Maintenance Of Blood Pressure Research Articles

Function and regulation of corin in physiology and disease.

Atrial natriuretic peptide (ANP) is of major importance in the maintenance of electrolyte balance and normal blood pressure. Reduced plasma ANP levels are associated with the increased risk of cardiovascular disease. Corin is a type II transmembrane serine protease that converts the ANP precursor to mature ANP. Corin deficiency prevents ANP generation and alters electrolyte and body fluid homeostasis. Corin is synthesized as a zymogen that is proteolytically activated on the cell surface. Factors that disrupt corin folding, intracellular trafficking, cell surface expression, and zymogen activation are expected to impair corin function. To date, CORIN variants that reduce corin activity have been identified in hypertensive patients. In addition to the heart, corin expression has been detected in non-cardiac tissues, where corin and ANP participate in diverse physiological processes. In this review, we summarize the current knowledge in corin biosynthesis and post-translational modifications. We also discuss tissue-specific corin expression and function in physiology and disease.

Brainstem Bleed after Chronic Subdural Hematoma Drainage

AbstractChronic subdural hematoma (CSDH) is one of the most frequent benign neurosurgical pathologies. Burr hole drainage is known to be safe, with low-morbidity and low-mortality rates. However, postoperative complications have been reported. We report the case of a 40-year-old lady who suffered a fatal brain stem hemorrhage after burr hole drainage for unilateral chronic SDH. Rapid decompression or sudden increase in cerebral blood flow were the probable factors for her brainstem bleed. Therefore, a slow rate of evacuation of CSDHs and maintenance of a correct blood pressure perioperatively are recommended to prevent serious complications.

Beneficiary and Adverse Effects of Phytoestrogens: A Potential Constituent of Plant-based Diet.

Phytoestrogens are non-endocrine, non-steroidal secondary derivatives of plants and consumed through a plant-based diet also named as "dietary estrogens". The major sources of phytoestrogens are soy and soy-based foods, flaxseed, chickpeas, green beans, dairy products, etc. The dietary inclusion of phytoestrogen based foods plays a crucial role in the maintenance of metabolic syndrome cluster, including obesity, diabetes, blood pressure, cancer, inflammation, cardiovascular diseases, postmenopausal ailments and their complications. In recent days, phytoestrogens are the preferred molecules for hormone replacement therapy. On the other hand, they act as endocrine disruptors via estrogen receptor-mediated pathways. These effects are not restricted to adult males or females and identified even in development. Since phytoestrogenic occurrence is high at daily meals for most people worldwide, they focused to study for its beneficiary effects towards developing pharmaceutical drugs for treating various metabolic disorders by observing endocrine disruption. The present review emphasizes the pros and cons of phytoestrogens on human health, which may help to direct the pharmaceutical industry to produce various phytoestrongen based drugs against various metabolic disorders.

Histomorphological Spectrum of Renal diseases: A Prospective Study for A Period of Two Years

INTRODUCTION: Kidneys are vital organs of the body with multiple functions like excretory, acid base balance and maintenance of blood pressure. Renal parenchyma is mostly subjected to noxious insults but is last to respond. Simple nephrectomy is done for irreversibly damaged kidney. Most common indication for nephrectomy is chronic pyelonephritis. Aim of the study is to analyze the histopathological patterns of renal lesions and to analyze age and sex distribution.
 MATERIALS AND METHODS: The study included a total number of 70 cases, during a period of 2 years i.e., from October 2017 to September 2019. All renal biopsies and nephrectomy specimens received in pathology department, SVS Medical College, Mahabubnagar, Telangana, India were included in the study.
 RESULTS: In our study, 70 cases were analyzed. Out of which majority of the lesions (25.7 % ) were in the age group of 21-40 years and showed male preponderance (68.5 %). Present study showed chronic pyelonephritis being the most common non-neoplastic lesion. Among malignant tumors renal cell carcinoma was most common.
 CONCLUSION: The present study reveals various histological patterns of lesions in renal biopsies and nephrectomy specimens. Our study reveals that non-neoplastic lesions are more commonly encountered lesions.

Effects of polycyclic aromatic hydrocarbons and abiotic stressors on Fundulus grandis cardiac transcriptomics

Following the 2010 Deepwater Horizon oil spill, extensive research has been conducted on the toxicity of oil and polycyclic aromatic hydrocarbons (PAHs) in the aquatic environment. Many studies have identified the toxicological effects of PAHs in estuarine and marine fishes, however, only recently has work begun to identify the combinatorial effect of PAHs and abiotic environmental factors such as hypoxia, salinity, and temperature. This study aims to characterize the combined effects of abiotic stressors and PAH exposure on the cardiac transcriptomes of developing Fundulus grandis larvae. In this study, F. grandis larvae were exposed to varying environmental conditions (dissolved oxygen (DO) 2, 6 ppm; temperature 20, 30 °C; and salinity 3, 30 ppt) as well as to a single concentration of high energy water accommodated fraction (HEWAF) (∑PAHs 15 ppb). Whole larvae were sampled for RNA and transcriptional changes were quantified using RNA-Seq followed by qPCR for a set of target genes. Analysis revealed that exposure to oil and abiotic stressors impacts signaling pathways associated with cardiovascular function. Specifically, combined exposures appear to reduce development of the systemic vasculature as well as strongly impact the cardiac musculature through cardiomyocyte proliferation resulting in inhibited cardiac function and modulated blood pressure maintenance. Results of this study provide a holistic view of impacts of PAHs and common environmental stressors on the cardiac system in early life stage estuarine species. To our knowledge, this study is one of the first to simultaneously manipulate oil exposure with abiotic factors (DO, salinity, temperature) and the first to analyze cardiac transcriptional responses under these co-exposures.

Intraoperative hypotension and neurological outcomes.

Intraoperative hypotension (IOH) may render patients at a risk of cerebral hypoperfusion with decreasing cerebral blood flow (CBF), and lead to postoperative neurological injury. On the basis of the literature in recent years, this review attempts to refine the definition of IOH and evaluate its impact on neurological outcomes. Although both absolute and relative blood pressure (BP) thresholds, with or without a cumulative period, have been used in collective clinical studies, no definitive threshold of IOH has been established for neurological complications, including perioperative stroke, postoperative cognitive disorder and delirium. The CBF is jointly modulated by multiple pressure processes (i.e. cerebral pressure autoregulation) and nonpressure processes, including patient, surgical and anaesthesia-related confounding factors. The confounding factors and variability in cerebral pressure autoregulation might impede evaluating the effect of IOH on the neurological outcomes. Furthermore, the majority of the evidence presented in this review are cohort studies, which are weak in demonstrating a cause--effect relationship between IOH and neurological complications. The maintenance of target BP based on the monitoring of regional cerebral oxygen saturation (rScO2) or cerebral pressure autoregulation seems to be associated with the decreased incidence of postoperative neurological complications. Despite the lack of a known threshold value, IOH is a modifiable risk factor targeted to improve neurological outcomes. Ideal BP management is recommended in order to maintain target BP based on the monitoring of rScO2 or cerebral pressure autoregulation.

Optimal blood pressure for the prevention of hypertensive nephropathy in nondiabetic hypertensive patients in Taiwan.

Hypertension is a global health burden. However, clinical reference for the adequate management of blood pressure (BP) to prevent renal injury has yet to be established. Thus, this study aimed to investigate whether optimal control and maintenance of BP at<140/90, < 130/80, or<120/70mmHg could prevent hypertensive nephropathy in nondiabetic hypertensive patients. A single-center observational study of 351 nondiabetic hypertensive patients was conducted in Taiwan. The average age of the participants was 64.0years, and approximately 57.8% of the participants were men. Kidney function was assessed using estimated glomerular filtration rate (eGFR). The baseline eGFR was 83.8±19.8mL/min/1.73 m2 . All patients were followed up every 3months and underwent office BP measurement and blood sampling. Renal events were defined as>25% and>50% decline in eGFR. During an average follow-up period of 4.2±2.3years, a>25% and>50% decline in eGFR was noted in 49 and 11 patients, respectively. The Cox regression analysis revealed that a baseline BP≥140/90mmHg (hazard ratio [HR]: 1.965; 95% confidence interval [CI]: 1.099-3.514, P=0.023) and≥130/80mmHg (HR: 2.799; 95% CI: 1.286-6.004, P=0.009) increased the risk of>25% decline in eGFR. Moreover, a baseline BP≥140/90mmHg (HR: 8.120; 95% CI: 1.650-39.956, P=0.010) and follow-up BP≥140/90mmHg (HR: 6.402; 95% CI: 1.338-30.637, P=0.020) increased the risk of>50% decline in eGFR. In conclusion, a stringent baseline BP<130/80mmHg and a follow-up BP<140/90mmHg can be considered optimal cutoff values for clinical practice to prevent hypertensive nephropathy.

Paradoxical hypertension

A host of physiologic factors contribute to the maintenance of blood pressure. Of these, intravascular volume is perhaps the most important. Thus, when confronted with low or elevated blood pressure, clinicians rightly consider reduced or elevated intravascular volume, respectively. Volume expansion is usually a correct response to hypotension; similarly, volume expansion in the context of hypertension is counter intuitive. As with any clinical heuristic, however, there are exceptions to this association. Scattered reports of paradoxical hypertension in patients with hypovolemia have appeared over the years. Although the physiology underpinning these cases is not clear, central or hormonal mechanisms have been suggested. Although this scenario is obviously rare, it is important to recognize. Despite their apparent hypertension, such patients actually require volume expansion, and pharmacologic lowering of blood pressure could be hazardous. In the current volume of The Journal, DePiero et al report a large series of children with severe diabetic ketoacidosis (DKA), who at some point during their therapy exhibited significant hypertension. Although the mechanism is also not certain, there is good evidence that central factors play a role in these children; specifically, the children had more severe acidosis and evidence of CNS involvement. The management of severe DKA is a clinical challenge, in which a dizzying array of interconnected physiologic perturbations can be present. Before intervening to address hypertension in a child with DKA, it is incumbent on clinicians to be aware of this phenomenon and not worsen the situation with an ill-advised therapy. Article page 156 ▸ Hypertension during Diabetic Ketoacidosis in ChildrenThe Journal of PediatricsVol. 223PreviewTo characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension. Full-Text PDF

Integrative crosstalk between hypoxia and the cold: Old data and new opportunities.

What is the topic of this review? The aim was to examine the influence of hypoxia on thermoregulatory and cardiovascular control in the cold. What advances does it highlight? Exposure to hypoxia seems to alter both thermoregulatory and cardiovascular control, but these conclusions are based on limited data, and this review highlights the need for future research in this area. Cold stress and hypoxia have been the subject of research for decades; however, humans often encounter these stressors together, such as in the alpine environment. Therefore, this review summarizes previous data with respect to the influence of hypoxia on thermoregulatory and cardiovascular control in the cold and presents new ideas for the future. Altogether, little to no evidence is available on the integrative and adaptive mechanisms by which the human body regulates heat conservation, oxygen delivery and maintenance of blood pressure.

A comparative assessment of intravenous norepinephrine and mephentermine during spinal anaesthesia for caesarean section

Background: The present study compared intravenous norepinephrine and mephentermine for maintenance of blood pressure during spinal anaesthesia for caesarean section in known patients. Materials & Methods: The present study was conducted on 62 females planed for elective surgery. Patients were divided into 2 groups of 31 each. Group I received bolus intravenous norepinephrine 8µg and group II received mephentermine 6mg for the maintenance of intraoperative systolic blood pressure. HR, SBP and DBP were recorded at every 2 min interval till 20 min and thereafter at every 5 min interval till the completion of surgery. Complications were also recorded. Results: There was fall in SBP from baseline till 15 minutes in both groups then started increasing till 60 minutes. There was fall in DBP from baseline till 20 minutes in both groups then started increasing till 60 minutes. The difference was non- significant (P>0.05). There were 6 cases in group I and 7 in group II having nausea/vomiting, shivering was seen 5 in group I and 6 in group II, headache 4 in group I and 3 in group II and hypertension 3 in group I and 4 in group II. The difference was non- significant (P>0.05). Conclusion: Authors found that intravenous norepinephrine was better than mephentermine in maintaining blood pressure.

Influence of Angiotensin II on cell viability and apoptosis in rat renal proximal tubular epithelial cells in in vitro studies.

Introduction:Angiotensin II (Ang II) is multifunctional peptide that plays an important role in blood pressure regulation and maintenance electrolyte homeostasis. It shows biological effects by activating two main receptors: AT1 and AT2. The aim of the present work was to investigate the effect of Ang II on NRK-52E cells in in vitro studies. Furthermore, an attempt was made to determine the effectiveness of the AT1 and AT2 receptor blocker activity (respectively, losartan and PD123319).Methods:The study was carried out using adherent NRK-52E cell line. Immunofluorescence and Western Blot method were used to confirm the presence of AT1 and AT2 receptors in the cells. The SRB and MTT tests showed decrease in the viability of NRK-52E cells incubated with Ang II in comparison to the control (without Ang II).Results:The blockade of the AT1 receptor caused an increase in cell viability in comparison to cells incubated with Ang II only. The blockade of AT2 receptor also triggered statistically significant increase in cell viability in comparison with cells only exposed to Ang II. Combined administration of blockers for both receptors (losartan and PD123319) decreased Ang II cytotoxicity against NRK-52E cell line. The apoptosis was only observed in cells incubated with Ang II in comparison with control cells. However, simultaneous use of both blockers caused statistically significant decrease in apoptosis.Conclusions:The result of our study indicates that Ang II causes damaging effect on NRK-52E cells by directing them to programmed cell death. It seems that not only does the AT2 receptor itself play an important role in the induction of apoptosis, but also its interaction with AT1 receptor does as well.

Contribution of selected vasoactive systems to blood pressure regulation in two models of chronic kidney disease.

It is generally accepted that angiotensin II plays an important role in high blood pressure (BP) development in both 2-kidney-1-clip (2K1C) Goldblatt hypertension and in partial nephrectomy (NX) model of chronic kidney disease (CKD). The contribution of sympathetic nervous system and nitric oxide to BP control in these models is less clear. Partial nephrectomy or stenosis of the renal artery was performed in adult (10-week-old) male hypertensive heterozygous Ren-2 transgenic rats (TGR) and normotensive control Hannover Sprague Dawley (HanSD) rats and in Wistar rats. One and four weeks after the surgery, basal blood pressure (BP) and acute BP responses to the consecutive blockade of renin-angiotensin (RAS), sympathetic nervous (SNS), and nitric oxide (NO) systems were determined in conscious rats. Both surgical procedures increased plasma urea, a marker of renal damage; the effect being more pronounced following partial nephrectomy in hypertensive TGR than in normotensive HanSD rats with a substantially smaller effect in Wistar rats after renal artery stenosis. We demonstrated that the renin-angiotensin system does not play so fundamental role in blood pressure maintenance during hypertension development in either CKD model. By contrast, a more important role is exerted by the sympathetic nervous system, the activity of which is increased in hypertensive TGR-NX in the developmental phase of hypertension, while in HanSD-NX or Wistar-2K1C it is postponed to the established phase. The contribution of the vasoconstrictor systems (RAS and SNS) was increased following hypertension induction. The role of NO-dependent vasodilation was unchanged in 5/6 NX HanSD and in 2K1C Wistar rats, while it gradually decreased in 5/6 NX TGR rats.

Sympathetically mediated increases in cardiac output, not restraint of peripheral vasodilation, contribute to blood pressure maintenance during hyperinsulinemia.

Vasodilatory effects of insulin support the delivery of insulin and glucose to skeletal muscle. Concurrently, insulin exerts central effects that increase sympathetic nervous system activity (SNA), which is required for the acute maintenance of blood pressure (BP). Indeed, in a cohort of young healthy adults, herein we show that intravenous infusion of insulin increases muscle SNA while BP is maintained. We next tested the hypothesis that sympathoexcitation evoked by hyperinsulinemia restrains insulin-stimulated peripheral vasodilation and contributes to sustaining BP. To address this, a separate cohort of participants were subjected to 5-s pulses of neck suction (NS) to simulate carotid hypertension and elicit a reflex-mediated reduction in SNA. NS was conducted before and 60 min following intravenous infusion of insulin. Insulin infusion caused an increase in leg vascular conductance and cardiac output (CO; P < 0.050), with maintenance of BP (P = 0.540). As expected, following NS, decreases in BP were greater in the presence of hyperinsulinemia compared with control (P = 0.045). However, the effect of NS on leg vascular conductance did not differ between insulin and control conditions (P = 0.898). Instead, the greater decreases in BP following NS in the setting of insulin infusion paralleled with greater decreases in CO (P = 0.009). These findings support the idea that during hyperinsulinemia, SNA-mediated increase in CO, rather than restraint of leg vascular conductance, is the principal contributor to the maintenance of BP. Demonstration in isolated arteries that insulin suppresses α-adrenergic vasoconstriction suggests that the observed lack of restraint of leg vascular conductance may be attributed to sympatholytic actions of insulin.NEW & NOTEWORTHY We examined the role of sympathetic activation in restraining vasodilatory responses to hyperinsulinemia and sustaining blood pressure in healthy adults. Data are reported from two separate experimental protocols in humans and one experimental protocol in isolated arteries from mice. Contrary to our hypothesis, the present findings support the idea that during hyperinsulinemia, a sympathetically mediated increase in cardiac output, rather than restraint of peripheral vasodilation, is the principal contributor to the maintenance of systemic blood pressure.

The Effect of NaCl Concentrations on the NCC and ENaC Interaction

The kidneys play a key role in maintenance of blood pressure. Within the nephron, the smallest functional unit of the kidney, the sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are co‐expressed in the second part of the Distal Convoluted Tubule (DCT2). These sodium transport proteins are critically important for regulating blood pressure. Recent studies have established that these two proteins closely associate and are likely bound together. Here, we seek to examine if changes in sodium chloride concentration alter the interaction between NCC and ENaC. We hypothesize that the change in ion concentrations will significantly influence the interaction between NCC and ENaC. After incubating 4 dishes of mouse DCT (mDCT15) cells with different sodium chloride concentrations for 30 minutes, Co‐immunoprecipitation (CO‐IP) was conducted to examine changes in interactions between NCC and ENaC. We have confirmed expression of NCC, ENaC and phospho‐NCC under experimental conditions. Experiments to determine whether the interaction between NCC and ENaC is changed are ongoing. With our results, our knowledge of how different ion concentrations influence the interaction of NCC and ENaC will be enhanced and will be used to better understand how this mechanistic relationship can lead to the development of new therapies or the better utilization of existing therapies that will serve to improve the treatment of hypertension and salt sensitivity.Support or Funding InformationR25 DK 101390: Summer Undergraduate Program in Renal Research (SUPERR)T32: 5T32DK007656‐28 (Dr. Keyona King‐Medina)VA Merit Awards: I01BX002322‐01 (RSH) and I01BX000994 (HC) (Dr. Robert S. Hoover)

Effect of Acute Leg Heating On Circulating Endothelin‐1 in Aged Humans

There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. However, the neurovascular and humoral mechanisms mediating this hypotensive response remain unknown. The purpose of this study was to test the hypothesis that circulating concentrations of the potent vasoconstrictor substance endothelin‐1 would be attenuated concurrently with arterial blood pressure in aged adults following exposure to acute leg heating. Thirteen young adults (6 female; age 25 ± 4; height 172 ± 9 cm; weight 74 ± 15 kg; mean ± SD) and 10 aged adults (6 female; age 69 ± 5; height 166 ± 4 cm; weight 71 ± 11 kg; mean ± SD) were exposed to 45 minutes of acute leg heating. Subjects wore a tube‐lined water‐circulating garment that allowed leg skin temperature to be clamped at ~40°C during heating. Intestinal temperature was measured throughout via a telemetric pill. Systemic vascular conductance was calculated as cardiac output divided by mean arterial pressure and measured prior to heating (pre‐heat) and 30 min after (recovery). Plasma endothelin‐1 concentrations were quantified at pre‐heat and recovery time points via an enzyme‐linked immunosorbent assay. Leg heating increased body core temperature in young adults by 0.4 ± 0.1 °C and by 0.8 ± 0.2 °C in aged adults (both P &lt; 0.05 vs. 0 change). Body core temperature remained modestly elevated for both groups in recovery (both P &lt; 0.05 vs. pre‐heat). Mean arterial blood pressure was well maintained in young adults following leg heating (pre‐heat, 86 ± 6 mmHg vs. recovery, 88 ± 7 mmHg; P = 0.4), but was markedly reduced in aged adults (pre‐heat, 101 ± 7 mmHg vs. recovery, 94 ± 6 mmHg; P &lt; 0.05). Systemic vascular conductance in young adults did not differ from pre‐heat (69 ± 3 ml min−1 mmHg−1) to recovery (70 ± 3 ml min−1 mmHg−1; P = 0.7), whereas conductance was increased in aged adults (pre‐heat, 55 ± 6 ml min−1 mmHg−1 vs. recovery, 62 ± 5 ml min−1 mmHg−1; P = 0.07). Plasma endothelin‐1 concentrations did not differ between groups at the pre‐heat time point (young adults, 1.13 ± 0.13 pg ml−1 vs. aged adults, 1.44 ± 0.11 pg ml−1; P = 0.4). Plasma endothelin‐1 increased in recovery by 0.23 ± 0.42 pg ml−1 for young adults and by 0.20 ± 0.43 pg ml−1 for aged adults (both P &lt; 0.05 vs. 0 change). These data suggest that increased circulating endothelin‐1 may contribute to the maintenance of arterial blood pressure in young adults following exposure to acute leg heating by limiting systemic vascular conductance. Despite an increase in plasma endothelin‐1 in aged adults, arterial blood pressure was reduced in parallel with an increase in systemic vascular conductance which suggests that endothelin‐1‐mediated vasoconstriction may be altered following leg heating. Alternatively, increased endothelin‐1 may be preventing a further deleterious reduction in arterial blood pressure in aged adults by restraining the increase in systemic vascular conductance.Support or Funding InformationNational Institutes of Health (R01AG059314) and laboratory startup funds from the University of North Texas Health Science Center.

CHARACTERIZING THE ROLE OF THE DORSOMEDIAL HYPOTHALAMIC NUCLEUS IN THE CARDIOGENIC SYMPATHETIC AFFERENT REFLEX IN RATS

Myocardial ischemia causes the production and release of metabolites such as bradykinin (BK), which stimulates cardiac spinal sensory afferents causing chest pain and an increase in sympathetic activity. This sympathetic reflex, which increases heart rate and blood pressure, is referred to as the cardiogenic sympathetic afferent reflex (CSAR). During myocardial ischemia, this sympathetic reflex activity is important for the maintenance of blood pressure and perfusion of vital organs. However, the increased sympathetic activity may also be detrimental because it further increases the oxygen demand of the ischemic myocardium. While the brain stem nuclei, such as the nucleus tractus solitarius and rostral ventrolateral medulla have been shown to play an important role in the CSAR, the role of other supramedullary nuclei and the sources that generate sympathetic activity in the CSAR are still not clear. We have previously characterized the role of the paraventricular nucleus (PVN) of the hypothalamus in the CSAR and shown that acute chemical inhibition of the PVN attenuates the CSAR. However, we also have shown that the CSAR recovers in rats after chronic ibotenic acid lesion of the PVN suggesting that other supramedullary sites are involved. The dorsomedial hypothalamic nucleus (DMH) is another important hypothalamic site that plays an important role in cardiovascular sympathetic regulation. However, little is known regarding the role of the DMH in the CSAR. In this study, we tested the hypothesis that “inhibition of the DMH attenuates the CSAR in rats”. Renal sympathetic nerve activity (RSNA) and blood pressure were recorded in anesthetized rats during epicardial application of BK (10 μg/ml). Bilateral microinjection of muscimol, a GABAA agonist (0.5 nmol in 50 nl), was used to inhibit the DMH. Vehicle injection into the DMH had no significant effect (n=6, P &gt; 0.05) on blood pressure or RSNA. In vehicle‐injected rats, epicardial BK application significantly increased (P &lt; 0.05) RSNA to 204.4 ±35.08% of baseline and mean arterial pressure from 103.4 ±2.02 mmHg to 118.1 ±4.73 mmHg. In a sperate group of rats (n=8) muscimol injection into the DMH significantly (P &lt; 0.05) reduced basal blood pressure from 98.0 ±4.66 mmHg to 77.1 ±7.33 mmHg but had no significant effect (P &gt; 0.05) on baseline RSNA. In this group of rats, epicardial BK application significantly increased (P &lt; 0.05) RSNA to 193.9 ±28.00% of baseline and increased mean arterial pressure from 77.1 ±7.33 mmHg to 89.29 ±8.48 mmHg. Whereas muscimol injection into the DMH appears to attenuate the overall magnitude of the blood pressure response it had no effect on the RSNA response to epicardial bradykinin. These results suggest that in the presence of intact spinal and medullary circuits inhibition of DMH does not play an important role in the generation of sympathetic activity in the CSAR. Whereas inhibition of DMH does not appear to impair the CSAR there is good evidence to show that disinhibition of DMH increases basal vasomotor activity and augment reflex sympathetic responsiveness. Thus, our next objective is to determine if activation of DMH augments the CSAR and if so to determine the medullary connections of these DMH neurons.Support or Funding InformationNHLBI R15HL145645‐01

Peripheral Chemoreceptors Hemodynamic Responses During Simulated Hemorrhage Under Hypoxia Conditions

BackgroundMaintaining baroreflex sensitivity is integral to ensuring blood pressure maintenance and end‐organ perfusion during hemorrhage. This is especially true under conditions of hypoxemia, where decreased tolerance to central hypovolemia is commonly observed. Hypoxia activates peripheral chemoreceptors and reduces baroreceptor‐vascular resistance reflex sensitivity. However, a direct role for the peripheral chemoreceptors in the hemodynamic response to hemorrhage in hypoxia remains unclear.ObjectiveWe tested the hypothesis that attenuation of peripheral chemoreceptor activity (low‐dose dopamine; 1–2 μg/kg/min) during acute hypoxia would promote maintenance of mean arterial pressure, pulse pressure, and other hemodynamic markers [heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR)] during simulated hemorrhage.MethodsTen healthy men (35±3 years, BMI 25±1 kg/m2) participated in a randomized, double‐blind, placebo controlled study. Participants completed two experimental visits (saline and low‐dose dopamine) at which lower body negative pressure (LBNP) was conducted during hypoxia (SpO2 ~85%; PaO2 ~52 mmHg) delivered via a non‐rebreather mask. Ventilation [V̇ (turbine transducer)], arterial blood pressure (brachial artery catheter), HR (ECG), and central venous pressure (peripherally inserted central catheter) were measured continuously and SV, CO, and TPR were calculated. Following a 5‐min rest, participants underwent LBNP for 5‐min at 3 intervals (−15, −30, and −45 mmHg). Outcome values were analyzed and compared using a mixed linear model (SAS PROC MIXED) with a direct product AR(1) covariance structure using indicator variables for saline vs. dopamine. Data from the mixed linear model are reported as an estimated change per 15 mmHg of LBNP.ResultsDopamine had no effect on hypoxia PaO2, PaCO2, V̇ or respiratory rate (all P&gt;0.05) and this relationship persisted throughout all LBNP stages. The mixed linear model showed no effect of dopamine vs. saline on changes in: central venous pressure (−1.1±0.4 vs −1.3±0.3 mmHg, P=0.15), mean arterial pressure (−4.7±2.3 vs −5.3±1.4 mmHg, P=0.25), pulse pressure (−6.7±1.5 vs −8.3±1.4 mmHg, P=0.50), HR (7.8±1.5 vs 6.1±1.5 bpm, P=0.41), SV (−10.9±1.9 vs −11.6±3.3 mL, P=0.41), CO (−0.3±0.2 vs −0.4±0.4 L · min−1, P=0.31) or TPR (0.2±0.4 vs 0.7±0.6 mmHg · L · min−1P=0.27).DiscussionIntravenous infusion of low‐dose dopamine designed to attenuate peripheral chemoreflex activity during acute hypoxia did not alter the integrated hemodynamic response to simulated hemorrhage. Our data suggests that peripheral chemoreceptors have a limited role during hypoxic central hypovolemia. More research is needed to understand the sensitivity and cross‐talk between chemoreceptors and baroreceptors during hemorrhage.Support or Funding InformationFunding: W81XWH‐13‐2‐0038 (DOD), DK90541 (NIH), UL1 TR000135 (NIH).

Suppressed Prazosin‐Sensitive Cardiovascular Regulation in Central Nervous System During Early Sepsis

Sepsis is the main cause of morbidity and mortality in ICU worldwide, with a resulting mortality rate of around 30–40%. The cardiovascular system in sepsis and septic shock is depressed, resulting in fluid‐refractory hypotension and hyporeactivity to vasoactive agents. In blood pressure (BP) neural control, tonic sympathetic nerve activity (SNA) through norepinephrine (NE) release is crucial for BP maintenance. Septic shock has been associated with SNA exacerbation, resulting in pro‐inflammatory activity and increased release of catecholamines. We hypothesized that α1‐adrenergic receptors (α1AR) in central nervous system (CNS) are less sensitive for NE in early sepsis, thus affecting autonomic modulation of cardiovascular function. To evaluate this hypothesis, we assessed BP and heart rate (HR) of anesthetized male rats subjected to cecal ligation puncture (CLP) model of sepsis, which was performed 6 h before the experiments. Control experiments were conducted in naïve rats. These animals received NE, administered by intracerebroventricular (icv; 10 μg/5 μL) or intravenous (iv; 3, 10, and 30 nmol/Kg) routes. In additional experiments, prazosin (5 μg/5 μL, icv), a selective α1AR antagonist, was given 15 min before a second icv administration of NE. In our experiments CLP generated a mortality rate of 50% in 36 h. Systemic administration of NE dose‐dependently increased the mean arterial pressure (MAP) by 9.2 ± 3.3, 74.6 ± 6.6 and 83.5 ± 4.6 mmHg in control group (n = 5), and by 8.9 ± 1.8, 48.9 ± 7.2 (p &lt; 0.05), and 72.1 ± 11.7 mmHg in CLP animals (n = 4) for doses of 3, 10 and 30 nmol/Kg, respectively. When administered by iv route, NE‐increased BP was accompanied by increased HR, with no differences between control and CLP groups. Central microinjection of NE increased MAP and decreased HR of both control and CLP groups. However, responses were significantly depressed in septic animals. For instance, icv injection of NE increased MAP by 53.6 ± 3.3 mmHg in control (n = 5), and 18.9 ± 3.9 mmHg in CLP group (n = 8, p &lt; 0.0001). Prazosin microinjection generated a similar pattern of slight and transitory reduction in BP of both control and CLP animals. In control animals, pretreatment with prazosin reduced NE‐increased MAP to 20.3 ± 2.6 mmHg (n = 5, p &lt; 0.0001). However, icv administered NE maintained its pressor effect by 12.7 ± 1.4 mmHg in CLP subjected rats (n = 6) even after pretreatment with prazosin. Moreover, prazosin reversed the bradycardia induced by icv NE from −41 ± 12 bpm to 11 ± 21 bpm (n = 5, p &lt; 0.05) in control animals, but had no effects in HR of CLP group. Our results disclose that mechanisms involved in tonic SNA stimulation by NE are depressed in CLP‐subjected rats during early sepsis stages, even before the establishment of hyporesponsiveness in peripheral cardiovascular system. The lack of prazosin effects in septic animals reinforces the development of neural sympathetic α1AR dysfunction and abnormal autonomic modulation of cardiovascular function in sepsis.Support or Funding InformationFinancial Support: CNPq (Brazil), with a Ph.D. fellowship to Matsubara, N. K. This study was approved by the Animal Ethics Committee of UFSC (6327180718).

Risk Factors and Mechanisms of Postoperative Delirium After Intracranial Neurosurgical Procedures

Postoperative delirium (POD) is a condition characterized by cerebral dysfunction or failure and associated with high morbidity and mortality, prolonged intensive care unit and hospital stay, increased costs and long-term disability. The risk factors can be divided into three categories: preoperative, intraoperative, and postoperative. POD is underrecognized, underdiagnosed, and undertreated condition which can also lead to potentially life-threatening conditions. Prevention and treatment of POD include adequate perioperative pain control, maintenance of optimal blood pressure, water-electrolyte balance, hypo- and hyperglycemia, sleep hygiene. Despite POD has been extensively studied in various types of surgery, there is not enough evidence on POD in intracranial neurosurgery. Patients undergoing open craniotomy might be at particular risk because on top of the above-mentioned factors, they also might have a direct neurosurgical brain injury. Future research on the POD in neurosurgical patients after intracranial interventions is needed. A bibliographic search was performed in the MEDLINE and PubMed virtual library. The following descriptors were used: POD, neurosurgery, anesthesia, and POD, postoperative pain management and POD, water and electrolyte imbalance and POD, neurochemistry of POD. We included in this review original and review articles in the English language. Majority of non-neurosurgical patients have multiple risk factors for POD (preoperative, intraoperative, and postoperative); patients undergoing intracranial neurosurgery on top of that might have additional risks associated with neurosurgical pathology (brain tumor, cerebral hemorrhage, and severe traumatic injury) as well as neurosurgery-induced brain injury can also appear to be a contributing factor.

Risk Factors and Mechanisms of Postoperative Delirium After Intracranial Neurosurgical Procedures.

Postoperative delirium (POD) is a condition characterized by cerebral dysfunction or failure and associated with high morbidity and mortality, prolonged intensive care unit and hospital stay, increased costs and long-term disability. The risk factors can be divided into three categories: preoperative, intraoperative, and postoperative. POD is underrecognized, underdiagnosed, and undertreated condition which can lead to potentially life-threatening conditions. Prevention and treatment of POD include adequate perioperative pain control, maintenance of optimal blood pressure, water-electrolyte balance, hypoglycemia, hyperglycemia, sleep hygiene. Despite POD has been extensively studied in various types of surgery, there is not enough evidence on POD in intracranial neurosurgery. Patients undergoing open craniotomy might be at particular risk because on top of the above-mentioned factors, they also can have a direct neurosurgical brain injury. Future research on the POD in neurosurgical patients after intracranial interventions is needed. A bibliographic search was performed in the MEDLINE and PubMed virtual library. The following descriptors were used: POD, neurosurgery, anesthesia and POD, postoperative pain management and POD, water and electrolyte imbalance and POD, neurochemistry of POD. We included in this review original and review articles in the English language. Majority of non-neurosurgical patients have multiple risk factors for POD (preoperative, intraoperative, and postoperative); patients undergoing intracranial neurosurgery might have additional risks associated with neurosurgical pathology (brain tumor, cerebral hemorrhage, and severe traumatic brain injury) as well as neurosurgery-induced brain injury can also appear to be a contributing factor.