Increase In Mean Arterial Blood Pressure Research Articles

Evaluation of the effectiveness of phenylephrine in hypotension management in anesthesia for cardiac surgery using extracorporeal circulation

Background: Phenylephrine is a vasoconstrictor often chosen to raise blood pressure during induction of anesthesia. The study aimed to evaluate the effectiveness of phenylephrine in hypotension treatment in anesthesia for cardiac surgery using extracorporeal circulation. Methods: Descriptive study and evaluation of phenylephrine response in 40 cardiac surgery patients using extracorporeal circulation. Results: During the induction phase, phenylephrine increased mean arterial blood pressure the most at time T2 (mean mean ∆BP was 26.2 ± 6.9), then the trend gradually decreased and remained within normal limits (p<0.05). The mean number of intravenous injections of phenylephrine during the induction period was 1.1 ± 0.3 times, the mean dose of phenylephrine used was 0.9 ± 0.3 µg/kg. During the extracorporeal circulation phase, phenylephrine increased mean blood pressure early, and persistently, peaking at T5 (mean ∆HATB of 17.4 ± 3.6 mmHg). The mean number of intravenous injections of phenylephrine during the extracorporeal circulation phase was 1 time, the mean dose of phenylephrine used was 0.8 ± 0.3 µg/kg. Conclusion: Phenylephrine is used effectively with a small number of injections and a moderate dose when treating hypotension in anesthesia for cardiac surgery using extracorporeal circulation.

Abstract P307: What A Difference Hypertension Makes: The Adventitia Hands Off To PVAT For Extracellular Matrix Remodeling As Blood Pressure Rises In The High Fat Fed Dahl SS Rat.

Tunica media extracellular matrix remodeling is well understood to occur in response to elevation of blood pressure, considered a protective response. Remodeling of other tunicas is not well known. We have a long-term hypothesis that perivascular adipose tissue (PVAT) is responsive to hypertension and likely remodels to assist the blood vessel in protection against higher pressures. Here, we used the tunica adventitia and PVAT of the thoracic aorta in measuring extracellular matrix genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% fat) or high fat (HF; 60%) diet. These times were picked given relative increases mean arterial blood pressure (mm Hg) in the HF vs control (mmHg increase; 8 week: 14±5; 24 week = 35±8; p<0.05). The adventitia and PVAT were dissected apart, RNA isolated, cDNA synthesized and run on RT2 profiler array kits for ECM and Cell Adhesion genes. Differentially expressed genes (HF 2 fold > Con) were determined in Cytoscape, followed by identification of Hub Genes and construction of a Gene Regulatory network. At 8 weeks on HF diet, the adventitia had 29 upregulated genes (vs Con diet) while the PVAT had none. By contrast, at 24 weeks on diet, the HF adventitia had 3 upregulated genes while PVAT had 47. The top two genes elevated at 8 weeks in adventitia where thrombospondin 1 and collagen 8a1. Surprisingly, at 24 weeks, thrombospondin 1 was one of the three top genes upregulated in PVAT. The following transcription factors were identified as regulators of those genes upregulated in the 8 week adventitia: Adarb1, Fos, Gm10323, Smad3 and Mapk1 . By contrast, the key transcription factors for DEGS in the 24 week PVAT were Stat1, Bcl6B, Tsnax, Pax8, and Jun. Adarb1 (Adenosine deaminase RNA specific B1) was also determined to be a key regulator in PVAT remodeling. These data support that the PVAT responds biologically once blood pressure is elevated.

Effect of controlled blood pressure increase on cerebral blood flow velocity and oxygenation in patients with subarachnoid haemorrhage.

Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF - and thereby oxygen delivery - passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH before any signs of delayed cerebral ischaemia (DCI) occurred. The study was carried out within 5 days after ictus. Data were recorded at baseline and after 20 min of noradrenaline infusion to increase mean arterial blood pressure (MAP) by a maximum of 30 mmHg and to an absolute level of no more than 130 mmHg. The primary outcome was the difference in middle cerebral artery blood flow velocity (MCAv) measured by transcranial Doppler (TCD), while differences in intracranial pressure (ICP), brain tissue oxygen tension (PbtO2 ), and microdialysis markers of cerebral oxidative metabolism and cell injury were assessed as exploratory outcomes. Data were analysed using Wilcoxon signed-rank test with correction for multiplicity for the exploratory outcomes using the Benjamini-Hochberg correction. Thirty-six participants underwent the intervention 4 (median, IQR: 3-4.75) days after ictus. MAP was increased from 82 (IQR: 76-85) to 95 (IQR: 88-98) mmHg (p-value: <.001). MCAv remained stable (baseline, median 57, IQR: 46-70 cm/s; controlled blood pressure increase, median: 55, IQR: 48-71 cm/s; p-value: .054), whereas PbtO2 increased significantly (baseline, median: 24, 95%CI: 19-31 mmHg; controlled blood pressure increase, median: 27, 95%CI: 24-33 mmHg; p-value <.001). The remaining exploratory outcomes were unchanged. In this study of patients with SAH, MCAv was not significantly affected by a brief course of controlled blood pressure increase; despite this, PbtO2 increased. This suggests that autoregulation might not be impaired in these patients or other mechanisms could mediate the increase in brain oxygenation. Alternatively, a CBF increase did occur that, in turn, increased cerebral oxygenation, but was not detected by TCD. clinicaltrials.gov (NCT03987139; 14 June 2019).

A mathematical model of vascular and hemodynamics changes in early and late forms of preeclampsia.

Preeclampsia-eclampsia syndrome is a leading cause of maternal mortality. The precise etiology of preeclampsia is still not well-defined and different forms exist, including early and late forms or preeclampsia, which may arise via distinctly different mechanisms. Low-dose aspirin administered at the end of the first trimester in women identified as high risk has been shown to reduce the incidence of early, but not late, preeclampsia; however, current risk factors show only fair predictive capability. There is a pressing need to develop accurate descriptions for the different forms of preeclampsia. This paper presents 1D fluid, solid, growth, and remodeling models for pregnancies complicated with early and late forms of preeclampsia. Simulations affirm a broad set of literature results that early forms of preeclampsia are characterized by elevated uterine artery pulsatility index (UA-PI) and total peripheral resistance (TPR) and lower cardiac output (CO), with modestly increased mean arterial blood pressure (MAP) in the first half of pregnancy, with elevation of TPR and MAP beginning at 20 weeks. Conversely, late forms of preeclampsia are characterized by only slightly elevated UA-PI and normal pre-term TPR, and slightly elevated MAP and CO throughout pregnancy, with increased TPR and MAP beginning after 34 weeks. Results suggest that preexisting arterial stiffness may be elevated in women that develop both early forms and late forms of preeclampsia; however, data that verify these results are lacking in the literature. Pulse wave velocity increases in early- and late-preeclampsia, coincident with increases in blood pressure; however, these increases are mainly due to the strain-stiffening response of larger arteries, rather than arterial remodeling-derived changes in material properties. These simulations affirm that early forms of preeclampsia may be associated with abnormal placentation, whereas late forms may be more closely associated with preexisting maternal cardiovascular factors; simulations also highlight several critical gaps in available data.

CTH/MPST double ablation results in enhanced vasorelaxation and reduced blood pressure via upregulation of the eNOS/sGC pathway.

Hydrogen sulfide (H2S), a gasotransmitter with protective effects in the cardiovascular system, is endogenously generated by three main enzymatic pathways: cystathionine gamma lyase (CTH), cystathionine beta synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST) enzymes. CTH and MPST are the predominant sources of H2S in the heart and blood vessels, exhibiting distinct effects in the cardiovascular system. To better understand the impact of H2S in cardiovascular homeostasis, we generated a double Cth/Mpst knockout (Cth/Mpst -/- ) mouse and characterized its cardiovascular phenotype. CTH/MPST-deficient mice were viable, fertile and exhibited no gross abnormalities. Lack of both CTH and MPST did not affect the levels of CBS and H2S-degrading enzymes in the heart and the aorta. Cth/Mpst -/- mice also exhibited reduced systolic, diastolic and mean arterial blood pressure, and presented normal left ventricular structure and fraction. Aortic ring relaxation in response to exogenously applied H2S was similar between the two genotypes. Interestingly, an enhanced endothelium-dependent relaxation to acetylcholine was observed in mice in which both enzymes were deleted. This paradoxical change was associated with upregulated levels of endothelial nitric oxide synthase (eNOS) and soluble guanylate cyclase (sGC) α1 and β1 subunits and increased NO-donor-induced vasorelaxation. Administration of a NOS-inhibitor, increased mean arterial blood pressure to a similar extent in wild-type and Cth/Mpst -/- mice. We conclude that chronic elimination of the two major H2S sources in the cardiovascular system, leads to an adaptive upregulation of eNOS/sGC signaling, revealing novel ways through which H2S affects the NO/cGMP pathway.

The Hypertensive Effect of Amphotericin B-Containing Liposomes (Abelcet) in Mice: Dissecting the Roles of C3a and C5a Anaphylatoxins, Macrophages and Thromboxane.

Liposomal amphotericin B (Abelcet) can cause infusion (anaphylactoid) reactions in patients whose mechanism is poorly understood. Here, we used mice to investigate the role of complement (C) receptors and the cellular sources of vasoactive mediators in these reactions. Anesthetized male NMRI and thromboxane prostanoid receptor (TP) or cyclooxygenase-1 (COX-1)-deficient and wild type C57Bl6/N mice were intravenously injected with Abelcet at 30 mg/kg. Mean arterial blood pressure (MABP) and heart rate (HR) were measured. In untreated mice, Abelcet caused a short (15 min) but large (30%) increase in MABP. C depletion with cobra venom factor (CVF) and inhibition of C5a receptors with DF2593A considerably prolonged, while C3aR inhibition with SB290157 significantly decreased the hypertensive effect. Likewise, the hypertensive response was abolished in COX-1- and TP-deficient mice. CVF caused a late hypertension in TP-deficient mice. Both macrophage depletion with liposomal clodronate and blockade of platelet GPIIb/IIIa receptors with eptifibatide prolonged the hypertensive effect. The early phase of the hypertensive effect is COX-1- and TP-receptor-dependent, partly mediated by C3aR. In contrast, the late phase is under the control of vasoactive mediators released from platelets and macrophages subsequent to complement activation and C5a binding to its receptor.

Low Dosing Norepinephrine Effects on Cerebral Oxygenation and Perfusion During Pediatric Shock.

BackgroundCerebral hypoperfusion and impaired oxygen delivery during pediatric critical illness may result in acute neurologic injury with subsequent long-term effects on neurodevelopmental outcome. Yet, the impact of norepinephrine on cerebral hemodynamics is unknown in children with shock. We aimed to describe the norepinephrine effects on cerebral perfusion and oxygenation during pediatric shock.Patients and MethodsWe conducted an observational multicentre prospective study in 3 French pediatric intensive care units. Children <18 years of age excluding traumatic brain injury were included in the study if they need norepinephrine for shock. Systemic and cerebral hemodynamics were compared between the time of initiation of norepinephrine (T0), and the steady-state (Tss). Cardiac output (CO) was measured using ultrasound. Cerebral perfusion was assessed on middle cerebral arteries (MCA) using transcranial doppler ultrasound. Cerebral tissue oxygen saturation (rScO2) was recorded using near infrared spectroscopy, and we calculated cerebral fractional tissue oxygen extraction (cFTOE = SpO2-rScO2/SpO2).Main ResultsFourteen children (median [IQR] age of 3.5[1; 13.5] years) were included. Norepinephrine at 0.2[0.1; 0.32] μg/kg/min significantly increased mean arterial blood pressure (61[56; 73] mmHg at Tss vs. 49[42;54] mmHg at T0, p=10−3) without change of CO. MCA velocities, pulsatility index, rScO2, and cFTOE did not significantly change between T0 and Tss. Some individuals observed variations in estimated CBF, which slightly improved in 7 patients, remained unchanged in 5, and was impaired in 2. No patient experienced significant variations of rScO2.ConclusionsLow-dosing norepinephrine, despite a homogeneous and significant increase in arterial blood pressure, had little effects on cerebral perfusion and oxygenation during pediatric shock. This reinforces the need for personalized tailored therapies in this population.Trial RegistrationClinicaltrials.gov, NCT 03731104. Registered 6 November, 2018. https://clinicaltrials.gov/ct2/show/NCT03731104.

Fluid bolus administration in children, who responds and how? A systematic review and meta-analysis.

Fluid boluses are frequently utilized in children. Despite their frequency of use, there is little objective data regarding the utility of fluid boluses, who they benefit the most, and what the effects are. This study aimed to conduct pooled analyses to identify those who may be more likely to respond to fluid boluses as well as characterize clinical changes associated with fluid boluses. A systematic review of the literature and meta-analysis was conducted to identify pediatric studies investigating the response to fluid boluses and clinical changes associated with fluid boluses. A total of 15 studies with 637 patients were included in the final analyses with a mean age of 650 days ± 821.01 (95% CI 586 to 714) and a mean weight of 10.5kg ± 7.19 (95% CI 9.94 to 11.1). The mean bolus volume was 12.14 ml/kg ± 4.09 (95% CI 11.8 to 12.5) given over a mean of 19.55 min ± 10.16 (95% CI 18.8 to 20.3). The following baseline characteristics were associated with increased likelihood of response [represented in mean difference (95% CI)]: greater age [207.2 days (140.8 to 273.2)], lower cardiac index [-0.5ml/min/m2 (-0.9 to -0.3)], and lower stroke volume [-5.1ml/m2 (-7.9 to -2.3)]. The following clinical parameters significantly changed after a fluid bolus: decreased HR [-5.6bpm (-9.8 to -1.3)], increased systolic blood pressure [7.7 mmHg (1.0 to 14.4)], increased mean arterial blood pressure [5.5 mmHg (3.1 to 7.8)], increased cardiac index [0.3ml/min/m2 (0.1 to 0.6)], increased stroke volume [4.3ml/m2 (3.5 to 5.2)], increased central venous pressure [2.2 mmHg (1.1 to 3.3)], and increased systemic vascular resistance [2.1 woods units/m2 (0.1 to 4.2)]. Fluid blouses increase arterial blood pressure or cardiac output by 10% in approximately 56% of pediatric patients. Fluid blouses lead to significant decrease in HR and significant increases in cardiac output, stroke volume, and systemic vascular resistance. Limited published data are available on the effects of fluid blouses on systemic oxygen delivery.

Diet-induced hypertension in rats is associated with increased renal vasoconstrictor response to angiotensin II after imitated endothelial dysfunction.

The mechanisms behind development of diet-induced hypertension remain unclear. The kidneys play a paramount role in blood volume and blood pressure regulation. Increases in renal vascular resistance lead to increased mean arterial blood pressure (MAP) due to reduced glomerular filtration rate and Na+ excretion. Renal vascular resistance may be increased by several factors, e.g. sympathetic output, increased activity in the renin-angiotensin system or endothelial dysfunction. We examined if a 14-week diet rich in fat, fructose or both led to increased renal vascular resistance and blood pressure. Sixty male Sprague-Dawley rats received normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat + Fruc) for 14weeks from age 4-weeks. Measurements included body weight (BW), telemetry blood pressures, renal blood flow in anesthetized rats, plasma concentrations of atrial natriuretic peptide and glucose, as well as vessel myography in renal segmental arteries. Body weight increased in both groups receiving high fat, whereas MAP increased only in the High Fat + Fruc group. Renal blood flow did not differ between groups showing that renal vascular resistance was not increased by the diets. After inhibiting nitric oxide and prostacyclin production, renal blood flow reductions to Angiotensin II infusions were exaggerated in the groups receiving high fructose. MAP correlated positively with heart rate in all rats tested. Our data suggest that diet-induced hypertension is not caused by an increase in renal vascular resistance. The pathophysiological mechanisms may include altered signaling in the renin-angiotensin system and increases in central sympathetic output in combination with reduced baroreceptor sensitivity leading to increased renal vasoconstrictor responses.

Deletion of the Transient Receptor Vanilloid‐1 (TRPV1) Channel in Rats Attenuates 2‐Kidney‐1‐Clip Hypertension

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel Trpv1‐/‐ rat using CRISPR/Cas9 and deletion of exon 3. Male and female Trpv1‐/‐ and wild‐type littermates (8‐12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male Trpv1‐/‐ and wild‐type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7‐9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male Trpv1‐/‐ versus wild‐type rats (125±8 vs 155±2 mmHg, respectively: P&lt;0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male Trpv1‐/‐ versus wild‐type rats (‐53±4 vs ‐86±3 mmHg, respectively; P&lt;0.001). On the other hand, female Trpv1‐/‐ and wild‐type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6‐9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female Trpv1‐/‐ versus wild‐type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female Trpv1‐/‐ versus wild‐type rats (‐64±7 vs ‐65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that Trpv1‐/‐ channels contribute to the established phase of renovascular hypertension in male rats.

Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats.

Aims: Long-term salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular superoxide dismutase (Ec-SOD) is a unique antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive reactive oxygen species (ROS). However, the underlying mechanism of Ec-SOD in the PVN remains unclear. Methods: Sprague–Dawley rats (150–200 g) were fed either a high salt diet (8% NaCl, HS) or normal salt diet (0.9% NaCl, NS) for 6 weeks. Each group of rats was administered with bilateral PVN microinjection of AAV-Ec-SOD (Ec-SOD overexpression) or AAV-Ctrl for the next 6 weeks. Results: High salt intake not only increased mean arterial blood pressure (MAP) and the plasma noradrenaline (NE) but also elevated the NAD(P)H oxidase activity, the NAD(P)H oxidase components (NOX2 and NOX4) expression, and ROS production in the PVN. Meanwhile, the NOD-like receptor protein 3 (NLRP3)–dependent inflammatory proteins (ASC, pro-cas-1, IL-β, CXCR, CCL2) expression and the tyrosine hydroxylase (TH) expression in the PVN with high salt diet were higher, but the GSH level, Ec-SOD activity, GAD67 expression, and GABA level were lower than the NS group. Bilateral PVN microinjection of AAV-Ec-SOD decreased MAP and the plasma NE, reduced NAD(P)H oxidase activity, the NOX2 and NOX4 expression, and ROS production, attenuated NLRP3-dependent inflammatory expression and TH, but increased GSH level, Ec-SOD activity, GAD67 expression, and GABA level in the PVN compared with the high salt group. Conclusion: Excessive salt intake not only activates oxidative stress but also induces the NLRP3-depensent inflammation and breaks the balance between inhibitory and excitability neurotransmitters in the PVN. Ec-SOD, as an essential anti-oxidative enzyme, eliminates the ROS in the PVN and decreases the blood pressure, probably through inhibiting the NLRP3-dependent inflammation and improving the excitatory neurotransmitter release in the PVN in the salt-induced hypertension.

2-Methoxyestradiol Ameliorates Angiotensin II-Induced Hypertension by Inhibiting Cytosolic Phospholipase A2α Activity in Female Mice.

[Figure: see text].

Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P&lt;0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P&lt;0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

P66Shc-mediated hydrogen peroxide production impairs nephrogenesis causing reduction of number of glomeruli

AimsAdaptor protein p66Shc, encoded by Shc1 gene, contributes to the pathogenesis of oxidative stress-related diseases. p66Shc ability to promote oxidative stress-related diseases requires phosphorylation of serine 36 residue (Ser36) and depends on translocation of p66Shc to the mitochondria. We tested the hypothesis that abnormal p66Shc-mediated reactive oxygen species (ROS) production could be critically involved in nephrons development during nephrogenesis. Main methodsWe have generated unique mutant rats (termed p66Shc-Del), which express endogenous p66Shc with a 9-amino acid deletion, and lack regulatory Ser36. H2O2 renal production was measured by enzymatic microelectrode biosensors. Nephron numbers in 3–5 weeks old p66Shc-Del rats were quantified using the acid maceration method. Key findingsp66Shc-Del rats, as wild type salt sensitive rats, display increased mean arterial blood pressure following chronic exposure to a high salt diet. In contrast to wild type rats, p66Shc-Del rats display increased H2O2 renal production and are characterized by a reduction in renal function. The number of glomeruli is significantly reduced in adult p66Shc-Del rats. SignificanceSince low nephron number is an established risk factor for kidney disease and hypertension in humans and rodents, our data suggest that H2O2 renal production, caused by irregular signaling of p66Shc, could be critical in regulating nephrogenesis and that abnormal p66Shc signaling negatively impacts kidney development and renal function by increasing susceptibility to diabetic nephropathy and hypertension-induced nephropathy.

Intravenous vasopressin leads to greater haemodynamic and respiratory responses in spontaneously hypertensive SHR rats than in normotensive controls

Introduction Increased activity of vasopressinergic system has been implicated in pathophysiology of essential hypertension. Intravenous or central administrations of vasopressin (AVP) were shown to affect not only hemodynamics, but also ventilatory function in rats. Receptors for AVP have been found in the brainstem structures involved in the control of breathing and in the carotid bodies. We hypothesized that given the involvement of AVP in essential hypertension and control of ventilation, AVP may differently affect hemodynamics and ventilation in spontaneously hypertensive (SHR) and in normotensive Wistar-Kyoto (WKY) rats. Purpose In the study we investigated the effects of intravenously administered AVP on hemodynamic and respiratory parameters under hypertensive and normotensive conditions. Methods The study was performed in urethane-anesthetizes adult male normotensive WKY (n=7) and hypertensive SHR rats (n=7). We implanted catheters into the femoral artery and femoral vein for recording mean arterial blood pressure (MABP) and for intravenous infusions, respectively. Additionally, we recorded minute ventilation (MV), respiratory rate (RR) and end-tidal CO2 (ET-CO2) via tracheal tube. We also placed subcutaneous ECG electrodes for heart rate (HR) monitoring. After obtaining baseline parameters, the arterial chemoreflex was triggered pharmacologically with intravenous (i.v.) administration of potassium cyanide (KCN) (30 microg/100 microL). After stabilization of hemodynamic and respiratory parameters, rats received i.v. administration of AVP (10ng/100μL) and recordings continued. Results SHR rats had significantly higher resting MABP, HR and MV than WKY controls. Both increases in MABP and MV and decrease in ET-CO2 were significantly greater in SHR than in WKY rats in response to pharmacologically triggered peripheral chemoreflex. One minute after administration of KCN, MV remained elevated above baseline and ET-CO2 was below baseline in SHR rats, whereas all respiratory parameters were normal in WKY rats. In SHR rats administration of AVP resulted in significantly greater increase in MABP than in WKY controls and was accompanied by reduction in MV and RR but no changes in HR. In WKY rats AVP resulted in smaller MABP increase accompanied by insignificant changes in respiratory parameters or HR. Conclusions Our findings confirm increased sensitivity of arterial chemoreflex in urethane-anesthetized SHR rats and suggest that AVP-dependent pressor and respiratory responses are enhanced in spontaneously hypertensive rats.

Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death. Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Ameliorative effect of apelin-13 against renal complications in L-NAME-induced preeclampsia in rats.

Pre-eclampsia (PE) accompanying acute liver and kidney injury has remained a master cause of both fetal and maternal mortality and morbidity. Vasoactive mediators, oxidative stress and inflammatory imbalanceshave an important role in PE pathogenesis. Apelin is an adipokine that improves endothelial dysfunction; has anti-inflammatory and antioxidant effects; moreover, its level reduced during PE. This study aimed to explore the effects of apelin-13 administration on preeclampsia-associated renal dysfunction and proteinuria. Thirty-three pregnant female rats were divided into three groups; group: 1 (normal pregnant rats), group: 2 (preeclamptic rats); where rats were injected subcutaneously with 75 mg L-NAME/ kg body weight/day beginning from 9th to 20th day of pregnancy andgroup 3 (apelin-13 treated preeclamptic rats); In which L-NAME-induced preeclamptic rats were subcutaneously injected with 6 × 10−8 mol apelin-13/kg body weight/twice daily starting from 6th to 20th day of pregnancy. In all groups, mean arterial blood pressure, total urine protein, serum urea, creatinine, nitric oxide (NO), endothelin-1 (ET-1), interleukin–6 (IL-6) and malondialdhyde (MDA) were measured. Histopathological examination of kidney tissues was also done. preeclamptic rats showed significantly increased mean arterial blood pressure, total urine proteins, serum urea, creatinine, ET-1, IL-6, and MDA, but revealed a significantly decreased serum NO level. On the other hand, apelin treatment significantly improved these parameters together with amelioration of kidney histoarchitecture in the treated group. In conclusion, apelin may be a potentially curative candidate for prohibiting kidney damage and have a therapeutic benefit in PE rat models.

The impact of the last ten minutes of surgery on hemorrhagic complications after laparoscopic sleeve gastrectomy. Case-control study.

IntroductionHemorrhagic complications after laparoscopic sleeve gastrectomy (LSG) are among the most common adverse events. The last 10 min of LSG are essential in terms of hemostasis.AimTo assess the blood pressure profile in the last 10 min of LSG in patients who experienced hemorrhagic complications after laparoscopic sleeve gastrectomy.Material and methodsWe performed a retrospective case-control study. The medical records of 867 patients who underwent primary LSG were analyzed. Cases were defined as patients who required surgical revision due to hemorrhagic complications within 72 h. Controls were matched (1 : 1) with cases by age, body mass index, gender, staple line reinforcement, comorbidities and surgeon’s experience. Comparison of the last three intraoperative blood pressure measurements at the end of surgery was made.ResultsThe bleeding rate was 3.0%. A total of 24 subjects (12 matched pairs) were included in the study. Cases had statistically significant increased mean arterial blood pressure (mm Hg) 5 min before the end of surgery (87.8 ±11.9 vs. 79.4 ±8.8 mm Hg, p = 0.049) and at the end of surgery (89.2 ±11.7 vs. 77.5 ±11.8 mm Hg, p = 0.011). Higher diastolic blood pressure measurements were observed 5 min before the end (72.1 ±10.7 vs. 62.8 ±8.1 mm Hg, p = 0.023) and at the end of surgery (74.2 ±10.0 vs. 60.8 ±11.2 mm Hg, p = 0.004).ConclusionsCompared with closely matched control subjects, patients with HC after LSG have increased mean arterial pressure in the last 5 min of surgery. This phenomenon has not been reported in the literature before.

Cerebrovascular Impedance During Hemodynamic Change in Rabbits: A Pilot Study.

Cerebrovascular impedance describes the relationship between pulsatile changes in arterial blood pressure (ABP) and cerebral blood flow (CBF). It is commonly defined by modulus and phase shift derived from Fourier spectra of ABP and CBF velocity (CBFV) signals under mostly steady-state conditions. The aim of this work was to assess heartbeat-to-heartbeat cerebrovascular impedance at heart rate frequency during controlled changes in mean ABP and intracranial pressure (ICP). Recordings of ABP in the femoral artery, transcranial Doppler CBFV in the basilar artery, and subarachnoid ICP were obtained from anesthetized rabbits with induced arterial hypotension (n=8 rabbits), arterial hypertension (n=5), or intracranial hypertension (n=7). Modulus of cerebrovascular impedance (|Z|) was estimated from amplitudes of ABP and CBFV. Phase shift of cerebrovascular impedance (PS) was estimated from time-frequency (TF) representations of phase shift between ABP and CBFV overlaid with a time-variant mask based on the fundamental frequency of ABP. Both |Z| and PS increased with increasing mean ABP. |Z| decreased with increasing mean ICP, but no change was observed in PS. The combined beat-to-beat and TF approach allows for the estimation of cerebrovascular impedance during transient hemodynamic changes. |Z| and PS follow the pattern of changes in CPP.

Interaction of Orexin A and Vasopressin in the Brain Plays a Role in Blood Pressure Regulation in WKY and SHR Rats.

BackgroundOrexin A (OXA) and vasopressin (AVP) exert a central hypertensive effect due to an increase in sympathetic nerve activity. To date, little is known about the interaction of these 2 neuropeptides in the central regulation of blood pressure. The present study compared the consequences of infusion into the left cerebral ventricle (ICV) of OXA on mean arterial blood pressure (MABP) in normotensive (WKY) and spontaneously hypertensive (SHR) rats, and explored whether the central pressor action of OXA in these 2 strains depends on activation of brain AVP V1a receptors (V1aR).Material/MethodsTen groups of experiments were performed on 12-week-old WKY and SHR rats implanted with ICV cannulas for infusion of OXA (3 nmol) and V1aR antagonist (V1aRANT, 500 ng), administered separately and together. Levels of V1aR and OXR in the medulla oblongata of WKY and SHR rats were compared in separate series.ResultsWe found that: 1) OXA significantly increased MABP only in WKY rats, 2) V1aRANT prevented an increase in MABP induced by OXA in WKY rats and decreased MABP in SHR rats, 3) OXA abolished the hypotensive action of V1aRANT in SHR rats, and 4) SHR rats had significantly higher levels of OX1R and V1aR proteins and OX1R mRNA in the brain medulla.ConclusionsThe present study shows that OXA and AVP can interact in the brain to affect blood pressure regulation, and that this interaction differs in normotension and hypertension.