F2-isoprostanes are stable lipid peroxidation products of arachidonic acid and their quantification provides a novel approach to the assessment of oxidative stress in vivo. F2-isoprostanes are ...present in increased amounts in adult hypercholesterolemia, but no data exist concerning children. We investigated urinary isoprostaglandin F2, type III production as an index of lipid peroxidation in 15 children presenting with type IIa hypercholesterolemia (serum total cholesterol, 290 SD +/- 70 mg/dl; low-density lipoprotein cholesterol, 210 SD +/- 90 mg/dl) compared with 15 sex- and age-paired control children (serum total cholesterol, 160 SD +/- 20 mg/dl). Urinary levels of isoprostaglandin F2alpha type III were measured by gas chromatography mass spectrometry. Urinary concentrations did not differ significantly in hypercholesterolemic children compared with control children (84.7 SD +/- 37 vs. 96 SD +/- 35 pmol/mmol creatinine, respectively). No significant correlation was found with total cholesterol, low-density-lipoprotein and high-density-lipoprotein cholesterol, and apolipoprotein B and A1 serum levels. F2-isoprostane urinary levels in children with type IIa hypercholesterolemia do not differ from those of age- and sex-matched control children and are not correlated to blood lipid parameters, suggesting that hypercholesterolemia is not associated with increased lipid peroxidation in childhood.
To investigate the effect of amlodipine on baroreflex sensitivity and sympathetic system activity, 36 patients with essential hypertension were randomized to once-daily, double-blind treatment with ...amlodipine 5 mg or placebo 5 mg for 60 days. Measurements with a Finapres device allowed calculation of baroreflex sensitivity and blood pressure (BP) variability. Adrenergic activity was assessed via measurements of lymphocyte β
2-adrenoceptors and plasma catecholamine concentrations. Compared with placebo, amlodipine significantly decreased BP, but did not significantly alter baroreflex sensitivity. Spectral analysis of Finapres data showed that, compared with placebo, amlodipine decreased the variability of systolic blood pressure, diastolic blood pressure, and RR interval in the low frequency band. There were no simultaneous changes in adrenergic function, however, suggesting that these effects of amlodipine were not mediated via sympathetic nervous system activation.
This multicenter, double-blind, parallel-group study was designed to assess the efficacy and the safety of fixed low dose combination perindopril 2 mg indapamide 0.625 mg (Per Ind) versus atenolol 50 ...mg (Ate). After a 4-week placebo run-in, 446 hypertensive patients (mean age: 55.8 ± 11.0 years) were randomised to receive Per Ind or Ate for 12 weeks. The primary outcome measures were the changes in trough supine systolic and diastolic blood pressure (sSBP, sDBP) between baseline and the last observation. Equivalence was assessed in an intention-to-treat analysis using a two one-sided tests procedure. Per Ind and Ate decreased sSBP by −20.5 mmHg and −20.1 mmHg, respectively; the 90% confidence interval −2.3; 1.5 of the intertreatment difference (−0.4 mmHg) fell within the predefined equivalence interval −8; +8 mmHg. Similarly, the sDBP decreased by −15.1 mmHg (Per Ind) and −16.2 mmHg (Ate) with an intertreatment difference of 1.1 mmHg whose 90% confidence interval −0.1; 2.2 mmHg fell within the predefined equivalence interval −4; +4 mmHg; thus antihypertensive efficacy of Per Ind and Ate were equivalent (P <0.001). In patients older than 65, Per Ind induces a statistically greater decrease in sSBP than Ate (P <0.05). Per Ind was well tolerated. Further controlled studies are needed to confirm these results on a long-term period.
Objective: to analyse the performance of a Windkessel blood pressure (BP) modeling of arterial compliance adjusted in a dynamic fashion according to a non-linear relationship between the arterial ...compliance (AC) and BP. Non invasive measurements of the radial BP waveform (MILLAR tonometry) were compared to those constructed by an electric simulator reproducing the model in a symmetrical network subdivided into 121 segments. We introduced at cardiac level the aortic stroke volume (Doppler echocardiography) and the dynamic values of compliance (relation of compliance-to pressure, constant or variable) whether the model was linear or non linear, measured by high resolution Doppler (NIUS 02) for each subject. Results: at the radial artery segment the modelled BP obtained by the non linear model of AC was not significantly different from the measured BP wave, while in the linear model (AC constant at mean BP level) the systolic BP was significantly underestimated. (*
P<0.05) Conclusion: this work shows the limits inherent in simplification of arterial compliance in the Windkessel model using constant parameters. This demonstrates the influence of the dynamic properties of the arterial wall in a conduction artery on the level of systolic and diastolic BP.
High blood pressure is almost constant in renal transplant patients for whom dysautonomia is frequently described. The main objective of this study was to analyse the variations in blood pressure and ...heart rate recorded by ambulatory measurement during changes in position in renal transplant patients.
Thirty-nine non-diabetic renal transplant patients with a renal transplant functioning for more than a year, were selected at random. Blood pressure was measured using the validated monitor Diasys Integra with a position sensor to discriminate between standing and sitting/lying.
Systolic blood pressure and heart rate were significantly higher when the patient was standing than when sitting/lying (+2.9 mmHg, P<0.05 and +9 beats/min, P<0.001 respectively) and diastolic blood pressure tends to be higher (+1.7 mmHg, NS) when standing. One minute after standing up, the heart rate rises by about 9 beats/min (P<0.001) while systolic and diastolic blood pressures do not vary significantly. Variations in systolic blood pressure and heart rate on changing position are therefore in the same direction as those recorded in elderly normotensive or hypertensive untreated subjects, but with a lower amplitude.
In most of non-diabetic functional renal transplant patients, there is an absence of an orthostatic decline in blood pressure. Thus, it could be considered that there is no real dysautonomia in this specific population.
Aim: The objective of this study was to compare the antihypertensive efficacy and safety of the angiotensin II antagonist olmesartan medoxomil and the ACE inhibitor ramipril in elderly patients with ...mild to moderate essential hypertension, grouped according to renal function.Methods: We performed a post hoc analysis of pooled data from two randomized, double-blind, parallel-group, multicentre studies. After a 2-week placebo wash-out period, 1453 mild to moderate hypertensive subjects were randomized to a 12-week treatment with olmesartan medoxomil 10 mg/day or ramipril 2.5 mg/day. After 2 and 6 weeks, doses were increased up to a maximum of 40 mg/day (olmesartan medoxomil) and 10 mg/day (ramipril) in non-normalized subjects (office systolic blood pressure SBP ≥ 140 mmHg or diastolic blood pressure DBP ≥90 mmHg in non-diabetic subjects and office SBP ≥ 130 mmHg or DBP ≥80 mm Hg in diabetic patients). Office blood pressure (BP) was measured at 0, 2, 6 and 12 weeks, 24-hour ambulatory BP at 0 and 12 weeks. 284 patients treated with olmesartan medoxomil 40 mg/day at the end of the double-blind period entered a 36-week, open-label follow-up. Renal function (Cockroft-Gault equation) was evaluated as normal or increased estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2, mild eGFR reduction (60–90 mL/min/1.73 m2) and moderate or severe eGFR reduction (<60 mL/min/1.73 m2).Results: 181 (12.7%) subjects had normal or increased eGFR, 840 (58.9%) mild eGFR reduction, and 405 (28.4%) moderate or severe eGFR reduction. Baseline-adjusted office BP reductions were superior with olmesartan medoxomil than with ramipril in normal or increased (olmesartan medoxomil — ramipril difference SBP: 5.0 mmHg 95% CI 9.1, 0.9, p = 0.018; DBP: 2.7 mmHg 4.8, 0.6, p = 0.011) and mildly reduced eGFR patients (SBP: 1.6 mmHg 3.5, 0.2, p = 0.080; DBP: 1.2 mmHg 2.3, 0.2, p = 0.022). In the group with moderately or severely reduced eGFR the two treatments were comparable (SBP: 1.9 mmHg 4.6, 0.9, p = 0.185; DBP: 0.8 mmHg 2.3, +0.7; p = 0.296). At 12 weeks, the rate of normalized patients was 46.1 % with olmesartan medoxomil versus 23.9% with ramipril (p = 0.002) in the normal, and 49.9% versus 42.7% (p = 0.037) in the mild eGFR reduction group. No significant differences in normalization rate were observed in the moderately or severely reduced eGFR group (olmesartan medoxomil 49.5% vs ramipril 46.3%, p = 0.519). eGFR did not show any significant change during treatment.Conclusions: Olmesartan medoxomil provides a more effective BP control, similar if not superior to that of ramipril, independently from the patient’s renal function status.
Aim: The objective of this study was to compare the antihypertensive efficacy and safety of the angiotensin II antagonist olmesartan medoxomil and the ACE inhibitor ramipril in elderly patients with ...mild to moderate essential hypertension, grouped according to renal function. Methods: We performed a post hoc analysis of pooled data from two randomized, double-blind, parallel-group, multicentre studies. After a 2-week placebo wash-out period, 1453 mild to moderate hypertensive subjects were randomized to a 12-week treatment with olmesartan medoxomil 10 mg/day or ramipril 2.5 mg/day. After 2 and 6 weeks, doses were increased up to a maximum of 40 mg/day (olmesartan medoxomil) and 10 mg/day (ramipril) in non-normalized subjects (office systolic blood pressure SBP ≥140 mmHg or diastolic blood pressure DBP ≥90 mmHg in non-diabetic subjects and office SBP ≥130 mmHg or DBP ≥80 mmHg in diabetic patients). Office blood pressure (BP) was measured at 0, 2, 6 and 12 weeks, 24-hour ambulatory BP at 0 and 12 weeks. 284 patients treated with olmesartan medoxomil 40 mg/day at the end of the double-blind period entered a 36-week, open-label follow-up. Renal function (Cockroft-Gault equation) was evaluated as normal or increased estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m 2, mild eGFR reduction (60-90 mL/min/1.73 m2) and moderate or severe eGFR reduction (<60 mL/min/1.73 m2). Results: 181 (12.7%) subjects had normal or increased eGFR, 840 (58.9%) mild eGFR reduction, and 405 (28.4%) moderate or severe eGFR reduction. Baseline-adjusted office BP reductions were superior with olmesartan medoxomil than with ramipril in normal or increased (olmesartan medoxomil - ramipril difference SBP: 5.0 mmHg 95% CI 9.1, 0.9, p = 0.018; DBP: 2.7 mmHg 4.8, 0.6, p = 0.011) and mildly reduced eGFR patients (SBP: 1.6 mmHg 3.5, 0.2, p = 0.080; DBP: 1.2 mmHg 2.3, 0.2, p = 0.022). In the group with moderately or severely reduced eGFR the two treatments were comparable (SBP: 1.9 mmHg 4.6, 0.9, p = 0.185; DBP: 0.8 mmHg 2.3, +0.7; p = 0.296). At 12 weeks, the rate of normalized patients was 46.1% with olmesartan medoxomil versus 23.9% with ramipril (p = 0.002) in the normal, and 49.9% versus 42.7% (p = 0.037) in the mild eGFR reduction group. No significant differences in normalization rate were observed in the moderately or severely reduced eGFR group (olmesartan medoxomil 49.5% vs ramipril 46.3%, p = 0.519). eGFR did not show any significant change during treatment. Conclusions: Olmesartan medoxomil provides a more effective BP control, similar if not superior to that of ramipril, independently from the patient's renal function status. Received for publication 28 August 2012; accepted for publication 19 September 2012. PUBLICATION ABSTRACT
Enoximone (a type III-selective phosphodiesterase inhibitor) and dobutamine (a beta-receptor agonist) are positive inotropic drugs frequently used in the postoperative management of coronary bypass ...surgery. The purpose of this study was to characterize their relaxant effects on the human internal mammary artery (IMA) and the gastroepiploic artery (GEA) and to test the hypothesis that their combination may have greater than additive relaxant effects. In organ baths, the relaxant effects of enoximone and dobutamine were tested on rings of IMA (n = 86) precontracted with U46619 (a thromboxane A2 mimetic), norepinephrine (NE), or KCl. The relaxant effects of dobutamine and enoximone also were tested on rings of GEA (n = 42) precontracted with U46619 and NE. The effect of the combination of enoximone and dobutamine were tested on rings of IMA (n = 24) precontracted with U46619 or NE. With respect to maximal relaxations induced by papaverine (10(-4) M), enoximone (< or =10(-3) M) caused full relaxations of IMA precontracted with NE, U46619, or KCI. Dobutamine (< or =10(-3) M) caused full relaxations of IMA precontracted with NE or KCI but only 46% (95% CI, 27-65) relaxation in the rings precontracted with U46619. Similar patterns of relaxation were observed in GEA rings, with dobutamine inducing partial relaxation in GEA precontracted with U46619. The pD2 values of enoximone and dobutamine were both significantly lower in segments precontracted with U46619. The in vitro threshold relaxant concentrations were in the upper limits or over the range of therapeutic plasma concentrations. The relaxant effect of the combination was significantly more important than the theoretic additive effect in IMA contracted with U46619 or NE. Enoximone and dobutamine are potent in vitro vasodilators but exert weak relaxant effects in IMA and GEA at concentrations in the therapeutic range. There is, however, a greater than additive vasorelaxant effect of the combination, suggesting that the vasorelaxant effect of the combination, in addition to the additive inotropic effect, may be beneficial to patients undergoing coronary bypass grafting.
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