Comparison of inhaled nitric oxide with aerosolized prostacyclin or analogues for the postoperative management of pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: This study aims to compare the effectiveness of inhaled prostacyclin or its analoguesversus nitric oxide (NO) in treating pulmonary hypertension (PH) after cardiac or pulmonary surgery remains unclear.

Methods: PubMed, Cochrane, and Embase databases were searched for literature published prior to December 2019 using the following keywords: inhaled, nitric oxide, prostacyclin, iloprost, treprostinil, epoprostenol, Tyvaso, flolan, and pulmonary hypertension. Randomized controlled trials and multiple-armed prospective studies that evaluated inhaled NO versus prostacyclin (or analogues) in patients for perioperative and/or postoperative PH after either cardiac or pulmonary surgery were included. Retrospective studies, reviews, letters, comments, editorials, and case reports were excluded.

Results: Seven studies with a total of 195 patients were included. No difference in the improvement of mean pulmonary arterial pressure (pooled difference in mean change= ?0.10, 95% CI: ?3.98 to 3.78, p?=?.959) or pulmonary vascular resistance (pooled standardized difference in mean change= ?0.27, 95% CI: ?0.60 to 0.05, p?=?.099) were found between the two treatments. Similarly, no difference was found in other outcomes between the two treatments or subgroup analysis.

Conclusions: Inhaled prostacyclin (or analogues) was comparable to inhaled NO in treating PH after cardiac or pulmonary surgery.

• Key messages

• This study compared the efficacy of inhaled prostacyclin or its analogues versus inhaled NO to treat PH after surgery. The two types of agent exhibited similar efficacy in managing MPAP, PVR, heart rate, and cardiac output was observed.

• Inhaled prostacyclin may serve as an alternative treatment option for PH after cardiac or pulmonary surgery.

     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Topography of median eminence somatostatinergic innervation

Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level.     

Metabolic response to beet fibre test meals

Test meals with 10.9 g dietary fibre from sugar beet and corresponding control meals were given to eight healthy subjects, aged 67 ± 9 years. The postprandial glucose, triglyceride, hormone and glycerol responses were monitored during 3 hours. After the beet fibre meal the insulin and C-peptide areas were reduced by 28 ( P < 0.01) and 22% ( P > 0.025), respectively, and the somatostatin levels increased by approximately 30% ( P > 0.05). Further, the maximum relative postprandial reduction of plasma glycerol levels was less evident after the fibre-rich meal than after the control meal (36 ± 4% v. 46 ± 4%, P < 0.05). There was no apparent difference in the overall glycaemic response between the meals. The triglyceride levels were similar after both test meals.
Suspension of beet fibre bread given to rats by oro-gastric intubation induced lower blood glucose response than a control bread at 15 and 30 min ( P < 0.001), respectively, but a similar insulin response.
The results suggest an effect of beet fibre on the rate of carbohydrate absorption, expressed as a lower insulin response in the healthy volunteers and a reduced glucose response in the rat.
The mechanism behind this effect in healthy subjects could possibly be mediated by an increased somatostatin response.     

红霉素对犬幽门括约肌压力影响及其与胃动素,生长抑素的关系

为探讨红霉素对犬幽门括约肌的作用及其机理，及其与血浆胃动素，生长抑素的关系。方法采用胃压力测量仪及放射免疫法，同步监测观察了１０条犬静脉滴ＥＭ前后和使用拮抗剂后的幽门压力、血浆ＭＴＬ，ＳＳ的变化，结论：ＥＭ具有增高犬胃幽门压力的作用，其作用机理除与血浆ＭＴＬ有着密切的关系外，血浆ＳＳ也可能共同参与了其调节机制。     

Cyclic analogues of Thr6-bradykinin,N8-Lys-bradykinin and endo-Lys8a-vespulakinin 1

Syntheses are described of the endo-Lys^8a-vespulakinin 1 and of cyclo-Thr⁶- and cyclo-N^ε-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys^8a-VSK-1 and Thr⁶-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the ε-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its N^α-Boc-[(Gal β)Thr³, (Gal β)Thr⁴]-analogue, were used to prepare N^α-(1–8 VSK 1)-cyclo-N^ε-kallidin and N^α-[(Gal β)Thr³, (Gal β)Thr⁴, 1–8 VSK 1]-cyclo-N^ε-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. © Munksgaard 1995.     

Effects of glucagon-like peptide 1 (7–36 amide) on whole-body protein metabolism in healthy man

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-¹³C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P  < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO₂ production during GLP-1 administration ( P  < 0.0005). Plasma insulin increased after 3 h of GLP-1 infusion to 1486 ± 145 pmol L⁻¹ vs. 185 ± 12 pmol L⁻¹ for saline ( P  < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.     

Lobucavir-induced proliferative changes in mice

Nucleoside analogues are used in the treatment of viral infections, including those caused by human immunodeficiency virus, cytomegalovirus, and herpes virus. These drugs are beneficial in the treatment of human disease, but are associated with toxicities that often limit their intended therapeutic use, including anemia, neutropenia, peripheral neuropathy, and myopathy. Some of these compounds have been reported to be carcinogenic in rodents. To investigate the carcinogenic potential of lobucavir, a nucleoside analogue, three groups of 60 male and female mice were orally administered lobucavir at daily doses of 10, 50, and 250 mg/kg (males) or 30, 150, and 750 mg/kg (females) over a period of 104 weeks. Two identical groups of 60 male and female mice each served as controls. The morphology and the incidence of neoplasms is described and compared with the tumor spectrum of other nucleoside analogues. Light microscopically, lobucavir-induced neoplastic lesions consisted of upper digestive tract squamous cell neoplasia in males and females; cervical, vaginal, and cutaneous squamous cell neoplasia in females; and Hardarian gland adenomas and adenocarcinomas in male mice. These results suggest that long-term administration of lobucavir causes neoplasia in mice, the spectrum of which resembles that observed after long-term administration of zidovudine or ganciclovir.