Lower Mean Arterial Blood Pressure Research Articles

222. Differential effects of RAAS inhibition, sympatheticinhibition and low sodium diet on blood pressure in women with a history of preeclampsia

Introduction Current guidelines for prevention of cardiovascular disease after preeclampsia lack sufficient evidence to recommend a particular blood pressure lowering strategy. Objective To investigate the most effective blood pressure lowering strategy in women with a history of preeclampsia with postpartum (borderline) hypertension. Methods Randomized, four-way, double-blind, crossover study in 8 women with a history of preeclampsia with diastolic blood pressure >80 mmHg and/or systolic blood pressure >120 mmHg (PALM-study, NTR4590). In each woman the effects of 8 weeks of renin-angiotensin-aldosterone system (RAAS) inhibition (losartan 100 mg), sympatheticinhibition (moxonidine 0.4 mg), low sodium diet (50 mmol NaCl/24 h) and placebo on 24-h blood pressure were determined. Nocturnal dipping was assessed as non-dipping is associated with increased cardiovascular risk. Data were analyzed using linear mixed models with subject*visit as random factor. Results No significant effect of blood pressure lowering strategy was observed on 24-h blood pressure, although a trend towards lower mean arterial blood pressure was observed on losartan (92 ± 7 mmHg) and low sodium diet (94 ± 14 mmHg) compared to placebo (97 ± 13 mmHg) and moxonidine (98 ± 13 mmHg). Nocturnal dipping of mean arterial blood pressure did significantly differ ( p strategy = 0.03), with increased dipping on low sodium diet (−18 ± 9 mmHg, p = 0.01) and losartan (−18 ± 5 mmHg, p 0.01), compared to placebo (−13 ± 3 mmHg) and moxonidine (−6 ± 6 mmHg). On moxonidine compliance was lowest and one patient needed to terminate the treatment prematurely because of side-effects. Discussion Equal beneficial effects of RAAS inhibition and low sodium diet were observed on 24-h blood pressure, especially on nocturnal dipping, in women with a history of preeclampsia. These findings fit with the previously reported increased salt-sensitivity and disturbances in RAAS after preeclampsia.

Effects of hemodynamic monitoring using a single-use transesophageal echocardiography probe in critically ill patients \u2013 study protocol for a randomized controlled trial

BackgroundHemodynamic instability is one of the leading causes of intensive care unit (ICU) admission. Early stabilization of hemodynamics is associated with improved outcome. The monitoring used to guide hemodynamic support may influence the time needed to achieve stable hemodynamics. Visualization of the heart using echocardiography offers the advantage of direct measurement of cardiac volumes and ventricular function. A miniaturized monoplane transesophageal echocardiography (TEE) probe was developed, allowing for almost continuous qualitative hemodynamic TEE assessment (hTEE) after brief bedside training. The primary objective of the study is to assess whether hemodynamic monitoring using the hTEE technology shortens time to resolution of shock in ICU patients in comparison to standard monitoring using a central venous catheter, pulmonary artery catheter, or conventional echocardiography.MethodsFive hundred consecutive subjects with circulatory shock (low mean arterial blood pressure (MAP) and signs of organ hypoperfusion) at the time of ICU admission are included in the study. The subjects are randomly assigned to one of four groups using a 2 × 2 factorial design stratified by method of hemodynamic monitoring (hTEE vs standard hemodynamic monitoring) and frequency of hemodynamic assessments (minimum every 4 h vs standard of care). The primary study outcome is the time from study inclusion to resolution of circulatory shock, defined as MAP > 60 mmHg for ≥ 4 h after discontinuation of vasopressors and inotropes. The hTEE monitoring consists of the acquisition of three defined echocardiography views: Transgastric mid-esophageal short axis with measurement of fractional area change of left ventricle, mid-esophageal four-chamber view with measurement of the ratio of right to left ventricular area, and mid-esophageal ascending aortic short-axis view with measurement of the superior vena cava collapsibility index. In the control groups, monitoring modalities, including conventional TTE and TEE but not hTEE, are at the discretion of the treating physician. The interpretation of hemodynamic monitoring and the subsequent changes in patient management are recorded after each hemodynamic assessment. Differences in the primary and further secondary time-to-event outcomes will be assessed using a competing risk model accounting for the competing risk of death.DiscussionThe effect of using echocardiography as a monitoring modality on relevant patient outcomes has not been established so far. The study at hand may be one of the first trials to provide detailed data on effectiveness and safety of echocardiography to guide treatment in patients with circulatory shock.Trial registrationClinicalTrials.gov, ID: NCT02048566. Registered on January 29, 2014.

Low Mean Arterial Blood Pressure is Independently Associated with Postoperative Acute Kidney Injury After Living Donor Liver Transplantation: A Propensity Score Weighing Analysis

BackgroundAs end-stage liver disease progresses, renal blood flow linearly correlates with mean arterial blood pressure (MBP) due to impaired autoregulation. We investigated whether the lower degree of postoperative MBP would predict the occurrence of postoperative acute kidney injury (AKI) after liver transplantation.Material/MethodsThis retrospective study enrolled 1,136 recipients with normal preoperative kidney function. Patients were categorized into two groups according to the averaged postoperative MBP: <90 mmHg (MBPbelow90) and ≥90 mmHg (MBPover90). The primary endpoint was occurrence of postoperative AKI, defined by the creatinine criteria of the Kidney Disease Improving Global Outcomes. The logistic regression model with inverse probability treatment weighting (IPTW) of propensity score was used to compare the risk of postoperative AKI between two groups.ResultsMBPbelow90 group (83.0±5.1 mmHg) showed higher prevalence and risk of postoperative AKI (74.2% versus 62.6%, p<0.001; IPTW-OR 1.34 [1.12–1.61], p=0.001) compared with MBPover90 group (97.3±5.2 mmHg). When stratified by quartiles of baseline cystatin C glomerular filtration ratio (GFR), the association between MBPbelow90 and postoperative AKI remained significant only with the lowest quartile (cystatin C GFR ≤85 mL/min/1.73 m2; IPTW-OR 2.24 [1.53–3.28], p<0.001), but not with 2nd–4th quartiles.ConclusionsOur results suggest that maintaining supranormal MBP over 90 mmHg may be beneficial to reduce the risk of post-LT AKI, especially for liver transplant recipients with cystatin C GFR ≤85 mL/min/1.73 m2.

Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU.

To describe the use of low-dose bolus epinephrine in critically ill children during an acute hypotensive episode or prearrest condition. Institutional Review Board approved, single-center, retrospective medical chart review. Large medical-surgical PICU within a freestanding, tertiary care children's hospital. Patients admitted to the PICU between June 1, 2015, and June 1, 2016, who received low-dose (≤ 5 µg/kg) IV bolus epinephrine. None. Twenty-four resuscitation episodes (63 doses; 19 patients) were analyzed. Median age and weight of patients were 9 years (interquartile range, 1-15 yr) and 38.5 kg (interquartile range, 12-54.8 kg). Median Pediatric Risk of Mortality III score was 17 (interquartile range, 10-27). Mean epinephrine dose was 1.3 ± 1.1 µg/kg. Median number of doses per patient was two. If more than one dose was provided, median dosing interval was 6.5 minutes. Heart rate and mean arterial blood pressure were compared at the time of epinephrine administration and 1-4 minutes (median = 1 min) following administration. Heart rate changed from 130 ± 41 to 150 ± 33 beats/min (p < 0.05), and mean arterial blood pressure changed from 51 ± 17 to 75 ± 27 mm Hg (p < 0.001). Variability in mean arterial blood pressure response was observed; nonresponders required extracorporeal membrane oxygenation; 66% of doses resulted in up to 100% mean arterial blood pressure increase, and 21% of doses resulted in greater than 100% mean arterial blood pressure increase. Doses below 1 µg/kg were associated with a lower mean arterial blood pressure increase than doses between 1 and 5 µg/kg (mean percent change in mean arterial blood pressure = 6.6% vs 60%, respectively). Children less than or equal to 2 years old had the greatest percentage increase in heart rate and mean arterial blood pressure. Provision of low-dose bolus epinephrine during periods of acute hypotension can result in a significant increase in mean arterial blood pressure and heart rate. This dosing strategy may provide temporary stabilization while other therapies are added or adjusted, but further research is needed.

Lower limb blood flow and mean arterial pressure during standing and seated work: Implications for workplace posture recommendations.

Sit-stand workstations are a popular workplace intervention. Organizations often require a medical professional's guidance for implementation. Therefore, it is important to understand potential negative outcomes associated with standing work, such as lower limb discomfort and peripheral vascular issues. The objective of this study was to compare changes in lower limb discomfort, blood pressure and blood flow accumulation during a light-load repetitive upper limb work task accomplished from seated and standing postures. At the Jewish Rehabilitation Hospital (Laval, Quebec, Canada), 16 participants were outfitted with Laser Doppler Flow (LDF) electrodes to measure blood flow in the lower limb, and a sphygmomanometer to measure lower limb mean arterial blood pressure (MAP). Participants completed simulated work over 34 min in standing and seated conditions. Repeated measures ANOVAs (Posture x Time) were used to assess the differences. There were significant effects for both Posture (p = 0.003) and Time (p = 0.007) for LDF-measured of blood flow accumulation in the soleus and the foot, with a mean increase of 77% blood flow over time in the standing posture, when compared to seated work. There was a significant ‘Posture × Time’ (p = 0.0034) interaction effect and a significant Posture (p = 0.0001) effect for MAP, with higher values in the standing posture by a mean of 37.2 mmHg. Posture had a significant effect (p < 0.001) on lower limb discomfort, with standing posture reporting higher levels. These results suggest that recommendations for using static standing work postures should be tempered, and physicians' guidance on workstation changes should consider the impacts on the lower limb.

Post-resuscitation Arterial Blood Pressure on Survival and Change of Capillary Density Following Cardiac Arrest and Resuscitation in Rats.

Transient global brain ischemia, induced by cardiac arrest and resuscitation, results in reperfusion injury leading to delayed selective neuronal cell loss and post-resuscitation mortality. This study determined the effects of post-resuscitation hypotension and hypothermia on long-term survival following cardiac arrest and resuscitation. The capillary density was also determined. Based on the mean arterial blood pressure (MABP) at 1h of recovery, the normotension group (MABP 80-120mmHg) and hypotension group (MABP <80mmHg) were defined. The overall survival was determined at 4days of recovery. Brain microvascular density was assessed using immunohistochemistry of the glucose transporter, GLUT-1. The pre-arrest MABP was similar in each group; at 1h after resuscitation, the MABP in the normotension groups was about 80% of their pre-arrest values; the hypotension group had a significantly lower MABP compared to the normotension group. The overall survival rate was lower in the hypotension group compared to the normotension group (36%, 4/11 vs. 67%, 14/21) under the normothermic condition. Brain blood flow in the hypotension group was lower (33% decrease) compared to the normotension group at 1-h post-resuscitation. Compared to the pre-arrest baseline, the capillary density was significantly increased at 14days of recovery (355 ± 42 vs. 469 ± 50, number/mm2) in the cortex. The capillary density in hippocampus was also increased at 4-30days following cardiac arrest and resuscitation. Our results suggest that rats able to maintain their post-resuscitation blood pressure at normotension, had higher brain blood flow during the early recovery phase, and improved survival outcome following cardiac arrest and resuscitation. In addition, cardiac arrest and resuscitation induced angiogenesis in brain in the first month of recovery.

Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study

BackgroundThis double-blind randomised controlled trial investigated whether normal saline or a balanced crystalloid has distinct effects on vasopressor use in patients undergoing major abdominal surgery. MethodsPatients received either normal saline 0.9% or an acetate-buffered crystalloid for intraoperative volume replacement in a goal-directed fashion. The primary outcome was need for vasopressors; the secondary outcomes were the total dose of catecholamines, total perioperative fluid, and unplanned intensive care admissions. ResultsThis study was terminated early for safety reasons. A total of 60 out of the planned 240 patients were randomized. Thirty patients received normal saline and 30 patients received the balanced crystalloid, with a total volume of 3427 (2732–4130) ml and 3144 (1673–4926), respectively. The normal-saline group developed hyperchloraemic metabolic acidosis. More patients needed vasopressors for circulatory support in the normal-saline group compared with the buffered crystalloid group (97% vs 67%, respectively; P=0.033). The median weight and anaesthesia duration-adjusted dose of norepinephrine were 0.11 (0.00–0.45) ng kg−1 min−1 and 0.00 (0.00–0.00) kg−1 min−1 in the normal-saline and balanced-crystalloid groups, respectively (P=0.003). Cox regression revealed that the need for vasopressors was related to a high volume of administered fluid, normal-saline resuscitation, and lower mean arterial blood pressure. There was no difference between the groups in total perioperative fluid and unplanned intensive-care-unit admissions. Between-group differences in the duration of anaesthesia did not influence the necessity for a vasopressor. ConclusionsCompared with patients receiving a balanced crystalloid, normal saline in patients undergoing major abdominal surgery was associated with an increased need for vasopressor support. This should be interpreted in view of the large volume of fluid resuscitation and the small sample size because of the preliminary termination of the study. Clinical trial registrationEudraCT 2014-004867-19, NCT 02414555.

A comparison between inhalational (Desflurane) and total intravenous anaesthesia (Propofol and dexmedetomidine) in improving postoperative recovery for morbidly obese patients undergoing laparoscopic sleeve gastrectomy: A double-blinded randomised controlled trial

Study objectiveLaparoscopic sleeve gastrectomy is commonly performed under total intravenous anaesthesia (TIVA) or balanced anaesthesia using an intravenous and inhalation agent. It is still unclear which anaesthesia regimen is better for this group of patients. The present study has been conducted to compare the use of the inhalation anaesthesia technique using desflurane with the TIVA technique, using propofol and dexmedetomidine. DesignProspective, randomised, double-blinded study. SettingMenoufia Univeristy Hospital. PatientsThis randomised trial was carried out on 100 morbidly obese patients undergoing laparoscopic sleeve gastrectomy. The patients were randomised into two equally sized groups; one group received the inhalation anaesthesia technique and the other received the TIVA technique. InterventionsAll patients received general anaesthesia, which was induced by propofol, remifentanil, and rocuronium. Anaesthesia was maintained using desflurane in oxygen air mixture in the inhalation group, whilst anaesthesia was maintained by intravenous infusion of propofol and dexmedetomidine in the TIVA group. MeasurementsIntra-operative vital signs, anaesthesia recovery time, postoperative nausea and vomiting, pain score, post-anaesthetic care unit (PACU) stay time, total first 24h post-operative analgesic needs and the onset of first bowel movement were recorded.Main resultsThe TIVA group had lower intra-operative heart rates and mean arterial blood pressure (P<0.0001). The TIVA group also had a lower post-operative visual analogue score for pain assessment (VAS) (P<0.0001), lower total analgesic requirements (P<0.0001), a lower incidence of nausea (P=0.01) and vomiting (P=0.03), and shorter PACU stays (P=0.01). There was no significant difference between groups with regard to the onset of bowel movement (P=0.16). ConclusionsTIVA using propofol and dexmedetomidine is a better anaesthetic regimen than inhalation anaesthesia using desflurane for laparoscopic sleeve gastrectomy in morbidly obese patients. The TIVA technique provided better postoperative recovery with fewer postoperative side effects and analgesic requirements. Clinical trial registery numberNCT03029715.

Acute Alcohol Binge Deteriorates Metabolic and Respiratory Compensation Capability After Blunt Chest Trauma Followed by Hemorrhagic Shock-A New Research Model.

The clinical relevance of blunt (thoracic) chest trauma (TxT) and hemorrhagic shock is indisputable due to the high prevalence of this injury type, as well as its close association with mortality and/or preventable deaths. Furthermore, there is an ongoing discussion about the influence of alcohol in trauma patients. Thus, we established a model of TxT followed by hemorrhagic shock with resuscitation (H/R) in alcohol-intoxicated rats. Depending on group allocation, 12 (subacute) or 2 (acute) hours before experimentation, the animals received a single oral dose of alcohol (ethanol [EtOH]) or saline (NaCl) followed by TxT, hemorrhagic shock (35±3mm Hg), and resuscitation (TxT+H/R). Arterial blood gas analyses and continuous monitoring of blood pressure were performed during the experimentation period. Survival during the experimentation procedure was determined. Subacute and acute EtOH group exhibited lower baseline mean arterial blood pressure values compared with the corresponding NaCl group, respectively. Both EtOH groups showed lower maximal bleed-out volume, which was necessary to induce hemorrhagic shock compared to NaCl groups, and the recovery during the resuscitation period was attenuated. During the experimentation in all groups, a trend to acidic pH was observed. Acute EtOH group showed lowest pH values compared to all other groups. Higher pCO2 values were observed in both EtOH groups. All groups developed negative base excess and decreasing HCO3- values until the end of hemorrhagic shock and showed increasing base excess and HCO3- values during resuscitation. Significantly higher mortality rate was found in the acute EtOH group. This study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality.

Association of hemodynamic variables with in-hospital mortality and favorable neurological outcomes in post-cardiac arrest care with targeted temperature management

PurposeAlthough hemodynamic instability is expected during the post-cardiac arrest period, the implications of hemodynamic parameters for outcomes remain unclear. Each phase of targeted temperature management (TTM) affects hemodynamic responses differently. This study aims to investigate the association of hemodynamic parameters with outcomes in patients receiving TTM after cardiac arrest. MethodsThe study prospectively enrolled patients who were treated with TTM (33°C for 24h) after cardiac arrest. We assessed clinical and hemodynamic variables at pre-specified time points in survivors and non-survivors as well as among those with favorable vs. poor neurologic outcomes at discharge. ResultsThe study analyzed the records of 95 patients who completed TTM; at discharge 54 (57%) were alive and 21 (22%) had favorable neurological outcomes. Heart rate(HR) at 24h>93/min, cardiac index (CI) at 12h<2.5l/min/m2 and lower average of mean arterial blood pressure(MAP) at 36h and 48h were independently associated with in-hospital mortality (P<0.05 by Cox regression analysis respectively). MAP at 48h between 84–110mm Hg and lower HR at 48h were significantly associated with better neurological outcome at discharge (P<0.05 for by logistic regression analysis respectively). ConclusionsOur results indicate that lower MAP and HR more than 93/min are associated with in-hospital mortality during the initial 48h after ROSC. CI at 12h<2.5l/min/m2 is associated with survival but not with neurological outcome. During the course of post-cardiac arrest TTM, these markers of hemodynamic status may be useful predictors of outcomes.

Short-term effects of extracorporeal graft rinse versus circulatory graft rinse in living donor liver transplantation. A prospective randomized controlled trial.

Living donor liver transplantation has shorter cold ischemia time, less preservative volume, and lower metabolic load compared to transplantation from deceased donors. We investigated the impact of rinsing the graft contents into the systemic circulation on operative course and postoperative outcomes. Donors had right hepatectomy, and grafts were preserved with cold histidine-tryptophan-ketoglutarate solution. On ending portal vein anastomosis, grafts were flushed by patient's portal blood either through incompletely anastomosed hepatic vein (extracorporeal rinse group, EcRg, n=40) or into systemic circulation (circulatory rinse group, CRg, n=40). The primary outcome objective was the lowest mean arterial blood pressure within 5min after portal unclamping as a marker for postreperfusion syndrome (PRS). Secondary objectives included hemodynamics and early graft's and patient's outcomes. Within 5min postreperfusion, mean arterial blood pressure was significantly lower in the CRg compared to the EcRg, yet this was clinically insignificant. Postoperative graft functions, early biliary and vascular complications, and three-month survival were comparable in both groups. Rinsing the graft into the circulation increased the incidence of PRS without significant impact on early graft or patient outcome in relatively healthy recipients.

Impaired cerebral autoregulation in preoperative newborn infants with congenital heart disease

ObjectivesTo characterize cerebral autoregulation (CA) in preoperative newborn infants with congenital heart disease (CHD). MethodsThis was a prospective, pilot study of term newborns with CHD who required intensive care. Continuous mean arterial blood pressure (MAP), cerebral tissue oxygen saturation (SCTO2) via near-infrared spectroscopy, and arterial oxygen saturation (SaO2) were collected. Significant low-frequency coherence between MAP and SCTO2 was used to define impaired CA in 20-minute epochs. Cerebral fractional tissue oxygen extraction (FTOE) = (SaO2 − SCTO2)/SaO2 was calculated. Spearman's and rank bi-serial correlations and logistic linear models accounting for multiple measures were used to identify associations with impaired CA and coherence. ResultsTwenty-four term neonates were evaluated for 23.4 ± 1.8 hours starting the first day of life. Periods of SaO2 variability >5% were excluded, leaving 63 ± 10 epochs per subject, 1515 total for analysis. All subjects demonstrated periods of abnormal CA, mean 15.3% ± 12.8% of time studied. Significant associations with impaired CA per epoch included greater FTOE (P = .02) and lack of sedation (P = .02), and associations with coherence included greater FTOE (P = .03), lack of sedation (P = .03), lower MAP (P = .006), and lower hemoglobin (P = .02). ConclusionsTerm newborns with CHD display time-varying CA abnormalities. Associations seen between abnormal CA and greater FTOE, lack of sedation, and lower hemoglobin suggest that impaired oxygen delivery and increased cerebral metabolic demand may overwhelm autoregulatory capacity in these infants. Further studies are needed to determine the significance of impaired CA in this population.

Hemodynamic Profile of Acute Kidney Injury Following the Fontan Procedure: Impact of Renal Perfusion Pressure.

Acute kidney injury (AKI) is common following cardiopulmonary bypass. Fontan completion may result in systemic venous hypertension and low cardiac output, reducing renal perfusion pressure (RPP) and further increasing the risk of AKI. We investigated the incidence and risk factors for post-Fontan AKI. Single-center retrospective study of children undergoing Fontan completion from 2005 to 2012. Demographic and hemodynamic variables were assessed for association with AKI. Subgroup analysis was performed on patients with high-grade AKI (creatinine increase of ≥2.0 × baseline). Vital sign data were collected hourly for the first postoperative day. A total of 186 patients underwent Fontan at 3.1 (2.5-3.8) years of age and 13.5 kg (12.2-15.1). Acute kidney injury occurred in 97 (52%) patients, with high-grade AKI in 52 (28%). Univariate analysis identified reduced RPP in patients with AKI compared to those without AKI, 50 (45-56) mm Hg versus 58 (54-61) mm Hg ( P < .0001), due to lower mean arterial blood pressure, 63 (60-69) versus 70 (66-73) mm Hg ( P < .0001), and higher central venous pressure, 14 (12-16) versus 13 (11-14) mm Hg, ( p < .0001). Multivariable logistic regression and classification tree analyses further identified elements of RPP as significant predictors of AKI, especially high-grade AKI. Postoperative intubation was linked to AKI development. Patients with AKI had decreased postoperative urine output with increased colloid requirements, duration of chest tube insertion, and hospital length of stay. Acute kidney injury occurs frequently following the Fontan procedure. Associated factors include reduced RPP, high colloid requirements, and postoperative intubation. Targeted hemodynamic interventions may serve to reduce the incidence of post-Fontan AKI.

Angiotensin II in Refractory Septic Shock

Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs

ABSTRACTThe effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.

Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters.

Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs). This study investigated the effects of repeated anaesthesia with either medetomidine-midazolam-fentanyl (MMF) or isoflurane (Iso) on physiological parameters in the GP. Twelve GPs were repeatedly administered with MMF or Iso in two anaesthesia sets. One set consisted of six 40-min anaesthesias, performed over 3 weeks (2 per week); the anaesthetic used first was randomized. Prior to Iso anaesthesia, atropine was injected. MMF anaesthesia was antagonized with AFN (atipamezole-flumazenil-naloxone). Abdominally implanted radio-telemetry devices recorded the mean arterial blood pressure (MAP), heart rate (HR) and core body temperature continuously. Additionally, respiratory rate, blood glucose and body weight were assessed. An operable state could be achieved and maintained for 40 min in all GPs. During the surgical tolerance with MMF, the GPs showed a large MAP range between the individuals. In the MMF wake- up phase, the time was shortened until the righting reflex (RR) returned and that occurred at lower MAP and HR values. Repeated Iso anaesthesia led to an increasing HR during induction (anaesthesias 2–6), non-surgical tolerance (anaesthesias 3–6) and surgical tolerance (anaesthesias 4, 6). Both anaesthetics may be used repeatedly, as repeating the anaesthesias resulted in only slightly different physiological parameters, compared to those seen with single anaesthesias. The regular atropine premedication induced HR increases and repeated MMF anaesthesia resulted in a metabolism increase which led to the faster return of RR. Nevertheless, Iso’s anaesthesia effects of strong respiratory depression and severe hypotension remained. Based on this increased anaesthesia risk with Iso, MMF anaesthesia is preferable for repeated use in GPs.

Experimental assessment of oxygen homeostasis during acute hemodilution: the integrated role of hemoglobin concentration and blood pressure

BackgroundLow hemoglobin concentration (Hb) and low mean arterial blood pressure (MAP) impact outcomes in critically ill patients. We utilized an experimental model of “normotensive” vs. “hypotensive” acute hemodilutional anemia to test whether optimal tissue perfusion is dependent on both Hb and MAP during acute blood loss and fluid resuscitation, and to assess the value of direct measurements of the partial pressure of oxygen in tissue (PtO2).MethodsTwenty-nine anesthetized rats underwent 40% isovolemic hemodilution (1:1) (or sham-hemodilution control, n = 4) with either hydroxyethyl starch (HES) (n = 14, normotensive anemia) or saline (n = 11, hypotensive anemia) to reach a target Hb value near 70 g/L. The partial pressure of oxygen in the brain and skeletal muscle tissue (PtO2) were measured by phosphorescence quenching of oxygen using G4 Oxyphor. Mean arterial pressure (MAP), heart rate, temperature, arterial and venous co-oximetry, blood gases, and lactate were assessed at baseline and for 60 min after hemodilution. Cardiac output (CO) was measured at baseline and immediately after hemodilution. Data were analyzed by repeated measures two-way ANOVA.ResultsFollowing “normotensive” hemodilution with HES, Hb was reduced to 66 ± 6 g/L, CO increased (p < 0.05), and MAP was maintained. These conditions resulted in a reduction in brain PtO2 (22.1 ± 5.6 mmHg to 17.5 ± 4.4 mmHg, p < 0.05), unchanged muscle PO2, and an increase in venous oxygen extraction. Following “hypotensive” hemodilution with saline, Hb was reduced to 79 ± 5 g/L and both CO and MAP were decreased (P < 0.05). These conditions resulted in a more severe reduction in brain PtO2 (23.2 ± 8.2 to 10.7 ± 3.6 mmHg (p < 0.05), a reduction in muscle PtO2 (44.5 ± 11.0 to 19.9 ± 12.4 mmHg, p < 0.05), a further increase in venous oxygen extraction, and a threefold increase in systemic lactate levels (p < 0.05).ConclusionsAcute normotensive anemia (HES hemodilution) was associated with a subtle decrease in brain tissue PtO2 without clear evidence of global tissue hypoperfusion. By contrast, acute hypotensive anemia (saline hemodilution) resulted in a profound decrease in both brain and muscle tissue PtO2 and evidence of inadequate global perfusion (lactic acidosis). These data emphasize the importance of maintaining CO and MAP to ensure adequacy of vital organ oxygen delivery during acute anemia. Improved methods of assessing PtO2 may provide an earlier warning signal of vital organ hypoperfusion.

Ultraschallgesteuerte Nervenblockade des Nervus femoralis und ischiadicus im Vergleich zur Epiduralanästhesie bei orthopädischen Eingriffen am Hund

Comparison of ultrasound-guided femoral and sciatic nerve block versus epidural anaesthesia with bupivacaine and morphine for orthopaedic surgery of the pelvic limb in dogs with respect to analgesic effectiveness, clinical utility and side effects. The study included 22 dogs (American Society of Anesthesiologists, ASA grades I and II) undergoing orthopaedic surgery distal to the mid-femoral bone. The study was designed as a randomized, prospective, blinded clinical trial. All dogs were randomly assigned to receive 0.5mg/kg bupivacaine (0.5%) and 0.1mg/kg morphine sulphate (1%) either as epidural anaesthesia (group EPI) or by ultrasound-guided femoral and sciatic nerve block (group LA). During surgery, the heart rate, respiratory rate, mean arterial pressure (MAP), end-tidal isoflurane concentrations and dose of rescue analgesia (fentanyl boluses of 5µg/kg i.v.) were measured. Pain severity was scored (short form of the Glasgow Composite Measure Pain Scale, GCMPS) before surgery and postoperatively at 2, 4, 6, 12 and 24 hours after extubation. Post-operative rescue analgesia consisted of methadone (0.2mg/kg i.v.), and was applied when the GCMPS >6. For statistical analysis, the Chi-square, Fisher, and Wilcoxon tests and one- and two-way ANOVA were applied. Differences were considered statistically significant at p<0.05. Only the MAP was significantly different between the two treatment groups. Intra- and postoperative MAP of group LA (111.2±11.2mmHg and 119.3± 18.2mmHg, respectively) was higher than in group EPI (86.6± 8.7mmHg and 95.2±13.1mmHg, respectively). None of the dogs developed urinary retention or ambulatory deficits when completely recovered from anaesthesia. No other side effects were noted. In conclusion, femoral and sciatic nerve blocks and epidural anaesthesia ensure comparable analgesic effects in canine patients undergoing orthopaedic surgery of the pelvic limb. The lower mean arterial blood pressure of group EPI was not of clinical relevance.

Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis

BackgroundTestosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin-stimulating agents (ESA). MethodsSingle-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal. ResultsMean testosterone level was 321±146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753±1784 vs. 4291±3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. ConclusionHypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis.

Parenteral Na2S, a fast-releasing H2S donor, but not GYY4137, a slow-releasing H2S donor, lowers blood pressure in rats.

Hydrogen sulfide (H2S) is involved in blood pressure regulation. We evaluated hemodynamic effects of Na2S and morpholin-4-ium (4-methoxyphenyl)(morpholino)phosphinodithioate (GYY4137), H2S donors. GYY4137 is the most widely studied slow-releasing H2S donor, however, its ability to release H2S under physiological conditions is unclear. Hemodynamics were recorded in anaesthetized Wistar-Kyoto rats at baseline and after intravenous (IV) or intraperitoneal (IP) administration of either a vehicle (20% dimethyl sulfoxide), GYY4137 or Na2S. The stability of GYY4137 in buffers and in plasma was evaluated with nuclear magnetic resonance. The vehicle, as well as GYY4137, given IV did not affect mean arterial blood pressure (MABP), whereas Na2S produced a significant decrease in MABP. Similarly, IP given Na2S, but not GYY4137, lowered MABP. In the buffers at pH of 7.4 and 5.5 and in rat plasma no reaction of GYY4137 was found during 18 hours of observation. In contrast, rapid decomposition of GYY4137 occurred in buffers at pH 2.0. In conclusion, parenteral GYY4137 does not exert a hemodynamic effect in Wistar-Kyoto rats. This seems to be due to the high stability of GYY4137 at physiological pH. Therefore, it is likely that widely reported biological effects of GYY4137 are not H2S-dependent but may depend on GYY4137 itself. However, the H2S-dependent biological effects of GYY4137 may be expected in tissues characterized by low pH.