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25 results on '"Ghasabyan, Arsen"'

2. Hemorrhagic shock and tissue injury provoke distinct components of trauma-induced coagulopathy in a swine model.

Author

Cralley, Alexis L., Moore, Ernest E., Coleman, Julia R., Vigneshwar, Navin, Bartley, Matt, Kissau, Daniel, Eitel, Andrew, Hom, Patrick, Mitra, Sanchayita, Ghasabyan, Arsen, Fragoso, Miguel, Guo, Zihan, Deguchi, Hiroshi, Griffin, John H., Cohen, Mitchell J., Silliman, Christopher C., Banerjee, Anirban, Hansen, Kirk, and Sauaia, Angela

Subjects
TISSUE wounds, INJURY complications, BIOLOGICAL models, THROMBOSIS, BLOOD proteins, ANIMAL experimentation, SWINE, THROMBELASTOGRAPHY, PROTEOLYTIC enzymes, RISK assessment, FIBRINOLYSIS, HEMORRHAGIC shock, BLOOD coagulation disorders, HISTONES, DESCRIPTIVE statistics, RESEARCH funding, CALCIUM, TISSUE plasminogen activator, DISEASE risk factors, DISEASE complications, BLOOD
Abstract

Introduction: Tissue injury (TI) and hemorrhagic shock (HS) are the major contributors to trauma-induced coagulopathy (TIC). However, the individual contributions of these insults are difficult to discern clinically because they typically coexist. TI has been reported to release procoagulants, while HS has been associated with bleeding. We developed a large animal model to isolate TI and HS and characterize their individual mechanistic pathways. We hypothesized that while TI and HS are both drivers of TIC, they provoke different pathways; specifically, TI reduces time to clotting, whereas, HS decreases clot strength stimulates hyperfibrinolysis. Methods: After induction of general anesthesia, 50 kg male, Yorkshire swine underwent isolated TI (bilateral muscle cutdown of quadriceps, bilateral femur fractures) or isolated HS (controlled bleeding to a base excess target of − 5 mmol/l) and observed for 240 min. Thrombelastography (TEG), calcium levels, thrombin activatable fibrinolysis inhibitor (TAFI), protein C, plasminogen activator inhibitor 1 (PAI-1), and plasminogen activator inhibitor 1/tissue-type plasminogen activator complex (PAI-1-tPA) were analyzed at pre-selected timepoints. Linear mixed models for repeated measures were used to compare results throughout the model. Results: TI resulted in elevated histone release which peaked at 120 min (p = 0.02), and this was associated with reduced time to clot formation (R time) by 240 min (p = 0.006). HS decreased clot strength at time 30 min (p = 0.003), with a significant decline in calcium (p = 0.001). At study completion, HS animals had elevated PAI-1 (p = 0.01) and PAI-1-tPA (p = 0.04), showing a trend toward hyperfibrinolysis, while TI animals had suppressed fibrinolysis. Protein C, TAFI and skeletal myosin were not different among the groups. Conclusion: Isolated injury in animal models can help elucidate the mechanistic pathways leading to TIC. Our results suggest that isolated TI leads to early histone release and a hypercoagulable state, with suppressed fibrinolysis. In contrast, HS promotes poor clot strength and hyperfibrinolysis resulting in hypocoagulability. [ABSTRACT FROM AUTHOR]

Published
2023
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3. Succinate Activation of SUCNR1 Predisposes Severely Injured Patients to Neutrophil-mediated ARDS.

Author

Nunns, Geoffrey R., Vigneshwar, Navin, Kelher, Marguerite R., Stettler, Gregory R., Gera, Lajos, Reisz, Julie A., D'Alessandro, Angelo, Ryon, Joshua, Hansen, Kirk C., Gamboni, Fabia, Moore, Ernest E., Peltz, Erik D., Cohen, Mitchell J., Jones, Kenneth L., Sauaia, Angela, Liang, Xiayuan, Banerjee, Anirban, Ghasabyan, Arsen, Chandler, James G., and Rodawig, Sophia

Published
2022
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7. Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

Author

Barrett, Christopher D., Moore, Hunter B., Moore, Ernest E., Wang, Janice, Hajizadeh, Negin, Biffl, Walter L., Lottenberg, Lawrence, Patel, Purvesh R., Truitt, Michael S., McIntyre, Robert C., Bull, Todd M., Ammons, Lee Anne, Ghasabyan, Arsen, Chandler, James, Douglas, Ivor S., Schmidt, Eric P., Moore, Peter K., Wright, Franklin L., Ramdeo, Ramona, and Borrego, Robert

Subjects
RESPIRATORY insufficiency, TISSUE plasminogen activator, COVID-19, SARS-CoV-2, ALTEPLASE, BRAIN imaging
Abstract

Background: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients.Research Question: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe?Study Design and Methods: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality.Results: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit.Interpretation: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality.Trial Registry: ClinicalTrials.gov; No.: NCT04357730; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Published
2022
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14. All animals are equal but some animals are more equal than others: Plasma lactate and succinate in hemorrhagic shock-A comparison in rodents, swine, nonhuman primates, and injured patients.

Author

Reisz, Julie A., Wither, Matthew J., Moore, Ernest E., Slaughter, Anne L., Moore, Hunter B., Ghasabyan, Arsen, Chandler, James, Schaub, Leasha J., Fragoso, Miguel, Nunns, Geoffrey, Silliman, Christopher C., Hansen, Kirk C., Banerjee, Anirban, Sheppard, Forest R., and D'Alessandro, Angelo

Published
2018
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17. Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy.

Author

Gonzalez, Eduardo, Moore, Ernest E., Moore, Hunter B., Chapman, Michael P., Chin, Theresa L., Ghasabyan, Arsen, Wohlauer, Max V., Barnett, Carlton C., Bensard, Denis D., Biffl, Walter L., Burlew, Clay C., Johnson, Jeffrey L., Pieracci, Fredric M., Jurkovich, Gregory J., Banerjee, Anirban, Silliman, Christopher C., and Sauaia, Angela

Published
2016
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25. Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes: A Post Hoc Analysis of the PAMPer and COMBAT Clinical Trials.

Author

Pusateri, Anthony E., Moore, Ernest E., Moore, Hunter B., Le, Tuan D., Guyette, Francis X., Chapman, Michael P., Sauaia, Angela, Ghasabyan, Arsen, Chandler, James, McVaney, Kevin, Brown, Joshua B., Daley, Brian J., Miller, Richard S., Harbrecht, Brian G., Claridge, Jeffrey A., Phelan, Herb A., Witham, William R., Putnam, A. Tyler, and Sperry, Jason L.

Published
2020
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