Effect of early administration of atropine on paradoxic sinus deceleration during dobutamine stress echocardiography.
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Adult↗
Biomedical subjects
Jamshid Shirani
Publications and source records attributed to Jamshid Shirani.
Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype.
The caveolin gene family consists of caveolins 1, 2, and 3. Caveolins 1 and 2 are co-expressed in many cell types, such as endothelial cells, fibroblasts, smooth muscle cells and adipocytes, where they form a heteroligomeric complex. In contrast, the expression of caveolin-3 is muscle-specific. Thus, the expression of caveolin-1 is required for caveolae formation in non-muscle cells, while the expression of caveolin-3 drives caveolae formation in striated muscle cell types (cardiac and skeletal). To create a truly caveolae-deficient mouse, we interbred Cav-1 null mice and Cav-3 null mice to generate Cav-1/Cav-3 double-knockout (Cav-1/3 dKO) mice. Here, we report that Cav-1/3 dKO mice are viable and fertile, despite the fact that they lack morphologically identifiable caveolae in endothelia, adipocytes, smooth muscle cells, skeletal muscle fibers, and cardiac myocytes. We also show that these mice are deficient in all three caveolin gene products, as caveolin-2 is unstable in the absence of caveolin-1. Interestingly, Cav-1/3 dKO mice develop a severe cardiomyopathy. At 2 months of age, analysis of Cav-1/3 dKO hearts via gated magnetic resonance imaging reveals a dramatic increase in left ventricular wall thickness, as compared with Cav-1-KO, Cav-3 KO, and wild-type mice. Further functional analysis of Cav-1/3 dKO hearts via transthoracic echocardiography demonstrates hypertrophy and dilation of the left ventricle, with a significant decrease in fractional shortening. As predicted, Northern analysis of RNA derived from the left ventricle of Cav-1/3 dKO mice shows a dramatic up-regulation of the atrial natriuretic factor message, a well-established biochemical marker of cardiac hypertrophy. Finally, histological analysis of Cav-1/3 dKO hearts reveals hypertrophy, disorganization, and degeneration of the cardiac myocytes, as well as chronic interstitial fibrosis and inflammation. Thus, dual ablation of both Cav-1 and Cav-3 genes in mice leads to a pleiotropic defect in caveolae formation and severe cardiomyopathy.
Adipocytes↗
Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain): an echocardiographic study.
Verapamil has been shown to attenuate the extent of myocardial injury in murine models of chronic Trypanosoma cruzi infection. Infected mice treated with verapamil have significantly lower myocardial expression of inducible nitric oxide synthase and cytokines and substantially less inflammatory infiltrate and myocyte necrosis at necropsy. In the present study, we examined the cardiac structural and functional correlates of verapamil treatment in CD1 mice infected with the Brazil strain of T. cruzi using serial transthoracic echocardiography. There were four groups: uninfected- untreated control, uninfected-verapamil-treated, infected-untreated control, and infected-verapamil-treated. Verapamil was given in drinking water (1 gm/l) continuously from the day of infection for a total of 120 days. Mice were evaluated at baseline, 40 and 150 days p.i. Mice in the untreated-infected group compared with the mice in the infected-verapamil-treated group showed thinning of the left ventricular wall (0.84 +/- 0.02-vs-0.92 +/- 0.04, P<0.05 mm), increase in the left ventricular end-diastolic diameter (3.27 +/- 0.15-vs-2.74 +/- 0.05 mm, P<0.05) and reduction in percent fractional shortening (37 +/- 2-vs-53 +/- 4%, P<0.05). No differences in these parameters were noted among mice in the uninfected-untreated and uninfected-verapamil-treated groups. Furthermore, right ventricular dilation was more severe in mice from the infected-untreated group as compared with those in the infected- verapamil-treated group (visual grade 1.9 +/- 0.4-vs-1.0 +/- 0.2, P<0.05). At necropsy, the extent of myocardial injury, as determined histologically, was significantly greater in the infected-untreated mice. These data provide cardiac structural and functional correlates for the previously observed cardioprotective effects of verapamil in chronic chagasic cardiomyopathy.
Animals↗
Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease.
Chagas' disease is an important cause of cardiomyopathy. Endothelin-1, a vasoactive peptide has been implicated in the pathogenesis of chagasic cardiomyopathy. C57BL/6 x 129sv and CD1 mice were thus, infected with trypomastigotes of Trypanosoma cruzi (Brazil strain) and these infected mice were compared with infected mice treated with phosphoramidon. This compound inhibits endothelin-converting enzyme and neutral endopeptidases and does not affect the growth of the parasite in culture. Phosphoramidon was given in a dose of 10mg/kg for the initial 15 days post-infection None of the C57Bl/6 x 129sv mice died as a result of infection. However, there was marked myocardial inflammation and fibrosis in infected, untreated mice. The hearts of the infected, phosphoramidon-treated mice showed significantly less pathology. Cardiac magnetic resonance imaging of infected mice revealed right ventricular dilation that was less severe in those treated with phosphoramidon. Phosphoramidon-treated CD1 mice survived the acute infection. Transthoracic echocardiography demonstrated left ventricular dilation and reduced percent fractional shortening and relative wall thickness. These alterations were also attenuated as a result of phosphoramidon treatment. These data suggest that endothelin-1 contributes to the pathogenesis of chagasic cardiomyopathy and interventions that inhibit the synthesis of endothelin-1 and/or neutral endopeptidase might have a protective effect on myocardial structure and function in murine Chagas' disease.
Animals↗
Role of cardiac myocyte-derived endothelin-1 in chagasic cardiomyopathy: molecular genetic evidence.
Trypanosoma cruzi is the aetiological agent of Chagas' disease, an important cause of chronic cardiomyopathy. We previously demonstrated a role for endothelin-1 (ET-1) in the pathogenesis of chagasic heart disease. In order to explore further the significance of ET-1 in chagasic heart disease, we infected ET-1 (flox/flox); alpha-MHC-Cre(+) (ET-1KO) mice, in which the ET-1 gene has been deleted from cardiac myocytes, with 10(4) T. cruzi (Brazil strain) trypomastigotes. As controls, we used ET-1 (flox/flox);Cre(-) (FLOX) and C57BL/6x129sv (WT) mice. All mice survived and were evaluated 150-160 days post-infection. Cardiac magnetic resonance imaging revealed a significant increase in right ventricular internal diameter in all infected animals except ET-1KO mice (control WT, 1.6+/-0.10 mm; infected WT, 2.8+/-0.15 mm; control FLOX, 2.04+/-0.02 mm; infected FLOX, 2.76+/-0.28 mm). There was no significant difference in right ventricular internal diameter between infected and uninfected ET-1KO mice (control ET-1KO, 1.83+/-0.11 mm; infected ET-1KO, 2.14+/-0.20 mm). In another series of experiments, transthoracic echocardiography was performed on uninfected as well as infected ET-1KO mice, and uninfected and infected FLOX mice. Both infected groups had an increased left ventricular end-diastolic diameter and reduced fractional shortening. In addition, relative wall thickness was also decreased in infected animals. However, the magnitude of these changes was less in infected ET-1KO mice. These data provide further support for a role for ET-1 in the pathogenesis of chronic chagasic heart disease, and indicate that cardiac myocytes are an important source of ET-1 in this disease.
Animals↗
Phosphoramidon treatment improves the consequences of chagasic heart disease in mice.
Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is an important cause of cardiomyopathy. Microvascular spasm and matrix dissolution, modulated by endothelin-1 (ET-1), is implicated in the pathogenesis of chagasic heart disease. To further elucidate the role of ET-1 in murine chagasic heart disease, C57BL/6 x 129sv mice were infected with T. cruzi (10(3) trypomastigotes of the Brazil strain). These mice are resistant to death during the acute phase but progress to chronic cardiomyopathy. Infected mice were compared with infected mice treated with phosphoramidon, a non-specific metalloprotease inhibitor that is also a potent inhibitor of endothelin-converting enzyme, at a dose of 10 mg/kg. Mice were treated with phosphoramidon for the initial 15 days post infection (PI). All mice were evaluated 200 days PI. Examination of infected, untreated mice revealed marked inflammation, vasculitis and fibrosis. The hearts of infected treated mice had significantly less pathology. Cardiac magnetic resonance imaging (MRI) revealed that right ventricular internal diameter (RVID) was significantly greater (P<0.05) in the infected untreated group (2.9+/-0.22 mm) as compared with the infected treated group (1.73+/-0.35 mm). In another experiment phosphoramidon treatment was also tested in CD1 mice, which have a high mortality during the acute phase of infection with 5 x 10(4) trypomastigotes of the Brazil strain. One group of CD1 mice was untreated while the other group received phosphoramidon for the initial 15 days PI. The mortality rate in untreated mice was 70% by day 35 PI, while all treated infected mice lived. The parasitemia in both groups was similar. The cardiac pathology was more severe in untreated mice. MRI revealed the RVID to be significantly greater in the untreated infected group as compared with the phosphoramidon-treated infected mice (2.74+/-0.03 mm versus 1.64+/-0.4 mm P<0.05). Transthoracic echocardiography revealed that the percentage fractional shortening was reduced in infected CD1 mice but not in those infected mice treated with phosphoramidon. There was no effect of phosphoramidon in uninfected mice. Phosphoramidon (100 microg/ml) had no effect on parasites in vitro. These data are consistent with the hypothesis that ET-1 contributes to the pathogenesis of murine chagasic cardiomyopathy and suggests that interventions targeting ET-1 would improve the outcome in chagasic heart disease.
Animals↗
Cross-sectional multiplane transesophageal echocardiographic measurements: comparison with standard transthoracic values obtained in the same setting.
BACKGROUND: Several algorithms developed for cost-effective use of transesophageal echocardiography (TEE) propose elimination of "screening" transthoracic echocardiographic (TTE) studies. Cross-sectional measurements obtained by TTE (left atrial diameter [LAD], left ventricular internal dimensions in diastole and systole [LVIDd, LVIDs], septal and posterior wall thickness in diastole [VSTd, PWTd], LV end-diastolic and end-systolic volumes [LVEDV and LVESV], and LV ejection fraction [LVEF]) have not been standardized for TEE. METHODS: Forty-six patients (age 27 to 85 years, 60 +/- 13 years, 25 [54%] women) underwent TEE and TTE studies. TTE was performed while the TEE probe was in place and the patient was still sedated. Standard TTE measurements were compared with corresponding TEE values obtained from mid-esophageal and transgastric views. RESULTS: Standard TTE measurements compared favorably with those obtained by TEE at the mid-esophageal three-chamber view for LAD (3.9 +/- 0.6 cm vs 4.0 +/- 0.7 cm, P = NS) and at the transgastric long-axis view for LVIDd (4.6 +/- 0.8 cm vs 4.7 +/- 0.8 cm, P = NS), LVIDs (3.1 +/- 0.9 cm vs 3.1 +/- 0.9 cm, P = NS), and VSTd (0.95 +/- 0.18 cm vs 0.98 +/- 0.19 cm, P = NS). Biplane TTE and TEE measurements of LVEDV (106 +/- 35 ml vs 112 +/- 38 ml, P = NS), LVESV (37 +/- 23 ml vs 37 +/- 25 ml, P = NS), and LVEF (67 +/- 14% vs 69 +/- 14%, P = NS) also correlated closely. The negative predictive values of TEE measurements for excluding abnormal LAD, LVIDd, VSTd, PWTd, and LVEF as defined by TTE were 83%, 94%, 95%, 97%, and 97%, respectively. CONCLUSION: Cross-sectional TEE measurements as obtained in this study are equivalent to standard TTE dimensions and provide reliable information that may facilitate interpretation of TEE studies in the absence of TTE information.
Adult↗
Assessment of Left Atrial Appendage Structure and Function by Transesophageal Echocardiography: A Review.
This article examines the transesophageal echocardiographic assessment of the left atrial appendage anatomy and function in individuals without significant structural heart disease and in those with atrial fibrillation with or without cardioembolism or mitral valve stenosis. We also summarize the available data in the usefulness of transesophageal echocardiographic studies in patients undergoing cardioversion for atrial fibrillation and percutaneous balloon valvuloplasty for mitral stenosis. Also, potential limitations and ongoing developments in the use of transesophageal echocardiography in the assessment of the left atrial appendage are outlined, and recommendations are given for the uniform reporting of quantitative data.
Journal Article↗
Mitral Stenosis, Sinus Venosus Atrial Septal Defect, and Partial Anomalous Pulmonary Venous Return: Diagnosis by Multiplane Transesophageal Echocardiography.
We describe a 42-year-old man with rheumatic mitral stenosis, sinus venosus atrial septal defect, and anomalous drainage of the right upper pulmonary vein to the superior vena cava. Transthoracic echocardiography (TTE) failed to identify the atrial septal defect and the partial anomalous pulmonary venous return. Transesophageal echocardiography (TEE), using a multiplane probe, was useful in delineating the abnormalities. To our knowledge, this is the first reported patient with rheumatic mitral stenosis and sinus venosus defect. (ECHOCARDIOGRAPHY, Volume 13, November 1996)
Journal Article↗
Use of pharmaceuticals in noninvasive cardiovascular diagnosis.
A number of pharmaceuticals are employed as diagnostic agents for cardiovascular diseases. Four groups of agents are reviewed here: 1) vasoactive substances employed as adjuncts to physical maneuvers in diagnosis of structural heart disease; 2) vasodilators used to produce heterogeneity of coronary flow; 3) sympathomimetic agents simulating the effects of exercise on the heart for the purpose of detection of coronary artery stenosis; and 4) ultrasonic contrast agents used to enhance myocardial imaging for the assessment of segmental wall motion. In the first group are amyl nitrate, a vasodilator, and methoxamine and phenylephrine, both vasopressors. The vasodilators of the second group are dipyridamole and adenosine. When combined with scintigraphic perfusion imaging or with echocardiographic assessment of segmental wall motion, these agents can detect single- or multiple-vessel coronary artery disease with sensitivity and specificity comparable to submaximal exercise. They are especially useful for preoperative risk assessment before noncardiac surgery. The sympathomimetic agents of the third group, dobutamine and arbutamine, increase myocardial contractility and heart rate, and dilate the peripheral vasculature. As with the vasodilators, when combined with nuclear or echocardiographic techniques they are equivalent to exercise in detection of coronary disease. They are especially useful in patients with bronchospastic disease and for assessment of myocardial viability. Agents from groups 2 and 3 have acceptable side-effect and safety profiles. The last group reviewed includes echocardiographic contrast agents that, in this investigative setting, are employed to enhance detection of segmental wall motion when used with agents from groups 2 and 3.
Cardiovascular Diseases↗