Right ventricular diastolic disfunction and its relation to left ventricular performance in patients with hypertension

The potential effects of propofol emulsion (Diprivan) on the neuromuscular transmission and muscular contraction were studied using in vitro and in vivo nerve-muscle preparations of rats. The contractions of the isolated rat diaphragm elicited by either indirect or direct electrical stimulation were inhibited by propofol emulsion at threshold concentrations of 42 and 112 mumol l-1, respectively. Similarly, the gastrocnemius muscle contractions induced by either indirect or direct electrical stimulation in vivo were inhibited by propofol emulsion administration as a bolus injection of 2.5 mg kg-1 intravenously, followed by intravenous infusion of 150 micrograms kg-1 min-1 for 1 h into rats. The inhibitory effects of propofol in both preparations were greater with indirect rather than direct stimulation. Propofol emulsion was found to be capable of enhancing the paralysis of the indirectly stimulated rat diaphragm in vitro and gastrocnemius muscle in vivo induced by either pipecuronium or succinylcholine. The combination of propofol and pipecuronium led to a synergistic inhibition of the neuromuscular transmission, while the combination of propofol and succinylcholine led to additive inhibition. Pretreatment with propofol emulsion at these threshold concentrations markedly inhibited the stimulant effects of aminophylline and digoxin on the indirectly and directly induced diaphragmatic contractions. Also, the enhancement effects of aminophylline on the indirectly and directly and of digoxin on indirectly induced rat gastrocnemius muscle contractions were markedly inhibited by propofol emulsion administration to rats. Pretreatment with propofol emulsion at the threshold concentrations enhanced the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly and enhanced the inhibitory effect of adenosine on the contractions elicited indirectly. Similarly, the inhibitory effects of verapamil on the indirectly and directly and of adenosine on indirectly induced rat gastrocnemius muscle contractions were markedly potentiated by propofol emulsion administration to rats. In addition, doubling the concentration of calcium in the bathing fluid produced no change in the inhibitory effects of propofol emulsion on either indirectly or directly elicited diaphragmatic contractions, while doubling the concentration of external magnesium potentiated the propofol effects. Pretreatment with 4-aminopyridine suppressed the inhibitory effects of propofol emulsion on diaphragmatic contractions elicited either indirectly or directly. These results suggest that propofol acts presynaptically to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction.     

Exercise capacity in patients with beta-thalassemia major: relation to left ventricular and atrial size and function

OBJECTIVES: The objective of this study was to examine the association between exercise capacity and echocardiographic indexes of atrial and ventricular function and size in patients with beta-thalassemia major. BACKGROUND: In patients with beta-thalassemia major, the assessment of cardiac function with echocardiography alone does not always correspond to their functional status. Peak oxygen uptake and anaerobic threshold, on the other hand, constitute 2 objective and reproducible determinants of exercise capacity in patients with heart failure. METHODS AND RESULTS: Forty consecutive patients (22 women and 18 men, 18 to 30 years old) who were in stable condition while receiving regular transfusions and 30 age- and sex-matched control subjects were studied. At 2 to 3 days after the last transfusion, each subject underwent complete echocardiographic study followed by cardiopulmonary exercise testing. Left atrial volumes (maximal [Vmax], at onset of atrial systolic [Vp], and minimal [Vmin]) and left ventricular volumes were measured with the biplane area-length method, and left atrial active emptying fraction (ACTEF) and left ventricular ejection (LVEF) fraction were calculated. Peak oxygen uptake (Vo 2 max) and anaerobic threshold (AT) were also estimated. After transfusion, patients with beta-thalassemia major had reduced Vo 2 max and AT and greater left atrial volume in comparison with control subjects. Also, ACTEF and LVEF were significantly lower in the patient group. Moreover, Vo2 max and AT were inversely related to Vmax (r = -0.74 and r = -0.80, respectively) and directly related to ACTEF (r = 0.85 and r = 0.82, respectively) in beta-thalassemia major, whereas they were poorly related to LVEF (r = 0.50 and r = 0. 53, respectively). In the control group, Vo 2 max and AT parameters were related to Vmax and ACTEF in a similar way to that in the beta-thalassemia group. CONCLUSIONS: In patients with beta-thalassemia major, exercise capacity does not correlate with left ventricular dimensions and function. On the contrary, left atrial size and systolic dysfunction are probably predictors of decreased exercise capacity.     

Relationship between atrial function, left ventricular isovolumic relation time, and early filling in dual chamber-paced patients

This investigation was performed to study atrial systolic function is response to modification of atrioventricular delay in a sample of 36 patients with a DDD pacemaker implanted for complete atrioventricular block. The relation between atrial systolic performance and diastolic-related parameters was also evaluated. Isovolumic relaxation time, early diastolic peak velocity, late (atrial) diastolic peak velocity, atrial filing fraction, and atrial ejection force were recorded at a pacing rate of 70 impulses/min and at atrioventricular delay of 200, 150, and 100 msec. Our data showed that the progressive shortening of atrioventricular delay induced a gradual increase in early peak velocity (median value 46 to 53 to 61.5 cm/sec, respectively, at 200, 150, and 100 msec intervals) and a gradual decrease in isovolumic relaxation time (median 92.6 to 81.5 to 69.7 msec at 200, 150, and 100 msec, respectively), atrial peak velocity (59 to 52 to 44.5 cm/sec at 200, 150, and 100 msec, respectively), atrial filling fraction (50.5% to 40% to 23.5% at 200, 150, and 100 msec, respectively), and atrial ejection force (17.2 to 14.7 to 8.5 kilodynes at 200, 150, and 100 msec, respectively). For every atrioventricular delay value detected, we found a significant correlation between isovolumic relaxation time and early peak velocity with atrial filling fraction and atrial ejection force. In addition, atrial ejection force was related directly to atrial filling fraction at studied atrioventricular delays. The two indexes of atrial systolic performance showed a parallel decrease by shortening the atrioventricular delay, and they can quantify atrial systolic performance equally in sequentially paced patients. Furthermore, our results are in accordance with the hypothesis that the interaction between the effectiveness of active left atrial emptying and isovolumetric relaxation time may play an important role in maintaining an ideal ventricular filling despite changes in atrial systolic function.     

Hemodynamic basis of mitral E transmission in the left ventricular cavity and its relation to the left ventricular relaxation process

Mitral E-wave transit time to the left ventricular outflow tract was measured as an E-Er interval in 30 subjects undergoing cardiac catheterization. The E-Er interval (range 30 to 190 ms) correlated with left ventricular peak negative dP/dt (r = -0.62, p = 0.0003) and tau (r = 0.74, p <0.0001) but not with left ventricular minimum, pre-A-wave, or end-diastolic pressures. We conclude that the E-Er interval is an easily obtainable Doppler measurement that reflects the left ventricular relaxation process.     

Measurement of the left ventricular mass using MRI with automatic determination of the endocardial and epicardial contours

This study describes a method of automatic border detection of the left ventricular endocardium and epicardium associating three methods of segmentation (increase of region, border detection and adaptive threshold), applicable to the evaluation of ventricular mass and volume by magnetic resonance imaging. Despite slight underestimation, the spin-echo sequence used in 9 small pigs provided a value of left ventricular mass close to that observed ex vivo (r = 0.97, SEE = 6.05 g). Clinical validation using a rapid gradient-echo sequence was undertaken and compared with manual border detection carried out by three independent, trained operators. The study population included healthy subjects and patients with global or segmental left ventricular dysfunction with or without ventricular deformation. The correlations between automatic and manual detection were satisfactory both for calculation of left ventricular mass (r = 0.93, SEE = 13 g) and measurement of surfaces (r = 0.91, SEE = 1.4 cm2). The concordance of the two methods was confirmed by the Bland and Altman test. Cardiac magnetic resonance imaging may provide accurate and reproducible measurements of left ventricular mass within acceptable acquisition and image processing times for routine use. Although the clinical value of such a method is accepted both for establishing the prognosis and guiding management, studies of the cost/efficacy ratio should be undertaken to situate magnetic resonance imaging with respect to other non-invasive techniques of investigation of left ventricular function.     

Long-term effects of delapril hydrochloride on procollagen type III amino-terminal peptide, left ventricular mass and left ventricular function in hypertensive patients

The long-term effect of delapril hydrochloride, a non-sulfhydryl angiotensin converting enzyme inhibitor, on serum concentrations of procollagen type III amino-terminal peptide (PIIIP) and left ventricular mass (LVM) and function were investigated in 15 hypertensive patients. Patients were treated with delapril hydrochloride 30 mg/day po for 12 months. Blood samples and an echocardiogram were obtained before treatment and after 6 and 12 months of treatment. Blood pressure, PIIIP, and LVM significantly decreased associated with an increase in left ventricular fractional shortening and mean systolic and diastolic posterior wall velocity at 6 and 12 months of treatment. Positive correlations between PIIIP and LVM (r=0.49, p<0.005) and negative correlations between PIIIP and left ventricular fractional shortening (r=-0.31, p<0.05) were found. Delapril hydrochloride reduced PIIIP and LVM and improved cardiac function in hypertensive patients.     

Left ventricular contractile performance, ventriculoarterial coupling, and left ventricular efficiency in hypertensive patients with left ventricular hypertrophy

Contractile performance of hypertrophied left ventricle may be depressed in arterial hypertension. Ventriculoarterial coupling is impaired when myocardial contractile performance is reduced and when afterload is increased. The left ventricular contractile performance and the ventriculoarterial coupling were evaluated in 30 hypertensive patients with moderate left ventricular hypertrophy and 20 control subjects. Left ventricular angiography coupled with the simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress/volume index, the slope of end-systolic pressure-volume relationship, ie, end-systolic elastance, effective arterial elastance, external work, and pressure-volume area. In hypertensive patients, left ventricular contractile performance, as assessed by end-systolic elastance/ 100 g myocardial mass, was depressed (4.35 +/- 1.13 v 5.21 +/- 1.89 mm Hg/mL/100 g in control subjects P < .02), when end-systolic stress-to-volume ratio was comparable in the two groups (3.85 +/- 0.99 g/cm2/mL in hypertensive patients versus 3.51 +/- 0.77 g/cm2/mL in control subjects). Ventriculoarterial coupling, evaluated through effective arterial elastance/end-systolic elastance ratio, was slightly higher in hypertensive patients (0.53 +/- 0.08 v 0.48 +/- 0.09 mm Hg/mL in control subjects, P < .05), and work efficiency (external work/pressure-volume area) was similar in the two groups (0.78 +/- 0.04 mm Hg/mL in hypertensive patients versus 0.80 +/- 0.03 mm Hg/mL in control subjects). This study shows that despite a slight depression of left ventricular contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with left ventricular hypertrophy. Thus, it appears that left ventricular hypertrophy might be a useful means of preserving the match between left ventricle and arterial receptor with minimal energy cost.     

Two-year follow-up study to evaluate the reduction of left ventricular mass and diastolic function in mild to moderate diastolic hypertensive patients

OBJECTIVE: To compare the effects of two antihypertensive agents, amlodipine and lisinopril, on left ventricular mass and diastolic filling in patients from primary care centers with mild to moderate diastolic hypertension. STUDY DESIGN: A second-year, open follow-up of a prospective, double-blind, randomized, parallel group, comparative study. METHODS: Male and female patients between 25 and 75 years-of-age with elevated diastolic blood pressure (four measurements > or = 95 mmHg from multiple measurements taken on three occasions and average diastolic blood pressure < 115 mmHg) were recruited from a population survey. After 4 weeks' placebo run-in, 71 patients were included of whom 60 finished the first study year and 51 finished the second study year. Patients were randomly assigned to receive doses of 5-10 mg amlodipine or 10-20 mg lisinopril, which were titrated on the basis of the effects on blood pressure. Primary endpoints were left ventricular mass index (LVMI) and early to atrial peak filling velocity. Office and ambulatory blood pressure were considered secondary endpoints. RESULTS: The decrease in blood pressure was equal for both treatment regimens in the first year. A statistically significant (P< 0.001) decrease in LVMI in both treatment groups was observed in the first year [-11.0 g/m2 (95% Cl -6.0 to -16.1) in the amlodipine group and -12.6 g/m2 (95% Cl -8.2 to -17.0) in the lisinopril group]. Early to atrial peak filling velocity did not change significantly within the treatment groups in the first year [+0.07 (95% CI -0.01 to +0.15) in the amlodipine group and +0.01 (95%9 Cl -0.06 to +0.08) in the lisinopril group. Blood pressure, LVMI and early to atrial peak filling velocity did not change in the second year of treatment. No significant differences in primary and secondary endpoints between treatment groups were found in the first or second year. Conclusion: The effects of amlodipine and lisinopril on left ventricular mass and early to atrial filling peak velocity after 2 years of treatment were similar and these effects were already observed after 1 year of treatment. Additional studies of longer duration (> or = 4 years) and with a larger sample size are recommended.     

心肌矢量应变和应变率成像技术对晚期肝硬化患者左心室局部收缩功能的评价

目的:应用心肌矢量应变和应变率成像技术(VSI)观察晚期肝硬化患者左心室局部收缩功能,探讨晚期肝硬化患者左心室局部收缩功能的改变.方法:VSI技术检测30例晚期肝硬化患者(患者组)及30例年龄匹配的正常对照者(对照组)左心室16节段室壁收缩期纵向、径向应变率及圆周方向运动速度.结果:患者组纵向应变率收缩期峰值(L-SRs)前间隔中间段、前壁心尖段、室间隔心尖段较对照组减低(P<0.05);患者组径向应变率收缩期峰值(R-SRs)值前间隔中间段、室间隔心尖段较对照组减低(P<0.05);患者组圆周方向运动速度收缩期峰值(C-Vs)前壁中间段、前间隔中间段较对照组减低(P<0.05).结论:晚期肝硬化患者在左心室整体收缩功能未受到明显影响以前,局部心肌已经出现收缩功能减低.     

Reversible left atrial dysfunction possibly due to afterload mismatch in patients with left ventricular dysfunction

OBJECTIVE: The aim of this study was to define the clinical-therapeutical approach to endometrial cancer now being followed in some of the most important centers of reference for gynecological cancer in North America by means of a questionnaire. STUDY DESIGN: The questionnaire focused on four principal areas: (1) surgical staging and therapy; (2) adjuvant treatment; (3) treatment modifications; and (4) management of advanced stages (FIGO III-IV). RESULTS: There were 48 evaluable responses (77%) received by the end of December 1994 which were considered for this analysis. Lymphadenectomy is utilized routinely in 26/48 centers (54.2%) and in selective clinical-pathological conditions in another 21/48 centers (43.5%). In the majority of centers (31/48; 64.6%) radical surgery is utilized for selected indications such as cervical involvement. Only 3/48 (6.2%) centers consider the vaginal approach totally inappropriate. The great majority (40/48; 83.3%) of the centers considered postsurgical adjuvant therapy to be necessary in FIGO Stage Ic. Brachytherapy is routinely performed in 3 centers (6.2%) in postsurgical management of Stage I endometrial cancer, while the majority of the centers (31/48; 64.6%) perform brachytherapy of the vaginal vault in certain clinical-pathological conditions. A wide variety of treatments are used for advanced stages (FIGO III-IV). CONCLUSIONS: It emerges that some controversial aspects exist on endometrial cancer treatment, and these conflicting data need a large-scale multicenter randomized clinical trial.     

Single-drug therapy and reduction of left ventricular mass in hypertension

Echocardiography has provided most of what is understood today about the relationships between human hypertension, cardiac anatomic and functional responses. It has proven its value in determining the effects of antihypertensive therapy on cardiac structure and function. A growing body of research supports initial concerns that not all drugs effective for blood pressure reduction are effective for reduction of left ventricular mass and regression of LVH. It has been of interest that agents initially believed to be ineffective for left ventricular mass reduction (principally diuretics and beta blockers) on the basis of pathophysiological theory and inadequate clinical trials, may in fact be quite effective for LVH regression, as well as improved cardiac outcomes. Hence, supposed inefficacy of these agents for this purpose should no longer be used as a reason to disregard long-standing recommendations of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension supporting the use of diuretics and beta blockers for the initial pharmacotherapy of hypertension.     

Is the time domain signal-averaged electrocardiogram helpful in patients with ventricular tachycardia without apparent structural heart disease?

The signal-average electrocardiogram (SAECG) has been a screening method for identifying patients at risk for ventricular tachycardia (VT) in the setting of coronary artery disease (CAD). Its significance in patients with VT unrelated to CAD or left ventricular dysfunction is undetermined. In order to define the value of SAECG in this patient population further, we compared the time domain SAECG at 25, 40, and 80 Hz filters in 35 patients with clinically symptomatic VT in the absence of structural heart disease was compared with 10 normal controls and 10 patients with CAD and inducible VT. SAECG data in patients without structural heart disease were intermediate between normal controls and patients with CAD. No single or combined SAECG criterion helped to differentiate between patients with inducible and noninducible VT. There was no concordance to other arrhythmia testing. It was concluded that signal-averaged electrocardiography may have little screening value in VT unrelated to CAD or left ventricular dysfunction.     

Association between insulin and blood pressure in relation to the influence of body mass index

The relationship between plasma insulin level and systolic blood pressure (SBP) was investigated by multiple linear regression procedure in 410 Chinese non-diabetics. The significant positive correlation between SBP and 2-hour plasma insulin (INS 2h) after 75g glucose load was found in the BMI (body mass index) 15.9-27.0 group (n = 287) after the adjustment for age, sex, BMI, smoking and plasma cholesterol (P = 0.01). However, this significant correlation was gradually diminished with the expansion of the BMI range, ie. P = 0.04 in the BMI 15.9-29.0 (n = 356) group, P = 0.07 in the BMI 15.9-31 (n = 389) group, and P = 0.12 in the BMI 15.9-33 (n = 402) group after the same adjustment of variables. Interestingly, the significant inverse correlation between insulin-BMI interaction term (product of BMI and insulin) and SBP was found (P = 0.04) in the presence of the significant positive correlation between 2-hour plasma insulin and SBP (P = 0.02) after adjustment of the above mentioned five factors in the whole group (BMI 15.9-42.2, n = 410). These results indicated that SBP is independently correlated with plasma insulin level in the studied population, and that the severer obesity may interfere the net effects of insulin on the elevating of blood pressure.     

Burden of illness, metabolic control, and complications in relation to depressive symptoms in IDDM patients

Relationships between demographic-, treatment-, and sickness-related factors, metabolic control (HbA1c), perceived burden of illness, and degree of depressive symptoms were examined in a group of 155 insulin-dependent diabetic patients, aged 35.3 +/- 8.9 years. The patients completed a questionnaire measuring depressive symptoms and three aspects of perceived burden of illness. No gender differences in HbA1c level or occurrence of late diabetic complications were found. Both men and women showed a modestly elevated degree of depression compared with norm groups. Self-reported burden of illness was strongly related to depression but was largely unrelated to objective disease-related measures. Level of depression was correlated neither with degree of metabolic control nor with the presence of such late diabetic complications as retinopathy and nephropathy. Some 44% of the variance in depression could be explained by worries about complications in those patients with the lowest HbA1c levels, by perceived restrictions in everyday life in patients with intermediate metabolic control, and by problems of glycaemic regulation in patients with poor metabolic control. Degree of depression was largely unrelated to disease severity, but was found to be related to the perceived daily burden of living with the disease, the specific worries and concerns associated with a depressed mood varying with degree of metabolic control.     

Assessment of left ventricular function by isometric handgrip exercise after thrombolysis in patients with refractory unstable angina

The handgrip test has been proposed for the evaluation of the hemodynamic reserve in patients with coronary artery disease and to quantitate the impairment of left ventricular (LV) function. The present study was designed to evaluate the effect of thrombolytic therapy in patients with refractory unstable angina in order to test the hypothesis that a reduction in intracoronary thrombosis could ameliorate their hemodynamic response to the handgrip test. During left heart catheterization, 20 patients with refractory unstable angina of recent onset performed a handgrip test before (HG1) and 24-72 hours after (HG2) being randomized to receive recombinant tissue-type plasminogen activator or placebo, according to a double-blind parallel group design. HG1 induced an increase in heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during baseline handgrip were highly different in individual patients, resulting in a trend toward an increase. Similarly, a different individual response was observed in the behavior of the isovolumetric and relaxation indices. In comparison with HG1, no difference was detected during HG2 in the 2 treatment groups with respect to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures, +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable angina of recent onset, the handgrip test performed before and after thrombolysis did not prove to be useful in assessing directional changes of LV performance, mainly because of the different individual response to the baseline handgrip test.