Prognostic Importance of Pulmonary Arterial Capacitance in Acute Decompensated Heart Failure With Preserved Ejection Fraction.

Background Although the prognostic importance of pulmonary arterial capacitance (PAC; stroke volume/pulmonary arterial pulse pressure) has been elucidated in heart failure with reduced ejection fraction, whether its significance in patients suffering from heart failure with preserved ejection fraction is not known. We aimed to examine the association of PAC with outcomes in inpatients with heart failure with preserved ejection fraction. Methods and Results We prospectively studied 705 patients (median age, 83 years; 55% women) registered in PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction). We investigated the association of echocardiographic PAC at discharge with the primary end point of all-cause death or heart failure rehospitalization with a mean follow-up of 384 days. We further tested the acceptability of the prognostic significance of PAC in a subgroup of patients (167/705 patients; median age, 81 years; 53% women) in whom PAC was assessed by right heart catheterization. The median echocardiographic PAC was 2.52 mL/mm Hg, with a quartile range of 1.78 to 3.32 mL/mm Hg. Univariable and multivariable Cox regression testing revealed that echocardiographic PAC was associated with the primary end point (unadjusted hazard ratio, 0.82; 95% CI, 0.72-0.92; P=0.001; adjusted hazard ratio, 0.86; 95% CI, 0.74-0.99; P=0.035, respectively). Univariable Cox regression testing revealed that PAC assessed by right heart catheterization (median calculated PAC, 2.82 mL/mm Hg) was also associated with the primary end point (unadjusted HR, 0.70; 95% CI, 0.52-0.91; P=0.005). Conclusions A prospective cohort study revealed that impaired PAC diagnosed with both echocardiography and right heart catheterization was associated with adverse outcomes in inpatients with heart failure with preserved ejection fraction. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

Cardiovascular disintegration: A conceptual, model-based approach to heart failure hemodynamics.

OBJECTIVE: The current understanding of heart failure (HF) largely centers round left ventricular (LV) function; however, disorders in serial integration of cardiovascular system may cause a hemodynamic picture similar to left-sided HF. Therefore, focusing only on LV function may be a limited and misleading approach. We hypothesized that cardiovascular system has four major integration points, and disintegration in any of these points may produce the hemodynamic picture of HF. METHODS: We used a computational model in which mechanical properties of each chamber were characterized using time-varying elastance, and vascular beds were modeled by series of capacitances and resistances. The required percent changes in stressed volume (Vstressed) was presented as a measure of congestion susceptibility. RESULTS: As mean systemic pressure is closely correlated with pulmonary capillary wedge pressure (PCWP), arteriovenous disintegration can create a diastolic dysfunction pattern, even without any change in diastolic function. For 10%, 20%, 30%, 40%, and 50% interventricular disintegration, required Vstressed for reaching a PCWP over 20 mmHg was decreased by 42.0%, 31.2%, 22.5%, 15%, and 8.3%, respectively. Systolodiastolic disintegration, namely combined changes in the end-diastolic and systolic pressure-volume curves and ventriculoarterial disintegration significantly decreases the required percent change in Vstressed for generating congestion. CONCLUSION: Four disintegration points can produce the hemodynamic picture of HF, which indicates that combination of even seemingly mild abnormalities is more important than an isolated abnormality in a single function of a single chamber. Our findings suggest that a "cardiovascular disintegration" perspective may provide a different approach for assessing the HF syndrome.

Extracardiac Abnormalities of Preload Reserve: Mechanisms Underlying Exercise Limitation in Heart Failure with Preserved Ejection Fraction, Autonomic Dysfunction, and Liver Disease.

While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.

What determines systemic blood flow in vertebrates?

In the 1950s, Arthur C. Guyton removed the heart from its pedestal in cardiovascular physiology by arguing that cardiac output is primarily regulated by the peripheral vasculature. This is counterintuitive, as modulating heart rate would appear to be the most obvious means of regulating cardiac output. In this Review, we visit recent and classic advances in comparative physiology in light of this concept. Although most vertebrates increase heart rate when oxygen demands rise (e.g. during activity or warming), experimental evidence suggests that this tachycardia is neither necessary nor sufficient to drive a change in cardiac output (i.e. systemic blood flow, Q̇sys) under most circumstances. Instead, Q̇sys is determined by the interplay between vascular conductance (resistance) and capacitance (which is mainly determined by the venous circulation), with a limited and variable contribution from heart function (myocardial inotropy). This pattern prevails across vertebrates; however, we also highlight the unique adaptations that have evolved in certain vertebrate groups to regulate venous return during diving bradycardia (i.e. inferior caval sphincters in diving mammals and atrial smooth muscle in turtles). Going forward, future investigation of cardiovascular responses to altered metabolic rate should pay equal consideration to the factors influencing venous return and cardiac filling as to the factors dictating cardiac function and heart rate.

Pulmonary arterial compliance is a useful predictor of pulmonary vascular disease in congenital heart disease.

Histopathological assessment of the pulmonary arteries is crucial to determine the surgical indications in patients with congenital heart disease (CHD) and intractable pulmonary vascular disease (PVD). We aimed to clarify whether pulmonary hemodynamic parameters can predict PVD in patients with CHD and pulmonary arterial hypertension (PAH) We performed histopathological evaluations of lung specimens and cardiac catheterizations in 27 patients with CHD-PAH. We divided these patients into the patients with and without PVD, and compared pulmonary hemodynamic parameters including pulmonary arterial compliance (Cp) between two groups. Age at lung biopsy was 4 (2-7) months. There were 16 patients with trisomy 21. Cardiac diagnosis included ventricular septal defect in 16, atrial septal defect in 5, atrioventricular septal defect in 4, and others in 2. There were 11 patients with histopathologically proven PVD (Heath-Edwards classification grade ≥ 3 in 5; the index of PVD ≥ 1.1 in 3; extremely thickened media in 6; hypoplasia of the pulmonary arteries in 3). Cp in the patients with PVD was significantly lower than that in patients without PVD (0.99 [0.74-1.42] vs 1.56 [1.45-1.88], p = 0.0047), although there was no significant difference in the ratio of systemic to pulmonary blood flow, pulmonary arterial pressure, and resistance between two groups. A Cp cutoff value of < 1.22 ml/mmHg m2 as a predictor of PVD yielded a sensitivity and a specificity of 93% and 64%, respectively. Pulmonary arterial compliance can be a predictor of PVD among patients with CHD-PAH.

Altered cardiovascular function is related to reduced BDNF in Parkinson's disease.

Brain-derived neurotrophic factor (BDNF) has been linked to cardiovascular health and function, however, the exact role is yet to be understood. The current study examined the relationship of circulatory BDNF with vascular function in Parkinson's disease (PD). ELISA was used to determine plasma BDNF in PD patients and healthy control (CT). Additionally, forearm resting blood flow (RBf), vascular resistance (RVr), venous capacitance (RVc), and venous outflow (RVo) as well as post occlusion blood flow (OcBf), vascular resistance (OcVr), venous capacitance (OcVc), and venous outflow (OcVo) were obtained using strain-gauge plethysmography. Simple linear regression showed that being PD patient can predict (p < 0.05) 12.9% of BDNF, 16.8% of RVc, 15.0% of OcVc, and 13.6% of OcVo. Subsequent stepwise regression included BDNF, RVc, OcVc, and OcVo, showed that being PD patient predicted (p < 0.05) 58.0% of BDNF, 47.7% of OcVo, and 15.1% of OcVc. Another simple linear regression demonstrated that BDNF predicted (p < 0.05) 18.5% of OcBf, 22.0% of OcVr, and 24.1% of OcVc in PD. In a subsequent stepwise linear regression, BDNF explained 26% ofOcVr (p = 0.008) and 42% of OcVc (p = 0.002) in PD. The study showed that BDNF is reduced and related to altered vascular function in PD. The results suggest that BDNF might contribute to preserving and maybe improving vascular function in PD.

Ethnic differences in stratum corneum functions between Chinese and Thai infants residing in Bangkok, Thailand.

BACKGROUND/OBJECTIVES: Ethnic and racial differences in infant skin have not been well characterized. The purpose of this study was to establish whether there are ethnic differences and similarities in the stratum corneum (SC) functions of Thai and Chinese infants. METHODS: Healthy infants 6 to 24 months of age (N = 60; 30 Thai, 30 Chinese) who resided in Bangkok, Thailand, were enrolled. Transepidermal water loss (TEWL) and SC hydration (capacitance) on the thigh, buttock, and upper arm were measured. Ceramide content was determined in the SC on the upper arm. RESULTS: SC hydration was not remarkably different between the two ethnicities at any site measured, but TEWL was significantly higher in Chinese infants than in Thai infants at all sites. Hydration of the SC was not significantly correlated with age in either ethnicity. TEWL had significant but weak correlations with age on the thigh and upper arm in Thai infants. Ceramide content was significantly higher in Chinese SC than in Thai SC. No relationship between ceramide content and TEWL or hydration was observed in either ethnicity. CONCLUSION: The significant differences in TEWL and ceramide contents between Chinese and Thai infant skin could prove useful in designing skin care and diapering products that are best suited for each ethnicity.

Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

Skeletonization of Left Internal Mammary Artery in Coronary Artery Bypass Grafting.

OBJECTIVE: To compare mean per-operative flow capacity between skeletonized and pedicled left internal mammary artery (LIMA) in patients undergoing coronary artery bypass grafting (CABG) surgery. STUDY DESIGN: Randomized control trial. PLACE AND DURATION OF STUDY: Department of Cardiac Surgery, Armed Forces Institute of Cardiology and National Institute of Heart Diseases (AFIC-NIHD), Rawalpindi, Pakistan from February to August, 2013. METHODOLOGY: Patients undergoing CABG for coronary artery disease, under 80 years, excluded by the exclusion criteria; and fulfilling the inclusion criteria were randomly assigned to two groups of 70 each. One group underwent skeletonized and the other underwent pedicled technique of LIMAharvesting. Free flow was checked just before anastamosis of each LIMAto the LAD, manually in blood flow in ml per minute during cardiopulmonary bypass by allowing it to bleed into a 100 ml container over 20 seconds. Aspecialized proforma was used to record the age, gender, weight, disease, type of IMA used, and free flow of the IMA. Data was analyzed using SPSS 18. RESULTS: The mean age of the patients was 57.16 years in 40 patients, ranging from 36 to 75 years. Disease pattern analysis showed 5%, 10.7% and 84.3% single, double and triple vessel coronary artery disease, respectively. There was significantly higher free flow in the skeletonized group than the pedicled group (p=0.04). CONCLUSION: Skeletonized IMAhad superior flow to pedicled IMAin addition to its traditional proven advantages, which justifies its further use as a conduit for myocardial revascularization.

Abdominal Aortic Hemodynamics in Intermittent Claudication Patients at Rest and during Dynamic Pedaling Exercise.

BACKGROUND: Lower-extremity exercise has been shown to eliminate adverse hemodynamics conditions, such as low and oscillating blood flow and wall shear stress, in the abdominal aortas of healthy young and older adults. METHODS: We use cine phase-contrast magnetic resonance imaging and a custom MRI-compatible exercise cycle to quantify hemodynamic changes because of pedaling exercise in patients diagnosed with intermittent claudication. RESULTS: With only an average heart increase of 35 ± 18% and exercise workload of 36 ± 16 watts, the patients experienced approximately 3- and 6-fold increases in blood flow, and 4- and 16-fold increases in wall shear stress at the supraceliac and infrarenal aortic locations, respectively. Also, all oscillations in flow and shear stress at rest were eliminated with exercise. CONCLUSIONS: Claudication patients experience 3- to 4-fold lower oscillations in flow and shear stress at rest as compared with healthy age-matched controls, likely because of reduced distal arterial compliance as a result of distal atherosclerosis. The magnitude of flow and shear oscillatory indices may be good indicators of distal arterial compliance and health, and may provide predictive power for the efficacy of focal interventions.

Exercise ventilatory parameters for the diagnosis of reactive pulmonary hypertension in patients with heart failure.

BACKGROUND: Reactive pulmonary hypertension (PH) in left heart disease is associated with poor prognosis. This study aimed to evaluate the diagnostic utility of exercise ventilatory parameters on cardiopulmonary exercise testing for the diagnosis of reactive PH in patients with heart failure (HF) and reduced ejection fraction. METHODS: This was a single-center, retrospective analysis of a prospectively collected database of 131 patients with HF who underwent in-hospital assessment for heart transplantation. Pulmonary hemodynamics was assessed by direct cardiac catheterization. Minute ventilation/carbon dioxide production (VE/VCO2) slope, partial pressure of end-tidal carbon dioxide (ETCO2) changes on exercise, oxygen pulse, and exercise oscillatory ventilation were determined from cardiopulmonary exercise testing. RESULTS: Sixty-one of 131 consecutive patients had reactive PH. VE/VCO2 slope (>41), change in ETCO2 on exercise (<1.2 mm Hg) and exercise oscillatory ventilation were independently associated with reactive PH. These 3 parameters in combination produced 3 possible diagnostic scenarios: (1) if all 3 criteria ("if all") were present, (2) if any 2 of the 3 criteria ("2 of 3") were present, and (3) if any of the criteria ("if any") were present. The corresponding positive/negative likelihood ratios for reactive PH if all 3 criteria were present were 3.73/0.83, if 2 of the 3 criteria were present were 2.19/0.45, and if any of the 3 criteria were present were 1.75/0.11. The posttest probability increased from 46% to 76% ("if all" present) and reduced to 9% (if none of the criteria was present). CONCLUSION: Ventilatory parameters on cardiopulmonary exercise test are associated with reactive PH in patients with HF. The absence of abnormalities in these 3 ventilatory parameters can effectively exclude reactive PH in patients with HF and poor ejection fraction.

Chemohypersensitivity and autonomic modulation of venous capacitance in the pathophysiology of acute decompensated heart failure.

Heart failure is increasing in prevalence around the world, with hospitalization and re-hospitalization as a result of acute decompensated heart failure (ADHF) presenting a huge social and economic burden. The mechanism for this decompensation is not clear. Whilst in some cases it is due to volume expansion, over half of patients with an acute admission for ADHF did not experience an increase in total body weight. This calls into question the current treatment strategy of targeting salt and water retention in ADHF. An alternative hypothesis proposed by Fallick et al. is that an endogenous fluid shift from the splanchnic bed is implicated in ADHF, rather than an exogenous fluid gain. The hypothesis states further that this shift is triggered by an increase in sympathetic tone causing vasoconstriction in the splanchnic bed, a mechanism that can translocate blood rapidly into the effective circulating volume, generating the raised venous pressure and congestion seen in ADHF. This hypothesis encourages a new clinical paradigm which focuses on the underlying mechanisms of congestion, and highlights the importance of fluid redistribution and neurohormonal activation in its pathophysiology. In this article, we consider the concept that ADHF is attributable to episodic sympathetic hyperactivity, resulting in fluid shifts from the splanchnic bed. Chemosensitivity is a pathologic autonomic mechanism associated with mortality in patients with systolic heart failure. Tonic and episodic activity of the peripheral chemoreceptors may underlie the syndrome of acute decompensation without total body salt and water expansion. We suggest in this manuscript that chemosensitivity in response to intermittent hypoxia, such as experienced in sleep disordered breathing, may explain the intermittent sympathetic hyperactivity underlying renal sodium retention and acute volume redistribution from venous storage sites. This hypothesis provides an alternative structure to guide novel diagnostic and treatment strategies for ADHF.

Aortic elastic properties and cognitive function in elderly individuals: the Ikaria Study.

BACKGROUND: The aim of this work was to evaluate the association between aortic elastic properties and cognitive function in elderly individuals, permanent inhabitants of Ikaria Island. METHODS: In 535 individuals (75 ± 6 years, 53% males) aortic distensibility (AoD) was non-invasively calculated from the aortic diameters measured with echocardiography and brachial artery pressure using the formula by Stefanadis et al.; cognitive status was evaluated using the Mini Mental State Examination (MMSE). RESULTS: 88% of the elders had normal values of MMSE score (i.e., ≥ 24). Elders who achieved MMSE score ≥ 24 had higher values of AoD (1.90 ± 2.06 vs. 1.08 ± 1.42, p < 0.001), as well as were more physically active (85% vs. 69%, p = 0.05), had higher educational status (8.5 ± 2.8 years vs. 6 ± 2 years, p = 0.001), higher creatinine clearance levels (70 ± 21 vs. 63 ± 23, p = 0.05) and lower pulse pressure (PP) values (63 ± 16 vs. 68 ± 18, p = 0.06), as compared with those individuals with MMSE < 24. Logistic regression analysis showed that for every unit increase in AoD there was a 25% higher likelihood of having MMSE ≥ 24 (OR per 1000 × mmHg(-1) = 1.25, 95%CI 0.99-1.58), after adjustments for age, gender, current smoking, cardiovascular disease, creatinine clearance, hypertension, diabetes mellitus, obesity, physical activity status and education status. Furthermore having PP levels in the upper tertile (> 70 mmHg), increases by 55% the likelihood of having MMSE < 24 (OR for above 70 mmHg = 0.45, 95%CI 0.22, 0.92), after the same adjustments were made. CONCLUSION: Arterial aging seems to affect cognitive function; a finding that states a novel research hypothesis about the pathophysiological mechanisms of mental functioning.

Visualization of peripheral vasodilative indices in human skin by use of red, green, blue images.

We propose a method to visualize the arterial inflow, the vascular resistance, and the venous capacitance in the skin tissue from red, green, blue (RGB) digital color images. The arterial inflow and the venous capacitance in the skin tissue are visualized based on an increase in the rate of change in the total blood concentration and the change of the total blood concentration during upper limb occlusion at a pressure of 50 mmHg. The resultant arterial inflow with the measured mean arterial pressure also provides an image of the vascular resistance in human skin. The arterial inflow, the vascular resistance, and the venous capacitance acquired by the method are well correlated with those obtained from the conventional strain-gauge plethysmograph. The correlation coefficients R between the estimated values by the method and the measurements by the SPG are calculated to be 0.83 (P < 0.001) for the arterial inflow, 0.77 (P < 0.01) for the vascular resistance, and 0.77 (P < 0.01) for the venous capacitance. The arterial inflow and the venous capacitance in the skin tissue are significantly higher in active subjects compared with the sedentary subjects, whereas the vascular resistance was significantly lower in the active subjects compared with the sedentary subjects. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular functions in human skin.

Congestive renal failure: the pathophysiology and treatment of renal venous hypertension.

Longstanding experimental evidence supports the role of renal venous hypertension in causing kidney dysfunction and "congestive renal failure." A focus has been heart failure, in which the cardiorenal syndrome may partly be due to high venous pressure, rather than traditional mechanisms involving low cardiac output. Analogous diseases are intra-abdominal hypertension and renal vein thrombosis. Proposed pathophysiologic mechanisms include reduced transglomerular pressure, elevated renal interstitial pressure, myogenic and neural reflexes, baroreceptor stimulation, activation of sympathetic nervous and renin angiotensin aldosterone systems, and enhanced proinflammatory pathways. Most clinical trials have addressed the underlying condition rather than venous hypertension per se. Interpreting the effects of therapeutic interventions on renal venous congestion are therefore problematic because of such confounders as changes in left ventricular function, cardiac output, and blood pressure. Nevertheless, there is preliminary evidence from small studies of intense medical therapy or extracorporeal ultrafiltration for heart failure that there can be changes to central venous pressure that correlate inversely with renal function, independently from the cardiac index. Larger more rigorous trials are needed to definitively establish under what circumstances conventional pharmacologic or ultrafiltration goals might best be directed toward central venous pressures rather than left ventricular or cardiac output parameters.

Using dynamic analysis of Laser-Doppler blood flowmetry to measure nasal mucosa bloody flow in postural changes.

BACKGROUND: The regulation of nasal mucosa blood flow (NMBF) is affected by multiple factors, such as the autonomic nervous system, medications, temperature, humidity, endocrine, even emotional stress and vision. The effects of postural changes on NMBF have been described in numerous studies. However, the results are far from consistent due to different experimental designs. OBJECTIVE: Dynamic analysis of Laser-Doppler blood flowmetry (LDBF) is employed to recognize the effect of postural changes on NMBF. METHODS: NMBF was continuously measured by LDBF in 14 participants with changing postures (sitting and supine). NMBF was measured in Blood Perfusion Unit (BPU), equivalent to the number of red blood cells multiplied by their mean velocity in a measured volume. RESULTS: NMBF increases significantly in a supine posture compared with that in a sitting posture. CONCLUSION: Our study demonstrates that NMBF is significantly influenced after initial postural change, suggesting that changes in posture may be regarded as an important factor regulating NMBF.

Prognostic role of pulmonary arterial capacitance in advanced heart failure.

BACKGROUND: Right ventricular (RV) dysfunction frequently occurs and independently prognosticates in left-sided heart failure. It is not clear which RV afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role, and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure. METHODS AND RESULTS: We reviewed 724 consecutive patients with heart failure who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated heart failure. PAC showed a strong inverse relation with PVR (r=-0.64) and wedge pressure (r=-0.73), and provides stronger prediction of significant RV failure than PVR (area under the curve ROC 0.74 versus 0.67, respectively, P=0.003). During a mean follow-up of 3.2±2.2 years, both lower PAC (P<0.0001) and higher PVR (P<0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio=0.92 [95% CI: 0.84-1.0, P=0.037]). Treatment of heart failure resulted in a decrease in PVR (270±165 to 211±88 dynes·s(-1)·cm(-5), P=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 mL/mm Hg, P<0.0001), leading to an increase in pulmonary arterial time constant (PVR×PAC) (0.29±0.12 to 0.37±0.15 second, P<0.0001). CONCLUSIONS: PAC bundles the effects of PVR and left-sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy.

The α2 isoform of the Na,K-pump is important for intercellular communication, agonist-induced contraction, and EDHF-like response in rat mesenteric arteries.

The specific role of different isoforms of the Na,K-pump in the vascular wall is still under debate. We have previously suggested that the α(2) isoform of the Na,K-pump (α(2)), Na(+), Ca(2+)-exchange (NCX), and connexin43 form a regulatory microdomain in smooth muscle cells (SMCs), which controls intercellular communication and contractile properties of the vascular wall. We have tested this hypothesis by downregulating α(2) in cultured SMCs and in small arteries with siRNA in vivo. Intercellular communication was assessed by using membrane capacitance measurements. Arteries transfected in vivo were tested for isometric and isobaric force development in vitro; [Ca(2+)](i) was measured simultaneously. Cultured rat SMCs were well-coupled electrically, but 10 µM ouabain uncoupled them. Downregulation of α(2) reduced electrical coupling between SMCs and made them insensitive to ouabain. Downregulation of α(2) in small arteries was accompanied with significant reduction in NCX expression. Acetylcholine-induced relaxation was not different between the groups, but the endothelium-dependent hyperpolarizing factor-like component of the response was significantly diminished in α(2)-downregulated arteries. Micromolar ouabain reduced in a concentration-dependent manner the amplitude of norepinephrine (NE)-induced vasomotion. Sixty percent of the α(2)-downregulated arteries did not have vasomotion, and vasomotion in the remaining 40% was ouabain insensitive. Although ouabain increased the sensitivity to NE in the control arteries, it had no effect on α(2)-downregulated arteries. In the presence of a low NE concentration the α(2)-downregulated arteries had higher [Ca(2+)](i) and tone. However, the NE EC50 was reduced under isometric conditions, and maximal contraction was reduced under isometric and isobaric conditions. The latter was caused by a reduced Ca(2+)-sensitivity. The α(2)-downregulated arteries also had reduced contraction to vasopressin, whereas the contractile response to high K(+) was not affected. Our results demonstrate the importance of α(2) for intercellular coupling in the vascular wall and its involvement in the regulation of vascular tone.

Correlation of arterial blood pressure and compliance with left ventricular structure and function in the very elderly.

There are very few data on the relationship between systolic blood pressure (SBP), diastolic blood pressure (DBP), arterial compliance, and left ventricular structure and function, particularly left ventricular hypertrophy (LVH), in the very elderly (>75 years). SBP and arterial stiffness increase with age, and the question is: which of the two is the main stimulus to LVH? This is a cross-sectional study to compare blood pressure and arterial stiffness measures with regard to their correlations with echocardiographic parameters of LV structure and function, controlling for age and cardiovascular risk factors, in a very elderly population. Arterial stiffness was determined by radial pulse waveform using pulse contour analysis. LV dimensions were measured by transthoracic M-mode echocardiography, and diastolic function by tissue Doppler measurements of diastolic mitral annular velocities. There were 179 subjects, all male, with a mean age of 81.8 years. Using age-adjusted partial correlations, SBP, DBP, and mean arterial pressure (MAP) were correlated with parameters of LV structure and function. Correlation coefficients were: SBP versus left ventricular mass index (LVMI), r = 0.246; SBP versus early diastolic mitral annular velocity (MAV), r = -0.179; DBP versus LVMI, r = 0.199; DBP versus MAV, r = -0.199; MAP versus LVMI, r = 0.276; and MAP versus MAV, r = -0.206, all with P < .05. However, neither capacitative nor reflective arterial compliance was significantly correlated with any parameter of LV structure and function. After controlling for age and 10 cardiovascular and metabolic risk factors, the correlation between blood pressure and the measured LV parameters was substantially unchanged, as was the lack of correlation between indices of arterial compliance and the LV indices. Arterial blood pressure is correlated with LV structure and function in the very elderly, but arterial stiffness, as measured by diastolic pulse contour analysis, is not.

Arterial strain measurement by implantable capacitive sensor without vessel constriction.

Cardiovascular disease caused 32.8% of deaths in the United States in 2008 [1]. The most important medical parameter is the arterial blood pressure. The origin of high or low blood pressure can mostly be found in the vessel compliance. With the presented implantable sensor, we are able to directly measure strain of arteries, as an indicator of arteriosclerosis. The sensor is designed as a cuff with integrated capacitive structures and is wrapped around arteries. With a new and innovative locking method, we could show that the system does not affect the arteries. This is demonstrated by theory as well as experimental in vivo investigations. Biocompatibility tests, confirmed by histological cuts and MRI measurements, showed that no stenosis, allergic reactions or inflammation occurs. The sensor shows excellent linear behavior with respect to stress and strain.