forensic autopsies, wherein LVT, LVD, and LVW were measured. MyB was measured in hematoxylin and eosin–stained paraffin sections. A series of clinical cases tabulating LVD and LVT was assembled from readily available publications. From postmortem data, a regression equation was derived to predict MyB from LVD and LVT. Applying this equation to the clinical data produced a scatter plot closely resembling that in the postmortem dataset. The equation derived here appears to provide valid predictions of cardiomyocyte sizes expected in histological measurements. The finding is the first of its kind and requires further testing for validation or rejection. This is offered as a provisional way to improve the determination of LVH using noninvasive measurements. How this improvement might enhance understanding of the mechanisms for hypertrophy is briefly explored, thus generating working hypotheses.

Microcirculation and left-ventricular hypertrophy

Microcirculation and left-ventricular hypertrophy

Protective Effects of Recombinant Human Erythropoietin against Pressure Overload-Induced Left Ventricular Remodeling and Premature Death in Mice

Chronic left ventricular (LV) pressure overload induced by hypertension is one of the most common causes of heart failure. Earlier reports have shown the cardioprotective effects of erythropoietin (EPO). In the present study, we tested the hypothesis that recombinant human EPO exerts a protective effect against pressure-overload induced LV remodeling. Mice subjected to transverse aortic constriction (TAC) (n = 70) were randomly assigned to the treatment with phosphate buffer solution (PBS) (TAC-PBS) or EPO (2,000 U/kg twice a week) (TAC-EPO). At 8 weeks after TAC, LV weight was comparably increased in both TAC groups compared with sham-operated mice (Sham) (both P < 0.001). The treatment with EPO improved the survival of TAC mice as compared with treatment with PBS (80 vs. 47%, P < 0.01), which was associated with reductions in the extent of myocardial fibrosis and the number of TUNEL positive cardiomyocytes (both P < 0.05). Echocardiography revealed that TAC increased LV chamber diameter and decreased LV fractional shortening compared with Sham (P < 0.05), which was ameliorated by the treatment with EPO (P < 0.05). In TAC-EPO as compared to TAC-PBS, phosphorylation of STAT3, Akt and eNOS was all increased, while phosphorylation of p38 was decreased (all P < 0.05). Importantly, the expression level of VEGF and the capillary density in LV myocardium were similar among the 3 groups. These results suggest that recombinant human EPO ameliorates the cardiac remodeling and the premature death associated with chronic LV pressure overload through the mechanisms independent of angiogenesis.

Effects of (−)-Epicatechin on Myocardial Infarct Size and Left Ventricular Remodeling After Permanent Coronary Occlusion

We examined the effects of the flavanol (-)-epicatechin on short- and long-term infarct size and left ventricular (LV) structure and function after permanent coronary occlusion (PCO) and the potential involvement of the protective protein kinase B (AKT)/extracellular signal-related kinase (ERK) signaling pathways. (-)-epicatechin reduces blood pressure in hypertensive patients and limits infarct size in animal models of myocardial ischemia-reperfusion injury. However, nothing is known about its effects on infarction after PCO. (-)-epicatechin (1 mg/kg daily) treatment was administered via oral gavage to 250 g male rats for 10 days before PCO and was continued afterward. The PCO controls received water. Sham animals underwent thoracotomy and treatment in the absence of PCO. Immunoblots assessed AKT/ERK involvement 2 h after PCO. The LV morphometric features and function were measured 48 h and 3 weeks after PCO. In the 48-h group, treatment reduced infarct size by 52%. There were no differences in hemodynamics among the different groups (heart rate and aortic and LV pressures). Western blots revealed no differences in AKT or ERK phosphorylation levels. At 3 weeks, PCO control animals demonstrated significant increases in LV end-diastolic pressure, heart and body weight, and LV chamber diameter versus sham. The PCO plus (-)-epicatechin group values were comparable with those of the sham plus (-)-epicatechin group. Treatment resulted in a 33% decrease in myocardial infarction size. The LV pressure-volume curves demonstrated a right shift in control PCO animals, whereas the (-)-epicatechin curves were comparable with those of the sham group. The LV scar area strains were significantly improved with (-)-epicatechin. These results demonstrate the unique capacity of (-)-epicatechin to confer cardioprotection in the setting of a severe form of myocardial ischemic injury. Protection is sustained over time and preserves LV structure and function. The cardioprotective mechanism(s) of (-)-epicatechin seem to be unrelated to AKT or ERK activation. (-)-epicatechin warrants further investigation as a cardioprotectant.

Baroreflex deficit blunts exercise training‐induced cardiovascular and autonomic adaptations in hypertensive rats

1. Baroreceptors regulate moment-to-moment blood pressure (BP) variations, but their long-term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex-mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long-term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50-70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re-established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension.

Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

The effects of aging on cardiovascular function and cardiac structure were determined in a rat model recommended for gerontological studies. A cross-sectional analysis assessed cardiac changes in male Fischer 344 x Brown Norway F1 hybrid rats (FBN) from adulthood to the very aged (n = 6 per 12-, 18-, 21-, 24-, 27-, 30-, 33-, 36-, and 39-mo-old group). Rats underwent echocardiographic and hemodynamic analyses to determine standard values for left ventricular (LV) mass, LV wall thickness, LV chamber diameter, heart rate, LV fractional shortening, mitral inflow velocity, LV relaxation time, and aortic/LV pressures. Histological analyses were used to assess LV fibrotic infiltration and cardiomyocyte volume density over time. Aged rats had an increased LV mass-to-body weight ratio and deteriorated systolic function. LV systolic pressure declined with age. Histological analysis demonstrated a gradual increase in fibrosis and a decrease in cardiomyocyte volume density with age. We conclude that, although significant physiological and morphological changes occurred in heart function and structure between 12 and 39 mo of age, these changes did not likely contribute to mortality. We report reference values for cardiac function and structure in adult FBN male rats through very old age at 3-mo intervals.

Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function

The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.

Cardiac Functional Analysis by Electrocardiography, Echocardiography and in situ Hemodynamics in Streptozotocin-Induced Diabetic Mice

Diabetic animal models are used extensively to dissect the mechanisms underlying diabetic cardiomyopathy. For such studies, detection of cardiac dysfunction is critical, and therefore, the present study comparatively examined cardiac function in mice 100 days after strepotozotocin (STZ)-induced diabetes using three complementary techniques: electrocardiography (ECG), echocardiography and left ventricular (LV) hemodynamic analysis. Histological changes were also assessed by periodic acid-Schiff (PAS)-positive materials and Masson's trichrome staining and immunohistochemical staining for type IV collagen. ECG monitoring for 2 hr in diabetic and control mice revealed no abnormality. By echocardiography, diabetic mice showed significant decreases in LV chamber diameter at end-diastole and end-systole but no other abnormalities, as compared to control mice. Hemodynamic evaluation in diabetic mice revealed that although basal parameters of cardiac function were similar to control, β-adrenergic responsiveness was significantly reduced in diabetic mice, indicating a loss of inotropic reserve and early myocardial dysfunction. Histological staining showed mild but significant increases in interstitial fibrosis in diabetic mice, confirming early diabetic cardiomyopathy. These results indicate that despite examination by ECG and resting hemodynamic may not sensitive approaches to reveal early diabetic cardiomyopathy, resting echocardiography and stressing hemodynamic analysis by evaluation of contractile provocation and inotropic reserve are able to uncover the evidence of early subtle mechanical dysfunction.

Long-term follow-up of dogs with patent ductus arteriosus.

Postocclusion survival data from dogs with left-to-right shunting patent ductus arteriosus (PDA) was available from 80 dogs, diagnosed from 1990 to 2000. Of these, 37 had undergone a procedure to close the ductus and were re-evaluated at the time of this study; clinical data from the follow-up examination was compared with that from the original examination. Radiographically, the right ventricle remained apparently enlarged, and the aortic bulge associated with dilation of the descending aorta did not disappear after closure. On M-mode echocardiography, left ventricular chamber diameter in diastole and systole and left ventricular posterior wall in systole decreased significantly. Mitral endocardiosis was a common feature. Residual flow was evident in 46 per cent of the animals. Late closure occurred in 8 per cent of the dogs, and trivial recanalisation in 19 per cent. The maximum survival time postclosure was 168 months and, after non-occlusion, 114 months, suggesting that dogs with PDA follow an unpredictable course. However, there was a significant difference in survival times between the corrected and non-corrected group.

Reference values for echocardiographic measurements in urban and rural populations of differing ethnicity: The Strong Heart Study

Discrepancies in reported reference values for left ventricular (LV) dimensions and mass may be due to imaging errors with early echocardiographic methods or effects of subject characteristics and inclusion criteria. To determine whether contemporary echocardiographic methods provide stable normal limits for left ventricular measurements in different populations, M-mode/2-dimensional echocardiography was applied in 176 American Indian participants in the Strong Heart Study and 237 New York City residents who were clinically normal. No consistent difference in any measure of LV size or function existed between populations. Upper normal limits (98th percentile) for LV mass were 96 g/m2 in women and 116 g/m2 in men and 3.27 cm/m for LV chamber diameter normalized for height. Thus contemporary M-mode/2D echocardiography provides reference ranges for LV measurements that approximate necropsy measurements and have acceptable stability in apparently normal white, African-American/Caribbean, and American Indian populations. (J Am Soc Echocardiogr 2001;14:601-11.)

Eprosartan reduces cardiac hypertrophy, protects heart and kidney, and prevents early mortality in severely hypertensive stroke-prone rats.

Eprosartan is a selective angiotensin II type I receptor antagonist approved for the treatment of hypertension. In the present studies, eprosartan's ability to provide end-organ protection was evaluated in a model of cardiomyopathy and renal failure in stroke-prone rats (SP). SP were fed a high fat (24.5% in food) and high salt (1% in water) diet (SFD). Eprosartan (60 mg/kg/day) or vehicle (saline control) (n = 25/group) was administered by intraperitoneally-implanted minipumps to these SP on the SFD for 12 weeks. Normal diet fed SP and WKY rats (n = 25/group) were also included for comparison (i.e. served as normal controls). Mortality, hemodynamics, and both renal and cardiac function and histopathology were monitored in all treatment groups. Eprosartan decreased the severely elevated arterial pressure (-12%; P < 0.05) produced by SFD but did not affect heart rate. Vehicle-treated SP-SFD control rats exhibited significant weight loss (-13%; P < 0.05) and marked mortality (50% by week 6 and 95% by week 9; P < 0.01). Eprosartan-treated SP-SFD rats maintained normal weight, and exhibited zero mortality at week 12 and beyond. Eprosartan prevented the increased urinary protein excretion (P < 0.05) that was observed in vehicle-treated SP-SFD rats. Echocardiographic (i.e. 2-D guided M-mode) evaluation indicated that SP-SFD vehicle control rats exhibited increased septal (+22.2%) and posterior left ventricular wall (+30.0%) thickness, and decreased left ventricular chamber diameter (-15.9%), chamber volume (-32.7%), stroke volume (-48.7%) and ejection fraction (-22.3%), and a remarkable decrease in cardiac output (-59.3%) compared to controls (all P < 0.05). These same parameters in eprosartan-treated SP-SFD rats were normal and differed markedly and consistently from vehicle-treated SP-SFD rats (i.e. treatment prevented pathology; all P < 0.05). Cardiac-gated MRI data confirmed the ability of eprosartan to prevent cardiac pathology/remodeling (P < 0.05). Histopathological analysis of hearts and kidneys indicated that eprosartan treatment significantly reduced end-organ damage (P < 0.01) and provided corroborative evidence that eprosartan reduced remodeling of these organs. Vehicle-treated SP-SFD rats exhibited a 40% increase in the plasma level of pro-atrial natiuretic factor that was reduced to normal by eprosartan (P < 0.05). These data demonstrate that eprosartan, at a clinically relevant dose, provides significant end-organ protection in the severely hypertensive stroke-prone rat. It preserves cardiac and renal structural integrity, reduces cardiac hypertrophy and indices of heart failure, maintains normal function of the heart and kidneys, and eliminates premature mortality due to hypertension-induced end-organ failure.

Treatment with dimethylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice: role of oxidative stress.

Oxidative stress might play an important role in the progression of left ventricular (LV) remodeling and failure that occur after myocardial infarction (MI). We determined whether reactive oxygen species (ROS) are increased in the LV remodeling and failure in experimental MI with the use of electron spin resonance spectroscopy and whether the long-term administration of dimethylthiourea (DMTU), hydroxyl radical (.OH) scavenger, could attenuate these changes. We studied 3 groups of mice: sham-operated (sham), MI, and MI animals that received DMTU (MI+DMTU). Drugs were administered to the animals daily via intraperitoneal injection for 4 weeks.OH was increased in the noninfarcted myocardium from MI animals, which was abolished in MI+DMTU. Fractional shortening was depressed by 65%, LV chamber diameter was increased by 53%, and the thickness of noninfarcted myocardium was increased by 37% in MI. MI+DMTU animals had significantly better LV contractile function and smaller increases in LV chamber size and hypertrophy than MI animals. Changes in myocyte cross-sectional area determined with LV mid-free wall specimens were concordant with the wall thickness data. Collagen volume fraction of the noninfarcted myocardium showed significant increases in the MI, which were also attenuated with DMTU. Myocardial matrix metalloproteinase-2 activity, measured with gelatin zymography, was increased with MI after 7 and 28 days, which was attenuated in MI+DMTU. Thus, the attenuation of increased myocardial ROS and metalloproteinase activity with DMTU may contribute, at least in part, to its beneficial effects on LV remodeling and failure. Therapies designed to interfere with oxidative stress might be beneficial to prevent myocardial failure.

Dobutamine-atropine stress echocardiography for the detection of coronary artery disease in patients with left ventricular hypertrophy. Importance of chamber size and systolic wall stress.

Left ventricular hypertrophy is a heterogeneous disorder with distinct morphologies. Changes in wall thickness, left ventricular chamber diameter, and mass alter systolic wall stress of the left ventricle and may influence ischemic threshold. Thus, the goal of this study was to investigate the effect of the different patterns of left ventricular hypertrophy on the accuracy of dobutamine-atropine stress echocardiography. Three-hundred eighty-six patients underwent multistage dobutamine-atropine stress echocardiography and diagnostic angiography. Echocardiograms were measured for mean and relative wall thicknesses, chamber size, left ventricular mass, and end-systolic wall stress. The patterns of ventricular hypertrophy were concentric hypertrophy (increased wall thickness and mass), eccentric hypertrophy (normal wall thickness and increased mass), and concentric remodeling (increased wall thickness and normal mass). The overall sensitivity, specificity, and accuracy of dobutamine-atropine stress echocardiography for the detection of coronary artery disease were 85%, 87%, and 86%, respectively. Increased left ventricular mass index alone did not affect accuracy. Sensitivity was markedly reduced (36%) only in those with concentric remodeling. The univariate predictors of false-negative studies were single-vessel left circumflex disease, increased wall thickness, small chamber size, hyperdynamic ejection fraction, and left ventricular concentric remodeling. Multivariate predictors were concentric remodeling (P<0.0001; odds ratio, 13.5), left ventricular ejection fraction >2 SD above normal (P<0.0001), and single-vessel left circumflex disease (P<0.0007; odds ratio, 7.6). Sensitivity was excellent in patients with small ventricles and normal wall thickness and in those with normal or large chambers regardless of wall thickness. Dobutamine-atropine stress echocardiography is an accurate test in most patients with left ventricular hypertrophy, but it is insensitive in the small subset with concentric remodeling.