Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition: a potential role of bradykinin.
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OBJECTIVES: This study was performed to determine whether angiotensin converting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and whether this is mediated by enhanced bradykinin activity. BACKGROUND: Abnormal coronary vasomotion due to endothelial dysfunction contributes to myocardial ischemia in patients with atherosclerosis, and its reversal may have an antiischemic action. Previous studies have shown that ACE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown. METHODS: In 19 patients with mild atherosclerosis, metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated during separate intracoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endothelium-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively. RESULTS: Enalaprilat did not alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (-5+/-1%) dilated (3+/-2%) with pacing in the presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5 ng/min) that did not alter resting diameter in the constricting segments also improved the abnormal response to a 6+/-1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27+/-4% (p < 0.001) remained unchanged after enalaprilat. CONCLUSIONS: Thus ACE inhibition: A) selectively improved endothelium-dependent but not-independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part, by increasing endogenous BK activity. (+info)
Endothelium-dependent relaxation by acetylcholine is impaired in hypertriglyceridemic humans with normal levels of plasma LDL cholesterol.
(26/7943)
OBJECTIVES: Patients with high triglyceride (of which very low density lipoproteins [VLDL] are the main carriers), but with normal low density lipoprotein (LDL) cholesterol levels, were examined for in vivo endothelium function status. BACKGROUND: Very low density lipoproteins inhibit endothelium-dependent, but not -independent, vasorelaxation in vitro. METHODS: Three groups were studied: 1) healthy volunteers (n = 10; triglyceride 1.24+/-0.14 mmol/liter, LDL cholesterol 2.99+/-0.24 mmol/liter); 2) hypertriglyceridemic (n = 11; triglyceride 6.97+/-1.19 mmol/liter, LDL cholesterol 2.17+/-0.2 mmol/liter, p < 0.05); and 3) hypercholesterolemic (n = 10; triglyceride 2.25+/-0.29 mmol/liter, LDL cholesterol 5.61+/-0.54 mmol/liter; p < 0.05) patients. Vasoactive responses to acetylcholine, sodium nitroprusside, noradrenaline, N(G)-monomethyl-L-arginine and postischemic hyperemia were determined using forearm venous occlusion plethysmography. RESULTS: Responses to acetylcholine (37 microg/min) were significantly dampened both in hypercholesterolemic (% increase in forearm blood flow: 268.2+/-62) and hypertriglyceridemic patients (232.6+/-45.2) when compared with controls (547.8+/-108.9; ANOVA p < 0.05). Responses to sodium nitroprusside (at 1.6 microg/min: controls vs. hypercholesterolemics vs. hypertriglyceridemic: 168.7+/- 25.1 vs. 140.6+/-38.9 vs. 178.5+/-54.5% increase), noradrenaline, N(G)-monomethyl-L-arginine and postischemic hyperemic responses were not different among the groups examined. CONCLUSIONS: Acetylcholine responses are impaired in patients with pathophysiologic levels of plasma triglycerides but normal plasma levels of LDL cholesterol. The impairment observed was comparable to that obtained in hypercholesterolemic patients. We conclude that impaired responses to acetylcholine normally associated with hypercholesterolemia also occur in hypertriglyceridemia. These findings identify a potential mechanism by which high plasma triglyceride levels may be atherogenic independent of LDL cholesterol levels. (+info)
Chordal force distribution determines systolic mitral leaflet configuration and severity of functional mitral regurgitation.
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OBJECTIVES: The purpose of this study was to investigate the impact of the chordae tendineae force distribution on systolic mitral leaflet geometry and mitral valve competence in vitro. BACKGROUND: Functional mitral regurgitation is caused by changes in several elements of the valve apparatus. Interaction among these have to comply with the chordal force distribution defined by the chordal coapting forces (F(c)) created by the transmitral pressure difference, which close the leaflets and the chordal tethering forces (FT) pulling the leaflets apart. METHODS: Porcine mitral valves (n = 5) were mounted in a left ventricular model where leading edge chordal forces measured by dedicated miniature force transducers were controlled by changing left ventricular pressure and papillary muscle position. Chordae geometry and occlusional leaflet area (OLA) needed to cover the leaflet orifice for a given leaflet configuration were determined by two-dimensional echo and reconstructed three-dimensionally. Occlusional leaflet area was used as expression for incomplete leaflet coaptation. Regurgitant fraction (RF) was measured with an electromagnetic flowmeter. RESULTS: Mixed procedure statistics revealed a linear correlation between the sum of the chordal net forces, sigma[Fc - FT]S, and OLA with regression coefficient (minimum - maximum) beta = -115 to -65 [mm2/N]; p < 0.001 and RF (beta = -0.06 to -0.01 [%/N]; p < 0.001). Increasing FT by papillary muscle malalignment restricted leaflet mobility, resulting in a tented leaflet configuration due to an apical and posterior shift of the coaptation line. Anterior leaflet coapting forces increased due to mitral leaflet remodeling, which generated a nonuniform regurgitant orifice area. CONCLUSIONS: Altered chordal force distribution caused functional mitral regurgitation based on tented leaflet configuration as observed clinically. (+info)
Changes in porcine transmitral flow velocity pattern and its diastolic determinants during partial coronary occlusion.
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OBJECTIVES: To define the mechanical determinants of transmitral flow and the effect of heart rate during regional ischemia. BACKGROUND: Myocardial ischemia changes the transmitral flow velocity pattern due to disease-induced changes in the heart's diastolic properties. METHODS: Regional ischemia was produced in 12 pigs by partially occluding the left anterior descending coronary artery until segment-length shortening in the ischemic region fell by 20%. Transmitral flow velocity patterns and their determinants were measured under two conditions, baseline and ischemia, at two heart rates, 70 and 90 beats/min. RESULTS: Regional ischemia had a significant effect on two determinants of filling: relaxation, which was slower, and chamber stiffness, which increased. These changes were associated with reduced contractility and increased myocardial stiffness, resulting in an early transmitral flow pattern that was flatter and narrower, but no change in the late flow pattern. Moderate increases in heart rate accelerated relaxation and decreased atrioventricular pressure gradient but had no effect on contractility or myocardial or chamber stiffness, resulting in an early transmitral flow pattern that was flatter and narrower and an increased late flow velocity. CONCLUSIONS: This model of regional ischemia leads to a flatter and narrower early transmitral flow velocity pattern and no change in late flow due to a combination of slowed left ventricular relaxation and increased chamber stiffness. Reflex increases in heart rate that accompany ischemia tend to mask this effect. (+info)
Cardiac function and morphology studied by two-dimensional Doppler echocardiography in unsedated newborn pigs.
(29/7943)
The newborn pig is currently the most used species in animal neonatal research. Valid non-invasive monitoring is important in particular for long-term survival of unsedated animals. In the unsedated newborn pig (n = 35, median age 24 h, range 7-48 h) we standardized two-dimensional Doppler echocardiography and determined the normal ranges for cardiac function. Probe positioning had to be adjusted to the V-shaped thorax and the mid-line position of the heart. Six out of the sixteen animals < 20 h had a patent ductus arteriosus compared with one of the twenty animals > 20 h old. One atrial septal defect (5 mm) and one small ventricular septal defect were diagnosed. The average heart size was 0.7-0.9% of body weight which is similar to human infants of the same size. The mean aortic diameter was 6.0 +/- 0.5 mm (mean +/- S.D.) and cardiac output was 0.38 +/- 0.08 l min-1; both correlate with body weight (r = 0.80 and 0.73, respectively). Tricuspid regurgitation velocity was 3.0 +/- 0.4 m s-1 (mean +/- S.D.), giving an estimated pressure gradient across the tricuspid valve of 37 +/- 9.7 mmHg. The aortic diameter and the heart weight per kg body weight are comparable to those reported for preterm neonates. The cardiac output and velocities across the four valves are more comparable with term neonates. (+info)
Effects of permanent dual-chamber pacing on mitral regurgitation in hypertrophic obstructive cardiomyopathy.
(30/7943)
AIMS: To assess the effects of chronic dual-chamber pacing on mitral regurgitation in hypertrophic obstructive cardiomyopathy. METHODS AND RESULTS: Twenty-three patients with hypertrophic obstructive cardiomyopathy and mitral regurgitation. treated with DDD pacing for 16 +/- 14 months, were included in the study. Mitral regurgitation was assessed by Doppler-echocardiography using semi-quantitative analysis (grades I-IV) and by measuring the maximum regurgitant jet area/left atrial area ratio. At the end of follow-up, DDD pacing reduced the outflow gradient from 93 +/- 37 mmHg to 31 +/- 30 mmHg (P<0.0001). Nine of the 14 patients who initially had > or =grade II mitral regurgitation improved by at least one grade, two of them exhibiting dramatic improvement (from grade IV and III to grade I). The regurgitant jet area/left atrial area ratio was reduced with DDD pacing from 20 +/- 13% to 11 +/- 6% (P<0.0001). Patients who had significant mitral regurgitation despite pacing were those whose outflow gradient remained high or those with mitral valve organic abnormalities (mitral annulus calcification or mitral valve prolapse). In the absence of organic abnormalities other than leaflet elongation, there was a significant correlation between the gradient value achieved with DDD pacing and the extent of mitral regurgitation (P<0.05). CONCLUSION: In the absence of organic mitral valve abnormalities, DDD pacing reduces in parallel mitral regurgitation and left ventricular outflow gradient. In such patients therefore, significant mitral regurgitation is not a contraindication to pacing. (+info)
Volume flow measurement in hemodialysis shunts using time-domain correlation.
(31/7943)
Volume flow was measured in 58 hemodialysis shunts (32 grafts and 26 radial fistulas) using the color velocity imaging-quantification method. This method is based on time-domain correlation for velocity calculation and integration of time-varying velocity profiles generated by M-mode sampling. Measurements were made in the brachial artery to estimate radial fistula flow or directly in the grafts. Intraoperator reproducibility was 14.9% for fistulas and 11.6% for grafts. Flow rate was significantly lower in abnormal shunts associated with a functional disorder or a morphologic complication (808 ml/min +/- 484) than in shunts associated with no abnormalities (1401 ml/min +/- 562). Receiver operating characteristic curves showed that a flow rate of 900 ml/min for fistulas and 1300 ml/min for grafts provided 81% and 79% sensitivity and 79% and 67% specificity, respectively. A functional disorder or a morphologic complication was associated with all fistulas and grafts in which flow rates were lower than 500 ml/min and 800 ml/min, respectively. (+info)
Signal-enhanced color Doppler sonography of deep venous thrombosis in the lower limbs and pelvis.
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Detection of Doppler signal tends to be more difficult in peripheral veins owing to low flow velocity. This can be caused by nonoccluding thrombosis, post-thrombotic wall changes, or a deep anatomic location of pelvic veins. The last-mentioned frequently is accompanied by interference by bowel gas. In addition, inappropriate insonation angles adversely affect the outcome of color-coded Doppler interrogation. The purpose of the present study was to evaluate the effectiveness of signal-enhanced color Doppler sonography on peripheral veins in 31 patients clinically suspected of having deep vein thrombosis. As a result of diagnostic uncertainty, additional enhanced studies were performed on 43 venous segments. The enhancement led to a decrease in false-positive results (from four patients to one patient) and false-negative results (from four patients to two patients) compared to unenhanced studies. Evaluation of the deeply located pelvic veins profited the most through signal enhanced Doppler sonography. (+info)