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Biomedical subjects

J D Thomas

Publications and source records attributed to J D Thomas.

At least 55 records · Page 3Linked to original sources

Respiratory variation of mitral and pulmonary venous Doppler flow velocities in constrictive pericarditis before and after pericardiectomy.

The objective of this study was to determine whether Doppler echocardiography is useful in assessing the effects of pericardiectomy in patients with constrictive pericarditis by studying the postoperative change in the respiratory variation of mitral inflow and pulmonary venous Doppler flows. The study population consisted of 35 cases with surgically proven constrictive pericarditis. Thirty-five patients had preoperative Doppler echocardiography, whereas 4 patients died of non-cardiac causes and 1 patient had a heart transplant before follow-up. Postoperative studies were performed at a mean of 1081 +/- 84 days (range 120-2700 days) after pericardiectomy. The mean (+/- SD) respiratory variation changed after surgery from a baseline value of 17% +/- 14% to 8% +/- 8% for peak mitral E velocity (P <.01); from 25% +/- 18% to 7% +/- 13% (P <.001) for pulmonary venous (PV) peak diastolic flow velocity, and from 21% +/- 13% to 11% +/- 13% (P =.009) for PV peak systolic flow velocity. The 23 patients who became asymptomatic after surgery had a significantly lower mean mitral and PV respiratory variation than the 7 patients who were NYHA class II (4% +/- 4% and 6% +/- 4% vs 21% +/- 6% and 19% +/- 10%, respectively, P <.0001 for both). Pulsed Doppler echocardiographic assessment of respiratory variation is useful for evaluating the outcome of pericardiectomy.

Aged↗

Prediction of coronary artery disease in patients undergoing operations for mitral valve degeneration.

OBJECTIVES: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. METHODS: A total of 722 patients (67% men; age, 61 +/- 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (< or =5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. CONCLUSION: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided.

Algorithms↗

Device-based change in left ventricular shape: a new concept for the treatment of dilated cardiomyopathy.

OBJECTIVE: We tested a unique new device, the Myosplint device (Myocor, Inc, Maple Grove, Minn), which is designed to change left ventricular shape, reduce left ventricular wall stress, and improve left ventricular systolic function. METHODS: Heart failure was induced in 15 dogs over 27 days by rapid pacing (230 beats/min). Seven animals underwent sham surgery, and 8 animals received 3 transventricular Myosplint devices each. Myosplint devices were tightened to create a symmetric bilobular left ventricular shape and were adjusted to produce a calculated 20% reduction in wall stress. Hemodynamic, 2-dimensional, and 3-dimensional echocardiographic studies were recorded at baseline, immediately after Myosplint placement (acute change), and at 1 month after both groups had a reduced rate (190 beats/min) of pacing designed to maintain heart failure. RESULTS: The Myosplint group had significant sustained improvements in left ventricular ejection fraction from baseline, to the acute change, to 1 month (19% +/- 5%; 36% +/- 8%; 39% +/- 13%) and reductions of left ventricular end-systolic volumes (73 +/- 9 mL; 34 +/- 5 mL; 42 +/- 12 mL) and end-systolic wall stress by 39% (341 +/- 68 10(3) dynes x cm(- 2) to 206 +/- 28 10(3) dynes x cm(-2)) acutely and 31% (372 +/- 83 10(3) dynes x cm(-2) to 250 +/- 40 10(3) dynes x cm(-2)) at 1 month. There were no significant changes in mitral regurgitation. CONCLUSION: Application of a Myosplint device to a dilated impaired left ventricle resulted in reduced wall stress and improved left ventricular systolic function that was sustained at 1 month. Device-based shape change is a promising new opportunity to treat patients with dilated cardiomyopathy.

Animals↗

Fetal alcohol effects: mechanisms and treatment.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Edward P. Riley. The presentations were (1) Does alcohol withdrawal contribute to fetal alcohol effects? by Jennifer D. Thomas and Edward P. Riley; (2) Brain damage and neuroplasticity in an animal model of binge alcohol exposure during the "third trimester equivalent," by Charles R. Goodlett, Anna Y. Klintsova, and William T. Greenough; (3) Ganglioside GM1 reduces fetal alcohol effects, by Basalingappa L. Hungund; and (4) Fetal alcohol exposure alters the wiring of serotonin system at mid-gestation, by F. Zhou, Y. Sari, Charles Goodlett, T. Powrozek, and Ting-Kai Li.

Animals↗

Assessment of internal mammary artery and saphenous vein graft patency and flow reserve using transthoracic Doppler echocardiography.

OBJECTIVE: To investigate transthoracic Doppler echocardiography in the identification of coronary artery bypass graft (CABG) flow for assessing graft patency. DESIGN: The initial study group comprised 45 consecutive patients with previous CABG undergoing elective cardiac catheterisation for recurrent ischaemia. The Doppler variables best correlated with angiographic graft patency were then tested prospectively in a further 84 patients (test group). SETTING: Three tertiary referral centres. INTERVENTIONS: Flow velocities in grafts were recorded at rest and during hyperaemia induced by dipyridamole (0.56 mg/kg/4 min), under the guidance of transthoracic colour Doppler flow mapping. Findings on transthoracic Doppler were compared with angiography. MAIN OUTCOME MEASURES: Feasibility of identifying open grafts by Doppler and diagnostic accuracy for Doppler detection of significant (>/= 70%) graft stenosis. RESULTS: In the test group the identification rate for mammary artery grafts was 100%, for saphenous vein grafts to left anterior descending coronary artery 91%, for vein grafts to right coronary artery 96%, and for vein grafts to circumflex artery 90%. Coronary flow reserve (the ratio between peak diastolic velocity under hyperaemia and at baseline) of < 1.9 (95% confidence interval 1.83 to 2.08) had 100% sensitivity, 98% specificity, 87.5% positive predictive value, and 100% negative predictive value for mammary artery graft stenosis. Coronary flow reserve of < 1.6 (95% CI 1.51 to 1.73) had 91% sensitivity, 87% specificity, 85.4% positive predictive value, and 92.3% negative predictive value for significant vein graft stenosis. CONCLUSIONS: Transthoracic Doppler can provide non-invasive assessment of CABG patency.

Analysis of Variance↗

Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans.

Shortened early transmitral deceleration times (E(DT)) have been qualitatively associated with increased filling pressure and reduced survival in patients with cardiac disease and increased left ventricular operating stiffness (K(LV)). An equation relating K(LV) quantitatively to E(DT) has previously been described in a canine model but not in humans. During several varying hemodynamic conditions, we studied 18 patients undergoing open-heart surgery. Transesophageal echocardiographic two-dimensional volumes and Doppler flows were combined with high-fidelity left atrial (LA) and left ventricular (LV) pressures to determine K(LV). From digitized Doppler recordings, E(DT) was measured and compared against changes in LV and LA diastolic volumes and pressures. E(DT) (180 +/- 39 ms) was inversely associated with LV end-diastolic pressures (r = -0.56, P = 0.004) and net atrioventricular stiffness (r = -0.55, P = 0.006) but had its strongest association with K(LV) (r = -0.81, P < 0.001). K(LV) was predicted assuming a nonrestrictive orifice (K(nonrest)) from E(DT) as K(nonrest) = (0.07/E(DT))(2) with K(LV) = 1.01 K(nonrest) - 0.02; r = 0.86, P < 0.001, DeltaK (K(nonrest) - K(LV)) = 0.02 +/- 0.06 mm Hg/ml. In adults with cardiac disease, E(DT) provides an accurate estimate of LV operating stiffness and supports its application as a practical noninvasive index in the evaluation of diastolic function.

Aged↗

Mitral inertance in humans: critical factor in Doppler estimation of transvalvular pressure gradients.

The pressure-velocity relationship across the normal mitral valve is approximated by the Bernoulli equation DeltaP = 1/2 rhoDeltav(2) + M. dv/dt, where DeltaP is the atrioventricular pressure difference, rho is blood density, v is transmitral flow velocity, and M is mitral inertance. Although M is indispensable in assessing transvalvular pressure differences from transmitral flow, this term is poorly understood. We measured intraoperative high-fidelity left atrial and ventricular pressures and simultaneous transmitral flow velocities by using transesophageal echocardiography in 100 beats (8 patients). We computed mean mitral inertance (M) by M = integral((DeltaP)-(1/2 x rho v(2))dt/integral(dv/dt)dt and we assessed the effect of the inertial term on the transmitral pressure-flow relation. ranged from 1.03 to 5.96 g/cm(2) (mean = 3.82 +/- 1.22 g/cm(2)). DeltaP calculated from the simplified Bernoulli equation (DeltaP = 1/2. rhov(2)) lagged behind (44 +/- 11 ms) and underestimated the actual peak pressures (2.3 +/- 1.1 mmHg). correlated with left ventricular systolic pressure (r = -0.68, P < 0.0001) and transmitral pressure gradients (r = 0.65, P < 0.0001). Because mitral inertance causes the velocity to lag significantly behind the actual pressure gradient, it needs to be considered when assessing diastolic filling and the pressure difference across normal mitral valves.

Adult↗

Estimation of diastolic intraventricular pressure gradients by Doppler M-mode echocardiography.

Previous studies have shown that small intraventricular pressure gradients (IVPG) are important for efficient filling of the left ventricle (LV) and as a sensitive marker for ischemia. Unfortunately, there has previously been no way of measuring these noninvasively, severely limiting their research and clinical utility. Color Doppler M-mode (CMM) echocardiography provides a spatiotemporal velocity distribution along the inflow tract throughout diastole, which we hypothesized would allow direct estimation of IVPG by using the Euler equation. Digital CMM images, obtained simultaneously with intracardiac pressure waveforms in six dogs, were processed by numerical differentiation for the Euler equation, then integrated to estimate IVPG and the total (left atrial to left ventricular apex) pressure drop. CMM-derived estimates agreed well with invasive measurements (IVPG: y = 0.87x + 0.22, r = 0.96, P < 0.001, standard error of the estimate = 0.35 mmHg). Quantitative processing of CMM data allows accurate estimation of IVPG and tracking of changes induced by beta-adrenergic stimulation. This novel approach provides unique information on LV filling dynamics in an entirely noninvasive way that has previously not been available for assessment of diastolic filling and function.

Animals↗

Assessment of the time constant of relaxation: insights from simulations and hemodynamic measurements.

The objective of this study was to use high-fidelity animal data and numerical simulations to gain more insight into the reliability of the estimated relaxation constant derived from left ventricular pressure decays, assuming a monoexponential model with either a fixed zero or free moving pressure asymptote. Comparison of the experimental data with the results of the simulations demonstrated a trade off between the fixed zero and the free moving asymptote approach. The latter method more closely fits the pressure curves and has the advantage of producing an extra coefficient with potential diagnostic information. On the other hand, this method suffers from larger standard errors on the estimated coefficients. The method with fixed zero asymptote produces values of the time constant of isovolumetric relaxation (tau) within a narrow confidence interval. However, if the pressure curve is actually decaying to a nonzero pressure asymptote, this method results in an inferior fit of the pressure curve and a biased estimation of tau.

Animals↗

Assessment of LV systolic function in atrial fibrillation using an index of preceding cardiac cycles.

The clinical assessment of left ventricular (LV) systolic function during atrial fibrillation (AF) is unreliable and difficult because of beat-to-beat variability. We evaluated an index for the estimation of LV systolic function in AF that is based on the relationship between the preceding (R-R1) and prepreceding (R-R2) R-R intervals. LV Doppler stroke volume (SV), ejection fraction (EF), peak aortic flow rate (AoF) and the maximum value of the first derivative of the LV pressure curve (dP/dt(max)) were evaluated in 13 healthy open-chest dogs during triggered AF. All parameters showed a significantly strong positive linear relationship with the ratio of R-R1/R-R2 (r = 0.65, 0.74, 0.75, and 0.70 for SV, EF, AoF, and dP/dt(max), respectively). The calculated value of LV systolic parameters at R-R1/R-R2 = 1 in the linear regression line showed a good relationship and an agreement with the measured average value of the parameter over all cardiac cycles (SV, 12.1 vs. 12.8 ml; EF, 49.6 vs. 51.2%; AoF, 1.37 vs. 1.48 l/min; and dP/dt(max), 2,323 vs. 2,454 mmHg/s). Using the LV systolic parameters estimated at R-R1/R-R2 = 1 in the linear regression line allows the LV contractile function to be accurately and reproducibly evaluated during AF and obviates the less-reliable process of averaging multiple cardiac cycles.

Animals↗

Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload.

Myocardial tissue Doppler echocardiography (TDE) has been proposed as a tool for the assessment of diastolic function. Controversy exists regarding whether TDE measurements are influenced by preload. In this study, left ventricular volume and high-fidelity pressures were obtained in eight closed-chest dogs during intermittent caval occlusion. The time constant of isovolumic ventricular relaxation (tau) was altered with varying doses of dobutamine and esmolol. Peak early diastolic myocardial (E(m)) and transmitral (E) velocities were measured before and after preload reduction. The relative effects of changes in preload and relaxation were determined for E(m) and compared with their effects on E. The following results were observed: caval occlusion significantly decreased E (DeltaE = 16.4 +/- 3.3 cm/s, 36.6 +/- 13.7%, P < 0.01) and E(m) (DeltaE(m) = 1. 3 +/- 0.4 cm/s, 32.5 +/- 26.1%, P < 0.01) under baseline conditions. However, preload reduction was similar for E under all lusitropic conditions (P = not significant), but these effects on E(m) decreased with worsening relaxation. At tau < 50 ms, changes in E(m) with preload reduction were significantly greater (DeltaE(m) = 2.8 +/- 0.6 cm/s) than at tau = 50-65 ms (DeltaE(m) = 1.2 +/- 0.2 cm/s) and at tau >65 ms (DeltaE(m) = 0.5 +/- 0.1 cm/s, P < 0.05). We concluded that TDE E(m) is preload dependent. However, this effect decreases with worsening relaxation.

Animals↗

A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p11.

Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2 diabetes revealed linkage to a previously unreported susceptibility locus on chromosome 18p11. This result improved with stringent subphenotyping using age- and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele sharing 0.6654) at a point between markers D18S976 and D18S391 when the most obese 20% of the sample was analyzed. Several genes on chromosome 18 have been suggested as metabolic disease candidates, but none of these colocalize with our linkage result. We conclude that our results provide support for the presence of a currently uncharacterized gene on chromosome 18p, certain alleles of which confer increased susceptibility to type 2 diabetes in conjunction with obesity. We additionally observed moderate evidence for linkage to chromosome 1, near marker D1S3462; chromosome 4, near marker D4S2361; chromosome 5, near marker D5S1505; and chromosome 17, near marker D17S1301.

Adult↗

Effect of cardiac output on mitral valve area in patients with mitral stenosis: validation and pitfalls of the pressure half-time method.

BACKGROUND AND AIM OF THE STUDY: The non-invasive evaluation of mitral valve area is often used in the assessment of patients with mitral stenosis. The pressure half-time method is commonly used to calculate valve area, but is inaccurate in many clinical scenarios. We sought to quantify the effects of changing cardiac output on the accuracy of mitral valve area determination. METHODS: Thirteen patients with mitral stenosis underwent routine stress echocardiography with resting and peak exercise results compared. A previously described and clinically validated mathematical model of the cardiovascular system was used to validate the clinical results. Seven different loading conditions for each of four different stenotic valve areas were modeled. RESULTS: In patients, with increasing cardiac output, pressure half-time decreased (-30.6+/-35.3 ms/l/min) and calculated valve area increased by 0.25+/-0.30 cm2/l/min. By continuity, it appeared that approximately half of this increase was due to actual valve orifice stretching, the remainder reflecting fundamental changes in the relationship between half-time and valve area. Mathematical modeling resulted in similar changes in pressure half-time and calculated valve area (0.06 to 0.12 cm2/l/min, p = 0.20 versus clinical results). CONCLUSION: Changes in cardiac output result in predictable changes in pressure half-time, and should be considered when performing serial examinations in patients with mitral stenosis.

Adult↗

[Measurement of left atrial and ventricular volumes in real-time 3D echocardiography. Validation by nuclear magnetic resonance].

The measurement of the left ventricular ejection fraction is important for the evaluation of cardiomyopathy and depends on the measurement of left ventricular volumes. There are no existing conventional echocardiographic means of measuring the true left atrial and ventricular volumes without mathematical approximations. The aim of this study was to test anew real time 3-dimensional echocardiographic system of calculating left atrial and ventricular volumes in 40 patients after in vitro validation. The volumes of the left atrium and ventricle acquired from real time 3-D echocardiography in the apical view, were calculated in 7 sections parallel to the surface of the probe and compared with atrial (10 patients) and ventricular (30 patients) volumes calculated by nuclear magnetic resonance with the simpson method and with volumes of water in balloons placed in a cistern. Linear regression analysis showed an excellent correlation between the real volume of water in the balloons and volumes given in real time 3-dimensional echocardiography (y = 0.94x + 5.5, r = 0.99, p < 0.001, D = -10 +/- 4.5 ml). A good correlation was observed between real time 3-dimensional echocardiography and nuclear magnetic resonance for the measurement of left atrial and ventricular volumes (y = 0.95x - 10, r = 0.91, p < 0.001, D = -14.8 +/- 19.5 ml and y = 0.87x + 10, r = 0.98, P < 0.001, D = -8.3 +/- 18.7 ml, respectively. The authors conclude that real time three-dimensional echocardiography allows accurate measurement of left heart volumes underlying the clinical potential of this new 3-D method.

Aged↗

MK-801 can exacerbate or attenuate behavioral alterations associated with neonatal alcohol exposure in the rat, depending on the timing of administration.

BACKGROUND: We have reported that administration of MK-801, an NMDA receptor antagonist, during ethanol withdrawal in the developing rat attenuates ethanol's adverse effects on behavioral development. In the present study, we altered the timing of MK-801 delivery in relation to the last alcohol dose to determine if its protective effects were specific to the ethanol withdrawal phase. METHODS: Five groups of rats were artificially reared and exposed to alcohol in a binge-like manner on postnatal day (PD) 6, producing peak blood alcohol levels of 335 mg/dl that cleared to 0 mg/dl by 33 hours. Four groups received MK-801 at various times after alcohol treatment (0, 9, 21, or 33 hr post-ethanol). The fifth alcohol-treated group received saline. Two artificially reared control groups were included: one was injected with saline and the other injected with 0.5 mg/kg MK-801. Finally, a normally reared suckle control group was also included. Activity level and performance on a spatial discrimination reversal-learning task were evaluated at PD 18 and PD 40, respectively. RESULTS: Administration of MK-801 at the same time as ethanol treatment (0 hr) produced a high rate of mortality. Ethanol exposure on PD6 increased activity level relative to controls. Administration of MK-801 at 0 hr exacerbated this ethanol-induced overactivity, whereas administration of MK-801 at 21 and 33 hr reduced the severity of ethanol-related overactivity. Similarly, ethanol exposure on PD 6 significantly increased the number of errors committed on a spatial discrimination reversal-learning task. MK-801 injections 9 hrs after ethanol exacerbated this effect, whereas MK-801 treatment 33 hrs after ethanol attenuated this effect. Thus, MK-801 administration at the time of ethanol treatment was highly toxic, whereas during the withdrawal period it was protective. CONCLUSION: These data are consistent with the hypothesis that ethanol exposure in the neonatal rat inhibits the NMDA receptor, producing a subsequent rebound in NMDA receptor activation and possible excitotoxicity during withdrawal. Both the acute inhibitory effects of ethanol and the excitatory effects of withdrawal may contribute to fetal alcohol effects.

Animals↗

[Real time 3D echocardiography].

Three-dimensional representation of the heart is an old concern. Usually, 3D reconstruction of the cardiac mass is made by successive acquisition of 2D sections, the spatial localisation and orientation of which require complex guiding systems. More recently, the concept of volumetric acquisition has been introduced. A matricial emitter-receiver probe complex with parallel data processing provides instantaneous of a pyramidal 64 degrees x 64 degrees volume. The image is restituted in real time and is composed of 3 planes (planes B and C) which can be displaced in all spatial directions at any time during acquisition. The flexibility of this system of acquisition allows volume and mass measurement with greater accuracy and reproducibility, limiting inter-observer variability. Free navigation of the planes of investigation allows reconstruction for qualitative and quantitative analysis of valvular heart disease and other pathologies. Although real time 3D echocardiography is ready for clinical usage, some improvements are still necessary to improve its conviviality. Then real time 3D echocardiography could be the essential tool for understanding, diagnosis and management of patients.

Animals↗

Automated quantification of mitral valve regurgitation based on normalized centerline velocity distribution.

Previous echocardiographic techniques for quantifying valvular regurgitation are limited by factors including uncertainties for orifice location and a hemispheric convergence assumption that often results in over- and underestimation of flow rate and regurgitant orifice area. Using computational fluid dynamics simulations, these factors were eliminated, allowing a more accurate assessment of regurgitation. A model was developed to allow automated quantification of regurgitant orifice diameter based on the centerline velocity data available from color M-mode echocardiography. The model, validated using in vitro unsteady flow data, demonstrated improved accuracy for orifice diameter (y=0.95x + 0.38, r=0.96) and volume (y=1.18x - 4.72, r=0.93).

Blood Flow Velocity↗