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Biomedical subjects

N Dalton

Publications and source records attributed to N Dalton.

At least 19 recordsLinked to original sources
PubMed2001

A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function.

The role of the cardiac myocyte as a mediator of paracrine signaling in the heart has remained unclear. To address this issue, we generated mice with cardiac myocyte-specific deletion of the vascular endothelial growth factor gene, thereby producing a cardiomyocyte-specific knockout of a secreted factor. The hearts of these mice had fewer coronary microvessels, thinned ventricular walls, depressed basal contractile function, induction of hypoxia-responsive genes involved in energy metabolism, and an abnormal response to beta-adrenergic stimulation. These findings establish the critical importance of cardiac myocyte-derived vascular endothelial growth factor in cardiac morphogenesis and determination of heart function. Further, they establish an adult murine model of hypovascular nonnecrotic cardiac contractile dysfunction.

Animals↗
PubMed2000

Intracoronary delivery of adenovirus encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity.

BACKGROUND: We tested the hypothesis that intracoronary injection of a recombinant adenovirus encoding adenylyl cyclase type VI (AC(VI)) would increase cardiac function in pigs. METHODS AND RESULTS: Left ventricular (LV) dP/dt and cardiac output in response to isoproterenol and NKH477 stimulation were assessed in normal pigs before and 12 days after intracoronary delivery of histamine followed by intracoronary delivery of an adenovirus encoding lacZ (control) or AC(VI) (1.4x10(12) vp). Animals that had received AC(VI) gene transfer showed increases in peak LV dP/dt (average increase of 1267+/-807 mm Hg/s; P=0.0002) and cardiac output (average increase of 39+/-20 mL. kg(-1). min(-1); P<0.0001); control animals showed no changes. Increased LV dP/dt was evident 6 days after gene transfer and persisted for at least 57 days. Basal heart rate, blood pressure, and LV dP/dt were unchanged, despite changes in cardiac responsiveness to catecholamine stimulation. Twenty-three hour ECG recordings showed no change in mean heart rate or ectopic beats and no arrhythmias. LV homogenates from animals receiving AC(VI) gene transfer showed increased AC(VI) protein content (P=0.0007) and stimulated cAMP production (P=0.0006), confirming transgene expression and function; basal LV AC activity was unchanged. Increased cAMP-generating capacity persisted for at least 18 weeks (P<0.0002). CONCLUSIONS: Intracoronary injection of a recombinant adenovirus encoding AC provides enduring increases in cardiac function.

Adenoviridae↗
PubMed2000

Effects of growth hormone on cardiac dysfunction and gene expression in genetic murine dilated cardiomyopathy.

Beneficial cardiac effects of growth hormone (GH) have been shown in heart failure in several settings, but studies are lacking on this and other forms of treatment in the cardiomyopathic (CM) mouse heart. In mice with dilated cardiomyopathy due to disruption of the muscle LIM protein (MLP) gene [MLP null mice (MLP-/-)], natural history was first assessed by an initial echocardiogram at 8 weeks and a later follow-up study (n = 31). In most mice, left ventricular (LV) dilation increased and/or function decreased by 5 months, and 3 of 12 mice followed for 9 months died. At the end of follow-up, 22 MLP-/- mice (average age 10.2 months) had both LV dilation and reduced LV function and were selected for studies of GH effects on cardiac function and gene expression; mice were randomized to vehicle (controls) or recombinant human (rh) GH and restudied after 2 weeks. In the GH-treated group compared to the control group, LV % fractional shortening and LV wall thickness (echocardiography) were increased, the LV dP/dtmax (catheter-tip micromanometry) was enhanced, and LV relaxation (tau) improved; however, the LV weight was not significantly increased. The LV expression of many genes was altered in MLP-/- mice, and several were influenced by GH. Thus, short-term RhGH treatment improved LV function in a setting of chronic cardiac deterioration and significantly reduced elevated LV mRNA expression of some (ANP, BNP) but not other members of the embryonic gene program. The MLP null cardiomyopathic mouse can be useful for exploring altered signaling and therapeutic interventions in heart failure.

Animals↗
PubMed1999

Cardiac-directed adenylyl cyclase expression improves heart function in murine cardiomyopathy.

BACKGROUND: We tested the hypothesis that increased cardiac myocyte adenylyl cyclase (AC) content increases cardiac function and response to catecholamines in cardiomyopathy. METHODS AND RESULTS: Transgenic mice with cardiac-directed expression of AC type VI (ACVI) were crossbred with mice with cardiomyopathy induced by cardiac-directed Gq expression. Gq mice had dilated left ventricles, reduced heart function, decreased cardiac responsiveness to catecholamine stimulation, and impaired beta-adrenergic receptor (betaAR)-dependent and AC-dependent cAMP production. Gq/AC mice showed improved basal cardiac function in vivo (P=0.01) and ex vivo (P<0.0005). When stimulated through the betaAR, cardiac responsiveness was increased (P=0.02), and cardiac myocytes showed increased cAMP production in response to isoproterenol (P=0.03) and forskolin (P<0.0001). CONCLUSIONS: Increasing myocardial ACVI content in cardiomyopathy restores cAMP-generating capacity and improves cardiac function and responsiveness to betaAR stimulation.

Adenylyl Cyclases↗
PubMed1999

Adenylylcyclase increases responsiveness to catecholamine stimulation in transgenic mice.

BACKGROUND: The cellular content of cAMP generated by activation of adenylylcyclase (AC) through the beta-adrenergic receptor (betaAR) is a key determinant of a cell's response to catecholamine stimulation. We tested the hypothesis that increased AC content, independently of betaAR number, increases responsiveness to catecholamine stimulation in vivo. METHODS AND RESULTS: Transgenic mice with cardiac-directed expression of ACVI showed increased transgene AC expression but no change in myocardial betaAR number or G-protein content. When stimulated through the betaAR, cardiac function was increased, and cardiac myocytes showed increased cAMP production. In contrast, basal cAMP and cardiac function were normal, and long-term transgene expression was not associated with abnormal histological findings or deleterious changes in cardiac function. CONCLUSIONS: The amount of AC sets a limit on cardiac beta-adrenergic signaling in vivo, and increased AC, independent of betaAR number and G-protein content, provides a means to regulate cardiac responsiveness to betaAR stimulation. Overexpressing an effector (AC) does not alter transmembrane signaling except when receptors are activated, in contrast to receptor/G-protein overexpression, which yields continuous activation and has detrimental consequences. Our findings establish the importance of AC content in modulating beta-adrenergic signaling in the heart, suggesting a new target for safely increasing cardiac responsiveness to betaAR stimulation.

Adenylyl Cyclases↗
PubMed1998

Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy.

Numerous studies have implicated Coxsackievirus in acute and chronic heart failure. Although enteroviral nucleic acids have been detected in selected patients with dilated cardiomyopathy, the significance of such persistent nucleic acids is unknown. To investigate the mechanisms by which restricted viral replication with low level expression of Coxsackieviral proteins may be able to induce cardiomyopathy, we generated transgenic mice which express a replication-restricted full-length Coxsackievirus B3 (CVB3) cDNA mutant (CVB3DeltaVP0) in the heart driven by the cardiac myocyte-specific myosin light chain-2v (MLC-2v) promoter. CVB3DeltaVP0 was generated by mutating infectious CVB3 cDNA at the VP4/VP2 autocatalytic cleavage site from Asn-Ser to Lys-Ala. Cardiac-specific expression of this cDNA leads to synthesis of positive- and negative-strand viral RNA in the heart without formation of infectious viral progeny. Histopathologic analysis of transgenic hearts revealed typical morphologic features of myocardial interstitial fibrosis and in some cases degeneration of myocytes, thus resembling dilated cardiomyopathy in humans. There was also an increase in ventricular atrial natriuretic factor mRNA levels, demonstrating activation of the embryonic program of gene expression typical of ventricular hypertrophy and failure. Echocardiographic analysis demonstrated the presence of left ventricular dilation and decreased systolic function in the transgenic mice compared with wild-type littermates, evidenced by increased ventricular end-diastolic and end-systolic dimensions and decreased fractional shortening. Analysis of isolated myocytes from transgenic mice demonstrate that there is defective excitation-contraction coupling and a decrease in the magnitude of isolated cell shortening. These data demonstrate that restricted replication of enteroviral genomes in the heart can induce dilated cardiomyopathy with excitation-contraction coupling abnormalities similar to pressure overload models of dilated cardiomyopathy.

Animals↗
PubMed1998

Loss of adrenergic control of the force-frequency relation in heart failure secondary to idiopathic or ischemic cardiomyopathy.

This study was designed to determine whether the force-frequency effect on myocardial contractility, known to be importantly regulated by the adrenergic nervous system in experimental animals, can be enhanced by beta-adrenergic receptor stimulation in patients with heart failure. Animal experiments have demonstrated that the positive force-frequency relation in most mammals is subject to enhancement by beta-adrenergic receptor stimulation during exercise or infusion of a beta-receptor agonist. In animal models of heart failure, this regulatory mechanism generally is lost. The response to progressive increases in heart rate to 150 to 160 beats/min by right atrial pacing before and during dobutamine infusion was studied in 3 relatively normal subjects and in 5 patients with severe dilated cardiomyopathy. Left ventricular (LV) pressure and its first derivative (LV dP/dt(max)) were measured with a micromanometer, and the time constant of LV relaxation was assessed. The slopes of the relations between heart rate and LV dP/dt(max) in control subjects were positive at baseline and the mean slope increased substantially and significantly during dobutamine infusion. In patients with heart failure, the heart rate versus LV dP/dt(max) relations were depressed and flattened without a descending limb. Dobutamine infusion shifted this relation upward slightly, without increase in mean slope, indicating lack of amplification. The rate of isovolumic relaxation significantly decreased as heart rate increased at baseline and was further shortened by dobutamine. In patients with heart failure, a depressed and flattened relation between heart rate and LV dP/dt(max) (force-frequency effect) did not show the amplification of myocardial contractility by beta-adrenergic stimulation observed in the normal heart. This abnormality in control of the force-frequency relation undoubtedly plays an important role in the impairment of cardiac function during exercise in heart failure.

Adrenergic beta-Agonists↗
PubMed1998

Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children.

We studied 34 apparently healthy children and 2 propositi from kindreds with familial juvenile hyperuricaemic nephropathy (FJHN) - a disorder characterised by early onset, hyperuricaemia, gout, familial renal disease and a similarly low urate clearance relative to glomerular filtration rate (GFR) [fractional excretion of uric acid (FEur) 5.1+/-1.6%] in young men and women. In addition to the propositi, 17 asymptomatic children were hyperuricaemic -- mean plasma urate (368+/-30 micromol/l), twice that of controls (154+/-41 micromol/l). Eight of them had a normal GFR ( > 80 ml/min per 1.73 m2), and 11 renal dysfunction, which was severe in 5. The FEur in the 14 hyperuricaemic children with a GFR > 50 ml/min was 5.0+/-0.5% and in the 5 with a GFR < or =50 ml/min was still low (11.5+/-0.2%) compared with controls (18.4+/-5.1%). The 17 normouricaemic children (185+/-37 micromol/l) had a normal GFR (>80 ml/min) and FEur (14.0+/-5.3%). The results highlight the dominant inheritance, absence of the usual child/adult difference in FEur in FJHN and presence of hyperuricaemia without renal disease in 42% of affected children, but not vice versa. Since early allopurinol treatment may retard progression to end-stage renal failure, screening of all relatives in FJHN kindreds is essential.

Adolescent↗
PubMed1997

Ras-dependent pathways induce obstructive hypertrophy in echo-selected transgenic mice.

To overcome the genetic and interindividual variability frequently noted in complex phenotypes, we used echocardiographic selection to develop a substrain of myosin light chain (MLC)-Ras (RAS) transgenic mice with an enhanced ventricular hypertrophic phenotype. These echo-selected mice were then compared with wild-type (WT) animals and a pressure overload hypertrophy model (transverse aortic constriction; TAC). Echocardiography demonstrated increased wall thickness in RAS compared with the other groups. We developed novel miniaturized physiological technology to quantitatively identify in vivo intraventricular gradients; increased systolic Doppler velocity was seen in the left ventricle (LV) in 69% of RAS vs. none of WT or TAC. Intracavitary pressure gradients were present in 3 of 10 RAS vs. none of TAC or WT. Passive diastolic LV stiffness was not different among the three groups. Myofibrillar disarray was present in all RAS animals and was significantly more extensive (21.7% area fraction) than in TAC (1.5%) or WT (0.0%). RAS mice had selective induction of natriuretic peptide genes in the LV, a pattern distinct from that induced by pressure overload. Juvenile mortality was significantly increased in the offspring of echo-selected RAS parents. We conclude that adaptation of echocardiography to the mouse permits selection for cardiac phenotypes, and that selectively inbred MLC-Ras transgenic mice faithfully reproduce the molecular, physiological, and pathological features of human hypertrophic cardiomyopathy (HCM). Because previous studies support the concept that hypertrophy in human HCM is secondary to dysfunction created by sarcomeric protein mutations, the current studies suggest that Ras-dependent pathways might play a similar role in forms of human HCM.

Age Factors↗
PubMed1997

Force-frequency relations in the failing rabbit heart and responses to adrenergic stimulation.

BACKGROUND: Recent experiments have documented the importance of beta-adrenergic regulation of the force-frequency relation (FFR) in the normal and failing heart. As in isolated human cardiac muscle, a descending limb of the FFR occurs at high frequencies in the intact rabbit heart, and therefore a new model of atrial pacing-induced heart failure was developed in the rabbit. Responses of the FFR to beta-adrenergic stimulation were then assessed in the conscious state before and after the induction of heart failure. METHODS AND RESULTS: Rapid atrial pacing for an average of 19.5 days in instrumented rabbits produced severe left ventricular dilation with reduced cardiac output (echocardiography) and depressed myocardial contractility and relaxation rate (left ventricular dP/dt, catheter-tip micromanometer), associated with reductions in beta-adrenergic receptor density and adenylyl cyclase activity. Before heart failure, heart rate was slowed in the conscious animal from 280 +/- 30 (SD) to about 225 beats/min using a sinus node inhibitor (zatebradine), and heart rate was then increased in steps by atrial pacing from 250 to 450 beats/min; the heart rate-versus-left ventricular dP/dtmax (FFR) response showed an ascending response (increasing contractility), with a descending limb at rates greater than 375 beats/min, and dobutamine infusion amplified the ascending limb of the FFR (increased slope) and attenuated the descending limb. In heart failure the basal FFR was severely depressed with a descending limb over 350 beats/min; dobutamine shifted the FFR upward somewhat without change in the slope of the ascending limb, whereas dobutamine prevented the descending limb of the FFR. Similar responses were observed in the relations between heart rate and cardiac output. CONCLUSIONS: A new model of heart failure in the conscious rabbit was developed using rapid atrial pacing and applied to study force-frequency effects. In heart failure, normal beta-adrenergic amplification of the ascending limb of the FFR by dobutamine was absent, but a marked descending limb of the FFR at higher heart rates was prevented by dobutamine. Observed reductions in components of the beta-adrenergic receptor system likely were responsible for impaired beta-adrenergic FFR amplification, but the mechanism(s) for the descending limb and its correction by dobutamine are not yet established. These responses of the FFR may influence importantly the ability of the failing heart to respond to exercise and stress.

Adrenergic beta-Agonists↗
PubMed1996

Transthoracic echocardiography in models of cardiac disease in the mouse.

BACKGROUND: Transthoracic echocardiography (M-mode and Doppler) offers a noninvasive approach for in vivo evaluation of the mouse heart. The present study examines its usefulness for assessing the morphological/functional phenotype of the left ventricle (LV) in several transgenic and surgical murine models of cardiac disease. METHODS AND RESULTS: Observations were made in 83 intact, anesthetized mice. In mice with a surgical arteriovenous fistula, volume overload and LV dilation were detected. In normal mice, echocardiographic indexes of increased contractility (dobutamine) were confirmed by LV dP/dtmax. In transgenic mice with overexpression of the beta 2-adrenergic receptor, heart rate and mean velocity of circumferential fiber shortening were increased, indicating enhanced contractility. In colony screening of transgenic mice overexpressing the H-ras gene, 45% had increased LV wall thickness (> 0.9 mm), and those showing a striking increase were selected for breeding. In mice with LV hypertrophy (aortic constriction) and normal mice, the actual LV mass determined by echocardiography correlated well (r = .93), and 95% confidence limits were determined. The maximum intraobserver and interobserver coefficients of variation for M-mode data were 0.03 +/- 0.29 mm (+/- 2 SD), < 10% for LV internal dimensions but 27% to 30% for wall thickness. CONCLUSIONS: These studies provide the first application of transthoracic echocardiography for morphological/functional characterization of the cardiac phenotype in transgenic and surgical murine models, including (1) high reliability for detecting LV chamber dilation and function; (2) reliability (and its limits) for determining abnormal LV wall thickness and LV mass; (3) identification of marked, sometimes asymmetrical, hypertrophy in a transgenic model of hypertrophic cardiomyopathy; and (4) usefulness for transgenic colony screening to identify markedly abnormal phenotypes.

Anesthesia↗
PubMed1994

Growth hormone-releasing activity of hexarelin in humans. A dose-response study.

Hexarelin is a new hexapeptide (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) that stimulates the release of growth hormone both in vitro and in vivo. In this double-blind, placebo-controlled, rising-dose study we evaluated the growth hormone releasing activity of hexarelin in healthy human subjects. Twelve adult male volunteers received single intravenous boluses of 0.5, 1 and 2.micrograms.kg-1 hexarelin as well as placebo. For safety, drug doses were given in a rising-dose fashion with placebo randomly inserted into the sequence. Plasma growth hormone concentrations increased dose-dependently after the injection of the peptide, peaking at about 30 min and then decreasing to baseline values within 240 min with a half-life of about 55 min. The mean peak plasma growth hormone concentrations (Cmax) were 3.9, 26.9, 52.3, 55.0 ng.ml-1 after 0, 0.5, 1 and 2 micrograms.kg-1, respectively. The corresponding areas under the curve of growth hormone plasma levels from drug injection to 180 min (AUC0-180) were 0.135, 1.412, 2.918 and 3.695 micrograms.min.ml-1. The theoretical maximum response (Emax) and the dose that produces half of the maximum response (ED50) were estimated using logistic regression. The calculated ED50 values were 0.50 and 0.64 microgram.kg-1 for Cmax and AUC0-180, respectively. The corresponding Emaxs were 55.1 ng.ml-1 and 3936 ng.min.ml-1, thus indicating that the effect after the 2 micrograms.kg-1 dose is very close to the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Biotinidase deficiency: early neurological presentation.

Three patients with biotinidase deficiency are described. Two presented at eight weeks of age with anticonvulsant-resistant fits, developmental delay and hypotonia. Treatment has been effective. The third developed ataxia and alopecia at 14 months and died suddenly at 19 months of age. In all three cases the diagnosis was not considered quickly enough. Biotinidase deficiency is a treatable cause of severe neurological problems.

Acidosis, Lactic↗
PubMed1991

Urinary growth hormone excretion during puberty in type 1 (insulin-dependent) diabetes mellitus.

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.

Acetylglucosaminidase↗
PubMed1991

Pericardial influences on right and left ventricular filling dynamics.

The influence of the pericardium on right and left ventricular filling was studied using two-dimensional and Doppler echocardiography in 14 open-chest dogs. Doppler echo parameters of filling included early (E) and late (A) velocities and their ratio (E/A) for the mitral and tricuspid valves. Right and left ventricular volumes were calculated from orthogonal two-dimensional echocardiographic images. Data were compared at three levels of left ventricular end-diastolic pressure (6 +/- 2, 13 +/- 3, and 21 +/- 4 mm Hg) at matched heart rates before and after pericardiectomy. The instantaneous diastolic pressure gradient was measured in 12 of the dogs. Pericardiectomy resulted in an increase in early mitral velocity, peak early diastolic pressure gradient, and E/A but not early mitral velocity normalized for end-diastolic volume. In contrast, for the tricuspid valve flow, pericardiectomy did not change E but caused a marked increase in A and a decrease in E/A. Right ventricular end-diastolic volumes at matched left ventricular end-diastolic volumes were similar before and after the pericardium was removed. However, removal of the pericardium caused a significant decrease of the slope for the right (86.0 +/- 27.0 x 10(-4) versus 50.0 +/- 19.5 x 10(-4) mm Hg/ml, p less than 0.01), but not left, ventricular ln end-diastolic pressure-volume relation (21.2 +/- 9.2 x 10(-3) versus 21.4 +/- 5.3 x 10(-3) mm Hg/ml, p = NS), and a decrease of the pressure intercept for the left (3.0 +/- 2.0 versus 1.6 +/- 0.9 mm Hg, p less than 0.05), but not right, ventricular ln end-diastolic pressure-volume relation (2.8 +/- 1.4 versus 1.4 +/- 0.8 mm Hg, p = NS). In conclusion, filling of the two ventricles is affected by the pericardium over a wide range of physiological ventricular volumes and pressures. At matched left ventricular end-diastolic volume, pericardiectomy causes a fundamental alteration in right, but not left, ventricular filling.

Animals↗
PubMed1990

Prevention of hepatocyte injury and lipid peroxidation by iron chelators and alpha-tocopherol in isolated iron-loaded rat hepatocytes.

These experiments were performed to characterize the relationship between lipid peroxidation and hepatocyte viability in iron overload. Hepatocytes were isolated from rats with chronic dietary iron overload and the effects of in vitro iron chelation on lipid peroxidation, cell viability and ultrastructure were studied over a 4-hr incubation period. Cell viability was significantly reduced at 3 and 4 hr in iron-loaded hepatocytes compared with controls and was preceded by an increase in iron-dependent lipid peroxidation. Similarly, extensive degenerative ultrastructural changes were observed in iron-loaded hepatocytes compared with controls after 4 hr of incubation. In vitro iron chelation with either deferoxamine or apotransferrin protected against lipid peroxidation, loss of viability and ultrastructural damage in iron-loaded hepatocytes. The addition of an antioxidant, alpha-tocopherol, also protected against lipid peroxidation and preserved cell viability over a 4-hr incubation. The protective effects of iron chelators and alpha-tocopherol support a strong association between iron-dependent lipid peroxidation and hepatocellular injury in iron overload.

Animals↗
PubMed1989

Doppler color flow mapping studies of jet formation and spatial orientation in obstructive hypertrophic cardiomyopathy.

To help clarify the mechanism of outflow tract obstruction and systolic anterior motion of the anterior leaflet of the mitral valve and their relation to the geometry of the left ventricle, we studied left ventricular outflow tract flow in 20 patients with hypertrophic cardiomyopathy (HCM) using two-dimensional Doppler flow mapping. We compared our results with outflow tract flow in 10 patients with isolated valvular aortic stenosis, (AS) and with those in 10 healthy volunteers. In HCM, a 94- to 145-degree angle (mean 111.4 +/- 11.9 degrees) developed between the direction of left ventricular outflow tract flow acceleration and aortic valve outflow, resulting in posterolaterally directed left ventricular outflow jets. The angle of the outflow jet and the peak velocity of the jet measured with continuous wave Doppler (as an indicator of the severity of obstruction) correlated well (r = -0.81, SEE = 7.8 degrees). Jet narrowing during ejection measured just proximal to the point of systolic anterior motion was 42 +/- 11% in HCM and was weakly correlated with peak jet velocity (r = 0.61, SEE = 8.9 degrees). Aliasing of left ventricular outflow occurred proximal to systolic anterior motion of the mitral valve, and color M-mode demonstrated temporal and spatial flow acceleration proximal to systolic anterior motion, providing evidence for obstruction at that site. In AS, left ventricular outflow tract jets were more parallel to the axis of aortic outflow (129 to 153 degree, 138.4 +/- 8.1 degrees). Jet narrowing was only 8 +/- 5% compared to HCM (both p less than 0.05), and flow acceleration occurred proximal to the stenotic valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗