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Biomedical subjects

Kenji Harada

Publications and source records attributed to Kenji Harada.

At least 19 recordsLinked to original sources

Noninvasive visualization and measurement of middle cardiac vein flow by transthoracic Doppler echocardiography.

Transthoracic Doppler echocardiography offers a noninvasive approach for imaging posterior descending coronary artery (PD) running in the posterior longitudinal sulcus along the middle cardiac vein (MCV). To evaluate whether the MCV flow velocity reserve can reflect the PD flow reserve, 22 children with various heart diseases were examined using transthoracic Doppler echocardiography. Introduction of a modified transthoracic two chamber view with the transducer rotated counterclockwise and angulated posteriorly allows visualization of the MCV and PD. Peak systolic flow velocity and average peak systolic flow velocity in the MCV and peak diastolic flow velocity and average peak diastolic flow velocity in the PD were measured at rest and hyperemic conditions (intravenous administration of adenosine of 0.16 mg/kg/min). Coronary flow reserve was defined as the ratio of peak hyperemic to basal average peak flow velocity. ATP infusion induced significant increases in the peak systolic flow velocity and average peak systolic flow velocity in the MCV. The mean MCV flow velocity reserve in the patients was 1.94 +/- 0.44. Significant increases in the peak diastolic flow velocity and the average peak diastolic flow velocity in the PD were also observed during ATP infusion, and the mean PD flow velocity reserve (2.19 +/- 0.62) was significantly higher than the GCV flow velocity reserve (p < 0.0001). There was a good correlation between the MCV flow velocity reserve and PD flow velocity reserve (r = 0.86, p < 0.0001). This study demonstrated that it was possible to measure the MCV flow velocity and MCV flow velocity reserve in pediatric patients by transthoracic Doppler echocardiography. The MCV flow reserve correlated highly with the PD flow reserve. However, the degree of the MCV flow during hyperemia was less than that of the PD flow. This underestimation should be considered when the reactive hyperemic response is evaluated from the MCV flow velocity.

Blood Flow Velocity↗

Regulation of hormone-sensitive lipase in islets.

An unique isoform of hormone-sensitive lipase (HSL) is expressed in beta-cells. Recent findings suggest that HSL could be involved in the regulation of glucose stimulated insulin secretion (GSIS), however, these findings are controversial. To test the hypothesis that HSL is involved in control of normal GSIS via changes in its expression and/or activity in response to stimuli, we examined the effects of free fatty acid (FFA) loading and glucagon like peptide-1 (GLP-1) stimulation on the regulation of HSL expression and activity. With prolonged FFA loading, there was increased expression of beta-cell HSL and increased HSL hydrolytic activity in clonal beta-cells. Short-term treatment with GLP-1 increased HSL activity without changing the expression of the beta-cell isoform of HSL. Basal insulin secretion was increased, whereas GLP-1 potentiation of GSIS was decreased in islets isolated from HSL-/- mice, as compared to islets from wild type mice. Furthermore, using PancChip 2.2 cDNA microarrays (NIDDK consortium), the gene expression profile in the islets of HSL-/- mice was compared with wild type mice. Results showed changes in several metabolic pathways due to changes in lipid homeostasis caused by inactivation of HSL. Quantitative PCR for selected genes also revealed changes in genes that are related to insulin secretion, such as UCP-2. Therefore, these results suggest that the beta-cell isoform of HSL is involved in maintaining lipid homeostasis in islets and contributes to the proper control of GSIS.

Animals↗

Probing the integrin-binding site within the globular domain of laminin-511 with the function-blocking monoclonal antibody 4C7.

In an attempt to elucidate the integrin-binding site within laminin-511 (alpha5beta1gamma1), we mapped the epitope for mAb 4C7, which recognizes the globular (G) domain of the laminin alpha5 chain and inhibits binding of integrin alpha6beta1 to laminin-511, using a series of recombinant laminin-511 mutants with deletions or substitutions in the G domain. Deletion of the LG2-5 modules only partially compromised the 4C7 binding activity, while deletion of all 5 LG modules completely abrogated the activity, indicating that the epitope for 4C7 resides in the LG1 module. In support of this conclusion, 4C7 reactivity was abolished when the LG1 module of laminin-511 was swapped with the corresponding module of laminin-111, but the reactivity was retained after swapping the LG2 or LG3 module. Despite the requirement of LG1 for 4C7 binding, a recombinant LG1 module failed to bind to 4C7 when expressed alone or in tandem with LG2, but exhibited significant 4C7 binding activity when expressed as an array of LG1-3. These results indicate that 4C7 recognizes an epitope in the LG1 module, whose active conformation is stabilized in the context of the LG1-3 modules. Despite their 4C7 binding activities, neither the recombinant LG1-3 fragment nor the LG2 and LG3 swap mutants were capable of binding to integrin alpha6beta1. Thus, the integrin binding activity does not necessarily parallel the 4C7 reactivity, and possibly requires a strictly defined conformation of the LG1 module which can only be attained within an array of the intact LG1-3 modules connected to the preceding coiled-coil domain.

Amino Acid Sequence↗

Acid-catalyzed transannular cyclization of 3aH-cyclopentene[8]annulene-1,4-(5H,9aH)-diones and some proposed mechanisms.

Bicyclic 3aH-cyclopentene[8]annulene-1,4-(5H,9aH)-diones underwent three types of acid-induced transannular reactions, Michael cyclization, [3 + 2] cycloaddition, and Friedel-Crafts ipso-alkylation, depending on the cyclopentenone ring substituent (Me or Ph) and the position of [8]annulenone substituent as well as the nature of acids (BF3, MeSO3H, CF3SO3H). The Me-substituent permitted the Michael reaction for all acids used to give tricyclic diones by the activation of cyclopentenone carbonyl group. However, the Ph-substituent inhibited the Michael reaction for BF3 and MeSO3H but allowed the [3 + 2] cycloaddition and Friedel-Crafts reaction for CF3SO3H depending on the position of annulenone substituent. These CF3SO3H reactions exhibited the following novel rearrangements, affording 2-naphthalenone and 7-acenaphthylene derivatives, respectively. The factors that control the reaction mode of these transannular cyclizations were discussed in view of the constraint twist-boat conformation of [8]annulenone ring as well as the ring substituent effects on the intramolecular cyclization. In addition, these [8]annulenone rings were found to easily undergo the intramolecular [2 + 2] photocyclization to provide the tetracyclic cage compounds which exhibited the facile cycloreversion under the influence of acid.

Acids↗

Site selectivity switch in Lewis acid catalysis. Mechanism and kinetic simulation of skeletal rearrangement of cyclobutene-fused homoquinones.

[reactions: see text] We investigated the site selectivity switch in BF3-catalyzed dual skeletal rearrangements of cyclobutene-fused diarylhomobenzoquinones by changing the stoichiometric amount of acid concentration. From the lower to the higher equivalency of BF3 x Et2O, the branching product ratios (path A/path B) obeyed nonlinear sigmoid curves against the equivalency of BF3 x Et2O. The observed selectivity profiles were simulated to elucidate factors that govern thermodynamic aspects (binding affinity K of each carbonyl function with acid) and kinetic aspects (rate constants k for the cyclobutene-ring cleavage).

Journal Article↗

High mobility group protein-B1 interacts with sterol regulatory element-binding proteins to enhance their DNA binding.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that are predominately involved in the regulation of lipogenic and cholesterogenic enzyme gene expression. To identify unknown proteins that interact with SREBP, we screened nuclear extract proteins with 35S-labeled SREBP-1 bait in Far Western blotting analysis. Using this approach, high mobility group protein-B1 (HMGB1), a chromosomal protein, was identified as a novel SREBP interacting protein. In vitro glutathione S-transferase pull-down and in vivo coimmunoprecipitation studies confirmed an interaction between HMGB1 and both SREBP-1 and -2. The protein-protein interaction was mediated through the helix-loop-helix domain of SREBP-1, residues 309-344, and the A box of HMGB1. Furthermore, an electrophoretic mobility shift assay demonstrated that HMGB1 enhances SREBPs binding to their cognate DNA sequences. Moreover, luciferase reporter analyses, including RNA interference technique showed that HMGB1 potentiates the transcriptional activities of SREBP in cultured cells. These findings raise the intriguing possibility that HMGB1 is potentially involved in the regulation of lipogenic and cholesterogenic gene transcription.

Animals↗

Usefulness of exercise-induced changes in plasma levels of brain natriuretic peptide in predicting right ventricular contractile reserve after repair of tetralogy of Fallot.

Elevated levels of brain natriuretic peptide (BNP) have been associated with ventricular dysfunction, and exercise tests have been used for assessing cardiac contractile reserve. We examined the relation between BNP and right ventricular (RV) contractile reserve during exercise in patients after repair of tetralogy of Fallot (TOF). A total of 45 patients, 26 of whom underwent repair of TOF at 2 to 3 years of age and 19 age-matched healthy children, were studied. Plasma levels of BNP were measured at baseline and at maximal exercise. Echocardiography combined with tissue Doppler imaging (TDI) was performed at rest and during supine bicycle submaximal exercise. The peak value of the first derivation of RV pressure (peak dP/dt) was measured by the continuous-wave Doppler method. The severity of pulmonary regurgitation (PR) (mild, moderate, or severe) was based on color Doppler findings. Plasma BNP levels were significantly higher in patients with TOF than in controls (44 +/- 34 vs 6 +/- 4 pg/ml, p <0.01). Exercise was associated with increased plasma BNP levels in both groups. A larger increment in BNP was noted in patients with TOF than in normal subjects (15 +/- 12 vs 2 +/- 2 pg/ml, p <0.01). The peak systolic myocardial velocity (Sa) and peak dP/dt values increased significantly in both groups during exercise; however, the magnitude of increase in both of these values was significantly less in patients with TOF than in controls (36 +/- 19% vs 70 +/- 19% and 42 +/- 11% vs 81 +/- 12%, respectively; p <0.01). There were significant correlations between the increment in BNP and changes in Sa and peak dP/dt values (r = -0.67 and -0.53, p <0.01, respectively), and the severity of PR (r = 0.74, p <0.01). Thus, exercise increases plasma levels of BNP, and greater increases are associated with impaired RV contractile reserve in patients with TOF with various degrees of PR.

Child↗

Mutational analysis of the "regulatory module" of hormone-sensitive lipase.

Hormone-sensitive lipase (HSL) is a rate-limiting enzyme in lipolysis that displays broad substrate specificity. HSL function is regulated by reversible phosphorylation that occurs within a 150 aa "regulatory module" of the protein. The current studies used mutational analysis to dissect the contribution of the "regulatory module" in HSL activity and substrate specificity. Deletion of the entire "regulatory module" or replacement of the "regulatory module" with the "lid" of lipoprotein lipase resulted in enzymatically inactive proteins. Deletion of sequentially longer stretches of the "regulatory module" resulted in a stepwise reduction in hydrolytic activity. Analysis of 7-19 amino acid deletional mutants that spanned the "regulatory module" showed that the N-terminal partial deletion mutants retained normal hydrolytic activity and activation by PKA. In contrast, the C-terminal partial deletion mutants displayed reduced hydrolytic activities, with preferential loss of activity against lipid-, as opposed to water-soluble, substrates. Single amino acid mutations of F650C, P651A, and F654D reduced activity against lipid-, but not water-soluble, substrates. The current results suggest that the length of the "regulatory module" and specific sequences within the C-terminal portion of the "regulatory module" of HSL (amino acids 644-683) are crucial for activity and appear to be responsible for determining lipase activity.

Amino Acid Motifs↗

Right ventricular pre-ejection myocardial velocity and myocardial acceleration in normal fetuses assessed by Doppler tissue imaging.

Myocardial acceleration during isovolumic contraction obtained from Doppler tissue imaging has been introduced as an index of right ventricular contractile function that is unaffected by the shape of the ventricle and loading conditions, but normal value of myocardial acceleration during isovolumic contraction and the effect of aging on the index are not known in normal fetuses. We studied 61 normal fetuses aged 20 to 39 weeks (29.8 +/- 5.1 weeks). Fetuses were divided into 4 age groups: 20 to 24 weeks (n = 11); 25 to 29 weeks (n = 20); 30 to 34 weeks (n = 20); and 35 to 39 weeks (n = 10). Using Doppler tissue imaging, peak pre-ejection myocardial velocity was measured at the base of right ventricular free wall from 4-chamber view. Myocardial acceleration was calculated by dividing pre-ejection velocity by the time interval from onset of the pre-ejection myocardial velocity to the time at peak velocity of this wave. The mean pre-ejection myocardial velocity was 5.0 +/- 1.1 cm/s. There was a stepwise increase in the pre-ejection myocardial velocity from the fetuses of 20 to 24 weeks to the fetuses of 35 to 39 weeks. The mean myocardial acceleration was 160 +/- 30 cm/s 2 . The mean myocardial acceleration did not differ between the fetuses aged 20 to 24 weeks (139 +/- 13 cm/s 2 ) and the fetuses aged 25 to 29 weeks (143 +/- 21 cm/s 2 ), but after 30 weeks increased with gestational age. For the total group combining the 4 different gestational age groups, the pre-ejection myocardial velocity and myocardial acceleration correlated with gestational age ( r = 0.85 and 0.75). This study demonstrated the gestational age-related changes in pre-ejection myocardial velocity and myocardial acceleration. The load-independent index of contractility, myocardial acceleration, increased mainly after 30 weeks' gestation.

Echocardiography, Doppler↗

Left ventricular geometry and myocardial contractility in patients with essential hypertension evaluated by myocardial velocity profile.

BACKGROUND: Left ventricular (LV) systolic function in the hypertensive heart has been evaluated considering geometric differences. The maximal systolic myocardial velocity gradient (Gmax) obtained from myocardial velocity profile can evaluate regional myocardial contractility. The purpose of this study was to assess LV myocardial contractility in the hypertensive heart using Gmax regarding geometric differences. METHODS: The study included 93 patients with essential hypertension. Gmax was correlated with relative wall thickness and LV mass index. LV myocardial contractility was assessed by classifying patients into normal geometry, concentric remodeling (CR), eccentric hypertrophy, and concentric hypertrophy (CH). RESULTS: Gmax has shown significant negative relationship with LV end-diastolic dimension. LV end-diastolic dimension in CH and eccentric hypertrophy groups was significantly greater than that in normal geometry and CR groups (CH vs CR, 4.9 vs 4.2 cm, P < .001). LV mass index was significantly greater in CH and eccentric hypertrophy groups than in the other groups (CH vs CR, 196 vs 122 g/m2, P < .001). Although there was no difference in relative wall thickness between CH and CR groups, Gmax was significantly smaller in CH than in CR group (1.8 vs 2.8 s(-1), P < .05). CONCLUSIONS: In patients with essential hypertension, LV myocardial contractility worsened corresponding to increase in LV dimension with similar wall thickness. Gmax obtained from myocardial velocity profile detected depressed myocardial contractility in patients with increased LV dimension.

Female↗

Kinetic evidence for remote pi-aryl participation in the BF3-catalyzed rearrangement of [2 + 2] photocycloadducts of diarylhomobenzoquinones with diphenylacetylene.

[reaction: see text] The BF(3)-catalyzed rearrangement of cyclobutene-fused m- and p-substituted diarylhomobenzoquinones exclusively gave the keto-alcohols via a Wagner-Meerwein vinyl-anion migration followed by the annulation of a delta-located endo-aryl group. The Hammett treatments for the endo/exo substituent effects, as well as the kinetic solvent effects, indicated that this reaction proceeds through the concerted S(N)2-like mechanism involving a rate-determining endo-aryl-assisted transition state.

Journal Article↗

Usefulness of tissue doppler imaging for assessing aortic wall stiffness in children with the Marfan syndrome.

The purpose of this study was to assess wall motion velocities of the abdominal aorta using tissue Doppler imaging (TDI) in 12 patients with Marfan syndrome and 30 age-matched normal controls. The patients with Marfan syndrome displayed an increased aortic stiffness index in the abdominal aorta, and significant relationships were observed between wall motion velocities of the abdominal aorta and the aortic stiffness index. Thus, TDI analyzes aortic expansion and contraction velocities and allows the identification of abdominal aortic stiffness in patients with Marfan syndrome.

Adolescent↗

p53 involvement in the pathogenesis of fatty liver disease.

Obesity is a major health problem in industrialized societies, and fatty liver disease (hepatic steatosis) is common in obese individuals. Oxidative stress originating from increased intracellular levels of fatty acids has been implicated as a cause of hepatocellular injury in steatosis, although the precise mechanisms remain to be elucidated. p53, widely known as a tumor suppressor, has been shown often to be activated in stressed cells, inducing cell cycle arrest or death. Here we demonstrate that p53 is involved in the molecular mechanisms of hepatocellular injury associated with steatosis. We found that p53 in the nucleus is induced in the liver from two mouse models of fatty liver disease, ob/ob and a transgenic mouse model that overexpresses an active form of sterol regulatory element-binding protein-1 in the liver (TgSREBP-1), the one with obesity and the other without obesity. This activation of the p53 pathway leads to the elevation of p21 mRNA expression, which can be considered an indicator of p53 activity, because ob/ob mice lacking p53 generated by targeting gene disruption exhibited the complete restoration of the p21 elevation to wild type levels. Consistent with these results, the amelioration of hepatic steatosis caused by Srebp-1 gene disruption in ob/ob mice lowered the p21 expression in a triglyceride content-dependent manner. Moreover, p53 deficiency in ob/ob mice resulted in a marked improvement of plasma alanine aminotransferase levels, demonstrating that p53 is involved in the mechanisms of hepatocellular injury. In conclusion, we revealed that p53 plays an important role in the pathogenesis of fatty liver disease.

Animals↗

Absence of hormone-sensitive lipase inhibits obesity and adipogenesis in Lep ob/ob mice.

Hormone-sensitive lipase (HSL) plays a crucial role in the hydrolysis of triacylglycerol and cholesteryl ester in various tissues including adipose tissues. To explore the role of HSL in the metabolism of fat and carbohydrate, we have generated mice lacking both leptin and HSL (Lep(ob/ob)/HSL(-/-)) by cross-breeding HSL(-/-) mice with genetically obese Lep(ob/ob) mice. Unexpectedly, Lep(ob/ob)/HSL(-/-) mice ate less food, gained less weight, and had lower adiposity than Lep(ob/ob)/HSL(+/+) mice. Lep(ob/ob)/HSL(-/-) mice had massive accumulation of preadipocytes in white adipose tissues with increased expression of preadipocyte-specific genes (CAAT/enhancer-binding protein beta and adipose differentiation-related protein) and decreased expression of genes characteristic of mature adipocytes (CCAAT/enhancer-binding protein alpha, peroxisome proliferator activator receptor gamma, and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1). Consistent with the reduced food intake, hypothalamic expression of neuropeptide Y and agouti-related peptide was decreased. Since HSL is expressed in hypothalamus, we speculate that defective generation of free fatty acids in the hypothalamus due to the absence of HSL mediates the altered expression of these orexigenic neuropeptides. Thus, deficiency of both leptin and HSL has unmasked novel roles of HSL in adipogenesis as well as in feeding behavior.

Adipocytes↗

Losartan improves regional left ventricular systolic and diastolic function in patients with hypertension: accurate evaluation using a newly developed color-coded tissue doppler imaging technique.

BACKGROUND: Angiotensin II receptor antagonists have recently been accepted as antihypertensive therapy. Tissue Doppler imaging (TDI) has been developed as a noninvasive tool to assess quantitatively regional myocardial motion abnormalities. This study was designed to determine whether our newly developed technique of color-coded TDI may be a useful means of quantifying the improvement in regional left ventricular (LV) myocardial contractility and relaxation after treatment with losartan in patients with hypertension. METHODS AND RESULTS: Losartan (50 to 100 mg) was administered for 6 months to 37 previously untreated patients with essential hypertension. Averaged myocardial velocity profiles (MVPs) for color-coded TDI were recorded in the ventricular septum and LV posterior wall before and after treatment. Peak myocardial velocities and peak myocardial velocity gradients (MVGs) in the LV walls were determined during systole and early diastole. The plasma concentration of transforming growth factor (TGF)-beta1 also was measured in all patients. Blood pressure and plasma TGF-beta1 level decreased after initiation of losartan therapy. The LV mass index and LV meridional end-systolic wall stress also decreased after treatment with losartan. LV geometry changed from a pattern consistent with concentric hypertrophy to normal geometry in 10 patients and to a pattern consistent with concentric remodeling in 5 patients, and from concentric remodeling to normal geometry in 5 patients after treatment with losartan. The ratio of early to late diastolic filling for the transmitral flow velocity increased after losartan treatment. The peak systolic and early diastolic myocardial velocities and MVGs in the ventricular septum and LV posterior wall increased after treatment with losartan, although the values 6 months after treatment with losartan were still lower than those in normal individuals. There were good correlations between changes in plasma TGF-beta1 level and changes in systolic and early diastolic MVGs 6 months after losartan. However, there were no significant correlations between changes in the systolic blood pressure and LV end-systolic wall stress and changes in the TDI parameters. CONCLUSION: Losartan improves regional LV function in patients with hypertension. Our newly developed averaged MVP and MVG measurements may be useful for accurately evaluating regional LV myocardial contractility and relaxation in these patients.

Aged↗

Quantitative assessment of right ventricular function using doppler tissue imaging in fetuses with and without heart failure.

BACKGROUND: Previous reports have established the use of Doppler tissue imaging (DTI) for noninvasive assessment of ventricular function, but the technique has not been validated for diagnosis of fetal cardiac failure. OBJECTIVE: The purpose of this study was to assess right ventricular (RV) function in fetuses with heart failure using DTI. METHODS: In all, 43 fetuses (36 control, 7 heart failure) were assessed using pulsed Doppler echocardiography combined with DTI. RV peak myocardial velocities during early diastole (Ea), atrial contraction, and systole were measured; and tricuspid peak velocities during early diastole (E) and atrial contraction. The ratio of E/Ea was used as an index of filling pressure were measured. From DTI, a Doppler-derived index of combined systolic/diastolic myocardial performance (DTI-Tei index) was measured. RESULTS: Compared with control fetuses, the mean Ea was significantly lower and the mean E was significantly higher in fetuses with heart failure, although these parameters did overlap between the 2 groups. The mean RV myocardial wall-motion velocity during atrial contraction, ratio of Ea/RV myocardial wall-motion velocity during atrial contraction, and RV myocardial wall-motion velocity during systole did not differ between the 2 groups. Compared with control fetuses, the mean E/Ea was significantly higher (9.71 +/- 0.91 vs 6.20 +/- 0.97; P <.0001) and the mean DTI-Tei index was significantly greater (0.79 +/- 0.11 vs 0.55 +/- 0.05; P <.0001) in fetuses with heart failure. In addition, the DTI-Tei index z score was >2 in all fetuses with heart failure. CONCLUSIONS: This study demonstrated a clinically important application of DTI-derived tricuspid annular velocities in fetuses with heart failure. Although DTI velocities were not sufficiently sensitive to identify fetuses with heart failure versus control fetuses, DTI-Tei index and E/Ea were useful and sensitive indicators of global RV dysfunction.

Blood Flow Velocity↗

Myocardial acceleration during isovolumic contraction as a new index of right ventricular contractile function and its relation to pulmonary regurgitation in patients after repair of tetralogy of Fallot.

BACKGROUND: Myocardial acceleration during isovolumic contraction (IVA) by Doppler tissue imaging has been proposed to be a new index of right ventricular contractile function that is unaffected by ventricular shape or loading conditions. OBJECTIVES: We sought to assess the use of IVA to evaluate right ventricular contractile function. METHODS: In all, 22 pediatric patients with pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) (8 +/- 3 years) and 27 age-matched children were examined. The degree of PR (mild, moderate, and severe) for patients with TOF was on the basis of pulsed and color Doppler findings. Using Doppler tissue imaging, the peak myocardial velocities during early diastole, late diastole, systole, and isovolumic contraction were recorded. RESULTS: Compared with healthy children, Doppler tissue imaging velocities for patients with TOF showed decreased myocardial velocities during early diastole (P =.007), late diastole (P <.0001), systole (P <.0001), and isovolumic contraction (P <.0001). Patients with TOF had a lower IVA when compared with healthy children (P <.0001). There was a stepwise decrease in the IVA from mild to severe PR. We found a significant relationship between the IVA and the degree of PR (r = -0.86, P <.0001). CONCLUSION: The analysis of IVA allows the assessment of right ventricular contractile function for patients with repaired TOF and various degrees of PR.

Acceleration↗

Effects of coil closure of patent ductus arteriosus on left anterior descending coronary artery blood flow using transthoracic Doppler echocardiography.

Transthoracic Doppler echocardiography provides noninvasive measurements of coronary blood flow in the left anterior descending coronary artery (LAD). This method has the potential to show the effects of acute changes in loading conditions on blood flow. Coil closure of patent ductus arteriosus (PDA) is a model of acute changes in blood pressure and left ventricular (LV) preload that influences coronary blood flow. We applied this technique to assess the coronary blood flow changes for patients with PDA before and immediately after PDA coil closure. We examined 9 patients (1.8 +/- 1.1 years) with simple PDA and 8 age-matched healthy children. LV dimensions and LV mass were measured. Maximum peak flow velocity and flow volume in the LAD were measured. Pulmonary to systemic flow ratios (Qp/Qs) were obtained by cardiac catheterization. After PDA coil closure, LV end-diastolic dimension decreased, and systolic and diastolic blood pressures increased significantly. The maximum peak flow velocity, LAD flow volume, and the ratio of LAD flow volume to LV mass increased significantly. The changes in maximum peak flow velocity and the ratio of LAD flow volume to LV mass (F/M) correlated positively with the changes in diastolic pressure and Qp/Qs. In 5 patients who had Qp/Qs > 1.5, the mean F/M was significantly lower compared with control subjects, but they increased to normal values after coil closure of PDA. PDA coil closure increases diastolic pressure and decreases Qp/Qs, resulting in improvement of myocardial perfusion. These findings provide new insights into the relationship between cardiac function and coronary circulation in pediatric patients with heart diseases associated with PDA.

Blood Circulation↗