Changes In Left Ventricular Dimensions Research Articles

The impact of anti-inflammatory cytokines provoked by CD163 positive macrophages on ventricular functional recovery after myocardial infarction

Present study aimed to investigate the impact of anti-inflammatory cytokines provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV) functional recovery after successful reperfusion in patients with acute myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage scavenger receptor. This process provokes secretion of anti-inflammatory atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was determined by echocardiography before PCI and 6months after PCI. %CD163 was defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the ratio of positively stained areas per total tissue. Patients were divided into two groups depending on the amount of CD163 (+)-cells: CD163>10% (CD163high, n=20) and CD163≤10% (CD163low, n=20). CD163high group had significantly higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was significantly lower in CD163high group. In subgroups with the final TIMI-3 flow (CD163high-Reflow, n=15 and CD163low-Reflow, n=20), the time to reperfusion, infarct size, LV dimensions and fractional shortening (%FS) before PCI were similar. Significant correlation was observed between %IL10 and changes in LV dimensions (diastole, r=-0.49, P=0.01; systole, r=-0.65, P<0.01) or %FS (r=0.51, P<0.01) at 6months after PCI. Plaque with CD163(+)-macrophages could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance the anti-inflammatory cytokine expression that aids in ventricular functional recovery if distal flow can be achieved by successful reperfusion.

Right Ventricular Involvement in Diabetic Cardiomyopathy

OBJECTIVETo compare magnetic resonance imaging-derived right ventricular (RV) dimensions and function between men with type 2 diabetes and healthy subjects, and to relate these parameters to left ventricular (LV) dimensions and function.RESEARCH DESIGN AND METHODSRV and LV volumes and functions were assessed in 78 men with uncomplicated type 2 diabetes and 28 healthy men within the same range of age using magnetic resonance imaging. Steady-state free precession sequences were used to assess ventricular dimensions. Flow velocity mapping across the pulmonary valve and tricuspid valve was used to assess RV outflow and diastolic filling patterns, respectively. Univariate general linear models were used for statistical analyses.RESULTSRV end-diastolic volume was significantly decreased in patients compared with healthy subjects after adjustment for BMI and pulse pressure (177 ± 28 mL vs. 197 ± 47 mL, P < 0.01). RV systolic function was impaired: peak ejection rate across the pulmonary valve was decreased (433 ± 54 mL/s vs. 463 ± 71 mL/s, P < 0.01) and pulmonary flow acceleration time was longer (124 ± 17 ms vs. 115 ± 25 ms, P < 0.05). Indexes of RV diastolic function were impaired: peak filling rate and peak deceleration gradient of the early filling phase were 315 ± 63 mL/s vs. 356 ± 90 mL/s (P < 0.01) and 2.3 ± 0.8 mL/s2 × 10−3 vs. 2.8 ± 0.8 mL/s2 × 10−3 (P < 0.01), respectively. All RV parameters were strongly associated with its corresponding LV parameter (P < 0.001).CONCLUSIONSDiabetic cardiomyopathy affects the right ventricle, as demonstrated by RV remodeling and impaired systolic and diastolic functions in men with type 2 diabetes, in a similar manner as changes in LV dimensions and functions. These observations suggest that RV impairment might be a component of the diabetic cardiomyopathy phenotype.

Correlation between hemoglobin level and left ventricular systolic functions and dimensions in children with chronic severe anemia

Background Chronic severe anemia is a connnon disease. Cardiac output may increase when the hemoglobin (Hb) level decreases to &lt; 7 g/dL for 3 months or more. Alteration of left ventricular (LV) function occurs frequently in children 'With chronic severe anemia, in the {onn of concentric LV hypertrophy, LV dilatation with or v.ithout LV hypertrophy, or systolic dysfunction. Objective To examine the correlation between Hb level and alteration of LV systolic function in children with chronic severe anemia. Methods We conducted a cross-sectional study in Adam Malik Hospital from October to December 2009. Subjects were chronic severely anemic children. Left ventricular systolic function (ejection fraction/EF, fractional shortening/FS) and dimensions (left ventricular end diastolic diameter/LVEDD and left ventricular end systolic diameter/LVESD) were measured using Hitachi EUB 5500 echocardiography unit. Univariate analysis and Pearson correlation were performed.Results Thirty children were enrolled in the study. The mean of age was 113.5 months (SD 53.24). Hb values ranged from 2.1 to 6.9 g/dL with mean value of 4.6 g/dL (SD 1.44). Mean duration of anemia was 3.9 months (SD 0.70). Chronic severe anemia was not associated \\lith decreased LV systolic function [EF 62.2% (SD 9.16), r =0.296, P=0.112; FS 33.8% (SD 7.26), r =0.115, P=0.545], nor LV dimension changes [LVEDD 40.2 mm (SD 6.85), r = -0.192, P=0.308; LVESD 26.2 mm (SD 4.98), r=-0.266, P=0.156]. Conclusion There was no correlation between Hb level in chronically anemic children and changes in LV systolic function or dimension.

Both Exogenous Subclinical Hyperthyroidism and Short-Term Overt Hypothyroidism Affect Myocardial Strain in Patients with Differentiated Thyroid Carcinoma

The cardiovascular effects of transitions from exogenous subclinical hyperthyroidism to short-term overt hypothyroidism in patients treated for differentiated thyroid carcinoma remain unclear. The present study aims at evaluating the changes in multidirectional myocardial strain using two-dimensional (2D) speckle tracking during this controlled transition from exogenous subclinical hyperthyroidism to overt hypothyroidism. The study included 14 patients with differentiated thyroid carcinoma on thyrotropin suppressive thyroxine substitution who were subsequently withdrawn from thyroxine for 4 weeks. Cardiac function was assessed by 2D speckle tracking echocardiography before and 1 and 4 weeks after withdrawal and compared with values obtained in a control group of 24 individuals. At baseline, the left ventricular dimensions were significantly higher in patients as compared with controls. Using 2D speckle tracking imaging, the patients had significantly impaired baseline myocardial systolic function in the circumferential (-16.0% ± 2.1% vs. -19.2% ± 3.0%, p = 0.001) and longitudinal (-17.1% ± 2.5% vs. -19.7% ± 3.0%, p = 0.001) directions as compared with controls. Withdrawal of thyroid hormone did not induce significant changes in left ventricular dimensions or systolic function. During the transition from exogenous subclinical hyperthyroidism to overt hypothyroidism, a significant improvement in circumferential and longitudinal systolic shortening was observed and returned to abnormal values when the patients were overt hypothyroid (circumferential strain: from -16.0% ± 2.1% to -18.6% ± 1.9% and -14.7% ± 2.8%, p < 0.005; longitudinal strain: from -17.1% ± 2.5% to -18.8% ± 1.4% and -16.3% ± 1.3%, p < 0.005). A U-shaped relationship between a range of thyroid hormone levels (from hyper- to hypothyroid concentrations) and myocardial strains was observed. The clinical consequences of these findings remain to be determined but may point out an increased myocardial vulnerability even in states of moderate subclinical hyperthyroidism and short-term hypothyroidism.

Gene transfer of the sarcoplasmic reticulum pump in the treatment of heart failure

This editorial refers to ‘Augmentation of left ventricularmechanics by recirculation-mediated AAV2/1-SERCA2agene delivery in experimental heart failure’ by JustinMariani et al. published in this issue on page 247–253.Therapy of congestive heart failure was revolutionized more than20 years ago by the introduction of angiotensin-convertingenzyme inhibitors and b-adrenoceptor blocking agents. Bothhave resulted in the improvement of symptoms and prognosis ofpatients with chronic heart failure. In the meantime, device-basedtherapies have been added to the therapeutic armamentarium.However, all attempts to directly address molecular alterations rel-evant to heart failure pathophysiology as treatment strategies havefailed. Because morbidity and mortality of heart failure patients arestill unacceptably high, there is an urgent need for new treatmentstrategies. Alterations of calcium cycling have been identified as asignificant contributor to heart failure pathophysiology, and there-fore, therapeutic strategies addressing calcium homeostasis seemlogical.

An Animal Model for Ectopy‐Induced Cardiomyopathy

Ectopy-induced cardiomyopathy is an increasingly recognized cause of reversible left ventricular (LV) dysfunction. The underlying mechanisms remain unknown. Our goal was to create an animal model for ectopy-induced cardiomyopathy. Eleven mongrel dogs underwent the implantation of a dual-chamber pacemaker. Four dogs served as the control group and seven as the paced group. In the paced group, the pacemaker was connected to two endocardial right ventricular leads, one inserted into the atrial port and the other one into the ventricular port with an atrioventricular delay adjusted to ensure the presence of coupled pacing simulating ventricular bigeminy. Echocardiographic measurements of LV size (LV end-diastolic diameter [LV-EDD], LV end-systolic diameter [LV-ESD]), LV ejection fraction (LVEF), and mitral regurgitation (MR) were obtained at baseline and after 4 weeks of monitoring or pacing in all dogs except one who had lead dislodgement. In the control group (n = 4), no significant changes in LV dimensions or function were noted. In the paced group (n = 6), LV-EDD and LV-ESD increased from 3.58 ± 0.65 cm and 2.47 ± 0.55 cm to 4.15 ± 0.59 cm and 3.21 ± 0.47 cm, respectively (P < 0.01). In addition, LVEF decreased from 60 ± 7% to 46 ± 9% (P < 0.05). No changes in MR were noted. We have shown that coupled pacing simulating ventricular bigeminy was feasible and resulted in increased LV dimensions and decreased LV function. By controlling the percentage of pacing, the coupling interval and the location of the pacing lead, this new model will allow the assessment of the relative roles of these variables in the development of ectopy-induced cardiomyopathy.

Invited Commentary

Invited Commentary

Intrathoracic and Ventricular Impedances are Associated with Changes in Ventricular Volume in Patients Receiving Defibrillators for CRT

Some implantable cardioverter defibrillators (ICD) are able to monitor intrathoracic impedance to detect pulmonary fluid overload. This is achieved by measuring impedance between the ICD case and the right ventricular (RV) lead. We hypothesized that the measured impedance would rise with improvement in left ventricular (LV) volumes during cardiac resynchronization therapy (CRT), and that such impedance changes would be more apparent when measured with an alternative pacing vector. We analyzed echocardiographic and impedance data from heart failure patients implanted with a CRT-ICD capable of intrathoracic impedance measurement for fluid accumulation diagnosis, and LV pacing impedance recording for lead integrity monitoring. In 127 out of 170 patients that received de novo CRT implantation, the LV end-systolic volume (LVESV) decreased at 6-month follow-up (LVESV at 6 month-LVESV at baseline <0: group A). For the remaining 43 patients (group B) the change was > or = 0. Despite comparable values at baseline (P = 0.262), the impedances of groups A and B gradually diverged soon after the implant, resulting in significant difference between the two groups at the 6-month visit (P = 0.001). The changes in LV dimensions produced larger differences between groups in the impedance measured between the LV and the RV leads (P < 0.001). The regression analysis demonstrated an inverse correlation between paired changes of volume and intrathoracic impedance. Higher correlation coefficient was obtained using the LV-to-RV measurement vector (r =-0.635, P < 0.001). The changes in ICD-measured impedance seem associated with the LV volume changes induced by CRT. Specifically, the LV-to-RV impedance estimations seem to better correlate with paired changes of ventricular volumes.

Effects of anesthetic induction in patients with diastolic dysfunction

To evaluate the effects of anesthetic induction on bi-ventricular function in patients with known preoperative left ventricular (LV) diastolic dysfunction undergoing coronary artery bypass grafting surgery (CABG). Fifty patients with diastolic dysfunction undergoing CABG were studied. Preoperative transthoracic echocardiographic (TTE) examination was performed on the day before surgery and transesophageal echocardiography (TEE) assessment was undertaken after induction of anesthesia with sufentanil, midazolam, isoflurane, and pancuronium. Mean arterial pressure (MAP) and heart rate (HR) were recorded. The diameters of the left atrium (LA) and right atrium (RA) and right ventricular (RV) end-diastolic area (EDA), end-systolic area (ESA) and fractional area change (FAC) were obtained from the apical 4-chamber view. The LV EDA, LV ESA and LV FAC were measured from a transgastric midpapillary view. Pulsed wave Doppler of the transmitral flow (TMF) and transtricuspid flow (TTF), pulmonary venous flow (PVF) and hepatic venous flow (HVF) were measured. Mitral (Em, Am) and tricuspid (Et, At) annulus velocities were assessed by tissue Doppler imaging (TDI). Assessment of diastolic dysfunction was graded from normal to severe using a validated score. Following induction of anesthesia, HR decreased (66 +/- 12 vs 55 +/- 9 beats.min(-1), P < 0.0001) while MAP remained unchanged (86.1 +/- 9.0 vs 85.6 +/- 26.5 mmHg, P = 0.94). The diameters of the LA, RA and RV chambers increased, and these increases were associated with opposite changes in LV dimensions. The RV FAC decreased, but the LV FAC remained unchanged. While most Doppler velocities decreased (P < 0.05), a greater reduction in the atrial components of the TMF, TTF and TDI ratios was observed. The LV diastolic function score improved after induction of anesthesia (100% of patients with a score > or = = 3 pre-induction compared to 58% of patients with a score > or = 3 post-induction; P = 0.0004). In patients with left ventricular diastolic dysfunction, cardiac dimensions and bi-ventricular filling patterns are significantly altered after induction of general anesthesia. These changes can be explained to some extent by a reduction in venous return with general anesthesia, reduced atrial contractility, and the effect of positive pressure ventilation. Although the LV diastolic function score improved after induction of anesthesia, it is difficult to dissociate this effect from that of altered loading conditions.

Acute left ventricular dilatation and shock-induced myocardial dysfunction*

Whether cardiac ventricles can acutely dilate during septic myocardial dysfunction. A prospective echocardiographic study was performed to assess changes of left ventricular dimensions over time in patients with septic shock. A 20-bed surgical intensive care unit of Pitié-Salpêtrière university hospital in Paris. Forty-five patients were studied over the first 10 days of septic shock. None. Left ventricular end-diastolic area (LVEDA), fractional area change (FAC), velocity time integral of the aortic flow, echocardiographic indices of left ventricular relaxation, and cardiac troponin I (cTnI) were measured at day 1, 2, 3, 4, 7, and 10. Three groups were defined: 29 patients without increased cTnI and cardiac impairment (group 1), eight patients with increased cTnI and left systolic ventricular dysfunction (group 2), and eight patients with increased cTnI and isolated impairment of left ventricular relaxation (group 3). At day 1, LVEDA was significantly higher in group 2 (13 +/- 3 cm/m, p < 0.05) compared with groups 1 (10 +/- 2 cm/m) and 3 (11 +/- 2 cm/m). LVEDA did not change in groups 1 and 3. In group 2, LVEDA and FAC returned within 10 days to values observed in groups 1 and 2. A significant correlation was found between aortic velocity time integral and LVDEA (r =.78, p = 0.022) and FAC (r =.89, p = 0.003) only in group 2. Acute and reversible left ventricular dilation accompanies septic shock-induced systolic left ventricular dysfunction. When septic myocardial abnormalities are limited to reversible impairment of left ventricular relaxation, left ventricular dimensions remain unchanged.

Age-related cardiac muscle sarcopenia: Combining experimental and mathematical modeling to identify mechanisms

Age-related skeletal muscle sarcopenia has been extensively studied and smooth muscle sarcopenia has been recently described, but age-related cardiac sarcopenia has not been previously examined. Therefore, we evaluated adult (7.5 ± 0.5 months; n = 27) and senescent (31.8 ± 0.4 months; n = 26) C57BL/6J mice for cardiac sarcopenia using physiological, histological, and biochemical assessments. Mice do not develop hypertension, even into senescence, which allowed us to decouple vascular effects and monitor cardiac-dependent variables. We then developed a mathematical model to describe the relationship between age-related changes in cardiac muscle structure and function. Our results showed that, compared to adult mice, senescent mice demonstrated increased left ventricular (LV) end diastolic dimension, decreased wall thickness, and decreased ejection fraction, indicating dilation and reduced contractile performance. Myocyte numbers decreased, and interstitial fibrosis was punctated but doubled in the senescent mice, indicating reparative fibrosis. Electrocardiogram analysis showed that PR interval and QRS interval increased and R amplitude decreased in the senescent mice, indicating prolonged conduction times consistent with increased fibrosis. Intracellular lipid accumulation was accompanied by a decrease in glycogen stores in the senescent mice. Mathematical simulation indicated that changes in LV dimension, collagen deposition, wall stress, and wall stiffness precede LV dysfunction. We conclude that age-related cardiac sarcopenia occurs in mice and that LV remodeling due to increased end diastolic pressure could be an underlying mechanism for age-related LV dysfunction.

Deleterious effects of sugar and protective effects of starch on cardiac remodeling, contractile dysfunction, and mortality in response to pressure overload

Little is known about the effects of the composition of dietary carbohydrate on the development of left ventricular (LV) hypertrophy (LVH) and heart failure (HF) under conditions of pressure overload. The objective of this study was to determine the effect of carbohydrate composition on LVH, LV function, and mortality in a mouse model of chronic pressure overload. Male C57BL/6J mice of 6 wk of age (n = 14-16 mice/group) underwent transverse aortic constriction (TAC) or sham surgery and were fed either standard chow (STD; 32% corn starch, 35% sucrose, 3% maltodextrin, and 10% fat expressed as a percent of the total energy), high-starch chow (58% corn starch, 12% maltodextrin, and 10% fat), or high-fructose chow (9% corn starch, 61% fructose, and 10% fat). After 16 wk of treatment, mice with TAC fed the STD or high-fructose diets exhibited increased LV mass, larger end-diastolic and end-systolic diameters, and decreased ejection fraction compared with sham. The high-starch diet, in contrast, prevented changes in LV dimensions and contractile function. Cardiac mRNA for myosin heavy chain-beta was increased dramatically in the fructose-fed banded animals, as was mortality (54% compared with 8% and 29% in the starch and STD banded groups, respectively). In conclusion, a diet high in simple sugar was deleterious, resulting in the highest mortality and expression of molecular markers of cardiac dysfunction in TAC animals compared with sham, whereas a high-starch diet blunted mortality, increases in cardiac mass, and contractile dysfunction.

Matrix Metalloproteinase (MMP)-7 Activates MMP-8 But Not MMP-13

Matrix Metalloproteinases (MMPs) are a class of zinc-dependent enzymes that degrade extracellular matrix components, particularly collagen. MMPs have been implicated in a diverse list of pathological processes, including cancer and cardiovascular disease. Recent efforts to bring MMP inhibitors to clinical trials, however, have proved disappointing. These failures are attributed, in part, to the non-selective nature of current inhibitors. The possibility also exists, however, that inhibition of a particular MMP type will lead to feedback accumulation of parallel MMP members. MMP-7, also known as matrilysin, has a broad list of substrates, including denatured collagen and other MMPs involved in the collagenolytic pathway, namely MMP-1, MMP-2, and MMP-9. Whether the additional collagenases, MMP-8 and MMP-13, are also activated by MMP-7 has not been explored. We show here that recombinant active MMP-7 was able to process MMP-8 to its active form in vitro, but did not activate MMP-13. In the left ventricles of mice lacking the MMP-7 gene, MMP-8 levels increased while MMP-13 levels decreased in vivo. The switch in MMP profile was not accompanied by a change in left ventricular dimensions or wall thickness. Together, these data suggest that MMP-8 is an in vivo substrate of MMP-7, and that the accumulation of pro-MMP-8 in the absence of MMP-7 downregulates pro-MMP-13 levels in order to maintain baseline collagenolytic function. The interplay between MMP-8 and MMP-13 suggest that these MMPs may play reciprocal roles. The design of selective MMP inhibitors, therefore, must take into consideration changes in parallel MMP types as a potential compensatory mechanism.

Drugs for Left Ventricular Remodeling in Heart Failure

Left ventricular (LV) remodeling (ie, enlargement and functional deterioration occurring over time) is among the main mechanisms of progression in heart failure (HF). LV dilatation and dysfunction are major negative prognostic markers in patients with HF. Treatments that are effective in limiting or even reversing this process can be expected to provide clinical benefit. Changes in LV dimensions rather than in ejection fraction should be used to monitor remodeling. Ejection fraction can be influenced by transient loading conditions and by agents that stimulate contractility at the expense of increased oxygen demand, whereas dimensional changes probably reflect structural modifications occurring in the myocardium. The neurohormonal antagonists that have been demonstrated to reduce mortality and morbidity in HF (angiotensin-converting enzyme inhibitors [ACE], beta-blockers, angiotensin receptor blockers, and aldosterone antagonists) are also able to inhibit or reverse remodeling. In reverse remodeling, beta-blockers appear to be superior to the other classes of drugs, with a stronger correlation between dose and effect, but it must be remembered that they have been tested as an addition to background therapy that may include ACE inhibitors. With regard to nonpharmacologic strategies, biventricular pacing is associated with functional improvement and reverse remodeling in patients with advanced HF and electromechanical dyssynchrony, and it recently has been demonstrated to improve survival in a randomized clinical trial.

Myocardial infarction and heart failure in the db/db diabetic mouse

Clinical studies have reported that the incidence and severity of myocardial infarction is significantly greater in diabetics compared with nondiabetics after correction for all other risk factors. The majority of studies investigating the pathophysiology of myocardial ischemia-reperfusion injury have focused on otherwise healthy animals. At present, there is a paucity of experimental investigations on the pathophysiology of heart failure in diabetic animals. We hypothesized that the severity of myocardial reperfusion injury and the development of congestive heart failure would be markedly enhanced in the db/db diabetic mouse. Accordingly, we studied the effects of varying durations of in vivo myocardial ischemia and reperfusion on the incidence of heart failure in db/db diabetic mice. Nondiabetic and db/db diabetic mice (10 wk of age) were subjected to 30, 45, or 60 min of left coronary artery occlusion and 28 days of reperfusion. Survival at 24 h of reperfusion was 100% in nondiabetic mice subjected to 30 min of myocardial ischemia and 88% in nondiabetic mice subjected to 45 min of myocardial ischemia. In contrast, survival was 53% in db/db diabetic mice subjected to 30 min of myocardial ischemia and 44% in db/db mice after 45 min of myocardial ischemia. Prolonged survival in nondiabetic mice was not significantly attenuated when compared during the 28-day follow-up period with all groups experiencing >90% survival. Prolonged survival was significantly decreased in db/db mice after both 30 and 45 min of myocardial ischemia compared with sham controls. Furthermore, we observed a significant degree or left ventricular dilatation, cardiac hypertrophy, and cardiac contractile dysfunction in db/db mice subjected to 45 min of myocardial ischemia and 28 days reperfusion. In nondiabetic mice subjected to 45 min of myocardial ischemia, we failed to observe any changes in left ventricular dimensions or fractional shortening. These studies provide a feasible experimental model system for the investigation of heart failure secondary to acute myocardial infarction in the db/db diabetic mouse.

Effect of Beta-Blocker Therapy on Myocardial Perfusion Defects in Thallium-201 Scintigraphy in Patients with Dilated Cardiomyopathy

Background: Thebeneficial effects of β-blocker therapy in patients with heart failure have been confirmed. However, the effects of β-blockers on myocardial perfusion defects are unclear. The aim of this study was to evaluate the effect of β-blockers on myocardial perfusion defects estimated by thallium-201 myocardial scintigraphy in patients with dilated cardiomyopathy (DCM) and to investigate the relationships between β-blocker treatment and myocardial damage and cardiac function. Methods:²⁰¹Tl and echocardiography were performed in 37 patients before and after 6 months of β-blocker therapy. Extent score (ES) by ²⁰¹Tl was used to quantitate myocardial perfusion defects before and after treatment. Results: ES was significantly decreased by β-blocker therapy. According to the change in ES, DCM patients were classified into three groups, patients who improved, patients showing no change and patients who deteriorated. In the improvement and no-change groups, β-blocker therapy induced a reduction in left ventricular dimensions and an associated increase in ejection fraction. However, in the deterioration group, left ventricular dimensions and ejection fraction were unchanged. There was a significant relationship between the change in left ventricular dimension at end-diastole and the change in ES. Conclusions: β-Blocker therapy could attenuate myocardial perfusion defects in some patients with DCM. The improvement in left ventricular function associated with β-blocker therapy may be related to the attenuation in myocardial perfusion defects.

Left Ventricular Dysfunction after Closure of Large Patent Ductus Arteriosus

Changes in left ventricular dimensions and performance were studied in 43 patients after transcatheter occlusion or surgical ligation of patent ductus arteriosus. The patients were assigned to 2 groups based on their ductal diameter: >/= 3.1 mm to group A (n = 27) and </= 3 mm to group B (n = 16). The mean age and weight of the groups were comparable. Before intervention, group A had a significantly larger mean left ventricular end-diastolic diameter than group B, while all patients had normal shortening fraction and ejection fraction. Within 1 month after intervention, left ventricular end-diastolic diameter showed a trend towards regression while shortening fraction and ejection fraction decreased significantly in group A. There were no significant changes in these parameters in group B. Between 1 and 6 months after intervention, left ventricular performance improved in most of the group A patients who were followed up. We conclude that closure of large ductus arteriosus in children leads to significant immediate deterioration of left ventricular performance, which appears to recover within a few months. Echocardiographic study before hospital discharge is recommended in these patients. Serious deterioration of ventricular performance after closure may warrant the use of angiotensin converting enzyme inhibitors.

DNA immunizations with M 2 muscarinic and β 1 adrenergic receptor coding plasmids impair cardiac function in mice

Autoimmune mediated myocardial damage is likely to be a pathogenic mechanism for acquired dilated cardiomyopathies. Evidence confirms that autoantibodies that bind to M 2 muscarinic (M 2AChR) and β 1 adrenergic receptors (β 1AR) are present in idiopathic dilated cardiomyopathy and Chagasic patients’ sera. To elucidate the role of these antibodies in cardiac functional impairment, we used a murine model immunized with plasmids encoding the M 2AChR or β 1AR via gene-gun bombardment. Anti-M 2AChR and β 1AR antibodies were detected over the course of 37 weeks. These antibodies were directed to the second extracellular loop (el2) of both receptors and the third intracellular loop (il3) of the M 2AChR. Peak antibody titers from weeks 2 to 5 against M 2AChR-el2 and β 1AR-el2 as well as elevated titers against M 2AChR-il3 were detected. Anti-M 2AChR-il3 and anti-β 1AR-el2 antibodies were predominant in IgG1 subclass immunoglobulins, suggesting a T-helper-2 biased lymphocyte response. Heart morphology and function was assessed by echocardiography over the course of 42 weeks. Data showed progressive decrease in left ventricular (LV) wall thickness and LV mass that was mostly evident for β 1AR-immunized mice albeit a small change in LV dimensions. Fractional shortening was altered and values of 41%, 37% and 48% were observed at week 42 for the M 2AChR, β 1AR and control groups respectively. In support of autonomic deregulation, a twofold increase in M 2AChR and a similar decrease in β 1AR density were observed in radioligand saturation assays for both experimental groups. Histological analysis revealed myofibril disarray and fibrosis, pointing towards remodeling as a consequence of the long-term presence of anti-receptor antibodies.

A chronic heart failure model by coronary artery ligation in the goat.

The availability of a reliable heart failure model in large animals is important. We report upon our efforts to develop a chronic heart failure model in seven goats using sequential ligation of the left anterior descending (LAD) coronary artery and its diagonal branch. After anesthesia and left thoracotomy, the LAD artery was ligated, and the diagonal vessel at the same level was ligated one hour later. Cardiac measurements were performed with a thermodilution catheter and by ultrasonography. Two months after the operation, the same measurements were made and animals were sacrificed for postmortem examinations of their hearts. Hemodynamic measurements, except cardiac output, showed no significant changes immediately after the coronary artery ligation. Echocardiographic measurements showed significant changes in the ejection fraction and fractional shortening without changes in left ventricular dimensions. Wall motion analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all animals immediately after coronary artery ligation. Five animals have undergone hemodynamic and ultrasonographic studies 2 months after coronary artery ligation. The results obtained from these animals showed significant increases in central venous pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary artery capillary wedge pressure, and a significant decrease in cardiac output. Increases in left ventricular dimensions and decreases in ejection fraction with fractional shortening in ultrasonographic studies were also observed. Pathologically, well-demarcated thin-walled anteroseptal infarcts, with chamber enlargement, were clearly seen with dilatation of the heart chambers in all specimens. Based on this study, we conclude that goats, like sheep, can provide a reliable model of chronic heart failure by coronary artery ligation and in view of the many advantages offered by goats, we believe that this animal model will be useful for cardiac experimentation.

Left ventricular systolic performance in failing heart improved acutely by left ventricular reshaping

Objective If the geometric distortion during dilated heart failure could be corrected, the tension on the myocytes would be decreased, thereby leading to an improvement in left ventricular systolic function. We tested the effects of the CardioClasp (CardioClasp Inc, Pine Brook, NJ), a left ventricular reshaping device, on the failing heart, and our empirical data were compared with computationally derived data. Methods Heart failure was induced by 4-week rapid cardiac pacing. At the terminal experiment, an isolated failing heart preparation (isovolumic contraction, n = 5) or an intact failing heart in vivo (n = 7) was used. The effects of the reshaping device on left ventricular performance were assessed by the slopes (Ees) of the left ventricular end-systolic pressure-volume relations, hemodynamics, and echocardiograph before and after placing the CardioClasp on the heart. The change in Ees as the result of left ventricular reshaping was also estimated from computed theoretical analysis and compared with empirical data. Results There was a significant change in left ventricular dimension after placing the CardioClasp on the heart. In isolated heart preparation, Ees significantly increased from 1.40 ± 0.44 mm Hg/mL to 2.42 ± 0.63 mm Hg/mL after placing the device on the heart but returned to the baseline level (1.46 ± 0.27 mm Hg) after removing it. Left ventricular developed pressure and left ventricular fractional area shortening were significantly increased as the result of left ventricular reshaping. Ees derived from computed theoretical analysis was highly correlated with confirming empirical data. Conclusions The CardioClasp can reshape the left ventricle and improve left ventricular systolic performance in failing hearts. 17,22