Johnson Lindsey M, Holcombe Susan J, Shearer Tara R, Watson Victoria, Gandy Jeffery, Southwood Louise L, Lynch Tymothy M, Schroeder Eric L, Fogle Callie A, Sordillo Lorraine M
Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI, United States.
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States.
Front Vet Sci. 2020 Apr 21;7:204. doi: 10.3389/fvets.2020.00204. eCollection 2020.
Identifying therapies that mitigate ischemic colonic injury and improve mucosal healing and intestinal viability are crucial to improving survival in horses with ≥360° large colon volvulus (LCV). Ethyl pyruvate is the ethyl ester of pyruvate with diverse pharmacologic effects that limit ischemic injury and hasten intestinal mucosal repair in preclinical rodents, sheep and swine models. The objective of this study was to determine the effects of ethyl pyruvate on systemic indices of colon viability, expression of inflammatory genes in whole blood, morbidity and survival after surgical correction of LCV compared to controls. Horses received either 150 mg/kg ethyl pyruvate in 1 liter lactated Ringer's solution (LRS) or 1 liter LRS intravenously (IV) every 6 h for 24 h following surgical recovery for correction of LCV. Colic duration, perioperative heart rate (HR), packed cell volume (PCV), total solids (TS), blood L-lactate concentration, surgical time, intraoperative episodes of hypoxemia and hypotension, expression of inflammatory cytokine genes, fecal consistency and survival to hospital discharge were compared between ethyl pyruvate treated horses and controls. Twenty-two horses, 12 receiving ethyl pyruvate and 10 controls, were enrolled in the study. Ethyl pyruvate was safely administered to horses following surgical correction of LCV. No significant effects of ethyl pyruvate on post-operative variables, including survival, were found. Seven of 12 ethyl pyruvate treated horses and 5/10 controls survived to hospital discharge. Higher HR, PCV and blood L-lactate concentration at the time of hospital admission, = 0.005, 0.01, 0.04, respectively, 24 h after surgery, = 0.001, 0.03, 0.02, respectively, were associated with death. Heart rate, = 0.005, 48 h after surgery was associated with death. Ethyl pyruvate was safely administered to horses following correction of LCV with no apparent adverse events but was not associated with improved post-operative outcomes including survival. A larger, randomized control trial is needed to fully evaluate the effectiveness of ethyl pyruvate. A major limitation of this investigation is the small sample size, making the study underpowered and creating a high possibility of type II error.
确定能够减轻缺血性结肠损伤、促进黏膜愈合和肠道活力的治疗方法对于提高患有≥360°大结肠扭转（LCV）的马匹的存活率至关重要。丙酮酸乙酯是丙酮酸的乙酯，在临床前啮齿动物、绵羊和猪模型中具有多种药理作用，可限制缺血性损伤并加速肠黏膜修复。本研究的目的是确定与对照组相比，丙酮酸乙酯对结肠活力的全身指标、全血中炎症基因的表达、LCV手术矫正后的发病率和存活率的影响。在LCV手术矫正恢复后，马匹每6小时静脉注射（IV）1升乳酸林格氏液（LRS）中含有的150mg/kg丙酮酸乙酯或1升LRS，持续24小时。比较了丙酮酸乙酯治疗组马匹和对照组之间的绞痛持续时间、围手术期心率（HR）、红细胞压积（PCV）、总固体（TS）、血L-乳酸浓度、手术时间、术中低氧血症和低血压发作、炎症细胞因子基因的表达、粪便稠度以及出院存活率。22匹马参与了该研究，其中12匹接受丙酮酸乙酯治疗，10匹作为对照。在LCV手术矫正后，丙酮酸乙酯已安全地施用于马匹。未发现丙酮酸乙酯对包括存活率在内的术后变量有显著影响。12匹接受丙酮酸乙酯治疗的马匹中有7匹、10匹对照组中有5匹存活至出院。入院时较高的HR、PCV和血L-乳酸浓度（分别为P = 0.005、0.01、0.04）以及术后24小时（分别为P = 0.001、0.03、0.02）与死亡相关。术后48小时的心率（P = 0.005）与死亡相关。在LCV矫正后，丙酮酸乙酯已安全地施用于马匹，未出现明显不良事件，但与包括存活率在内的术后改善结果无关。需要进行更大规模的随机对照试验来全面评估丙酮酸乙酯的有效性。本研究的一个主要局限性是样本量小，使得研究效力不足并产生II型错误的可能性很高。
