Efficacy and safety of olmesartan medoxomil­amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.

Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3.

There remain no approved therapies for rare but devastating neuronopathic glyocosphingolipid storage diseases, such as Sandhoff, Tay-Sachs, and Gaucher disease type 3. We previously reported initial optimization of the scaffold of eliglustat, an approved therapy for the peripheral symptoms of Gaucher disease type 1, to afford 2, which effected modest reductions in brain glucosylceramide (GlcCer) in normal mice at 60 mg/kg. The relatively poor pharmacokinetic properties and high Pgp-mediated efflux of 2 prompted further optimization of the scaffold. With a general objective of reducing topological polar surface area, and guided by multiple metabolite identification studies, we were successful at identifying 17 (CCG-222628), which achieves remarkably greater brain exposure in mice than 2. After demonstrating an over 60-fold improvement in potency over 2 at reducing brain GlcCer in normal mice, we compared 17 with Sanofi clinical candidate venglustat (Genz-682452) in the CBE mouse model of Gaucher disease type 3. At doses of 10 mg/kg, 17 and venglustat effected comparable reductions in both brain GlcCer and glucosylsphingosine. Importantly, 17 achieved these equivalent pharmacodynamic effects at significantly lower brain exposure than venglustat.

Association between ambient particulate matter (PM10) and incidence of diabetes in northwest of China: A prospective cohort study.

OBJECTIVES: We aimed to assess the association between long-term exposure to ambient PM10 and risk of diabetes incidence, based on the "Jinchang Cohort" platform in the Northwest of China. METHODS: We selected 19884 subjects who had not yet developed diabetes in the baseline and had completed survey information from "Jinchang Cohort". The residential address was used to match the nearest pollution monitoring station for each subject, and the average concentration of PM10 from baseline to follow-up were used as an estimate of individual exposure level. Cox regression model and restricted cubic splines functions were used to evaluate the effects of PM10 on the incidence of diabetes and the dose-response relationship after adjusting for confounding covariates. RESULTS: We observed 791 new-onset diabetics with a total follow-up of 45254.16 person-years (incidence rate of 17.48 per 1000 person-years). The risk of diabetes incidence increased by 17% (HR = 1.17, 95%CI: 1.08-1.26) per 10µg/m3 increase in environmental PM10, and the risk rises gradually with the rise of PM10 concentration. Comparing with the first quartile of PM10, the fully adjusted HRs (95%CI) for incident diabetes from the second to the fourth quartile of PM10 were 1.15 (95%CI: 0.93-1.43), 1.50 (95%CI: 1.22-1.84) and 1.44 (95%CI: 1.15-1.79), respectively (P for trend<0.001). Stratified analyses suggested that the risk of diabetes incidence associated with ambient PM10 was higher in female, young to middle-aged people, overweight and obese subjects, and subjects with FPG level at baseline lower than 5.6 mmol/L. CONCLUSIONS: Long-term exposure to ambient PM10 significantly associated with a higher risk of diabetes development. Some urgent strategies may be advocated to reduce air pollution that can aid in preventing the prevalence of diabetes in the population.

Synthesis of CID-cleavable protein crosslinking agents containing quaternary amines for structural mass spectrometry.

Two novel cyclic quaternary amine crosslinking probes are synthesized for structural mass spectrometry of protein complexes in solution and for analysis of protein interactions in organellar and whole cell extracts. Each exhibits high aqueous solubility, excellent protein crosslinking efficiencies, low collision induced dissociation (CID) energy fragmentation efficiencies, high stoichiometries of reaction, increased charges of crosslinked peptide ions, and maintenance of overall surface charge balance of crosslinked proteins.

Design, synthesis, and biological activity of 5'-phenyl-1,2,5,6-tetrahydro-3,3'-bipyridine analogues as potential antagonists of nicotinic acetylcholine receptors.

Starting from a known non-specific agonist (1) of nicotinic acetylcholine receptors (nAChRs), rationally guided structural-based design resulted in the discovery of a small series of 5'-phenyl-1,2,5,6-tetrahydro-3,3'-bipyridines (3a-3e) incorporating a phenyl ring off the pyridine core of 1. The compounds were synthesized via successive Suzuki couplings on a suitably functionalized pyridine starting monomer 4 to append phenyl and pyridyl substituents off the 3- and 5-positions, respectively, and then subsequent modifications were made on the flanking pyridyl ring to provide target compounds. Compound 3a is a novel antagonist, which is highly selective for α3ß4 nAChR (Ki=123nM) over the α4ß2 and α7 receptors.

Design and synthesis of triarylacrylonitrile analogues of tamoxifen with improved binding selectivity to protein kinase C.

The clinical selective estrogen receptor modulator tamoxifen is also a modest inhibitor of protein kinase C, a target implicated in several untreatable brain diseases such as amphetamine abuse. This inhibition and tamoxifen's ability to cross the blood brain barrier make it an attractive scaffold to conduct further SAR studies toward uncovering effective therapies for such diseases. Utilizing the known compound 6a as a starting template and guided by computational tools to derive physicochemical properties known to be important for CNS permeable drugs, the design and synthesis of a small series of novel triarylacrylonitrile analogues have been carried out providing compounds with enhanced potency and selectivity for PKC over the estrogen receptor relative to tamoxifen. Shortened synthetic routes compared to classical procedures have been developed for analogues incorporating a ß-phenyl ring, which involve installing dialkylaminoalkoxy side chains first off the α and/or α' rings of a precursor benzophenone and then condensing the resultant ketones with phenylacetonitrile anion. A second novel, efficient and versatile route utilizing Suzuki chemistry has also been developed, which will allow for the introduction of a wide range of ß-aryl or ß-heteroaryl moieties and side-chain substituents onto the acrylonitrile core. For analogues possessing a single side chain off the α- or α'-ring, novel 2D NMR experiments have been carried out that allow for unambiguous assignment of E- and Z-stereochemistry. From the SAR analysis, one compound, 6c, shows markedly increased potency and selectivity for inhibiting PKC with an IC50 of 80nM for inhibition of PKC protein substrate and >10µM for binding to the estrogen receptor α (tamoxifen IC50=20µM and 222nM, respectively). The data on 6c provide support for further exploration of PKC as a druggable target for the treatment of amphetamine abuse.

Synthesis and structure-activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors.

Recent evidence suggests atypical protein kinase C (aPKC) isoforms are required for both TNF- and VEGF-induced breakdown of the blood-retinal barrier (BRB) and endothelial permeability to 70kDa dextran or albumin. A chemical library screen revealed a series of novel small molecule phenylthiophene based inhibitors of aPKC isoforms that effectively block permeability in cell culture and in vivo. In an effort to further elucidate the structural requirements of this series of inhibitors, we detail in this study a structure-activity relationship (SAR) built on screening hit 1, which expands on our initial pharmacophore model. The biological activity of our analogues was evaluated in models of bona fide aPKC-dependent signaling including NFκB driven-gene transcription as a marker for an inflammatory response and VEGF/TNF-induced vascular endothelial permeability. The EC50 for the most efficacious inhibitors (6, 32) was in the low nanomolar range in these two cellular assays. Our study demonstrates the key structural elements that confer inhibitory activity and highlights the requirement for electron-donating moieties off the C-4 aryl moiety of the 2-amino-3-carboxy-4-phenylthiophene backbone. These studies suggest that this class has potential for further development into small molecule aPKC inhibitors with therapeutic efficacy in a host of diseases involving increased vascular permeability and inflammation.

Regular exercise-induced increased number and activity of circulating endothelial progenitor cells attenuates age-related decline in arterial elasticity in healthy men.

BACKGROUND: Deficiency in number and activity of circulating EPCs is associated with reduced arterial elasticity in humans with advancing aging. Physical exercise can increase the number and activity of circulating EPCs in humans. Here we investigated whether regular exercise-induced enhanced circulating endothelial progenitor cells (EPCs) improves age-related decline in arterial elasticity in healthy men. METHODS: In a cross-sectional study, the number and activity of circulating EPCs as well as brachial-ankle pulse wave velocity (baPWV) of young and older sedentary or endurance-trained healthy men were studied. Then we observed the effect of regular exercise on circulating EPCs and baPWV of 10 older and 10 young sedentary healthy men. RESULTS: In both sedentary and endurance-trained men, the number and activity of circulating EPCs were significantly low in older men compared with young men, which was paralleled to increased baPWV. After three months of regular exercise, the number and activity of circulating EPCs increased, and the baPWV of 10 older and 10 young sedentary healthy men decreased. However, the increased number and activity of circulating EPCs and decreased baPWV of older sedentary healthy men were higher. There was a close correlation between circulating EPCs and baPWV. Multivariate analysis identified proliferative activity of circulating EPCs as an independent predictor of baPWV. CONCLUSIONS: The present study demonstrates for the first time that regular physical exercise-induced enhanced circulating EPCs attenuates age-related decline in arterial elasticity in healthy men. These findings provide novel insights into the protective effects of exercise on age-related vascular injury.

Synthesis and structure-activity relationships of novel substituted 8-amino, 8-thio, and 1,8-pyrazole congeners of antitubercular rifamycin S and rifampin.

A series of rifamycin S and rifampin analogues incorporating substituted 8-amino, 8-thio, and 1,8-pyrazole substituents has been synthesized. The compounds were made by activation of the C-8 phenol as a sulfonate ester, followed by displacement with selected nitrogen and sulfur nucleophiles. The analogues were screened in assays to quantify their antitubercular activity under both aerobic and anaerobic conditions, and for inhibition of wild-type Mycobacterium tuberculosis (MTB) RNAP and rifamycin-resistant MTB RNAP (S450L) via an in vitro rolling circle transcription assay. Additionally, the MIC(90) values were determined for these analogues against Escherichia coli strains. Although none of the analogues displayed superior enzymatic or microbiological activity to their parent scaffolds, the results are consistent with the Rif C-8 hydroxyl acting as a hydrogen bond acceptor with S450 and that Rif resistance in the S450L mutant is due to loss of this hydrogen bond. Representative analogues were also evaluated in the human pregnane X receptor (PXR) activation assay.

Enhanced external counterpulsation attenuates atherosclerosis progression through modulation of proinflammatory signal pathway.

OBJECTIVE: Shear stress may be the most crucial local factor affecting atherogenesis. The present study investigated the effect of exposure to increased shear stress promoted by enhanced external counterpulsation (EECP) on the progression of atherosclerosis and the underlying inflammation-related molecular mechanisms in a porcine model of hypercholesterolemia. METHODS AND RESULTS: Hypercholesterolemic pigs were subjected to a 7-week EECP intervention while being fed a high-cholesterol diet. EECP resulted in a 34.38% increase of mean wall shear stress and a significantly lower pulsatility index in the brachial artery. The animals receiving EECP showed a marked reduction in atherosclerotic lesion size in the coronary artery and abdominal aorta compared with the hypercholesterolemic control group, associated with a decrease in macrophage accumulation. The expression of a set of genes involved in inflammation (including C-reactive protein [CRP], complement 3a, vascular cell adhesion molecule-1 [VCAM-1], and inducible nitric oxide synthase), mitogen-activated protein kinase (MAPK)-p38 phosphorylation, and nuclear factor-kappaB (NF-kappaB) activation, was attenuated. CONCLUSIONS: These findings suggested that long-term EECP exerts a retarding effect on atherosclerosis by downregulating proinflammatory gene expression. The underlying mechanisms are related to chronic exposure to increased pulsatile shear stress promoted by EECP; this exposure suppresses the overactivation of the MAPK-P38/NF-kappaB/VCAM-1 signaling pathway induced by hypercholesterolemia.

Enhanced external counterpulsation inhibits intimal hyperplasia by modifying shear stress responsive gene expression in hypercholesterolemic pigs.

BACKGROUND: Enhanced external counterpulsation (EECP) is a circulation assist device that may improve endothelial dysfunction by increasing shear stress. Chronic exposure of vascular endothelial cells and vascular smooth muscle cells to relatively high physiological shear stress has antiproliferative and vasoprotective effects. The present study hypothesizes that EECP inhibits intimal hyperplasia and atherogenesis by modifying shear stress-responsive gene expression. METHODS AND RESULTS: Thirty-five male pigs were randomly assigned to 3 groups: high-cholesterol diet (n=11), high-cholesterol diet plus EECP (n=17), and usual diet (control; n=7). The coronary arteries and aortas were collected for histopathological study and immunohistochemical and Western blot analysis. The peak diastolic arterial wall shear stress during EECP increased significantly compared with before EECP (49.62+/-10.71 versus 23.92+/-7.28 dyne/cm2; P<0.001). Intimal hyperplasia was observed in the coronary arteries of the high-cholesterol diet group, whereas in animals receiving EECP, the intima-to-media area ratio was significantly decreased by 41.59% (21.27+/-10.00% versus 36.41+/-16.69%; P=0.008). Hypercholesterolemia attenuated the protein expression of endothelial NO synthase and enhanced the phosphorylation of extracellular signal-regulated kinases 1/2. EECP treatment alleviated these adverse changes. CONCLUSIONS: EECP reduces hypercholesterolemia-induced endothelial damage, arrests vascular smooth muscle cell proliferation and migration, decreases proliferating cell nuclear antigen proliferative index, suppresses extracellular matrix formation, and eventually inhibits intimal hyperplasia and the development of atherosclerosis by increasing the arterial wall shear stress, which in turn activates the endothelial NO synthase/NO pathway and probably suppresses extracellular signal-regulated kinases 1/2 overactivation.

Mechanism of action and structural requirements of constrained peptide inhibitors of RGS proteins.

Regulators of G-protein signaling (RGS) accelerate guanine triphosphate hydrolysis by Galpha-subunits and profoundly inhibit signaling by G protein-coupled receptors. The distinct expression patterns and pathophysiologic regulation of RGS proteins suggest that inhibitors may have therapeutic potential. We previously reported the design of a constrained peptide inhibitor of RGS4 (1: Ac-Val-Lys-[Cys-Thr-Gly-Ile-Cys]-Glu-NH2, S-S) based on the structure of the Galphai switch 1 region but its mechanism of action was not established. In the present study, we show that 1 inhibits RGS4 by mimicking and competing for binding with the switch 1 region of Galphai and that peptide 1 shows selectivity for RGS4 and RGS8 versus RGS7. Structure-activity relationships of analogs related to 1 are described that illustrate key features for RGS inhibition. Finally, we demonstrate activity of the methylene dithioether-bridged peptide inhibitor, 2, to modulate muscarinic receptor-regulated potassium currents in atrial myocytes. These data support the proposed mechanism of action of peptide RGS inhibitors, demonstrate their action in native cells, and provide a starting point for the design of RGS inhibitor drugs.

[Effects of enhanced external counterpulsation in atherosclerosis and NF-kappaB expression: a pig model with hypercholesterolemia].

OBJECTIVE: To study the effects of enhanced external counterpulsation (EECP) on the vascular morphology, and endothelial function using experimentally induced hypercholesterolemic pigs. METHODS: Thirty five male pigs were randomly divided into three groups: 7 normal control animals, 11 hypercholesterolemic animals, and 17 hypercholesterolemic animals receiving EECP. Serum cholesterol was measured. The coronary arteries and aortas were sampled for histopathologic and ultrastructural examination. The NF-kappaB protein expression of porcine coronary arteries was investigated by immunofluorescence. RESULTS: Compared with the normal controls, serum cholesterol levels were significantly higher in the hypercholesterolemic animals with or without EECP. The plaque/intimal area ratio of the aorta decreased significantly in animals receiving EECP [(3.33 +/- 2.40)%, versus (12.03 +/- 7.12)% in those without EECP, P < 0.05]. Lipid deposition, endothelial damage and proliferation of smooth muscle cells were less severe in animals receiving EECP than those not. Moreover, activation and expression of NF-kappaB also decreased significantly (P < 0.05) in animals receiving EECP. CONCLUSIONS: EECP improves the morphology and function of vascular endothelium, and retards the development and progression of atherosclerosis, likely through the inhibition of NF-kappaB signaling pathway.

Reduced arterial elasticity is associated with endothelial dysfunction in persons of advancing age: comparative study of noninvasive pulse wave analysis and laser Doppler blood flow measurement.

BACKGROUND: Endothelial dysfunction is the earliest marker for age-related abnormalities in vascular function, and examination of endothelial function has important clinical relevance. The present study was performed to evaluate effects of aging on arterial elasticity by using pulse waveform analysis and to investigate whether the changes in arterial elasticity might be used as a noninvasive measure for endothelial dysfunction. METHODS: A total of 24 healthy male volunteers were divided into young (n = 12) and elderly (n = 12) groups. Endothelial function was evaluated by delivering acetylcholine (Ach) and sodium nitroprusside (SNP) to the forearm vessels using iontophoresis, respectively, and measured blood flow using laser Doppler fluximetry. Large and small artery elasticity indices were noninvasively assessed using pulse wave analysis. RESULTS: Basal blood flow was similar between the young and elderly groups (14.58 +/- 3.4 v 13.52 +/- 3.41 PU, P = NS). Peak blood flow induced by Ach was significantly reduced in the elderly group compared with the young group (83.4 +/- 11.9 v 93.75 +/- 10.87 PU, P < .05). However, peak blood flow induced by SNP was similar in the two groups (119.17 +/- 16.76 v 128.33 +/- 21.29 PU, P = NS). In parallel, C1 large artery elasticity and C2 small artery elasticity indices were significantly reduced in the elderly group compared with the young group (11.42 +/- 1.67 v 16.75 +/- 2.09 mL/mm Hg x 10, P < .001; and 7.67 +/- 1.56 v 10.75 +/- 1.86 mL/mm Hg x 100, P < .001, respectively). The Ach-induced peak blood flow correlated with C1 large and C2 small artery elasticity indices. CONCLUSIONS: Advancing age is associated with endothelial dysfunction and reduced arterial elasticity. Reduced arterial elasticity parallels changes in impaired endothelium dependent vasodilation. It appears that reduced arterial elasticity may be used as a noninvasive measure for the determination of endothelial function.

Structure-based design, synthesis, and activity of peptide inhibitors of RGS4 GAP activity.

One of the principal roles of the multifunctional regulator of G-protein signaling (RGS) proteins is to terminate G-protein-coupled receptor (GPCR) signaling by binding to the G-protein Galpha subunit, thus acting as GTPase-activating proteins (GAPs). In principle, then, selective inhibitors of this GAP function would have potential as therapeutic agents, as they could be used to augment the effects of endogenous or exogenous GPCR agonists. Using the published RGS4-G(ialpha1) X-ray structure, we have designed and synthesized a series of cyclic peptides, modeled on the G(ialpha) switch I region, that inhibit RGS4 GAP activity, presumably by blocking the interaction between RGS4 and G(ialpha1). These compounds should prove useful for elucidating RGS-mediated activity and serve as a starting point for the development of a novel class of therapeutic agent.

In vivo adaptive response of the peripheral conduit artery in patients with borderline systolic hypertension.

OBJECTIVE: To investigate elastic changes of the radial artery, a medium-sized muscular peripheral conduit artery, in patients with borderline systolic hypertension. METHODS: Using a non-invasive high-resolution echo-tracking device coupled to a photoplethysmography (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured radial artery elastic parameters of 20 patients with borderline systolic hypertension and 20 normal subjects according to Langewouters model. RESULTS: The diameter of the radial artery of control subjects and those with borderline systolic hypertension at the isobaric level of 100 mmHg and mean arterial pressure was similar, but the compliance and distensibility at similar conditions in patients with borderline systolic hypertension did not further reduced and even increased. CONCLUSION: In patients with borderline systolic hypertension, the adaptive responses of the radial artery compliance and distensibility to increased pressure were directed to maintain its elasticity, contributing to the homeostasis of the cardiovascular system.

[Effects of external counterpulsation on the pulsatility of blood pressure and blood flow in dogs].

Pulsatile blood flow plays an important role in maintaining normal vascular endothelial function. Quantitative measurement of pulsatility of artery blood pressure and blood flow in dogs and effects of enhanced external counterpulsation (EECP) on the pulsatility were taken in this study. Common carotid artery blood pressure and blood flow were measured in 6 beagle dogs that had suffered from an acute myocardial infarction 6 weeks before. A 6F tip transducer catheter was inserted into the right common carotid artery to measure blood pressure, and blood flow was measured in the left common carotid artery by an electromagnetic blood flow probe under anesthesia before and during EECP. Blood pulse pressure, pulsatility index (ratio of peak pressure to end diastolic pressure) and standard deviation of blood pressure were calculated to evaluate the pulsatility of arterial blood pressure. Blood pulse flow, pulsatility index (ratio of peak flow to trough flow) and standard deviation of blood flow were calculated to evaluate the pulsatility of blood flow. Mean vascular resistance (MVR) was calculated as MVR = mean blood pressure/mean blood flow. Blood pulse pressure, pulsatility index and standard deviation of blood pressure were elevated from 30 +/- 9 mmHg, 1.26 +/- 0.05 and 8.7 +/- 2.5 mmHg to 43 +/- 8 mmHg (P < 0.05), 1.54 +/- 0.13 and 12.4 +/- 2.0 mmHg (P < 0.05) before and during EECP, respectively. Blood pulse flow, pulsatility index and standard deviation of blood flow were elevated from 317 +/- 48 ml/min, 2.85 +/- 0.21 and 96 +/- 21 ml/min to 447 +/- 88 ml/min, 4.56 +/- 0.90 and 131 +/- 39 ml/min before and during EECP (P < 0.05). MVR was decreased from 578 +/- 72 before EECP to 476 +/- 85 Wood units during EECP(P < 0.05). These data demonstrate that EECP gives an elevation of pulsatility to blood pressure and blood flow, thus it may lead to the decrease of vascular resistance.

[Effects of external counterpulsation on the pulsatility of blood pressure in human subjects].

Pulsatile blood flow plays an important role in maintaining normal vascular endothelial function. Quantitative measurement of pulsatility of human arterial blood pressure and the influence of enhanced external counterpulsation (EECP) on the pulsatility were investigated in this study. Eight healthy young male volunteers aged 22 to 35 were included. A 4F tip transducer catheter was inserted under local anaesthesia into the radial artery up to the aortic arch. Intraarterial blood pressure was recorded before and during EECP. Blood pulse pressure, pulsatility index (ratio of peak pressure to end diastolic pressure) and standard deviation of blood pressure in 5 cardiac cycle was calculated to evaluate the pulsatility of arterial blood pressure. The results showed that blood pulse pressure, pulsatility index and standard deviation of blood pressure were elevated from 47 +/- 5 mmHg, 1.64 +/- 0.11 and 13.6 +/- 1.5 mmHg to 77 +/- 3 mmHg, 2.46 +/- 0.25 and 19.3 +/- 2.2 mmHg before and during EECP respectively (P < 0.05). Decreasing of systolic pressure and increasing of diastolic pressure during counterpulsation were also observed. EECP gives an elevation of pulsatility to human blood pressure.