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David N. Herndon - One of the best experts on this subject based on the ideXlab platform.

  • Safety of Nebulized Epinephrine in Smoke Inhalation Injury.
    Journal of Burn Care & Research, 2017
    Co-Authors: Guillermo Foncerrada, Francisco Lima, Robert P. Clayton, Perenlei Enkhbaatar, David N. Herndon, Ronald P Mlcak, Oscar E. Suman
    Abstract:

    : This pilot study was conducted to profile safety of nebulized racemic epinephrine when used as a therapy for smoke inhalation injury in severely burned children. We enrolled 16 patients who were 7 to 19 years of age ([mean ± SD], 12 ± 4 years) with burns covering more than 30% of the TBSA (55 ± 17%) and smoke inhalation injury, as diagnosed by bronchoscopy at burn center admission. Patients were randomized to receive either standard of care (n = 8), which consisted of nebulized acetylcysteine, nebulized heparin, and nebulized albuterol, or to receive standard of care plus nebulized epinephrine (n = 8). Primary endpoints were death, chest pain, and adverse changes in Cardiopulmonary Hemodynamics (arrhythmia, arterial blood pressure, electrocardiographic [ST segment] changes, and peak inspiratory pressure). Additional endpoints included total days on ventilator, pulmonary function, and physiological Cardiopulmonary measurements at intensive care unit discharge. No adverse events were observed during or after the nebulization of epinephrine, and no deaths were reported that were attributable to the administration of nebulized epinephrine. The groups did not significantly differ with regard to age, sex, burn size, days on ventilator, pulmonary function, or Cardiopulmonary fitness. Results of this pilot trial indicate epinephrine to be safe when administered to pediatric burn patients with smoke inhalation injury. Current data warrant future efficacy studies with a greater number of patients.

  • adipose derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
    PLOS ONE, 2017
    Co-Authors: Koji Ihara, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Dannelys Perezbello, Christina Nelson, Anita Randolph, Suzan Alharbi, Hira Hanif, David N. Herndon
    Abstract:

    Background Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, thus significantly increasing the mortality of burn patients. Adipose-derived stem cells (ASCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and ecfficacy of ASCs, in a well-characterized clinically relevant ovine model of ARDS. Methods Female sheep were surgically prepared. ARDS was induced by cooled cotton smoke inhalation. Following injury, sheep were ventilated, resuscitated with lactated Ringer’s solution, and Cardiopulmonary Hemodynamics were monitored for 48 hours in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein content in plasma and lung lymph fluid. Sheep were randomly allocated to two groups: 1) ASCs: infused with 200 million of ASCs in 200mL of PlasmaLyteA starting 1 hours post-injury, n = 5; 2) control, treated with 200mL of PlasmaLyteA in a similar pattern, n = 5. Results Lung lymph flow increased 9-fold in control sheep as compared to baseline. Protein in the plasma was significantly decreased, while it was increased in the lung lymph. The treatment with ASCs significantly attenuated these changes. Treatment with ASCs almost led to the reversal of increased pulmonary vascular permeability and lung water content. Pulmonary gas exchange was significantly improved by ASCs. Infusion of the ASCs did not negatively affect pulmonary artery pressure and other hemodynamic variables. Conclusions ASCs infusion was well tolerated. The results suggest that intravenous ASCs modulate pulmonary microvascular hyper-permeability and prevent the onset of ARDS in our experimental model.

  • abstract 19670 adipose derived mesenchymal stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
    Circulation, 2015
    Co-Authors: Koji Ihara, David N. Herndon, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Ernesto Lopez, Hal K Hawkins, Donald S Prough, Perenlei Enkhbaatar
    Abstract:

    Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, significantly increasing the mortality of burn patients. Mesenchymal stem cells (MSCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and efficacy of MSCs in a well-characterized clinically relevant ovine model of ARDS. Methods: Female sheep (30-40 kg) were surgically prepared 5-7 days prior the study. ARDS was induced by cooled cotton smoke inhalation. Following the injury, sheep were ventilated, resuscitated with lactated Ringer’s solution and Cardiopulmonary Hemodynamics was monitored for 48 h in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein in plasma and lung lymph. Sheep were randomly allocated to two groups: 1) MSCs: infused with 5 million/kg of intravenous MSCs over 30min starting 1 h post-injury, n=5; 2) control, treated with a vehicle in a similar pattern (200ml of PlasmaLyte A), n=5. Results: Lung lymph flow, an index of pulmonary transvascular fluid flux was ~7-fold increased in control sheep compared to baseline. This was associated with a significant protein decrease in plasma and its increase in lung lymph. The treatment with MSCs significantly attenuated these changes (Table). Moreover, the treatment with MSCs almost reversed increased pulmonary vascular permeability index {(lung lymph proteinхlung lymph flow)/plasma protein} and reduced lung water content (Lung wet-to-dry weight ratio). Pulmonary gas exchange was significantly improved by MSCs (PaO2/FiO2 was 406±101 in MSCs and 262±127 in control at 24 hrs, p Conclusions: MSCs infusion was well tolerated. The results suggest that intravenous MSCs modulate pulmonary microvascular hyper-permeability and prevent onset of ARDS.

Koji Ihara - One of the best experts on this subject based on the ideXlab platform.

  • adipose derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
    PLOS ONE, 2017
    Co-Authors: Koji Ihara, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Dannelys Perezbello, Christina Nelson, Anita Randolph, Suzan Alharbi, Hira Hanif, David N. Herndon
    Abstract:

    Background Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, thus significantly increasing the mortality of burn patients. Adipose-derived stem cells (ASCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and ecfficacy of ASCs, in a well-characterized clinically relevant ovine model of ARDS. Methods Female sheep were surgically prepared. ARDS was induced by cooled cotton smoke inhalation. Following injury, sheep were ventilated, resuscitated with lactated Ringer’s solution, and Cardiopulmonary Hemodynamics were monitored for 48 hours in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein content in plasma and lung lymph fluid. Sheep were randomly allocated to two groups: 1) ASCs: infused with 200 million of ASCs in 200mL of PlasmaLyteA starting 1 hours post-injury, n = 5; 2) control, treated with 200mL of PlasmaLyteA in a similar pattern, n = 5. Results Lung lymph flow increased 9-fold in control sheep as compared to baseline. Protein in the plasma was significantly decreased, while it was increased in the lung lymph. The treatment with ASCs significantly attenuated these changes. Treatment with ASCs almost led to the reversal of increased pulmonary vascular permeability and lung water content. Pulmonary gas exchange was significantly improved by ASCs. Infusion of the ASCs did not negatively affect pulmonary artery pressure and other hemodynamic variables. Conclusions ASCs infusion was well tolerated. The results suggest that intravenous ASCs modulate pulmonary microvascular hyper-permeability and prevent the onset of ARDS in our experimental model.

  • abstract 19670 adipose derived mesenchymal stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
    Circulation, 2015
    Co-Authors: Koji Ihara, David N. Herndon, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Ernesto Lopez, Hal K Hawkins, Donald S Prough, Perenlei Enkhbaatar
    Abstract:

    Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, significantly increasing the mortality of burn patients. Mesenchymal stem cells (MSCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and efficacy of MSCs in a well-characterized clinically relevant ovine model of ARDS. Methods: Female sheep (30-40 kg) were surgically prepared 5-7 days prior the study. ARDS was induced by cooled cotton smoke inhalation. Following the injury, sheep were ventilated, resuscitated with lactated Ringer’s solution and Cardiopulmonary Hemodynamics was monitored for 48 h in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein in plasma and lung lymph. Sheep were randomly allocated to two groups: 1) MSCs: infused with 5 million/kg of intravenous MSCs over 30min starting 1 h post-injury, n=5; 2) control, treated with a vehicle in a similar pattern (200ml of PlasmaLyte A), n=5. Results: Lung lymph flow, an index of pulmonary transvascular fluid flux was ~7-fold increased in control sheep compared to baseline. This was associated with a significant protein decrease in plasma and its increase in lung lymph. The treatment with MSCs significantly attenuated these changes (Table). Moreover, the treatment with MSCs almost reversed increased pulmonary vascular permeability index {(lung lymph proteinхlung lymph flow)/plasma protein} and reduced lung water content (Lung wet-to-dry weight ratio). Pulmonary gas exchange was significantly improved by MSCs (PaO2/FiO2 was 406±101 in MSCs and 262±127 in control at 24 hrs, p Conclusions: MSCs infusion was well tolerated. The results suggest that intravenous MSCs modulate pulmonary microvascular hyper-permeability and prevent onset of ARDS.

Rajeev Saggar - One of the best experts on this subject based on the ideXlab platform.

  • brief report effect of ambrisentan treatment on exercise induced pulmonary hypertension in systemic sclerosis a prospective single center open label pilot study
    Arthritis & Rheumatism, 2012
    Co-Authors: Dinesh Khanna, Shelley Shapiro, Daniel E Furst, Paul Maranian, P J Clements, Fereidoun Abtin, Shiv Dua, John A Belperio, Rajeev Saggar
    Abstract:

    Objective Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in Hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum–associated ePH treated with open-label daily ambrisentan. Methods Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal Hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and Cardiopulmonary Hemodynamics. Results Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm5; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (−4.1 mm Hg; P = 0.02), and total pulmonary resistance (−93.0 dynes × seconds/cm5; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. Conclusion Exercise Hemodynamics and exercise capacity in patients with SSc spectrum–associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH.

Perenlei Enkhbaatar - One of the best experts on this subject based on the ideXlab platform.

  • Safety of Nebulized Epinephrine in Smoke Inhalation Injury.
    Journal of Burn Care & Research, 2017
    Co-Authors: Guillermo Foncerrada, Francisco Lima, Robert P. Clayton, Perenlei Enkhbaatar, David N. Herndon, Ronald P Mlcak, Oscar E. Suman
    Abstract:

    : This pilot study was conducted to profile safety of nebulized racemic epinephrine when used as a therapy for smoke inhalation injury in severely burned children. We enrolled 16 patients who were 7 to 19 years of age ([mean ± SD], 12 ± 4 years) with burns covering more than 30% of the TBSA (55 ± 17%) and smoke inhalation injury, as diagnosed by bronchoscopy at burn center admission. Patients were randomized to receive either standard of care (n = 8), which consisted of nebulized acetylcysteine, nebulized heparin, and nebulized albuterol, or to receive standard of care plus nebulized epinephrine (n = 8). Primary endpoints were death, chest pain, and adverse changes in Cardiopulmonary Hemodynamics (arrhythmia, arterial blood pressure, electrocardiographic [ST segment] changes, and peak inspiratory pressure). Additional endpoints included total days on ventilator, pulmonary function, and physiological Cardiopulmonary measurements at intensive care unit discharge. No adverse events were observed during or after the nebulization of epinephrine, and no deaths were reported that were attributable to the administration of nebulized epinephrine. The groups did not significantly differ with regard to age, sex, burn size, days on ventilator, pulmonary function, or Cardiopulmonary fitness. Results of this pilot trial indicate epinephrine to be safe when administered to pediatric burn patients with smoke inhalation injury. Current data warrant future efficacy studies with a greater number of patients.

  • abstract 19670 adipose derived mesenchymal stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
    Circulation, 2015
    Co-Authors: Koji Ihara, David N. Herndon, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Ernesto Lopez, Hal K Hawkins, Donald S Prough, Perenlei Enkhbaatar
    Abstract:

    Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, significantly increasing the mortality of burn patients. Mesenchymal stem cells (MSCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and efficacy of MSCs in a well-characterized clinically relevant ovine model of ARDS. Methods: Female sheep (30-40 kg) were surgically prepared 5-7 days prior the study. ARDS was induced by cooled cotton smoke inhalation. Following the injury, sheep were ventilated, resuscitated with lactated Ringer’s solution and Cardiopulmonary Hemodynamics was monitored for 48 h in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein in plasma and lung lymph. Sheep were randomly allocated to two groups: 1) MSCs: infused with 5 million/kg of intravenous MSCs over 30min starting 1 h post-injury, n=5; 2) control, treated with a vehicle in a similar pattern (200ml of PlasmaLyte A), n=5. Results: Lung lymph flow, an index of pulmonary transvascular fluid flux was ~7-fold increased in control sheep compared to baseline. This was associated with a significant protein decrease in plasma and its increase in lung lymph. The treatment with MSCs significantly attenuated these changes (Table). Moreover, the treatment with MSCs almost reversed increased pulmonary vascular permeability index {(lung lymph proteinхlung lymph flow)/plasma protein} and reduced lung water content (Lung wet-to-dry weight ratio). Pulmonary gas exchange was significantly improved by MSCs (PaO2/FiO2 was 406±101 in MSCs and 262±127 in control at 24 hrs, p Conclusions: MSCs infusion was well tolerated. The results suggest that intravenous MSCs modulate pulmonary microvascular hyper-permeability and prevent onset of ARDS.

Martin Westphal - One of the best experts on this subject based on the ideXlab platform.

  • short term effects of glipizide an adenosine triphosphate sensitive potassium channel inhibitor on Cardiopulmonary Hemodynamics and global oxygen transport in healthy and endotoxemic sheep
    Shock, 2006
    Co-Authors: Matthias Lange, Csaba Szabo, Hugo Van Aken, William Williams, Daniel L Traber, Fritz Daudel, Katrin Broking, Andrew L Salzman, Hans G Bone, Martin Westphal
    Abstract:

    In severe sepsis and septic shock, hemodynamic support is often complicated by a tachyphylaxis against exogenous catecholamines. Because activation of adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels plays a pivotal role in the pathogenesis of hyperdynamic vasodilatory shock, we hypothesized that it may be beneficial to administer a specific K(ATP) channel inhibitor to prevent, or at least attenuate, hemodynamic dysfunction in sepsis. The present study was designed as a prospective and controlled laboratory experiment to elucidate the short-term effects of glipizide, a specific K(ATP) channel inhibitor, on Cardiopulmonary Hemodynamics and global oxygen transport in healthy sheep and sheep with endotoxemia. Ten adult ewes were anesthetized and operatively instrumented with a pulmonary artery, a femoral artery, and a foley catheter. After 24 h of recovery, healthy sheep received glipizide as a bolus infusion (4 mg/kg over 15 min). After 24 h of recovery, a continuous infusion of endotoxin (Salmonella typhosa, 10 ng.kg.(-1)min) was started in the same sheep and administered for the next 17 h. After 16 h of endotoxemia, glipizide was given as described above. Administration of glipizide was followed by a transient, but significant, increase in mean arterial pressure in both healthy controls (95 +/- 3 mmHg vs. 101 +/- 2 mmHg, P < 0.05) and sheep with endotoxemia (86 +/- 3 mmHg vs. 93 +/- 3 mmHg, P < 0.05). However, the increase in mean arterial pressure was longer lasting in ewes with endotoxemia. Cardiac index, oxygen delivery index, arterial lactate concentrations, and arterial pH were not significantly affected by glipizide. Therefore, administration of glipizide may represent a beneficial therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome. Additional studies are required to determine the effects of continuous infusion of glipizide in the presence of systemic inflammation.

  • short term effects of glipizide an adenosine triphosphate sensitive potassium channel inhibitor on Cardiopulmonary Hemodynamics and global oxygen transport in healthy and endotoxemic sheep
    Shock, 2006
    Co-Authors: Matthias Lange, Csaba Szabo, Hugo Van Aken, William Williams, Daniel L Traber, Fritz Daudel, Katrin Broking, Andrew L Salzman, Hans G Bone, Martin Westphal
    Abstract:

    ABSTRACTIn severe sepsis and septic shock, hemodynamic support is often complicated by a tachyphylaxis against exogenous catecholamines. Because activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels plays a pivotal role in the pathogenesis of hyperdynamic vasodilatory shock,