Anandi Krishnan

Abstract

To examine the role of limb posture on vascular conductance during rapid changes in vascular transmural pressure, we determined brachial (n = 10) and femoral (n = 10) artery post-occlusive reactive hyperemic blood flow (RHBF, ultrasound/Doppler) and vascular conductance in healthy humans with each limb at three different positions-horizontal, up and down. Limb posture was varied by raising or lowering the arm or leg from the horizontal position by 45°. In both limbs, peak RHBF and vascular conductance were highest in the down or horizontal position and lowest in the up position (arm up 338 ± 38, supine 430 ± 52, down 415 ± 52 ml/min, P < 0.05; leg up 1,208 ± 88, supine 1,579 ± 130, down 1,767 ± 149 ml/min, P < 0.05). In contrast, the maximal dynamic fall in blood flow following peak RHBF (in ml/s/s) in both limbs was highest in the limb-down position and lowest with the limb elevated (P < 0.05). These data suggest that the magnitude and temporal pattern of limb reactive hyperemia is in part related to changes in vascular transmural pressure and independent of systemic blood pressure and sympathetic control.

View details for DOI 10.1007/s00421-010-1769-z

View details for Web of Science ID 000291602200018

View details for PubMedID 21161263

Abstract

The maximum capacity of a hydrophobic adsorbent is interpreted in terms of square or hexagonal (cubic and face-centered-cubic, FCC) interfacial packing models of adsorbed blood proteins in a way that accommodates experimental measurements by the solution-depletion method and quartz-crystal-microbalance (QCM) for the human proteins serum albumin (HSA, 66 kDa), immunoglobulin G (IgG, 160 kDa), fibrinogen (Fib, 341 kDa), and immunoglobulin M (IgM, 1000 kDa). A simple analysis shows that adsorbent capacity is capped by a fixed mass/volume (e.g. mg/mL) surface-region (interphase) concentration and not molar concentration. Nearly analytical agreement between the packing models and experiment suggests that, at surface saturation, above-mentioned proteins assemble within the interphase in a manner that approximates a well-ordered array. HSA saturates a hydrophobic adsorbent with the equivalent of a single square or hexagonally-packed layer of hydrated molecules whereas the larger proteins occupy two-or-more layers, depending on the specific protein under consideration and analytical method used to measure adsorbate mass (solution depletion or QCM). Square or hexagonal (cubic and FCC) packing models cannot be clearly distinguished by comparison to experimental data. QCM measurement of adsorbent capacity is shown to be significantly different than that measured by solution depletion for similar hydrophobic adsorbents. The underlying reason is traced to the fact that QCM measures contribution of both core protein, water of hydration, and interphase water whereas solution depletion measures only the contribution of core protein. It is further shown that thickness of the interphase directly measured by QCM systematically exceeds that inferred from solution-depletion measurements, presumably because the static model used to interpret solution depletion does not accurately capture the complexities of the viscoelastic interfacial environment probed by QCM.

View details for DOI 10.1016/j.biomaterials.2010.09.075

View details for Web of Science ID 000285675200003

View details for PubMedID 21035180

Abstract

A Doppler signal converter has been developed to facilitate cardiovascular and exercise physiology research. This device directly converts audio signals from a clinical Doppler ultrasound imaging system into a real-time analog signal that accurately represents blood flow velocity and is easily recorded by any standard data acquisition system. This real-time flow velocity signal, when simultaneously recorded with other physiological signals of interest, permits the observation of transient flow response to experimental interventions in a manner not possible when using standard Doppler imaging devices. This converted flow velocity signal also permits a more robust and less subjective analysis of data in a fraction of the time required by previous analytic methods. This signal converter provides this capability inexpensively and requires no modification of either the imaging or data acquisition system.

View details for DOI 10.1152/ajpheart.00713.2009

View details for Web of Science ID 000277301400037

View details for PubMedID 20173048

Abstract

Adsorption isotherms constructed from time-and-concentration-dependent advancing contact angles thetaa show that the profound biochemical diversity among ten different blood proteins with molecular weight spanning 10-1000 kDa has little discernible effect on the amount adsorbed from aqueous phosphate-buffered saline (PBS) solution after 1 h contact with a particular test surface selected from the full range of observable water wettability (as quantified by PBS adhesion tension tauoa=gammaolv cos thetaoa; where gammaolv is the liquid-vapor interfacial tension and thetaoa is the advancing PBS contact angle). The maximum advancing spreading pressure, Pimaxa, determined from adsorption isotherms decreases systematically with tauoa for methyl-terminated self-assembled monolayers (CH3 SAM, tauo=-15 mN/m), polystyrene spun-coated onto electronic-grade SiOx wafers (PS, tauo=7.2 mN/m), aminopropyltriethoxysilane-treated SiOx surfaces (APTES, tauo = 42 mN/m), and fully water wettable SiOx (tauo=72 mN/m). Likewise, the apparent Gibbs' surface excess [Gammasl-Gammasv], which measures the difference in the amount of protein adsorbed Gamma (mol/cm2) at solid-vapor (SV) and solid-liquid (SL) interfaces, decreases with tauo from maximal values measured on the CH3 SAM surface through zero (no protein adsorption in excess of bulk solution concentration) near tauo=30 mN/m (thetaa=65 degrees). These latter results corroborate the conclusion drawn from independent studies that water is too strongly bound to surfaces with tauo>or=30 mN/m to be displaced by adsorbing protein and that, as a consequence, protein does not accumulate within the interfacial region of such surfaces at concentrations exceeding that of bulk solution ([Gammasl-Gammasv]=0 at tauo=30 mN/m). Results are collectively interpreted to mean that water controls protein adsorption to surfaces and that the mechanism of protein adsorption can be understood from this perspective for a diverse set of proteins with very different amino acid compositions.

View details for DOI 10.1021/la703310k

View details for Web of Science ID 000253941000042

View details for PubMedID 18229964

Abstract

Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment (n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to approximately 33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Delta502 +/- 111; post ketorolac: Delta348 +/- 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block (P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.

View details for DOI 10.1152/ajpheart.00258.2007.

View details for Web of Science ID 000249237800068

View details for PubMedID 17604332

Abstract

Concentration-dependent, interfacial-shear rheology and interfacial tension of albumin, IgG, fibrinogen, and IgM adsorbed to the aqueous-buffer/air surface is interpreted in terms of a single viscoelastic layer for albumin but multi-layers for the larger proteins. Two-dimensional (2D) storage and loss moduli G(') and G(''), respectively, rise and fall as a function of bulk-solution concentration, signaling formation of a network of interacting protein molecules at the surface with viscoelastic properties. Over the same concentration range, interfacial spreading pressure Pi(LV) identical with gamma(lv)(o)-gamma(lv) rises to a sustained maximum Pi(LV)(max). Mixing as little as 25 w/v% albumin into IgG at fixed total protein concentration substantially reduces peak G('), strongly suggesting that albumin acts as rheological modifier by intercalating with adsorbed IgG molecules. By contrast to purified-protein solutions, serially diluted human blood serum shows no resolvable concentration-dependent G(')and G('').

View details for DOI 10.1016/j.biomaterials.2006.02.005

View details for Web of Science ID 000236783000009

View details for PubMedID 16504286

Abstract

Contact-angle goniometry confirms that interfacial energetics of protein adsorption to the hydrophobic solid/aqueous-buffer (solid-liquid, SL) surface is not fundamentally different than adsorption to the aqueous-buffer/air (liquid-vapor, LV) interface measured by pendant-drop tensiometry. Adsorption isotherms of 9 globular blood proteins with molecular weight (MW) spanning from 10 to 1000 kDa on methyl-terminated self-assembled monolayer surfaces demonstrate that (i) proteins are weak surfactants, reducing contact angles by no more than about 15 degrees at maximum solution concentrations ( approximately 10 mg/mL); (ii) the corresponding dynamic range of spreading pressure Pi(a) < 20 mN/m; and (iii) the maximum spreading pressure Pi(max) (a) for these diverse proteins falls within a relatively narrow 5 mN/m band. As with adsorption to the LV interface, we find that concentration scaling substantially alters perception of protein interfacial activity measured by Pi(a). Proteins appear more similar than dissimilar on a weight/volume basis whereas molarity scaling reveals a systematic ordering by MW, suggesting that adsorption is substantially driven by solution concentration rather than diversity in protein amphilicity. Scaling as a ratio-to-physiological-concentration demonstrates that certain proteins exhibit Pi(max)(a) at-and-well-below physiological concentration whereas others require substantially higher solution concentration to attain Pi(max)(a). Important among this latter category of proteins is blood factor XII, assumed by the classical biochemical mechanism of plasma coagulation to be highly surface active, even in the presence of overwhelming concentrations of other blood constituents such as albumin and immunoglobulin that are shown by this work to be among the class of highly surface-active proteins at physiologic concentration. The overarching interpretation of this work is that water plays a dominant, controlling role in the adsorption of globular-blood proteins to hydrophobic surfaces and that energetics of hydration control the amount of protein adsorbed to poorly water-wettable biomaterials.

View details for PubMedID 16104049

Abstract

A systematic study of water-air (liquid-vapor, LV) interfacial tension gamma(lv) of blood plasma and serum derived from four different mammalian species (human, bovine, ovine and equine) reveals nearly identical concentration-dependence (dgamma(lv)/dlnC(B); where C(B) is plasma/serum dilution expressed in v/v concentration units). Comparison of results to a previously-published survey of purified human-blood proteins further reveals that dgamma(lv)/dlnC(B) of plasma and serum is surprisingly similar to that of purified protein constituents. It is thus concluded that any combination of blood-protein constituents will be substantially similar because dgamma(lv)/dlnC(B) of individual proteins are very similar. Experimental results are further interpreted in terms of a recently-developed theory emphasizing the controlling role of water in protein adsorption. Accordingly, the LV interphase saturates with protein adsorbed from bulk solution at a fixed weight-volume concentration ( approximately 436 mg/mL) independent of protein identity or mixture. As a direct consequence, dgamma(lv)/dlnC(B) of purified proteins closely resembles that of mixed solutions and does not depend on the relative proportions of individual proteins comprising a mixture. Thus variations in the plasma proteome between species are not reflected in dgamma(lv)/dlnC(B) nor is serum different from plasma in this regard, despite being depleted of coagulation proteins (e.g. fibrinogen). A comparison of pendant-drop and Wilhelmy-balance tensiometry as tools for assessing protein gamma(lv) shows that measurement conditions employed in the typical Wilhelmy plate approach fails to achieve the steady-state adsorption state that is accessible to pendant-drop tensiometry.

View details for DOI 10.1016/j.biomaterials.2004.09.016

View details for Web of Science ID 000226968200008

View details for PubMedID 15621233

Abstract

A principal conclusion drawn from observations of time- and concentration-dependent liquid-vapor (LV) interfacial tension gamma(lv) of a diverse selection of proteins ranging from albumin to ubiquitin spanning nearly three decades in molecular weight (MW) is that concentration scaling substantially alters perception of protein interfacial activity as measured by reduction in gamma(lv). Proteins appear more similar than dissimilar on a weight/volume basis, whereas molarity scaling reveals a "Traube-rule" ordering by MW, suggesting that adsorption is substantially driven by solution concentration rather than diversity in protein amphilicity. Scaling as a ratio-to-physiological-concentration demonstrates that certain proteins exhibit the full possible range of interfacial activity at and well-below physiological concentration, whereas others are only weakly surface active within this range, requiring substantially higher solution concentration to achieve reduction in gamma(lv). Important among this latter category of proteins are the blood factors XII and XIIa, assumed by the classical biochemical mechanism of plasma coagulation to adsorb to procoagulant surfaces, even in the presence of overwhelming concentrations of other blood constituents such as albumin and immunoglobulin that are shown by this work to be among the class of highly surface-active proteins at physiologic concentration. A comparison of pendant drop and Wilhelmy balance tensiometry as tools for assessing protein interfacial activity shows that measurement conditions employed in the typical Wilhelmy plate approach fails to achieve the steady-state adsorption condition that is accessible to pendant drop tensiometry.

View details for PubMedID 14762935

View details for DOI 10.1021/la035308t

View details for Web of Science ID 000186694500053