Perioperative use of angiotensin-converting-enzyme inhibitors and angiotensin receptor antagonists.

STUDY OBJECTIVE: Clinical repercussions of perioperative treatment with ACEIs/ARBs. DESIGN: Systematic review according to PRISMA statement. SETTING: Perioperative period. PATIENTS: 29 studies 11 cases/cases series, 12 observational studies and 6 randomized studies. MEASUREMENTS: Arterial blood pressure differences, refractory hypotension, other comorbidities. MAIN RESULTS: The studies show different results regarding the topics measured. They are divided in the results regarding blood pressure, long term morbidities and effects in neuraxial anesthesia. CONCLUSIONS: Withholding AECI/ARBs on the morning prior to surgery could be recommended as a potentially effective measure, with a low level of evidence, in order to reduce the appearance of hypotension in the perioperative period of non-cardiac surgery.

Monitoring systemic oxidative stress in an animal model of amyotrophic lateral sclerosis.

A mutant form of the ubiquitous copper/zinc superoxide dismutase (SOD1) protein has been found in some patients with amyotrophic lateral sclerosis (ALS). We monitored oxidative stress in an animal model of ALS, the SOD(G93A) mouse, which develops a disease similar to ALS with an accelerated course. The aim of this work was to show that ALS damages several organs and tissues, from an oxidative stress point of view. We measured lipid and protein oxidative damage in different tissue homogenates of SOD(G93A) mice. The biomarkers that we analyzed were malondialdehyde + 4-hydroxyalkenal (MDA + 4-HDA) and carbonyls, respectively. The spinal cord and brain of SOD(G93A) mice showed increased lipid peroxidation after 100 or 130 days compared to age-matched littermate controls. The CNS was most affected, but lipid peroxidation was also detected in the skeletal muscle and liver on day 130. No changes were observed in protein carbonylation in the homogenates. Our results are consistent with a multisystem etiology of ALS and suggest that oxidative stress may play a primary role in ALS pathogenesis. Thus, oxidative stress represents a potential biomarker that might be useful in developing new therapeutic strategies for ALS.

Circadian rhythms of dopamine and dihydroxyphenyl acetic acid in the mouse striatum: effects of pinealectomy and of melatonin treatment.

The existence of dopamine (DA)-melatonin (aMT) relationships is well documented in several brain areas of the mammalian central nervous system such as the retina and hypothalamus or the nigrostriatal system. For instance, aMT tempers 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal damage in C57BL/6 mice. In this mouse strain however, rhythmic production of aMT and its possible interaction with striatal DA is still unclear. In the present work we investigated circadian variations in pineal production of aMT and striatal DA levels in C57BL/6 mice. Effects of pinealectomy and aMT administration were also assessed. Intact, pinealectomized and pinealectomized + aMT-treated mice and their respective control groups were sacrificed at six different times during the 24-hour period. In control animals, aMT displayed a circadian rhythm with a narrow peak at midnight. The peak of aMT coincided with the nadir of the DA rhythm present in the striatum. Shortly after the decrease of DA levels, an increase in 3,4-dihydroxyphenylacetic acid (DOPAC), the main DA metabolite, was observed. The rhythmic changes of DA and DOPAC levels in the striatum were blunted by pinealectomy, whereas administration of aMT (0.1-10 mg/kg) during 6 days to pinealectomized mice restored the rhythms in a dose-dependent manner. Striatal levels of 3-methoxytyramine and homovanillic acid did not change during the 24-hour cycle. The serotonergic system, assessed by the determination of 5-hydroxytryptamine and 5-hydroxyindole-3-acetic acid concentration in striatum, did not show significant time-dependent changes in control animals and was not affected by pinealectomy or aMT treatment. These data substantiate the existence of a link between pineal function, melatonin secretion and DA circadian rhythm in the mouse striatum.

Evaluation of plasma levels of melatonin after midazolam or sodium thiopental anesthesia in children.

Midazolam and sodium thiopental are two commonly used drugs in anesthesia for minor surgical procedures in children. A relationship exists between benzodiazepines (BNZ), barbiturates and melatonin. Whereas these drugs increase pineal melatonin production, the indoleamine amplifies the effects of both BNZ and barbiturates on the central nervous system (CNS). Our purpose was thus to analyze the plasma levels of melatonin before and during midazolam or sodium thiopental anesthesia in children subjected to ambulatory surgical procedures. Midazolam (0.4 mg/kg) or sodium thiopental (5 mg/kg) were administered i.v. to 33 and 32 children (aged between 2 and 14 yr), respectively, and blood samples were taken before and 5, 10 and 20 min after the drugs were administered. Melatonin was measured in plasma by a commercial radioimmunoassay kit previously standardized in our laboratory. The results showed that neither midazolam nor sodium thiopental anesthesia significantly affected the levels of melatonin studied at anytime. Significant correlations were found comparing the levels of melatonin between the different times studied. These results suggest that midazolam or sodium thiopental did not affect melatonin production by the pineal gland, thus avoiding a possible potentiating effect of the indoleamine on the central effects of these drugs during anesthesia. However, the possibility that changes in melatonin had been masked by the antioxidant role of the neurohormone are discussed.