Rate of Intraoperative Crystalloid Administration During Thoracic Surgery Is Causal in Reducing Postoperative Hospital Length of Stay.

Background: Studies in thoracic surgery have long raised concerns that intraoperative administration of intravenous fluids exacerbates or causes postoperative complications and hence advocate fluid restriction. Methods: This retrospective 3-year study investigated the role of intraoperative crystalloid administration rates on the duration of postoperative hospital length of stay (phLOS) and on the incidences of previously reported adverse events (AEs) in 222 consecutive patients following thoracic surgery. Results: Higher rates of intraoperative crystalloid administration were significantly associated with shorter phLOS (P=0.0006) and with less variance in phLOS. Dose-response curves showed progressive decreases in the postoperative incidences of surgical, cardiovascular, pulmonary, renal, other, and long-term AEs with higher intraoperative crystalloid administration rates. Conclusion: The rate of intravenous crystalloid administration during thoracic surgery was significantly associated with duration of and variance in phLOS, and dose-response curves showed progressive decreases in the incidences of AEs associated with this surgery. We cannot confirm that restrictive intraoperative crystalloid administration benefits patients undergoing thoracic surgery.

Perioperative Efficiency of Sugammadex Following Laparoscopic Cholecystectomy in Clinical Practice.

Background: Studies have proposed that the routine use of the modified gamma-cyclodextrin, sugammadex, could provide perioperative time savings. However, these investigations have been limited to small group analyses. The purpose of this study was to test the effectiveness of sugammadex on perioperative times when compared to neostigmine under general clinical practice conditions following rocuronium-induced neuromuscular blockade for laparoscopic cholecystectomy. Methods: Following institutional review board approval, data from 1,611 consecutive surgical records for laparoscopic cholecystectomy were reviewed. Patient characteristics, type of primary neuromuscular blocking reversal agent, operating room (OR) discharge times, and postanesthesia care unit (PACU) recovery times were the measures of interest. Equivalence testing was used to determine the between-group differences of the reversal agents in the two perioperative time periods of interest. Results: OR discharge times averaged 10.9 (95% CI, 10-11.8) minutes for patients administered sugammadex and 8.9 (95% CI, 8.2-9.7) minutes for patients administered neostigmine. PACU recovery times averaged 77.6 (95% CI, 74.1-81.1) minutes for sugammadex and 68.6 (95% CI, 65.9-71.3) minutes for neostigmine. Equivalence testing demonstrated no improvement in the two perioperative times with sugammadex. Conclusion: These results suggest no perioperative time savings with sugammadex when compared to neostigmine following laparoscopic cholecystectomy under general clinical practice conditions.

Preoperative Administration of Hycet Elixir Reduces Hospital Length of Stay After Pediatric Outpatient Adeno/Tonsillectomy.

Background: Postoperative wound pain is commonly observed in the pediatric postanesthesia care unit (PACU) following tonsillectomy, adenoidectomy, and adenotonsillectomy (adeno/tonsillectomy), which contributes to increased medical care costs and delayed facility discharge. The purpose of this study was to review the benefits of preoperative administration of Hycet elixir (2.5 mg hydrocodone and 108 mg acetaminophen per 5 mL) in a pediatric population aged 1 to 9 years following adeno/tonsillectomy. Methods: Patient demographics, comorbidities, surgical and anesthetic times, need for postoperative rescue therapies, and PACU recovery and length of stay times were measured in pediatric patients who received preoperative administration of Hycet elixir (0.2 mg/kg hydrocodone) for adeno/tonsillectomy in an outpatient setting compared to a control group. Results: The Hycet elixir group had significant reductions in PACU and hospital lengths of stay and significant reductions in the need for postoperative rescue analgesics. No significant differences were observed in emergence times or in the incidences of unplanned hospital admission between the control and Hycet elixir groups. Conclusion: These data show that the preoperative administration of Hycet elixir is well tolerated in the pediatric patient population undergoing adeno/tonsillectomy and appears to significantly reduce the need for postoperative rescue analgesics and postoperative care times. These data support the use of preoperative administration of Hycet elixir in this patient population.

Novel Opiate-Free Anesthetic Technique for Major Urologic Procedures.

OBJECTIVES: We postulated that an opiate-free (OF) general anesthesia (GA) technique could adequately control a patient's pain without adversely affecting recovery. We compared patients undergoing major urologic procedures with and without opiate-based GA. METHODS: A propensity-matched analysis was performed comparing hospital length of stay, postoperative nausea and vomiting, ileus occurrence, postanesthesia care unit, and total opiate consumption, as well as sedation and hemodynamic variables. The data are expressed as medians and were analyzed with the Wilcoxon rank-sum test. P < 0.05 indicate statistical significance. RESULTS: In total, 166 patients were evaluated in both the OF group and the opiate-based treatment group. American Society of Anesthesiologists classification and age were comparable, with most surgeries being laparoscopic and confined to the bladder, kidney, and prostate gland. The median opiate consumption in morphine equivalents in the postanesthesia care unit was 7.7 mg (range 5-11.7 mg) for the OF cohort versus 11.7 mg (range 5-17.3 mg) for the control group (P < 0.001). Similarly, the median total postoperative opiate consumption in morphine equivalents was 23.9 mg (range 13.8-42.4 mg) for the OF group compared with 32.1 mg (range 17.38-57.51 mg) for the control group (P = 0.0081). The median hospital length of stay for the OF group was 1.4 days (range 1.2-2.3 days) versus 1.3 days (range 1.2-2.4 days) for the control group (P = 0.8466). CONCLUSIONS: There was a statistically significant difference in opiate consumption postoperatively for patients who underwent an OF technique compared with a conventional opiate-based technique. This technique appears to be a possible alternative approach, without any apparent untoward consequences during admission.

The Modified Early Warning Score as a Predictive Tool During Unplanned Surgical Intensive Care Unit Admission.

Background: The Modified Early Warning Score (MEWS) has been proposed to warn healthcare providers of potentially serious adverse events. We evaluated this scoring system during unplanned escalation of care in hospitalized surgical patients during a 1-year period. Methods: Following institutional review board approval, all consecutive, unplanned surgical admissions into the surgical intensive care unit (SICU) during 2016 were entered into this study. MEWS and patient demographics during bedside evaluation for SICU admission were extracted from electronic medical records. Logistic regression was used to analyze the association of MEWS with the incidence of future mortality. P values were set at <0.01 for statistical significance. Results: In this series of 263 consecutive patients, the incidence of mortality following unplanned escalation of care was 29.3% (confidence interval [CI] 24.1% to 35.0%), ranging from 22% to 57%, with all positive MEWS values. The association of MEWS with future mortality was not statistically significant (P=0.0107). A misclassification rate of 0.29 (CI 0.24 to 0.35) was observed with this association. Conclusion: MEWS provided no clinical benefit as an early warning system, as mortality was elevated throughout the MEWS scale in this clinical setting. The high misclassification rate indicates MEWS does not provide discriminatory support for patients at risk for mortality.

The Effect of the IPACK Block on Pain After Primary TKA: A Double-Blinded, Prospective, Randomized Trial.

BACKGROUND: The purpose of this study was to determine if infiltration of local anesthetic between the interspace between the popliteal artery and capsule of the knee (IPACK) provides benefit in total knee arthroplasty. METHODS: Patients were randomized into continuous adductor canal block with IPACK block or continuous adductor canal block with sham subcutaneous saline injection. Only the anesthesiologist performing the block was aware of randomization status. After surgery, a blinded assessor recorded opioid consumption, pain scores, and gait distance. RESULTS: There were 35 patients in the IPACK group and 34 in the NO IPACK group. There was no difference demographically between the groups. In the postanesthesia care unit (PACU), the average (P = .0122) and worst (P = .0168) pain scores at rest were statistically lower in the IPACK group. There was no difference in the pain scores during physical therapy (P = .2080). There was no difference in opioid consumption in the PACU (P = .7928), or at 24 hours (P = .7456). There was no difference in pain scores on POD 1 in the AM (P = .4597) or PM (P = .6273), or in the walking distance (P = .5197). There was also no difference in length of stay in the PACU (P = .9426) or hospital (P = .2141). CONCLUSION: The IPACK group had lower pain scores at rest in the PACU, but this is likely not clinically significant. The routine use of the IPACK is not supported by the results of this study. There may be indications for the use of the IPACK block as a rescue block or in patients who have contraindications to our standard multimodal treatment regimen or in patients with chronic pain or opioid dependence.

Total intravenous anesthesia improves intraoperative visualization during surgery for high-grade chronic rhinosinusitis: a double-blind randomized controlled trial.

BACKGROUND: Total intravenous anesthesia (TIVA) has been proposed as a method to reduce blood loss during endoscopic sinus surgery (ESS). Impaired sinonasal visualization due to mucosal bleeding may be burdensome in cases of chronic rhinosinusitis (CRS) with high-grade inflammatory disease, suggesting a role for TIVA in that disease subgroup. METHODS: A double-blind, randomized controlled trial was conducted of adults undergoing ESS at a tertiary medical center. Patients considered for inclusion had high-grade CRS defined as either sinonasal polyposis or a preoperative Lund-Mackay score of ≥12. Subjects were randomized to receive either TIVA or inhaled anesthesia (IA) during ESS. The primary outcome measure was intraoperative visibility as rated by 3 blinded reviewers utilizing the 10-point Wormald Surgical Field Grading Scale. Secondary outcomes included operative blood loss, complications, and change in quality of life evaluated by the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: A total of 72 patients were randomized into TIVA (n = 37) and IA (n = 35) study arms. Aggregate median (interquartile range) Wormald scores across all reviewers demonstrated a more favorable visual field with TIVA compared to IA (3.5 [2.4-3.9] vs IA 4.1[3.0-5.8], p = 0.0089). There was significantly less blood loss in the TIVA group compared to the IA group (200 mL [100-450] vs 300 mL [200-500], p = 0.046). Baseline patient characteristics were comparable between cohorts with no significant postoperative complications. No significant changes were detected between postoperative SNOT-22 scores at 3 months (p = 0.278) and at 6 months (p = 0.396) following ESS. CONCLUSION: TIVA contributes to improved intraoperative visualization and decreased blood loss in patients undergoing ESS for high-grade inflammatory sinus disease.

Novel Regional Techniques for Total Knee Arthroplasty Promote Reduced Hospital Length of Stay: An Analysis of 106 Patients.

BACKGROUND: Novel regional techniques, including the adductor canal block (ACB) and the local anesthetic infiltration between the popliteal artery and capsule of the knee (IPACK) block, provide an alternative approach for controlling pain following total knee arthroplasty (TKA). This study compared 3 regional techniques (femoral nerve catheter [FNC] block alone, FNC block with IPACK, and ACB with IPACK) on pain scores, opioid consumption, performance during physical therapy, and hospital length of stay in patients undergoing TKA. METHODS: All patients had a continuous perineural infusion, either FNC block or ACB. Patients in the IPACK block groups also received a single injection 30-mL IPACK block of 0.25% ropivacaine. Pain scores and opioid consumption were recorded at postanesthesia care unit discharge and again at 8-hour intervals for 48 hours. Physical therapy performance was measured on postoperative days (POD) 1 and 2, and hospital length of stay was recorded. RESULTS: We found no significant differences in the 3 groups with regard to baseline patient demographics. Although we observed no differences in pain scores between the 3 groups, opioid consumption was significantly reduced in the FNC with IPACK group. Physical therapy performance was significantly better on POD 1 in the ACB with IPACK group compared to the other 2 groups. Hospital length of stay was significantly shorter in the ACB with IPACK group. CONCLUSION: This study demonstrated that an IPACK block reduced opioid consumption by providing effective supplemental analgesia following TKA compared to the FNC-only technique. ACB with IPACK provided equivalent analgesia and improved physical therapy performance, allowing earlier hospital discharge.

Duration of Nil Per Os is causal in hospital length of stay following laparoscopic bariatric surgery.

INTRODUCTION: A recent bariatric surgical study demonstrated an inverse relationship of intraoperative hydration with the incidence of extended hospital length of stay (ehLOS: >1 postoperative hospital day). In that study, a post hoc analysis of the preoperative duration of Nil Per Os (NPO) past midnight revealed a significant dose-response association on the incidence of ehLOS, with the lowest incidence (10-12 %) predicted within the 2-5-h NPO interval. As NPO is associated with a state of compensatory dehydration, the objectives of this study were to prospectively examine the role of decreasing preoperative NPO intervals on the incidence of ehLOS in a similar bariatric surgical population and to establish causality of this association. METHODS: Following IRB approval, 168 bariatric surgeries were analyzed following institution of a revised oral water ad libitum policy until 2 h prior to surgery on the incidence of ehLOS. The role of duration of NPO on the incidence of ehLOS was assessed by logistic fit graphs and misclassification rates on the two groups. A statistical process control chart monitored the efficacy of the revised NPO guidelines. RESULTS: There were statistically significant, but not clinical, differences in the incidences of histories of anemia, gastroesophageal reflux disease, previous percutaneous cardiac intervention/percutaneous transluminal coronary artery angioplasty, or preoperative albumin levels between the two groups. There were no perioperative pulmonary aspirations of gastric contents in either group. Following reduction of the oral hydration interval to ≥2 h, a 13-15 % incidence of ehLOS was observed within the 2-5-h NPO interval with similar misclassification rates observed between the two groups. CONCLUSIONS: Allowing bariatric patients access to ad libitum water for up to 2 h prior to surgery decreased the incidence of ehLOS. Comparison of the dose-response curves within the 2-5-h NPO intervals before and after introduction of the revised NPO guidelines was similar and confirms causality.

Distal Peripheral Nerve Blocks in the Forearm as an Alternative to Proximal Brachial Plexus Blockade in Patients Undergoing Hand Surgery: A Prospective and Randomized Pilot Study.

PURPOSE: Limited data exist regarding the role of perineural blockade of the distal median, ulnar, and radial nerves as a primary anesthetic in patients undergoing hand surgery. We conducted a prospective and randomized pilot study to compare these techniques to brachial plexus blocks as a primary anesthetic in this patient population. METHODS: Sixty patients scheduled for hand surgery were randomized to receive either an ultrasound-guided supraclavicular, infraclavicular, or axillary nerve block (brachial plexus blocks) or ultrasound-guided median, ulnar, and radial nerve blocks performed at the level of the mid to proximal forearm (forearm blocks). The ability to undergo surgery without analgesic or local anesthetic supplementation was the primary outcome. Block procedure times, postanesthesia care unit length of stay, instances of nausea/vomiting, and need for narcotic administration were also assessed. RESULTS: The 2 groups were similar in terms of the need for conversion to general anesthesia or analgesic or local anesthetic supplementation, with only 1 patient in the forearm block group and 2 in the brachial plexus block group requiring local anesthetic supplementation or conversion to general anesthesia. Similar durations in surgical and tourniquet times were also observed. Both groups reported similarly low numerical rating scale pain scores as well as the need for postoperative analgesic administration (2 patients in the forearm block group and 1 in the brachial plexus block group reported numerical rating scale pain scores > 0 and required opioid administration in the postanesthesia care unit). Block procedure characteristics were similar between the 2 groups. CONCLUSIONS: Forearm blocks may be used as a primary anesthetic in patients undergoing hand surgery. Further research is warranted to determine the appropriateness of these techniques in patients undergoing surgery in the thumb or proximal to the hand. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Airway risk factors for the Miller laryngoscope blade.

STUDY OBJECTIVE: The purpose of this study was to analyze previously reported airway risk factors in the performance of Miller laryngoscopy and orotracheal intubation. DESIGN: Prospective, observational study. SETTING: Operating rooms. PATIENTS: A total of 978 American Society of Anesthesiologists I-III adults requiring general orotracheal anesthesia for elective surgery. INTERVENTIONS: None. MEASUREMENTS: Nine previously reported airway risk factors used in predicting difficult laryngoscopy, modified McCormack-Lehane views observed during initial unaided Miller blade laryngoscopy, and number of attempts or need for alternate airway tools to facilitate orotracheal intubation. MAIN RESULTS: Orotracheal intubation occurred in 941 of 978 (96.2%) patients with the Miller blade, although 8 patients required 3 attempts, with the remaining 37 patients requiring alternate airway tools. There were no failed orotracheal intubations. Multivariable analysis revealed that modified Mallampati class, thyromental distance, and ability to prognath were associated with progressively inferior modified Cormack-Lehane views, whereas modified Mallampati class, height, and head and neck extension were associated with progressive difficulty with orotracheal intubation. CONCLUSIONS: The Miller blade is highly successful in the performance of direct laryngoscopy for orotracheal intubation. These findings suggest that different sets of airway risk factors affect the process of laryngoscopy and orotracheal intubation.

Epsilon-Aminocaproic Acid Has No Association With Thromboembolic Complications, Renal Failure, or Mortality After Liver Transplantation.

OBJECTIVES: To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. DESIGN: Retrospective, observational, cohort study design. SETTING: Single-center, university hospital. PARTICIPANTS: The study included 708 adult liver transplantations performed from 2008 to 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. CONCLUSIONS: The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation.

Impact of Anesthetic Predictors on Postpartum Hospital Length of Stay and Adverse Events Following Cesarean Delivery: A Retrospective Study in 840 Consecutive Parturients.

BACKGROUND: Cesarean deliveries are increasing, and associated postoperative adverse events are extending hospitalizations. The aims of the present study were to analyze the role of anesthestic predictors during cesarean delivery on the incidences of extended postpartum hospital length of stay (>4 postoperative days) and adverse events. METHODS: The medical records of 840 consecutive patients who underwent cesarean delivery during a 1-year period were abstracted. Previously reported anesthetic predictors underwent recursive partitioning with 5-fold cross-validation and with LogWorth values ≥2.0 statistically significant at the <0.01 level. RESULTS: In this study of 840 cesarean delivery patients, 120 parturients (14.3%; confidence interval 12.1%-16.8%) experienced extended postpartum hospital length of stay (>4 hospital days). One anesthetic predictor associated with extended postpartum hospital length of stay was type of anesthetic technique: a 25.6% incidence in parturients receiving general or epidural anesthesia compared to a 9.6% incidence in parturients receiving either spinal or combined spinal-epidural anesthesia (LogWorth value of 7.3). When the amount of intravenous fluids intraoperatively administered to Americian Society of Anesthesiologists Physical Status III and IV parturients was ≥2,000 mL, the incidence of extended postpartum hospital length of stay decreased from a baseline value of 30.0% to 17.3% (LogWorth value of 2.8). The incidence of adverse events ranged from 0%-5.0%. All regional anesthetic techniques were significantly associated with a decreased incidence of adverse events: 0.7% with spinal anesthesia, 1.9% with epidural anesthesia, and 3.2% with combined spinal-epidural anesthesia when compared to the 51.4% incidence associated with general anesthesia (LogWorth value of 4.0). CONCLUSION: These findings suggest that type of anesthetic technique and amount of intraoperative fluids administered during cesarean delivery have important effects on the incidences of extended postpartum hospital length of stay and adverse events following cesarean delivery.

Distal peripheral nerve blockade for patients undergoing hand surgery: a pilot study.

BACKGROUND: Data are limited regarding the use of peripheral nerve blockade at the level of the forearm, and most studies regard these procedures as rescue techniques for failed or incomplete blocks. The purpose of the study was to investigate patients undergoing hand surgery with distal peripheral nerve (forearm) blocks and compare them with patients having similar procedures under more proximal brachial plexus blockade. No investigations comparing distal nerve blockade to proximal approaches are currently reported in the literature. METHODS: Medical records were retrospectively reviewed for patients who had undergone hand surgery with a peripheral nerve block between November 2012 and October 2013. The primary outcome was the ability to provide a primary anesthetic without the need for general anesthesia or local anesthetic supplementation by the surgical team. Secondary outcome measures included narcotic administration during the block and intraoperative procedures, block performance times, and the need for rescue analgesics in the post anesthesia care unit (PACU). RESULTS: No statistical difference in conversion rates to general anesthesia was observed between the two groups. Total opiate administration for the block and surgical procedure was lower in the forearm block group. There was no difference in block performance times or need for rescue analgesics in the PACU. CONCLUSIONS: Forearm blocks are viable alternatives to proximal blockade and are effective as a primary anesthetic technique in patients undergoing hand surgery. Compared to the more proximal approaches, these blocks have the benefits of not causing respiratory compromise, the ability to be performed bilaterally, and may be safer in anticoagulated patients.

The adductor canal block provides effective analgesia similar to a femoral nerve block in patients undergoing total knee arthroplasty--a retrospective study.

STUDY OBJECTIVE: To determine the ability of an ultrasound-guided single-shot adductor canal block to provide adequate analgesia and improve performance during physical therapy. DESIGN: A retrospective chart review. SETTING: All procedures were performed at Ochsner Medical Center. MEASUREMENTS: Patient demographics as well as the type of peripheral nerve block performed. Pain scores and opioid consumption were recorded at postanesthesia care unit discharge and again at 8 ± 3, 16 ± 3, and 24 ± 3 hours. In addition, physical therapy performance was analyzed. MAIN RESULTS: There were no significant differences in pain scores or cumulative hydromorphone requirements between the adductor canal block group and the femoral nerve block group at any of the time points analyzed. Gait distance measured during physical therapy sessions in the adductor canal block group was superior compared with the femoral nerve block group. CONCLUSION: Within the first 24 hours, a single-shot adductor canal block provides equally effective analgesia when compared with a femoral nerve block and improves postoperative physical therapy performance.

Role of intraoperative fluids on hospital length of stay in laparoscopic bariatric surgery: a retrospective study in 224 consecutive patients.

BACKGROUND: Studies are unclear regarding optimal intraoperative fluid management during laparoscopic bariatric surgery. The purpose of this 1-year study was to investigate the role of intraoperative fluid administration on hospital length of stay (hLOS) and postoperative complications in laparoscopic bariatric surgery. METHODS: Patient data analyzed included previously reported demographics, comorbidities, and intraoperative fluid administration on the duration of hLOS and incidence of postoperative complications. RESULTS: Logistic regression analysis of demographic and comorbidity variables revealed that BMI (P = 0.0099) and history of anemia (P = 0.0084) were significantly associated with hLOS (C index statistic, 0.7). Lower rates of intraoperative fluid administration were significantly associated with longer hLOS (P = 0.0005). Recursive partitioning observed that patients who received <1,750 ml of intraoperative fluids resulted in longer hLOS when compared to patients who received ≥ 1,750 ml (LogWorth = 0.5). When intraoperative fluid administration rates were defined by current hydration guidelines for major abdominal surgery, restricted rates (<5 ml/kg/h) were associated with the highest incidence of extended hLOS (>1 postoperative day) at 54.1 % when compared to 22.9 % with standard rates (5-7 ml/kg/h) and were lowest at 14.5 % in patients receiving liberal rates (>7 ml/kg/h) (P < 0.0001). Finally, lower rates of intraoperative fluid administration were significantly associated with delayed wound healing (P = 0.03). CONCLUSIONS: The amount of intravenous fluids administered during laparoscopic bariatric surgery plays a significant role on hLOS and on the incidence of delayed wound healing.

Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats.

The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis. Human ASCs transfected with the COX-1 lentiviral vector (ASCCOX-1) display enhanced COX-1 activity while exhibiting similar differentiation potential compared with untransduced (native) ASCs. PH was induced in rats with MCT, and the rats were subsequently treated with intratracheal injection of ASCCOX-1 or untransduced ASCs. The intratracheal administration of ASCCOX-1 3 × 10(6) cells on day 14 after MCT treatment significantly attenuated MCT-induced PH when hemodynamic values were measured on day 35 after MCT treatment whereas administration of untransduced ASCs had no significant effect. These results indicate that intratracheally administered ASCCOX-1 persisted for at least 21 days in the lung and attenuate MCT-induced PH and right ventricular hypertrophy. In addition, vasodilator responses to the nitric oxide donor sodium nitroprusside were not altered by the presence of ASCCOX-1 in the lung. These data emphasize the effectiveness of ASCCOX-1 in the treatment of experimentally induced PH.

Vasodilator responses to acetylcholine are not mediated by the activation of soluble guanylate cyclase or TRPV4 channels in the rat.

The effects of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), an inhibitor of the activation of soluble guanylate cyclase (sGC) on responses to NO donors acetylcholine (ACh) and bradykinin (BK) were investigated in the pulmonary and systemic vascular beds of the rat. In these studies the administration of ODQ in a dose of 5 mg/kg iv attenuated vasodilator responses to five different NO donors without inhibiting responses to ACh and BK in the systemic and pulmonary vascular beds of the rat. Vasodilator responses to ACh were not inhibited by l-NAME or the transient receptor vanilloid type 4 (TRPV4) antagonist GSK-2193874, which attenuated vasodilator responses to the TRPV4 agonist GSK-1016790A. ODQ did not inhibit vasodilator responses to agents reported to act in an NO-independent manner or to vasoconstrictor agents, and ODQ did not increase blood methemoglobin levels, suggesting that off target effects were minimal. These results show that ODQ in a dose that inhibited NO donor-mediated responses did not alter vasodilator responses to ACh in the pulmonary and systemic vascular beds and did not alter systemic vasodilator responses to BK. The present results indicate that decreases in pulmonary and systemic arterial pressures in response to ACh are not mediated by the activation of sGC or TRPV4 channels and that ODQ can be used to study the role of the activation of sGC in mediating vasodilator responses in the rat.