Reduction In Systemic Blood Pressure Research Articles

Flow restoration during mechanical thrombectomy for large vessel occlusion is associated with an immediate reduction of systemic blood pressure.

Managing blood pressure in patients with large vessel occlusion affects infarct size and clinical outcomes. We examined how restoring blood flow impacts systemic blood pressure during mechanical thrombectomy. Patients with large vessel occlusion in the anterior circulation undergoing mechanical thrombectomy between June 2016 and January 2018 were screened. We included those treated under local anesthesia or conscious sedation and analyzed standardized anesthesia protocols to assess systolic and diastolic blood pressure levels throughout the procedure. The primary outcome was the change of blood pressure, compared 5 min before versus 5 min after the last recanalization attempt. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction score ⩾ 2b. Of 134 patients, 117 (87%) achieved successful angiographic reperfusion, showing a notable systolic blood pressure drop 5 min after flow restoration (10.2 ± 14.6 vs 3.24 ± 8.65 mm Hg, p = 0.009). Successful angiographic reperfusion was a significant predictor for this decrease in multivariable logistic regression: OR = 1.34 (95% CI: 1.03-1.73, p = 0.0299). Among 66 patients not given circulation-affecting meds, a significant systolic pressure reduction was also observed (155 ± 17 mm Hg to 148 ± 17 mm Hg ; p < 0.001). No diastolic pressure changes were significant. Flow restoration was associated with an immediate reduction of systolic blood pressure values in patients undergoing mechanical recanalization under local anesthesia or conscious sedation. This suggests a complex interplay between endovascular stroke therapy and cardiovascular hemodynamics.

Hydrogen Inhalation Reduces Lung Inflammation and Blood Pressure in the Experimental Model of Pulmonary Hypertension in Rats.

Hydrogen has been shown to exhibit selective antioxidant properties against hydroxyl radicals, and exerts antioxidant and anti-inflammatory effects. The monocrotaline-induced model of pulmonary hypertension is suitable for studying substances with antioxidant activity because oxidative stress is induced by monocrotaline. On day 1, male Wistar rats were subcutaneously injected with a water-alcohol solution of monocrotaline or a control with an only water-alcohol solution. One group of monocrotaline-injected animals was placed in a plastic box that was constantly ventilated with atmospheric air containing 4% of molecular hydrogen, and the two groups of rats, injected with monocrotaline or vehicle, were placed in boxes ventilated with atmospheric air. After 21 days, hemodynamic parameters were measured under urethane narcosis. The results showed that, although hydrogen inhalation had no effect on the main markers of pulmonary hypertension induced by monocrotaline injection, there was a reduction in systemic blood pressure due to its systolic component, and a decrease in TGF-β expression, as well as a reduction in tryptase-containing mast cells.

EFFICACY OF INTRAVENOUS DEXMEDETOMIDINE VERSUS MAGNESIUM SULPHATE FOR CONTROLLED HYPOTENSION IN FUNCTIONAL ENDOSCOPIC SINUS SURGERY: A RANDOMIZED DOUBLEBLIND STUDY.

Background &amp; Aim: Controlled hypotension is an anaesthestic technique in which there is deliberate reduction of systemic blood pressure during general anaesthesia. The aim of our study was to compare the efcacy of intravenous dexmedetomidine and magnesium sulphate for controlled hypotension in functional endoscopic sinus surgery. A randomized, Method: prospective, and double-blind study was carried out, which included 92 patients of either sex of ASA grade I &amp; II who underwent elective FESS. Patients were randomly assigned to two groups: Group D, patients received dexmedetomidine 1 µg/kg infused over 10 minutes before induction of anesthesia, followed by continuous infusion of 0.4-0.8μg/kg/hr. Group M, Patients received intravenous MgSO4 40 mg/kg infused over 10 minutes before induction of anesthesia, followed by continuous infusion of 10 to 15 mg/Kg/hr. Results: There was no signicant difference in MAP and HR between both the groups. Average category scale was lower (p&lt;0.001) and surgeon's satisfaction score was higher (p&lt;0.001) in group D when its compared group M. Blood loss was less in group D than group M. Incidence of Bradycardia &amp; Hypotension in group D was 15.22% &amp; 36.96% while in group M was 2.17% &amp; 13.04%. The difference in incidence of Bradycardia &amp; Hypotension in both the groups was statistically signicant. Both dexmedetomidine and MgSO4 provide satisfac Conclusion: tory controlled hypotension in FESS. However, dexmedetomidine is found to be more effective in terms of good surgical eld, less blood loss, better surgeon satisfaction score.

Analysis of four non-drug measures in the treatment of arterial hypertension: a literature review

Systemic arterial hypertension (SAH) can be conceptualized as a chronic degenerative disease of multifactorial nature, in most cases asymptomatic, that fundamentally compromises the balance of the vasodilator and vasoconstrictor systems that maintain the vasomotor tone, leading to a reduction in the lumen of the vessels and damage to the organs they irrigate. In practice, SAH is characterized by an increase in blood pressure levels above what is recommended for a given age group. The objective was to analyze four non-drug measures in the treatment of systemic arterial hypertension which are: dietary control, alcohol control, tobacco control, and physical exercise. This study was based on a bibliographic review in databases and considered systematic review, case report, clinical trial, and included publications in Portuguese and English. SAH is a highly prevalent disease with a high negative social impact. Early identification of hypertensive patients and effective treatment are of great clinical importance. Identification of possibly reversible causes is a fundamental part in the clinical management of these patients. It was concluded that nutritional therapy and lifestyle changes associated with pharmacological therapy can promote benefits in the reduction of systemic blood pressure. Thus, it is of utmost importance to stimulate and make the population aware of the need for adherence to pharmacological antihypertensive treatment along with non-drug therapy, thus contributing to the reduction of morbidity, mortality and health care costs.

Mechanism of canagliflozin-induced vasodilation in resistance mesenteric arteries and the regulation of systemic blood pressure

Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is reported to produce beneficial cardiovascular effects including a reduction in arterial contractility, and blood pressure. However, whether canagliflozin could directly relax resistance mesenteric arteries, underlying molecular mechanism and its role in regulating systemic blood pressure remain unclear. Here, we investigated the mechanism of regulation of small mesenteric artery contractility and its relevance for blood pressure regulation. Our pressure myography data showed that canagliflozin application rapidly produces a concentration-dependent vasodilation in mesenteric arteries. Such vasodilation was inhibited by concurrent inhibition of smooth muscle cell voltage-gated K+ channels KV1.5 (by 1 μM DPO-1), KV2.1 (by 100 nM guangxitoxin), and KV7 (by 10 μM linopirdine) but not by the inhibition of small-, intermediate-, and large-conductance Ca2+-activated K+ channels (SKCa by 1 μM apamin, IKCa 10 μM TRAM-34, and BKCa by 10 μM paxilline, respectively), ATP-sensitive (KATP) channels (by 10 μM glibenclamide), or SERCA pump (by 0.1 μM thapsigargin). Inhibition of SGLTs (by 1 μM phlorizin or the inhibition of endothelial signaling did not alter canagliflozin-evoked vasodilation. Consistently, acute canagliflozin treatment (4 mg/kg body weight) lowered systemic blood pressure in vivo. Overall, our data suggests that canagliflozin stimulates KV1.5, KV2.1, and KV7 channels, leading to vasodilation and a reduction of systemic blood pressure.

The acute effect of systemic blood pressure reduction on intraocular pressure in hypertensive patients.

OBJECTIVES:Previous studies have shown an association between systemic hypertension and intraocular pressure (IOP). We analyzed the relationship between the decreases of the blood pressure (BP) and IOP in hypertensive patients.METHODS:The study includes a total of 214 patients: 158 hypertensive and 56 normotensive patients as study and control groups, respectively. The IOP of each eye in both the groups was measured once with a noncontact tonometer at presentation and an hour after BP reduction to normal in the study group. We analyzed the reduction in IOP with decreasing BP.RESULTS:In the study group, the mean IOP was 15.29 ± 4.05 mmHg in the right and 15.11 ± 3.78 mmHg in the left eyes. The mean IOP measured an hour after the patients became normotensive was 13.78 ± 4.06 mmHg in the right and 13.51 ± 3.82 in the left eyes. There was a statistically significant decrease in the IOPs (P < 0.001). The mean IOP in the control group was 13.54 ± 3.51 mmHg in the right and 13.20 ± 3.33 mmHg in the left eyes. The mean IOP at presentation in the study and control groups was found to be significantly different (P < 0.001).CONCLUSIONS:Patients in the study group showed a significantly higher IOP compared to patients in the normotensive group. Furthermore, patients in the study group showed a significant reduction in IOP after BP reduction. This may indicate that uncontrolled hypertension poses a risk for prolonged higher IOP. Prolonged higher IOP can be considered a risk factor for the glaucoma.

Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels.

The antidiabetic drug empagliflozin is reported to produce a range of cardiovascular effects, including a reduction in systemic blood pressure. However, whether empagliflozin directly modulates the contractility of resistance-size mesenteric arteries remains unclear. Here, we sought to investigate if empagliflozin could relax resistance-size rat mesenteric arteries and the associated underlying molecular mechanisms. We found that acute empagliflozin application produces a concentration-dependent vasodilation in myogenic, depolarized and phenylephrine (PE)-preconstricted mesenteric arteries. Selective inhibition of smooth muscle cell voltage-gated K+ channels KV1.5 and KV7 abolished empagliflozin-induced vasodilation. In contrast, pharmacological inhibition of large-conductance Ca2+-activated K+ (BKCa) channels and ATP-sensitive (KATP) channels did not abolish vasodilation. Inhibition of the vasodilatory signaling axis involving endothelial nitric oxide (NO), smooth muscle cell soluble guanylyl cyclase (sGC) and protein kinase G (PKG) did not abolish empagliflozin-evoked vasodilation. Inhibition of the endothelium-derived vasodilatory molecule prostacyclin (PGI2) had no effect on the vasodilation. Consistently, empagliflozin-evoked vasodilation remained unaltered by endothelium denudation. Overall, our data suggest that empagliflozin stimulates smooth muscle cell KV channels KV1.5 and KV7, resulting in vasodilation in resistance-size mesenteric arteries. This study demonstrates for the first time a novel mechanism whereby empagliflozin regulates arterial contractility, resulting in vasodilation. Due to known antihypertensive properties, treatment with empagliflozin may complement conventional antihypertensive therapy.

Role of Ca V 3.1 Channels in Myogenic Tone and Blood Pressure Regulation in Mouse Mesenteric Arteries

The myogenic response is a fundamental mechanism whereby intraluminal pressure elicits arterial constriction pursuant to maintenance of tissue perfusion. Smooth muscle [Ca2+] is a key determinant of constriction, a process intimately tied to L-type (CaV1.2) Ca2+ channel activity. While important, other Ca2+ channels are expressed and could contribute to pressure regulation within defined voltage ranges. In this regard, this study examined the role of T-type Ca2+ channels, using mesenteric arterioles from wild type (WT) and CaV3.1-/- mice. Using pressure myography, experiments first revealed that CaV3.1-/- arterioles displayed decidedly less myogenic tone than WT, particular at lower pressures (20 – 60 mmHg) where membrane potential is hyperpolarized. We next showed with rapid Ca2+ imaging that reduced myogenic tone in CaV3.1-/- arteries resulted from diminished Ca2+ waves generation, asynchronous events dependent upon Ca2+ release from the sarcoplasmic reticulum. In contrast, blockade of L-type Ca2+ channels with nifedipine (200 nM) had no effect on Ca2+ waves, akin to previous findings. The proximity ligation assay confirmed a close association (<40 nm) between IP3R and CaV3.1, in WT and not knockout arterioles. In whole animals, this diminishment of myogenic tone coincided with a reduction in systemic blood pressure at rest. Intriguingly, this hypotension response did not impact blood pressure response to chronic AngII infusion. Taken together, this data suggests that CaV3.1 channels are contributors to tone development at low intraluminal pressures and that this effect is indirect through a Ca2+-induced Ca2+ release mechanism involving the sarcoplasmic reticulum. Further experiments are being extended to define the role of CaV3.1 in other pathophysiological models.

Clinical Management of Syncope in Emergency Department Based on Risk Stratification : A Review Literature

Background: Background Syncope is a frequent problem among patients who present to the ED, accounts for 3% of emergency department admission and 1% of hospitalization. It is characterized by a comparatively short and self-limited loss of consciousness, which is caused by temporary cerebral hypoperfusion. Objective: Therefore, Risk stratification performed in the ED can guide triage decisions, and Risk-stratifying patients into low, moderate, and high-risk groups can assist medical decisions and determine the patient’s disposition. Discussion: The central point of syncope progression pathophysiology is the reduction of systemic blood pressure (BP) with a drop in global cerebral blood flow. Based on the European Society of Cardiology (ESC) syncope practice guidelines, syncope is classified into three categories, Neurally-mediated syncope (neural reflex syncope), Orthostatic hypotension, Cardiac syncope. Proper evaluation of syncope cases could in turn enable timely hospitalization and treatment by syncope experts. Assessment of a patient with syncope can be difficult, requiring a wide variety of medical testing with high health care costs. Sometimes, even after a careful examina- tion, it may not be possible to determine a definitive etiology for syncope. Given these uncertainties, about one-third of emergency room (ER) syncope/collapse patients are referred for assessment to the hospital, including non to low-risk patients. establish the urgency of any further work-up. Conclusion: Syncope assessment and treatment are very difficult, and syncope cases should be treated and dispositioned properly using proper risk stratification guidelines.

How Periodontal Disease and Presence of Nitric Oxide Reducing Oral Bacteria Can Affect Blood Pressure.

Nitric oxide (NO), a small gaseous and multifunctional signaling molecule, is involved in the maintenance of metabolic and cardiovascular homeostasis. It is endogenously produced in the vascular endothelium by specific enzymes known as NO synthases (NOSs). Subsequently, NO is readily oxidized to nitrite and nitrate. Nitrite is also derived from exogenous inorganic nitrate (NO3) contained in meat, vegetables, and drinking water, resulting in greater plasma NO2 concentration and major reduction in systemic blood pressure (BP). The recycling process of nitrate and nitrite to NO (nitrate-nitrite-NO pathway), known as the enterosalivary cycle of nitrate, is dependent upon oral commensal nitrate-reducing bacteria of the dorsal tongue. Veillonella, Actinomyces, Haemophilus, and Neisseria are the most copious among the nitrate-reducing bacteria. The use of chlorhexidine mouthwashes and tongue cleaning can mitigate the bacterial nitrate-related BP lowering effects. Imbalances in the oral reducing microbiota have been associated with a decrease of NO, promoting endothelial dysfunction, and increased cardiovascular risk. Although there is a relationship between periodontitis and hypertension (HT), the correlation between nitrate-reducing bacteria and HT has been poorly studied. Restoring the oral flora and NO activity by probiotics may be considered a potential therapeutic strategy to treat HT.

Cerebral blood flow regulation in end-stage kidney disease.

Patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) experience an increased risk of cerebrovascular disease and cognitive dysfunction. Hemodialysis (HD), a major modality of renal replacement therapy in ESKD, can cause rapid changes in blood pressure, osmolality, and acid-base balance that collectively present a unique stress to the cerebral vasculature. This review presents an update regarding cerebral blood flow (CBF) regulation in CKD and ESKD and how the maintenance of cerebral oxygenation may be compromised during HD. Patients with ESKD exhibit decreased cerebral oxygen delivery due to anemia, despite cerebral hyperperfusion at rest. Cerebral oxygenation further declines during HD due to reductions in CBF, and this may induce cerebral ischemia or "stunning." Intradialytic reductions in CBF are driven by decreases in cerebral perfusion pressure that may be partially opposed by bicarbonate shifts during dialysis. Intradialytic reductions in CBF have been related to several variables that are routinely measured in clinical practice including ultrafiltration rate and blood pressure. However, the role of compensatory cerebrovascular regulatory mechanisms during HD remains relatively unexplored. In particular, cerebral autoregulation can oppose reductions in CBF driven by reductions in systemic blood pressure, while cerebrovascular reactivity to CO2 may attenuate intradialytic reductions in CBF through promoting cerebral vasodilation. However, whether these mechanisms are effective in ESKD and during HD remain relatively unexplored. Important areas for future work include investigating potential alterations in cerebrovascular regulation in CKD and ESKD and how key regulatory mechanisms are engaged and integrated during HD to modulate intradialytic declines in CBF.

Correction: Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure.

PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, producing vasodilation. Flow-mediated PKD2 channel activation leads to calcium influx that activates SK/IK channels and eNOS serine 1176 phosphorylation in ECs. These signaling mechanisms produce arterial hyperpolarization and vasodilation. In contrast, EC PKD2 channels do not contribute to acetylcholine-induced vasodilation, suggesting stimulus-specific function. EC-specific PKD2 knockout elevated blood pressure in mice without altering cardiac function or kidney anatomy. These data demonstrate that flow stimulates PKD2 channels in ECs, leading to SK/IK channel and eNOS activation, hyperpolarization, vasodilation and a reduction in systemic blood pressure. Thus, PKD2 channels are a major component of functional flow sensing in the vasculature.

Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism

IntroductionGreater reduction in estimated glomerular filtration rate (eGFR) after specific treatment for primary aldosteronism (PA) reflects improvement in glomerular hyperfiltration associated with PA and leads to better patient outcomes. However, little is known regarding the mechanisms underlying eGFR reduction after treatment for PA.MethodsWe analyzed data from the nationwide PA registry in Japan. Patients were assigned to adrenalectomy (n = 438) and mineralocorticoid receptor (MR) antagonist (n = 746) groups. We assessed associations between changes in blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), and eGFR before and 6 months after treatment for both groups.ResultsIn a multivariable linear regression, the adjusted β values (95% confidence interval [CI]) for change in eGFR after treatment were −2.76 (−4.29, −1.22) ml/min per 1.73 m2 for PRA (per 3.2 ng/ml per hour), and 1.97 (1.08, 2.85) ml/min per 1.73 m2 for PAC (per 236.1 pg/ml) in the adrenalectomy group; and −0.45 (−0.89, −0.01) ml/min per 1.73 m2 for PRA and −0.72 (−1.62, 0.18) ml/min per 1.73 m2 for PAC in the MR antagonist group. Change in mean arterial pressure after treatment was not significantly associated with change in eGFR in either group. Changes in PRA and PAC but not BP before and 6 months after treatment for PA were associated with greater reductions in eGFR.ConclusionPost-treatment improvements in glomerular hyperfiltration may be attributable to decreased MR activity in the kidneys, but not to reductions in systemic BP.

P0210ASSOCIATIONS BETWEEN CHANGES IN RENIN ACTIVITY AND ALDOSTERONE LEVELS AND CHANGES IN KIDNEY FUNCTION AFTER TREATMENT FOR PRIMARY ALDOSTERONISM: A LARGE MULTICENTER COHORT STUDY IN JAPAN

Abstract Background and Aims Greater reduction in estimated glomerular filtration rate (eGFR) after treatment for primary aldosteronism (PA) reflects improvement of glomerular hyperfiltration associated with PA and leads to better patient outcomes. However, little is known regarding the mechanisms underlying eGFR reduction after treatment for PA. Method We analyzed data from the nationwide PA registry in Japan. Patients were assigned to adrenalectomy (n=419) and mineralocorticoid receptor (MR) antagonist (n=674) groups. We assessed associations between changes in BP, plasma renin activity and aldosterone levels, and eGFR after treatment for both groups. Results Reduction in eGFR after treatment was greater in the surgical compared to MR antagonist treatment group (median -11.0; 95% CI, -12.2 to -9.8 ml/min/1.73 m2 vs. -3.5; 95% CI, -4.3 to -2.7 ml/min/1.73 m2; p &amp;lt;0.001). In a multivariable linear regression, the adjusted betas (95% confidence interval) for change in eGFR after treatment for each standard deviation higher level of plasma renin activity and aldosterone were -2.12 (-4.10, -0.14) and 2.41 (1.20, 3.62) ml/min/1.73 m2, respectively, in the adrenalectomy group, and -0.65 (-1.28, -0.02) and –0.64 (-2.04, 0.76) ml/min/1.73 m2, respectively, in the MR antagonist group. Plasma renin activity Change in mean arterial pressure after treatment was not associated with change in eGFR in either group. Conclusion Changes in plasma renin activity and aldosterone levels but not BP, after treatment for PA were associated with greater reductions in eGFR. Post-treatment improvements in glomerular hyperfiltration may be attributable to suppressed MR activity within the kidneys, not to reductions in systemic blood pressure. It is important for clinicains not only to treat PA, but also to confirm adequate suppressed MR activity after treatment for correction of glomerular hyperfiltration.

Epinephrine stress testing during cardiac catheterization in patients with aortic coarctation

The severity of aortic coarctation (CoA) may be underestimated during cardiac catheterization. We aimed to investigate whether epinephrine stress testing improves clinical decision making and outcome in CoA. We retrospectively evaluated CoA patients >50 kg with a peak systolic gradient (PSG) ≤20 mm Hg during cardiac catheterization who underwent epinephrine stress testing. Subsequent interventional management (stenting or balloon dilatation), complications, and medium-term clinical outcome were assessed. Fifty CoA patients underwent cardiac catheterization with epinephrine stress testing. Patients with a high epinephrine PSG (>20 mm Hg; n = 24) were younger and more likely to have a hypertensive response to exercise compared to patients with a low epinephrine PSG (≤20 mm Hg; n = 26). In total, 21 patients (88%) with a high epinephrine PSG underwent intervention, and 20 patients (77%) with a low epinephrine PSG were treated conservatively. After a mean follow-up of 25 ± 18 months, there was a lower prevalence of hypertension in patients with a high epinephrine PSG who underwent intervention compared to patients with a low epinephrine PSG treated conservatively (19% vs. 76%; P = .001). In a multivariate model, intervention was independently associated with a 14.3-mm Hg reduction in systolic blood pressure (P = .001) and a decrease in the use of antihypertensive agents. In CoA patients with a low baseline PSG but high epinephrine PSG, percutaneous intervention is associated with a substantial reduction in systemic blood pressure and the use of antihypertensive medication. Accordingly, epinephrine stress testing may be a useful addition in the evaluation of CoA.

Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure.

PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, producing vasodilation. Flow-mediated PKD2 channel activation leads to calcium influx that activates SK/IK channels and eNOS serine 1176 phosphorylation in ECs. These signaling mechanisms produce arterial hyperpolarization and vasodilation. In contrast, EC PKD2 channels do not contribute to acetylcholine-induced vasodilation, suggesting stimulus-specific function. EC-specific PKD2 knockout elevated blood pressure in mice without altering cardiac function or kidney anatomy. These data demonstrate that flow stimulates PKD2 channels in ECs, leading to SK/IK channel and eNOS activation, hyperpolarization, vasodilation and a reduction in systemic blood pressure. Thus, PKD2 channels are a major component of functional flow sensing in the vasculature.

SGLT-2 inhibitors in Diabetic Kidney Disease: What Lies Behind their Renoprotective Properties?

Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensinaldosterone- system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD. A systematic literature search of bibliographic databases was conducted to identify preclinical studies and randomized trials evaluating the effects SGLT-2 inhibitors on DKD. Preclinical studies performed in animal models of DKD support the renoprotective action of SGLT-2 inhibitors showing that these agents exert albuminuria-lowering effects and reverse glomerulosclerosis. The renoprotective action of SGLT-2 inhibitors is strongly supported by human studies showing that these agents prevent the progression of albuminuria and retard nephropathy progression to ESRD. This beneficial effect of SGLT-2 inhibitors is not fully explained by their glucose-lowering properties. Attenuation of glomerular hyperfiltration and improvement in a number of surrogate risk factors, including associated reduction in systemic blood pressure, body weight, and serum uric acid levels may represent plausible mechanistic explanations for the cardio-renal protection offered by SGLT-2 inhibitors. Furthermore, the tubular cell metabolism seems to be altered towards a ketone-prone pathway with protective activities. SGLT-2 inhibition emerges as a novel therapeutic approach of diabetic with anticipated benefits towards cardio-renal risk reduction. Additional research efforts are clearly warranted to elucidate this favorable effect in patients with overt DKD.

Circulatory effects of dexmedetomidine in early sepsis: a randomised controlled experimental study.

We designed this experimental study with a view to evaluate the effects of dexmedetomidine (DEX) on cardiac performance and systemic and peripheral hemodynamics in healthy and early-stage endotoxemia swine models. Our study hypothesis was that DEX can ensure hemodynamic stability during the course of endotoxemia. Thirty-two male pigs (25-27kg) were assigned into four groups: (1) no intervention (group A), (2) DEX 0.8μg/kg was administered in non-septic animals (group B), (3) sepsis induced by intravenous Escherichia coli endotoxin (group C) and (4) DEX 0.8μg/kg was administered in septic animals (group D). Hemodynamic parameters such as heart rate, mean blood pressure, central venous pressure, pulmonary artery pressures, pulmonary artery occlusion pressure, pulmonary vascular resistance and cardiac output were continuously recorded. Central venous oxygen saturation was also measured in order to obtain a complete evaluation of cardiovascular response to sepsis. Heart rate was decreased, whilst mean arterial pressure decrease was alleviated after DEX administration in septic animals. In addition, central venous pressure was stable in animals with sepsis after DEX infusion. Sepsis dramatically elevated pulmonary function indicators but DEX succeeded in ameliorating this effect. The important decrease measured in central venous oxygen saturation in both sepsis groups reflected the decreased perfusion of tissues that takes place at the end of early sepsis. Our findings support the hypothesis that DEX has beneficial effects on heart rate and pulmonary artery pressure, whilst reduction in systemic blood pressure occurs at acceptable levels.

SUN-436 Severe Hyponatremia as the Presenting Feature of Partially Empty Sella

Introduction: We report a case of severe acute on chronic hyponatremia meeting the laboratory diagnostic criteria of SIADH. Subsequent evaluation showed secondary adrenal insufficiency due to partially empty sella. Hyponatremia completely resolved following hydrocortisone treatment. Clinical Case: A 76-year-old man with history of hypothyroidism and SIADH was admitted with weakness, fatigue, and leg cramps for the past 3 months. He was staying in a cabin with a broken air conditioner during the summer when his symptoms started. Physical exam revealed mild dry mucus membranes, normal skin turgor, capillary refill less than 2 sec., bradycardia, and no skin hyperpigmentation. He was found to have acute-on-chronic hyponatremia with a serum sodium of 115 mEq/L (baseline 124 mEq/L-130 mEq/L), which worsened with initial volume resuscitation. Lasix and salt tablets were not effective treatment. Other labs showed a low serum osmolality (241 mOsm/kg), high urine osmolality (598 mOsm/kg), high urine sodium (121 mmol/L), low serum uric acid (2.7 mg/dL, n 3.3-8.5 mg/dL), normal TSH, and a low normal AM cortisol (5.7 ug/dL, n 4.0-17.0 ug/dL). A subsequent cosyntropin stimulation test confirmed adrenal insufficiency with a 60 min cortisol of 10.3 ug/dL. ACTH was inappropriately normal (23 pg/mL, n 7-69 pg/mL) indicating a central etiology. In addition, he had a mildly elevated prolactin (23 ng/mL, n 4-15 ng/mL), inappropriately normal TSH (2.83 uIU/mL, n 0.30-4.50 uIU/mL), low normal total T4 (5 ug/dL, n 4.9-11.7 ug/dL), and a mildly low total T3 (52.3 ng/dL, n 58.0-159.0 ng/dL) suggesting a possible secondary hypothyroidism. A pituitary MRI revealed partially empty sella without evidence of pituitary adenoma. The patient was started on stress-dose hydrocortisone with subsequent increased urine output (4 L within 8 h of initial treatment) and increased serum sodium as well. To prevent rapid sodium correction, one dose of desmopressin was given with a low rate hypertonic saline to equilibrate the desmopressin effect. Hydrocortisone was tapered to maintenance dose, and the fluid restriction was discontinued to prevent dehydration. His home Levothyroxine dose was increased, and he was discharged with a serum sodium of 133 mEq/L. As an outpatient, his sodium has normalized with continued treatment. Discussion: Secondary adrenal insufficiency is characterized by euvolemic hyponatremia with biochemical features of SIADH without hyperkalemia. ADH increases due to the lack of cortisol negative feedback loop and the reduction in systemic blood pressure and cardiac output from cortisol deficiency. Hyponatremia corrects rapidly with steroid treatment, which turns off ADH and causes free water excretion. Desmopressin and hypertonic saline can be effectively used to prevent or stop rapid sodium correction. An interesting feature about this case is that partially empty sella is the cause for hypopituitarism.

Electrical Remodeling of Ventricular Repolarization Abnormality after Treatment in Pheochromocytoma: U Wave Finding in a Retrospective Analysis.

Background Pheochromocytoma is a rare neuroendocrine tumor, clinically characterized by high blood pressure, palpitations, and headache. It is often associated with abnormalities of the ventricular repolarization phase; the dispersion of ventricular repolarization is the basis for ventricular arrhythmias (torsion de point, ventricular tachycardia or ventricular fibrillation). Objectives Analysis of abnormal ventricular repolarization focused on the presence and amount of U wave in patients affected by pheochromocytoma and its modification after surgery. Materials and Methods We reviewed pathology records of 722 patients admitted for adrenal nodule or suspected chromaffin-cell tumor and identified 39 patients affected by pheochromocytoma. Metanephrine, normetanephrine, and 3-methoxytyramine have been assessed by determining concentrations in 24-hour urine collection. Standard 12-lead electrocardiogram records have been reviewed with analysis of heart rate, P wave, PR interval, QRS duration, QTc, and U wave. Then we selected and compared 22 patients of 39 affected by pheochromocytoma, with both clinical and electrocardiographic data before and after surgery. Results In our cohort of 39 patients affected by pheochromocytoma, we found U wave in ECG, before treatment, in 82.8 percent of patients, while only 37.0 percent after treatment (p<0.001) and we observed a statistically significant correlation between this wave and the urinary metanephrine. After surgery, in the selected 22 patients, we observed a clear significant reduction in systemic blood pressure, fasting glucose, metanephrine, normetanephrine, and 3-methoxytyramine. We found a significant reduction of U wave presence and leads involved in these patients after surgery (90.9% versus 9%). We observed a linear correlation between the amount of U waves in 12-lead electrocardiogram and metanephrine (r2=0.333, p=0.015), 3-methoxytyramine levels (r2=0.458, p=0.006), and tumor size (r2=0.429, p=0.003). Conclusions In our retrospective analysis, patients affected by pheochromocytoma presented U wave in electrocardiogram. The presence and amount of U wave were associated with the metanephrine levels and the tumor size with significant reduction after surgical removal.