Hemodynamics of ventricular-arterial coupling under enhanced external counterpulsation: An optimized dual-source lumped parameter model.

BACKGROUND AND OBJECTIVE: Enhanced external counterpulsation (EECP) is a mechanically assisted circulation technique widely used in the rehabilitation and management of ischemic cardiovascular diseases. It contributes to cardiovascular functions by regulating the afterload of ventricle to improve hemodynamic effects, including increased diastolic blood pressure at aortic root, increased cardiac output and enhanced blood perfusion to multiple organs including coronary circulation. However, the effects of EECP on the coupling of the ventricle and the arterial system, termed ventricular-arterial coupling (VAC), remain elusive. We aimed to investigate the acute effect of EECP on the dynamic interaction between the left ventricle and its afterload of the arterial system from the perspective of ventricular output work. METHODS: A neural network assisted optimization algorithm was proposed to identify the ordinary differential equation (ODE) relation between aortic root blood pressure and flow rate. Based on the optimized order of ODE, a lumped parameter model (LPM) under EECP was developed taking into consideration of the simultaneous action of cardiac and EECP pressure sources. The ventricular output work, in terms of aortic pressure and flow rate cooperated with the LPM, was used to characterize the VAC of ventricle and its afterload. The VAC subjected to the principle of minimal ventricular output work was validated by solving the Euler-Poisson equation of cost function, ultimately determining the waveforms of aortic pressure and flow rate. RESULTS: A third-order ODE can precisely describe the hemodynamic relationship between aortic pressure and flow rate. An optimized dual-source LPM with three energy-storage elements has been constructed, showing the potential in probing VAC under EECP. The LPM simulation results demonstrated that the VAC in terms of aortic pressure and flow rate yielded to the minimal ventricular output work under different EECP pressures. CONCLUSIONS: The ventricular-arterial coupling under EECP is subjected to the minimal ventricular output work, which can serve as a criterion for determining aortic pressure and flow rate. This study provides insight for the understanding of VAC and has the potential in characterizing the performance of the ventricular and arterial system under EECP.

A numerical study on the siphonic effect of enhanced external counterpulsation at lower extremities with a coupled 0D-1D closed-loop personalized hemodynamics model.

Enhanced external counterpulsation (EECP) is a treatment and rehabilitation approach for ischemic diseases, including coronary artery disease. Its therapeutic benefits are primarily attributed to the improved blood circulation achieved through sequential mechanical compression of the lower extremities. However, despite the crucial role that hemodynamic effects in the lower extremity arteries play in determining the effectiveness of EECP treatment, most studies have focused on the diastole phase and ignored the systolic phase. In the present study, a novel siphon model (SM) was developed to investigate the interdependence of several hemodynamic parameters, including pulse wave velocity, femoral flow rate, the operation pressure of cuffs, and the mean blood flow changes in the femoral artery throughout EECP therapy. To verify the accuracy of the SM, we coupled the predicted afterload in the lower extremity arteries during deflation using SM with the 0D-1D patient-specific model. Finally, the simulation results were compared with clinical measurements obtained during EECP therapy to verify the applicability and accuracy of the SM, as well as the coupling method. The precision and reliability of the previously developed personalized approach were further affirmed in this study. The average waveform similarity coefficient between the simulation results and the clinical measurements during the rest state exceeded 90%. This work has the potential to enhance our understanding of the hemodynamic mechanisms involved in EECP treatment and provide valuable insights for clinical decision-making.

A real-time patient-specific treatment strategy for enhanced external counterpulsation.

Diastolic/systolic blood pressure ratio (D/S) ≥ 1.2 is the gold standard of enhanced external counterpulsation (EECP) treatment, but it does not show a clear clinical correspondence with the configuration of the EECP mode. As such, a single target results in different treatment effects in different individuals. The local haemodynamic effect (wall shear stress, WSS) of EECP on vascular endothelial cells is conducive to promote the growth of collateral circulation vessels and restore the blood supply distal to the stenosis lesion. Considering the haemodynamic effects of WSS on human arteries, this study developed a real-time patient-specific treatment strategy of EECP for patients with cardio-cerebrovascular diseases. Based on patient-specific haemodynamic data from 113 individuals, an optimization algorithm was developed to achieve the individualization of a 0D lumped-parameter model of the human circulatory system, thereby simulating the patient-specific global haemodynamic effects. 0D/3D coupled cardio-cerebrovascular models of two subjects were established to simulate the local WSS. We then established statistical models to evaluate clinically unmeasurable WSS based on measurable global haemodynamic indicators. With the aim of attaining appropriate area- and time-averaged WSS (ATAWSS, 4-7 Pa), as evaluated by global haemodynamic indicators, a closed-loop feedback tuning method was developed to provide patient-specific EECP treatment strategies. Results showed that for clinical data collected from 113 individuals, the individualized 0D model can accurately simulate patient-specific global haemodynamic effects (average error <5%). Based on two subjects, the statistical models can be used to evaluate local ATAWSS (error <6%) for coronary arteries and for cerebral arteries. An EECP mode planned by the patient-specific treatment strategy can promote an appropriate ATAWSS within a 16 s calculation time. The real-time patient-specific treatment strategy of EECP is expected to improve the long-term outcome for each patient and have potential clinical significance.

Enhanced external counterpulsation improves sleep quality in chronic insomnia: A pilot randomized controlled study.

PURPOSE: To investigate the short-term efficacy of enhanced external counterpulsation (EECP) on chronic insomnia. METHODS: This is a pilot randomized, participant-blind, and sham-controlled study. Forty-six participants with chronic insomnia were randomly assigned in a 1:1 ratio to receive EECP or sham EECP intervention (total of 35 sessions with 45 min each). The primary outcome was Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes included sleep diary, Hospital Anxiety and Depression Scale (HADS), Short-Form Health Survey (SF12), flow mediated dilation (FMD), serum biomarkers of melatonin, cortisol, interleukin-6, and high sensitivity C-reactive protein. Outcomes were assessed after treatment and at 3-month follow-up. RESULTS: The PSQI was significantly decreased in both EECP and sham groups after 35-session intervention (13.74 to 6.96 in EECP and 13.04 to 9.48 in sham), and EECP decreased PSQI more than sham EECP (p = 0.009). PSQI in two groups kept improved at 3-month follow-up. After treatment, the total sleep time, sleep efficiency, FMD value and SF12 mental component of EECP group were significantly improved, and group differences were found for these outcomes. At follow-up, total sleep time, sleep efficiency and SF12 mental component of EECP group remained improved, and group difference for SF12 mental component was found. Post-treatment and follow-up HADS-A significantly decreased in both groups, with no differences between groups. Post-treatment serum biomarkers showed no differences within and between groups. LIMITATION: Lack of objective sleep measurement. CONCLUSION: EECP could improve sleep quality and mental quality of life in chronic insomnia and the therapeutic effect maintained for 3 months.

Enhanced external counterpulsation increases coronary flow reserve in coronary microvascular disease.

OBJECTIVES: To investigates the outcomes of enhanced external counterpulsation (EECP) among coronary microvascular disease (CMD) patients. METHODS: Coronary microvascular disease patients were separated into the EECP (n=41) and control cohorts (n=42). Prior to and following the 4-week EECP program, coronary flow reserve (CFR) was recorded using transthoracic Doppler echocardiography. The serum endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) contents were analyzed by ELISA. Quality of life (QoL) was assessed by the Seattle Angina Questionnaire (SAQ) and the Canadian Cardiovascular Society (CCS) angina class. RESULTS: After four weeks, CFR was substantially enhanced in the EECP versus control cohort (p<0.05). Endothelin-1 was strongly diminished whereas eNOS was considerably upregulated in the EECP cohort. EECP also enhanced patients' SAQ scores and decreased the CCS angina class. CONCLUSION: Enhanced external counterpulsation may improve CFR and enhance the CMD patient QoL.

Influence of enhanced external counterpulsation on endothelial function: a meta-analysis of randomized controlled trials.

OBJECTIVES: Enhanced external counterpulsation (EECP) is an effective and noninvasive treatment for patients with refractory angina and chronic heart failure. However, previous studies evaluating the influence of EECP on endothelial function showed inconsistent results. This systematic review and meta-analysis was conducted to evaluate the effects of EECP on endothelial function measured by brachial artery flow-mediated dilation (FMD). DESIGN: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials comparing the influence of EECP versus usual care on FMD in adult population. A random-effects model incorporating the potential influence of heterogeneity was used to pool the results. RESULTS: Nineteen studies with 1647 patients were included in the meta-analysis. Compared with usual care or conventional therapy, additional treatment with EECP for 3-7 weeks was associated with a significantly improved FMD (mean difference [MD]: 1.96%, 95% confidence interval [CI]: 1.57-2.36, p < 0.001, I2 = 52%). Subgroup analysis showed consistent results in patients with coronary artery disease and in patients with other diseases (p for subgroup difference = 0.21). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p < 0.001). Results of subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% (MD: 2.69, 95% CI: 2.27-3.10, p < 0.001; I2 = 15%) compared to those with baseline FMD < 5% (MD: 1.49, 95% CI: 1.13-1.85, p < 0.001; I2 = 0%; p for subgroup difference < 0.001). CONCLUSIONS: EECP may be effective in improving endothelial function measured by FMD.

Enhanced external counterpulsation, focusing on its effect on kidney function, and utilization in patients with kidney diseases: a systematic review.

Background: Enhanced external counterpulsation (EECP) is provided by a noninvasive device positively affecting cardiovascular function via mechanisms called diastolic augmentation and systolic unloading. The renal aspects of EECP therapy have not been extensively investigated. Objectives: To assess the effect of EECP on renal function and to determine the application in patients with kidney disease. Methods: MEDLINE, EMBASE, SCOPUS, and Cochrane CENTRAL databases were searched for all studies involving EECP treatments. The title and abstract of all searched literatures were screened, and those focusing on renal outcome or conducting in kidney disease patients were selected. Results: Eight studies were included in the qualitative analysis. EECP increases stroke volume, mean arterial pressure, renal artery blood flow, renal plasma flow, glomerular filtration rate (GFR), plasma atrial natriuretic peptide, urine volume, and urinary sodium chloride excretion, but reduces the plasma concentration of renin and endothelin-1 in healthy subjects. A single session of EECP after radioactive contrast exposure could provide increased contrast clearance, and this reduces contrast-induced kidney injury in patients, irrespective of previous kidney function. Thirty-five-hour sessions of EECP treatment were illustrated to increase long-term estimated GFR in patients with chronic angina and heart failure. In cirrhotic patients, EECP fails to improve GFR and renal vascular resistance. EECP device could maintain blood pressure, decrease angina symptoms, and increase cardiac perfusion in hemodialysis patients. Conclusion: EECP treatment potentially increases renal perfusion and prevents kidney injury in several conditions. EECP possibly provides beneficial effects on hemodynamics and cardiac function in hemodialysis patients.

Enhanced external counterpulsation treatment regulates blood flow and wall shear stress metrics in femoral artery: An in vivo study in healthy subjects.

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-basedapproach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries.

The Effect of EECP on Ischemic Heart Failure: a Systematic Review.

PURPOSE OF REVIEW: Heart failure is a serious global health problem, and coronary artery disease is one of the main causes. At present, the treatment options for ischemic heart failure (IHF) are limited. This article mainly aims to explore the evidence of enhanced external counterpulsation (EECP) as a non-invasive cardiac rehabilitation method in patients with IHF and to make a preliminary exploration of its mechanisms. RECENT FINDINGS: According to the existing evidence, the standard course of EECP is safe in patients with IHF and can significantly improve the quality of life of these patients. The effect of EECP on systolic function is still unclear, while EECP has a significant improvement effect on cardiac diastolic function. At the same time, this treatment can reduce the re-hospitalization rate and emergency visit rate of patients within 6 months. In terms of mechanisms, in addition to the immediate hemodynamic effect, existing evidence mostly suggests that its improvement of cardiac function may come from its upregulation of shear stress to improve myocardial perfusion. EECP is safe to use in patients with stable ischemic heart failure, and it can improve the performance status of patients and may be beneficial to cardiac function and reduce the short-term re-hospitalization rate.

Treatment strategy of different enhanced external counterpulsation frequencies for coronary heart disease and cerebral ischemic stroke: A hemodynamic numerical simulation study.

BACKGROUND AND OBJECTIVES: Currently, enhanced external counterpulsation (EECP) devices mainly produce one counterpulsation per cardiac cycle. However, the effect of other frequencies of EECP on the hemodynamics of coronary and cerebral arteries is still unclear. It should be investigated whether one counterpulsation per cardiac cycle leads to the optimal therapeutic effect in patients with different clinical indications. Therefore, we measured the effects of different frequencies of EECP on the hemodynamics of coronary and cerebral arteries to determine the optimal counterpulsation frequency for the treatment of coronary heart disease and cerebral ischemic stroke. METHODS: We established 0D/3D geometric multi-scale hemodynamics model of coronary and cerebral arteries in two healthy individuals, and performed clinical trials of EECP to verify the accuracy of the multi-scale hemodynamics model. The pressure amplitude (35 kPa) and pressurization duration (0.6 s) were fixed. The global and local hemodynamics of coronary and cerebral arteries were studied by changing counterpulsation frequency. Three frequency modes, including one counterpulsation in one, two and three cardiac cycles, were applied. Global hemodynamic indicators included diastolic / systolic blood pressure (D/S), mean arterial pressure (MAP), coronary artery flow (CAF), and cerebral blood flow (CBF), whereas local hemodynamic effects included area-time-averaged wall shear stress (ATAWSS) and oscillatory shear index (OSI). The optimal counterpulsation frequency was verified by analyzing the hemodynamic effects of different frequency modes of counterpulsation cycles and full cycles. RESULTS: In the full cycle, CAF, CBF and ATAWSS of coronary and cerebral arteries were the highest when one counterpulsation per cardiac cycle was applied. However, in the counterpulsation cycle, the global and local hemodynamic indicators of coronary and cerebral artery reached the highest when one counterpulsation in one cardiac cycle or two cardiac cycles was applied. CONCLUSIONS: For clinical application, the results of global hemodynamic indicators in the full cycle have more clinical practical significance. Combined with the comprehensive analysis of local hemodynamic indicators, it can be concluded that for coronary heart disease and cerebral ischemic stroke, applying one counterpulsation per cardiac cycle may provide the optimal benefit.

A study on the immediate effects of enhanced external counterpulsation on physiological coupling.

Introduction: Enhanced external counterpulsation (EECP) is a non-invasive assisted circulation technique for its clinical application in the rehabilitation and management of ischemic cardiovascular and cerebrovascular diseases, which has complex physiological and hemodynamic effects. However, the effects of EECP on the coupling of physiological systems are still unclear. We aimed to investigate the immediate effects of EECP on the coupling between integrated physiological systems such as cardiorespiratory and cardiovascular systems. Methods: Based on a random sham-controlled design, simultaneous electrocardiography, photoplethysmography, bio-electrical impedance, and continuous hemodynamic data were recorded before, during and after two consecutive 30 min EECP in 41 healthy adults. Physiological coupling strength quantified by phase synchronization indexes (PSI), hemodynamic measurements and heart rate variability indices of 22 subjects (female/male: 10/12; age: 22.6 ± 2.1 years) receiving active EECP were calculated and compared with those of 19 sham control subjects (female/male: 7/12; age: 23.6 ± 2.5 years). Results: Immediately after the two consecutive EECP interventions, the physiological coupling between respiratory and cardiovascular systems PSIRES-PTT (0.34 ± 0.14 vs. 0.49 ± 0.17, P = 0.002), the physiological coupling between cardiac and cardiovascular systems PSIIBI-PTT (0.41 ± 0.14 vs. 0.52 ± 0.16, P = 0.006) and the total physiological coupling PSItotal (1.21 ± 0.35 vs. 1.57 ± 0.49, P = 0.005) in the EECP group were significantly lower than those before the EECP intervention, while the physiological coupling indexes in the control group did not change significantly (P > 0.05). Conclusion: Our study provides evidence that the PSI is altered by immediate EECP intervention. We speculate that the reduced PSI induced by EECP may be a marker of disturbed physiological coupling. This study provides a new method for exploring the mechanism of EECP action and may help to further optimize the EECP technique.

Cerebral multi-autoregulation model based enhanced external counterpulsation treatment planning for cerebral ischemic stroke.

Enhanced external counterpulsation (EECP) treatment for cerebral ischemic stroke patients with differing severity of stenosis, is subject to uncertainties due to the varying effects of the cerebral autoregulation mechanism on haemodynamics. The current study reports the development of a cerebral multi-autoregulation (MR) mathematical model, based on cerebral arteriole regulation of neurogenic, vascular smooth muscle reflex and shear stress mechanisms which takes into account the severity of stenosis. The model was evaluated by comparison to authentic clinical measurements of cerebral autoregulatory efficiency. Then it was applied to a 0D/3D geometric multi-scale haemodynamic model of a cerebral artery. Haemodynamic indicators were calculated under different pressurization durations of EECP to evaluate the efficacy for different stenosis lesions. Moderate stenosis of 50% to 60% produced excessive time-averaged wall shear stress in the distal area of the stenosis (>7 Pa) during prolonged pressurization and may result in damage to vascular endothelial cells. However, prolonged pressurization did not result in haemodynamic risk for severe stenosis of 70% to 80%, indicating that the duration of pressurization may be extended with increasing severity of stenosis. The current MR model accurately simulated cerebral blood flow and has relevance to the simulation of cerebral haemodynamics in a clinical setting.

Novel Concepts in the Management of Angina in Coronary Artery Disease.

Coronary artery disease remains a condition with high prevalence and detrimental effects on the quality of life of affected individuals. Its most frequent manifestation, stable angina pectoris, may be challenging to manage despite the available antianginal pharmacotherapy and adequate risk factor control, especially in subjects not amenable to revascularization. In the direction of refractory angina pectoris, several approaches have been developed over the years with varying degrees of success. Among the most recognized techniques in managing angina is enhanced external counterpulsation, which utilizes mechanical compression of the lower extremities to increase blood flow to the heart. Moving to coronary sinus reduction, it leads to an increase in coronary sinus backward pressure, ultimately augmenting myocardial blood flow redistribution to ischemic regions and ameliorating chronic angina. Clinical trial results of the above-mentioned techniques have been encouraging but are based on small sample sizes to justify their widespread application. Other interventional approaches, such as transmyocardial laser revascularization, extracorporeal shockwave myocardial revascularization, and spinal cord stimulation, have been met with either controversial or negative results, and their use is not recommended. Lastly, angiogenic therapy with targeted intramyocardial vascular endothelial growth factor injection or CD34+ cell therapy may be beneficial and warrants further investigation. In this review, we summarize the current knowledge in the field of angina management, highlighting the potential and the gaps in the existing evidence that ought to be addressed in future larger-scale, randomized studies before these techniques can be safely adapted in the clinical practice of patients with refractory angina pectoris.

Enhanced external counterpulsation modulates the heartbeat evoked potential.

Introduction: Accumulating evidence suggests that enhanced external counterpulsation (EECP) influences cardiac functions, hemodynamic characteristics and cerebral blood flow. However, little is known about whether or how the EECP affects the brain-heart coupling to produce these physiological and functional changes. We aimed to determine if the brain-heart coupling is altered during or after EECP intervention by assessing the heartbeat evoked potential (HEP) in healthy adults. Methods: Based on a random sham-controlled design, simultaneous electroencephalography and electrocardiography signals as well as blood pressure and flow status data were recorded before, during and after two consecutive 30-min EECP in 40 healthy adults (female/male: 17/23; age: 23.1 ± 2.3 years). HEP amplitude, frequency domain heart rate variability, electroencephalographic power and hemodynamic measurements of 21 subjects (female/male: 10/11; age: 22.7 ± 2.1 years) receiving active EECP were calculated and compared with those of 19 sham control subjects (female/male: 7/12; age: 23.6 ± 2.5 years). Results: EECP intervention caused immediate obvious fluctuations of HEP from 100 to 400 ms after T-peak and increased HEP amplitudes in the (155-169) ms, (354-389) ms and (367-387) ms time windows after T-peak in the region of the frontal pole lobe. The modifications in HEP amplitude were not associated with changes in the analyzed significant physiological measurements and hemodynamic variables. Discussion: Our study provides evidence that the HEP is modulated by immediate EECP stimuli. We speculate that the increased HEP induced by EECP may be a marker of enhanced brain-heart coupling. HEP may serve as a candidate biomarker for the effects and responsiveness to EECP.

Enhanced external counterpulsation improves dysfunction of forearm muscle caused by radial artery occlusion.

Objective: This study aimed to investigate the therapeutic effect of enhanced external counterpulsation (EECP) on radial artery occlusion (RAO) through the oscillatory shear (OS) and pulsatile shear (PS) models of human umbilical vein endothelial cells (HUVECs) and RAO dog models. Methods: We used high-throughput sequencing data GSE92506 in GEO database to conduct time-series analysis of functional molecules on OS intervened HUVECs, and then compared the different molecules and their functions between PS and OS. Additionally, we studied the effect of EECP on the radial artery hemodynamics in Labrador dogs through multi-channel physiological monitor. Finally, we studied the therapeutic effect of EECP on RAO at the histological level through Hematoxylin-Eosin staining, Masson staining, ATPase staining and immunofluorescence in nine Labrador dogs. Results: With the extension of OS intervention, the cell cycle decreased, blood vessel endothelial cell proliferation and angiogenesis responses of HUVECs were down-regulated. By contrast, the inflammation and oxidative stress responses and the related pathways of anaerobic metabolism of HUVECs were up-regulated. Additionally, we found that compared with OS, PS can significantly up-regulate muscle synthesis, angiogenesis, and NO production related molecules. Meanwhile, PS can significantly down-regulate inflammation and oxidative stress related molecules. The invasive arterial pressure monitoring showed that 30Kpa EECP treatment could significantly increase the radial artery peak pressure (p = 0.030, 95%CI, 7.236-82.524). Masson staining showed that RAO significantly increased muscle interstitial fibrosis (p = 0.002, 95%CI, 0.748-2.128), and EECP treatment can reduce this change (p = 0.011, 95%CI, -1.676 to -0.296). ATPase staining showed that RAO significantly increased the area of type II muscle fibers (p = 0.004, 95%CI, 7.181-25.326), and EECP treatment could reduce this change (p = 0.001, 95%CI, -29.213 to -11.069). In addition, immunofluorescence showed that EECP increased angiogenesis in muscle tissue (p = 0.035, 95%CI, 0.024-0.528). Conclusion: EECP improves interstitial fibrosis and hypoxia, and increases angiogenesis of muscle tissue around radial artery induced by RAO.

Tolerability safety and effectiveness of enhanced external counterpulsation versus individual shear rate therapy in patients with lower extremity atherosclerotic disease: A prospective pilot clinical trial.

AIMS: We aimed to investigate the tolerability, safety, and effectiveness of enhanced external counterpulsation therapy (EECP) versus individual shear rate therapy (ISRT) in patients with lower extremity atherosclerotic disease (LEAD). METHODS: Eighteen patients (age: 73.1 ± 6 years) underwent EECP and ISRT, each daily over five consecutive days in a cross-over design with a 1 week resting period in between the two regimens. A quality-of-life questionnaire was used to assess the therapy experience. Oxygen saturation (SO2 ), relative hemoglobin amount (rHb) and blood flow (Flow) in the capillary-venous-system (microcirculation) of the skin were monitored continuously during all therapy sessions using the micro-lightguide spectrophotometer, also known as oxygen to see (O2C). The effects of EECP and ISRT on the renal function and skeletal muscles were evaluated using serial blood and urine tests. RESULTS: EECP therapy had to be terminated early before the end of the 5th session in 10 patients (55.6%) because of discomfort. Four patients (22.2%) experienced signs of critical limb ischaemia under EECP. The total score of the quality-of-life questionnaire was significantly higher (= better tolerated) post-ISRT compared with EECP. Microcirculation monitoring revealed that ISRT significantly increased the SO2 , blood flow and rHb during the therapy. All three parameters remained significantly increased in the observation period after ISRT. The serum levels of creatin kinase and myoglobin increased significantly under EECP. CONCLUSIONS: ISRT significantly improves tolerability, safety, and effectiveness over EECP in patients with LEAD.

Effect of the enhanced external counterpulsation combined with drug on social function and efficacy in patients with depressive episodes / 四川精神卫生

ObjectiveTo observe the effect of the enhanced external counterpulsation （EECP） combined with drug on social function and efficacy in patients with depressive episodes， so as to provide references for the treatment of depressive episodes. MethodsA total of 66 hospitalized patients who was in hospital at department of psychiatry of the Second Xiangya Hospital of Central South University， met the criteria of Diagnostic and Statistical Manual of Mental Disorders，fifth edition（DSM-5） diagnosis of depressive episode or bipolar disorder depressive episode from May 2019 to March 2020 were included by simple random sampling. The participants were divided into study group （n=36） and control group （n=30） according to the random number table method. Both groups received conventional drug treatment， and the study group recieved the EECP intervention at same time. The Depression symptoms and social function were assessed before and after treatment by using Hamilton Depression Scale-24 item （HAMD-24） and Sheehan Disability Scale （SDS）. Treatment efficacy of the two groups was compared. ResultsAfter the intervention， the HAMD-24 and SDS scores in both groups were lower than those before treatment， the differences were statistically significant （t=8.149， 5.791， 8.016， 3.488， P˂0.01）. And the SDS score of the study group was siginficantly lower than that of the control group （t=-3.008， P<0.05）. The total effective rate of treatment in the study group was higher than that of the control group， and the difference was statistically significant （90.63% vs. 63.33%， χ²=8.725， P˂0.05）. ConclusionEECP therapy combined with drug has better efficacy on the patients with depressive episodes， and it can improve social function effectively.

Enhanced external counterpulsation ameliorates endothelial dysfunction and elevates exercise tolerance in patients with coronary artery disease.

Purpose: Enhanced external counterpulsation (EECP) is a new non-drug treatment for coronary artery disease (CAD). However, the long-term effect of EECP on endothelial dysfunction and exercise tolerance, and the relationship between the changes in the endothelial dysfunction and exercise tolerance in the patients with coronary heart disease are still unclear. Methods: A total of 240 patients with CAD were randomly divided into EECP group (n = 120) and control group (n = 120). All patients received routine treatment of CAD as the basic therapy. Patients in the EECP group received 35 1-h daily sessions of EECP during 7 consecutive weeks while the control group received the same treatment course, but the cuff inflation pressure was 0-10 mmHg. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI), and inner diameter (ID) of the right carotid artery were examined using a Color Doppler Ultrasound and used to calculate the fluid shear stress (FSS). Serum levels of human vascular endothelial cell growth factor (VEGF), vascular endothelial cell growth factor receptor 2 (VEGFR2), and human angiotensin 2 (Ang2) were determined by enzyme-linked immunosorbent assay (ELISA). Exercise load time, maximal oxygen uptake (VO2max ), metabolic equivalent (METs), anaerobic threshold (AT), peak oxygen pulse (VO2max/HR) were assessed using cardiopulmonary exercise tests. Results: After 1 year follow-up, the EDV, PSV, ID, and FSS were significantly increased in the EECP group (P < 0.05 and 0.01, respectively), whereas there were no significant changes in these parameters in the control group. The serum levels of VEGF and VEGFR2 were elevated in the EECP and control groups (all P < 0.05). However, the changes in VEGF and VEGFR2 were significantly higher in the EECP group than in the control group (P < 0.01). The serum level of Ang2 was decreased in the EECP group (P < 0.05) and no obvious changes in the control group. As for exercise tolerance of patients, there were significant increases in the exercise load time, VO2max, VO2max/HR, AT and METs in the EECP group (all P < 0.05) and VO2max and METs in the control group (all P < 0.05). Correlation analyses showed a significant and positive correlations of VEGF and VEGFR2 levels with the changes in FSS (all P < 0.001). The correlations were still remained even after adjustment for confounders (all Padjustment < 0.001). Linear regression displays the age, the medication of ACEI (angiotensin-converting enzyme inhibitors) or ARB (angiotensin receptor blockers), the diabetes and the changes in VEGF and VEGFR2 were positively and independently associated with the changes in METs after adjustment for confounders (all Padjustment < 0.05). Conclusion: The data of our study suggested that EECP is a useful therapeutic measurement for amelioration of endothelial dysfunction and long-term elevation of exercise tolerance for patients with coronary heart disease. Clinical trial registration: [http://www.chictr.org.cn/], identifier [ChiCTR1800020102].

Non-Invasive Pulsatile Shear Stress Modifies Endothelial Activation; A Narrative Review.

The monolayer of cells that line both the heart and the entire vasculature is the endothelial cell (EC). These cells respond to external and internal signals, producing a wide array of primary or secondary messengers involved in coagulation, vascular tone, inflammation, and cell-to-cell signaling. Endothelial cell activation is the process by which EC changes from a quiescent cell phenotype, which maintains cellular integrity, antithrombotic, and anti-inflammatory properties, to a phenotype that is prothrombotic, pro-inflammatory, and permeable, in addition to repair and leukocyte trafficking at the site of injury or infection. Pathological activation of EC leads to increased vascular permeability, thrombosis, and an uncontrolled inflammatory response that leads to endothelial dysfunction. This pathological activation can be observed during ischemia reperfusion injury (IRI) and sepsis. Shear stress (SS) and pulsatile shear stress (PSS) are produced by mechanical frictional forces of blood flow and contraction of the heart, respectively, and are well-known mechanical signals that affect EC function, morphology, and gene expression. PSS promotes EC homeostasis and cardiovascular health. The archetype of inducing PSS is exercise (i.e., jogging, which introduces pulsations to the body as a function of the foot striking the pavement), or mechanical devices which induce external pulsations to the body (Enhanced External Pulsation (EECP), Whole-body vibration (WBV), and Whole-body periodic acceleration (WBPA aka pGz)). The purpose of this narrative review is to focus on the aforementioned noninvasive methods to increase PSS, review how each of these modify specific diseases that have been shown to induce endothelial activation and microcirculatory dysfunction (Ischemia reperfusion injury-myocardial infarction and cardiac arrest and resuscitation), sepsis, and lipopolysaccharide-induced sepsis syndrome (LPS)), and review current evidence and insight into how each may modify endothelial activation and how these may be beneficial in the acute and chronic setting of endothelial activation and microvascular dysfunction.

Reduction in risk of contrast-induced nephropathy in patients with chronic kidney disease and diabetes mellitus by enhanced external counterpulsation.

Objective: To evaluate the efficacy of enhanced external counterpulsation (EECP) in the prevention of contrast-induced nephropathy (CIN) in patients with combined chronic kidney disease (CKD) and diabetes mellitus (DM) by comparing the changes in renal function-related indicators in patients before and after coronary angiography (CAG) or percutaneous coronary intervention (PCI). Methods: There were 230 subjects consecutively included in the study. Of these, 30 cases with DM underwent rehydration therapy, and 200 cases underwent EECP therapy in addition to rehydration therapy, comprising 53 patients with DM and 147 patients without. All the patients were tested to measure the renal function indicators before and after CAG/PCI. Results: The postoperative results of blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), B2 microglobulin, and high-sensitivity C-reactive protein in the three groups showed a statistically significant difference (P < 0.05). After EECP therapy, patients with DM showed a significant decrease in BUN (9.1 ± 4.2 vs. 7.2 ± 3.0, t = 3.899, P < 0.001) and a significant increase in eGFR (41.5 ± 12.7 vs. 44.0 ± 15.6, t = -2.031, P = 0.047), while the patients without DM showed a more significant difference (P < 0.001). Patients with DM showed a lower percentage of elevated Scr (66.7% vs. 43.4%, P = 0.042), a higher percentage of elevated eGFR (30.0% vs. 52.8%, P = 0.044), and a lower incidence of CIN (16.7% vs. 3.8%, P = 0.042) after EECP therapy. Conclusion: Treatment with EECP can reduce Scr in patients with combined CKD and DM post CAG/PCI, increase eGFR, and decrease the incidence of CIN.