Systolic and diastolic ventricular function in the normal and extra-embryonic venous clipped chicken embryo of stage 24: a pressure-volume loop assessment.

OBJECTIVES: Fluid mechanical forces affect cardiac development. In the chicken embryo, permanent obstruction of the right lateral vitelline vein by clipping reduces the mechanical load on the embryonic myocardium, which has been shown to induce a spectrum of outflow tract anomalies. Insight into the effects of this intervention on the mechanical function of the developing myocardium could contribute to a better understanding of the relationship between hemodynamics and cardiac morphogenesis. We aimed to explore the effects of clipping on intrinsic systolic and diastolic ventricular function at stage 24 in the chicken embryo METHODS: Cardiac pressure-volume relationships enable load-independent quantification of intrinsic ventricular systolic and diastolic properties. We determined ventricular function by pressure-volume loop analysis of in-ovo stage-24 chicken embryos (n = 15) 2 days after venous obstruction at 2.5 days of incubation (stage 17, venous clipped embryos). Control embryos (n = 15) were used for comparison. RESULTS: End-systolic volume was significantly higher in clipped embryos (0.36 +/- 0.02 microL vs. 0.29 +/- 0.02 microL, P = 0.002). End-systolic and end-diastolic pressure were also increased compared with control animals (2.93 +/- 0.07 mmHg vs. 2.70 +/- 0.08 mmHg, P = 0.036 and 1.15 +/- 0.06 mmHg vs. 0.82 +/- 0.05 mmHg, P < 0.001, respectively). No significant differences were demonstrated for other baseline hemodynamic parameters. Analysis of pressure-volume relationships showed a significantly lower end-systolic elastance in the clipped embryos (slope of end-systolic pressure-volume relationship: 2.91 +/- 0.24 mmHg/microL vs. 7.53 +/- 0.66 mmHg/microL, P < 0.005) indicating reduced contractility. Diastolic stiffness was significantly increased in the clipped embryos (slope of end-diastolic pressure-volume relationship: 1.54 +/- 0.21 vs. 0.60 +/- 0.08, P < 0.005), indicating reduced compliance. CONCLUSION: Venous obstruction apparently interferes with normal myocardial development, resulting in impaired intrinsic systolic and diastolic ventricular function. These changes in ventricular function may precede morphological derangements observed in later developmental stages.     

The Effects of Amlodipine on Left Ventricular Mass and Diastolic Function in Concentric and Eccentric Left Ventricular Hypertrophy

BACKGROUND: The effects of the antihypertensive therapy with amlodipine (5-10 mg/day) on left ventricular mass and diastolic function were examined in 30 mild to moderate essential hypertensive patients who have left ventricular hypertrophy (LVH) and diastolic dysfunction. METHODS AND RESULTS: Each patient's left ventricular mass was measured, and left ventricular diastolic function was assessed by echocardiographic Doppler examination at entry, and at 3 and 6 months after the initiation of the treatment. Amlodipine reduced both blood pressure (from 164 +/- 14/104 +/- 6 mmHg to 134 +/- 9/83 +/- 4 mmHg) and left ventricular mass index (from 160 +/- 30 g/m(2) to 137 +/- 26 g/m(2)) significantly at 3 months and both parameters maintained at these levels for 6 months. When the patients were classified according to the type of the LVH, a significant regression in left ventricular mass index was seen only in the patients who had concentric LVH was a relative wall thickness >/=0.44 (n = 16), but not in the eccentric LVH group (n = 14), although both groups were not significantly different from each other regarding the basal hemodynamic parameters, baseline left ventricular mass index and the decrease in blood pressure in response to amlodipine treatment. The mitral inflow E/A ratio did not show any significant change in either group. CONCLUSIONS: Amlodipine produced significant regression in LVH only in the patients with concentric LVH, but not those with eccentric LVH, while it did not change the diastolic dysfunction. Therefore, the type of LVH seems to be an important feature in determining the effects of antihypertensive treatment on left ventricular mass index.     

Evaluation of different methods of treatment of patients with stable stenocardia combined with arterial hypertension according to echocardiographic data

The authors evaluated the influence of three alternative methods of treatment of coronary artery disease (CAD) and stable exertional stenocardia accompanied by arterial hypertension on systolic and diastolic left ventricular (LV) function. The three methods were: conventional therapy with monocinque, chronotherapy with monocinque, and therapy with a combination of monocinque and melatonin. All the 65 patients aged 44 to 69 years underwent echoCG with Vivid 7 ultrasound scanner (USA) before and after the treatment. The study showed that chronotherapy with monocinque had the most favorable effect on LV diastolic function, which manifested by an increase in peak E from 0.47 +/- 0.02 to 0.53 +/- 0.02 m/s (p = 0.006) and peak E/peak A ratio from 0.77 +/- -0.05 to 0.93 +/- 0.05 (P = 0.002), as well as a decrease in peak A from 0.65 +/- 0.03 to 0.56 +/- 0.03 m/s (p = 0.05). Complex treatment with monocinque and melatonin improved systolic and diastolic LV function better than did conventional therapy. The favorable influence on myocardial contractility manifested by a reduction in end systolic LV size from 3.66 +/- 0.04 to 3.42 +/- 0.02 cm (p < 0.001), end diastolic LV volume from 126.7 +/- 1.3 to 118.4 +/- 1.1 ml (p < 0.001), and end systolic LV volume from 55.1 +/- 1.0 to 47.0 +/- 0.8 ml (p < 0.001), as well as an increase in ejection fraction from 56.5 +/- 0.9 to 60.3 +/- 0.8% (p = 0.003) and shortening fraction from 27.9 +/- 1.3 to 33.0 +/- 0.4% (p = 0.001). The normalizing effect on LV diastolic function manifested by an increase in peak E from 0.46 +/- 0.02 to 0.54 +/- 0.02 m/sec (p = 0.009) and peak E/peak A ratio from 0.68 +/- 0.05 to 0.82 +/- 0.05 (p = 0.002).     

Effects of nisoldipine and lisinopril on left ventricular mass and function in diabetic nephropathy

OBJECTIVE: To compare the effects of the calcium channel blocker, nisoldipine, and the ACE inhibitor, lisinopril, on left ventricular mass (LVM) and systolic function in type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: M-mode echocardiography was performed in 50 hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo, Japan) every 3 months. Three patients dropped out and seven patients were excluded due to technical difficulties. RESULTS: The 24-h diastolic blood pressure was reduced from 83 to 80 mmHg in the nisoldipine group (P = 0.06) and from 85 to 80 mmHg in the lisinopril group (P = 0.02). The decline in systolic blood pressure was not significant with any of the two treatments, and no difference in reduction of blood pressure was seen between groups. LVM corrected for body surface area (LVMI) was comparable between groups at baseline and increased from 96 +/- 5 to 107 +/- 6 g/m2 (mean +/- SEM; P = 0.007) in the nisoldipine group and from 95 +/- 4 to 103 +/- 5 g/m2 (P = 0.03) in the lisinopril group. The mean difference between the change in LVMI in the two groups was 2.9 (95% CI 6.8 to 12.7) g/m2. The prevalence of left ventricular hypertrophy rose from 18 (95% CI 6-30) to 30% (16-44) during the study period. A multiple linear regression analysis revealed that after 1 year of treatment, LVMI increased with higher systolic blood pressure level and declining glomerular filtration rate (R2 = 0.25). Fractional shortening was within normal range at baseline, 42 +/- 1 vs. 41 +/- 1% with nisoldipine and lisinopril, respectively, and did not change during follow-up. CONCLUSIONS: Antihypertensive treatment with nisoldipine or lisinopril to bring diastolic blood pressure level within the normal target range does not hinder a rise in LVMI in type 1 diabetic patients with diabetic nephropathy.     

Left ventricular performance during prolonged exercise: absence of systolic dysfunction

We assessed left ventricular systolic and diastolic performance during and after prolonged exercise under controlled conditions in a group of healthy, trained men. Previous studies have examined the effects of prolonged effort on left ventricular function, yet it remains unclear whether or not left ventricular dysfunction (e.g. cardiac fatigue) can be produced under such conditions. We studied 15 healthy men, aged 27+/-1 years (mean+/-S.E.M.). Subjects exercised on bicycles at a constant work rate (60% of maximum oxygen uptake per min) for 150 min. Measurements of gas exchange, blood pressure and haematocrit were obtained, concurrent with the assessment of left ventricular function using equilibrium radionuclide angiography, at rest, during exercise (every 30 min) and after 30 min of recovery. Fluid replacement was provided and monitored during the exercise period. The baseline resting and exercise ejection fractions were 66+/-2% and 78+/-2% respectively. During exercise, subjects consumed 1816+/-136 ml of fluid, and the haematocrit had increased at 120 min of exercise (from 47.2%+/-0.6 to 49.9+/-0.8%; P<0.05). There was no change in either systolic or diastolic blood pressure throughout the exercise period, but heart rate drifted upwards from 141+/-2 beats/min after 30 min to 154+/-3 beats/min after 150 min (P<0.05). There was a small decline (8%; P<0.05) in end-diastolic volume at 150 min. No changes were observed in left ventricular ejection fraction, the pressure/volume ratio or end-systolic volume. After 30 min of sitting in recovery, heart rate was still higher than the pre-exercise value (84+/-3 compared with 69+/-2 beats/min; P<0.05), as were measures of peak filling rate and time to peak filling (P<0.05). The ejection fraction in the post-exercise recovery period was similar to the pre-exercise value. The results indicate that prolonged exercise of moderate duration may not induce abnormal left ventricular systolic function or cardiac fatigue during exercise.     

The effects of cardioselective and non-selective beta-adrenoceptor blockade on the hypokalaemic and cardiovascular responses to adrenomedullary hormones in man

Adrenaline was infused intravenously in nine normal volunteers to plasma concentrations similar to those found after myocardial infarction. This study was undertaken on three occasions after 5 days' treatment with placebo or the beta-adrenoceptor antagonists, atenolol or timolol. Adrenaline increased the systolic pressure by 11 mmHg, decreased the diastolic pressure by 14 mmHg, and increased the heart rate by 7 beats/min. These changes were prevented by atenolol. However, after timolol the diastolic pressure rose (+19 mmHg) and heart rate fell (-8 beats/min). Adrenaline caused the corrected QT interval (QTc) to lengthen (0.36 +/- 0.02 s to 0.41 +/- 0.06 s). No significant changes were found in the QTc when subjects were pretreated with atenolol or timolol. The serum potassium fell from 4.06 to 3.22 mmol/l after adrenaline. Serum potassium fell to a lesser extent to 3.67 mmol/l after atenolol and actually increased to 4.25 mmol/l after timolol. Adrenaline-mediated hypokalaemia appears to result from the stimulation of a beta 2-adrenoceptor linked to membrane Na+/K+-ATPase causing potassium influx.     

Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans

BACKGROUND: St John's wort (Hypericum perforatum) is a popular over-the-counter antidepressant. Its antidepressive effect has been attributed in part to inhibition of monoamine transporters and monoamine oxidase, on the basis of in vitro studies. METHODS: In a double-blind, randomized, placebo-controlled, crossover study, 16 healthy subjects (11 men and 5 women; mean age, 31 +/- 5 years) ingested either St John's wort (300 mg three times daily) or placebo for 7 days. Imipramine treatment (50 mg three times daily) in 7 subjects served as a positive control. After treatment, physiologic and biochemical tests included cardiovascular reflex testing, graded head-up tilt testing, and plasma catecholamine determinations. RESULTS: St John's wort had no effect on blood pressure, heart rate, heart rate variability, or blood pressure variability, regardless of the test condition. St John's wort had no effect on plasma concentrations of norepinephrine and its main metabolite, dihydroxyphenylglycol, whereas plasma dihydroxyphenylacetic acid (DOPAC; the main metabolite of dopamine) concentrations increased in every subject (1661 +/- 924 pg/mL versus 1110 +/- 322 pg/mL with placebo, P=.04). In contrast, imipramine increased resting blood pressure (124 +/- 10 mmHg/71 +/- 5 mmHg versus 110 +/- 8 mmHg/61 +/- 6 mmHg with placebo, P=.005 for systolic values and P=.003 for diastolic values) and heart rate (74 +/- 7 beats/min versus 62 +/- 6 beats/min with placebo, P=.005) and elicited a marked orthostatic tachycardia (increase in heart rate of 43 +/- 17 beats/min versus 26 +/- 8 beats/min with placebo, P=.006). CONCLUSIONS: Our findings challenge the concept that St John's wort elicits a major change in norepinephrine uptake or monoamine oxidase activity in vivo. The consistent increase in plasma DOPAC concentrations might suggest a novel mode of action or an inhibitory effect on dopamine beta-hydroxylase that should be followed up. We propose that a combination of physiologic and biochemical profiling may help better define the mode of action and potential side effects of herbal remedies.     

Comparison of myocardial tissue Doppler with transmitral flow Doppler in left ventricular hypertrophy

We sought to determine the most useful echocardiographic measurements for assessment of diastolic function in patients with left ventricular hypertrophy (LVH) and normal systolic function. We compared myocardial Doppler velocities of the basal inferoposterior wall with mitral inflow pulsed wave Doppler velocities in 11 healthy volunteers (age, 36 +/- 6 years), 25 patients (age, 64 +/- 14 years) without LVH, and 37 patients (age, 67 +/- 14 years) with LVH and otherwise normal echocardiograms. The discriminatory measurements were myocardial A-wave duration (120 +/- 18 versus 98 +/- 20 and 92 +/- 12 ms, P <.0001), myocardial isovolumetric relaxation time (124 +/- 45 versus 95 +/- 48 and 78 +/- 25 ms, P =.0035), mitral A-wave velocity (0.98 +/- 0.37 versus 0.73 +/- 0.28 m/s and 0.61 +/- 0.22 m/s, P =.009), and mitral E-wave deceleration time (257 +/- 93 versus 201 +/- 85 ms and 184 +/- 83 ms, P =.015), which were significantly increased, and myocardial E-wave velocity (0.84 +/- 0.04 m/s versus 0.13 +/- 0.03 m/s and 0.14 +/- 0.03 m/s, P <.0001), which was significantly decreased, in patients with LVH compared with patients without LVH and normal volunteers, respectively. Left ventricular posterior wall thickness correlated with myocardial isovolumetric relaxation time (r = 0.52, P <.0001) and myocardial A-wave duration (r = 0.59, P <.0001), negatively with myocardial E wave (r = -0.43, P <.0001), and showed no correlation with mitral inflow parameters except mitral inflow A wave (r = 0.43, P =.002). On multivariate analysis using these variables, myocardial isovolumetric relaxation time (P =.0014) and A-wave duration (P =.001) were the only 2 variables that correlated with posterior wall thickness (multiple R = 0.71). In the presence of LVH and preserved left ventricular systolic function, myocardial relaxation time and velocities are more sensitive than mitral Doppler inflow parameters in detecting abnormal left ventricular relaxation.     

Magnetic resonance assessment of aortic pulse wave velocity, aortic distensibility, and cardiac function in uncomplicated type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (DM2) may augment arterial stiffening and thereby modulates left ventricular (LV) function. Cardiovascular magnetic resonance (CMR) is well suited to assess aortic pulse wave velocity (PWV) and aortic distensibility, both markers of arterial stiffness, without the use of geometric assumptions. Furthermore, CMR is a reliable method for assessing left ventricular (LV) function. The purpose of this study was to assess LV function, PWV, and aortic distensibility in patients with DM2 using MR. METHODS: Fourteen patients with well controlled, uncomplicated DM2, and 16 age and gender matched healthy subjects were included. PWV was calculated based on MR velocity mapping at two predefined aortic locations. Aortic distensibility was measured in the mid ascending aorta. LV volumes were measured by fast gradient-echo imaging to assess systolic function. Furthermore, mitral inflow was measured by MR velocity mapping to assess diastolic LV function. RESULTS: Mean PWV was higher in patients as compared to healthy subjects (6.83 +/- 1.60 m/s vs. 5.65 +/- 0.75 m/s, p < 0.05). This difference was independent of blood pressure. PWV correlated significantly (p < 0.05) with fasting plasma glucose and insulin levels. Aortic distensibility was lower in patients as compared to healthy subjects (4.50 x 10(- 3)+/- 2.24 x 10(- 3) mmHg(- 1) vs. 7.42 x 10(- 3)+/- 3.34 x 10(- 3) mmHg(- 1), p < 0.05). Distensibility correlated negatively with PWV and positively with LV diastolic function (p < 0.05). CONCLUSION: A combined CMR assessment of aortic PWV, aortic distensibility, and heart function reveals abnormal PWV and distensibility in patients with DM2, independent of blood pressure. Furthermore, aortic distensibility correlates with diastolic left ventricular function.     

Left and right ventricular diastolic functions in patients with rheumatoid arthritis without clinically evident cardiovascular disease

The aim of this study was to assess the prevalence of diastolic dysfunction of the left ventricle (LV) and of the right ventricle in patients with rheumatoid arthritis (RA) without clinically evident cardiovascular manifestations and to estimate whether there is a correlation between the duration of RA and the degree of LV diastolic dysfunction. The study included 81 patients (61 females and 20 males) with RA without clinically evident heart disease (group 1) and 40 healthy subjects (29 females and 11 males) who served as a control group (group 2). Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects. There were significant differences between patients with RA vs. control group with regard to early diastolic flow velocity (E), atrial flow velocity (A) and the E/A ratio (0.68 +/- 0.19 m/s vs. 0.84 +/- 0.14 m/s, p < 0.001; 0.73 +/- 0.15 m/s vs. 0.66 +/- 0.13 cm/s, p = 0.01; and 0.97 +/- 0.3 vs. 1.32 +/- 0.37, p < 0.001, respectively). There was significant difference between groups regarding the right ventricular early diastolic (Er)/atrial (Ar) flow velocities (Er/Ar ratio) (1.07 +/- 0.3 vs. 1.26 +/- 0.3, p = 0.002). There was a weak correlation between transmitral E/A ratio and the duration of RA (r = - 0.22, p = 0.001). Myocardial performance index (MPI) appeared to differ little in patients with RA as compared with control group (0.51 +/- 0.1 vs. 0.52 +/- 0.2, p = NS). In patients with RA without clinically evident cardiovascular disease, the left ventricular diastolic function and the right ventricular diastolic function are reduced. Left ventricular wall thickness, dimensions, systolic function and MPI were found to be normal. LV diastolic function had a weak correlation with the duration of RA.     

Heart rate variability in arrhythmogenic right ventricular cardiomyopathy correlation with clinical and prognostic features

The identification of subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC) at higher risk for sudden death is an unresolved issue. An influence of the autonomic activity on the genesis of ventricular arrhythmias was postulated. Heart rate variability (HRV) analysis provides a useful method to measure autonomic activity, and is a predictor of increased risk of death after myocardial infarction. For these reasons, the aim of the study was to evaluate HRV and its correlations with ventricular arrhythmias, heart function, and prognostic outcome in patients with ARVC. The study included 46 patients with ARVC who were not taking antiarrhythmic medications. The diagnosis was made by ECG, echocardiography, angiography, and endomyocardial biopsy. Exercise stress test and Holter monitoring were obtained in all patients. Time-domain analysis of HRV was expressed as the standard deviation of all normal to normal NN intervals (SDNN) detected during 24-hour Holter monitoring. Thirty healthy subjects represented a control group for HRV analysis. The mean follow-up was 10.8 +/- 1.86 years. SDNN was reduced in patients with ARVC in comparison with the control group (151 +/- 36 vs 176 +/- 34, P = 0.00042). Moreover, there was a significant correlation of this index with the age of the patients (r = - 0.59, P < 0.001), with the left (r = 0.44, P = 0.002) and right (r = 0.47, P = 0.001) ventricle ejection fraction, with the right ventricular end diastolic volume (r = - 0.62, P < 0.001), and with the ventricular arrhythmias, detected during the same Holter record used for HRV analysis (patients with isolated ventricular ectopic beats < 1,000/24 hours, 184 +/- 34; patients with isolated ventricular ectopic beats > 1,000/24 hours and/or couplets, 156 +/- 25; patients with repetitive ventricular ectopic beats (> or = 3) and/or ventricular tachycardia, 129 +/- 25; P < 0.001). During follow-up two patients showed a transient but significant reduction of SDNN and a concomitant increase of the arrhythmic events. In eight patients an episode of sustained ventricular tachycardia occurred, but the mean SDNN of this subgroup did not differ from the mean value of the remaining patients (152 +/- 15 vs 150 +/- 39; P = NS). Only one subject died after heart transplantation during follow-up (case censored). Time-domain analysis of HRV seems to be a useful method to assess the autonomic influences in ARVC. A reduction of vagal influences correlates with the extent of the disease. The significant correlation between SDNN and ventricular arrhythmias confirmed the influences of autonomic activity in the modulation of the electrical instability in ARVC patients. However, SDNN was not predictive of spontaneous episodes of sustained ventricular tachycardia.     

Regression of left ventricular hypertrophy and control of hypertension in the spontaneously hypertensive rat (SHR): oxprenolol versus hydrochlorothiazide

The control of hypertension with antihypertensive agents, in the spontaneously hypertensive rats (SHR) can result in regression of established cardiac hypertrophy. This study compared the effects of therapy with oxprenolol (Ox) and with hydrochlorothiazide (Htz) for (1) regression of established left ventricular hypertrophy (LVH) and (2) blood pressure control. Three groups of SHR and 3 comparable groups of Wistar-Kyoto (WKY) rats, matched for age, sex and body wt, were treated with tap water (Gp I), 60-200 mg hydrochlorothiazide kg-1 day-1 (Gp II) and 15-500 mg oxprenolol kg-1 day-1 (Gp III) for 13 weeks. Systolic and diastolic blood pressures (SBP, DBP mmHg), left ventricular wt/body wt ratio (LVwt/Bwt mg g-1) and left ventricular wall thickness (LVWT mm) were recorded. Oxprenolol lowered both systolic (mean +/- S.E. mmHg, 130 +/- 7 vs 189 +/- 8; P less than 0.01) and diastolic blood pressures (mean +/- S.E. mmHg, 104 +/- 6 vs 159 +/- 6; P less than 0.001) and caused regression of left ventricular hypertrophy (mean +/- S.E. mg g-1, 2.91 +/- 0.06 vs 3.10 +/- 0.09; P less than 0.05). In contrast, hydrochlorothiazide did not control blood pressure (mean +/- S.E. mmHg, 183 +/- 5 vs 189 +/- 6 and 152 +/- 5 vs 156 +/- 6), but it did cause regression of left ventricular hypertrophy (mean +/- S.E. mg g-1, 2.67 +/- 0.03 vs 3.10 +/- 0.09; P less than 0.01). Left ventricular wall thickness, measured in the mid-ventricular region, was significantly reduced only by hydrochlorothiazide (mean +/- S.E. mm, 2.76 +/- 0.06 vs 3.21 +/- 0.01; P less than 0.05). These results suggest that regression of left ventricular hypertrophy can occur with or without control of hypertension in the SHR.     

QT interval dispersion in ventricular beats: a noninvasive marker of susceptibility to sustained ventricular arrhythmias

Increased QT dispersion (QTd) calculated from sinus beats has been shown to identify patients prone to sustained VT. However, predictive accuracy of this parameter is limited. Electrophysiological properties of the myocardium may be altered by a premature ventricular beats, which is a well-established trigger for sustained VT. Therefore, the author hypothesised that QTd in spontaneous or paced ventricular beats may improve identification of patients with inducible sustained VT. In 28 consecutive patients (men, mean age 61 +/- 13 years) who underwent programmed ventricular stimulation, the values of QTd calculated in sinus and ventricular beats were compared between inducible and noninducible patients. The mean QTd values obtained using three different methods differed significantly, QTd in paced ventricular beats being the highest, QTd in spontaneous ventricular beats was intermediate, and QTd in sinus beats was the lowest (83.9 +/- 30 vs 63.0 +/- 29 ms vs 53.9 +/- 27 ms, P < 0.0001 and P < 0.004, respectively). In 13 (46%) patients sustained VT was induced. QTd values were significantly higher in inducible than noninducible patients (QTd sinus beats: 67.5 +/- 31 vs 42.1 +/- 11 ms, P = 0.02; QTd spontaneous ventricular beats: 79.3 +/- 35 vs 46.7 +/- 13 ms, P = 0.008, and QTd-paced ventricular beats: 104.8 +/- 32 vs 65.9 +/- 9 ms, P = 0.0009). The receiver operator characteristic curves showed that at a sensitivity level of 100%, the highest specificity for identification of inducible patients had QTd measured in paced ventricular beats (87%) followed by QTd in spontaneous ventricular beats (45%), and QTd in sinus beats (40%). In conclusion, (1) QTd in ventricular beats is greater than in sinus beats, and (2) QTd calculated from paced ventricular beats identifies patients with inducible sustained VT better than QTd measured during sinus rhythm.     

Reversal of left ventricular diastolic dysfunction after kidney-pancreas transplantation in type 1 diabetic uremic patients

OBJECTIVE: Diastolic function is frequently impaired in diabetic patients. Our aim was to evaluate the effects of glycometabolic control achieved by pancreas transplantation on left ventricular function in uremic type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Left ventricular systolic and diastolic functions were evaluated using radionuclide ventriculography in 42 kidney-pancreas transplant patients and 26 kidney-alone recipients who had similar clinical characteristics before transplantation. Patients were grouped according to 6, 24, and 48 months of follow-up. Control subjects consisted of 20 type 1 diabetic patients. RESULTS: The left ventricular ejection fraction was normal in all of the patients. However, kidney-pancreas transplant patients with 4 years of graft function had a higher ejection fraction (75.7 +/- 1.8%) than kidney-alone patients with 4 years of graft function (65.3 +/- 2.8%, P = 0.02) and type 1 diabetic patients (61.3 +/- 3.7%, P = 0.004). In patients with 4 years of graft function, normal diastolic parameters were evident in kidney-pancreas but not in kidney-alone or in type 1 diabetic patients (peak filling rate: 4.46 +/- 0.15 end diastolic volume (EDV)/s in kidney-pancreas patients vs. 2.73 +/- 0.24 EDV/s [P < 0.01] and 3.39 +/- 0.30 EDV/s [P < 0.01] in kidney-alone and type 1 diabetic patients, respectively; time-to-peak filling rate: 141.9 +/- 7.8 ms in kidney-alone patients vs. 209.4 +/- 13.5 ms in kidney-alone patients [P < 0.01]; peak filling rate/peak ejection rate ratio: 1.10 +/- 0.04 in kidney-pancreas patients vs. 0.81 +/- 0.08 in kidney-alone patients [P < 0.01]). A significant reduction in diastolic dysfunction rate was observed only in kidney-pancreas patients. CONCLUSIONS: Kidney-pancreas transplantation results in complete insulin independence, a better glycometabolic pattern and blood pressure control, an improvement of left ventricular function, and a reversal of diastolic dysfunction.     

Selective peripheral dopamine-1 receptor stimulation with fenoldopam in human essential hypertension.

SKF 82526-J, or fenoldopam, a benzazepine derivative, is a selective dopamine-1 (DA-1) agonist devoid of activity at dopamine-2, alpha- or beta-adrenergic receptors. We studied SKF 82526-J in 10 patients with essential hypertension and five normal control subjects on constant 150-meq sodium, 60 meq potassium intake. In the hypertensive patients, during a 6-d placebo period supine blood pressure and heart rate were stable at 156 +/- 6/105 +/- 4 mmHg and 76 +/- 5 beats/min, respectively. In response to a single oral dose of 100 mg of SKF 82526-J, supine blood pressure decreased to a nadir of 141 +/- 5/89 +/- 8 mmHg (P less than 0.0001) at 90 min and remained decreased at 145 +/- 6/99 +/- 3 mmHg (P less than 0.0001) at 4 h. Heart rate increased to 91 +/- 5 beats/min (P less than 0.002), but returned to control levels (82 +/- 5 beats/min) at 4 h. Renal blood flow increased from 371 +/- 57 to a peak of 659 +/- 104 ml/min and renal vascular resistance fell from 34 +/- 5 to 19 +/- 2 dyn sec cm-5 X 10(3) (P less than 0.01). Urine volume, sodium and fractional sodium excretion, and plasma renin activity were increased as a result of SKF 82526-J administration. During the ensuing 3 wk of SKF 82526-J, blood pressure remained decreased and returned to control levels after placebo administration. In contrast, in normal subjects SKF 82526-J administration was associated with a small transient reduction in diastolic pressure only. These results suggest that reduced dopaminergic activity expressed at the peripheral DA-1 receptor may contribute to the pathophysiology and/or maintenance of increased blood pressure in essential hypertension. In addition, the results suggest that peripheral DA-1 receptor stimulation with SKF 82526-J may be efficacious in the treatment of human essential hypertension.     

Circulatory adaptation to orthostatic stress in healthy 10-14-year-old children investigated in a general practice.

1. The magnitude and time course of circulatory adaptation to active standing were investigated in healthy premenarchic girls and boys (n = 24; 10-14 years old) by non-invasive measurement of heart rate and continuous finger blood pressure (Finapres). 2. Four subjects (two girls, two boys) showed presyncopal symptoms after 4-9 min of free standing. 3. In the 20 non-fainting subjects, changes in blood pressure and heart rate upon standing did not differ between girls (n = 10) and boys (n = 10). In the initial phase of standing (first 30 s) systolic and diastolic blood pressures dropped by 22 +/- 14 (mean +/- SD) and 16 +/- 7 mmHg, respectively, at 8 +/- 2 s. Blood pressure subsequently recovered and showed an overshoot in all subjects. The transient drop in blood pressure was accompanied by an increase in heart rate of 40 +/- 7 beats/min. These characteristic transient changes were not observed with passive head-up tilt. During the early steady-state phase (2 min), systolic blood pressure was similar to the supine value and diastolic blood pressure rose by 11 +/- 5 mmHg. Heart rate increased by 25 +/- 11 beats/min. In six of the subjects (three girls, three boys) the increase in heart rate exceeded 30 beats/min (postural tachycardia). Little further changes were observed during prolonged (10 min) standing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Normal fluctuations in pulmonary artery pressures and cardiac output in patients with severe left ventricular dysfunction.

BACKGROUND: One barrier to accurate interpretation of changes in hemodynamic pressures and cardiac output is lack of data about what constitutes a normal fluctuation. Few investigators have examined normal fluctuations in these parameters and none have done so in patients with left ventricular dysfunction. AIMS: To describe normal fluctuations in pulmonary artery pressures and cardiac output in patients with left ventricular dysfunction. METHODS: Hemodynamically stable advanced heart failure patients (N=39; 55+/-6 years old; 62% male) with left ventricular dysfunction (mean ejection fraction 22+/-5%) were studied. Cardiac output and pulmonary artery pressures were measured every 15 min for 2 h. RESULTS: Mean+/-standard deviation fluctuations were as follows: pulmonary artery systolic pressure=7+/-4 mmHg; pulmonary artery diastolic pressure=6+/-3 mmHg; pulmonary capillary wedge pressure=5+/-3 mmHg; cardiac output=0.7+/-0.3 l/min. The coefficient of variation for fluctuations in pulmonary artery systolic pressure was 6.7%, in pulmonary artery diastolic pressure was 9.3%, in pulmonary capillary wedge pressure was 9.2%, and in cardiac output was 7.2%. CONCLUSIONS: Values that vary <8% for pulmonary artery systolic pressure, <11% for pulmonary artery diastolic pressure, <12% for pulmonary capillary wedge pressure, and <9% for cardiac output from baseline represent normal fluctuations in these parameters in patients with left ventricular dysfunction.     

The peak atrioventricular pressure gradient to transmitral flow relation: kinematic model prediction with in vivo validation.

Physiologists and cardiologists estimate peak transvalvular pressure gradients (DeltaP) by Doppler echocardiographic imaging of peak flow velocities using the simplified Bernoulli relationship: DeltaP (mm Hg) = 4V(2) (m/s). Because left ventricular filling is initiated by mechanical suction, V can be predicted by the motion of a simple harmonic oscillator by the parametrized diastolic filling formalism that characterizes E-wave contours by 3 unique simple harmonic oscillator parameters: initial displacement (x(o) cm); spring constant (k g/s(2)); and damping constant (c g/s). Parametrized diastolic filling predicts peak atrioventricular pressure gradient as kx(o), the peak simple harmonic oscillator force. For validation, simultaneous (micromanometric) left ventricular pressure and E-wave data from 19 patients were analyzed. Model-predicted peak gradient (kx(o)) was compared with actual gradient (DeltaP(cath)) and with 4V(2). Multiple linear regression results for all patients yielded highly significant relation between kx(o) and DeltaP(cath) (kx(o) = m(1)DeltaP(cath) + b(1), where m(1) = 40.7 +/- 8.0 dyne/mm Hg, b(1) = 1540 +/- 116 dyne, r(2) = 0.97, P <.001). Regression analysis showed no significant correlation between 4V(2) and DeltaP(cath) (4V(2) = m(2)DeltaP(cath) + b(2), where m(2) = 0.01 +/- 0.03, m(2)/s(2)/mm Hg and b(2) = 2.07 +/- 0.44 m(2)/s(2), P = nonsignificant). We conclude that E-wave analysis by parametrized diastolic filling predicts peak atrioventricular gradients reliably and more accurately than 4V(2).     

Effects of delapril in combination with indapamide on blood pressure and left ventricular mass in elderly hypertensive patients

We present a single-blinded, placebo-controlled trial of the effects on blood pressure and left ventricular mass and of the safety of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1) with sitting systolic/diastolic blood pressure of 160-200/95-115 mm Hg (at the end of the placebo period). After a 2-week placebo run-in, patients took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. Twenty-four-hour ambulatory blood pressure was monitored and M- and B-mode echocardiography were performed before and after 24 weeks of treatment. Blood pressure decreased from 156 +/- 1.5/101 +/- 1 mm Hg before treatment to 133 +/- 1/73 +/- 1 mm Hg after treatment. The total blood pressure burden also decreased; the percentage of measurements with a systolic blood pressure > or = 140 mm Hg and a diastolic blood pressure > or = 90 mm Hg decreased from 48.7% +/- 5%/31.5% +/- 4.3% to 23.5% +/- 4%/20.5% +/- 2.9% (p < 0.0005 and p < 0.05). The area under the curve of the 24-hour blood pressure decreased from 250 +/- 41/103 +/- 21 mm Hg to 97 +/- 21/37 +/- 8.5 mm Hg (p < 0.001 and p < 0.005). The left ventricular mass index (LVMI) in the 15 patients with pretreatment left ventricular hypertrophy was reduced after therapy from 167.5 +/- 8.5 g/m 2 to 152.2 +/- 7.6 g/m 2 (p < 0.05). A positive correlation was observed between percent changes of the area under the curve of the 24-hour diastolic blood pressure and percent changes of LVMI (r = 0.6; p < 0. 05) in the 15 patients with left ventricular hypertrophy. Only 2 patients reported side effects: 1 developed skin rash and 1 developed headache. The safety of the treatment was confirmed by laboratory tests. In elderly hypertensive patients, the combination of delapril and indapamide at low doses reduced blood pressure and had favorable effects on LVMI with few side effects.     

The effect of rosiglitazone on overweight subjects with type 1 diabetes

OBJECTIVE: To evaluate the safety and effectiveness of rosiglitazone in the treatment of overweight subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 50 adult type 1 diabetic subjects with a baseline BMI > or =27 kg/m(2) were randomly assigned in a double-blind fashion to take insulin and placebo (n = 25) or insulin and rosiglitazone 4 mg twice daily (n = 25) for a period of 8 months. Insulin regimen and dosage were modified in all subjects to achieve near-normal glycemic control. RESULTS: Both groups experienced a significant reduction in HbA(1c) (A1C) level (rosiglitazone: 7.9 +/- 1.3 to 6.9 +/- 0.7%, P < 0.0001; placebo: 7.7 +/- 0.8 to 7.0 +/- 0.9%, P = 0.002) and a significant increase in weight (rosiglitazone: 97.2 +/- 11.8 to 100.6 +/- 16.0 kg, P = 0.008; placebo: 96.4 +/- 12.2 to 99.1 +/- 15.0, P = 0.016). Baseline measures of BMI (P = 0.001), total daily insulin dose (P = 0.002), total cholesterol (P = 0.005), HDL cholesterol (P = 0.001), and LDL cholesterol (P = 0.02) were predictors of improvement in A1C level only in the group treated with rosiglitazone. Total daily insulin dose increased in subjects taking placebo (74.0 +/- 33.8 to 82.0 +/- 48.9 units, P < 0.05 baseline vs. week 32), but it decreased slightly in subjects taking rosiglitazone (77.5 +/- 28.6 to 75.3 +/- 33.1 units). Both systolic blood pressure (137.4 +/- 15.6 vs. 128.8 +/- 14.8 mmHg, baseline vs. week 32, P < 0.02) and diastolic blood pressure (87.2 +/- 9.4 vs. 79.4 +/- 7.2 mmHg, P < 0.0001) improved in the group treated with rosiglitazone. The total incidence of hypoglycemia did not differ between groups. CONCLUSIONS: Rosiglitazone in combination with insulin resulted in improved glycemic control and blood pressure without an increase in insulin requirements, compared with insulin- and placebo-treated subjects, whose improved glycemic control required an 11% increase in insulin dose. Weight gain and hypoglycemia were similar in both groups at the end of the study. The greatest effect of rosiglitazone occurred in subjects with more pronounced markers of insulin resistance.