Reduction In Arterial Pressure Research Articles

Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation.

For both healthy individuals and patients with type 2 diabetes (T2D), the hemodynamic response to regular physical activity is important for regulating blood glucose, protecting vascular function, and reducing the risk of cardiovascular disease. In addition to these benefits of regular physical activity, evidence suggests even a single bout of dynamic exercise promotes increased insulin-mediated glucose uptake and insulin sensitivity during the acute recovery period. Importantly, post-exercise hypotension (PEH), which is defined as a sustained reduction in arterial pressure following a single bout of exercise, appears to be blunted in those with T2D compared to their non-diabetic counterparts. In this short review, we describe research that suggests the sustained post-exercise vasodilation often observed in PEH may sub-serve glycemic regulation following exercise in both healthy individuals and those with T2D. Furthermore, we discuss the interplay of enhanced perfusion, both macrovascular and microvascular, and glucose flux following exercise. Finally, we propose future research directions to enhance our understanding of the relationship between post-exercise hemodynamics and glucose regulation in healthy individuals and in those with T2D.

Excessive Blood Pressure Response to Clonidine in Hospitalized Patients With Asymptomatic Severe Hypertension.

There are limited and nonconcordant data on the rapidity and safety of blood pressure response to clonidine in the setting of asymptomatic severe hypertension. We evaluated the blood pressure response to clonidine in hospitalized patients with asymptomatic severe hypertension. We performed a review of hospitalized, noncritically ill patients receiving clonidine within 6 hours of developing asymptomatic severe hypertension (systolic blood pressure [SBP] >180 or diastolic blood pressure [DBP] >110 mm Hg in the absence of acute hypertension-mediated target organ damage). The incidence of mean arterial pressure (MAP) reduction by ≥30% at 4 hours after clonidine was the primary endpoint. We identified 200 relevant patient encounters (median age 63 years, 48.5% women). Median time to clonidine following asymptomatic severe hypertension was 2.8 hours. A total of 20 (10%) patients had ≥30% MAP reduction within 4 hours after clonidine, and 32 (16%) patients had ≥30% reduction in either SBP, DBP, or MAP. Older age, female sex, and preexisting vascular disease were associated with ≥30% MAP reductions (P < 0.05). Only patient sex and clonidine dose of 0.3 mg were significant in multivariable models. There were 14 adverse events observed within 24 hours of administration of clonidine; most (9) were acute kidney injury. There were no ischemic (myocardial, cerebrovascular) events. A substantial minority of hospitalized patients with asymptomatic severe hypertension experience precipitous blood pressure decline with clonidine, and though blood pressure declines more precipitously in women and those receiving higher doses (0.3 mg specifically), the response to clonidine is generally not predictable on clinical grounds.

Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats

BackgroundDelta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics.MethodsAnesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg−1·min−1 normal saline, group LE received 2 ml·kg−1·min−1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg−1·min−1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated.ResultsAll three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4–20.7] versus 7.2 [5.9–8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0–29.1] versus 11.3 [10.7–13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9–11.7] versus 5.6 [4.5–7.0], p = 0.060).ConclusionsOur data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.

The Efficacy of Inferior Vena Cava Diameter, Perfusion Index and Pleth Variability Index on Predicting Hypotension in Spinal Anesthesia

Objective: One of the most common side effects of spinal anesthesia (SA) is hypotension. The aim of the study was to evaluate the efficacay of inferior vena cava (IVC) diameter measurements, perfusion index (PI) and pleth variability index (PVI) values in determining the risk of developing hypotension after SA. Materials and Methods: This study was conducted on 81 patients who underwent transurethral prostatectomy. Before administration of SA, PI and PVI values, IVC diameters (IVCmin: during inspiration and IVCmax: during expiration) and IVC collapsibility index (IVCCI) values and non-invasive blood pressure were recorded. Patients with a baseline systolic arterial pressure reduction rate of ≥25% were determined as the group developing hypotension. IVC diameter measurements were measured immediately after SA then 5 min, and at the end of the operation. The heart rate, mean arterial pressure, PI and PVI values were recorded at regular intervals. Results: Hypotension occured in 32 patients (39.5%). In the hypotensive group, IVCmax and IVCmin values were observed lower and IVCCI values higher. The optimal threshold value of IVCmin was ≤0.99 and threshold value of IVCCI was &gt;%44.5 for predicting hypotension after SA. Conclusion: While IVCmin and IVCCI values were effective in determining hypotension risk after SA, PI and PVI values were not. To predict hypotension by IVC diameter measurements after SA will allow a more effective intervention and avoid hypotension.

Pulmonary Hypertension and COVID-19.

Coronavirus disease 2019 (COVID-19) is a primary respiratory infectious disease, which can result in pulmonary and cardiovascular complications. From its first appearance in the city of Wuhan (China), the infection spread worldwide, leading to its declaration as a pandemic on March 11, 2020. Clinical research on SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) suggests that the virus may determine changes in the pulmonary hemodynamics through mechanisms of endothelial dysfunction, vascular leak, thrombotic microangiopathy, and venous thromboembolism that are similar to those leading to pulmonary hypertension (PH). Current available studies report echocardiographic signs of PH in approximately 12 to 13% of hospitalized patients with COVID-19. Those with chronic pulmonary obstructive disease, congestive heart failure, pulmonary embolism, and prior PH are at increased risk to develop or worsen PH. Evidence of PH seems to be associated with increased disease severity and poor outcome. Because of the importance of the pulmonary hemodynamics in the pathophysiology of COVID-19, there is growing interest in exploring the potential therapeutical benefits of inhaled vasodilators in patients with COVID-19. Treatment with inhaled nitric oxide and prostacyclin has shown encouraging results through improvement of systemic oxygenation, reduction of systolic pulmonary arterial pressure, and prevention of right ventricular failure; however, data from randomized control trials are still required.

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

733 Evaluation of pulmonary pressures in patients underwent to MitraClip

Abstract Mitral regurgitation (MR) is the second most frequent valve heart disease in Europe and its underlying mechanism primary-organic (due to disease of the mitral leaflets), or secondary-functional (where valve leaflets and chordae are structurally normal and MR results from alterations in left ventricle and left atrium geometry), determines the therapeutic approach. Transcatheter Edge-to-Edge Repair (TEER) with MitraClip implantation is a minimal-invasive treatment that according to 2021 ESC Guidelines should be considered (class indication IIa) in selected symptomatic patients with severe MR despite optimal medical therapy, not eligible for surgery and fulfilling COAPT trial inclusion criteria, suggesting an increased chance of responding to treatment. Optimal valve morphology features for TEER are central pathology (second scallop), no leaflet calcifications, mitral valve area &amp;gt;4 cm2, mobile length of posterior leaftel &amp;gt;10 mm, coaptation depth &amp;lt;11mm, normal leaflet strength and mobility, flail width &amp;lt;15 mm, flail gap &amp;lt;10 mm. TEER may be considered (class IIb) only in selected cases when the COAPT criteria are not fulfilled with the aim of improving symptoms and quality of life. MR occurs during systole, that at normal heart rates represents 30–50% of the cardiac cycle. As such, marked left atrial (LA) pressure elevation is present only transiently, representing less of a drive to development of secondary pulmonary hypertension compared to chronic LA pressure elevation seen in severe mitral stenosis. Anyway, in patients with severe MR echocardiography often reveals elevated systolic pulmonary artery pressure (PAPs) and MitraClip implantation usually is associated with a slight increase of the trans-mitral gradient with possible repercussions on pulmonary pressures. To better describe the effect of MitraClip implantation on pulmonary pressures and clinical outcomes we did a retrospective study enrolling in the period 2012–2021 25 patients with severe mitral regurgitation treated with TEER. We aimed to evaluate the clinical outcomes (symptoms, signs of heart failure, NYHA functional class) and the pulmonary pressures assessed by an echocardiographic examination before and after the intervention. At 6-month follow-up all patients with repaired mitral regurgitation showed an improvement in the NYHA class (from IV to II) and no need for re-hospitalization. We observed a trend in the reduction of the mean sistolic pulmonary arterial pressure of 2.68 mmHg ± 15 mmHg (P 0.39, 95% C.I. −9.03 to 3.67) with an unchanged left ventricle ejection fraction. Moreover, the echocardiographic exam showed a normalization of the S and D waves pattern in the pulmonary veins at the PW Doppler evaluation. We can assume that the clinical improvement and the reduction of dyspnoea in these patients underwent TEER is related to a reduction of pressures in the pulmonary circulation regardless of the ejection fraction. This finding could be used as a tool that the cardiologist has to evaluate in the echocardiography lab to reveal a new mitral valve disfunction. Considering the small sample, a greater number of patients will be enrolled to highlight the statistical significance.

Comparison the Effect of Etomidate vs. Thiopentone on Left Ventricular Strain and Strain Rate at the Time of Anesthesia Induction in Patients Undergoing Elective Coronary Artery Bypass Surgery: A Randomized Double Blind Controlled Trial

AbstractMyocardial strain imaging with speckle tracking echocardiography (STE) is getting popularity because it does not depends on insonation angle and has shown good correlation with intraoperative and postoperative ventricular function in patients with coronary artery disease. The impact of thiopentone and etomidate induction on myocardial function was studied and compared on sixty patients undergoing elective coronary artery bypass grafting. Three loops for each views (apical 4 chamber, apical 2 chamber, and apical long axis ) were acquired at base line (T0) and 1 minute (T1) after induction for offline analysis. In Group T, significant increase in HR from the base line values (67.8 ± 13.8 vs 79.2 ± 15.6, p = 0.001) occurred post induction, where as in Group E it remain near to the base line (71.7 ± 8.3 vs 70.1± 8.9, p = 0.345). A reduction in mean arterial pressure (MAP) was noted in both the groups after the injection of the allocated drug. There was no significant difference in the index of contractility (ICON) (T0 vs T1: 48.7 ± 10.6 vs 47.0 ± 11.7, p = 0.120) in Group E where as in Group T there was a reduction in the ICON value (T0 vs T1: 45.0 ± 10.7 vs 41.0 ± 8.4, p = 0.005). A similar picture was also noted in systemic vascular resistance index. A significant decrease in cardiac index (CI) was seen in Group E (T0 vs T1: 2.7 ± 0.4 vs 2.5 ± 0.4, p = 0.027), however it remain near to the base line in Group T. There occurred no changes in stroke index (SI) in Group E (T0 vs T1: 38.7 ± 6 vs 37.0± 5.3, p = 0.134), where as a significant decrease was noted after injection of thiopental (T0 vs T1: 38.0 ± 6.2 vs 36.1± 4.9, p = 0.049). A significant decline in cardiac performance index (CPI) was also recorded in Group E (T0 vs T1: 0.57 ± 0.15 vs 0.52 ± 0.12, p = 0.032), and not in Group T. There was decrease in left ventricular ejection fraction (LVEF) after the injection of both the drugs (Group E, T0 vs T1: 57 ± 3.7 vs 54± 3.7, p= 0.001; and Group T, T0 vs T1: 57 ± 3.7 vs 54± 3.7, p = 0.001). In Group E, global longitudinal peak systolic strain (GLPSS) showed no change after the injection of the drug (T0 vs T1: −13.2 ± 2.2 vs −13.1± 2.3, p = 0.631). However, a significant decrease in GLPSS (T0 vs T1: −13.5 ± 1.5 vs – 10 ± 1.8, p = 0.001) after injection of thiopental. Longitudinal peak systolic strain rate (LPSSR) was significantly decreased in all echocardiographic views after the injection of respective drugs. However, the decrease in LPSSR was significantly less in Group E in comparison to Group T.To conclude, STE provides accurate and reliable real time quantitative regional and global LV assessment. Use of thiopentone for anesthesia induction is associated with more profound impairment of LV function in comparison to etomidate as assessed by a decreased longitudinal peak systolic strain rate and global longitudinal peak systolic strain. Further studies are warranted to understand the exact clinical impact, which may influence the choice of intravenous induction agent based upon preoperative patient characteristics.

Plasma metabolomics in the perioperative period of defect repair in patients with pulmonary arterial hypertension associated with congenital heart disease.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD-PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO3), bicarbonate in superior vena cava (svcHCO3), and the partial pressure of dissolved CO2 gas in radial artery (aPCO2) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO3, svcHCO3, and aPCO2, would be of great value in disease monitoring and evaluating future therapeutic interventions.

Intraoperative Hypotension and Acute Kidney Injury after Noncardiac Surgery in Infants and Children: A Retrospective Cohort Analysis.

Age- and sex-specific reference nomograms for intraoperative blood pressure have been published, but they do not identify harm thresholds. The authors therefore assessed the relationship between various absolute and relative characterizations of hypotension and acute kidney injury in children having noncardiac surgery. The authors conducted a retrospective cohort study using electronic data from two tertiary care centers. They included inpatients 18 yr or younger who had noncardiac surgery with general anesthesia. Postoperative renal injury was defined using the Kidney Disease Improving Global Outcomes definitions, based on serum creatinine concentrations. The authors evaluated potential renal harm thresholds for absolute lowest intraoperative mean arterial pressure (MAP) or largest MAP reduction from baseline maintained for a cumulative period of 5 min. Separate analyses were performed in children aged 2 yr or younger, 2 to 6 yr, 6 to 12 yr, and 12 to 18 yr. Among 64,412 children who had noncardiac surgery, 4,506 had creatinine assessed preoperatively and postoperatively. The incidence of acute kidney injury in this population was 11% (499 of 4,506): 17% in children under 6 yr old, 11% in children 6 to 12 yr old, and 6% in adolescents, which is similar to the incidence reported in adults. There was no association between lowest cumulative MAP sustained for 5 min and postoperative kidney injury. Similarly, there was no association between largest cumulative percentage MAP reduction and postoperative kidney injury. The adjusted estimated odds for kidney injury was 0.99 (95% CI, 0.94 to 1.05) for each 5-mmHg decrease in lowest MAP and 1.00 (95% CI, 0.97 to 1.03) for each 5% decrease in largest MAP reduction from baseline. In distinct contrast to adults, the authors did not find any association between intraoperative hypotension and postoperative renal injury. Avoiding short periods of hypotension should not be the clinician's primary concern when trying to prevent intraoperative renal injury in pediatric patients.

Large-Bore Aspiration Thrombectomy: Catalyst for a Revolution in Treating Pulmonary Embolism

Large-Bore Aspiration Thrombectomy: Catalyst for a Revolution in Treating Pulmonary Embolism

Role of Renal Sympathetic Nerves in GLP-1 (Glucagon-Like Peptide-1) Receptor Agonist Exendin-4-Mediated Diuresis and Natriuresis in Diet-Induced Obese Rats.

BackgroundThe gut‐derived hormone GLP‐1 (glucagon‐like peptide‐1) exerts beneficial effects against established risk factors for chronic kidney disease. GLP‐1 influences renal function by stimulating diuresis and natriuresis and thus lowering arterial blood pressure. The role of the sympathetic nervous system has been implicated as an important link between obesity with elevated arterial pressure and chronic kidney disease. The primary aim of this study was to determine the contribution of renal sympathetic nerves on intrapelvic GLP‐1‐mediated diuresis and natriuresis in high‐fat diet (HFD)‐induced obese rats.Methods and ResultsObesity was induced in rats by HFD for 12 weeks, followed by either surgical bilateral renal denervation or chronic subcutaneous endopeptidase neprilysin inhibition by sacubitril for a week. Diuretic and natriuretic responses to intrapelvic administration of the GLP‐1R (GLP‐1 receptor) agonist exendin‐4 were monitored in anesthetized control and HFD rats. Renal GLP‐1R expression and neprilysin expression and activity were measured. The effects of norepinephrine on the expression of GLP‐1R and neprilysin in kidney epithelial LLC‐PK1 cells were also examined. We found that diuretic and natriuretic responses to exendin‐4 were significantly reduced in the HFD obese rats compared with the control rats (cumulative urine flow at 40 minutes, 387±32 versus 650±65 µL/gkw; cumulative sodium excretion at 40 minutes, 42±5 versus 75±10 µEq/gkw, P<0.05). These responses in the HFD rats were restored after ablation of renal nerves (cumulative urine flow at 40 minutes, 625±62 versus 387±32 µL/gkw; cumulative sodium excretion at 40 minutes, 70±9 versus 42±5 µEq/gkw, P<0.05). Renal denervation induced significant reductions in arterial pressure and heart rate responses to intrapelvic GLP‐1 in the HFD rats. Renal denervation also significantly increased the GLP‐1R expression and reduced neprilysin expression and activity in renal tissues from the HFD rats. Chronic subcutaneous neprilysin inhibition by sacubitril increased GLP‐1–induced diuretic and natriuretic effects in the HFD rats. Finally, exposure of the renal epithelial cells to norepinephrine in vitro led to downregulation of GLP‐1R expression but upregulation of neprilysin expression and activity.ConclusionsThese results suggest that renal sympathetic nerve activation contributes to the blunted diuretic and natriuretic effects of GLP‐1 in HFD obese rats. This study provides significant novel insight into the potential renal nerve–neprilysin–GLP‐1 pathway involved in renal dysfunction during obesity that leads to hypertension.

Acute autonomic effects of rose oxide on cardiovascular parameters of Wistar and spontaneously hypertensive rats

AimsAnti-inflammatory molecules, such as rose oxide (RO), are likely to exert therapeutic effects in systemic arterial hypertension (SAH), a disease associated with abnormal immune responses. We aimed to investigate acute autonomic effects of RO on hemodynamic parameters of Wistar and spontaneously hypertensive rats (SHR). MethodsRats were anesthetized and femoral artery and veins were cannulated. Next day, blood pressure (BP) and heart rate (HR) were recorded. Acute effects of RO (1.25, 2.5, or 5.0 mg/kg; iv) on BP, HR, and variability of systolic arterial pressure (SAP) and pulse interval (PI) were assessed. The effects of RO were also investigated in SHR, which received atropine (2 mg/kg), propranolol (4 mg/kg), or hexamethonium (20 mg/kg) 15 min before receiving RO. Vasorelaxant effects of RO (10–10 to 10–4 M) on aortic rings of rats were also assessed. Key findingsIn Wistar rats, none of the RO doses evoked significant changes in BP, HR, and variability of SAP and PI. On the other hand, in SHR, RO elicited reduction in mean arterial pressure (MAP), and prevented the increase in the low frequency power (LF) of the SAP spectra. Pretreatment with atropine or propranolol did not alter hypotension, but attenuated RO-induced bradycardia. Hexamethonium prevented RO-induced hypotension and bradycardia. RO exerted vasorelaxant effects on aortic rings with (Wistar and SHR) or without functional endothelium (SHR only). SignificanceRose oxide, a monoterpene with anti-inflammatory properties, acts as an antihypertensive molecule due to its ability to acutely promote hypotension and bradycardia in spontaneously hypertensive rats.

50 Years Ago in TheJournalofPediatrics: The Search for Safe and Effective Treatment of Acute Severe Hypertension in Childhood

McLaine PN, Drummond KN. Intravenous diazoxide for severe hypertension in childhood. J Pediatr 1971;79:829-32. Children with acute presentations of severe hypertension require prompt therapy to avoid end-organ effects of uncontrolled hypertension such as hypertensive encephalopathy. Usually, an intravenous antihypertensive agent is preferred, given their more rapid onset of action compared with oral medications. No matter what agent is chosen, a major concern in treating such patients is to avoid rapid hypotension, which can lead to cerebral ischemia, especially in those with chronic hypertension. McLaine and Drummond provide one of the first descriptions of using an intravenously administered drug for children with acute severe hypertension. They gave bolus doses of diazoxide, a potassium channel activator, to 16 children aged 16 days to 16 years with severe hypertension, defined as blood pressure (BP) >140/90 mm Hg. The children all had hypertension secondary to kidney disease, and many were receiving other antihypertensive agents. Reduction of mean arterial pressure occurred within 10 minutes, with reductions of 25%-35% or more of pretreatment BP levels. Although this effect would be considered excessive according to current recommendations,1Seeman T. Hamdani G. Mitsnefes M. Hypertensive crisis in children and adolescents.Pediatr Nephrol. 2019; 34: 2523-2537Crossref PubMed Scopus (25) Google Scholar the authors reported no side effects, even though in 3 patients, the diastolic BP briefly dropped to zero! Today, intravenous diazoxide is no longer in use for the treatment of acute severe hypertension—clinicians have recognized that its use is riskier than other agents such as labetalol or hydralazine. However, even these agents have safety concerns. For example, in our analysis of the use of intravenous hydralazine in hospitalized children with acute hypertension,2Flynn J.T. Bradford M.C. Harvey E.M. Intravenous hydralazine in hospitalized children and adolescents with hypertension.J Pediatr. 2016; 168: 88-92Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar approximately 30% of doses resulted in drops of mean arterial pressure that exceeded the current recommendation of no greater than a 25% reduction.1Seeman T. Hamdani G. Mitsnefes M. Hypertensive crisis in children and adolescents.Pediatr Nephrol. 2019; 34: 2523-2537Crossref PubMed Scopus (25) Google Scholar So, the search for safe and effective treatment of acute severe hypertension in childhood continues. In the absence of prospective clinical trials in this patient population, we can at least apply the findings of pioneers like McLaine and Drummond to improve patient safety and avoid untoward outcomes.

The benefits of giving: Effects of prosocial behavior on recovery from stress.

Individuals regularly face stress, and the manner in which they cope with that stress is a crucial component in predicting stress recovery. While many engage in self-rewarding behaviors to feel better, these behaviors can come with a cost. The current study tested the effect of engaging in a different behavior after experiencing stress-prosocial behavior. Given the health benefits associated with giving to others, it is plausible that engaging in prosocial behavior is more successful in reducing the psychological and physiological responses to stress. To test this, participants underwent the Trier Social Stress Test and then either sent a gift card to a person of their choosing, received a gift card for themselves, or selected the more aesthetically pleasing gift card. Measures of self-reported mood, heart rate, blood pressure, salivary alpha-amylase, and cortisol were collected throughout the session. While the manipulation did not elicit differences in psychological or hormonal measures, the giving group showed a significantly greater downregulation of their heart rate, diastolic blood pressure, and mean arterial pressure while recovering from the stressor. Additionally, those in the giving group who evidenced greater prosocial sentiment showed a larger reduction in diastolic blood pressure and mean arterial pressure. A follow-up study suggested that these behaviors may be engaging different reward components, as those who gave a gift card reported greater "liking" while those who received a gift card reported greater "wanting". Overall, the findings show that engaging in prosocial behavior following a stressor can help to downregulate physiological stress responses.

A randomized, prospective, open label comparative study of the efficacy of azilsartan and ramipril in the management of hypertension in patients with type-2 diabetes mellitus

Background: Patients with diabetes are prone to have hypertension. Hypertension is risk factors for complications of the vascular system, cardiovascular diseases and leads to atherosclerosis. It has been estimated that the diabetics tend to have about two times more risk of having hypertension than the general population. Objective of current study is to study and compare the efficacy of azilsartan and ramipril in the management of Hypertensive patients with type 2 diabetes mellitusMethods: randomized, prospective, open label comparative study was carried out among 60 known cases of diabetes mellitus type-2 with hypertension. Patients were randomly allocated into two groups: group-A (N=30) taking ACE Inhibitor tablet ramipril 5 mg Once daily orally. Group-B (N=30) taking angiotensin II receptor antagonist tablet azilsartan 40 mg once daily orally. At the commencement of the trial, patients were subjected to thorough clinical examination with necessary investigations and base line values were recorded.Results: Both the groups were comparable for age, sex and treatment taken. There was a significant reduction in the mean arterial pressure (17.43 for azilsartan group vs. 14.5 for ramipril group) (mmHg), creatinine clearance (mean reduction of 18.8 for azilsartan group vs. 13.94 for ramipril group), and urinary albumin excretion (mean reduction of 29.74 in azilsartan group vs. 17.25 for ramipril group). In azilsartan group the reduction was more in all parameters compared to ramipril group without effecting renal parameters.Conclusions: Azilsartan was more effective in reducing the mean arterial pressure (mmHg), creatinine clearance as well as urinary albumin excretion in Hypertensive patients with Type 2 diabetes mellitus without effecting renal parameters.

Safety, tolerability, and pharmacokinetics (PK) of treprostinil palmitil inhalation powder (TPIP): a phase 1, randomised, double-blind, single- and multiple-dose study

Abstract Background/Introduction Use of treprostinil in the treatment of pulmonary arterial hypertension (PAH) is limited by a short half-life and dose-limiting adverse events. TPIP, a dry powder formulation of the treprostinil prodrug treprostinil palmitil, is under investigation for PAH. In preclinical models, TPIP provided sustained treprostinil release in the lung and demonstrated sustained reduction of pulmonary arterial pressures. Purpose To examine the safety, tolerability, and PK of single- and multiple-dose administration of once-daily (QD) TPIP in healthy volunteers. Methods In this phase 1 study, healthy adults (aged 18–45 years) were randomised to receive single or multiple QD inhalation doses of TPIP. Single-dose participants received TPIP 112.5, 225, 450, or 675 μg (n=6 per dose) or placebo (n=2). Multiple-dose participants received TPIP 225 μg QD for 7 days (n=6), 112.5 μg QD for 4 days followed by 225 μg QD for 3 days (n=6), or placebo for 7 days (n=4). Results Of 42 randomly assigned participants who received ≥1 dose, 41 (97.6%) completed the study. Of the single-dose TPIP–treated participants, 70.8% (n=17/24) experienced a treatment-emergent adverse event (TEAE) vs 0% (0/2) of placebo-treated participants; the most common TEAEs (≥15%) among TPIP-treated participants were cough (45.8%), dizziness (29.2%), throat irritation (20.8%), nausea (16.7%), and hypotension (16.7%). Of the multiple-dose TPIP–treated participants, 83.3% (n=10/12) experienced a TEAE vs 50.0% of placebo-treated participants (2/4); the most common TEAEs were cough (58.3% TPIP vs 50.0% placebo), headache (50.0% vs 0%), nausea (33.3% vs 0%), and dizziness (25.0% vs 0%). Overall, 69.0% of participants (29/42) experienced mild TEAEs and 16.7% (7/42) experienced moderate TEAEs; no severe or serious TEAEs occurred. TEAEs were more frequent with increasing TPIP doses. Participants titrated from TPIP 112.5 μg QD to 225 μg QD experienced fewer TEAEs than those who received 225 μg QD at treatment initiation; all TEAEs were mild. After single-dose TPIP treatment, treprostinil exposure was dose proportional, with mean (CV%) Cmax = 78.4–717 pg/mL (38.6-72.9%) and AUC(0–∞) = 1.09–5.48 h·ng/mL (11.5–30.0%). At steady-state (225 μg), the mean (CV%) of Cmax, Cmin, and AUC(0–t) were 193–228 pg/mL (32.9–46.4%), 17.6–22.8 ng/mL (43.7%-64.4%) and 1.68–1.82 ng·h/mL (28.7–36.6%), respectively. No steady-state accumulation was observed. Elimination t1/2 was 8.7–11.6 h after a single dose and 6.8–8.8 h at steady state. Plasma concentrations of treprostinil palmitil were below the limit of quantification (100 pg/mL) at all time points measured. Conclusions In this phase 1 study, single and multiple TPIP dosing was generally well tolerated in healthy volunteers, with a PK profile that supports QD dosing. TEAEs were dose related; most were mild, none were severe or serious, and a titration schedule improved tolerability. These results support further examination of TPIP in patients with PAH. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Insmed Incorporated

Machine learning model to predict hypotension after starting continuous renal replacement therapy

Hypotension after starting continuous renal replacement therapy (CRRT) is associated with worse outcomes compared with normotension, but it is difficult to predict because several factors have interactive and complex effects on the risk. The present study applied machine learning algorithms to develop models to predict hypotension after initiating CRRT. Among 2349 adult patients who started CRRT due to acute kidney injury, 70% and 30% were randomly assigned into the training and testing sets, respectively. Hypotension was defined as a reduction in mean arterial pressure (MAP) ≥ 20 mmHg from the initial value within 6 h. The area under the receiver operating characteristic curves (AUROCs) in machine learning models, such as support vector machine (SVM), deep neural network (DNN), light gradient boosting machine (LGBM), and extreme gradient boosting machine (XGB) were compared with those in disease-severity scores such as the Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II. The XGB model showed the highest AUROC (0.828 [0.796–0.861]), and the DNN and LGBM models followed with AUROCs of 0.822 (0.789–0.856) and 0.813 (0.780–0.847), respectively; all machine learning AUROC values were higher than those obtained from disease-severity scores (AUROCs < 0.6). Although other definitions of hypotension were used such as a reduction of MAP ≥ 30 mmHg or a reduction occurring within 1 h, the AUROCs of machine learning models were higher than those of disease-severity scores. Machine learning models successfully predict hypotension after starting CRRT and can serve as the basis of systems to predict hypotension before starting CRRT.

Persistent Right Ventricle Dilatation in SARS-CoV-2–Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support

ObjectivesVenovenous extracorporeal membrane oxygenation (ECMO) support may be considered in experienced centers for patients with acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection refractory to conventional treatment. In ECMO patients, echocardiography has emerged as a clinical tool for implantation and clinical management; but to date, little data are available on COVID-related ARDS patients requiring ECMO. The authors assessed the incidence of right ventricular dilatation and dysfunction (RvDys) in patients with COVID-related ARDS requiring ECMO.DesignSingle-center investigation.SettingIntensive care unit (ICU).ParticipantsA total of 35 patients with COVID-related ARDS requiring ECMO, consecutively admitted to the ICU (March 1, 2020, to February 28, 2021).InterventionsSerial echocardiographic examinations. RvDys was defined as RV end-diastolic area/LV end-diastolic area >0.6 and tricuspid annular plane excursion <15 mm.Measurements and Main ResultsThe incidence of RvDys was 15/35 (42%). RvDys patients underwent ECMO support after a longer period of mechanical ventilation (p = 0.006) and exhibited a higher mortality rate (p = 0.024) than those without RvDys. In nonsurvivors, RvDys was observed in all patients (n = nine) who died with unfavorable progression of COVID-related ARDS. In survivors, weaned from ECMO, a significant reduction in systolic pulmonary arterial pressures was detectable.ConclusionsAccording to the authors’ data, in COVID-related ARDS requiring ECMO support, RvDys is common, associated with increased ICU mortality. Overall, the data underscored the clinical role of echocardiography in COVID-related ARDS supported by venovenous ECMO, because serial echocardiographic assessments (especially focused on RV changes) are able to reflect pulmonary COVID disease severity.

Neuroinflammation and Microglial Activation at Rostral Ventrolateral Medulla Underpin Cadmium-Induced Cardiovascular Dysregulation in Rats.

PurposeCadmium is a heavy metal and environmental toxicant known to act on the central cardiovascular regulatory mechanisms, and one of its brain targets is the rostral ventrolateral medulla (RVLM), a brainstem site that maintains blood pressure and sympathetic vasomotor tone. The present study assessed the hypothesis that cadmium elicits cardiovascular dysregulation by inducing neuroinflammation and microglial activation, two potential cellular mechanisms, in RVLM.MethodsAdult male Sprague–Dawley rats were used for measuring cardiovascular responses after intravenous administration of cadmium. We further conducted real-time PCR, immunofluorescence staining, in situ determination of mitochondrial superoxide, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay (ELISA) to identify cytokine and chemokine mRNA expression, microglia activation, superoxide production, and necrotic and apoptotic cell death in RVLM.ResultsWe found animals maintained under propofol anesthesia, intravenous administration of cadmium acetate (4 mg/kg) resulted in an increase, followed by a rebound and a secondary decrease in spontaneous baroreflex-mediated sympathetic vasomotor tone, a progressive reduction in mean arterial pressure and heart rate, alongside augmentation of pro-inflammatory cytokine and chemokine in RVLM. All those cardiovascular and neuroinflammatory events were reversed by pretreatment with an anti-inflammatory drug, pentoxifylline (50 mg/kg, i.p.). There were also concurrent microglial activation, reactive oxygen species production, hypoxia, reduced blood flow, and necrotic and apoptotic cell death in RVLM.ConclusionBased on these biochemical, pharmacological and morphological observations, we conclude that neuroinflammation and microglial activation at RVLM, and their downstream cellular mechanisms, causally underpin cadmium-induced cardiovascular dysregulation.