Lower Systolic Arterial Pressure Research Articles

Mixed Shock Complicating Cardiogenic Shock: Frequency, Predictors, and Clinical Outcomes.

Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity. We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters. Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure (P=0.043), hepatic injury (P=0.049), and suspected/definite infection (P=0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P=0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P=0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; Padj=0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; Padj<0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; Padj=0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; Padj=0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; Padj=0.008). MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality.

Abdominal perfusion in canine patients with pyometra and sepsis evaluated by Doppler and contrast-enhanced ultrasound

BackgroundSepsis is a condition characterized by organic dysfunction, leading to hemodynamic instability and high morbidity and mortality rates in humans and animals. Early identification of perfusion changes and appropriate management of sepsis are crucial for improving patient prognosis. Currently, the Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA) scores are widely studied for sepsis identification and evaluation of organ dysfunction. However, these scores do not assess gastrointestinal involvement, which is common in this condition. Contrast-enhanced ultrasound (CEUS) and Doppler have been considered promising diagnostic techniques for detecting changes in vascularization and microcirculation in a non-invasive and safe manner, particularly in the gastrointestinal system. This study aimed to evaluate duodenal perfusion using CEUS, as well as abdominal aortic and cranial mesenteric artery blood flow using Doppler ultrasound, and systolic arterial pressure (SAP) in 17 bitches with pyometra and in 10 healthy animals.ResultsThe variables were compared between the pyometra and control groups, as well between patients with and without sepsis determined by the SOFA or SIRS scores. Pyometra was found to cause a reduction in abdominal aortic blood flow volume, aortic peak systolic velocity, and resistivity index as evaluated by Doppler ultrasound. Patients with sepsis according to the SOFA criteria only presented lower SAP. In contrast, sepsis animals identified by the SIRS score exhibited lower SAP, aortic peak systolic velocity, aortic blood flow volume, and aortic resistivity index and additionally, higher peak intensity of contrast in the duodenal wall.ConclusionsPyometra causes a reduction in abdominal aortic blood flow, which is more pronounced in animals with sepsis identified by the SIRS criteria. These animals also exhibited a decrease in systolic blood pressure and an increase in duodenal perfusion, as evident by CEUS. However, these changes were not observed in patients with sepsis identified by the SOFA criteria. The alterations in intestinal perfusion observed in animals with sepsis indicate the presence of inflammation or dysfunction. In this regard, CEUS proves to be a valuable technique for detecting subtle changes in tissue hemodynamics that may not be apparent in conventional exams.

Clinical profile and arrhythmic burden in MINOCA

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is considered to be a puzzling clinical phenomenon with unclear prognosis. This study aims to compare the clinical characteristics, impact of arrythmias and prognosis of MINOCA with MI with obstructive coronary artery disease (MICAD). Methods Data was obtained from our university hospital database. Patients with MI between 28 August 2018 and 31 December 2020 were included in the study. Subjects were divided in 2 groups: 1 - MINOCA; 2 -MICAD. Follow-up analysis included death from any cause, major adverse cardiac events (MACE: cardiac death, MI, stroke), readmissions due to cardiovascular causes, and in-hospital mortality. Median follow up was 18 months. Results MINOCA occurred in 49 (11 %) out of 443 pts with MI. There were no differences in age (p=0.732). In MINOCA group there were more females (34.7% vs 22.8%, p&amp;lt;0.001), never smokers (30.6% vs 21.8%, p&amp;lt;0.001), lower rates of hypertension (67.3% vs 73.8%, p=0.036), diabetes (18.3% vs 29.9%, p&amp;lt;0.001), hyperlipidaemia (28,5 % vs 35.7%, p=0.475), stroke in anamnesis (2.0% vs 6.8%, p&amp;lt;0.001), preavious MI (2.0% vs 22.8%, p&amp;lt;0.001). Symptoms at admission didn't differ between the two groups, however MINOCA group had lower mean heart rate (72±15 vs 87±19, p&amp;lt;0.001), lower systolic arterial pressure (139±22 vs 145±28, p&amp;lt;0.001). There were no significant differences between STEMI or NSTEMI: 55.1 % and 44.9 % in the MINOCA group vs 53.8 % and 46.2 % in MICAD (p=0.534). MINOCA patients had lower C-RP levels (19 vs 56 mg/L, p&amp;lt;0.001), high-sensitivity cardiac troponin T levels: (112 vs 376 ng/L, p&amp;lt;0.001) and lower BNP levels (99±26.9 vs 142±64.2, p&amp;lt;0.001). Left ventricular dysfunction (EF &amp;lt; 50 %) was more prevalent in the MICAD group (16.3% vs 27.9%, p&amp;lt;0.001). There was no need in inotropic support in MINOCA patients (0% vs 4.8%, p=0.04). Atrial fibrillation (AF) was more often found in MICAD group (4.1% vs 6.8%, p &amp;lt;0.001). There were no diffrenecs in ventricular arrhythmias during admmision in both groups. Death rates were lower in hospital (0% vs 2.8%, p=0.131) and during the follow up period (8.1% vs 10.9 %, p=0.369). There was no significant difference in MACE outcomes (p=0.612) and readmission of cardiovascular causes (p=0.310) in both groups. Independent predictors for MACE in MINOCA patients were older age (≥60 years), females, reduced LVEF and atrial fibrillation. Conclusion MINOCA patients had lower prevalence of classic cardiovascular risk factors, no clinical differences at admission, lower levels of C-RP and high-sensitivity cardiac troponin T, preserved left ventricle EF, lower in- hospital and during follow up death rate, but no significant difference in MACE outcomes. Older age, females, reduced LVEF and atrial fibrillation are considered to be predictors of MACE in MINOCA. Further research is needed to provide more evidence on the optimal management.

Can we predict the coronary angiography result?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction It is estimated that 5-15% of patients admitted with suspected acute myocardial infarction (AMI) have no significant lesions on coronary angiography (&amp;gt;50%), an entity called MINOCA. Objective To identify predictors of non-significant coronary lesions in patients admitted with AMI Methods Based on a multicenter retrospective study, data collected from admissions between 2013 and 2020. Patients (pts) without data on cardiovascular history or uncompleted clinical data were excluded. Pts were divided in 2 groups (G): GA – pts with significant coronary lesions; GB - pts with non-significant coronary lesions. Results MINOCA occurred in 1561 (20.6%) out of 6029 pts with AMI. There were no differences between G regarding age (p=0.745). GB pts were more frequently females (35.9% vs 24.9%, p&amp;lt;0.001), had lower rates of smoking habits (21.9% vs 26.9%, p&amp;lt;0.001), arterial hypertension (70.7% vs 73.4%, p=0.036), diabetes (31.1% vs 36.7%, p&amp;lt;0.001), past history of MI (13.9% vs 23.5%, p&amp;lt;0.001) and past history of stroke (5.0% vs 7.5%, p=0.002). There were no differences between G regarding symptoms at admission (p=0.359). At admission, GB had lower mean heart rate (76±18 vs 78±19, p=0.037), lower systolic arterial pressure (141±25 vs 144±28, p&amp;lt;0.001), lower rates of KK&amp;gt;1 (10% vs 12.2%, p=0.037), higher rates of atrial fibrillation (AF) (8.8% vs 6.8%, p=0.026), higher rates of normal ST-T segment (50.9% vs 29.6%, p&amp;lt;0.001), and lower BNP levels (99±36.9 vs 157±64, p&amp;lt;0.001). During hospitalization, GB pts used less diuretics (18.1% vs 26.1%, p&amp;lt;0.001) and inotropes (0.5% vs 1.8%, p=0.007). GB had a lower prevalence of left ventricle dysfunction (&amp;lt;50%) (20.4% vs 29.3%, p&amp;lt;0.001), and less need of mechanical ventilation (0.1% vs 1.0%, p&amp;lt;0.001), non-invasive ventilation (0.1% vs 1.6%, p&amp;lt;0.001) and provisory pacing (0.1% vs 0.5%, p=0.011). Logistic regression confirmed that being a female (p&amp;lt;0.001, OR 2.7), a non-smoker (p=0.002, OR 1.4), a non-diabetic (p=0.001, OR 1.45), AF (p=0.001, OR 1.8), normal QRS (p&amp;lt;0.001, OR 1.9) and normal LV function (p=0.009. OR 1.5) were predictors of MINOCA. The G were similar regarding in-hospital MACE outcomes (in-hospital death, stroke or MI) (p=0.658) and 1 year outcomes, namely 1 year mortality (p=0.709) and readmission of cardiovascular causa (p=0.290). Conclusion Several clinical factor may help us predicting which patients will have a coronary angiography without significant lesions. However, the absence of significant lesions is not predictive of better in-hospital and 1 year prognosis.

Bedside intra-aortic balloon pump implant in cardiac intensive care unit

Abstract Funding Acknowledgements Type of funding sources: None. Background Intra-aortic balloon pumping (IABP) support has been progressively reappraised, especially for the acute decompensated heart failure (ADHF) cardiogenic shock (CS) scenario(1). IABP features an easy implantation technique and can rapidly be deployed bedside. This avoids the need of patient transfer to the catheterization laboratory (CathLab) and the inherent risk of destabilization and makes it an attractive approach in case of unstable hemodynamics. However, despite decades of IABP utilization, no data is available on the safety and feasibility of the IABP bedside implant. Aim Aim of this study was to assess the safety and feasibility of bedside IABP implant and to characterize the phenotype of patients who receive this support. Methods We retrospectively reviewed all consecutive patients who received bedside IABP in the last 12 months. For comparison purposes we also selected all consecutive patients who underwent IABP implant in the CathLab in the same timespan. Major vascular complication was defined as thoracic aortic dissection, access-related vascular injury leading to either death, unplanned percutaneous/surgical intervention, need for ≥4 blood unit transfusions, amputation for distal embolization, or irreversible end-organ damage. All analyses were performed with R. Results A total of 77 patients were included: 22 (28.6%) received bedside, and 55 (71.4%) CathLab IABP implant. A total of 62 (81.6%) patients were male, age was 73 (64-79) years, and invasive mechanical ventilation was required in 54 (70.1%): no differences were observed between groups. Bedside IABP implant was guided by trans-esophageal echocardiography in 10 (45.5%) and trans-thoracic echocardiography in 12 (54.5%) patients. Patients in the bedside IABP cohort had more often pre-existing heart failure (HF, 72.7 vs 32.7%; p=0.001), presented with ADHF (45.5 vs 12.7%; p=0.002) and in overt CS (77.3 vs 34.5%; p&amp;lt;0.001). They also demonstrated lower systolic arterial pressure [90.0 (86.2-102.5) vs 123.0 (104.5-140.0) mmHg; p=0.007], lower left ventricular ejection fraction [LVEF, 20 (15-25) vs 25 (20-35)%; p&amp;lt;0.001] and higher serum lactate [5.4 (3.6-8.5) vs 2.0 (1.3-3.7) mmol/L; p=0.001]. Despite worse baseline conditions than the CathLab group, bedside IABP cohort experienced a similar in-hospital mortality (22.7 vs 18.2%; p=0.649), similar major bleeding events (27.3 vs 12.7%; p=0.124), and similar major vascular complications (4.5 vs 5.5%; p=0.871). No patient experienced cerebrovascular events. Conclusion In this single-center experience, bedside IABP implant appeared safe and feasible. No difference was observed in terms of in-hospital mortality or major vascular complications between the bedside and CathLab groups, despite worse clinical conditions in the bedside IABP group. This strategy was often employed in critically-ill patients with ADHF with CS, were IABP use is increasing.

436 POSTOPERATIVE SYSTOLIC HYPOTENSION IN FRACTURED NECK OF FEMUR PATIENTS

Abstract Introduction Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP 2) found an association between reduced intraoperative systolic arterial pressure (SAP) and postoperative mortality at five and 30 days. We sought to determine the incidence of hypotension in the postoperative period, rather than just intraoperatively, in a small sample of patients with fractured neck of femur. Method We performed a retrospective review of the notes, electronic vital signs and electronic general practice records from 40 patients with fractured neck of femur. We identified the latest SAP performed at their general practice (if done within one year before admission). We noted the pre-operative baseline SAP reading from the ward as well as the lowest SAP during several time periods: the pre-operative period; the fracture surgery; the recovery room; and during each 24-h period postoperatively until the fifth postoperative day. Results A SAP recording from general practice within the previous year was only accessible in 21 (53%) of patients, but where it was accessible, it was within 20% of the immediate preoperative SAP in 14 (66%) of patients. The incidence of relative hypotension (&amp;lt; 80% preoperative SAP) was 54% in the operating theatre, 41% in the recovery room, 65% on the ward during the remainder of the first postoperative 24 h, 55% during postoperative day 2, 53% during day 3, 33% during day 4 and 41% during day 5. Conclusions Postoperative hypotension was common in our sample. In our analysis, the highest incidence was on the ward during the first 24 hours postoperatively. However, 41% of patients still had hypotension 5 days postoperatively.

Effects of physical exercise combined with captopril or losartan on left ventricular hypertrophy of hypertensive rats

ABSTRACT Background: Left ventricular hypertrophy (LVH) is an endpoint of hypertensive cardiac alterations. Renin-angiotensin-aldosterone system (RAAS) blockers are among the most effective on LVH regression. Physical exercise combined to antihypertensive drug contributes to arterial pressure (AP) control and LVH prevention. We evaluated the effects of physical exercise combined to captopril or losartan during eight weeks for spontaneously hypertensive rats (SHR) on some cardiac parameters. Methods: SHR (n=5-6 per group) were sedentary or trained 5 days a week in treadmill during 8 weeks; and they were treated with daily oral captopril (12.5, 25, or 50mg/kg), losartan (2.5, 5, or 10mg/kg), or vehicle. At the end, it was obtained systolic AP (SAP), electrocardiogram (ECG), and hearts metalloproteinase 2 (MMP-2) activity and histology. Results: Captopril 25 and 50 mg/kg, and losartan 10 mg/kg lowered SAP of sedentary and trained SHR. Losartan 5 mg/kg combined with physical exercise also lowered SAP. Combined with exercise, captopril 50 mg/kg lowered 13.6% of QT interval, 14.2% of QTc interval, and 22.8% of Tpeak-Tend compared to sedentary SHR. Losartan 5 and 10mg/kg lowered QT interval of sedentary and trained SHR. Losartan 2.5, 5 and 10mg/kg combined with physical exercise lowered respectively 25.4%, 24.8%, and 31.8% of MMP-2 activity. Losartan (10mg/kg) combined with exercise reduced cardiomyocyte diameter. Conclusion: These data support the hypothesis of physical exercise combined with RAAS blockers could improve the benefits on hypertensive LVH treatment.

Is pelvic floor muscle training able to alter the response of cardiovascular autonomic modulation and provide a possible cardiovascular benefit to pregnant women?

To evaluate the acute and chronic effect of an exercise protocol of pelvic floor muscles (PFMs) contraction on the heart period (HP) and systolic arterial pressure (SAP) variabilities and baroreflex sensitivity (BRS) at rest in pregnant women; and to evaluate if this progressive exercise protocol was well-tolerated by the pregnant women studied. We evaluated 48 women at 18 weeks of pregnancy by vaginal palpation, vaginal manometry, and cardiopulmonary exercise test. They were divided in control (CG; 31.75 ± 3.91 years) and training groups (TG; 30.71 ± 3.94 years). At 19 and 36 weeks of pregnancy, electrocardiogram and noninvasive peripheral SAP data were collected at rest before and after 10 PFM contractions. TG performed PFMT from the 20th to the 36th week. HP and SAP variabilities were analyzed by spectral and symbolic analysis. The baroreflex was evaluated by cross-spectral analysis between the HP and SAP series. The groups did not differ in relation to VO2 , HP and SAP variabilities, and BRS at the beginning of the protocol. TG increased the endurance of the PFM after training. PFM contraction did not change the HP and SAP variabilities, and BRS at the 18th week. After the training, the TG presented lower SAP mean, lower BF of SAP variability, and higher BRS than CG. Acute PFM contractions did not alter HP and SAP variabilities and BRS, but PFMT resulted in a lower SAP mean and higher BRS in trained pregnant when compared to the untrained.

Protective Effects of Dexmedetomidine and Oxycodone in Patients Undergoing Limb Ischemia-Reperfusion.

BackgroundTourniquet-related complications are a common clinical problem. In the present study, we compared the effects of dexmedetomidine vs. oxycodone in patients undergoing limb ischemia-reperfusion.Material/MethodsFifty-four patients undergoing unilateral lower-extremity surgery under combined spinal and epidural anesthesia were randomly assigned to a control (ischemia-reperfusion, I/R) group, a dexmedetomidine (Dex) group, and an oxycodone (Oxy) group. Tourniquet-induced hemodynamic parameters changes among groups were compared. The serum concentration of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), fatty acid binding protein 3 (FABP3), endothelin-1 (ET-1), and brain-derived neurotrophic factor (BDNF) were measured using ELISA before anesthesia and at 30 min and at 6 h after tourniquet release.ResultsIn the control group, tourniquet use caused significant increases in systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), and rate-pressure product. Compared with Oxy, Dex significantly decreased heart rate (HR). Both Dex and Oxy lowered SAP compared with the control group. No significant difference was observed in DAP between Dex and Oxy. The levels of MDA, TNF-α, IL-6, FABP3, and ET-1 were significantly higher, while the SOD and BDNF were significantly lower compared to baseline in the I/R group, but the variation range of those agents was significantly smaller in the Dex and Oxy groups, and the measured values were comparable between the 2 groups.ConclusionsCompared with Dex, Oxy was not inferior in mitigating tourniquet-induced hyperdynamic response, ameliorating the inflammatory reaction, and protecting remote multiple organs in lower-extremity surgery patients.

Exacerbation of ulcer as a cause of Mellory-Weiss syndrome. Case reports

Aim. To analyze the results of treatment of patients with Mellory-Weiss syndrome (MWS) and describe a number of MWS cases, caused by exacerbation of the ulcer. To detect the characteristic features of the course of disease and possible variants of unfavorable outcome.&#x0D; Materials and methods. There were analyzed the results of treatment of 176 patients with MWS, who received hospital treatment from 2008 to 2018. Fifteen MWS cases, caused by ulcer exacerbation, were described. Statistical analysis was conducted; features of disease course were revealed. A clinical case of unfavorable variant of the disease course is presented.&#x0D; Results. The study included 176 patients. Mellory-Weiss syndrome, caused by ulcer, was registered in 15 of them (main group). The patients of the main group had pain syndrome, lower systolic arterial pressure, lower hemoglobin and erythrocyte amount at admission to hospital. The paper presents the variant of extremely unfavorable course of disease, when relapse of bleeding occurred not from laceration of the mucous membrane, but from the ulcer.&#x0D; Conclusions. According to our observations, ulcer is a relatively frequent cause of MWS development and takes the second place after alcohol etiology. Such patients have peculiar features of disease course, which require different approach to diagnosis and management.

A New Triage Method for Burn Disasters: Fast Triage in Burns (FTB).

BackgroundThere are few triage methods based on patient age and extent of burn. However, in case of mass casualties, age might be hard to define. Burn segregation in mass-casualty accidents requires an easy, fast, and effective method. Triage in burns should also segregate casualties requiring treatment in burn centers. The aim of this study was to create a proprietary segregation algorithm dedicated to mass-casualty incidents.Material/MethodsA retrospective analysis of 939 burned patients admitted to the Clinical Department of Burns, Plastic and Reconstructive Surgery, Military Institute of Medicine (MIM) in Warsaw and to the Center for the Treatment of Burns (CTB) in Siemianowice Śląskie in 2012 and 2013 was performed. The aim was to reveal which early factors could be used during segregation of burn victims in mass-casualty incidents on the battlefield and in civilian circumstances. Only easy and quick-to-evaluate factors that can be examined without medical equipment and laboratory tests were used in creating the proprietary triage algorithm.ResultsAs a result of our study, we created an algorithm for fast triage in mass-casualty situations. The algorithm is based on parameters that can be easily evaluated without additional equipment. To create the algorithm, we used factors that had the strongest impact on mortality prediction in severely burned patients, in multifactor analysis: advanced age (p<0.001. OR=1.04), extent of the deep burn (p<0.001. OR=1.1), and low systolic arterial pressure (p<0.001. OR=0.96).ConclusionsThe FTB (Fast Triage in Burns) algorithm is a new triage method dedicated for massive burn events in civilian circumstances. The FTB algorithm is a simple, quick, and credible means of segregating burn victims. The algorithm is dedicated to use in pre-hospital care, during mass-casualty events both in civilian and battlefield circumstances. The aim is to be able to evaluate burn victims immediately, without access to medical equipment or additional tests and to evaluate indications for burn center care. It is a unique method designed to be used during segregation in isolated burn mass-casualty incidents.

SmartPilot® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study

BackgroundBoth under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery. MethodsThis prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the “appropriate anaesthesia zone” defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45–60 and systolic arterial pressure of 80–140 mm Hg. Postoperative complications were recorded for one month in a blinded manner. ResultsOf 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0–40) vs 5 (0–116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2–20) vs 8 (2–60) days, P=0.017). ConclusionsSmartPilot® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients. Clinical trial registrationNCT 02556658.

Effects of repeated yearly exposure to exercise-training on blood pressure and metabolic syndrome evolution.

To study if repeated yearly training programs consolidate the transient blood pressure (BP) improvements of one exercise program into durable adaptations. Obese middle-age individuals with metabolic syndrome (MetS) underwent high-intensity aerobic interval training during 16 weeks (November to mid-March) in 3 consecutive years [training group (TRAIN); N = 23]. Evolution of MetS components was compared with a matched-group that remained sedentary [control group (CONT); N = 26]. At the end of the first training program (0-4 months), TRAIN lowered systolic arterial pressure, blood glucose, waist circumference and MetS Z-score below CONT (-8.5 ± 2.5 mmHg; -19.9 ± 2.6 mg/dl; -3.8 ± 0.1 cm and -0.3 ± 0.1, respectively, all P < 0.05). With detraining (month 4-12) TRAIN adaptations relapsed to the levels of baseline (month 0) except for BP. A second exercise program (month 12-16) lowered blood glucose and waist circumference below CONT (-19.0 ± 2.0 mg/dl; -4.1 ± 0.1 cm). After detraining (month 16-24) BP, blood glucose and Z-score started below CONT values (-6.8 ± 0.9 mmHg; -24.6 ± 2.5 mg/dl and -0.4 ± 0.05, respectively, all P < 0.05) and those differences enlarged with the last training program (month 24-28). Ten-year atherosclerotic cardiovascular disease risk estimation increased only in CONT (8.6 ± 1.1-10.1 ± 1.3%; year 2-3; P < 0.05). At least two consecutive years of 4-month aerobic interval training are required to chronically improve MetS (Z-score). The chronic effect is mediated by BP that does not fully return to pretraining values allowing a cumulative improvement. On the other hand, sedentarism in MetS patients during 3 years increases their predicted atherosclerotic diseases risk. CLINICALTRIALS. NCT03019796.

Comparison of NK-1 Receptor Antagonist (Maropitant) to Morphine as a Pre-Anaesthetic Agent for Canine Ovariohysterectomy.

ObjectiveTo compare the NK-1 receptor antagonist maropitant to morphine during and after surgery in dogs undergoing ovariohysterectomy (OHE).Methods30 healthy female dogs were randomly divided to receive either a pre-anaesthetic dose of morphine (0.5 mg/kg SQ) or maropitant (1 mg/kg, SQ) prior to OHE. Anaesthesia was induced with propofol and maintained with isoflurane. Expired isoflurane concentration, heart rate (HR), systolic arterial pressure (SAP) and respiratory rate were measured. Post-operative pain scores and appetite were evaluated during the recovery period. Rescue analgesia (morphine 0.1 mg/kg IV) was administered as needed post-operatively based on blinded pain score assessments.ResultsAlthough clinically comparable; during surgical stimulation, the maropitant group had lower HR (108±18 vs 115±24 bpm; p = 0.04), lower SAP (114±23 vs 125±23 mmHg; p = 0.003) and required slightly lower percent of isoflurane anaesthetic (1.35±0.2 vs 1.51±0.4%; p = 0.005), when compared to the morphine group. In the recovery period, the maropitant group had lower pain scores at extubation (1.7±0.7 vs 3.4±2.3; p = 0.0001) and were more likely to eat within 3 hours after extubation (64.7 vs 15.3%). However, post-operative rescue analgesia requirements were similar between groups. All other measured parameters were similar between groups. The overall difference observed between groups was small and all monitored and measured parameters were within the expected range for anesthetized dogs.Clinical SignificanceNo major differences in cardiorespiratory parameters or anaesthetic requirements were observed between maropitant and morphine when used as a pre-anesthetic agent for OHE. Further studies are necessary to fully elucidate the benefits of maropitant as a pre-anaesthetic agent for canine OHE.

Role of vascular smooth muscle PPARγ in regulating AT1 receptor signaling and angiotensin II-dependent hypertension.

Peroxisome proliferator activated receptor γ (PPARγ) has been reported to play a protective role in the vasculature; however, the underlying mechanisms involved are not entirely known. We previously showed that vascular smooth muscle-specific overexpression of a dominant negative human PPARγ mutation in mice (S-P467L) leads to enhanced myogenic tone and increased angiotensin-II-dependent vasoconstriction. S-P467L mice also exhibit increased arterial blood pressure. Here we tested the hypotheses that a) mesenteric smooth muscle cells isolated from S-P467L mice exhibit enhanced angiotensin-II AT1 receptor signaling, and b) the increased arterial pressure of S-P467L mice is angiotensin-II AT1 receptor dependent. Phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase (ERK1/2) was robustly increased in mesenteric artery smooth muscle cell cultures from S-P467L in response to angiotensin-II. The increase in ERK1/2 activation by angiotensin-II was blocked by losartan, a blocker of AT1 receptors. Angiotensin-II-induced ERK1/2 activation was also blocked by Tempol, a scavenger of reactive oxygen species, and correlated with increased Nox4 protein expression. To investigate whether endogenous renin-angiotensin system activity contributes to the elevated arterial pressure in S-P467L, non-transgenic and S-P467L mice were treated with the AT1 receptor blocker, losartan (30 mg/kg per day), for 14-days and arterial pressure was assessed by radiotelemetry. At baseline S-P467L mice showed a significant increase of systolic arterial pressure (142.0±10.2 vs 129.1±3.0 mmHg, p<0.05). Treatment with losartan lowered systolic arterial pressure in S-P467L (132.2±6.9 mmHg) to a level similar to untreated non-transgenic mice. Losartan also lowered arterial pressure in non-transgenic (113.0±3.9 mmHg) mice, such that there was no difference in the losartan-induced depressor response between groups (−13.53±1.39 in S-P467L vs −16.16±3.14 mmHg in non-transgenic). Our results suggest that interference with PPARγ in smooth muscle: a) causes enhanced angiotensin-II AT1 receptor-mediated ERK1/2 activation in resistance vessels, b) and may elevate arterial pressure through both angiotensin-II AT1 receptor-dependent and -independent mechanisms.

Early activation of the kynurenine pathway predicts early death and long-term outcome in patients resuscitated from out-of-hospital cardiac arrest.

BackgroundThe kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post–cardiac arrest shock, early death, and long‐term outcome.Methods and ResultsPlasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12‐month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3‐hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3‐hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3‐hydroxyanthranilic acid had lower 24‐hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3‐hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12‐month poor outcome and significantly improved risk reclassification.ConclusionsKP is activated early after cardiac arrest and is associated with severity of post–cardiac arrest shock, early death, and poor long‐term outcome.

Association between decreased blood pressure and azotaemia in canine babesiosis.

Acute tubular necrosis (ATN) was described in canine babesiosis. Hypotension is considered as one of the factors which influence the development of hypoxic renal damage. In this study hypotension defined as mean arterial pressure (MAP) < 80 mmHg was detected in 7 out of 48 dogs (14.6%) infected with Babesia canis. Lower systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and MAP were detected in azotaemic dogs infected with B. canis. Statistically significant negative correlations between blood pressures (SAP, DAP and MAP) and serum creatinine and urea concentrations showed the influence of decreased blood pressure on the development of azotaemia and is probably also associated with ATN in canine babesiosis.

VAMP3 mediates NKCC2 trafficking in thick ascending limbs and is required for normal renal function and blood pressure

In the thick ascending limb of Henle's loop (TAL), trafficking of NKCC2 into the apical membrane is essential for NaCl absorption and blood pressure control. The vesicle associated membrane protein 3 (VAMP3), a membrane fusion protein of the SNARE family, is expressed in the kidney. VAMP3 is localized apically in TALs and co‐immunoprecipitates with NKCC2. The role of VAMP3 on Na excretion and NKCC2 trafficking is unknown. We hypothesized that VAMP3 mediates NKCC2 exocytic delivery and maintains normal TAL function and renal Na excretion. We used adenovirus‐mediated in vivo gene silencing to decrease VAMP3 expression in rat outer medullas and measured NKCC2 exocytic delivery by surface biotinylation in TAL suspensions. Silencing VAMP3 by 68 ± 10% did not affect VAMP2/7/8 expression in TALs but blocked NKCC2 exocytic delivery rate by 91 ± 6% (p&lt;0.05) and decreased total NKCC2 expression by 59 ± 8% (p&lt;0.05). We studied the role of VAMP3 in urinary Na (UNa) excretion and blood pressure in VAMP3 knockout (KO) mice. VAMP3 KOs exhibited reduced NKCC2 expression by 44 ± 12% (p&lt;0.05), elevated UNa excretion (wild type: 251 ± 11 vs VAMP3 KO: 294 ± 13 μmol/day, p&lt;0.05) and lower systolic arterial pressure (WT: 114 ± 2 vs VAMP3 KO: 95 ± 2 mmHg, p&lt;0.05). We conclude that VAMP3 mediates NKCC2 trafficking to the apical membrane and maintains NKCC2 expression. VAMP3 is required for normal Na excretion and blood pressure control. Funding: NIH, AHA

Coronary Artery Bypass Surgery for Patients with Severe Cerebrovascular Atherosclerosis: Importance of Preoperative Assessment and Perioperative Management

Objective: Cerebrovascular atherosclerosis is known to play a crucial role in perioperative stroke in coronary arterial bypass grafting (CABG). This study is to identify the degree of severity of cerebrovascular lesions for which patients can still undergo CABG with an acceptably low risk in current techniques. Methods: Cerebrovascular atherosclerosis was evaluated and graded for 200 consecutive patients prior to CABG. Grading was initially based on the level of stenosis in carotid, vertebral, and cerebral arteries: grade-0: normal or mild stenosis in cerebral arteries or stenosis % - 69% in others; grade-2: severe in cerebral arteries or 70% - 89% in others; grade-3: occlusion in cerebral arteries or 90% - 100% in others. The grading was finally adjusted to a risk of regional ischemia by considering symptoms, number of lesions, and brain perfusion in scintigram. Therefore, some patients were up-graded. Off-pump CABG was scheduled for all patients. The lowest systolic arterial pressure during surgery was differently controlled in each grade: grade-0: ≥70 mmHg; grade-1: ≥80 mmHg; grade-2: ≥80 mmHg with intra-aortic balloon pump (IABP); grade-3: ≥90 mmHg with IABP; grade-4: ≥90 mmHg with IABP and administration of thyamiral. Results: Grade-1 and -2 included 38 and 29 patients respectively. Grade-3 initially included 36 patients and 14 of them were up-graded to grade-4 (extremely high risk patients). Stroke was seen in one patient (0.5%), for whom mild speaking disturbance occurred on the fifth day from CABG. Conclusion: Patients with severe cerebrovascular atherosclerosis can undergo CABG with a low risk of stroke. Intraoperative management of blood pressure may be critical for stroke prevention in CABG.

Selective α1-adrenoceptor antagonist (controlled release tablets) in preoperative management of pheochromocytoma

The objective of this article is to evaluate the efficacy of Doxazosin Mesylate Controlled Release Tablets for preoperative treatment of patients with pheochromocytoma. Between 2003 and 2008, 67 patients with confirmed diagnoses of pheochromocytoma were enrolled in this study. According to the drug used in preoperative management, patients were divided into two groups: Doxazosin Mesylate pretreatment group (n=36) and Phenoxybenzamine pretreatment group (n=31). Surgery was performed only in patients who met the optimal preoperative condition. The hematocrit decreased significantly (P<0.001) after antiadrenergic therapy in patients pretreated with phenoxybenzamine or doxazosin. There was no significant difference between the fluid intakes during operation in both groups. The systolic arterial pressures both before and after induction of anesthesia were all significantly higher in the doxazosin patients than in the phenoxybenzamine group (P<0.05). After tumor removed, the lowest systolic arterial pressure was significantly higher in doxazosin group than in phenoxybenzamine group (P<0.05). The fluctuation of systolic arterial pressure during operation was more stable in doxazosin group than in phenoxybenzamine group (P<0.05). Doxazosin mesylate controlled release tablet was as effective as phenoxybenzamine in preoperative volume expansion. Although phenoxybenzamine provided better arterial pressure control, patients pretreated with DOX experienced more stable perioperative hemodynamic changes, shorter preoperative management periods and more simple medication.