Platelets as Regulators of Inflammation and Tissue Injury After Cardiac Surgery
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Acute kidney injury
研究概览
简要总结
Platelets are increasingly recognized as a potent and ubiquitously present source of inflammatory activation. Importantly, antiplatelet therapy has been shown to significantly reduce major adverse events such as renal injury in cardiac surgery patients. However, in current practice, concerns of excessive bleeding-not platelet activation and thrombosis-shape clinical decisions.
The investigators have recently seen, that a significant drop in platelet numbers following cardiac surgery is associated with increased mortality and risk of acute kidney injury. The investigators hypothesize that such thrombocytopenia is a result of excessive perioperative platelet activation and resultant release of inflammatory and tissue injurious signals by activated platelets. Platelet activation will be characterized during and after cardiac surgery and examine its correlation with inflammatory responses and perioperative end-organ injury.
详细描述
Distant organ injury is a frequent consequence of cardiovascular surgery involving cardio-pulmonary bypass. Acute kidney injury (AKI), the most common complication, occurs in 30%-40% of cardiac surgery patients and, even with moderate damage, significantly increases mortality and healthcare costs. Although organ injury has been linked to inflammation, the mechanisms that initiate and propagate these events remain poorly defined. As the median age and medical complexity of cardiac patients increases, the challenge - and opportunity - to improve organ protection lies in identifying modifiable targets.
The investigators preliminary work provides primary evidence that activated platelets play a novel role in the initiation of tissue injurious and inflammatory responses at the microvascular interface. As such, platelets aggregate in close proximity to perivascular mast cells, a cell type that can rapidly launch powerful inflammatory responses through release of preformed effectors. Platelet activation alone is sufficient to stimulate these mast cells in vitro while, conversely, pharmacological inhibition of platelets reduce mast cell-dependent inflammation and end organ injury after rat circulatory arrest.
Based on compelling experimental data and evidence of human relevance, the investigators have formed our central hypothesis that platelet activation is an important trigger of inflammatory and tissue injurious responses after cardiopulmonary bypass through stimulation of perivascular mast cells. The objective is to define the pathophysiologic relevance of the platelet/mast cell interaction to end organ injury, and to identify targets for novel strategies of organ protection in cardiac surgery patients.
Specific Aim: Define platelet activation as a risk factor for end organ injury in cardiac surgery patients.
The investigators preliminary data strongly suggest that thrombocytopenia after cardiac surgery is linked to AKI and increased mortality. In a prospective study of 100 patients undergoing coronary artery bypass graft (CAGB) surgery, the investigators will define platelet activation and consumption as the likely cause of this thrombocytopenia, and establish the association between platelet activation in general with markers of mast cell activation, systemic inflammation, and AKI.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •all patients undergoing elective CABG procedures
排除标准
- •patients with a history of:
- •renal injury (creatinine > 1.5 mg/dL)
- •hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal),
- •severe pulmonary insufficiency (requiring home oxygen therapy),
- •EF < 20%,
- •IABP use preoperatively,
- •liver, heart, or lung transplant
结局指标
主要结局
Acute kidney injury
时间窗: 30 days
AKI according to KDIGO criteria
次要结局
- systemic inflammatory response activation, as measured by serum TNFa levels(perioperative)
- platelet activation, as measured by serum platelet factor 4 levels(perioperative)
- systemic inflammatory response activation, as measured by serum IL8 levels(perioperative)
- hospital length of stay(30-days)
- Intensive care unit length of stay(30-day)
- systemic inflammatory response activation, as measured by serum Chymase levels(perioperative)
- systemic inflammatory response activation, as measured by serum IL6 levels(perioperative)
- platelet activation, as measured by p-selection levels(perioperative)
- major adverse cardiac events(30-day)