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Introduction Preterm babies increasingly survive the neonatal period as a result of advanced care practices. Accordingly, anesthesiologists are likely to encounter these patients with greater frequency. Ex-premature infants and term neonates are known to have an increased risk of post-operative apneas following surgery and anaesthesia. Methods Following approval from the Institutional Review Board, we performed a retrospective chart review of neonates 0-28 days of age who underwent general anaesthesia procedures over two years. Data collected included age days, sex, weight, gestational age, American Society of Anaesthesiologists (ASA) physical status, type of anaesthetic (general/regional/spinal), airway management, surgical procedure, intraoperative adverse events, duration of anaesthesia, medications administered, post-operative recovery location, the occurrence of apneic events, medical co-morbidities, duration of post anaesthesia care unit (PACU) admission, a requirement for neonatal intensive care unit (NICU) admission, and duration of hospital admission. Results A total of 239 charts were reviewed from January 1, 2015, to December 31, 2016. Ninety-five cases were excluded for required postoperative mechanical ventilation. For the remaining 144 cases, the mean age was 12.8 days, 65% male, 35% female, mean gestational age 38.6 weeks, mean post-menstrual age 40.5 weeks, mean ASA status 3.5, and mean weight 3.46 kg. Post-operative apnea was observed in two neonates (1.4%). Risk factors for postoperative apnea included lower gestational age at birth (median 37.5 vs. 39.1 weeks, p=0.26), lower post-menstrual age (median 38.5 vs. 41.0 weeks, p=0.18), and lower weight (median 2.8 vs. 3.5kg, p=0.27), respectively. ASA classification, preoperative anaemia, and known pathology were all significant risk factors for apnea (p<0.05). Significant factors from the bivariate analysis were preoperative anaemia, known pathology, age, duration of anaesthesia, weight, intraoperative fentanyl, and amount of neuromuscular blocker. Age and preoperative anaemia were significant predictors for recovery location. The odds of going to PACU vs NICU/PICU for post-operative recovery were 7.4 times greater for every two weeks greater age (95% CI=(2.80-19.31), p<0.001).  Conclusion This study corroborates previous findings of predictive risk factors for post-anaesthesia apnea in preterm and term neonates. Previously reported risk factors, including low gestational/post-menstrual age, lower weight, and intraoperative narcotic use, were likely contributors to one of the apneic events in our study. A larger sample size is warranted to confirm a valid predictive model. Standardized universal guidelines would be useful in eliminating local variation in PACU monitoring and discharge criteria in this vulnerable age group., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Fanelli et al.)

Septic shock, the most severe complication associated with sepsis, is manifested by tissue hypoperfusion due, in part, to cardiovascular and autonomic dysfunction. In many cases, the splanchnic circulation becomes vasoplegic. The celiac-superior mesenteric ganglion (CSMG) sympathetic neurons provide the main autonomic input to these vessels. We used the cecal ligation puncture (CLP) model, which closely mimics the hemodynamic and metabolic disturbances observed in septic patients, to examine the properties and modulation of Ca2+ channels by G protein-coupled receptors in acutely dissociated rat CSMG neurons. Voltage-clamp studies 48 hr post-sepsis revealed that the Ca2+ current density in CMSG neurons from septic rats was significantly lower than those isolated from sham control rats. This reduction coincided with a significant increase in membrane surface area and a negligible increase in Ca2+ current amplitude. Possible explanations for these findings include either cell swelling or neurite outgrowth enhancement of CSMG neurons from septic rats. Additionally, a significant rightward shift of the concentration-response relationship for the norepinephrine (NE)-mediated Ca2+ current inhibition was observed in CSMG neurons from septic rats. Testing for the presence of opioid receptor subtypes in CSMG neurons, showed that mu opioid receptors were present in ~70% of CSMG, while NOP opioid receptors were found in all CSMG neurons tested. The pharmacological profile for both opioid receptor subtypes was not significantly affected by sepsis. Further, the Ca2+ current modulation by propionate, an agonist for the free fatty acid receptors GPR41 and GPR43, was not altered by sepsis. Overall, our findings suggest that CSMG function is affected by sepsis via changes in cell size and α2-adrenergic receptor-mediated Ca2+ channel modulation.

A computational methodology based on Metropolis Monte Carlo (MC) and the weighted histogram analysis method (WHAM) has been developed to calculate the absolute binding free energy between functionalized nanocarriers (NC) and endothelial cell (EC) surfaces. The calculated NC binding free energy landscapes yield binding affinities that agree quantitatively when directly compared against analogous measurements of specific antibody-coated NCs (100 nm in diameter) to intracellular adhesion molecule-1 (ICAM-1) expressing EC surface in in vitro cell-culture experiments. The effect of antibody surface coverage (σ(s)) of NC on binding simulations reveals a threshold σ(s) value below which the NC binding affinities reduce drastically and drop lower than that of single anti-ICAM-1 molecule to ICAM-1. The model suggests that the dominant effect of changing σ(s) around the threshold is through a change in multivalent interactions; however, the loss in translational and rotational entropies are also important. Consideration of shear flow and glycocalyx does not alter the computed threshold of antibody surface coverage. The computed trend describing the effect of σ(s) on NC binding agrees remarkably well with experimental results of in vivo targeting of the anti-ICAM-1 coated NCs to pulmonary endothelium in mice. Model results are further validated through close agreement between computed NC rupture-force distribution and measured values in atomic force microscopy (AFM) experiments. The three-way quantitative agreement with AFM, in vitro (cell-culture), and in vivo experiments establishes the mechanical, thermodynamic, and physiological consistency of our model. Hence, our computational protocol represents a quantitative and predictive approach for model-driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.

Endothelial cells (EC) of angiogenic tumor vasculature are characterized by altered expression of molecular markers on their surface. Numerous peptides have been identified that specifically bind tumor angiogenic endothelium, including the tripeptide arginine-arginine-leucine (RRL). We hypothesized that ultrasound contrast microbubbles (MB) targeted via linkage with RRL would specifically adhere to tumor angiogenic endothelium versus normal myocardium, and that this selective adhesion could be detected ultrasonically. Microbubbles were conjugated to cyclic peptides containing either RRL (RRL-MB) or a glycine control sequence (control-MB). As measured in a parallel plate flow chamber, in vitro adhesion of RRL-MBs was three times greater to cultured tumor-derived ECs than to normal ECs (P < 0.01), demonstrating selective binding of RRL-MBs to tumor endothelium. Mice bearing s.c. Clone C or PC3 tumors were given i.v. injections of fluorescent RRL to show in vivo localization to tumor vasculature or were ultrasonically imaged following i.v. injections of targeted contrast MBs. Ultrasound images showed strong RRL-MB contrast enhancement within the tumors but not the control tissue myocardium. Control-MBs caused minimal enhancement in either tissue. Quantitative acoustic videointensity was significantly greater for the tumors than the hearts (5 +/- 1 versus 0.5 +/- 1 intensity units; P = 0.001). These data show that ultrasound contrast MBs targeted to tumor vasculature via RRL preferentially adhere to tumor versus normal vasculature and that this selective adherence can be detected with ultrasound. Targeted microbubbles may thus offer a noninvasive contrast-enhanced ultrasound imaging technique for the functional imaging of tumor neovascularization, and may have further implications for therapeutic tumor targeting.

Background: Noninvasive techniques for detecting acute cardiac transplant rejection are limited. We hypothesized that ultrasound contrast microbubbles targeted to the endothelial cell (EC) inflammatory marker intercellular adhesion molecule-1 (ICAM-1) would selectively bind to rejecting versus nonrejecting myocardium and that myocardial contrast echocardiography can therefore detect acute rejection., Methods and Results: Lipid-based microbubbles were conjugated to anti-rat ICAM-1 (MBICAM) or isotype control antibody (MBControl). In vitro MBICAM adhesion to cultured rat ECs, as assessed in a parallel plate flow apparatus, was greater to inflammatory versus normal ECs (11+/-3 versus 3+/-2 microbubbles/EC, P<0.005). In vivo abdominal heterotopic heart transplantation was performed in rats (rejection group: Brown Norway to Lewis strain; control group: Lewis to Lewis or Brown Norway to Brown Norway). Triggered myocardial contrast echocardiography was performed during intravenous MBICAM or MBControl (2.5x10(6)) injection on postoperative day 5. Myocardial videointensity from adhered MBICAM was significantly higher in rejecting (n=8) versus control (n=7) rats (10+/-4 versus 1+/-4 U, P=0.01). Postmortem histology showed normal myocardium in control rats, whereas allograft myocardium demonstrated grade III to IV rejection and strong immunohistochemical ICAM-1 staining., Conclusions: Preferential adherence of ICAM-1-targeted microbubbles to rejecting versus nonrejecting rat cardiac transplant myocardium can be detected ultrasonically. Targeted microbubbles may thus offer a noninvasive ultrasound imaging technique for the detection of acute cardiac transplant rejection and other processes characterized by endothelial dysfunction.