Alvaro N. Gurovich

Central, peripheral and resistance arterial reactivity: fluctuates during the phases of the menstrual cycle

The purpose of this study was to document the temporal changes in vascular reactivity occurring simultaneously in central, peripheral and microvascular resistance arteries in the same cohort of women during the normal menstrual cycle. Twenty-three (n = 23) women (mean age (±SD) = 19 ± 1 y) were tested during four phases of a normal menstrual cycle. Delineation of the four phases occurred as follows: (1) the early follicular phase; (2) the late follicular (LF) phase; (3) the early luteal (EL) phase; and (4) the late luteal phase. Non-invasive measurement of central hemodynamics and peripheral artery pulse wave velocity (PWV) were performed using applanation tonometry. Measurement of peripheral endothelial function was determined by flow-mediated dilation (FMD) testing in the brachial artery and venous occlusion plethysmography in the forearm and calf resistance arteries. Additionally, plasma NOx and 17β-estradiol (E) concentrations were measured. Both central (aortic) and peripheral blood pressure (BP) were lowest (P < 0.05) during the LF phase and BP reduction was sustained (P < 0.05) into the EL phase. The timing and amplitude of the reflected pressure wave were attenuated only during the LF phase (P < 0.05). No temporal changes were observed in either central (carotid-femoral) or peripheral PWV (femoral-dorsalis pedis, carotid-radial). Peak forearm and calf blood flow during reactive hyperemia were greatest in LF. Brachial FMD was greatest during the LF phase (P < 0.05). Plasma E and NOx concentrations were highest during the LF phase (P < 0.05). Young premenopausal women experienced an overwhelming pattern of reduced BP and increased systemic vascular reactivity during the LF phase prior to ovulation.

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

Exercise training ameliorates age-related impairments in endothelium-dependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise-trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained or remained sedentary for 10 wk. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or glutathione peroxidase-1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and glutathione peroxidase-1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise training-induced enhancement of endothelial function occurs, in part, through an increase in ROS signaling.

Redox Balance in the Aging Microcirculation: New Friends, New Foes, and New Clinical Directions

Please cite this paper as: Muller‐Delp, Gurovich, Christou, and Leeuwenburgh (2012). Redox Balance in the Aging Microcirculation: New Friends, New Foes, and New Clinical Directions. Microcirculation 19(1), 19–28.

Enhanced external counterpulsation creates acute blood flow patterns responsible for improved flow-mediated dilation in humans.

Enhanced external counterpulsation (EECP) is a FDA-approved treatment for patients with coronary artery disease and unstable angina. Although beneficial effects of EECP have been linked to central/cardiac adaptations, recent findings have shown peripheral/vascular effects. Here, we sought to determine EECP-induced blood flow patterns and their association with vascular function. The present study was designed to investigate endothelium-mediated arterial vasodilation changes after one 45-min session of either EECP or Sham EECP in 18 randomly assigned apparently healthy, young men (25±4 years). Brachial (b) and femoral (f) flow-mediated dilation (FMD) were assessed before and within 10 min after completing EECP or Sham. After 20 min of EECP, peak blood flow velocity (V) and brachial and femoral artery diameters (D) were recorded live for 2 min. In addition, a blood sample was drawn from the earlobe to determine hematocrit and then to calculate blood viscosity (μ) and density (ρ), Reynolds number (Re=V*D*ρ/μ), and endothelial shear stress (ESS=2μ*V/D). EECP increased retrograde shear stress and retrograde-turbulent blood flow in the femoral artery and antegrade-laminar shear stress in the brachial artery. fFMD was increased after EECP compared with Sham and baseline (fFMD=13.1±3.7 vs. 7.9±4.6% and 7.8±4.5%, respectively, P<0.05) and bFMD was increased after EECP compared with baseline (bFMD=10.6±4.8 vs. 7.0±3.5%, P<0.05), despite different blood flow patterns. These results provide novel evidence that a single session of EECP-induced blood flow patterns improve endothelial function in peripheral muscular conduit arteries.

The acute effects of smokeless tobacco on central aortic blood pressure and wave reflection characteristics

The main objectives of this study were to examine the acute effect of a single dose of smokeless tobacco (ST) on central aortic blood pressure and wave reflection characteristics. Fifteen apparently healthy male subjects (aged 30.6 ± 6.2 y) were given a 2.5 g oral dose of ST after baseline measurements were recorded. Pulse wave analysis using radial artery applanation tonometry was performed in triplicate at baseline (0 min) and at 10-min intervals during (10, 20 and 30 min) and after (40, 50 and 60 min) ST use. An acute dose of ST was associated with a significant increase in heart rate (HR), central aortic systolic and diastolic blood pressure, peripheral brachial systolic and diastolic blood pressure, and aortic augmentation index normalized to a fixed heart rate of 75 bpm (AIx@75). Furthermore, ejection duration and round trip travel time of the reflected pressure wave (Δt p) were significantly decreased as a result of one time ST use. As a result of changes in aortic pressure wave reflection characteristics, there was a significant increase in wasted left ventricular pressure energy (LVEw) and the tension–time index (TTI) as a result of ST use. In conclusion, one time use of ST elicits significant transient increases in HR, central aortic pressures, AIx@75, the TTI and LVEw. Chronic users subjected to decades of elevated central pressures and left ventricular work may have an increased cardiovascular risk as central aortic pressures are even more strongly related to cardiovascular outcomes than peripheral blood pressures.

Aortic Pulse Wave Analysis Is Not a Surrogate for Central Arterial Pulse Wave Velocity

Arterial Stiffness (AS) is a primary cardiovascular risk factor. AS increases myocardial oxygen demand and LV work and decreases coronary perfusion. Pulse Wave Velocity (PWV) is considered the gold standard for assessing AS. However, PWV testing is time consuming and impractical in the clinical setting. The purpose of this study was to determine if Pulse Wave Analysis (PWA) parameters obtained with applanation tonometry can be used to predict PWV. Radial artery PWA testing and aortic PWV measurements were performed on 77 apparently healthy subjects. A correlation matrix between all the studied variables and a stepwise multiple regression were performed. The best regression equation was obtained with central PWV as the dependent variable and Age, Height, Weight, Brachial Systolic and Diastolic Blood pressures, normalized and non-normalized Augmentation Index, Cardiac Cycle time, Ejection Duration, reflected wave round trip travel time, and time to peak pressure as independent variables. Finally, a Bland-Altman test was performed to determine the agreement between measured and predicted PWV. No significant correlations between PWV and PWA parameters were found. The resulting stepwise regression equation was PWV = 1.76 + 0.044*Age + 0.023*SBP (R = 0.544, Adj-R 2 = 0.28, P < 0.001). No agreement between measured and predicted PWV was observed using the Bland-Altman test. Although the regression equation is significant, the adjusted coefficient of determination shows that the model could explain just 28% of PWV variability. These findings suggest that PWA should not be used as a surrogate measure for assessing aortic PWV and stiffness.

Association of Age With Timing and Amplitude of Reflected Pressure Waves During Exercise in Men

BACKGROUND Increased elastic conduit artery stiffness with aging is associated with early wave reflection and increased wasted left ventricular pressure energy (LVE(W)). The effects of aging on central hemodynamics during exercise have not been well characterized. This study sought to investigate changes in central hemodynamics during cycle exercise in young, middle-aged, and older men. METHODS Central blood pressure and wave reflection characteristics were measured noninvasively using radial artery applanation tonometry at rest and during cycling exercise (45, 55, and 65% of predicted maximum heart rate (HR(max))) in 14 young (24 ± 1 years), 16 middle-aged (49 ± 2 years) and 13 older (73 ± 2 years) men. RESULTS Repeated measures analysis of variance revealed significant group-by-time interactions for heart rate, central diastolic blood pressure (DBP), central pulse pressure (PP), PP amplification (PPA), central aortic pressure augmentation (AP), aortic augmentation index (AI(X)), and LVE(W). Magnitude of change from baseline was significantly different in the older group compared to young and middle-aged groups in response to exercise at 65% of predicted HR(max) for AP (+3 ± 1 mm Hg vs. -7 ± 1, P < 0.001 and -3 ± 1 mm Hg, P < 0.001) and LVE(W) (+724 ± 215 dynes s/cm(2)·min vs. -494 ± 199, P < 0.001 and -315 ± 192, P < 0.001). CONCLUSIONS This study suggests that changes in the timing and amplitude of reflected pressure waves during exercise alter the hemodynamic response to exercise with aging. In response to exercise, AP and LVE(W) increased in older subjects while young and middle-aged subjects exhibited a decline in AP and no change in LVE(W).

Pulse wave analysis and pulse wave velocity techniques: are they ready for the clinic?

interestingly describe animportant factor when arterial stiffness is clini-cally assessed: subject’s body position. Althoughthis is an important question, especially ifwe want to bring this research tool to the clinicin a regular basis, there are several other factorsthat should be considered. The purpose of thepresent commentary is to briefly review past,present, and future of Pulse Wave Analysis andPulse Wave Velocity and to discuss if thesetechniques are ready for clinical use.Pulsewaveanalysis(PWA)wasfirstdevel-oped in the nineteenth century by Mohamed.

Flow-mediated dilation is associated with endothelial oxidative stress in human venous endothelial cells

Flow-mediated dilation (FMD) is recognized as a non-invasive endothelial function bioassay. However, FMD’s relationship with endothelial cell oxidative stress in humans is yet to be determined. Here, we sought to determine if FMD was associated with endothelial nitric oxide synthase (eNOS) and endothelial oxidative stress in humans. Twenty-seven apparently healthy young men (26.5±5.9 years) underwent brachial artery FMD testing and endothelial cell biopsy from a forearm vein. Non-normalized FMD (%) and three different brachial artery FMD normalizations were performed: (1) peak shear rate (%/SR); (2) area under the SR curve until peak dilation (%/AUC); and (3) AUC 30 seconds before peak dilation (%/AUC30). Immunofluorescence quantification was used to assess eNOS expression and nitrotyrosine (NT), a criterion marker of endothelial oxidative stress. Values for eNOS and NT expression were reported as a ratio of endothelial cell to human umbilical vein endothelial cell average pixel intensity. NT expression was significantly correlated with FMD normalized by AUC30 (r = −0.402, p<0.05). Other FMD normalizations and non-normalized FMD were not significantly correlated with NT expression (r range = −0.364 to −0.142, all p>0.05). There were no significant correlations between eNOS expression and normalized and non-normalized FMD (r range = −0.168 to −0.066, all p>0.05). In conclusion, brachial artery FMD is associated with venous endothelial cell oxidative stress. However, this association is observed only when FMD is normalized by AUC30.

Validity of a Novel Wristband Tonometer for Measuring Central Hemodynamics and Augmentation Index

BACKGROUND Central hemodynamic and augmentation indices are independent predictors of cardiovascular events and all-cause mortality that can be estimated noninvasively by pulse wave analysis. The purpose of this study was to assess the reliability and validity of a newly engineered wristband tonometer for acquiring radial artery pressure waveforms. METHODS Radial artery pulse pressure waveforms were evaluated with an established pencil-type and a novel wristband tonometer in 31 participants (aged 30.2±9.5 years) resting in a supine position. Pulse wave analysis was executed using the same validated generalized transfer function (SphygmoCor) for both tonometers. RESULTS A significant difference in time to data acquisition between tonometers was observed (-70.2±147.7 s; P < 0.05; wristband faster). The wristband tonometer had significantly lower within-subject coefficients of variation (CV) compared with the pencil-type tonometer in aortic pulse wave height (-2.67% ± 5.51%; P < 0.05) and time to reflection (-2.26% ± 6.16%; P < 0.01). No other differences in CV were observed. Slight but statistically significant mean differences between tonometers were observed in aortic systolic blood pressure (ASBP; 0.43±1.08 mm Hg; P < 0.05; wristband lower), aortic pulse pressure (APP; 0.43±0.96 mm Hg; P < 0.05; wristband lower), and round-trip travel time of the reflected pressure wave (Δtp; 3.58±12.86 ms; P < 0.05; wristband higher). However, ASBP, APP, and Δtp measurements were highly correlated (r = 0.9970, r = 0.9953, and r = 0.8838, respectively, P <0.0001) between tonometers; within-subject and between tonometer significant mean differences were within clinical ranges. CONCLUSIONS This novel, hands-free platform may be interchangeable with the commonly used pencil-type tonometer, heralding new directions in noninvasive in vivo vascular research and clinical application.