Phenylephrine Infusion Research Articles

Use of Remifentanil for Open in utero Fetal Myelomeningocele Repair Maintains Uterine Relaxation with Reduced Volatile Anesthetic Concentration

Introduction: Open fetal repair of myelomeningocele (MMC) is an option for prenatally diagnosed spina bifida. Historically, high-dose volatile anesthetic was used for uterine relaxation but is associated with fetal cardiovascular depression. We examined the impact of administering a supplemental remifentanil infusion on the concentration of inhaled anesthetic required for intraoperative uterine relaxation. Methods: We retrospectively analyzed 22 consecutive patients who underwent open fetal MMC repair with desflurane anesthesia from 2014 to 2018. The anesthetic protocol was modified to include high-dose opioid with remifentanil in 2016. We examined intraoperative end-tidal desflurane concentrations, vasopressor use, incidence of umbilical artery Doppler abnormalities, and incidence of preterm labor and delivery. Results: Patients (n = 11) who received desflurane and remifentanil (Des/Remi) were compared to patients (n = 11) who received desflurane (Des) alone. Intraoperatively, the maximum end-tidal desflurane required to maintain uterine relaxation was lower in the Des/Remi group (7.9 ± 2.2% vs. 13.1 ± 1.2%, p < 0.001). The mean phenylephrine infusion rate was also lower in the Des/Remi group (36 ± 14 vs. 53 ± 10 mcg/min, p = 0.004). Discussion: Use of opioid with supplemental remifentanil was associated with lower volatile anesthetic dosing and decreased vasopressor use; fetal outcomes were not different. Remifentanil may allow for less volatile anesthetic use while maintaining adequate uterine relaxation.

Effects of continuous infusion of phenylephrine vs. norepinephrine on parturients and fetuses under LiDCOrapid monitoring: a randomized, double-blind, placebo-controlled study

BackgroundHypotension following spinal anesthesia (SA) during cesarean delivery (CD) occurs commonly and is related with maternal and fetal complications. Norepinephrine infusion is increasingly used for prevention of post-SA hypotension; however, its effects as compared to the traditional phenylephrine infusion remain unclear. This study aimed to compare the effects of phenylephrine and norepinephrine administered as continuous infusion during elective CD on maternal hemodynamic parameters and maternal and fetal outcomes.MethodsThis prospective, single-center, randomized, controlled study included 238 consecutive term parturients who underwent CD from February 2019 to October 2019. They were randomized to receive continuous infusion of 0.25 μg/kg/min phenylephrine, 0.05 μg/kg/min norepinephrine, or placebo. Hemodynamic monitoring was performed at 10 time points using LiDCOrapid. We analyzed umbilical vein (UV), umbilical artery (UA), and peripheral vein (PV) blood gas indexes and recorded intraoperative complications.ResultsIn phenylephrine group, the systolic blood pressure (SBP) remain during the whole operation. Compared to the control group, phenylephrine, but not norepinephrine, significantly increased the systemic vascular resistance (SVR) to counteract the SA-induced vasodilatation, 3 min following norepinephrine/phenylephrine/LR administration (T4): 957.4 ± 590.3 vs 590.1 ± 273.7 (P < 0.000001); 5 min following norepinephrine/phenylephrine/LR administration (T5): 1104 ± 468.0 vs 789.4 ± 376.2 (P = 0.000002). at the time of incision (T6): 1084 ± 524.8 vs 825.2 ± 428.6 (P = 0.000188). Parturients in the phenylephrine group had significantly lower UV (1.91 ± 0.43) (P = 0.0003) and UA (2.05 ± 0.61) (P = 0.0038) lactate level compared to controls. Moreover, the UV pH value was higher in the phenylephrine than in the control group7.37 ± 0.03(P = 0.0013). Parturients had lower incidence of nausea, tachycardia, hypotension in phenylephrine group.ConclusionsIn this dataset, continuous phenylephrine infusion reduced the incidence of SA-induced hypotension, ameliorated SVR, while decreasing overall maternal complications. Phenylephrine infusions are considered the better choice during CD because of the significant benefit to the fetus.Trial registrationClinicaltrial.gov Registry, NCT03833895, Registered on 1 February 2019.

Nitric oxide is fundamental to neurovascular coupling in humans.

Preclinical models have demonstrated that nitric oxide is a key component of neurovascular coupling; this has yet to be translated to humans. We conducted two separate protocols utilizing intravenous infusion of a nitric oxide synthase inhibitor and isovolumic haemodilution to assess the influence of nitric oxide on neurovascular coupling in humans. Isovolumic haemodilution did not alter neurovascular coupling. Intravenous infusion of a nitric oxide synthase inhibitor reduced the neurovascular coupling response by ∼30%, indicating that nitric oxide is integral to neurovascular coupling in humans. Nitric oxide is a vital neurovascular signalling molecule in preclinical models, yet the mechanisms underlying neurovascular coupling (NVC) in humans have yet to be elucidated. To investigate the contribution of nitric oxide to NVC in humans, we utilized a visual stimulus paradigm to elicit an NVC response in the posterior cerebral circulation. Two distinct mechanistic interventions were conducted on young healthy males: (1) NVC was assessed during intravenous infusion of saline (placebo) and the non-selective competitive nitric oxide synthase inhibitor NG -monomethyl-l-arginine (l-NMMA, 5 mg kg-1 bolus & subsequent 50 μg kg-1 min-1 maintenance dose; n = 10). The order of infusion was randomized, counterbalanced and single blinded. A subset of participants in this study (n = 4) underwent a separate intervention with phenylephrine infusion to independently consider the influence of blood pressure changes on NVC (0.1-0.6 μg kg-1 min-1 constant infusion). (2) NVC was assessed prior to and following isovolumic haemodilution, whereby 20% of whole blood was removed and replaced with 5% human serum albumin to reduce haemoglobin concentration (n = 8). For both protocols, arterial and internal jugular venous blood samples were collected at rest and coupled with volumetric measures of cerebral blood flow (duplex ultrasound) to quantify resting cerebral metabolic parameters. l-NMMA elicited a 30% reduction in the peak (P = 0.01), but not average (P = 0.11), NVC response. Neither phenylephrine nor haemodilution influenced NVC. Nitric oxide signalling is integral to NVC in humans, providing a new direction for research into pharmacological treatment of humans with dementia.

Comparison of Continuous Infusion of Epinephrine and Phenylephrine on Hemodynamics During Spinal Anesthesia for Cesarean Delivery: A Randomized Controlled Trial

PurposePhenylephrine is a commonly used vasopressor for the treatment of spinal-induced hypotension in obstetric patients, but it is associated with reflex bradycardia and a corresponding decrease in cardiac output. This study aims to assess the effectiveness of continuous epinephrine versus phenylephrine infusion in the prevention of postspinal maternal hypotension. MethodsEighty-two women undergoing cesarean delivery were randomly divided into the epinephrine group (group E) and the phenylephrine group (group P). The patients received a continuous infusion of phenylephrine 1 μg kg−1 min−1 or epinephrine 0.1 μg kg−1 min−1 synchronously with intrathecal administration. Hemodynamic parameters were recorded, and umbilical cord blood gases were analyzed after delivery. The incidence of maternal hypotension, bradycardia, nausea, and vomiting was recorded. FindingsBlood pressure, heart rate, and cardiac output after spinal anesthesia induction were greater in group E than in group P (P < 0.05). In addition, there was a significant difference in the incidence of bradycardia (5% vs 22.5%, P = 0.02) and mean (SD) umbilical artery pH (7.31 [0.07] vs 7.28 [0.06], P = 0.04) between the groups. ImplicationsWith the dose of 0.1 μg kg−1 min−1, infusion of epinephrine is more effective at maintaining blood pressure close to baseline during spinal anesthesia with a lower decrease in maternal heart rate and cardiac output compared with phenylephrine. Epinephrine may be superior to phenylephrine in terms of the incidence of bradycardia and umbilical artery pH. chictr.org.cn identifier: ChiCTR-IIC-17010960.

Old cells die hard - sympatholysis and the ageing erythrocyte.

Old cells die hard - sympatholysis and the ageing erythrocyte.

Real‐time simulation device for mean arterial pressure of hypotensive patient subjected phenylephrine infusion

This Letter presents the implementation in a hardware device of the mean arterial pressure (MAP) response model of patients subjected to the infusion of the vasoconstrictor drug phenylephrine, enabling the development of automatic control systems in the future. The proposed model was firstly developed in a software platform with Simulink/MatLab using block libraries based on previous research carried out with animals and then implemented on hardware using a single-board computer with microcontroller and code generated in C/C++. The responses of MAP were simulated and compared using the proposed software and hardware model, considering the dynamic effects of several patients. The results showed that the hardware model presented 0.43% as the largest absolute percentage error observed in all trials, for an injection rate of the drug varying in steps with levels of 40 ml/h

Abstract 265: Systemic Inflammation and Cardiac Macrophage Infiltration Accompany Stretch-induced Myocardial Injury in Swine Subjected to Transient Pressure Overload

Objective: Transient pressure overload (TPO) elicits stretch-induced myocyte injury in the absence of ischemia or infarction, but the extent to which this is associated with inflammation is unclear. The present study was designed to assess immune activation after TPO in swine and compare the inflammatory cytokine profile to that observed after myocardial infarction (MI). Methods: Swine received a brief infusion of phenylephrine (18 mg/hr iv; 30-60 min) to induce TPO and were studied for 1 hr (n=5), 3 hr (n=6), or 24 hr (n=6) before analysis of myocardial macrophage gene expression (CD68) via qPCR. Serial blood sampling was performed to assess neutrophil and monocyte counts as well as circulating cardiac troponin I (cTnI), IL-6, TNF-α, and CRP. Cytokine levels were compared to those from a separate group (n=5) subjected to a 60 min LAD occlusion to produce MI. Results: TPO increased circulating cTnI (from 20±5 ng/L to 340±58 ng/L at 3 hr and 1520±616 ng/L at 24 hr; p&lt;0.01) without evidence of infarction. Compared with controls (n=6), swine subjected to TPO exhibited increased CD68 gene expression at 1, 3, and 24 hr ( A ). This was accompanied by a rise in peripheral blood neutrophils and monocytes ( B ) as well as an elevation in circulating IL-6, TNF-α, and CRP that was comparable to that observed after MI ( C ). Conclusion: Myocyte injury following TPO elicits mobilization of neutrophils and monocytes and a rise in circulating inflammatory cytokines comparable to that observed after MI. This is accompanied by an increase in cardiac macrophages and may be an important mechanism by which repetitive episodes of TPO lead to interstitial fibrosis and diastolic dysfunction without anatomic hypertrophy.

Nitric oxide in the insular cortex modulates baroreflex responses in a cGMP-independent pathway

Insular cortex is a brain structure involved in the modulation of autonomic activity and cardiovascular function. The nitric oxide/cyclic guanosine-3′,5′-monophosphate pathway is a prominent signaling mechanism in the central nervous system, controlling behavioral and physiological responses. Nevertheless, despite evidence regarding the presence of nitric oxide-synthesizing neurons in the insular cortex, its role in the control of autonomic and cardiovascular function has never been reported. Thus, the present study aimed to investigate the involvement of nitric oxide/cyclic guanosine-3′,5′-monophosphate pathway mediated by neuronal nitric oxide synthase (nNOS) activation within the insular cortex in the modulation of baroreflex responses in unanesthetized rats. For this, we evaluated the effect of bilateral microinjection of either the nitric oxide scavenger carboxy-PTIO, the selective neuronal nitric oxide synthase inhibitor Nω-Propyl-l-arginine or the soluble guanylate cyclase inhibitor ODQ into the insular cortex on the bradycardia evoked by blood pressure increases in response to intravenous infusion of phenylephrine, and the tachycardia caused by blood pressure decreases evoked by intravenous infusion of sodium nitroprusside. Bilateral microinjection of either NPLA or carboxy-PTIO into the insular cortex increased the reflex bradycardic response, whereas the reflex tachycardia was decreased by these treatments. Bilateral microinjection of the soluble guanylate cyclase inhibitor into the insular cortex did not affect any parameter of baroreflex function evaluated. Overall, our findings provide evidence that insular cortex nitrergic signaling, acting via neuronal nitric oxide synthase, plays a prominent role in control of baroreflex function. However, control of reflex responses seems to be independent of soluble guanylate cyclase activation.

A Clinical Trial on the Effects of Different Regimens of Phenylephrine on Maternal Hemodynamic After Spinal Anesthesia for Cesarean Section.

BackgroundPhenylephrine is used to prevent and treat hypotension during spinal anesthesia for cesarean delivery.ObjectivesThe present study aims to investigate the effects of different regimens of phenylephrine on blood pressure of candidates for the cesarean section.MethodsIn this double-blind, randomized clinical trial, a total of 120 candidates of elective cesarean delivery under spinal anesthesia was randomly categorized into three groups. Groups 1, 2, and 3 received bolus and prophylactic saline (control group), prophylactic bolus phenylephrine (100 µg), and prophylactic phenylephrine infusion (50 µg/min), respectively. The incidence of hypotension, maternal hemodynamics, hypertension, rescue phenylephrine dose, nausea, and vomit were compared between the groups.ResultsIn all the three groups, the incidence of nausea and vomit, bradycardia, hypertension, and neonatal Apgar score were not statistically different (P > 0.05). However, the adjuvant phenylephrine dose requirement was remarkably different. Moreover, the mean systolic blood pressure differed significantly in the second and 7th minutes after the spinal block (P < 0.05). 35% in the first group, 15% in the second group, and 2.5% in the third group had hypotension (P = 0.001). Apart from the first measurement after spinal anesthesia, the mean heart rate showed no significant difference between the groups.ConclusionsThe use of prophylactic phenylephrine infusion is recommended to control the optimal blood pressure in parturients undergoing cesarean section after spinal anesthesia.

Effect of phenylephrine infusion on hypotension induced by the beach chair position: A prospective randomized trial.

Background:The beach chair position (BCP), used during shoulder surgery, is associated with hypotension, bradycardia, and risk of cerebral hypoperfusion. Phenylephrine is commonly used as a first treatment of choice of intraoperative hypotension during surgery. We evaluated the hemodynamic effects of 2 doses of intravenous phenylephrine infusion administered before being placed in BCP for arthroscopic shoulder surgery. The primary endpoint was the incidence of hypotension after positional change.Methods:Sixty-six patients were randomized to receive either intravenous normal saline (group NS) or intravenous phenylephrine infusion (0.5 μg/kg/min, group LP or 1.0 μg/kg/min, group HP) for 5 minutes before being placed in the BCP. Mean arterial pressure(MAP), heart rate, stroke volume variation, and cardiac index were measured before and after positional change.Results:The total incidence of hypotension after the BCP was 93.65%, but was not significantly different among the 3 groups. However, there was a significant difference in trends between the groups for MAP for 5 minutes after BCP (P = .028). Comparison of changes in MAP at 1 minute compared to post-induction MAP was significantly different between group HP and group NS (P = .014).Conclusion:Infusion of 0.5 and 1.0 μg/kg/min of phenylephrine for 5 minutes before the BCP has no preventive effect for incidence of hypotension. However, this study showed that 1.0 μg/kg/min of phenylephrine infusion for 5 minutes can attenuate the severity of hypotension.

Does an Earlier or Late Intravenous Injection of Ondansetron Affect the Dose of Phenylephrine Needed to Prevent Spinal-Anesthesia Induced Hypotension in Cesarean Sections?

BackgroundThere was controversy about ondansetron can reduce the incidence of spinal-induced hypotension and decrease the consumption of vasopressor in cesarean delivery with spinal anesthesia. We hypothesized that different timing of ondansetron administration may contribute to the controversy. Therefore, we aimed to determine the effect of different timing of ondansetron administration on the dose requirement of preventing phenylephrine via comparing the ED50 of prophylactic phenylephrine.MethodsSeventy-five parturients were finally enrolled in this prospective, randomized, double-blinded dose finding study. Ondansetron or placebo was administered 5 min or 15 min before intrathecal injection. Up-down allocation method was used to determine the dose of prophylactic phenylephrine for each parturient in the three groups. The initial infusion rate of first patient was 0.5 µg/kg/min. Then, the rate for next patient was varied with increasing or decreasing of 0.05 μg/kg/min according to the response of the previous patient. An effective dose was defined as no hypotension occurred during the study period. An ineffective dose was defined as hypotension occurred during the study period. Study period in this study is from intrathecal injection to neonatal delivery. ED50 of phenylephrine infusion was calculated by probit regression.ResultsThe ED50 of intravenous phenylephrine calculated by probit analysis was 0.33 (95% CI 0.20 to 0.38) µg/kg/min and 0.36 (95% CI 0.32 to 0.38) µg/kg/min in group A and B, and 0.41 (95% CI 0.37 to 0.44) µg/kg/min in group C for patients undergoing cesarean delivery with combined spinal-epidural anesthesia.ConclusionAn earlier administration of 4 mg prophylactic ondansetron contributed no benefits for lowing the dose of prophylactic phenylephrine compared to a late administration, but can decrease the dose of preventing phenylephrine in patients undergoing cesarean delivery with combined spinal-epidural anesthesia. This finding may be useful for clinical practice and further studies.

Study protocol for an exploratory interventional study investigating the feasibility of video-based non-contact physiological monitoring in healthy volunteers by Mapping Of Lower Limb skIn pErfusion (MOLLIE)

IntroductionSkin perfusion varies in response to changes in the circulatory status. Blood flow to skin is reduced during haemodynamic collapse secondary to peripheral vasoconstriction, whereas increased skin perfusion is frequently...

In Response.

In Response.

Dose-Response Study of 4 Weight-Based Phenylephrine Infusion Regimens for Preventing Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia

(Anesth Analg. 2020;130:187–193) When performing a cesarean delivery, anesthesiologists are most likely to use spinal anesthesia or combined spinal-epidural anesthesia, although these methods are associated with high rates of hypotension. Phenylephrine is considered to be an acceptable vasopressor for hypotension prevention, but not much research has been done to determine the optimal dose for prophylactic phenylephrine infusions. The few studies that have examined phenylephrine infusions did not use infusion rates that had been properly adjusted for patient body weight, so more research is warranted. These investigators conducted their study to examine the dose-response relationship for a fixed-rate, weight-based phenylephrine infusion under combined spinal-epidural anesthesia during cesarean delivery. In addition, the authors aimed to determine the infusion dose that would adequately prevent hypotension for 50% (ED50) and 90% (ED90) of patients.

Efficacy and safety of intravenous phenylephrine and mephentermine for management of hypotension during spinal anaesthesia: A single blind prospective and comparative study among patients undergoing cesarean section

Hypotension is a common side effect when neuraxial analgesia is administered to the obstetric population. To find out the efficacy of mephentermine and phenylephrine for management of hypotension following spinal anesthesia in cesarean section. The study has been undertaken at the Department of Anesthesiology of ESI- PGIMSR, Manicktala, Kolkata, after obtaining approval from Institute Ethical Committee. Uni-centric randomized, single blind, prospective &amp; comparative study.Unpaired Student’s t-test, chi-square test, Fisher’s exact test. The 40-female scheduled for elective caesarean section were randomly divided into two groups of 20 each. Subarachnoid block was performed with 2.2mL of 0.5% hyperbaric bupivacaine. Prophylactic infusion of vasopressor started at a rate of 60 ml/h 0f 50 mcg/min for phenylephrine (group P, n=20) and 600 mcg/min for mephentermine (Group M, n=20) Hemodynamic parameters were monitored. At the end of surgery and the patients were transferred to the postoperative care unit (PACU).Considering absolute values of hypotension, both groups are comparable in terms of preventing hypotension; however, phenylephrine had better control of maintenance over blood pressure than that of mephentermine. Reactive hypertension is common in phenylephrine infusion. Bradycardia is more prevalent in phenylephrine infusion than that of mephentermine while tachycardia is more common in mephentermine. Side effects like dyspnea, nausea/vomiting, headache is more common during hypotensive episodes. None of the drugs causes any untoward effect on fetus.

Augmentation of endothelium-dependent vasodilatory signalling improves functional sympatholysis in contracting muscle of older adults.

The ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction (functional sympatholysis) is critical for maintaining blood flow during exercise-mediated sympathoexcitation. Functional sympatholysis and endothelial function are impaired with ageing, resulting in compromised blood flow and oxygen delivery to contracting skeletal muscle during exercise. In the present study, intra-arterial infusion of ACh or ATP to augment endothelium-dependent signalling during exercise attenuated α1 -adrenergic vasoconstriction in the contracting muscle of older adults. The vascular signalling mechanisms capable of functional sympatholysis are preserved in healthy ageing, and thus the age-related impairment in functional sympatholysis probably results from the loss of a functional signal (e.g. plasma [ATP]) as opposed to an intrinsic endothelial dysfunction. The ability of contracting skeletal muscle to attenuate sympathetic α-adrenergic vasoconstriction ('functional sympatholysis') is impaired with age. In young adults, increasing endothelium-dependent vasodilatory signalling during mild exercise augments sympatholysis. In the present study, we tested the hypothesis that increasing endothelium-dependent signalling during exercise in older adults can improve sympatholysis. In 16 older individuals (Protocol 1, n=8; Protocol 2, n=8), we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (FVC) to local intra-arterial infusion of phenylephrine (PE; α1 -agonist) during (i) infusion of an endothelium-dependent vasodilator alone (Protocol 1: ACh or Protocol 2: low dose ATP); (ii) mild handgrip exercise (5% maximum voluntary contraction; MVC); (iii) moderate handgrip exercise (15% MVC); and (iv) mild or moderate handgrip exercise+infusion of ACh or ATP to augment endothelium-dependent signalling. PE caused robust vasoconstriction in resting skeletal muscle during control vasodilator infusions (ΔFVC: ACh: -31±3 and ATP: -30±4%). PE-mediated vasoconstriction was not attenuated by mild or moderate intensity exercise (ΔFVC: 5% MVC: -30±9; 15% MVC: -33±8%; P>0.05vs. control ACh and ATP), indicative of impaired sympatholysis, and ACh or ATP infusion during mild exercise did not impact this response. However, augmentation of endothelium-dependent signalling via infusion of ACh or ATP during moderate intensity exercise attenuated PE-mediated vasoconstriction (ΔFVC: -13±1 and -19±5%, respectively; P<0.05vs. all conditions). Our findings demonstrate that, given a sufficient stimulus, endothelium-dependent sympatholysis remains intact in older adults. Strategies aimed at activating such pathways represent a viable approach for improving sympatholysis and thus tissue blood flow and oxygen delivery in older adults.

Uterine Exteriorization Compared With In Situ Repair of Hysterotomy After Cesarean Delivery: A Randomized Controlled Trial.

To compare the effect of exteriorized with in situ uterine repair on intraoperative nausea and vomiting during elective cesarean delivery under spinal anesthesia using a phenylephrine infusion. This study was a randomized double-blinded controlled trial of 180 women undergoing elective cesarean delivery using a standardized anesthetic protocol. Patients were randomized to exteriorization (n=90) or in situ uterine repair (n=90). The spinal anesthetic, phenylephrine infusion, and blood pressure management were all standardized. The primary outcome was postdelivery intraoperative nausea and vomiting using a 4-point scale (0-3). A sample size of 80 patients per group was needed to demonstrate a 50% reduction in intraoperative nausea and vomiting with in situ repair. From November 2015 through July 2018, 180 patients were enrolled. Incidence of postdelivery intraoperative nausea and vomiting was 39% in the exteriorization group compared with 22% in the in situ group (P=.01). Incidence of hypotension (80% vs 50%; P<.001) and tachycardia (33% vs 17%; P=.02) was significantly higher in the exteriorization group, and more phenylephrine boluses were administered to this group (median 4 boluses [first and third quartiles 1.25-7] vs 2 [0-4]; P<.001). The duration of surgery, blood loss, and postoperative hemoglobin decline were similar between groups. In situ uterine repair for elective cesarean delivery under spinal anesthesia with a phenylephrine infusion is associated with less postdelivery intraoperative nausea and vomiting. ClinicalTrials.gov, NCT02587013.

Spinal cord autoregulation using near-infrared spectroscopy under normal, hypovolemic, and post-fluid resuscitation conditions in a swine model: a comparison with cerebral autoregulation

BackgroundFew studies have investigated spinal cord autoregulation using near-infrared spectroscopy (NIRS). Here, we assessed spinal cord autoregulation under normal, hypovolemic, and post-fluid resuscitation conditions compared with cerebral autoregulation.MethodsTen pigs (36.1 ± 1.1 kg) were anesthetized with 2.5% isoflurane, before phenylephrine administration at 0.5, 1, 2, and 5 μg kg−1 min−1 in a stepwise fashion at 10-min intervals (baseline), followed by similar administration of sodium nitroprusside (SNP). Hypovolemia was induced by a 600-ml bleed (25% estimated total blood volume). Only phenylephrine was readministered (same protocol). Hypovolemia was reversed by infusing 600 ml hydroxyethyl starch, before readministering phenylephrine and SNP. The relationships between mean arterial pressure (MAP) and cerebral, thoracic, and lumbar spinal cord tissue oxygenation indices (TOIs) were evaluated.ResultsThoracic and lumbar spinal cord TOIs were approximately 15% and 10% lower, respectively, than the cerebral TOI at similar MAPs. The average relationship between MAP and each TOI showed an autoregulatory pattern, but negative correlations were observed in the cerebral TOI during phenylephrine infusion. A 600-ml bleed lowered each relationship < 5% and subsequent fluid resuscitation did not change the relationship. Individual oxygenation responses to blood pressure indicated that the spinal cord is more pressure-passive than the cerebrum. Paradoxical responses (an inverse relationship of tissue oxygenation to MAP) were observed particularly in cerebrum during phenylephrine infusion and were rare in the spinal cord.ConclusionsSpinal cord autoregulation is less robust than cerebral autoregulation and more pressure-dependent. Similar to cerebral oxygenation, spinal cord oxygenation is volume-tolerant but is more sensitive to hypotension.

Essential hypertension is associated with blunted smooth muscle cell vasodilator responsiveness and is reversed by 10-20-30 training in men

Essential hypertension is associated with impairments in vascular function and sympathetic nerve hyperactivity; however, the extent to which the lower limbs are affected remains unclear. We examined the leg vascular responsiveness to infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (PEP) in 10 hypertensive men [HYP: age 59.5 ± 9.7 (means ± SD) yr; clinical and nighttime blood pressure: 142 ± 10/86 ± 10 and 141 ± 11/83 ± 6 mmHg, respectively; and body mass index (BMI): 29.2 ± 4.0 kg/m2] and 8 age-matched normotensive counterparts (NORM: age 57.9 ± 10.8 yr; clinical and nighttime blood pressure: 128 ± 9/78 ± 7 and 116 ± 3/69 ± 3 mmHg, respectively; and BMI: 26.3 ± 3.1 kg/m2). The vascular responsiveness was evaluated before and after 6 wk of 10-20-30 training, consisting of 3 × 5 × 10-s sprint followed by 30 and 20 s of low- to moderate-intensity cycling, respectively, interspersed by 3 min of rest. Before training, the vascular responsiveness to infusion of SNP was lower (P < 0.05) in HYP compared with NORM, with no difference in the responsiveness to infusion of ACh and PEP. The vascular responsiveness to infusion of SNP and ACh improved (P < 0.05) with training in HYP, with no change in NORM. With training, intra-arterial systolic blood pressure decreased (P < 0.05) by 9 mmHg in both HYP and NORM whereas diastolic blood pressure decreased (5 mmHg; P < 0.05) in HYP only. We provide here the first line of evidence in humans that smooth muscle cell vasodilator responsiveness is blunted in the lower limbs of hypertensive men. This impairment can be reversed by 10-20-30 training, which is an effective intervention to improve the responsiveness of smooth muscle cells in men with essential hypertension.

Inorganic Nitrate Supplementation Blunts Vasoconstrictor Responsiveness During Exercise in Patients with Type 2 Diabetes

Patients with type 2 diabetes (T2D) have exaggerated α1‐ and α2‐vasoconstrictor responsiveness during exercise indicating reduced functional sympatholysis. Nitric oxide (NO) is purported to offset α‐mediated vasoconstriction during exercise (i.e., is sympatholytic). Given T2D have attenuated NO bioavailability, supplementation with inorganic nitrate (an exogenous source of NO) may reduce α1‐ and/or α2‐vasoconstrictor responsiveness during exercise in T2D. Thus, we examined if 8wks of inorganic nitrate supplementation (250mg daily, NO3 group) reduced vasoconstrictor responsiveness to intra‐arterial infusions of phenylephrine (PE, α1‐agonist) and/or dexmedetomidine (DEX, α2‐agonist) during handgrip exercise in T2D relative to a placebo (PL group). Handgrip exercise trials lasted for 6min at 20% maximum grip strength. Steady‐state (SS) blood flow was achieved during the first 3min with either PE or DEX infused during the latter 3min. Forearm blood flow (FBF, ml/min) was calculated using brachial artery diameter and blood velocity measured via Doppler ultrasound. Forearm vascular conductance (FVC, ml/min/100mmHg), a surrogate of vasodilation, was calculated using FBF and mean arterial pressure (MAP). Both FBF and FVC were calculated from data averaged over the final 30sec of rest and SS exercise. Vasoconstrictor responsiveness for all trials was quantified as: ((SS FVCwith drug − SS FVCpre‐drug)/SS FVCpre‐drug)x100%. The magnitude of sympatholysis was calculated as the difference in %vasoconstriction at rest and exercise for both α‐agonists. After baseline assessments, T2D were randomly assigned to the NO3 (n=17, 13M/4F, 58±9yrs, 31.8±5.2kg/m2) or PL (n=17, 12M/5F, 58±9yrs, 32.3±5.3kg/m2) supplementation groups. Following supplementation, there were no differences in resting α1‐ or α2‐vasoconstrictor responsiveness observed between groups (group‐by‐time p=0.86 and 0.15, respectively). The NO3 group had greater increases in FBF (164±68 to 185±70ml/min, p&lt;0.05) and FVC (136±53 to 164±61ml/min/100mmHg, p&lt;0.05) responses to exercise (Δ from rest) relative to the PL group (149±66 to 149±65ml/min and 129±64 to 133±60ml/min/100mmHg, p=0.93 and 0.59, respectively). No between‐group differences were observed for α1‐mediated vasoconstrictor responsiveness during exercise or the corresponding magnitude of sympatholysis (group‐by‐time p=0.41 and 0.90, respectively). However, the NO3 group had reduced α2‐mediated vasoconstrictor responsiveness during exercise (−23.4±6.9 to −20.2±5.6% vs. −24.0±7.9 to −26.5±10.5%) with concomitant improvement in the magnitude of sympatholysis (−26.1±12.9 to −38.1±19.4 vs. −25.1±15.9 to −24.7±15.6) compared to the PL cohort, respectively (p&lt;0.05 for both). Principally, we found 8wks of inorganic nitrate supplementation augments the hyperemic (FBF) and vasodilatory (FVC) responses to exercise in T2D. Additionally, these beneficial effects could be attributable to decreased α2‐mediated vasoconstrictor responsiveness in contracting skeletal muscle (i.e., improved functional sympatholysis).Support or Funding InformationAmerican Diabetes Association 1‐16‐1CTA‐015.