The journal of trauma and acute care surgery · 2013
Effects of histone deacetylase inhibition on 24-hour survival and end-organ injury in a porcine trauma model: a prospective, randomized trial.
Сравнительное исследованиеСтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Nelson Daniel W, Porta Christopher R, McVay Derek P, Salgar Shashikumar K, Martin Matthew J
Аннотация
BACKGROUND: Valproic acid (VPA) is a histone deacetylase inhibitor that has been shown to improve early resuscitation from hemorrhagic shock. We sought to examine whether there is a sustained benefit of VPA in a survival model of severe injury.
METHODS: Yorkshire swine (n = 36) were randomized to three groups as follows: (a) control, (b) VPA (single dose), and (c) VPA (two doses at 12 hours apart). Animals underwent a 35% volume-controlled hemorrhage, followed by aortic cross-clamping for 50-minute duration, at which time VPA (400 mg/kg) was administered intravenously. Animals then underwent protocol guided resuscitation with crystalloid and vasopressor infusions for up to 24 hours. The primary end point was animal survival; secondary end points included hemodynamics, physiology, and histologic evidence of end-organ injury.
RESULTS: Mean duration of survival was significantly longer in the control group (15.8 hours, n = 11) compared with single-dose VPA (12.6 hours, n = 9, p < 0.02). Redosing VPA at 12 hours provided no survival benefit. During cross-clamp, animals that received VPA required significantly less lidocaine compared with the control animals (32.8 mg vs. 159.4 mg, p = 0.03). Animals that received VPA also required significantly greater quantities of intravenous fluids per hour (p < 0.01) and higher epinephrine doses (p = 0.01). VPA administration was associated with earlier evidence of cardiac suppression (decreased cardiac output, increased pulmonary wedge pressures, and systemic vascular resistance; p < 0.05). VPA was associated with renal end-organ histologic protection and improved levels of blood urea nitrogen and creatinine at all time points (p < 0.05).
CONCLUSION: Despite previous reports citing improved early outcomes with VPA administration, VPA did not improve resuscitation or mortality in a survival model with severe injury. VPA did show some evidence of prolonged renal protection. No benefit of redosing VPA was identified. VPA had a cardiac depressant effect that may be dose dependent and should be studied further.
METHODS: Yorkshire swine (n = 36) were randomized to three groups as follows: (a) control, (b) VPA (single dose), and (c) VPA (two doses at 12 hours apart). Animals underwent a 35% volume-controlled hemorrhage, followed by aortic cross-clamping for 50-minute duration, at which time VPA (400 mg/kg) was administered intravenously. Animals then underwent protocol guided resuscitation with crystalloid and vasopressor infusions for up to 24 hours. The primary end point was animal survival; secondary end points included hemodynamics, physiology, and histologic evidence of end-organ injury.
RESULTS: Mean duration of survival was significantly longer in the control group (15.8 hours, n = 11) compared with single-dose VPA (12.6 hours, n = 9, p < 0.02). Redosing VPA at 12 hours provided no survival benefit. During cross-clamp, animals that received VPA required significantly less lidocaine compared with the control animals (32.8 mg vs. 159.4 mg, p = 0.03). Animals that received VPA also required significantly greater quantities of intravenous fluids per hour (p < 0.01) and higher epinephrine doses (p = 0.01). VPA administration was associated with earlier evidence of cardiac suppression (decreased cardiac output, increased pulmonary wedge pressures, and systemic vascular resistance; p < 0.05). VPA was associated with renal end-organ histologic protection and improved levels of blood urea nitrogen and creatinine at all time points (p < 0.05).
CONCLUSION: Despite previous reports citing improved early outcomes with VPA administration, VPA did not improve resuscitation or mortality in a survival model with severe injury. VPA did show some evidence of prolonged renal protection. No benefit of redosing VPA was identified. VPA had a cardiac depressant effect that may be dose dependent and should be studied further.