Systolic Amplitude Research Articles

Increased morning blood pressure surge and coronary microvascular dysfunction in patient with early stage hypertension

Morning blood pressure surge (MBPS) is defined as an excessive increase in blood pressure (BP) in the morning from the lowest systolic BP during sleep, and it has been reported as a risk factor for cardiovascular events in current clinical studies. In this study, we evaluated the association between the rate of BP variation derived from ambulatory BP monitoring data analysis and coronary microvascular function in patients with early stage hypertension. One hundred seventy patients with prehypertension and Stage 1 hypertension who fulfilled the inclusion and exclusion criteria were included in the study. We divided our study population into two subgroups according to the median value of coronary flow reserve (CFR). Patients with CFR values <2.5 were defined as the impaired CFR group, and patients with CFR values ≥2.5 were defined as the preserved CFR group, and we compared the MBPS measurements of these two subgroups. CFR was measured using transthoracic Doppler echocardiography (TTDE). Ambulatory 24-hour systolic and diastolic BP, uric acid, systolic MBPS amplitude, diastolic MBPS amplitude, high-sensitivity C-reactive protein, and mitral flow E/A ratio were statistically significant. These predictors were included in age- and gender-adjusted multivariate analysis; ambulatory 24-hour systolic BP (ß = 0.077, P < .001; odds ratio [OR] = 1.080; 95% confidence interval [CI] [1.037–1.124]) and systolic MBPS amplitude (ß = 0.043, P = .022; OR = 1.044; 95% CI [1.006–1.084]) were determined to be independent predictors of impaired CFR (Hosmer–Lemeshow test, P = .165, Nagelkerke’s R2 = 0.320). We found that increased changes in MBPS values in patients with prehypertension and Stage 1 hypertension seemed to cause microvascular dysfunction in the absence of obstructive coronary artery disease.

Age-dependent and ‘pathologic’ changes in ICG waveforms resulting from superposition of pre-ejection and ejection waves

Impedance cardiography (ICG) is a popular bioimpedance application used for the non-invasive evaluation of the left ventricular stroke volume and contractility. It implies the correct determination of ejection start and end points and the amplitudes of certain peaks in a differentiated impedance cardiogram. An accurate identification of ejection onset by ICG is often problematic, especially in cardiologic patients, due to the peculiar character of the waveforms. A simple theoretical model was employed to test the consequences of the hypothesis that two major processes can contribute to the formation of an impedance systolic wave: (1) the pre-ejection changes in heart geometry and the surrounding vessels produced by ventricular contraction during the isovolumic phase, and (2) the expansion of aorta and adjacent arteries during the ejection per se. The former process initiates the pre-ejection wave while the latter triggers the ejection wave, both of which contribute to the impedance pulse waves associated with the heartbeats. A new two-bell model predicts a potential mechanism responsible for the abnormal shapes of ICG derivative dZ/dt due to the presence of the pre-ejection waves and explains the related errors in systolic time intervals and amplitude parameters derived from such ICG waveforms. It also advances an alternative viewpoint on the nature of the dZ/dt B-point notch. An appropriate decomposition method opens a promising way to avoid the masking effects of these waves and to correctly determine the onset of ejection as well as the corresponding peak amplitudes from the ‘pathologically shaped’ ICG signals.

New strategies for prevention and treatment of splenic artery steal syndrome after liver transplantation

To explore a prophylactic procedure to prevent splenic artery steal syndrome (SASS), as well as a therapeutic intervention to correct it. Forty-three liver transplant patients were enrolled in a non-randomized controlled trial, with the eligible criterion that the diameter of the splenic artery is more than 5 mm and/or 1.5 times of the diameter of the hepatic artery. The procedure of splenic artery banding was performed in 28 of the 43 patients, with the other 15 patients studied as a control group. SASS and other complications were compared between these two groups. A new therapeutic intervention, temporary incomplete blockade of the splenic artery with a balloon, was performed to treat SASS in this study. The incidence of SASS was decreased by banding the splenic artery (0/28 vs 5/15, P = 0.006), and the same result was observed in total complications associated with prophylactic procedures (2/28 vs 6/15, P = 0.014). Five patients in the control group developed SASS within 5 d after OLT, 2 of whom were treated by coil embolization of the splenic artery, whereas the other 3 by temporary blockade of the splenic artery. Reappeared or better hepatic arteries with improved systolic amplitude and increased diastolic flow were detected by Doppler ultrasonography in all the 5 patients. Local splenic ischemic necrosis and nonanastomotic biliary stricture were diagnosed respectively in one patient treated by coil embolization, and no collateral complication was detected in patients treated by temporary blockade of the splenic artery. SASS should be avoided during the operation by banding the splenic artery. Temporary blockade of the splenic artery is a new safe and effective intervention for SASS.

Clinical and echocardiographic predicators of postoperative atrial fibrillation.

Postoperative atrial fibrillation is the most common arrhythmiaafter coronary artery bypass grafting,with a reported incidence of 10% to 60%. Preoperative clinical and echocardiographic data, especially the atrial electromechanical interval, predict postoperative atrial fibrillation in elective coronary artery bypass patients. A prospective study evaluated preoperative clinical and echocardiographic data in 192 patients who underwent elective coronary artery bypass from 2010 to 2012. 18 (9.37%) patients developed postoperative atrial fibrillation. Compared to patients without postoperative atrial fibrillation, these 18 had significantly longer intensive care unit and hospital stays, they were significantly older (58.62 ± 10.02 vs. 53.22 ± 8.23 years; p = 0.02), with a larger left atrial volume (83.39 ± 8.31 vs. 55.47 ± 8.37 cm(3), p = 0.001), longer atrial electromechanical interval (133.67 ± 8.15 vs. 98.05 ± 6.71 ms p < 0.0001), and lower tissue Doppler imaging systolic velocity wave amplitude (6.6 ± 1 vs. 9.4 ± 2.2 cm·s(-1); p = 0.001); they also had a higher prevalence of hypertension (61.11% vs. 38.5%; p = 0.04). Using 115 ms as the cutoff value of atrial electromechanical interval enabled us to detect patients who developed postoperative atrial fibrillation with 100% sensitivity, 77% specificity, 78% positive predictive value, and 100% negative predictive value. Older hypertensive patients are at higher risk of developing postoperative atrial fibrillation. Preoperative measurement of atrial electromechanical interval by tissue Doppler echocardiography is a useful predictor of postoperative atrial fibrillation in coronary artery bypass patients.

Patterns of cardiac dysfunction coinciding with exertional breathlessness in hypertrophic cardiomyopathy

ObjectiveThe commonest cause of breathlessness in hypertrophic cardiomyopathy (HCM) is left ventricular outflow tract (LVOT) obstruction which improves with its removal. However, in the absence of outflow tract obstruction, as in dilated cardiomyopathy, patients may be limited by similar symptoms, thus suggesting a potential common mechanism for the two conditions. We aimed to assess cardiac function at the time of symptoms in a group of unselected patients with HCM to identify other patterns of cardiac dysfunction which coincide with their breathlessness. MethodsWe studied 37 HCM patients (aged 55±15years, 13 female) with septal thickness >15mm and 17 controls (aged 58±12years, 12 female) using Doppler echocardiography, at rest and at peak dobutamine stress. Stress end points were symptoms, >20mmHg drop in systolic blood pressure, arrhythmia, or maximum dobutamine dosage of 40μg/kg/min. ResultsAt rest: LV systolic function was maintained (EF 68±7 v 76±12%, respectively), LVOT velocity raised (p<0.005), lateral and septal long axis amplitude reduced (p<0.05 and p<0.005, respectively) and dyssynchronous and QRS duration was also broader (p<0.005) in patients compared to controls. At peak stress: Overall LVOT velocities were higher in patients than controls (4.3±1.7 v 1.7±1.0m/s, p<0.005, respectively) due to systolic anterior movement of the mitral valve and mitral regurgitation developing. In the 15 patients who did not develop significant LVOT obstruction (velocity <4m/s), LV ejection time increased and peak systolic amplitude did not increase. In the 10 patients with neither LVOT obstruction nor restrictive filling, QRS duration prolonged by 12ms (p <0.05), post-ejection shortening worsened and peak systolic amplitude fell (p<0.005). Also, LV ejection time prolonged by 5s/min (p<0.05), filling time failed to increase as it did in controls (p<0.005) and Tei index was higher than controls (p<0.01). ConclusionExertional breathlessness in HCM is associated with LV outflow tract obstruction and functional mitral regurgitation in almost two thirds of patients. The remaining one third have either resistant restrictive physiology or dyssynchronous cavity at fast heart rate. Despite similar exercise limiting breathlessness in the three groups, means of management should be quite different.

On Using Maximum a Posteriori Probability Based on a Bayesian Model for Oscillometric Blood Pressure Estimation

The maximum amplitude algorithm (MAA) is generally utilized in the estimation of the pressure values, and it uses heuristically obtained ratios of systolic and diastolic oscillometric amplitude to the mean arterial pressure (known as systolic and diastolic ratios) in order to estimate the systolic and diastolic pressures. This paper proposes a Bayesian model to estimate the systolic and diastolic ratios. These ratios are an improvement over the single fixed systolic and diastolic ratios used in the algorithms that are available in the literature. The proposed method shows lower mean difference (MD) with standard deviation (SD) compared to the MAA for both SBP and DBP consistently in all the five measurements.

Cyclical modulation of human ventricular repolarization by respiration.

Background: Respiratory modulation of autonomic input to the sinus node results in cyclical modulation of heart rate, known as respiratory sinus arrhythmia (RSA). We hypothesized that the respiratory cycle may also exert cyclical modulation on ventricular repolarization, which may be separately measurable using local endocardial recordings. Methods and Results: The study included 16 subjects with normal ventricles undergoing routine clinical electrophysiological procedures for supraventricular arrhythmias. Unipolar electrograms were recorded from 10 right and 10 left ventricular endocardial sites. Breathing was voluntarily regulated at 5 fixed frequencies (6, 9, 12, 15, and 30 breaths per min) and heart rate was clamped by RV pacing. Activation-recovery intervals (ARI: a surrogate for APD) exhibited significant (p < 0.025) cyclical variation at the respiratory frequency in all subjects; ARI shortened with inspiration and lengthened with expiration. Peak-to-peak ARI variation ranged from 0–26 ms; the spatial pattern varied with subject. Arterial blood pressure also oscillated at the respiratory frequency (p < 0.025) and lagged behind respiration by between 1.5 s and 0.65 s from slowest to fastest breathing rates respectively. Systolic oscillation amplitude was significantly greater than diastolic (14 ± 5 vs. 8 ± 4 mm Hg ± SD, p < 0.001). Conclusions: Observations in humans with healthy ventricles using multiple left and right ventricular endocardial recordings showed that ARI action potential duration (APD) varied cyclically with respiration.

Abstract 9254: Downregulation of SR Ca 2+ -ATPase as a Contributing Cause of Impaired Cardiomyocyte Basal and Beta-Adrenergic Regulation of [Ca 2+ ]i with Myocyte Dysfunction in Monkeys with Chronic Heavy Alcohol Consumption

Background . Recent evidence indicates that the main effect of chronic alcohol ingestion is the loss of left ventricle (LV) contractility that progressively induces the development of alcoholic cardiomyopathy (ACM) and heart failure. However, the mechanisms underlying this sequela of events remain unclear. We tested the hypothesis that chronic alcohol-intake-caused progressive LV dysfunction is intrinsic to cardiomyocytes, and that impaired SR Ca 2+ -ATPase (SERCA 2a) function may play a key role. Methods . We compared the expression and activity of cardiac SERCA 2a and assessed myocyte contractile, [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses to isoproterenol (ISO, 10 -8 M), a β-adrenergic receptor (AR) agonist, in isolated myocytes obtained from biopsied LV tissues of cynomolgus monkeys: 6 normal controls (N) and 6 monkeys who chronically self-administered high levels of alcohol (HA) (4% alcohol, 3.3±0.7 g/kg) for 12 months. Results. Compared with controls, in alcoholic myocytes, SERCA 2a protein expression was decreased 56% (0.50 vs 0.89) and Ca 2+ -dependent activity of SERCA 2a was decreased 69% (32.7 vs 107.2 nmol/mg protein/min) (p&lt;0.05). This change of SERCA 2a was associated with significant decreases in basal cell systolic amplitude (SA) (79%, HA: 6.4±1.3% vs N: 11.5±1.6%), velocity of shortening (dL/dt max ) (38%, 64.8±5.0 vs 104.8±6.0 μm/s), velocity of relengthening (dR/dt max ) (39%, 54.2±4.7 vs 88.4±5.3 μm/s), and a 34% prolonged time to peak of shortening. In the alcoholic myocytes, the peak [Ca 2+ ] iT (33%, HA: 0.21±0.05 vs N: 0.31±0.05) was significantly reduced, but the diastolic [Ca 2+ ] iT was increased and the decline of [Ca 2+ ] i was slower. These alterations were accompanied by diminished ISO-stimulated positive inotropic effect. Compared with normal controls, in alcoholic cardiomyocytes, ISO (10 -8 M) significantly blunted the increases in SA (HA: 27% vs N: 60 %), dL/dt max (49% vs 79%), dR/dt max (24% vs 38%) and [Ca 2+ ] iT (16% vs 32%). Conclusions. Chronic heavy alcohol intake causes downregulation of cardiac SERCA 2a with depressed myocyte contractile performance and abnormal myocyte basal and β-adrenergic regulation of [Ca 2+ ] i . These findings support a mechanistic role of chronic alcohol-induced cardiac SERCA 2a dysfunction in ACM.

Changes in some indices of the cardiovascular system in different mental tasks

In order to study the effects of the type of mental activity on the function of the cardiovascular system in humans, the following indices were used: the heart rate (HR), RR interval, variation magnitude (VM), systolic wave amplitude (SWA), and pulse wave transit time (PWTT). These indices were recorded when the subjects solved verbal-logical or spatial mental tasks. The HR was substantially increased during solving of the spatial tasks as compared to solving of the verbal-logical tasks, whereas the SWA showed the opposite changes. The latencies of the performance of the tasks of various types were similar in the subjects; therefore, the changes in the autonomic indices did not depend on the difficulties of the mental tasks. They rather depended on specific features of the mental processes involved in the performance of the tasks of different types. Thus, changes in the HR and the decreased SWA, which was related to elevated blood pressure, represent the effect of the sympathetic nervous system on the heart function during solving verbal-logical tasks. Our data demonstrate that the HR and blood pressure can be used as additional indices for the development of new techniques for assessment of different types of mental processes together with the indices of electrical brain activity.

Acute Effects of Low Doses of Ethanol on Left and Right Ventricular Function in Young Healthy Subjects

Moderate-to-high blood concentrations of ethanol acutely impair conventional echocardiographic measures of left ventricular (LV) performance, but the effects of low concentrations are unclear. This study explored the acute effects of low blood concentrations of ethanol on sensitive and load-independent indices of LV and right ventricular (RV) function. This is a crossover experimental study conducted in 64 young healthy volunteers. Participants were asked to drink a light dose of Italian red wine equivalent to 0.5 mg/kg of ethanol, and an equal volume of fruit juice in separate experiments. The following measurements were taken at baseline and 60 minutes after the challenges: tissue Doppler mitral annulus systolic velocity (S') and excursion (MAPSE), early diastolic velocity (E'), its ratio to late diastolic velocity (E'/A'), and the ratio of mitral-to-myocardial early diastolic velocities (E/E'); and tricuspid annulus systolic velocity (tricuspid S') and amplitude (TAPSE), early diastolic velocity (tricuspid E'), and its ratio to late diastolic velocity (tricuspid E'/A'). Blood ethanol concentration after wine intake was 0.48 ± 0.06 g/l. Compared with the control challenge, ethanol yielded a decrease in all measures of LV function (S', -9.7%; E', -11.2%; E'/A', -13.4%; MAPSE, -8.8%; p < 0.05 for all). Among indices of RV function, increases in tricuspid E'/A' ratio and TAPSE were observed (+24.5% and +9.0%, respectively; p < 0.05 for both). Low blood concentrations of ethanol acutely impair LV function and increase some indices of RV function in young healthy individuals.

172 Increasing anti-oxidant capacity reverses iron overload mediated dysfunction in cardiomyocytes

IntroductionIron overload-cardiomyopathy (IOCM) is an increasing clinical problem worldwide. 70% of patients who receive compulsory blood transfusion die of IOCM, with increased susceptibility to arrhythmias and sudden death. We have...

Mitral annular longitudinal function preservation after mitral valve repair: The MARTE study

BackgroundIn patients with chronic mitral regurgitation (MR), undergoing surgical mitral valve repair, current Guidelines only recommend standard echocardiographic indices i.e. left ventricular (LV) ejection fraction (EF), and LV end-systolic and end-diastolic diameters as preoperative variables. However LV EF is often preserved until advanced stages of the valve disease. Aim of this study was to evaluate changes in LV systolic longitudinal function, 3months after mitral valve repair in patients with chronic degenerative MR and normal preoperative EF. MethodsWe measured M-mode mitral lateral annulus systolic excursion (MAPSE) and Tissue Doppler (TD) peak systolic annular velocity (Sm) in 31 patients with moderate to severe MR and normal EF (59.9±4.7%) candidates for mitral valve repair, preoperatively and 3months after surgery. ResultsAfter mitral valve repair, Sm increased from 7.8±1.4 to 9.6±2.2cm/s (p<0.0001) and MAPSE increased from 1.33±0.26 to 1.55±0.25cm (p=0.0013). EF decreased from 59.9±4.7 to 51.3±5.9% (p<0.0001). As expected, LV diameters and volumes, wall thicknesses, midwall fractional shortening (mFS), and left atrial (LA) size were all reduced after surgery. ConclusionsThis study suggests that assessment of LV long axis systolic velocity and amplitude of excursion by echocardiography is more sensitive than simple determination of EF for revealing the beneficial impact of MR surgery on overall systolic function.

Variability of maximum systolic amplitude of ΔZ/Δt curve in pregnancy. Perennial observations

Maximum systolic amplitude is quite an important component of the impedance cardiogram ΔZ/Δt curve. Its values make it possible to calculate many hemodynamic indices. Therefore it is necessary to keep informed about monthly, annual and perennial maximum systolic amplitude trend. We can produce the measuring data of the maximum systolic amplitude for a fifteen-year period (from 1994 to 2009). The impedance cardiograms were obtained with the help of an electric impedance analyzer "RA-5" (1 mA, 70 kHz) with disk ECG electrodes. The data analyzed were taken from the pregnant women with non-complicated pregnancy (n=5709). We have analyzed the average monthly and annual changes of the maximum systolic amplitude ΔZ/Δt curve. It allowed us to reveal the six-year periodicity of the maximum systolic amplitude changes. There were discovered statistically significant peak values difference of the amplitude (p>0.001). The data obtained should be taken into consideration when using impedance cardiography in clinical practice. The article is supplied with tables and diagrams.

Intramural Dyssynchrony from Acute Right Ventricular Apical Pacing in Human Subjects with Normal Left Ventricular Function

Ventricular pacing causes early myocardial shortening at the pacing site and pre-stretch at the opposing ventricular wall. This contraction pattern is energetically inefficient and may lead to decreased cardiac function. This study was designed to describe the acute effects of right ventricular apical (RV(a)) pacing on dyssynchrony and systolic function in human subjects with normal left ventricular (LV) function and compare these effects to pacing from alternate ventricular sites. Patients (n = 26) undergoing an electrophysiology evaluation were studied during atrial pacing (AAI) and dual chamber pacing from the RV(a), left ventricular free wall (LV(fw)), and the combination of RV(a) and LV(fw) (BiV). Tissue Doppler imaging was used to measure intramural dyssynchrony by utilizing an integrated cross-correlation synchrony index (CCSI) from the apical 4-chamber view. RV(a) and BiV pacing significantly reduced systolic function as measured by longitudinal systolic contraction amplitude (SCA(long)) (p < 0.05) and LV velocity time integral (VTI) (p < 0.05) compared to AAI and LV(fw) pacing. RV(a) (and to a lesser extent BiV) pacing resulted in septal and lateral intramural dyssynchrony as indicated by significantly (p < 0.05) lower CCSI values as compared to AAI. CCSI was significantly (p < 0.05) worse during RV(a) than LV(fw) pacing. In patients with normal LV function, acute ventricular pacing in the RV(a) alone, or in conjunction with LV(fw) pacing (BiV), results in impaired regional and global LV systolic function and intramural dyssynchrony as compared to LV(fw) pacing alone.

Influence of respiratory rate on the variability of blood volume pulse characteristics

Photoplethysmogram (PPG) measures have been proven useful for the quantification of sympathetic reactivity and continuous monitoring of vascular reactivity. This study was designed to delineate the influence of respiratory rate on the variability of various PPG characteristics in time and frequency domains. PPG, electrocardiogram (ECG) and respiration were simultaneously recorded for 2 min from eight healthy volunteers during paced respiration of 6, 12 and 18 cycles min−1. The PPG characteristics such as peak-to-peak interval (PPI), systolic peak amplitude, slope, Tcrest, Tdecay and pulse transit time (PTT) were computed for every pulse. In time domain, the mean of amplitude, slope and Tcrest were not significantly different amongst three different respiratory rates. However, the mean of Tdecay, PPI and PTT were significantly increased (p < 0.05, p < 0.05 and p < 0.01, respectively) during respiration of 6 cycles min−1 compared to 12 cycles min−1. The maximal spectral powers of the variability of all PPG measures were centred on the respiratory frequency in frequency domain. In conclusion, the results that the amplitude and slope in time domain are not altered by the respiratory frequency suggest their application in faithful assessment of cardiovascular reactivity. As the variability of PPI, Tdecay and PTT are altered by the slow respiration, the influence of respiration on these time derivatives should not be ignored during interpretation of vascular reactivity.

Abstract 5326: S100A1 Prevents Arrhythmogenic Diastolic Sarcoplasmic Reticulum Calcium Leak In Ventricular Cardiomyocytes

Background: S100A1 is an inotropic calcium (Ca) sensor protein in cardiomyocytes interacting with the cardiac ryanodine receptor (RyR2). Previous studies of our group have shown that S100A1 protein can decrease Ca spark frequency in permeabilized ventricular cardiomyocytes (CMs). We therefore hypothesized that S100A1 might prevent arrhythmogenic sarcoplasmic reticulum (SR) Ca leak in CMs. Methods and Results: Ventricular rat cardiomyocytes were enzymatically isolated and transfected either with 10 MOI of a CMV-GFP control or CMV-S100A1/CMV-GFP adenovirus resulting in GFP fluorescence in &gt;99% of cultured GFP-CMs and S100A1-CMs as assessed by epifluorescent microscopy after 24-hours. Expression analysis revealed a 3-fold increase in S100A1 protein in S100A1-CM levels compared to GFP-CM. Confocal line-scan microscopy yielded a 50% reduction in Ca spark frequency in rhodamin2-AM loaded quiescent S100A1-CMs and epifluorescent imaging showed a 20% and 50% increase in the SR Ca content and systolic Ca transient amplitude, respectively, in FURA2-AM loaded 2Hz-stimulated S100A1-CM (37°C, 1.8 mM Ca) compared with GFP-CMs. Pathophysiological diastolic SR Ca leak was induced subjecting 2Hz-stimulated FURA2-AM loaded CMs to 0.5 mM caffeine and 10–7 M isoproterenol (caff/iso) as previously published by Isner and co-workers. As expected, this protocol resulted in permanent diastolic Ca waves in 100% (n=60/60) of 2Hz-stimulated iso/caff-treated GFP-CMs and was accompanied by significantly increased diastolic Ca levels and reduced systolic Ca transient amplitudes compared with iso-treated GFP-CMs. However, S100A1 efficiently protected more than 80% of iso/caff treated S100A1-CMs (n=49/60 cells, P&lt;0.05 vs. iso/caff GFP-CMs) from diastolic Ca waves and further alterations of CM Ca handling. Importantly, similar results were obtained in caff/iso-treated failing rat GFP- and S100A1-CMs (data not shown). Conclusions: Here we show for the first time that S100A1 can both diminish the physiological SR Ca leak and protect from arrhythmogenic Ca waves in CMs. Given its beneficial effects in the context of experimental HF animal models, S100A1 therapeutic inotropic actions might be complemented by an antiarrhythmic effect targeting dysfunctional RyR2.

Renal artery stenosis: Extracting quantitative parameters with a mathematical model fitted to magnetic resonance blood flow data

To investigate the feasibility of quantitative parameter extraction from a mathematical model fitted to renal artery magnetic resonance flow data. A total of 16 subjects, eight patients, and eight normal controls, were examined with cine phase-contrast velocity measurements, and blood flow data from the aorta and both renal arteries were extracted by means of contour detection. A mathematical model with eight parameters describing the time, duration, and amplitude of the systolic acceleration and the diastolic deceleration was fitted to the aorta and renal artery blood flow data from each subject. The curve fitting was evaluated with R(2) values. Statistical analysis was performed with unpaired Wilcoxon tests and stepwise logistic regression. A total of three data sets out of 48 yielded R(2) values below 0.80 and were considered unreliable for parameter estimation. Basal flow was significantly, and systolic peak amplitude almost significantly, lower in stenotic arteries. Logistic regression indicated that two parameters describing basal flow and the duration of acceleration can accurately predict stenosis. The results suggest that it is technically feasible to fit a mathematical model to renal blood flow data, extracting quantitative parameters that may prove useful for quantification and diagnosis of renal artery stenosis.

Abstract 1506: Upregulation of Cardiac AT 1 Receptor Signaling Inhibits Myocyte Contractile Performance, [Ca 2+ ] i Transient, and Ca 2+ Current in Alcoholic Dogs: Insights into the Underlying Molecular Mechanism

Background. Chronic alcohol ingestion is accompanied by sustained renin-angiotensin system (RAS) activation followed by progressive left ventricular (LV) myocyte dysfunction. This suggests a role for angiotensin II (AII) in the development of alcoholic cardiomyopathy (ACM). We tested the hypothesis that chronic alcohol intake may cause upregulation of AII AT 1 receptors and altered cardiac inotropic response to AII stimulation, thus contributing to the development of ACM. Methods. We compared LV myocyte AT 1 - and AT 2 -receptor mRNA and protein levels, myocyte contractile function, [Ca 2+ ] i transients ([Ca 2+ ] iT ), and Ca 2+ current (I Ca,L ) in response to AII (10 −6 M) in 16 instrumented dogs over 6 months. Eight animals received alcohol (once per day orally, providing 33% of total daily caloric intake), and eight were controls. Myocytes were isolated from LV myocardial biopsy tissues. Results . Compared with controls, the alcoholic myocytes showed increased AT 1 mRNA (0.69 vs 0.33) and protein levels (0.79 vs 0.37) ( p &lt;0.01). Conversely, AT 2 mRNA (0.18 vs 0.16) and protein concentration (0.16 vs 0.14) were relatively unchanged. Importantly, in alcoholic myocytes, the increased AT 1 receptors were associated with altered myocyte inotropic response to AII. In control myocytes, superfusion of AII (10 −6 M) increased myocyte systolic amplitude (SA, 14.9 vs 12.4%) and the maximum rate of shortening (dL/dt max , 203.1 vs 153.9 μm/s) accompanied by significant increases in [Ca 2+ ] iT (1.52 vs 1.21) and I Ca,L (4.0 vs 3.3 pA/pF). In alcoholic myocytes, this positive response was reversed. AII caused significant decreases in SA (3.4 vs 5.8 %), dL/dt max (50.5 vs 78.9 μm/s), and the maximum rate of relaxation (dR/dt max, 37.5 vs 59.6 μm/s) associated with reduced [Ca 2+ ] iT (0.86 vs 1.12) and I Ca,L (1.5 vs 2.1 pA/pF) ( p &lt;0.05). These AII-induced changes in alcoholic myocytes were abolished by incubation of alcoholic myocytes with an AT 1 receptor blocker, losartan (10 −5 M), or pretreatment with a G i inhibitor, PTX (2 μg/ml, 36°C, 5h). Conclusions. In a canine model, chronic alcohol consumption produces upregulation of LV myocyte AII AT 1 receptors and alters myocyte functional response to AII stimulation, which may promote the development of ACM.

Restrictive Right Ventricular Physiology: Its Presence and Symptomatic Contribution in Patients With Pulmonary Valvular Stenosis

The aim of this study was to examine whether restrictive right ventricular (RV) physiology (the presence of antegrade pulmonary arterial flow in late diastole) occurred in patients with moderate to severe isolated pulmonary valvular stenosis (PVS) and to estimate its prevalence and relationship to RV function and patient symptoms. Little is published about RV diastolic performance in adult patients with PVS. A total of 43 consecutive patients (age 44 +/- 10 years) with moderate to severe PVS referred to Royal Brompton Hospital from 2002 to 2005 were retrospectively studied. Patient New York Heart Association (NYHA) functional class was recorded. The RV (lateral tricuspid annulus motion) long-axis movement was measured by M-mode and pulsed-wave (PW) tissue Doppler imaging (TDI). Restrictive RV physiology was assessed by PW Doppler echocardiography. Eighteen patients (42%) had restrictive RV physiology. They were more symptomatic (NYHA functional class 1.8 +/- 0.5 vs. 1.3 +/- 0.5; p < 0.001) and had poorer RV long-axis function (TDI peak systolic velocity 7.3 +/- 2.1 cm/s vs. 9.7 +/- 2.7 cm/s; TDI early diastolic velocity 6.6 +/- 1.6 cm/s vs. 8.5 +/- 2.4 cm/s; RV long-axis systolic amplitude 1.3 +/- 0.2 cm vs. 1.5 +/- 0.3 cm; p < 0.01 for all) compared with other PVS patients despite similar RV ejection fraction, myocardial performance index, and RV systolic pressure. The presence of restrictive RV physiology (odds ratio [OR] 6.05, 95% confidence interval [CI] 1.45 to 10.29; p = 0.01) and peak pulmonary valve pressure gradient (OR 1.07, 95% CI 1.01 to 1.13; p = 0.04) were the 2 independent echocardiographic predictors for decreased exercise tolerance in patients on multivariate analysis. Restrictive RV physiology is common in PVS patients. Its presence is related to a worse deterioration in RV long-axis function and decreased exercise tolerance in patients.

Ventricular long-axis function is of major importance for long-term survival in patients with heart failure

Objective:To assess the importance of ventricular systolic and diastolic long-axis (LAX) function in comparison with short-axis (SAX) function for prediction of long-term survival in patients with heart failure.Design:Prospective epidemiological study.Setting:University...