Comparison of cardiac,hepatic, and renal effects of arginine vasopressin and noradrenaline during porcine fecal peritonitis: a randomized controlled trial

Introduction

Infusing arginine vasopressin (AVP) in vasodilatory shock usually decreases cardiac output and thus systemic oxygen transport. It is still a matter of debate whether this vasoconstriction impedes visceral organ blood flow and thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis whether low-dose AVP is safe with respect to liver, kidney, and heart function and organ injury during resuscitated septic shock.

Methods

After intraperitoneal inoculation of autologous feces, 24 anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned to noradrenaline alone (increments of 0.05 μg/kg/min until maximal heart rate of 160 beats/min; n = 12) or AVP (1 to 5 ng/kg/min; supplemented by noradrenaline if the maximal AVP dosage failed to maintain mean blood pressure; n = 12) to treat sepsis-associated hypotension. Parameters of systemic and regional hemodynamics (ultrasound flow probes on the portal vein and hepatic artery), oxygen transport, metabolism (endogenous glucose production and whole body glucose oxidation derived from blood glucose isotope and expiratory ¹³CO₂/¹²CO₂ enrichment during 1,2,3,4,5,6-¹³C₆-glucose infusion), visceral organ function (blood transaminase activities, bilirubin and creatinine concentrations, creatinine clearance, fractional Na⁺ excretion), nitric oxide (exhaled NO and blood nitrate + nitrite levels) and cytokine production (interleukin-6 and tumor necrosis factor-α blood levels), and myocardial function (left ventricular dp/dt_max and dp/dt_min) and injury (troponin I blood levels) were measured before and 12, 18, and 24 hours after peritonitis induction. Immediate post mortem liver and kidney biopsies were analysed for histomorphology (hematoxylin eosin staining) and apoptosis (TUNEL staining).

Results

AVP decreased heart rate and cardiac output without otherwise affecting heart function and significantly decreased troponin I blood levels. AVP increased the rate of direct, aerobic glucose oxidation and reduced hyperlactatemia, which coincided with less severe kidney dysfunction and liver injury, attenuated systemic inflammation, and decreased kidney tubular apoptosis.

Conclusions

During well-resuscitated septic shock low-dose AVP appears to be safe with respect to myocardial function and heart injury and reduces kidney and liver damage. It remains to be elucidated whether this is due to the treatment per se and/or to the decreased exogenous catecholamine requirements.     

False positives in plasma ammonia measurement and their clinical impact in a pediatric population

OBJECTIVE: Plasma ammonia measurement is greatly influenced by pre-analytical conditions, which may lead to false positives. We wanted to evaluate the prevalence and clinical impact of plasma ammonia false positives in a pediatric population. DESIGN AND METHODS: Over a 28-month period, charts of patients with elevated ammonemia were retrospectively reviewed to identify false positives defined as elevated concentrations that subsequently normalized without plausible explanation for the elevations. RESULTS: 1880 Ammonia measurements were available in 479 patients. Elevated results that subsequently normalized were found in 86 patients. Forty-one (48%) of these patients had most likely falsely elevated ammonemia. Additional blood sampling and laboratory testing were the most frequent consequences of false positives. CONCLUSION: There is a high proportion of false positives among elevated plasma ammonia measurements. Capillary samples and delay between sampling and centrifugation are possible contributing factors. Clinical consequences of false positives were most often limited.     

Establishing a link between heart rate and pain in healthy subjects: a gender effect.

Heart rate (HR) is currently used by rehabilitation clinicians as a complementary objective measure of pain. The premise is that, as pain increases, HR should also increase. However, this relationship is not clearly established. The goal of this study was to verify the relationship between HR and pain perception. Thirty-nine healthy volunteers participated in this experimental study. Painful stimuli were induced by a 2-minute immersion of the hand in hot water (47 degrees C). HR was recorded before and during the stimulation and was matched to a pain rating. We observed a rise of 11% in HR after 2 minutes of immersion. There was a significant intrasubject correlation between HR and pain intensity (r = 0.50, P < .001) and pain unpleasantness (r = 0.55, P < .001). Furthermore, there was a strong gender effect in the intersubject correlations. Men presented a strong correlation between mean HR and mean pain perception (intensity: r = 0.77, unpleasantness: r = 0.86), whereas this relationship was absent in women (intensity: r = -0.2, unpleasantness: r = 0.001). In conclusion, results show that, for healthy volunteers, experimental pain can elicit a rise in HR up to 11%. Moreover, the relationship between HR response and pain is gender related. Considering that a positive relationship between HR and pain perception was only found in men, these results do not support a clinical significance of the use of HR for pain evaluation in women. Clinical implications need to be further evaluated with patients before clinicians can use HR as a complementary tool in pain assessment. PERSPECTIVE: A positive correlation between HR and pain was observed for men but not for women. These differences underline the importance of taking into account gender differences in the development of complementary pain assessment. Further research should be conducted to verify the role of sex hormones on heart rate and pain.     

A prominent role for amygdaloid complexes in the Variability in Heart Rate (VHR) during Rapid Eye Movement (REM) sleep relative to wakefulness

Rapid eye movement sleep (REMS) is associated with intense neuronal activity, rapid eye movements, muscular atonia and dreaming. Another important feature in REMS is the instability in autonomic, especially in cardiovascular regulation. The neural mechanisms underpinning the variability in heart rate (VHR) during REMS are not known in detail, especially in humans. During wakefulness, the right insula has frequently been reported as involved in cardiovascular regulation but this might not be the case during REMS. We aimed at characterizing the neural correlates of VHR during REMS as compared to wakefulness and to slow wave sleep (SWS), the other main component of human sleep, in normal young adults, based on the statistical analysis of a set of H(2)(15)O positron emission tomography (PET) sleep data acquired during SWS, REMS and wakefulness. The results showed that VHR correlated more tightly during REMS than during wakefulness with the rCBF in the right amygdaloid complex. Moreover, we assessed whether functional relationships between amygdala and any brain area changed depending the state of vigilance. Only the activity within in the insula was found to covary with the amygdala, significantly more tightly during wakefulness than during REMS in relation to the VHR. The functional connectivity between the amygdala and the insular cortex, two brain areas involved in cardiovascular regulation, differs significantly in REMS as compared to wakefulness. This suggests a functional reorganization of central cardiovascular regulation during REMS.     

Dual function of MyD88 in RAS signaling and inflammation, leading to mouse and human cell transformation

Accumulating evidence points to inflammation as a promoter of carcinogenesis. MyD88 is an adaptor molecule in TLR and IL-1R signaling that was recently implicated in tumorigenesis through proinflammatory mechanisms. Here we have shown that MyD88 is also required in a cell-autonomous fashion for RAS-mediated carcinogenesis in mice in vivo and for MAPK activation and transformation in vitro. Mechanistically, MyD88 bound to the key MAPK, Erk, and prevented its inactivation by its phosphatase, MKP3, thereby amplifying the activation of the canonical RAS pathway. The relevance of this mechanism to human neoplasia was suggested by the finding that MyD88 was overexpressed and interacted with activated Erk in primary human cancer tissues. Collectively, these results show that in addition to its role in inflammation, MyD88 plays what we believe to be a crucial direct role in RAS signaling, cell-cycle control, and cell transformation.     

Initial Experience of Single-Port Surgery Assisted by Percutaneous Instruments for Gastric Bypass: a Combination of Safety and Minimally Invasive Surgery

Background

We present here the first reported cases of patients undergoing gastric bypass with a hybrid technique that involves a new concept of percutaneous instruments and provides the advantages of minimally invasive single-port surgery while maintaining the triangulation, safety, and timing of operative procedures.

Methods

This was a prospective pilot study of eight patients selected for gastric bypass between December 2011 and January 2012 and treated by a technique that combined single SSL port and percutaneous surgical set PPS. We performed hand-sewn gastrojejunostomy in all cases. We analyzed preliminary results at 1 month and focused on the feasibility of the technique, duration of surgery, perioperative complications, and cosmetic results. The Ethics Committee of our institution approved this study and we obtained the informed consent of each patient.

Results

We completed the procedure successfully in all patients. No conversions to laparotomy or classic laparoscopy were required. The average time of surgery was 112 min (85–155). Length of hospital stay was 4 days (3–5). One patient was re-admitted on the seventh postoperative day for gastrointestinal bleeding from the gastrojejunostomy suture and treated by endoscopic clipping. Residual scars were less than 2 cm for the single midline port and 2 mm for the percutaneous instruments.

Conclusions

This new technique combines the advantages of single-port surgery with the safety of conventional laparoscopy by using percutaneous instruments and leaves minimal scarring. It is likely that the use of percutaneous instrumentation will become widespread in all areas of laparoscopic surgery.