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Davinder S Jassal

Publications and source records attributed to Davinder S Jassal.

At least 19 recordsLinked to original sources

Cardiomyocyte-specific overexpression of nitric oxide synthase 3 prevents myocardial dysfunction in murine models of septic shock.

Myocardial dysfunction contributes to the high mortality of patients with endotoxemia. Although nitric oxide (NO) has been implicated in the pathogenesis of septic cardiovascular dysfunction, the role of myocardial NO synthase 3 (NOS3) remains incompletely defined. Here we show that mice with cardiomyocyte-specific NOS3 overexpression (NOS3TG) are protected from myocardial dysfunction and death associated with endotoxemia. Endotoxin induced more marked impairment of Ca(2+) transients and cellular contraction in wild-type than in NOS3TG cardiomyocytes, in part, because of greater total sarcoplasmic reticulum Ca(2+) load and myofilament sensitivity to Ca(2+) in the latter during endotoxemia. Endotoxin increased reactive oxygen species production in wild-type but not NOS3TG hearts, in part, because of increased xanthine oxidase activity. Inhibition of NOS by N(G)-nitro-l-arginine-methyl ester restored the ability of endotoxin to increase reactive oxygen species production and xanthine oxidase activity in NOS3TG hearts to the levels measured in endotoxin-challenged wild-type hearts. Allopurinol, a xanthine oxidase inhibitor, attenuated endotoxin-induced reactive oxygen species accumulation and myocardial dysfunction in wild-type mice. The protective effects of cardiomyocyte NOS3 on myocardial function and survival were further confirmed in a murine model of polymicrobial sepsis. These results suggest that increased myocardial NO levels attenuate endotoxin-induced reactive oxygen species production and increase total sarcoplasmic reticulum Ca(2+) load and myofilament sensitivity to Ca(2+), thereby reducing myocardial dysfunction and mortality in murine models of septic shock.

Actin Cytoskeleton↗

Comparison of multidetector computed tomography and two-dimensional transthoracic echocardiography for left ventricular assessment in patients with heart failure.

Along with coronary evaluation, 64-slice multidetector computed tomography (MDCT) permits comprehensive assessment of left ventricular (LV) anatomy and function; however, how it compares with 2-dimensional transthoracic echocardiography (TTE) in patients with heart failure (HF) is not known. In this study, we compared 25 patients with ejection fractions of <45% who underwent TTE and MDCT. The global ejection fraction by TTE versus MDCT was 36 +/- 8% versus 38 +/- 12% (r = 0.67, p = NS). The mean LV end-diastolic and end-systolic diameters by TTE and MDCT were 56 +/- 8 and 46 +/- 9 mm and 58 +/- 12 and 47 +/- 11 mm, respectively (r = 0.71 and 0.77, respectively, both p >0.20). The mean lateral and septal wall thicknesses by TTE and MDCT were 10 +/- 1.4 and 11 +/- 1.5 mm and 10 +/- 1.3 and 10 +/- 1.4 mm (r = 0.77 and 0.76, respectively, both p >0.20). The mean LV end-diastolic and end-systolic volumes and stroke volume by TTE and MDCT were 123 +/- 45, 78 +/- 31, and 44 +/- 21 ml and 140 +/- 58, 92 +/- 43, and 48 +/- 24 ml, respectively (r = 0.62, 0.67, and 0.60, respectively, all p >0.20). The regional wall motion assessment correlation was good between the 2 modalities (kappa = 0.61). The interobserver correlation between the 2 MDCT readers ranged from good (r = 0.72 for LV end-diastolic volume) to excellent (r = 0.84 for septal wall thickness). In conclusion, MDCT provides comparable results to TTE for LV structure and functional assessment among patients with HF.

Echocardiography↗

Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon.

BACKGROUND: Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. METHODS AND RESULTS: We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler-derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, > 60% of participants had increased cTnT > 99th percentile of normal (> 0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (> or = 0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P<0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r=-0.70, P<0.001) and inversely with training mileage (r=-0.71, P<0.001). Compared with athletes training > 45 miles/wk, athletes who trained < or = 35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16+/-5% versus 25+/-4%, P<0.001), myocyte injury (cTnT 0.09 versus < 0.01 ng/mL, P<0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P<0.001). CONCLUSIONS: Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Athletic Injuries↗

The impact of spontaneous echocardiographic contrast in patients with left atrial enlargement undergoing cardiac valvular surgery.

OBJECTIVE: The aim of this study was to evaluate the impact of either left atrial or aortic spontaneous echocardiographic contrast (SEC), as identified on intraoperative transesophageal echocardiography, on short-term morbidity and mortality in patients with left atrial enlargement undergoing cardiac valvular surgery. DESIGN: Retrospective and observational. SETTING: Single-center, university teaching hospital. PARTICIPANTS: The authors identified 197 patients (105 males and 92 females; mean age, 68 +/- 14 years) with left atrial enlargement who underwent surgical intervention for valvular heart disease from January 1, 2004 to January 1, 2005. MAIN RESULTS: Of the total population, 40 patients (20.3%) showed left atrial SEC, and 10 patients (5.1%) showed aortic SEC. On multivariate analysis, increasing left atrial size and the absence of mitral regurgitation were independent predictors for the presence of left atrial SEC. On multivariate analysis, the presence of atrial fibrillation and a dilated descending aorta were predictive of aortic SEC. Although the identification of left atrial SEC was an echocardiographic marker of an increased risk for thromboembolic events postoperatively, this finding did not hold true for the presence of aortic SEC. CONCLUSIONS: Intraoperative identification of left atrial dilatation or aortic dilatation is predictive of SEC in the left atrium or descending aorta, respectively. The identification of left atrial SEC is an echocardiographic marker of an increased risk for thromboembolic events in this high-risk population.

Academic Medical Centers↗

Sustained improvement in left ventricular diastolic function after alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

AIMS: Impaired diastolic function is responsible for many of the clinical features of hypertrophic cardiomyopathy. In patients with hypertrophic obstructive cardiomyopathy (HOCM) whose symptoms are refractory to medical therapy, alcohol septal ablation (ASA) reduces left ventricular (LV) outflow tract gradient, with short-term improvement in LV diastolic function. Little is known about the longer term impact of ASA on diastolic function. METHODS AND RESULTS: We evaluated LV diastolic function at baseline and 1- and 2-year follow-up after successful ASA. In 30 patients (58+/-15 years, 22 men) who underwent successful ASA, New York Heart Association class was lower at 1-year follow-up compared with baseline (3.0+/-0.5 to 1.5+/-0.7; P<0.0001). LV outflow tract gradient (76+/-37 to 19+/-12; P<0.0001), interventricular septal thickness (19+/-2 to 14+/-2; P<0.0001), and left atrial volume (26+/-5 to 20+/-4; P<0.0001) were decreased. Significant improvement in E-wave deceleration time, isovolumic relaxation time, early diastolic mitral lateral annular velocity (E'), mitral inflow propagation velocity (V(p)), ratio of transmitral early LV filling velocity (E) to early diastolic Doppler tissue imaging of the mitral annulus (E/E'), and E/V(p) were observed at 1 year following successful ASA. These changes persisted in the subset cohort (n=21) for whom 2-year data were available. CONCLUSION: Successful ASA for HOCM leads to significant and sustained improvement in echocardiographic measures of diastolic function, which may contribute to improved functional status after successful ASA.

Adult↗

Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury.

AIMS: Currently available non-invasive imaging methods frequently fail to detect alterations in left ventricular (LV) function despite histological evidence of injury. Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. METHODS AND RESULTS: TDI-derived peak endocardial systolic velocity (V(ENDO)) and strain rate (SR), as well as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. V(ENDO) and SR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both V(ENDO) and SR correlated with the decrease in dP/dt(MAX), and the change in V(ENDO) correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. CONCLUSION: In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction.

Animals↗

Mitral valve ring dehiscence with an aorta-left atrial fistula.

In an era with the increasing use of various imaging modalities including echocardiography, ventriculography and cardiac magnetic resonance (CMR) imaging, one must be aware of the limitations of each discipline. We report a case of an individual who presented with both a partial dehiscence of a mitral valve annuloplasty ring and an aorta-left atrium fistula following surgical management of infective endocarditis that was correctly identified using transesophageal echocardiographic imaging.

Aorta↗

Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumour suppression.

AIMS: The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has previously been shown to protect against DOX-induced cardiomyocyte injury in vitro. Here, we addressed whether iloprost is cardioprotective in vivo and whether it compromises the anti-tumour efficacy of DOX. METHODS AND RESULTS: Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6 mice. DOX treatment was commenced from when tumours became visible. Iloprost was administered from prior to DOX treatment until sacrifice. Echocardiography and invasive haemodynamic measurements were performed immediately before sacrifice. As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of which were attenuated by iloprost. Also, iloprost alone had no effect on tumor growth and indeed, did not alter the DOX-induced suppression of this growth. CONCLUSION: In a murine model, iloprost attenuated the acute cardiac injury and dysfunction induced by DOX therapy without compromising its chemotherapeutic effect.

Animals↗

Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury.

To learn whether nitric oxide (NO) inhalation can decrease myocardial ischemia-reperfusion (I/R) injury, we studied a murine model of myocardial infarction (MI). Anesthetized mice underwent left anterior descending coronary artery ligation for 30, 60, or 120 min followed by reperfusion. Mice breathed NO beginning 20 min before reperfusion and continuing thereafter for 24 h. MI size and area at risk were measured, and left ventricular (LV) function was evaluated using echocardiography and invasive hemodynamic measurements. Inhalation of 40 or 80 ppm, but not 20 ppm, NO decreased the ratio of MI size to area at risk. NO inhalation improved LV systolic function, as assessed by echocardiography 24 h after reperfusion, and systolic and diastolic function, as evaluated by hemodynamic measurements 72 h after reperfusion. Myocardial neutrophil infiltration was reduced in mice breathing NO, and neutrophil depletion prevented inhaled NO from reducing myocardial I/R injury. NO inhalation increased arterial nitrite levels but did not change myocardial cGMP levels. Breathing 40 or 80 ppm NO markedly and significantly decreased MI size and improved LV function after ischemia and reperfusion in mice. NO inhalation may represent a novel method to salvage myocardium at risk of I/R injury.

Administration, Inhalation↗

Surgical management of infective endocarditis: early predictors of short-term morbidity and mortality.

BACKGROUND: Infective endocarditis is a diagnostic and therapeutic challenge that ultimately requires surgical intervention in 20% of all cases. Early determinants of morbidity and mortality in this high risk population are not well described. METHODS: The aim of this study was to determine preoperative clinical, microbiological, electrocardiographic, and echocardiographic variables that predicted the need for permanent pacemaker implantation and in-hospital death in a surgical cohort of patients with active infective endocarditis. RESULTS: We identified 91 patients (61 males and 30 females, mean age 58 +/- 16 years) who underwent surgical intervention for active culture-positive infective endocarditis as defined by the Duke criteria. Native valve infective endocarditis was present in 78 (85.7%) and prosthetic valve endocarditis in 13 (14.3%) of cases. The aortic valve was infected in 61 (67.0%), the mitral in 35 (38.5%), and multiple valves in 8 patients (8.8%). The most common indication for surgical intervention was intractable heart failure. Twenty-two patients (24.2%) required pacemakers, while there were 14 (15.4%) in-hospital deaths. In age-adjusted and gender-adjusted analyses, the presence of left bundle branch block on preoperative electrocardiogram (ECG) and presence of depressed left ventricular systolic function (ejection fraction [EF] < 50%) predicted the need for a permanent pacemaker implantation, while the presence of depressed left ventricular function predicted in-hospital mortality. CONCLUSIONS: Preoperative ECG findings of left bundle branch block and reduced left ventricular function may allow for early risk stratification of this high risk population.

Adult↗

Myocardial adaptation to short-term high-intensity exercise in highly trained athletes.

We aimed to clarify the myocardial adaptation to short-term high-intensity exercise among trained athletes. We screened 17 participants in the 2004 World Indoor Rowing Championships before and after a 2000-m sprint. Echocardiography included standard measurements and tissue Doppler-derived strain (epsilon), strain rate, and 2-dimensionally derived speckle-tracking imaging for left ventricular (LV) torsion. LV volumes and ejection fraction were unchanged after exercise. There was a reduction in early and an increase in late diastolic filling velocities and a decrease in the flow propagation velocity. Annular systolic velocities, slope of the systolic acceleration, septal and lateral epsilon, and speckle tracking-derived torsion were increased. The increased LV torsion was a result of increased basal and apical rotation. Right ventricular apical epsilon decreased. In conclusion, maximal intensity short-duration exercise was associated with attenuation of LV diastolic function, augmentation of LV systolic function, and a reduction in apical right ventricular contractility.

Adaptation, Physiological↗

Delayed enhancement cardiac MR imaging in noncompaction of left ventricular myocardium.

A 49-year-old female with a history of paroxysmal atrial fibrillation, presented with worsening dyspnea on minimal exertion. During the follow-up period, transthoracic echocardiography and cardiac magnetic resonance imaging (CMR) were consistent with the diagnosis of noncompaction of the left ventricle. Delayed-enhancement CMR demonstrated hyperenhancement of the prominent trabeculations located at the mid and apical portions of the left ventricle, suggesting areas of fibrosis. Although previous cases of left ventricular noncompaction diagnosed with CMR have been described in the literature, this is the first case to describe the utility of delayed-enhancement imaging in the pathohistological confirmation of myocardial fibrosis and scarring in the hypertrabeculated myocardium.

Contrast Media↗

A continuous murmur.

A 61-year-old male with a history of a mechanical Bjork-Shiley aortic valve replacement in 1977 and repair of an ascending aortic root dissection in 1993, presented with a 2-week history of fatigue and exertional dyspnea. Echocardiography confirmed the presence of an aortic pseudoaneurysm with a fistulous connection between the aorta and right atrium, which subsequently underwent successful repair. Although there have been several cases describing the development of an aortic pseudoaneurysm after aortic dissection repair, our case is the first to describe an aorta-atrial fistula as a long-term complication of a previous aortic dissection repair.

Aortic Dissection↗

Surgical management of infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: Although retrospective reviews evaluating the surgical management of infective endocarditis (IE) have been conducted in Europe and in the USA, few data exist regarding management of the condition in Canada. The study aim was to evaluate the surgical management of individuals with culture-positive active IE at a Canadian tertiary care university hospital. METHODS: A retrospective analysis was performed of 74 patients (53 males, 21 females; mean age 56 +/- 14 years) with a preoperative diagnosis of acute IE between 1995 and 2003 at the Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia. Preoperative clinical variables evaluated included the Duke criteria for endocarditis, correlation between preoperative echocardiographic imaging and intraoperative findings, and postoperative morbidity and mortality. RESULTS: Native valve endocarditis (NVE) was present in 60 patients, and prosthetic valve endocarditis (PVE) in 14. All patients met the Duke criteria for endocarditis. Correlation between preoperative transesophageal echocardiography (TEE) and surgical findings (vegetations 63%, abscesses 96%, leaflet perforation 100%) was superior when compared with preoperative transthoracic echocardiography (vegetations 43%, abscesses 75%, leaflet perforation 89%). There were low rates of postoperative morbidity (reoperation 8%, stroke 5%). Overall in-hospital mortality was 14% (seven NVE, 12%; three PVE, 21%). CONCLUSION: Herein is presented the largest and most current case series of patients treated surgically for active IE. The results demonstrate excellent agreement between preoperative TEE and intraoperative surgical findings in the current era of surgical management of this condition.

Adult↗

Infective endocarditis in the era of intracardiac devices: an echocardiographic perspective.

Although the role of echocardiography is well established in the management of native valve and prosthetic valve endocarditis, the recent introduction of intracardiac devices, including pacemakers, implantable defibrillators, closure devices, and ventricular assist devices, has expanded its utility. Echocardiography permits the direct imaging of valvular vegetations, and it allows for the identification of structural complications of endocarditis. It is useful for characterizing the hemodynamic consequences of the infection. It can also provide prognostic information concerning risk of embolization and/or need for cardiac surgery. This article reviews the roles of transthoracic echocardiography and transesophageal echocardiography in the evaluation of patients with native valve endocarditis, prosthetic valve endocarditis, and infections involving a variety of nonvalvular cardiovascular devices.

Clinical Trials as Topic↗