Baseline Mean Arterial Pressure Research Articles

Counteracting Angiotensinogen Small-Interfering RNA-Mediated Antihypertensive Effects With REVERSIR.

Ssmall-interfering RNA (siRNA) targeting hepatic AGT (angiotensinogen) mRNA depletes AGT, lowering blood pressure for up to 6 months. However, certain situations may require a rapid angiotensin increase. The reverse siRNA silencing, RVR technology is a potential approach to counteract siRNA effects. Spontaneously hypertensive rats received 10 mg/kg AGT siRNA, and 3 weeks later were given AGT-RVR (1, 10, or 20 mg/kg). One week after AGT-RVR dosing, a redose of AGT siRNA assessed its post-AGT-RVR effectiveness for 2 weeks. Additionally, the impact of AGT-RVR after an equihypotensive dose of valsartan (4 mg/kg per day) was examined. Baseline mean arterial pressure (MAP) was 144±1 mm Hg. AGT siRNA reduced MAP by ≈16 mm Hg and AGT by >95%, while renin increased 25-fold. All AGT-RVR doses restored MAP to baseline within 4 to 7 days. Notably, 10 and 20 mg/kg restored AGT and renin to baseline, while 1 mg/kg allowed ≈50% AGT restoration, with renin remaining above baseline. A second AGT siRNA treatment, following 1-mg/kg AGT-RVR, reduced MAP to the same degree as the initial dose, while following 10 mg/kg AGT-RVR, it resulted in ≈50% of the first dose's MAP effect at 2 weeks. The valsartan-induced MAP reduction was unaffected by AGT-RVR. In spontaneously hypertensive rats, angiotensinogen-RVR dose-dependently reversed AGT siRNA-induced AGT reduction, normalizing MAP. MAP normalization persisted even with 50% recovered AGT levels, likely due to upregulated renin maintaining adequate angiotensin generation. Post-AGT-RVR dosing, a second AGT siRNA dose lowered MAP again.

Efficacy Assessment of Cerebral Perfusion Augmentation Through Functional Connectivity in an Acute Canine Stroke Model.

Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of NEH (Norepinephrine and Hydralazine), a cerebral perfusion augmentation therapy, on RSN integrity in a hyper-acute canine stroke model. Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Post-occlusion, the treatment group received intra-arterial Norepinephrine (0.1-1.52 μg/kg/min, adjusted for 25-45 mmHg above baseline mean arterial pressure) and Hydralazine (20mg). Resting-state fMRI data were acquired with a 3.0 T scanner using a BOLD-sensitive EPI sequence (TR/TE=1400 ms/20ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm FWHM), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis (ICA) and weighted whole-brain ROI-to-ROI connectome, pre-and post-MCAO. NEH therapy significantly maintained connectivity post-MCAO in the Higher-order Visual and Parietal RSNs, as evidenced by thresholded statistical mapping (TFCE p-corr > 0.95). However, this preservation was network-dependent, with no significant changes in the Primary Visual and Sensorimotor networks. NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity following ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable endpoint for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation. NEH＝ Norepinephrine and Hydralazine; RSN＝ Resting-State Network; ICA = Independent Component Analysis; rsfMRI = resting-state Functional Magnetic Resonance Imaging; MCAO = Middle Cerebral Artery Occlusion; TFCE = Threshold-Free Cluster Enhancement.

The effect of hypertension on cerebrovascular carbon dioxide reactivity in atrial fibrillation patients.

Atrial fibrillation (AF) and hypertension (HTN) are both associated with impaired cerebrovascular carbon dioxide reactivity (CVRCO2), an indicator of cerebral vasodilatory reserve. We hypothesised that CVRCO2 would be lower in patients with both AF and HTN (AF + HTN) compared to normotensive AF patients, due to an additive effect of AF and HTN on CVRCO2. Forty AF (68 ± 9 years) and fifty-seven AF + HTN (68 ± 8 years) patients underwent transcranial Doppler ultrasound measurement of middle cerebral artery blood velocity (MCA Vm) during stepped increases and decreases in end-tidal carbon dioxide (PETCO2). A cerebrovascular conductance index (CVCi) was calculated as the ratio of MCA Vm and mean arterial pressure (MAP). CVRCO2 was determined from the linear slope for MCA Vm and MCA CVCi vs PETCO2. Baseline MAP was higher in AF + HTN than AF (107 ± 9 vs. 98 ± 9 mmHg, respectively; p < 0.001), while MCA Vm was not different (AF + HTN:49.6 [44.1-69.0]; AF:51.7 [45.2-63.3] cm.s-1; p = 0.075), and CVCi was lower in AF + HTN (0.46 [0.42-0.57] vs. 0.54 [0.44-0.63] cm.s-1.mmHg-1; p < 0.001). MCA Vm CVRCO2 was not different (AF + HTN: 1.70 [1.47-2.19]; AF 1.74 [1.54-2.52] cm/s/mmHg-2; p = 0.221), while CVCi CVRCO2 was 13% lower in AF + HTN (0.013 ± 0.004 vs 0.015 ± 0.005 cm.s-1.mmHg-1; p = 0.047). Our results demonstrate blunted cerebral vasodilatory reserve (determined as MCA CVCi CVRCO2) in AF + HTN compared to AF alone. This may implicate HTN as a driver of further cerebrovascular dysfunction in AF that may be important for the development of AF-related cerebrovascular events and downstream cognitive decline. We demonstrated reduced cerebrovascular CO2 responsiveness in atrial fibrillation with hypertension (AF+HTN) vs. atrial fibrillation (AF). Furthermore, AF per se (as opposed to normal sinus rhythm) predicts reduced cerebrovascular CO2 responsiveness. Our findings suggest additional cerebrovascular dysfunction in AF+HTN vs. AF.

COMPARISON OF THE VARIABILITY OF RECOVERY PROFILE AND HEMODYNAMIC EFFECTS OF NEUROMUSCULAR BLOCKADE WITH CISATRACURIUM VERSUS ATRACURIUM

A randomized controlled trial was conducted at the Main Operation Theatre of Jinnah Postgraduate Medical Centre (JPMC) in Karachi to compare the recovery profile and hemodynamic effects of cisatracurium and atracurium among patients undergoing laparoscopic cholecystectomy. The study was conducted from 20th July 2019 to 19th January 2020 and included 68 patients aged between 20 to 50 years undergoing elective laparoscopic cholecystectomy under general anesthesia. Patients with a history of allergy to the study drugs, neuromuscular, pulmonary, renal, or hepatic diseases, smoking, pregnancy, or breastfeeding, and those on preoperative medication such as antipsychotics, aminoglycosides, steroids, or neuroleptics were excluded. The patients were randomly divided into two groups. In Group 1, comprising 34 patients, cisatracurium (0.2 mg/kg) was administered, whereas in Group 2, also with 34 patients, atracurium (0.5 mg/kg) was given. Neuromuscular blocking agents were administered three minutes before intubation. The primary outcomes measured were the recovery profile and hemodynamic effects. In Group 1 (cisatracurium), the baseline mean arterial pressure (MAP) was recorded as 98.40 ± 8.02 mmHg, which increased to 112.20 ± 8.88 mmHg before intubation, resulting in a change of 13.56 ± 5.59 mmHg. In contrast, in Group 2 (atracurium), the baseline MAP was 94.10 ± 7.91 mmHg, which rose to 109.07 ± 8.35 mmHg before intubation, indicating a change of 16.50 ± 4.38 mmHg. The study concluded that cisatracurium is more effective in exhibiting neuromuscular blocking properties than atracurium in patients undergoing laparoscopic cholecystectomy under general anesthesia.

Sex differences in the purinergic 2 receptor-mediated blood pressure response to treadmill exercise in rats with simulated peripheral artery disease.

We investigated the role played by ATP-sensitive purinergic 2 (P2) receptors in evoking the pressor response to treadmill exercise in male and female rats with and without femoral arteries that were ligated for ∼72 h to induce simulated peripheral artery disease (PAD). We hypothesized that PPADS (P2 receptor antagonist, 10 mg iv) would reduce the pressor response to 4 min of treadmill exercise (15 m·min-1, 1° incline) and steady-state exercise plasma norepinephrine (NE) values in male and female rats, and that the magnitude of effect of PPADS would be greater in rats with simulated PAD ("ligated") than in sham-operated rats. In males, PPADS significantly reduced the difference between steady-state exercise and baseline mean arterial pressure (ΔMAP) response to treadmill exercise in sham (n = 8; pre-PPADS: 12 ± 2, post-PPADS: 1 ± 5 mmHg; P = 0.037) and ligated (n = 4; pre-PPADS: 20 ± 2, post-PPADS: 11 ± 3 mmHg; P = 0.028) rats with a similar magnitude of effect observed between groups (P = 0.720). In females, PPADS had no effect on the ΔMAP response to treadmill exercise in sham (n = 6; pre-PPADS: 9 ± 2, post-PPADS: 7 ± 2 mmHg; P = 0.448) or ligated (n = 6; pre-PPADS: 15 ± 2, post-PPADS: 16 ± 3 mmHg; P = 0.684) rats. When NE values were grouped by sex independent of ligation/sham status, PPADS significantly reduced plasma NE in male (P = 0.016) and female (P = 0.027) rats. The data indicate that P2 receptors contribute to the sympathetic response to exercise in both male and female rats but that the sympathoexcitatory role for P2 receptors translates into an obligatory role in the blood pressure response to exercise in male but not in female rats.NEW & NOTEWORTHY Here, we demonstrate that purinergic 2 (P2) receptors contribute significantly to the blood pressure response to treadmill exercise in male rats both with and without simulated PAD induced by femoral artery ligation. We found no role for P2 receptors in the blood pressure response to treadmill exercise in female rats, thus revealing clear sex differences in P2 receptor-mediated blood pressure control during exercise.

Clinical and biochemical predictors of longitudinal changes in left atrial structure and function: A general population study.

There is a need for better understanding the factors that modulate left atrial (LA) dysfunction. Therefore, we determined associations of clinical and biochemical biomarkers with serial changes in echocardiographic indexes of LA function in the general population. We measured LA maximal and minimal volume indexes (LAVImax and LAVImin) by echocardiography and LA reservoir strain (LARS) by two-dimensional speckle-tracking in 627 participants (mean age 50.8 years, 51.2% women) at baseline and after 4.8 years. During follow-up, LARS decreased significantly in men (-.90%, P=.033) but not in women (-.23%, P= .60). In stepwise regression analysis, stronger decrease in LARS over time was associated with male sex, a higher age, body mass index (BMI), mean arterial pressure (MAP) and serum insulin at baseline and with a greater increase in BMI and MAP over time (P≤.018). Similarly, an increased risk of developing or retaining abnormal LARS was observed in older participants, in subjects with a higher baseline BMI, MAP, heart rate (HR), troponin T and ΔMAP, and in those who used β-blockers at baseline. Both LAVImax and LAVImin increased significantly over time (P≤.0007). This increase was associated with a higher baseline age, pulse pressure and a lower HR at baseline and a greater increase in pulse pressure over time (P≤.029). Higher serum insulin and D-dimer were independently associated with a stronger increase in LAVImin (P≤.0034). Subclinical worsening in LA dysfunction was associated with older age, hypertension, obesity, insulin resistance and troponin T levels. Cardiovascular risk management strategies may delay LA deterioration.

Efficacy of Magnesium Sulphate and Dexmedetomidine in Controlled Hypotension for Functional Endoscopic Sinus Surgery: A Randomised Clinical Study

Introduction: The treatment of nasal sinus diseases with Functional Endoscopic Sinus Surgery (FESS) is a wellestablished and popular method. This procedure is performed under general anaesthesia or local anaesthesia. Intentional induction of hypotension has helped limit intraoperative blood loss. A bloodless surgical field improves visibility and lowers the possibility of damaging nearby structures, achieved by reducing the baseline Mean Arterial Pressure (MAP) by 30% or maintaining MAP at 60-70 mmHg. Aim: To compare the efficacy of dexmedetomidine and Magnesium Sulphate (MgSO4 ) in producing hypotensive anaesthesia during FESS. Materials and Methods: This randomised clinical study was conducted at BLDE Shri BM Patil Medical College and Research Centre, Vijayapura, Karnataka, India, from January 2021 to July 2022. In this study, 70 patients, aged 18 to 60 years of either sex, admitted for FESS surgeries under general anaesthesia with American Society of Anaesthesiologists (ASA) Grade 1 and 2 were randomly divided into two groups: 35 patients in the dexmedetomidine group and 35 patients in the MgSO4 group. Dexmedetomidine was given to group D as a loading dose of 1 µg/kg, followed by an infusion of 0.5 µg/kg/h, and MgSO4 was given to group M as a loading dosage of 40 mg/kg, followed by an infusion of 15 mg/kg/h. MAP was kept above 65 mmHg during induced hypotension. Parameters studied included Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), MAP. Data was analysed using International Business Machines (IBM) Statistical Package for Social Sciences (SPSS) Statistics Software Version 23.0. A p-value &lt;0.05 was considered statistically significant. Results: The demographic profiles regarding age, gender, ASA grade, and duration of surgery in both groups were comparable and showed no significant differences. At 30 minutes of surgery, MAP in group D was found to be statistically lower than that in group M with a p-value of 0.0001. Dexmedetomidine induced a significant reduction in HR, which was statistically validated with a p-value of 0.004 at 15 minutes. A statistically significant reduction in MAP was found in group D compared to group M at the time of intubation and later at 10 minutes (p-value=0.005) and 15 minutes (p-value=0.006). Conclusion: The target MAP of 60-70 mmHg or a 30% reduction from the baseline MAP was achieved significantly earlier in group D as compared with group M. Group D had lower infusion dosages, better surgical field visibility, and caused less bleeding. The dexmedetomidine group experienced extended sedation and postoperative recovery

Oral Clonidine versus Ivabradine for Attenuating Stress Response in Functional Endoscopic Sinus Surgery: A Randomised Placebo-controlled Study

Introduction: Peri-anaesthetic haemodynamic alterations, such as hypertension and tachycardia, can cause increased bleeding during Functional Endoscopic Sinus Surgery (FESS), impairing the visibility of the surgical field and resulting in scarring, adhesions, and prolonged surgery time. Various strategies involving pharmacological techniques have been used to mitigate these unfavourable reflexes. Alpha-2 agonists, such as Clonidine, are currently being employed to attenuate sympathoadrenal stimulation caused by tracheal intubation and surgery. Ivabradine is a new drug that selectively lowers Heart Rate (HR) by inhibiting cardiac funny current channels. Aim: To compare the effects of premedication with oral Clonidine versus oral Ivabradine on attenuating haemodynamic stress response and improving the quality of the surgical field in FESS. Materials and Methods: The present randomised, placebocontrolled, double-blind study was conducted in the Department of Anaesthesiology and Intensive care at Rajendra Hospital, Government Medical College, Patiala, Punjab, India from April 2021 to December 2022 on 90 American Soceity of Anaesthelogists ( ASA) Physical status I and II adult patients (aged 18-60 years) undergoing FESS. Group A (n=30) received oral Ivabradine 5 mg, Group B (n=30) received oral Clonidine 0.2 mg, and Group C (n=30) received oral placebo tablets 2 hours before surgery. Haemodynamic parameters, including HR and Mean Arterial Pressure (MAP), quality of the intraoperative surgical field, postoperative sedation score, Visual Analogue Scale (VAS) score, time to analgesia request, blood loss, and adverse effects, were recorded. Descriptive statistics were used to calculate mean±Standard Deviation (SD) and percentage. Analysis of Variance (ANOVA), Tukey post-hoc test, Kruskal-wallis H test, and Pearson’s Chi-square were applied as appropriate. Results: The mean ages were 33.87±12.84, 35.03±12.93, and 40.9±14.46 years for Groups A, B, and C, respectively. The mean weights were 60.5±8.91, 57.83±5.66, and 57.9±5.42 kg, and the mean duration of surgery was 88.67±4.29, 88.8±4.29, and 88.03±3.93 minutes for Groups A, B, and C, respectively. There were no significant differences in terms of gender, ASA score, and type of surgery between the groups. Baseline HR and MAP were comparable among the groups. HR was significantly lower in both Groups A and B compared to Group C at all time intervals (p-value &lt;0.001). Both drugs significantly attenuated tachycardia and hypertension in response to cardiovascular stress induced by laryngoscopy, endotracheal intubation, and extubation. However, Group B showed significantly better control of MAP throughout the intraoperative period and at extubation. The average category scale score, estimated blood loss, and postoperative VAS Score were all significantly lower in Group B than in Group A. Postoperative sedation scores were significantly higher in Group B, and the time to first rescue analgesic was longest in Group B (p&lt;0.05). No significant side effects were observed. Conclusion: Both Clonidine and Ivabradine effectively attenuated the haemodynamic stress response. Clonidine provided better control of MAP, resulting in reduced bleeding, improved operative field visibility, and lower postoperative analgesic requirements compared to Ivabradine.

Inferior vena cava collapsibility index as a predictor of hypotension after induction of general anesthesia in hypertensive patients

BackgroundHypertensive patients are more susceptible to develop hypotension after the induction of general anesthesia (GA), most likely due to hypovolemia. An inferior vena cava collapsibility index (IVCCI) > 40–50% can predict hypotension after the induction of GA in the general population by variable accuracies. The current study aimed to investigate IVCCI% as a predictor of postinduction hypotension in hypertensive patients undergoing noncardiac surgery.MethodsUltrasound IVCCI % was assessed for all controlled hypertensive patients immediately before induction of GA. After induction of GA, patients were diagnosed with postinduction hypotension if their systolic arterial pressure (SAP) dropped by ≥ 30% of the baseline value and/or mean arterial pressure (MAP) dropped to < 65 mmHg up to 15 min after intubation. The receiver operating characteristic (ROC) curve of IVCCI% was compared to patients’ classification either developing hypotension after induction of GA or not as a gold standard.ResultsOf the 153 patients who completed the study, 62 (40.5%) developed hypotension after the induction of GA, and 91 (59.5%) did not. An IVCCI > 39% predicted the occurrence of postinduction hypotension with high accuracy (84%) (AUC 0.908, P < 0.001). The area of uncertainty (by gray zone analysis) of IVCCI lies at values from 39 to 45%. This gray zone included 21 patients (13.7% of all patients).ConclusionAn inferior vena cava collapsibility index > 39% before anesthetic induction can be a simple noninvasive reliable predictor of hypotension after the induction of GA for hypertensive patients not treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and undergoing noncardiac surgery.Trial registrationThis clinical trial was approved by the Institutional Review Board (IRB) at Zagazig University (ZUIRB #9424 dated 03/04/2022), and patients’ informed consent for participation in the study was obtained during the period from May 2022 to May 2023. All study procedures were carried out in accordance with the ethical standards of the Helsinki Declaration of 2013.

Sodium glucose co-transporter-2 (SGLT) inhibitors in patients with compensated cirrhosis and diabetes: A prospective study

Aims and objective: Diabetes in patients with cirrhosis is common. SGLT-2 inhibitors are newer class of antidiabetic drugs with pleiotropic effects. Its safety and efficacy has not been evaluated in patients with advanced cirrhosis and diabetes. We evaluated safety and efficacy of SGLT-2 inhibitors in patients with compensated cirrhosis and diabetes. Material and method: Consecutive patients with compensated cirrhosis and diabetes who were started on SGLT-2 inhibitors were enrolled and followed every month for six months. Their clinical and biochemical parameters which include liver and kidney function tests, urine test, glycosylated haemoglobin (HbA1c), transient elastography (fibroscan), Mean Arterial Pressure (MAP) and change in weight since treatment initiation were noted. Any relevant side effects (urinary and genital infection, hypotension) were noted. Results: Twenty patients [(M:F: 13:7), age (55±11 yr), CTP score (6±1.3), etiology of cirrhosis (NASH related 17, HBV, n=1 and HCV, n=2), baseline MAP (91±5 mmHg)] were enrolled. Five patients had hypertension and taking angiotensin converting enzyme (ACE) inhibitors and 15 patients were also on carvidelol. Mean Fibroscan was (37±11kPa), large varices (n=3), small varices (n=16) and no varices were seen in one patient. All patients were followed up for 6 months. Patient were on dapagliflogin (n=11, 55%), empagliflogin (n=6, 30%) and remogliflogin (n=3, 15%). Twelve (60%) patients were also on metformin and 7 (35%) on Dipeptidyl peptidase 4(DPP4) inhibitors. Significant improvement was seen in total bilirubin Baseline (B), 1.19±0.5, Month 3 (Mo 3), 1.02±0.4 and Month 6 (Mo 6), 1.01±0.3 mg/dl], AST (B, 50.8±20.8, Mo 3, 49.4±20.5, Mo 6, 42.8±13.0 IU/L) and GGT (B, 63.8±24.5, Mo 3, 66.5±31.0 and Mo 6, 58.3±21.4 IU/dl) level at month 3 and 6. Glycemic index improved at month 3 and 6 and significant weight loss was seen at month 3 and 6. Serum creatinine, serum sodium level and mean arterial pressure remained unchanged at month 6. Urinary tract infection occurred in n=3 (15%), genital infection in (n=2, 10%) and compliant of frothy urine was seen in (n=4, 20%) without discontinuation of medicines.

Raising Systemic Blood Pressure to Delay Irreversible Intestinal Ischemia in a Swine Model of Proximal Superior Mesenteric Artery Occlusion

IntroductionAcute proximal superior mesenteric artery (SMA) occlusion is highly lethal, and adjuncts are needed to mitigate ischemic injury until definitive therapy. We hypothesized that raising mean arterial pressure (MAP) >90 mmHg with norepinephrine may delay irreversible bowel ischemia by increasing gastroduodenal artery (GDA) flow despite possible pressor-induced vasospasm. Methods12 anesthetized swine underwent laparotomy, GDA flow probe placement, and proximal SMA exposure and clamping. Animals were randomized between conventional therapy (CT) versus targeted MAP >90 mmHg (MAP push; MP) where norepinephrine was titrated after 45 min of SMA occlusion. Animals were followed until bowel death or 4 h. Kaplan–Meier bowel survival, mean normalized GDA flow, and histology were compared. Results12 swine (mean 57.8 ± 7.6 kgs) were included, six per group. Baseline weight, HR, MAP and GDA flows were not different. Within 5 min following SMA clamping, all 12 animals had an increase in MAP without other intervention from 81.7 to 105.5 mmHg (29.1%, P < 0.01) with a concomitant 74.9% increase in GDA flow as compared to baseline (P < 0.01). Beyond 45 min postclamp, MAP was greater in the MP group as intended, as were GDA flows. Median time to irreversibly ischemic bowel was 31% longer for MAP push animals (CT: 178 versus MP: 233 min, P = 0.006), Hazard Ratio of CT 8.85 (95% CI: 1.86-42.06); 3/6 MP animals versus 0/6 CT animals with bowel survived to predetermined end point. ConclusionsIn this swine model of acute complete proximal SMA occlusion, increasing MAP >90 mmHg with norepinephrine was associated with an increase in macrovascular blood flow through the GDA and bowel survival. Norepinephrine was not associated with worse bowel survival and a MAP push may increase the time window where ischemic bowel can be salvaged.

Maternal Hyperglycemia Induces Autonomic Dysfunction and Heart Failure in Older Adult Offspring.

Offspring exposed to an adverse fetal environment, such as gestational diabetes, may manifest increased susceptibility to several chronic diseases later in life. In the present study, the cardiovascular function of three different ages of offspring from diabetic rats was evaluated. Diabetes mellitus was induced in pregnant rats by a single dose of streptozotocin (50 mg/kg). The offspring from diabetic (OD) and control rats (OC) were evaluated at three different ages: 6, 12 or 18 months. In the corresponding OC groups, fasting glycemia, baseline mean arterial pressure, and sympathetic tonus increased in the OD rats at 12 (OD12) and 18 (OD18) months of age, while cardiac hypertrophy was observed in all OD groups. Cardiac function evaluation in vivo showed low left ventricular systolic pressure and+dP/dt in the OD18 rats, suggesting a systolic dysfunction. OD12 and OD18 groups showed high left ventricle end-diastolic pressure, suggesting a diastolic dysfunction. OD groups showed an age-related impairment of both baroreflex-mediated tachycardia and baroreflex-mediated bradycardia in OD12 and OD18 rats. In isolated hearts from OD18 rats, both inotropic and tachycardiac responses to increasing isoproterenol were significantly reduced compared to the corresponding OC group. These results suggest that gestational diabetes triggers the onset of hyperglycemia hypertension with impaired baroreflex sensitivity and heart failure in older age of offspring, representing important risk factors for death. Therefore, ensuring optimal glycemic control in diabetic pregnancy is important and serves as a key to preventing cardiovascular disease in the offspring in their older age.

Investigation of the Optimum Baseline Blood Pressure for Spinal Anesthesia to Guide Vasopressor Management for Elective Cesarean Delivery: A Case-Control Design.

Current guidelines recommend prophylactic vasopressor administration during spinal anesthesia for cesarean delivery to maintain intraoperative blood pressure above 90% of the baseline value. We sought to determine the optimum baseline mean arterial pressure (MAP) reading to guide the management of spinal hypotension. We performed a secondary analysis of data collected from normotensive patients presenting for elective cesarean delivery in a tertiary care institution from October 2018 to August 2020. We compared the magnitude of hypotension in patients who reported nausea versus those who did not, using a case-control design. Baseline MAPs at last office visit, morning of surgery, or operating room (pre-spinal) were determined. We calculated the duration and degree of hypotension using the area under the curve (AUC) when the MAP of the respective patient was below 90% of each baseline. The patients who experienced nausea (n=45) had longer and more profound periods of hypotension than those who did not develop nausea (n=240). A comparison of AUC using MAP baseline at the last office visit or on the morning of surgery showed a statistically significant between-group difference, P=0.02, and P=0.005, respectively, and no significant between-group difference when 90% of the MAP baseline in the operating room was used. Patients had the highest preoperative MAP in the operating room and the AUC was similar for those with and without nausea when the pre-spinal MAP baseline was used. Therefore, maintaining higher intraoperative blood pressure using individual pre-spinal MAP as baseline should reduce intraoperative maternal nausea.

Angiotensinergic and GABAergic transmission in the medial preoptic area: role in urinary bladder and cardiovascular control in female rats.

Introduction: The medial preoptic area (mPOA) participates in thermoregulatory control and blood pressure modulation as shown by studies with electrical stimulation of this area or cobalt chloride injection, a non-selective synapse inhibitor. This study aimed to investigate whether angiotensin II (Ang II) and GABA could act or not in the mPOA to mediate the cardiovascular and micturition control pathways. Methods: Female Wistar rats were submitted to stereotaxic surgery for implantation of a guide cannula into the mPOA 7days prior to the experiments. Afterwards, the animals were isoflurane- anesthetized and submitted to the catheterization of the femoral artery and vein and urinary bladder cannulation for mean arterial pressure (MAP), heart rate (HR), and intravesical pressure (IP) recordings, respectively. After the baseline MAP, HR, and IP recordings for 15min, Ang II (0.1nM, 1μL), losartan (AT-1 receptor antagonist, 100nM, 1μL), GABA (50mM, 1μL) or saline (1μL) were injected into the mPOA, and the variables were measured for additional 30min. In a different group of rats, the AT-1 receptor, angiotensin II converting enzyme (ACE), and GABAa receptor gene expression was evaluated in mPOA samples by qPCR. The data are as mean ± SEM and submitted to One-way ANOVA (Tukey posttest) or paired Student t-test (P <0.05). Results: The injection of Ang II into the mPOA evoked a significant hypotension (-37±10mmHg, n = 6, p = 0.024) and bradycardia (-47 ± 20bpm, p = 0.030) compared to saline (+1 ± 1mmHg and +6 ± 2bpm, n = 6). A significant increase in IP was observed after Ang II injection into the mPOA (+72.25 ± 17.91%, p = 0.015 vs. -1.80 ± 2.98%, n = 6, saline). No significant changes were observed in MAP, HR and IP after the losartan injection in the mPOA compared to saline injection. Injection of GABA into the mPOA evoked a significant fall in MAP and HR (-68 ± 2mmHg, n = 6, p < 0.0001 and -115 ± 14bpm, n = 6, p = 0.0002 vs. -1 ± 1mmHg and +4 ± 2bpm, n = 6, saline), but no significant changes were observed in IP. The AT-1 receptor, ACE and GABAa receptor mRNA expression was observed in all mPOA samples. Discussion: Therefore, in female rats, Ang II mediated transmission in the mPOA is involved in the cardiovascular regulation and in the control of central micturition pathways. A phasic control dependent on AT-1 receptors in the mPOA seems to be involved in the regulation of those cardiovascular and intravesical 3 parameters. In contrast, GABAergic transmission in the mPOA participates in the pathways of cardiovascular control in anesthetized female rats, nevertheless, this neurotransmission is not involved in the micturition control.

Dose-related effects of norepinephrine on early-stage endotoxemic shock in a swine model

BackgroundThe benefits of early use of norepinephrine in endotoxemic shock remain unknown. We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model. MethodsVasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs. Treatment included fluid resuscitation and administration of different doses of norepinephrine, to induce return to baseline mean arterial pressure (MAP). Fluid management, hemodynamic, microcirculation, inflammation, and organ function variables were monitored. All animals were supported for 6 h after endotoxemic shock. ResultsInfused fluid volume decreased with increasing norepinephrine dose. Return to baseline MAP was achieved more frequently with doses of 0.8 µg/kg/min and 1.6 µg/kg/min (P <0.01). At the end of the shock resuscitation period, cardiac index was higher in pigs treated with 0.8 µg/kg/min norepinephrine (P <0.01), while systemic vascular resistance was higher in those receiving 0.4 µg/kg/min (P <0.01). Extravascular lung water level and degree of organ edema were higher in animals administered no or 0.2 µg/kg/min norepinephrine (P <0.01), while the percentage of perfused small vessel density (PSVD) was higher in those receiving 0.8 µg/kg/min (P <0.05) and serum lactate was higher in the groups administered no and 1.6 µg/kg/min norepinephrine (P <0.01). ConclusionsThe impact of norepinephrine on the macro- and micro-circulation in early-stage endotoxemic shock is dose-dependent, with very low and very high doses resulting in detrimental effects. Only an appropriate norepinephrine dose was associated with improved tissue perfusion and organ function.

Effects of Remimazolam Anesthesia with Two Induction Doses on Hemodynamics and Recovery Profile in Older Patients: Comparison with Propofol Anesthesia.

Remimazolam has advantages such as hemodynamic stability and rapid onset. We investigated the effects of induction doses on hemodynamics and recovery profiles for remimazolam compared to propofol in older patients. Sixty-nine patients aged >65 years were randomly assigned to either the propofol anesthesia group (P group) or the remimazolam anesthesia group with an induction dose of 6 mg/kg/h (R6 group) or 12 mg/kg/h (R12 group), followed by 1 mg/kg/h. P group was anesthetized with 4 µg/mL of propofol effect-site concentration (Ce) with target-control infusion, followed by 2.5-3 µg/mL of Ce. The primary outcome was the difference between the baseline mean arterial pressure (MAP) and the lowest MAP during anesthesia (ΔMAP). ΔMAP was comparable between the P, R6, and R12 groups (43.8 ± 13.8 mmHg, 39.2 ± 14.3 mmHg, and 39.2 ± 13.5 mmHg, p = 0.443). However, the frequencies of vasoactive drug use were 54.5%, 17.4%, and 30.4% (p = 0.029), and the median doses of ephedrine 3 (0-6) mg, 0 (0-0) mg, and 0 (0-0) mg (p = 0.034), which were significantly different. This study showed remimazolam anesthesia with an induction dose of 6 mg/kg/h, rather than 12 mg/kg/h, could reduce the requirement for vasoactive drugs compared to propofol anesthesia.

Effect of Nasal Submucosal Injection of Low-concentration Epinephrine on Visual Field Visualization in Endoscopic Sinus Surgery: A Systematic Review and Meta-analysis.

Objective: To determine whether nasal submucosal injection of low-concentration epinephrine improved the surgical field visualization and physician satisfaction compared to placebo or without intervention. Methods: A literature search of PubMed, Scopus, Web of Science, Cochrane library, China National Knowledge Infrastructure, and Wanfang Database was conducted from inception to January 10, 2023. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analyses were performed using Review Manager (RevMan version 5.3; the Cochrane Collaboration). Quality was assessed by 2 reviewers using the Cochrane Risk of Bias Tool. And we used funnel plots to visually assess the risk of publication bias. Results: We included a total of 11 studies with 492 patients, all of which were randomized controlled trials. Among the studies, 4 had a low risk of bias, 4 had a moderate risk of bias, and 3 had a high risk of bias. Five studies reported visual bleeding grade in the surgical field (P = 0.07) and total blood loss (P = 0.16), 8 studies reported preoperative baseline heart rate (P = 0.58) and baseline mean arterial pressure (MAP) (P = 0.78), and 9 studies reported intraoperative heart rate (P = 0.27) and MAP (P = 0.56), which showed no significant differences in these parameters between the 2 groups. None of these outcomes were statistically significant between the epinephrine group and the control group. Conclusion: There is insufficient evidence to support the nasal submucosal application of low-concentration epinephrine to improve surgical field dryness and reduce total surgical bleeding.

GABAergic and glutamatergic transmission reveals novel cardiovascular and urinary bladder control features in the shell nucleus accumbens

The shell Nucleus Accumbens (NAcc) projects to the lateral preoptic area, which is involved in the central micturition control and receives inputs from medullary areas involved in cardiovascular control. We investigated the role of GABAergic and glutamatergic transmission in the shell NAcc on intravesical pressure (IP) and cardiovascular control. Male Wistar rats with guide cannulas implanted bilaterally in the shell NAcc 7 days prior to the experiments were anesthetized with 2% isoflurane in 100% O2 and subjected to cannulation of the femoral artery and vein for mean arterial pressure (MAP) and heart rate recordings (HR) and infusion of drugs, respectively. The urinary bladder (UB) was cannulated for IP measurement. A Doppler flow probe was placed around the renal arterial for renal blood flow (RBF) measurement. After the baseline MAP, HR, IP and RBF recordings for 15 min, GABA or bicuculline methiodate (BMI) or L-glutamate or kynurenic acid (KYN) or saline (vehicle) were bilaterally injected into the shell NAcc and the variables were measured for 30 min. Data are as mean ± SEM and submitted to Student́s t test. GABA injections into the shell NAcc evoked a significant fall in MAP and HR and increased IP and RC compared to saline. L-glutamate in the shell NAcc increased MAP, HR and IP and reduced RC. Injections of BMI and KYN elicited no changes in the variables recorded. Therefore, the GABAergic and glutamatergic transmissions in neurons in the shell NAcc are involved in the neural pathways responsible for the central cardiovascular control and UB regulation.

Etomidate Versus Propofol for Monitored Anesthesia Care During Endoscopic Retrograde Cholangiopancreatography: A Prospective Randomized Controlled Trial.

Background and objectives Propofol-based sedation is one of the most commonly used methods for endoscopic retrograde cholangiopancreatography (ERCP). The commonest complications during ERCP are in the form of adverse cardiopulmonary events as a result of sedation. Etomidate has a more stable cardiovascular and respiratory profile than propofol and has been used forsedation in simple gastrointestinal endoscopy but has not been studied for procedural sedation in ERCP. The objective of the present study was to compare the safety and feasibility of etomidate and propofol for sedation during ERCP procedures. Methods This single-center, randomized trial included 100 American Society of Anesthesiologists (ASA) physical status class I to II patients who were scheduled for ERCP. All patients received midazolam 0.02 mg/kg, lignocaine (2%) 1 mg/kg, and fentanyl 1 µg/kg intravenously, followed by etomidate or propofol according to the group allocation. The primary outcome was to compare the mean arterial pressure (MAP) at various timepoints between the two groups and secondary outcomes were to compare oxygen saturation, induction and recovery times, and adverse events. Transient hypotension was defined as any decrease in MAPbelow 60 mmHg or 20% below the baseline. Transient hypoxia was defined as desaturation (saturation of peripheral oxygen (SpO2) <92%) lasting for more than 10 seconds requiring airway intervention. Results Fifty patients were enrolled in each group (Group E: etomidate and Group P: propofol). Transient hypotension occurred in eight (16%) patients in Group P, and two (4%) patients in Group E (P= 0.045). Baseline MAP was comparable between the two groups but was significantly lower in Group P at three timepoints during the study. Nine (18 %) patients in Group P had a transient hypoxic episode, compared to none in Group E (p= 0.006). The induction and recovery times were similar in the two groups. Conclusions Etomidate offers better hemodynamic and respiratory stability than propofol and can be recommended for use during ERCP in ASA I/II patients.

Hypotension during transsphenoidal pituitary surgery associated with increase in plasma levels of brain injury markers.

Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2 = .20, p < .001) and ∆NfLpeak (r2 = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.