Rise In Mean Arterial Pressure Research Articles

Haemodynamic Responses Following Lidocaine Infusion on Hypertensive Patient Undergoing Laparoscopic Cholecystectomy

Many pharmacological methods have been evaluated to attenuate the adverse haemodynamic responses resulting from airway manipulation and pneumoperitoneum. Intravenous lidocaine infusion is one of them; bolus dose of intravenous lidocaine is used to reduce haemodynamic changes resulting from intubation and extubation reflex whereas intraoperative infusion of lidocaine has been used for post-operative analgesia in laparoscopic cholecystectomy. This randomized controlled trial was conducted to observe the effectiveness of lidocaine infusion in obtundation of haemodynamic responses on hypertensive patient undergoing laparoscopic cholecystectomy. A total number of 80 patients were enrolled in this study. Patients were allocated into two groups by computer generated random chart according to a 1:1 ratio. The patients of group A were given general anaesthesia with placebo normal saline infusion and the patients of group B were given general anaesthesia with lidocaine infusion (1.5mg/kg). Mean differences of blood pressure (SBP & MAP) and heart rate at different time periods from baseline were compared between two groups. The demographic profiles were almost similar between the groups (p>0.05). In comparison between two groups, heart rate, systolic blood pressure and mean arterial pressure rise from baseline value was more in normal saline group (group A) than lidocaine test group (group B) during peri-intubation, pneumoperitoneum and peri-extubation period. Statistical difference was significant between two groups (p<0.05) in different haemodynamic parameters. Adverse events such as tachycardia premature ventricular contraction (PVC) and hypertension were observed much more in group A, which was higher than that of group B. We observed that administration of lidocaine infusion attenuates haemodynamic responses of hypertensive patient during laparoscopic cholecystectomy. CBMJ 2024 July: vol. 13 no. 02 P: 148-157

Analgesic and hemodynamic effects of intravenous magnesium sulfate infusion versus lidocaine infusion in patients undergoing thyroid surgery for toxic goiter resection: a randomized controlled study

Background Anesthesia for toxic goiter resection is challenging as manipulation of the thyroid gland and inadequate postoperative pain control could lead to hemodynamic instability due to stress and a neurohormonal response. Both magnesium sulfate and lidocaine are known for their analgesic effects and decreasing stress response. Herein, we compared the previous two medications regarding intraoperative hemodynamics and postoperative analgesia. Patients and methods 57 patients who underwent toxic goiter resection were enrolled in this prospective randomized trial (group M received magnesium sulfate, group L received lidocaine, and group C received normal saline). Intraoperative hemodynamics and postoperative analgesic profiles were assessed. Results Both injection groups expressed significantly lower pain scores compared with control group at Post anaesthesia care unit (PACU) and one-hour postoperative. Postoperative fentanyl consumption was significantly lower, and the time to first analgesic request was significantly prolonged in Magnesium and Lidocaine groups than in the control group. The previous beneficial effects were more prominent in the Magnesium Group compared with the Lidocaine Group. There was no significant difference in mean arterial pressure (MAP) and heart rate (HR) among the three study groups at the baseline, after the end of infusion, and after induction. Nonetheless, there was a significant rise in mean arterial pressure and heart rate values in the control group compared with the Magnesium and Lidocaine Groups with intubation and during the first hour of surgery. Conclusion Both magnesium sulfate and lidocaine have beneficial hemodynamic stabilizing and analgesic effects in patients undergoing thyroid surgery for toxic goiter, with a slight superiority for magnesium.

Novel predictors of response to therapy with terlipressin and albumin in hepatorenal syndrome-acute kidney injury.

A combination of terlipressin and albumin is the first-line pharmacologic treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI). We assessed the response rates to terlipressin-albumin therapy in patients with HRS-AKI and determined early predictors of treatment response and survival. A total of 84 patients with HRS-AKI (International Club of Ascites definition 2015) treated with terlipressin-albumin were included. Predictors of HRS reversal were identified by logistic regression analysis. Survival analysis was performed using the Kaplan-Meier method, and Cox regression models were used to determine independent predictors of mortality. Complete response to therapy was observed in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete treatment response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (ΔRRI) by day 3 of treatment. Independent predictors of HRS reversal were the presence of SIRS at baseline (P=0.022; odds ratio [OR] 15.74, 95% confidence interval [CI] 1.47-167.82) and ΔRRI ≥5% by day 3 of treatment (P=0.048; OR 6.67, 95%CI 1.021-43.62). Mean transplant-free survival at 6 months was significantly better in treatment responders (148 vs. 90 days, P<0.001). Independent predictors of 6-month mortality were response to treatment (P=0.004) and model for end-stage liver disease-sodium >23 (P=0.018). SIRS and ΔRRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation.

Acute Kidney Injury in Patients with Liver Disease.

AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.

Baseline Hemodynamics Including Aortic and Pulmonary Blood Flow in a Chronic Bovine Model

The use of large animal models in the preclinical setting has expanded and become increasingly valuable for evaluating the safety and efficacy of new therapies and devices. Here, we report normal hemodynamic values, including aortic and pulmonary blood flow, in a bovine model at rest and during exercise after a control procedure. We performed a left lateral thoracotomy and implanted fluid-filled pressure lines (aortic pressure, right atrial pressure, left atrial pressure, pulmonary artery pressure) and left (systemic) and right (pulmonary) flow probe lines. Throughout the postoperative period, the calf’s physiologic pressures, vital signs, aortic and pulmonary blood flow, and pulmonary and systemic vascular resistance were recorded hourly at rest and during treadmill exercise evaluations. When pressures and flow rates at baseline and during treadmill trials were compared, we observed a physiologic response to exercise similar to that seen in humans, with a sympathetic discharge that increased systolic blood pressure. However, the rise in mean arterial pressure was much lower due to an overall decrease in vascular resistance, which increased blood flow. This study provides investigators, device engineers, and manufacturers with normal bovine cardiovascular physiology data that can be used for technical consideration during device development for preclinical trials.

CARD27: The Effect of Permissive Hypertension on Cerebral Perfusion in VAD Patients with Embolic Stroke

Study: This study aims to investigate the effect of permissive hypertension, a deliberate rise in Mean Arterial Pressure (MAP), on cerebral perfusion in Left Ventricular Assist Device (LVAD) patients with embolic stroke. Methods: A previously published Lumped Parameter Model (LPM) of the human circulation, including pulmonary and systemic circulation, as well as all four cardiac chambers and an LVAD, is divided into circulation of the upper and lower body. The upper circulation is further divided into extracranial and intracranial vessels to study brain perfusion as a function of MAP, as well as peripheral and intracranial resistance. Actual LVAD H-Q characteristic curves model the instantaneous LVAD response to a rise in MAP and the differential increase in resistance between the intracranial region suffering a stroke and the remaining circulation. The resulting changes in intracranial flow rate as MAP increases and vascular resistance is altered are analyzed. Increased resistance in intracranial vasculature is incorporated into a model of a typical embolic stroke, and its influence on cerebral perfusion is studied for a range of LVAD speeds and MAP values. Results: In LVAD patients with embolic stroke, intracranial flow significantly decreases as MAP is allowed to rise. These findings are robust at any LVAD speed, consistent with a significant reduction in LVAD flow with increased afterload. This counterintuitive result of permissive hypertension in LVAD patients is captured by the LPM model of embolic stroke, whereby the increase in intracranial resistance decreases cerebral perfusion even further via a decrease in total cardiac output associated with the increase in MAP. Third-generation LVADs are known to be afterload sensitive. Our results show that a mere increase in MAP from 70 to 80 mmHg decreases cerebral blood flow by a commensurate 15%, thus increasing infarct size, which is quite deleterious (see Fig. 1). Our study confirms there is no role for permissive hypertension in LVAD patients with embolic stroke. Figure 1. Cranial flow rate (Qcranial) as a function of MAP for no embolism (purple) and embolism (teal) cases and for 2400 RPM (circles) and 2800 RPM (squares) LVAD speeds.

Stretch‐induced Myocardial Injury and Inflammation After Transient Vasopressin‐Mediated Left Ventricular Pressure Overload in Swine

ObjectiveUsing the α1‐adrenergic agonist phenylephrine (PE), we have previously demonstrated that an acute episode of transient pressure overload (TPO) elicits stretch‐induced myocardial injury and reversible left ventricular (LV) systolic dysfunction. Although this was accompanied by leukocyte mobilization, a rise in inflammatory cytokine levels, and increased pro‐inflammatory gene expression in the heart, the extent to which this resulted from direct activation of α1‐adrenergic receptors on immune cells vs. an inflammatory response to mechanical stretch‐induced myocardial injury is unclear. Accordingly, the present study was designed to determine if an inflammatory response to myocardial injury is evident when TPO is produced by vasopressin (VP), a vasoconstrictor without direct α1‐adrenergic agonist properties.MethodsHemodynamic and echocardiographic parameters were assessed in propofol‐anesthetized swine before, during, and after a 30‐minute infusion of VP (VP‐TPO; 0.04 U/kg/min, n=7) to increase LV end‐diastolic pressure (EDP) to ~30mmHg. Serial jugular venous blood sampling was performed to quantify circulating cardiac troponin I (cTnI), leukocytes, and inflammatory cytokines (TNF‐α and IL‐6) at baseline and 3‐hours after cessation of VP‐TPO. Leukocyte and cytokine levels were compared with those observed after PE‐mediated TPO in a separate group of animals (PE‐TPO; n=6).ResultsVP elicited a significant rise in mean arterial pressure (91±5 to 165±11 mmHg) and LV EDP (10±1 to 29±2 mmHg; both p&lt;0.05 vs. baseline). This was accompanied by a significant rise in LV end‐diastolic volume (73±5 to 110±7 mL) and end‐systolic volume (20±3 to 53±6 mL), as well as a reduction in LV ejection fraction (EF; 72±3 to 52±3 %; all p&lt;0.05 vs. baseline). One hour after cessation of VP‐TPO, LV EF remained depressed vs. baseline (60±3 %; p&lt;0.05) and circulating cTnI levels began to rise, reaching a concentration that was ~10‐fold higher than baseline concentrations at the 3‐hour post‐TPO timepoint (18±5 to 118±21 ng/L; p&lt;0.05). These changes were accompanied by a significant rise in circulating neutrophils, monocytes, TNF‐α, and IL‐6 that was similar to that observed after PE‐TPO (Figure).ConclusionsVP‐TPO elicits myocardial injury, leukocyte mobilization, and an acute rise in circulating pro‐inflammatory cytokines, thereby recapitulating several features of PE‐TPO in the absence of direct α1‐adrenergic stimulation. These findings suggest that stretch‐induced myocardial injury provokes an inflammatory response that may play an important role in promoting the development of cardiac fibrosis and diastolic dysfunction after exposure to repetitive episodes of TPO.

Novel predictors of response to therapy with terlipressin and albumin in Hepatorenal Syndrome-Acute Kidney Injury

Background and Aim: Prognostication of response to pharmacological treatment of Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI), is crucial to identify patients with a low likelihood of treatment response, and fast track them for liver transplantation. We assessed the response rates to terlipressin-albumin therapy in HRS-AKI and determined early predictors of treatment response and survival. Methods: 84 patients diagnosed to have HRS-AKI (as per new ICA definition) and treated with terlipressin-albumin were included. Demographic, clinical, and laboratory variables obtained at baseline and changes during treatment were analyzed as predictors of HRS reversal by logistic regression analysis. Cox-regression models were used for assessing the association of variables with overall survival. Results: A complete response to therapy was seen in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (Delta-RRI) by day 3 of treatment. Variables with independent predictive value of HRS reversal were the presence of SIRS at baseline (p=0.022;OR-15.749(CI:1.478-167.82)) and Delta-RRI >5% by day 3 (p=0.048;OR=6.67(CI:1.021-43.625)). Non-responders had higher mortality as compared to treatment responders at one month (27% vs 9%) and six months (74% vs 45%). Mean transplant-free survival at six months was significantly longer in complete responders (148 days vs 90 days,p<0.001). Response to treatment(HR-0.527;p=0.004) and MELD Na > 23(HR-1.071; p=0.018) were independent predictors of six-month mortality. Conclusions: SIRS and Delta-RRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation. In HRS-AKI, renal resistive index is a measure of the intrarenal vasoconstriction, and SIRS reflects the exaggerated systemic inflammation, both of which are reversed by terlipressin, leading to enhanced treatment response.

A5 noradrenergic-projecting C1 neurons activate sympathetic and breathing outputs in anaesthetized rats.

What is the central question of this study? C1 neurons innervate pontine noradrenergic cell groups, including the A5 region: do A5 noradrenergic neurons contribute to the activation of sympathetic and respiratory responses produced by selective activation of the C1 group of neurons. What is the main finding and its importance? The increase in sympathetic and respiratory activities elicited by selective stimulation of C1 neurons is reduced after blockade of excitatory amino acid within the A5 region, suggesting that the C1-A5 pathway might be important for sympathetic-respiratory control. Adrenergic C1 neurons innervate and excite pontine noradrenergic cell groups, including the ventrolateral pontine noradrenergic region (A5). Here, we tested the hypothesis that C1 activates A5 neurons through the release of glutamate and this effect is important for sympathetic and respiratory control. Using selective tools, we restricted the expression of channelrhodopsin2 under the control of the artificial promoter PRSx8 to C1 neurons (69%). Transduced catecholaminergic terminals within the A5 region are in contact with noradrenergic A5 neurons and the C1 terminals within the A5 region are predominantly glutamatergic. In a different group of animals, we performed retrograde lesion of C1 adrenergic neurons projecting to the A5 region with unilateral injection of the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-SAP) directly into the A5 region during the hypoxic condition. As expected, hypoxia (8% O2 , 3h) induced a robust increase in fos expression within the catecholaminergic C1 and A5 regions of the brainstem. Depletion of C1 cells projecting to the A5 regions reduced fos immunoreactivity induced by hypoxia within the C1 region. Physiological experiments showed that bilateral injection of kynurenic acid (100mM) into the A5 region reduced the rise in mean arterial pressure, and sympathetic and phrenic nerve activities produced by optogenetic stimulation of C1 cells. In conclusion, the C1 neurons activate the ventrolateral pontine noradrenergic neurons (A5 region) possibly via the release of glutamate and might be important for sympathetic and respiratory outputs in anaesthetized rats.

Prophylactic Perioperative Terlipressin Therapy for Preventing Acute Kidney Injury in Living Donor Liver Transplant Recipients: A Systematic Review and Meta-Analysis

Acute kidney injury (AKI) is common in the perioperative transplant period and is associated with poor outcomes. Few studies reported a reduction in AKI incidence with terlipressin therapy by counteracting the hemodynamic alterations occurring during liver transplantation. However, the effect of terlipressin on posttransplant outcomes has not been systematically reviewed. A comprehensive search of electronic databases was performed. Studies reporting the use of terlipressin in the perioperative period of living donor liver transplantationwere included. We expressed the dichotomous outcomes as risk ratio (RR, 95% confidence interval [CI]) using the random effects model. The primary aim was to assess the posttransplant risk of AKI. The secondary aims were to assess the need for renal replacement therapy (RRT), vasopressors, effect on hemodynamics, blood loss during surgery, hospital and intensive care unit (ICU) stay, and in-hospital mortality. A total of nine studies reporting 711 patients (309 patients in the terlipressin group and 402 in the control group) were included for analysis. Terlipressin was administered for a mean duration of 53.44±28.61h postsurgery. The risk of AKI was lower with terlipressin (0.6 [95% CI, 0.44-0.8]; P=0.001). However, on sensitivity analysis including only four randomized controlled trials (I2= 0; P= 0.54), the risk of AKI was similar in both the groups (0.7 [0.43-1.09]; P=0.11). The need for RRT was similar in both the groups (0.75 [0.35-1.56]; P=0.44). Terlipressin therapy reduced the need for another vasopressor (0.34 [0.25-0.47]; P<0.001) with a concomitant rise in mean arterial pressure and systemic vascular resistance by 3.2mm Hg (1.64-4.7; P<0.001) and 77.64dynecm-1.sec-5 (21.27-134; P=0.007), respectively. Blood loss, duration of hospital/ICU stay, and mortality were similar in both groups. Perioperative terlipressin therapy has no clinically relevant benefit.

Intradialytic hypertension prevalence and predictive factors: A single centre study

Introduction: Intradialytic hypertension (IDH) is associated with significant vascular and cardiac adverse outcomes. Objectives: This study was performed to know the prevalence and factors predicting IDH. Patients and Methods: A single-center cross-sectional observational study at a tertiary care hospital. After ethics committee approval and informed consent, all patients over 18 years on twice weekly hemodialysis were included, those on peritoneal dialysis and acute kidney injury excluded. Primary outcome was prevalence of IDH based on three definitions and secondary outcome was predictive factors. IDH was defined as ≥10 mm Hg surge in systolic blood pressure (SBP) between pre-and postdialysis in 4 of 6 successive sessions or &gt;15 mm Hg rise in mean arterial pressure (MAP) between start and end of dialysis or symptomatic rise in blood pressure requiring intervention. SBP and MAP were measured on standardized monitors before, hourly and 30 minutes post dialysis. Results: Of 136 patients, prevalence of intra-dialytic hypertension was 78/136 (57%), 33/136 (24%), 15/136 (11%) based on systolic rise, rise in MAP and symptomatic rise in BP respectively. Among those with systolic rise, diabetes mellitus (P= 0.03), undernourishment (P=0.03), inter-dialytic weight gain &gt;3 kg (P&lt; 0.001) and dialysis vintage &gt; 3 years (P&lt; 0.001) were significantly associated with IDH. Conclusion: IDH prevalence varied from 11 to 57% with different definitions. Diabetes mellitus, under nutrition, inter-dialytic weight gain &gt;3 kg and dialysis vintage &gt;3 years predicted IDH.

42. INTRADIALYTIC HYPERTENSION AND SIX MONTH – ALL CAUSE MORTALITY IN HEMODIALYSIS PATIENTS

Background: Hemodialysis is safe and beneficial for CRF patient. However, there are several complications during hemodialysis process including intradialytic hypertension (IDH). IDH has been associated with poor outcomes in hemodialysis patients. But only a few studies have investigated the relationship of IDH with mortality in patients undergoing hemodialysis. Objective: This study aims to determine the relationship between IDH and 6 month-all cause mortality in hemodialysis patients. Method: The cohort design study was carried out in October 2019 to March 2020 at the Hemodialysis Unit of Roemani Muhammadiyah Hospital Semarang. The dependent variable was IDH that defined as rise in Mean Arterial Pressure (MAP) &gt;15 mmHg within or immediately post dialysis. The mortality was investigated over 6 months after the baseline measurements. Result: Among 85 respondents, it was found that 22 (25.9%) respondents categorized into IDH group and 63 (74.1%) categorized into non IDH group. The respondents consisted of 54 (63.5%) males and 31 (36.5%) females. The mean delta MAP in the IDH and non IDH group was (mean ± standard error, 22.6 ± 7.9 vs −5 ± 12.3). From the Kaplan Meier survival curve described that non IDH group had higher survival rate than the IDH group (96.8% vs 77.3%, p = 0.004). From Cox regression study we found a significant relationship between IDH and 6-month all cause mortality in hemodialysis patients (p = 0.018; Hazard ratio: 7.305). Conclusion: There was a significant relationship between IDH and 6 month – all cause mortality in hemodialysis patients.

Robot-assisted pelvic urologic surgeries: is it feasible to perform under reduced tilt?

To evaluate the feasibility and outcomes of performing robot-assisted pelvic surgery at a reduced angle of Trendelenburg position. This was a prospective case-control study of 67 patients in 2:1 ratio. Controls were operated with steep Trendelenburg position of 30°, whereas cases were operated using a graduated method to achieve minimal optimal angle of operating table. Various body habitus parameters, console time, blood loss, rise in mean arterial pressure (MAP) and end-tidal carbon-dioxide (ET-CO2), duration of ileus, postoperative stay and complications were recorded. All demographic profile and body habitus parameters were comparable among two groups except age which was lower in Reduced-Tilt group. Cases were operated at a mean angle of 20.5 ± 3.1° compared to 30° in control group. Rise in MAP, ET-CO2 and facial swelling were significantly low in Reduced-Tilt group compared to control. Notably blood loss, duration of ileus, postoperative stay and complications were also low in patients with Reduced Tilt. Various body habitus parameters were analysed with multiple regression analysis to predict minimal angle required for performing surgery with Reduced Tilt. BMI, xiphisterno-umbilical distance, umbilical-pubic-symphyseal distance and subcostal angle were found to predict the same. Robot-assisted pelvic surgeries can be performed in reduced Trendelenburg tilt which is associated with less hemodynamic and respiratory stress, complication rates and early postoperative recovery. BMI, subcostal angle, xiphisterno-umbilical distance and umbilical-pubic-symphyseal distance can predict the feasible angle of tilt.

2-7INTRADIALYTIC HYPERTENSION AMONG REGULAR HEMODIALYSIS PATIENTS FOR MORE THAN FIVE YEARS

Background: Intradialytic hypertension was a prevalence complication of ≈5% to 15% regular hemodialysis patients and predicted cardiovascular mortality. Objectives: This study aims to described prevalence of intradialytic hypertension in regular hemodialysis patients who undergone hemodialysis for more than five years. Methods: We conducted a cross-sectional study of regular hemodialysis patients aged above 18 years who undergone hemodialysis more than 5 years. Intradialytic hypertension was defined as a rise in mean arterial pressure &gt;15 mm Hg within or immediately post-dialysis. Results: This study composed of 46 (56.1%) males and 36 (43.9%) females, aged 53.49 ± 11.2973 years. Most of the patients, 73 (89%) undergone hemodialysis twice weekly and 68 (82.9%) patients with AV fistula access. 51 (62.2%) subjects were achieved Kt/V target more than equal to 1.8. Mean of hemoglobin, albumin, Tsat, Ferritin, Calcium and Phosphor were 10.75 ± 1.87 g/dL, 4.04 ± 0.42 g/dL, 31.73 ± 15.94%, 808.76 ± 878.69 ng/mL, 10.07 ± 9.65 mg/dL, and 6.24 ± 2.44 mg/dL respectively. Intradialytic hypertension was found at 9.8% (8 subjects) among HD patients for more than equal to 5 years. This study was the same as other studies that found intradialytic hypertension 5 to 15% among regular hemodialysis patients. Conclusions: Prevalence of Intradialytic hypertension in Sanglah Hospital was high in regular hemodialysis patients who undergone hemodialysis for more than five years.

A murine model of the exercise pressor reflex.

The decerebrate mouse provides a novel working model of the exercise pressor reflex (EPR). The decerebrate mouse model of the EPR is similar to the previously described decerebrate rat model. Studying the EPR in transgenic mouse models can define exact mechanisms of the EPR in health and disease. The exercise pressor reflex (EPR) is defined by a rise in mean arterial pressure (MAP) and heart rate (HR) in response to exercise and is necessary to match metabolic demand and prevent premature fatigue. While this reflex is readily tested in humans, mechanistic studies are largely infeasible. Here, we have developed a novel murine model of the EPR to allow for mechanistic studies in various mouse models. We observed that ventral root stimulation (VRS) in an anaesthetized mouse causes a depressor response and a reduction in HR. In contrast, the same stimulation in a decerebrate mouse causes a rise in MAP and HR which is abolished by dorsal rhizotomy or by neuromuscular blockade. Moreover, we demonstrate a reduced MAP response to VRS using TRPV1 antagonism or in Trpv1 null mice while the response to passive stretch remains intact. Additionally, we demonstrate that intra-arterial infusion of capsaicin results in a dose-related rise in MAP and HR that is significantly reduced by a selective and potent TRPV1 antagonist or is completely abolished in Trpv1 null mice. These data serve to validate the development of a decerebrate mouse model for the study of cardiovascular responses to exercise and further define the role of the TRPV1 receptor in mediating the EPR. This novel model will allow for extensive study of the EPR in unlimited transgenic and mutant mouse lines, and for an unprecedented exploration of the molecular mechanisms that control cardiovascular responses to exercise in health and disease.

A Murine Model of the Exercise Pressor Reflex

The exercise pressor reflex (EPR) is an involuntary response to exercise. It is defined by a rise in mean arterial pressure (MAP) and heart rate (HR) in response to muscle contraction and is necessary for providing adequate blood flow to the exercising muscle to match metabolic demand and prevent premature fatigue. Proper function of this reflexive response is essential to healthy cardiovascular responses to exercise. Animal models available to test the EPR such as cat, dog, and rabbit have been utilized extensively to gain physiological information across species but generating disease or translating observations to humans has been challenging in these models. While this reflex can be tested rapidly and non‐invasively in humans, an elucidation of the mechanisms that regulate this reflex at the cellular and molecular level limit the utility of such studies. To test the EPR in the setting of heart failure, we previously developed a reliable and reproducible decerebrate rat model that allowed us to study the EPR in cardiomyopathic animals. We observed that this model yielded similar responses to exercise to those observed in humans. Here, we have developed a novel murine model of the EPR to allow for unlimited exploration of physiological and pathological cellular and molecular mechanisms in a variety of transgenic and genetically modified mouse lines. Like the rat model, we observed that ventral root stimulation (VRS; to evoke contraction of skeletal muscle) in an anesthetized mouse causes a depressor response and a reduction in HR. In contrast, the same stimulation in a decerebrate mouse causes a rise in MAP and HR. The responses observed in the decerebrate murine preparation are abolished by disruption of afferent innervation of the muscle via dorsal rhizotomy or by neuromuscular blockade. Moreover, we demonstrate that TRPV1 antagonism in wild type (WT) mice and Trpv1 null mice display a reduced MAP response to VRS while the response to mechanosensitive stimulation (passive stretch) remains intact. Additionally, we demonstrate that intra‐arterial infusion of capsaicin (a TRPV1 agonist) results in a dose related rise in MAP and HR that is significantly reduced by a selective and potent TRPV1 antagonist and, further, that these responses are completely abolished in Trpv1 null mice. Lastly, we observe no role of the Piezo2 receptor in mediating the EPR under physiological conditions. These data serve to validate the development of a decerebrate mouse model for the study of cardiovascular responses to exercise and further define the role of the TRPV1 receptor in mediating the EPR. This novel model will allow for extensive study of the EPR in unlimited transgenic and mutant mouse lines, thus allowing for an unprecedented exploration of the molecular mechanisms that control cardiovascular responses to exercise in health and disease.

Effectiveness of Intravenous Dexmedetomidine vs. Fentanyl for Attenuation of Haemodynamic Response to Pneumoperitoneum in Laparoscopic Cholecystectomy: A Randomised Double Blind Study

Introduction: Laparoscopy is a widely performed minimal invasive surgical procedure, wherein various haemodynamic changes are faced by anaesthesiologists during Pneumoperitoneum (PNP). Aim: To compare the effectiveness of dexmedetomidine vs fentanyl for attenuating the haemodynamics response to PNP in Laparoscopic Cholecystectomy (LC). Materials and Methods: A total of 84 patients of 18-50 years age, American Society of Anaesthesiologists (ASA) Class I/II of either sex for elective LC were included. The patients were divided into two groups (A, B) of 42 patients each. Group A received dexmedetomidine and Group B received fentanyl. Both the drugs were given as loading dose of one μg/kg over ten min followed by maintenance 0.2 μg/kg/h throughout the surgery. Haemodynamic parameters were recorded at different time intervals throughout the surgery. In recovery room patients were observed for postoperative analgesia by using Visual Analogue Scale (VAS), sedation level using RAMSAY Sedation score at every 30 minutes till the time of giving first rescue analgesia and side effects, if any. Results: Intraoperatively, throughout the period of PNP, Group A showed statistically better attenuation of haemodynamic responses in comparison to Group B (p&lt;0.05). After creating PNP, rise in Mean Arterial Pressure (MAP) was observed in both group A and group B, 99.38±6.32 and 103.43±9.81, respectively but this rise was more in group B which was statistically significant (p&lt;0.05) throughout the surgery except 40 minutes after PNP creation. Time to first rescue analgesia or mean duration of postoperative analgesia (VAS&gt;3) was significantly longer in dexmedetomidine group (102.14±32.50 minutes) than fentanyl group (42.86±15.03 minutes). There was better control of pain but more sedation in Group A than in Group B. Conclusion: This study concludes that intravenously administered dexmedetomidine shows better attenuation of haemodynamic responses to CO2 insufflation as compared to fentanyl. Dexmedetomidine also provides better sedation and has more analgesic sparing effect.

Comparison of Superior Vena Cava and Inferior Vena Cava Diameter Changes by Echocardiography in Predicting Fluid Responsiveness in Mechanically Ventilated Patients.

Context:Resuscitation of critically ill patients requires an accurate assessment of the patient's intravascular volume status. Passive leg raise cause auto transfusion of fluid to the thoracic cavity.Aims:This study aims to assess and compare the efficacy of superior vena cava (SVC) and inferior vena cava (IVC) diameter changes in response to passive leg raise (PLR) in predicting fluid responsiveness in mechanically ventilated hemodynamically unstable critically ill patients.Methods:We enrolled 30 patients. Predictive indices were obtained by transesophageal and transthoracic echocardiography and were calculated as follows: (Dmax − Dmin)/Dmax for collapsibility index of SVC (cSVC) and (Dmax − Dmin)/Dmin for distensibility index of IVC (dIVC), where Dmax and Dmin are the maximal and minimal diameters of SVC and IVC. Measurements were performed at baseline and 1 min after PLR. Patients were divided into responders (increase in cardiac index (CI) ≥10%) and nonresponders (NR) (increase in CI <10% or no increase in CI).Results:Among those included, 24 (80%) patients were R and six were NR. There was significant rise in mean arterial pressure, decrease in heart rate, and decrease in mean cSVC from baseline to 1 min after PLR among responders. The best threshold values for discriminating R from NR was 35% for cSVC, with sensitivity and specificity of being 100%, and 25% for dIVC, with 54% sensitivity and 86.7% specificity. The areas under the receiver operating characteristic curves for cSVC and dIVC regarding the assessment of fluid responsiveness were 1.00 and 0.66, respectively.Conclusions:cSVC had better sensitivity and specificity than dIVC in predicting fluid responsiveness.

The effect of the EP3 antagonist DG-041 on male mice with diet-induced obesity

Background/aimsThe prostaglandin E2 (PGE2) EP3 receptor has a multifaceted role in metabolism. Drugs targeting EP3 have been proposed as therapeutics for diabetes; however, studies utilizing global EP3 knockout mice suggest that EP3 blockade increases obesity and insulin resistance. The present studies attempt to determine the effect of acute EP3 antagonist treatment on the diabetic phenotype. MethodsDG-041 was confirmed to be a high affinity antagonist at the mouse EP3 receptor by competition radioligand binding and by blockade of EP3-mediated responses. DG-041 pharmacokinetic studies were performed to determine the most efficacious route of administration. Male C57BL/6 × BALB/c (CB6F1) mice were fed diets containing 10%, 45%, or 60% calories from fat to induce obesity. Changes to the metabolic phenotype in these mice were evaluated after one week treatment with DG-041. ResultsSubcutaneous injections of DG-041 at 20 mg/kg blocked the sulprostone-evoked rise in mean arterial pressure confirming the efficacy of this administration regime. Seven day treatment with DG-041 had minimal effect on body composition or glycemic control. DG-041 administration caused a reduction in skeletal muscle triglyceride content while showing a trend toward increased hepatic triglycerides. ConclusionShort term EP3 administration of DG-041 produced effective blockade of the EP3 receptor and decreased skeletal muscle triglyceride content but had no significant effects on the diabetic phenotype.

Prenatal Sildenafil Therapy Improves Cardiovascular Function in Fetal Growth Restricted Offspring of Dahl Salt-Sensitive Rats.

Fetal growth restriction (FGR) is associated with increased risk for cardiovascular and renal disorders in later life. Prenatal sildenafil improves birth weight in FGR animal models. Whether sildenafil treatment protects against long-term cardiovascular and renal disease in these offspring is unknown. The aim of this study is to test the hypothesis that prenatal sildenafil ameliorates cardiovascular and renal function in FGR offspring of Dahl salt-sensitive rats. Sildenafil citrate (60 mg/kg per day) or control gel diet (containing 0.3% salt) was administered from gestational day ten until birth. In male and female offspring, the mean arterial pressure was measured by telemetry in 1 subset from week 5 until week twenty. Echocardiographic parameters, glomerular filtration rate, and fractional electrolyte excretion were determined in another subset at week 9. Aortic and mesenteric artery rings were prepared to assess endothelial-dependent (acetylcholine) and -independent (sodium nitroprusside) vasorelaxation (week 10). The rise in mean arterial pressure per week was attenuated in treated versus untreated male offspring. Mesenteric arteries showed an increased endothelium-dependent relaxation and improved endothelium-independent relaxation in treated versus control male offspring. No differences in aortic relaxation, echocardiographic parameters or renal function were observed between groups. Prenatal sildenafil treatment subtly improves cardiovascular but not renal function in the offspring of this FGR rat model. Translationally, in utero treatment could be beneficial for cardiovascular programming in a sex-specific manner; however, caution is warranted since recent human trials have been halted because of potentially deleterious neonatal side effects when treating pregnancies complicated with severe FGR with sildenafil.