Blood Flow Control Mechanisms Research Articles

Comparative Evaluation of Soft Tissue Reaction to Titanium and Polyetheretherketone Customized Healing Abutments: a Split-Mouth Randomised Clinical Trial

Aim. This study aimed to evaluate the peri-implant soft tissue response to customized healing abutments (CHAs) made of titanium and polyetheretherketone (PEEK). Methods. Titanium and PEEK CHAs were mounted on bone-level dental implants in bilateral edentulous patients in a randomized split-mouth study design. After a three-week healing period, the clinical parameters of the peri-implant soft tissues were assessed. The value of marginal bone resorption was measured by cone-beam computed tomography. In addition, peri-implant crevicular fluid samples were obtained to identify periodontal pathogenic bacteria, cytokine levels, and active neutrophil collagenase (aMMP-8) concentration. Microcirculation and oxygenation parameters were assessed using laser Doppler flowmetry and optical tissue oximetry. In addition, wavelet analysis was conducted to study blood flow control mechanisms. Results. Out of the 23 participants initially recruited, 20 were assessed after titanium and PEEK CHA installation due to losses to follow-up. The peri-implant soft tissue around 27 titanium and 25 PEEK CHAs was evaluated during follow-ups. No differences were found in the values of marginal bone resorption, cytokine levels, or total bacterial load (p>0.05). PEEK CHAs demonstrated lower bleeding on probing values, less plaque accumulation, and faster relief of ischemia and hypoxia. Although aMMP-8 concentration was higher in the PEEK group, the values were within normal limits. Conclusions. The results of this comparative study showed a positive soft tissue response to PEEK CHAs. However, further studies comparing the effectiveness of different materials for CHAs should be carried out, considering their specific physical properties and processing protocols.

Vascular Signaling Plasticity Reprograms Blood Delivery Mechanisms to Meet Fluctuating Neuronal Energy Needs

Neuronal computation is metabolically expensive and depends on precision delivery of energy substrates—oxygen and glucose—via tightly coordinated blood flow to ensure that energy demands are continually met. This is facilitated by neurovascular coupling (NVC)—a range of mechanisms matching neural activity to local blood flow. These NVC mechanisms are typically considered invariant, and whether they are reshaped according to ever-changing neuronal metabolic needs has not been examined. We present evidence that neural activity continually reprograms the blood flow control mechanisms embedded in the local vasculature, a process we refer to as ‘vascular signaling plasticity’ (VSP). Using an established enrichment paradigm, we find that animals housed in conditions that increase input to the barrel cortex for 7 days exhibit profound neuronal plasticity in this region. This resculpts local vascular reactivity to elevate blood delivery. Indeed, VSP results in increased basal capillary blood flow and augmented activity of vasodilatory agents in vivo manifesting as increased red blood cell (RBC) flux responses to capillary stimulation and upstream diameter changes measured using 2-photon laser scanning microscopy. Moreover, the sensitivity of capillaries to stimulation is also dramatically elevated in an ex vivo isolated capillary-arteriole preparation. Using K+-mediated capillary-to-arteriole electrical signaling as a springboard to study the molecular underpinnings of VSP, we find that this process induces a ~70% increase in the density of strong inward rectifier K+ (Kir2.1) currents in capillary endothelial cells, which profoundly augments the retrograde hyperpolarization generated by these channels to control upstream diameter at the level of the penetrating arteriole. Through whole-cell patch clamp electrophysiology, we characterize the mechanism of VSP induction and recapitulate this phenomenon in vitro. We validate our findings through Crispr/Cas9-mediated endothelial cell-specific knockout of the transcription factor responsible for VSP induction. Our data thus recast the vasculature as a plastic, brain-wide activity sensing network that is continually reshaped at the molecular level by local neuronal input, leading to precisely-tuned blood delivery to meet continually fluctuating neural energy needs. VSP represents a new dimension to brain plasticity that may underpin a range of vital physiological processes and is likely disrupted in numerous brain pathologies with a blood flow component. This work was supported by the American Heart Association (23POST1023086), and NIH grants 1DP2NS121347, 1R01AG066645, and 5R01NS115401. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vascular signaling plasticity reprograms neurovascular coupling pathways to precisely match energy delivery to neuronal metabolic needs

Neuronal computation is metabolically expensive and relies on the timely delivery of energy substrates via tightly controlled blood flow to prevent energetic deficits. The range of mechanisms responsible for this coupling of neural activity to blood flow are collectively termed ‘neurovascular coupling’ (NVC). These NVC mechanisms are typically assumed to be invariant and the possibility that they may be plastic, allowing reshaping of energy delivery according to ever-shifting neuronal metabolic needs, has not been considered. We present evidence that neuronal activity resculpts blood flow control mechanisms inherent to the endothelium, which forms the inner lining of all blood vessels, through a process we refer to as vascular signalling plasticity (VSP). Using an environmental enrichment paradigm, we find that housing mice in an environment that increases input to the barrel cortex drives profound synaptic plasticity within this network. This is accompanied by a remarkable resculpting of local vascular reactivity, augmenting the efficacy of mechanisms that signal for an increase in blood flow. This increase in sensitivity manifests as an increase red blood cell flux to capillary stimulation with extracellular K+, which activates strong inward rectifier K+ (Kir2.1) channel-dependent capillary-to-arteriole electrical signalling to elicit hyperemia. To support this augmentation, we find that VSP induces a ~70% increase in the density of Kir2.1 channels in endothelial cells membranes which is underlain by transcriptional and translational changes in capillary ECs. Using an ex vivo capillary-arteriole preparation, we demonstrate that this increase in membrane Kir2.1 channels translates into a profound shift in the sensitivity of capillaries to K+ stimulation to evoke upstream arteriolar dilation. Together, these results suggest that increasing neuronal energy consumption leads to a profound potentiation of the retrograde hyperpolarization generated by the endothelium during activity, enhancing upstream dilation at the penetrating arteriole and augmenting blood delivery to match enhanced local needs. Our data thus recast the capillary bed as a plastic, brain-wide, neural activity sensing network that is modulated at the molecular level by local neural input. This allows fine-tuning of existing blood delivery mechanisms to meet continually fluctuating neural energy needs. VSP represents a novel facet of brain plasticity that may be utilised by various physiological processes and may be disrupted in aging and in the broad range of brain pathologies that have a vascular component. Support for this work was provided by the NIH National Institute on Aging and National Institute of Neurological Disorders and Stroke (1R01AG066645, 5R01NS115401 [PI: S. Sakadžić], and 1DP2NS121347-01, to T.A.L), the American Heart Association (Awards 17SDG33670237 and 19IPLOI34660108 to T.A.L) and an NIH S10 grant (S10 OD026698, to University of Maryland School of Medicine CIBR Core Confocal Facility). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Skin microcirculation in patients with arterial hypertension and in patients with a combination of arterial hypertension and type II diabetes mellitus

Introduction . Common combination of arterial hypertension (AH) with type 2 diabetes mellitus (DM2) which has a negative impact on the incidence and prognosis of coronary artery disease (CAD) imposes a requirement to study their interdependent effects, primarily at the microcirculation (MC) level. Aim. To study peculiarities of functional state of skin MC in patients with a combination of AH and DM2 compared to patients with AH. Materials and methods . Two groups of patients were examined: group 1 (n=66) – patients with a combination of AH and DM2, and group 2 (n=93) – patients with AH. Skin MC was assessed by laser Doppler flowmetry. Basal blood flow, amplitude-frequency spectrum of its oscillations, occlusion indicators, and incidence of various hemodynamic MC types were assessed. Results . In patients with a combination of AH and DM2, progressive deterioration of MC indicators was detected, compared to patients with AH without DM2. Statistically significant differences were revealed in more pronounced tone of the precapillary segment of the microvascular bed (myogenic tone 60.5 [37.4; 83.6] vs 49.1 [31.3; 61.0] units; р=0.014). Impaired function of active blood flow control mechanisms with increase in the role of passive regulation factors was found, as evidenced by lower modulation index (1.3 units in group 1 vs 2.8 units in group 2). In patients with a combination of AH and DM2, there were detected the strengthening of arterio-venous shunts bypassing the capillary bed and blood flow productivity reduction (increase in indicator of bypass grafting up to 1.6 [1.0; 2.1] units) compared to patients with AH and without DM2 up to 1.2 [0.8; 1.5] units; р=0.037), limitation of vasodilation blood flow reserve which amounted to 173.4 % [135.3; 195.4] vs 184.9 % [166.1; 231.3] (р=0.025). Conclusion . More significant changes in microhemocirculation were registered in patients with a combination of AH and DM2 compared to patients with AH. It was characterized by constriction of the microvascular bed precapillary segment with restriction of capillary blood flow, strengthening of arterio-venous shunts bypassing with formation of venous congestion, and reduction of MC reserve potential.

Using laser Doppler flowmetry with wavelet analysis to study skin blood flow regulations after cupping therapy.

The purpose of this study was to use laser Doppler flowmetry (LDF) with wavelet analysis to investigate skin blood flow control mechanisms in response to various intensities of cupping therapy. To the best of our knowledge, this is the first study to assess skin blood flow control mechanism in response to cupping therapy using wavelet analysis of laser Doppler blood flow oscillations. Twelve healthy participants were recruited for this repeated-measures study. Three different intensities of cupping therapy were applied using 3 cup sizes at 35, 40, and 45mm (in diameter) with 300mmHg negative pressure for 5minutes. LDF was used to measure skin blood flow (SBF) on the triceps before and after cupping therapy. Wavelet analysis was used to analyze the blood flow oscillations (BFO) to assess blood flow control mechanisms. The wavelet amplitudes of metabolic and cardiac controls after cupping therapy were higher than those before cupping therapy. For the metabolic control, the 45-mm cupping protocol (1.65±0.09) was significantly higher than the 40-mm cupping protocol (1.40±0.10, P<.05) and the 35-mm cupping protocol (1.35±0.12, P<.05). No differences were showed in the cardiac control among the 35-mm (1.61±0.20), 40-mm (1.64±0.24), and 45-mm (1.27±0.25) cupping protocols. The metabolic and cardiac controls significantly contributed to the increase in SBF after cupping therapy. Different intensities of cupping therapy caused different responses within the metabolic control and not the cardiac control.

CHOROIDAL BLOOD FLOW: Review and Potential Explanation for the Choroidal Venous Anatomy Including the Vortex Vein System.

To review control mechanisms for blood flow in the choroid, propose a system by which venous outflow is controlled by a Starling resistor, and propose an explanation for the choroidal venous architectural anatomy. The main blood flow control mechanisms were reviewed including autoregulation, neurovascular coupling, and myogenic regulation. Applicable blood flow control mechanisms in the brain, a high flow organ in a low compliance outer shell, were used to examine analogous processes that may be occurring in the choroid. There does not seem to be effective autoregulation in the choroid, although myogenic mechanisms may be present. There is a sophisticated neural innervation that provides partial control. Like the brain, the eye has a high pulsatile blood flow rate and is encased in a noncompliant casing. As part of modulating pulsatile pressure in the cranium, the brain uses venous storage and a Starling resistor effect to modulate venous outflow. An analogous function in the eye could be provided by the choroid, which contains fascicles of large veins that converge in vortices to drain out of the eye. This vortex area seems to be where the Starling resistor effect is possible. This mechanism would have important impact on theories of many ocular diseases including central serous chorioretinopathy and spaceflight-associated neuroocular syndrome. Control of blood flow is critical in the choroid, and this control seems to extend to the venous outflow system. Abnormalities in venous outflow may critically affect function in predictable pathogenic mechanisms.

Evidence for improved systemic and local vascular function after long-term passive static stretching training of the musculoskeletal system.

Vascular function and arterial stiffness are important markers of cardiovascular health and cardiovascular co-morbidity. Transitional phases of hypoemia and hypermia, with consequent fluctuations in shear rate, occuring during repetitive passive stretching adminstration (passive stretching training) may constitute an effective stimulus to induce an amelioration in vascular function, arterial stiffness and vascular remodelling by improving central and local blood flow control mechanisms. Vascular function, arterial stiffness and vascular remodelling were evaluated before and after 12weeks of passive stretching training and after 6weeks from training cessation, in the femoral, popliteal (treated with stretching), and brachial arteries (untreated) of both sides. After passive stretching training, vascular function and arterial remodelling improved, and arterial stiffness decreased in all the arteries, suggesting modifications of both central and local blood flow control mechanisms. Passive stretching-induced improvements related to central mechanisms seemed to have a short duration, as they returned to pre-training baseline within 6weeks from training cessation, whereas those more related to a local mechanism persisted in the follow-up. Acute passive stretching (PS) effects on blood flow ( ), shear rate ( ), and vascular function in the feeding arteries of the stretched muscle have been extensively investigated; however, few data are available on vascular adjustments induced by long-term PS training. We investigated the effects of PS training on vascular function and stiffness of the involved (femoral and popliteal) and uninvolved (brachial) arteries. Our hypothesis was that PS-induced changes in and would improve central and local mechanisms of control. Thirty-nine participants were randomly assigned to bilateral PS (n=14), monolateral PS (n=13) or no PS training (n=12). Vascular function was measured before and after 12weeks of knee extensor and plantar flexor muscles' PS training by single passive limb movement and flow-mediated dilatation (FMD). Central (carotid-femoral artery PWV, PWVCF ) and peripheral (carotid-radial artery PWV, PWVCR ) arterial stiffness was measured by pulse-wave velocity (PWV), together with systolic (SBP) and diastolic (DBP) blood pressure. After PS training, increases of 30%, 25% and 8% (P<0.05) in femoral Δ , popliteal and brachial artery FMD%, respectively, occurred in both PS training groups. A decrease in PWVCF , PWVCR , SBP and DBP (-25%, -17%, -4% and -8%, respectively; P<0.05) was noted. No changes occurred in controls. Vascular function improved and arterial stiffness reduced in the arteries involved and uninvolved with PS training, suggesting modifications in both central and local control mechanisms. PS-induced improvements had a short duration in some of vascular function parameters, as they returned to baseline within 6weeks of PS training cessation.

Blood Flow Control of the Microcirculation by KATP Channels in Ventricular Myocytes

The metabolic demands of the working myocardium underlies the control of blood flow to the cardiac myocytes. However, little is known about the details of the signals that are generated by metabolic need and how these signals are linked into a rapid‐response negative feedback control of blood flow. Here, using the state‐of‐the‐art confocal microscopy and whole mount immunostaining techniques and other fluorescent labels, we have investigated both the anatomic organization of the vasculature and the control mechanisms of blood flow. Our results show the key cellular elements of the system are connected to each other electrically by means of gap junctions (Connexin 43). They connect ventricular myocytes to capillary endothelial cells which are connected to pericytes and the small artery endothelium. Gap junctions thus allow the time‐averaged hyperpolarization of ventricular myocytes (due to the opening of ATP‐sensitive K+ channels (KATP) following metabolic need) to produce hyperpolarization in the rest of the system. By this means relaxation of the pericytes and the smooth muscle cells could produce an increase in blood flow with O2 and nutrition to the ventricular myocytes. Initial results showing this physiological feedback control system that appear to manage blood flow control in heart were tested in a perfused mouse cardiac papillary muscle preparation. The functional changes of arterioles and capillaries in the ex vivo heart were monitored using high‐speed confocal microscopes that include a combination of XY (Nipkow disk) and point‐scanner confocals. Our results suggest that KATP opener pinacidil caused perfusion pressure decrease (blood flow increase) while KATP blocker glibenclamide causes perfusion pressure increase in paced or quiescent heart, indicating the functional involvement of KATP channels in local blood flow control. Pinacidil‐induced perfusion pressure reduction does not differ on smooth muscle specific Kir6.1 mutated mice, suggesting the least role of smooth muscle KATP in the local blood flow regulation. An additional contribution to blood flow elevation may be attributed to extracellular K+ ([K+]o) increases (from ventricular myocyte KATP and other K+ channels), which leads to the hyperpolarization of capillary endothelial cells through the activation of inward rectifier K+ channels (Kir). Thus, the activation of KATP in cardiomyocytes caused by metabolic increase links to the local increase in blood flow. Taken together, these data provide compelling evidence that blood flow control in the mammalian heart is a classic negative‐feedback signaling mechanism that links the metabolism of ventricular myocytes to locally increased blood flow through an electrically controlled signaling system.

Wavelet-based analysis of plantar skin blood flow response to different frequencies of local vibration

Objective: The objectives of this study were to investigate the response of plantar skin blood flow (SBF) to different frequencies of local vibration (LV) and investigate the mechanisms of blood flow control in response to the different frequencies of LV using wavelet analysis. Approach: Twelve healthy participants were recruited to test the effects of three frequencies [0 Hz (sham control), 35 Hz and 100 Hz at 1 mm amplitude] of 10 min LV on the skin of the right first metatarsal head. A repeated measures design was used in this study and the order of vibration frequencies was randomly assigned to participants while they lay on a mat table. Laser Doppler flowmetry was used to measure SBF on the first metatarsal head before and after LV for 10 min. SBF after vibration was expressed as a ratio of SBF before vibration. Wavelet analysis was used to characterize changes in SBF control mechanisms. Main results: Our results showed that the SBF with the 100 Hz protocol (1.56 ± 0.19) was significantly higher than for the 35 Hz (1.29 ± 0.18, p < 0.05) and 0 Hz (0.85 ± 0.11, p < 0.01) protocols. Wavelet analysis demonstrated that metabolic endothelial control (SBF oscillations of 0.0095–0.02 Hz) and neurogenic control (SBF oscillations of 0.02–0.05 Hz) were associated with the increase in SBF after LV at 100 Hz. Significance: LV at 100 Hz results in a significant increase in SBF compared with 35 Hz and 0 Hz vibrations. Such an increase in SBF is related to the regulation of metabolic endothelial (0.0095–0.02 Hz) and neurogenic (0.02–0.05 Hz) controls. This is the first study to demonstrate that 100 Hz LV stimulates an increase in plantar SBF compared with 35 Hz and 0 Hz vibrations through the frequency intervals of 0.0095–0.02 and 0.02–0.05 Hz of SBF oscillations.

A mathematical model of cerebral blood flow control in anaemia and hypoxia.

The control of cerebral blood flow in hypoxia, anaemia and hypocapnia is reviewed with an emphasis on the links between cerebral blood flow and possible stimuli. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model demonstrates that hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, an effect exacerbated when blood flow regulation is impaired. The suitability of brain hypoxia as a common regulator of cerebral blood flow in hypoxia and anaemia was explored, although we failed to find support for this hypothesis. Rather, cerebral blood flow appears to be related to arterial oxygen concentration in both anaemia and hypoxia. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model simulation assesses the physiological plausibility of some currently hypothesized cerebral blood flow control mechanisms in hypoxia and anaemia, and also examines the impact of anaemia and hypoxia on brain hypoxia. In addition, carbon dioxide is examined for its impact on brain hypoxia in the context of concomitant changes associated with anaemia and hypoxia. The model calculations are based on a single compartment of brain tissue with constant metabolism and perfusion pressure, as well as previously developed equations describing oxygen and carbon dioxide carriage in blood. Experimental data are used to develop the control equations for cerebral blood flow regulation. The interactive model illustrates that there are clear interactions of anaemia, hypoxia and carbon dioxide in the determination of cerebral blood flow and brain tissue oxygen tension. In both anaemia and hypoxia, cerebral blood flow increases to maintain oxygen delivery, with brain hypoxia increasing when cerebral blood flow control mechanisms are impaired. Hypocapnia superimposes its effects, increasing brain hypoxia. Hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, and this effect is exacerbated when blood flow regulation is degraded by conditions that negatively impact cerebrovascular control. Differences in brain hypoxia in anaemia and hypoxia suggest that brain oxygen tension is not a plausible sensor for cerebral blood flow control.

A mathematical model for thermoregulation in endotherms including heat transport by blood flow and thermal feedback control mechanisms: changes in coat, metabolic rate, blood fluxes, ventilation and sweating rates

Thermoregulation in endotherms allows the maintenance of the body temperature independent of ambient temperature. Experimental data have revealed complex interactions between the physiological mech...

A Mathematical Model for Thermoregulation in Endotherms Including Heat Transport by Blood Flow and Thermal Feedback Control Mechanisms: Changes in Coat, Metabolic Rate, Blood Fluxes, Ventilation and Sweating Rates

Thermoregulation in endotherms allows the maintenance of the body temperature independent of ambient temperature. Experimental data have revealed complex interactions between the physiological mechanisms of thermoregulation and environmental conditions. We derive a nonlinear partial integro-differential dynamical model based on physical first principles and fundamental physiological mechanisms to understand the role of some thermal control mechanisms in the thermoregulation process of endotherms. The model is composed of four layers representing different tissues and it incorporates six thermal feedback control mechanisms. These mechanisms are heat production due to metabolic rate and heat exchange within the body given its internal structure, and the model considers heat exchange due to conduction, heat transport by blood flow, heat exchange with the ambient through convection, radiation, and evaporation from the respiratory tract and superficial evaporation in both passive and active situations. Our model sheds new light on previous explanations about the classic metabolism-ambient temperature U-shaped curve.

Inter-individual Relationships between Sympathetic Arterial Baroreflex Function and Cerebral Perfusion Control in Healthy Males.

Maintenance of adequate cerebral perfusion during normal physiological challenges requires integration between cerebral blood flow (CBF) and systemic blood pressure control mechanisms. Previous studies have shown that cardiac baroreflex sensitivity (BRS) is inversely related to some measures of cerebral autoregulation. However, interactions between the sympathetic arterial baroreflex and cerebral perfusion control mechanisms have not been explored. To determine the nature and magnitude of these interactions we measured R–R interval, blood pressure, CBF velocity, and muscle sympathetic nerve activity (MSNA) in 11 healthy young males. Sympathetic BRS was estimated using modified Oxford method as the relationship between beat-to-beat diastolic blood pressure (DBP) and MSNA. Integrated control of CBF was quantified using transfer function analysis (TFA) metrics derived during rest and Tieck's autoregulatory index following bilateral thigh cuff deflation. Sympathetic BRS during modified Oxford trials was significantly related to autoregulatory index (r = 0.64, p = 0.03). Sympathetic BRS during spontaneous baseline was significantly related to transfer function gain (r = −0.74, p = 0.01). A more negative value for sympathetic BRS indicates more effective arterial baroreflex regulation, and a lower transfer function gain reflects greater cerebral autoregulation. Therefore, these findings indicate that males with attenuated CBF regulation have greater sympathetic BRS (and vice versa), consistent with compensatory interactions between blood pressure and cerebral perfusion control mechanisms.

Plateau Waves of Intracranial Pressure and Partial Pressure of Cerebral Oxygen.

This study investigates 55 intracranial pressure (ICP) plateau waves recorded in 20 patients after severe traumatic brain injury (TBI) with a focus on a moving correlation coefficient between mean arterial pressure (ABP) and ICP, called PRx, which serves as a marker of cerebrovascular reactivity, and a moving correlation coefficient between ABP and cerebral partial pressure of oxygen (pbtO2), called ORx, which serves as a marker for cerebral oxygen reactivity. ICP and ICPamplitude increased significantly during the plateau waves, whereas CPP and pbtO2 decreased significantly. ABP, ABP amplitude, and heart rate remained unchanged. In 73 % of plateau waves PRx increased during the wave. ORx showed an increase during and a decrease after the plateau waves, which was not statistically significant. Our data show profound cerebral vasoparalysis on top of the wave and, to a lesser extent, impairment of cerebral oxygen reactivity. The different behavior of the indices may be due to the different latencies of the cerebral blood flow and oxygen level control mechanisms. While cerebrovascular reactivity is a rapidly reacting mechanism, cerebral oxygen reactivity is slower.

Inter‐individual Relationships Between Sympathetic Arterial Baroreflex Function and Cerebral Perfusion Control in Healthy Males

Maintenance of adequate cerebral perfusion during normal physiological challenges requires integration between cerebral blood flow (CBF) and systemic blood pressure (BP) control mechanisms. Previous studies have shown that cardiac baroreflex sensitivity (BRS) is inversely related to some measures of CA. However, interactions between the sympathetic baroreflex and cerebral perfusion control mechanisms have not been explored. To explore the nature and magnitude of these interactions we measured R-R interval, blood pressure, cerebral blood flow velocity (transcranial Doppler) and muscle sympathetic nerve activity (MSNA) in 8 healthy young males. Sympathetic BRS was estimated using modified Oxford method as the relationship between beat-to-beat diastolic blood pressure (DBP) and MSNA. Integrated CBF control was quantified using transfer function analysis (TFA) metrics derived during rest and Tieck's autoregulatory index (ARI) following bilateral thigh cuff deflation. Sympathetic BRS was positively related to low frequency TFA gain (slope= -0.001562μV/mmHg, r2= 0.06, p= 0.027) and inversely related to ARI (slope= 0.6441, r2=0.5, p= 0.057). Resting integrated MSNA per 100 heartbeats was also inversely related to ARI (slope=-2963, r2= 0.5, p= 0.036). These findings indicate that males with attenuated cerebral blood flow regulation have greater sympathetic BRS, consistent with compensatory interactions between BP and cerebral perfusion control mechanisms. Such interactions may explain the physiological diversity inherent in closed circulatory systems.

Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat.

Bone health and cardiovascular function are compromised in individuals with type 2 diabetes mellitus (T2DM). The purpose of this study was to determine whether skeletal vascular control mechanisms are altered during the progression of T2DM in Zucker diabetic fatty (ZDF) rats. Responses of the principal nutrient artery (PNA) of the femur from obese ZDF rats with prediabetes, short-term diabetes, and long-term diabetes to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilation and potassium chloride, norepinephrine (NE), and a myogenic vasoconstrictor were determined in vitro. Few changes in the PNA vasomotor responses occurred for the prediabetic and short-term diabetic conditions. Endothelium-dependent and -independent vasodilation were reduced, and NE and myogenic vasoconstriction were increased in obese ZDF rats with long-term diabetes relative to lean age-matched controls. Differences in endothelium-dependent vasodilation of the femoral PNA between ZDF rats and controls were abolished by the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. The passive pressure-diameter response of the femoral PNA was also lower across a range of intraluminal pressures with long-term T2DM. Regional bone and marrow perfusion and vascular conductance, measured in vivo using radiolabeled microspheres, were lower in obese ZDF rats with long-term diabetes. These findings indicate that the profound impairment of the bone circulation may contribute to the osteopenia found to occur in long bones during chronic T2DM.

Changes in Cerebral Partial Oxygen Pressure and Cerebrovascular Reactivity During Intracranial Pressure Plateau Waves.

Plateau waves in intracranial pressure (ICP) are frequently recorded in neuro intensive care and are not yet fully understood. To further investigate this phenomenon, we analyzed partial pressure of cerebral oxygen (pbtO2) and a moving correlation coefficient between ICP and mean arterial blood pressure (ABP), called PRx, along with the cerebral oxygen reactivity index (ORx), which is a moving correlation coefficient between cerebral perfusion pressure (CPP) and pbtO2 in an observational study. We analyzed 55 plateau waves in 20 patients after severe traumatic brain injury. We calculated ABP, ABP pulse amplitude (ampABP), ICP, CPP, pbtO2, heart rate (HR), ICP pulse amplitude (ampICP), PRx, and ORx, before, during, and after each plateau wave. The analysis of variance with Bonferroni post hoc test was used to compare the differences in the variables before, during, and after the plateau wave. We considered all plateau waves, even in the same patient, independent because they are separated by long intervals. We found increases for ICP and ampICP according to our operational definitions for plateau waves. PRx increased significantly (p=0.00026), CPP (p<0.00001) and pbtO2 (p=0.00007) decreased significantly during the plateau waves. ABP, ampABP, and HR remained unchanged. PRx during the plateau was higher than before the onset of wave in 40 cases (73%) with no differences in baseline parameters for those with negative and positive ΔPRx (difference during and after). ORx showed an increase during and a decrease after the plateau waves, however, not statistically significant. PbtO2 overshoot after the wave occurred in 35 times (64%), the mean difference was 4.9±4.6Hg (mean±SD), and we found no difference in baseline parameters between those who overshoot and those who did not overshoot. Arterial blood pressure remains stable in ICP plateau waves, while cerebral autoregulatory indices show distinct changes, which indicate cerebrovascular reactivity impairment at the top of the wave. PbtO2 decreases during the waves and may show a slight overshoot after normalization. We assume that this might be due to different latencies of the cerebral blood flow and oxygen level control mechanisms. Other factors may include baseline conditions, such as pre-plateau wave cerebrovascular reactivity or pbtO2 levels, which differ between studies.

To reheat, or to not reheat: that is the question: The efficacy of a local reheating protocol on mechanisms of cutaneous vasodilatation

The aim of this study is to determine the effect of repeated bouts of local skin heating on the roles of nitric oxide synthase (NOS) and sympathetic nerves in cutaneous vasodilatation. In 3 repeated-heating protocols skin blood flux of the forearm and leg was measured using laser-Doppler flowmetry and data are presented as cutaneous vascular conductance (CVC; flux/blood pressure). Local heating was performed from 33°C (thermoneutral) to 42°C at 0.5°C·10s−1, allowed to cool passively for ~60-min, then reheated at the same rate. In protocol 1, CVC was measured in response to repeated heating. In protocol 2, NOS was inhibited with NG-nitro-l-arginine methyl ester (L-NAME) and in protocol 3, sympathetic nerve blockade was achieved with bretylium tosylate (BT), both infused via intradermal microdialysis. In protocol 1, there were no differences (P>0.05) in CVC at either the forearm (88±4 vs. 86±4%max) or the leg (97±4 vs. 96±6%max) between heating bouts. In protocol 2, no differences (P>0.05) in CVC were observed between heating bouts at L-NAME treated sites at either the forearm (55±3 vs. 51±4%max) or the leg (71±3 vs. 70±4%max) . In protocol 3, there were differences (P<0.001) between BT treated sites when comparing the first and second bouts of heating for both the forearm (75±3 vs. 88±4%max) and the leg (79±3 vs. 97±4%max). The effect of sympathetic blockade on CVC responses to local heating was abolished following repeated bouts of heating. Consequently, it is our suggestion that when examining mechanisms of skin blood flow control, investigators use single bouts of local heating.

Quantitative Analysis of Vasodilatory Action of Quercetin on Intramural Coronary Resistance Arteries of the Rat In Vitro

BackgroundDietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme.Aims1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin.MethodsCoronary arterioles (70–240 µm) were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer.ResultsThe spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10−9 moles/lit concentration (p<0.05), while 10−5 moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10–100 mmHg) at 10−7 moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10−5moles/lit) induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova), this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation). A further 2–8% contraction could be elicited by the NO blocker L-NAME (10−4 moles/lit).ConclusionThese results demonstrate that circulating levels of quercetin (10−7 moles/lit) exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall.

Comparative study of the upper and lower limb skin blood flow control mechanisms in patients with essential hypertension

To investigate limb specific differences in cutaneous vascular function in patients (n=33) with essential hypertension (EHT). In this observational cross-sectional study, baseline skin blood flow and the response to local heating were measured with a laser Doppler flowmeter (LDF) from the volar region of the forearm and the gaiter area of the foot at supine rest. The fractal analysis, detrended fluctuation analysis (DFA), was used to calculate the correlation properties of skin blood flow, LDF signal. The paired t-test and repeated measures ANOVA were used to determine the response to local heating and compare the scaling exponents of different anatomical locations respectively. We found three linear scaling regions that describe the fractal behavior of LDF signal with their slopes, scaling exponents. For cardiac (α(C)) and cardio-respiratory (α(CR)) scaling exponents, thermal hyperemia (T) induced greater change in the leg (α(C)=1.49 ± 0.26; α(CT)=1.62 ± 0.20 p<0.01 and α(CR)=0.84 ± 0.29 α(CRT)=0.42 ± 0.28 p<0.001) than in forearm (α(C)=1.28 ± 0.13; α(CT)=1.33 ± 0.13 p>0.05 and α(CR)=0.73 ± 0.15; α(CRT)=0.65 ± 0.018 p<0.05). Local scaling exponents (α(L) ≈ α(LT) ~ 1) were not significantly different (p>0.05) and, local lines did not shift in parallel with local heating in both extremities. The results of the present study suggest that skin microvascular function is impaired in both extremities in EHT patients. However, myogenic response is not uniform in both extremities and pronounced response to local thermal hyperemia has been observed in the gaiter area compared with the volar region. Further studies are needed to determine if these limb specific microvascular differences is the result of posture-induced structural and functional adaptation.