Moderate, Short-Term, Local Hyperglycemia Attenuates Forearm Endothelium-Dependent Vasodilation After Transient Ischemia-Reperfusion in Human Volunteers.

OBJECTIVE: Acute hyperglycemia causes endothelial dysfunction in diabetic patients, abolishes ischemic pre- and postconditioning, and is an independent predictor of adverse outcome after myocardial infarction in nondiabetic patients. Its effects on endothelial-dependent vasodilation are controversial in healthy subjects. The authors studied the effect of moderate short-term local hyperglycemia on forearm endothelium-dependent vasodilation in healthy volunteers. DESIGN: Randomized, crossover, blinded, 2-visit, pilot design. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: Five male and 3 female healthy adult volunteers (23±4 years; height 171±13 cm; weight 66±9 kg; [mean±standard error of the mean]). INTERVENTIONS: At each visit, volunteers received an infusion through a brachial artery catheter of either 0.9% saline or dextrose in the experimental, non-dominant arm, to establish mild forearm hyperglycemia. Hemodynamics and forearm blood flow (FBF; plethysmography) were measured at baseline, during brachial artery infusions of acetylcholine in consecutive increments (5, 10, and 15 µg/min), before ischemia (20 min, blood pressure cuff at 200 mmHg), and after 15 minutes of reperfusion. Blood glucose and insulin concentrations were determined from venous samples. The effect of duration of intra-arterial dextrose on FBF was examined. MEASUREMENTS AND MAIN RESULTS: Dextrose increased steady-state blood glucose concentration in the experimental but not the control arm (dominant arm). Dextrose increased FBF compared with saline (4.5±0.5 v 2.6±0.4 mL/min/100 g of tissue, respectively). Acetylcholine caused similar increases in FBF in the absence and presence of dextrose (+239±90% v+203±75%, respectively, during 15 µg/min). The duration of dextrose did not affect this acetylcholine-induced vasodilation. Acetylcholine-stimulated increases in FBF were attenuated in dextrose-treated versus saline after reperfusion (+180±18% v+257±53%, respectively, during 10 µg/min). Interventions in the experimental arm did not affect FBF in the control arm. CONCLUSION: These results indicated that moderate, short-term, local hyperglycemia induced by intra-arterial administration of dextrose attenuated forearm endothelial-dependent vasodilation after ischemia-reperfusion injury in healthy volunteers.

Short-Term Angiotensin Subtype 1 Receptor Blockade Does Not Alter the Circulatory Responses to Sympathetic Nervous System Modulation in Healthy Volunteers Before and During Sevoflurane Anesthesia: Results of a Pilot Study.

OBJECTIVE: The mechanism of perioperative hypotension in patients taking an angiotensin-receptor blocker up to the time of surgery remains unclear. This study tested the hypothesis that short-term angiotensin-receptor blocker treatment attenuated the sympathetic and vascular responses to autonomic stimuli in volunteers undergoing anesthesia. DESIGN: Randomized, crossover, blinded, pilot design. SETTING: Zablocki Veterans Affairs Medical Center, Milwaukee, WI. PARTICIPANTS: The study comprised 8 male and 6 female healthy, young volunteers (age 23±1.2 years [mean±standard error of the mean]). INTERVENTIONS: Volunteers were studied after receiving oral placebo or 50 mg of losartan (angiotensin-receptor blocker) for 3 days before each test day. The effectiveness of angiotensin-receptor blocker treatment was confirmed using the mean arterial blood pressure response to intravenous angiotensin II (1-µg bolus). Eight volunteers underwent direct mean arterial pressure and forearm bloodflow measurements during conscious baseline, a cold pressor test, induction of anesthesia, tracheal intubation, maintenance of anesthesia with 1 minimum alveolar concentration of sevoflurane, and airway irritation with 12% desflurane. Six volunteers experienced mean arterial pressure responses to 0.1 mg of phenylephrine at baseline and during 1 minimum alveolar concentration of sevoflurane. MEASUREMENTS AND MAIN RESULTS: Comparisons were made over time and across groups. Angiotensin-receptor blocker treatment significantly reduced-mean arterial pressure and forearm vascular resistance (forearm blood flow/mean arterial pressure) over time and blocked the mean arterial pressure response to angiotensin-II challenge. The changes in mean arterial pressure and forearm vascular resistance in response to all stressors did not differ between treatments. Mean arterial pressure increases from phenylephrine were preserved. CONCLUSIONS: In healthy, young volunteers, sympathetically-mediated responses from the short-term use of an angiotensin-receptor blocker were not altered and most likely did not contribute to perioperative hypotension during the intraoperative period.

The effectiveness of oxygen delivery and reliability of carbon dioxide waveforms: a crossover comparison of 4 nasal cannulae.

BACKGROUND: Effective O2 delivery and accurate end-tidal CO2 (ETCO2) sampling are essential features of nasal cannulae (NCs) in patients with compromised respiratory status. We studied 4 NC designs: bifurcated nasal prongs (NPs) with O2 delivery and CO2 sensing in both NPs (Hudson), separate O2/CO2 NPs (Salter), and CO2 sensing in NPs with cloud O2 delivery outside the NPs via multi vents (Oridion) and dual vents (Medline). We hypothesized that design differences between NCs would influence O2 delivery and ETCO2 detection. METHODS: Forty-five healthy volunteers, 18 to 35 years, participated in an unrestricted, randomized block design, each subject serving as their own control in a 4-period crossover study design of 4 NCs during one session. Monitoring included electrocardiogram, posterior pharynx O2 sampling from a Hauge Airway (Sharn Anesthesia Products, Tampa, FL), and NC ETCO2. In 11 volunteers, radial artery blood was sampled from a catheter for partial pressures of O2 and carbon dioxide (PaO2 and PaCO2) determination. Per randomization, each NC was positioned, and data were collected over 2 minutes (ETCO2, pharyngeal O2, PaO2, and PaCO2) during room air and during O2 fresh gas flows (FGFs) of 2, 4, and 6 Lpm. Statistical analyses were performed with SAS Analytics Pro, Version 9.3, and JMP Statistical Software, Version 11 (SAS Institute Inc., Cary, NC), significance at P < 0.05. RESULTS: Blood gas analyses indicated PaCO2 during steady state at each experimental time period remained unchanged from physiologic baseline. PaO2 did not differ between NC devices at baseline or 2 Lpm O2. The PaO2 at 4 Lpm from the separate NPs and bifurcated NCs was significantly higher than the multi-vented NC. Pharyngeal O2 with the NC with separate NPs was significantly higher than multivented and dual-vented cloud delivery NCs at 2, 4, and 6 Lpm FGF. Pharyngeal O2 with the NC with bifurcated NPs was significantly higher than the multi-vented NC at 2 Lpm, and higher than cloud delivery NCs at 4 and 6 Lpm FGF. ETCO2 was significantly lower with the NC with bifurcated NPs compared to the other 3 NCs, consistent with errant CO2 tracings at higher FGF. CONCLUSIONS: NCs provide supplemental inspired O2 concentrations for patients with impaired pulmonary function. Accurate measures of ETCO2 are helpful in assessing respiratory rate and determining whether CO2 retention is occurring from hypoventilation. These findings suggest the NC with separate NPs was the most effective in delivering O2 and the most consistent at providing reliable CO2 waveforms at higher FGFs.

Balancing carcinoid crisis and right ventricular dysfunction during tricuspid and pulmonic valve replacement for carcinoid heart disease: A case report.

INTRODUCTION AND IMPORTANCE: Carcinoid tumors are rare malignancies of neuroendocrine origin that can manifest with a constellation of systemic symptoms including right-sided cardiac involvement. Many patients with carcinoid heart disease require valve replacement, but intraoperative management of carcinoid syndrome varies within the literature. CASE PRESENTATION: A 72-year-old man with carcinoid syndrome underwent tricuspid and pulmonic valve replacement with multiple episodes of carcinoid crisis intraoperatively as well as right ventricular dysfunction after cardiopulmonary bypass. CLINICAL DISCUSSION: Octreotide is the mainstay in prevention and treatment of intraoperative carcinoid crisis, but reported dosages and timing varies significantly. The use of exogenous catecholamines is also controversial as they are thought to paradoxically worsen carcinoid symptoms. Our patient was managed successfully with both an octreotide infusion and intermittent boluses, as well as exogenous catecholamines for right ventricular support during and after cardiopulmonary bypass. CONCLUSION: The management of carcinoid syndrome in patients undergoing valve surgery for carcinoid heart disease is dependent on timely prevention and treatment of carcinoid crisis and effective mitigation of right ventricular dysfunction.

No Room to "Lean In": A Qualitative Study on Gendered Barriers to Promotion and Leadership.

INTRODUCTION: The gender gap in professorship and leadership roles persists in academic medicine, whereas reasons for these disparities remain unclear. MATERIALS AND METHODS: Open-ended text responses to a 2013 faculty engagement survey were analyzed by using the grounded theory and consensual qualitative analysis techniques. The authors grouped 491 faculty's text responses into descriptive codes and three themes: (1) No Obstacles, (2) Barriers to Success, and (3) Concerns Regarding Processes. Demographics of codes were compared by using chi-square analysis. RESULTS: Male faculty identified barriers that included negative views of leadership or leaders. Female faculty, especially those in clinical roles, expressed barriers related to role overload, including that the demands of their current positions prevented advancement or addition of further roles, no matter how desirable further roles may be. Women also shared that considerable self-promotion was required to receive acknowledgement of their work and support by leadership. CONCLUSION: A proposed framework depicts male and female faculty's concerns on a continuum. No Obstacle and Process Concerns were relatively gender neutral, whereas large gender disparities occurred within the Barriers to Success theme. Women's barriers largely revolved around internal obstacles (I can't do any more), and men's barriers largely revolved around external factors (leaders are impeding my progress). Resources are needed to mitigate work overload specifically for female faculty, and to ensure that all faculty are both engaged in advanced career opportunities and encouraged to pursue leadership positions.

Anesthesia Preoperative Clinic Evaluation of Obstructive Sleep Apnea Using Nasal Fiberoptic Videoendoscopy: A Pilot Study Comparison with Polysomnography.

BACKGROUND: Nasal fiberoptic videoendoscopy is an established technique to assess upper airway pathology in conscious and sedated patients. OBJECTIVES: The authors conducted a prospective proof-of-concept pilot study to evaluate whether airway narrowing detected using nasal fiberoptic videoendoscopy in the anesthesia preoperative clinic was capable of defining the severity of obstructive sleep apnea (OSA) in patients scheduled for elective surgery. METHODS: After application of topical local anesthesia (4% lidocaine with phenylephrine), sixteen patients (ASA physical status 2 or 3) underwent nasal fiberoptic videoendoscopy in sitting position. The magnitudes of retropalatal and retrolingual luminal narrowing were assessed as predictors of OSA. Patients also underwent polysomnography and completed STOP-Bang questionnaires. The endoscopist's clinical impression of OSA severity based on the history and airway examination was quantified. RESULTS: Retropalatal luminal narrowing and STOP-Bang score ≥ 4 predicted OSA severity as either "none or mild" or "moderate to severe" in 13 (81%) and 9 (56%) of 16 patients who underwent polysomnography, respectively. OSA severity was significantly (Spearman's rank correlation coefficient) associated with retropalatal airway narrowing (P = 0.0048), STOP-BANG score (P = 0.0072), and body mass index (P = 0.0091), whereas clinical impression and retrolingual pharyngeal narrowing were not (P=0.093 and P = 0.11, respectively). CONCLUSIONS: The current results suggest that nasal fiberoptic videoendoscopy quantification of retropalatal airway narrowing may be a useful tool for assessing the severity of OSA in the anesthesia preoperative clinic. The current findings document a proof-of-concept feasibility of nasal fiberoptic videoendoscopy as a screening tool for OSA in conscious patients during preoperative evaluation that may justify further prospective clinical trials of this technique.

Role of S-nitrosothiol transport in the cardioprotective effects of S-nitrosocysteine in rat hearts.

The objective of this study was to determine if prior exposure of rat hearts to S-nitrosocysteine (CysNO) was able to provide protection against reperfusion injury. We probed NO release using the extracellular NO scavenger oxyhemoglobin (oxyHb), and we examined the involvement of the amino acid transport system L (L-AT), a known transporter of CysNO, using the L-AT competitor, L-leucine (L-Leu). Isolated (9- to 12-week-old Wistar male) rat hearts (six to eight per group) were perfused with CysNO (10 microM) for 30 min with or without the L-AT competitor L-Leu (1 mM) before 30 min of ischemia. Cardiac function was assessed before, during, and after treatment and during 120 min of reperfusion after ischemia. Functional recovery (rate-pressure product) was significantly improved in the CysNO group compared to hearts in the CysNO+L-Leu group and the control group (p<0.05). Necrosis, measured by triphenyltetrazolium chloride staining, was significantly reduced in CysNO hearts (p<0.05) and this improvement was reversed by L-Leu. The NO scavenger oxyHb (20 microM) was perfused either concomitant with CysNO or just before ischemia. In neither case did oxyHb affect the cardioprotection afforded by CysNO. OxyHb alone, given in either time window, did not alter the course of ischemia-reperfusion injury. When nitrite was used in place of CysNO, no protective effects were observed. Perfusion with CysNO increased tissue S-nitrosothiol (RSNO) levels from an unmeasurable background to a value of about 15.7+/-4.1 pmol RSNO/mg protein, as measured by triiodide-based chemiluminescence in the presence and absence of mercury(II) chloride. In the presence of L-Leu, this value dropped to 0.4+/-0.3 pmol RSNO/mg protein. This study demonstrates that exposure to CysNO before ischemia increases tissue S-nitrosothiol levels, improves postischemic contractile dysfunction, and attenuates necrosis. The mechanism of cardioprotection requires the uptake of CysNO via the L-AT and does not seem to involve NO release either during CysNO exposure or during ischemia. This suggests that the protective effects of CysNO are mediated through the posttranslational modification of cellular proteins through an NO-independent transnitrosation mechanism.