Ashour Mahmoud, Hajjar Waseem, Al-Kattan Khaled, Essa Mohammed, Al-Motrafi Abed Al-Rhaman, Al-Saddique Ahmed, El-Bakry Abdelkareem
Division of Thoracic Surgery (37), King Khalid University Hospital, College of Medicine, King Saud University, P.O. Box 7805, Riyadh 11472, Saudi Arabia.
Eur J Cardiothorac Surg. 2004 May;25(5):839-43. doi: 10.1016/j.ejcts.2003.12.010.
Heparin has long been thought to be biosynthesized and stored in the granules of mast cells that are most prevalent in the lungs and gastro-intestinal tract. In response to stimuli such inflammation and trauma, mast cells degranulate and consequently release heparin. This prospective study was designed to investigate if operative trauma during lung mobilization could enhance heparin release into both the pulmonary and systemic circulations.
Prospective investigations and data collection were carried out on 34 patients undergoing elective thoracotomies for 19 patients with chronic inflammatory disease and 15 with lung carcinoma. Heparin assay using the high performance liquid chromatography method was carried out on four blood samples from each patient. Sample 1 was taken pre-operatively from the radial artery. Intra-operatively following lung mobilization and prior to excision, sample 2 was taken from the draining pulmonary vein and at the same time, sample 3 from the radial artery. Postoperatively, the next morning, sample 4 was taken from the radial artery.
The mean values for serum heparin levels in pg/ml of samples 1-4 were found to be 205.1 (SD+/-282.1), 366.0 (SD+/-371.7), 337.2 (SD+/-225.3) and 250.8 (SD+/-282.2), respectively. These results show that intraoperative serum heparin levels (samples 2 and 3) are significantly higher (P = 0.0016, P = 0.0014, respectively) than pre-operative values (sample 1). The difference between sample 2 (pulmonary) and sample 3 (systemic circulation) was not significant (P = 0.6508). Although postoperative heparin levels (sample 4) were found to be higher than pre-operative values, yet it was not statistically significant (P = 0.1340). The mean of pre-operative heparin levels in patients with lung carcinoma and inflammatory diseases were 136.2 (SD+/-62.6) and 259.4 (SD+/-368.3), respectively. Intra-operatively, heparin levels increased to 260.9 (SD+/-139.7) and 449 (SD+/-470.7), respectively. These results suggest that the mean heparin level for patients with inflammatory lung diseases was higher than that for carcinoma patients.
Within the context of lung surgery for carcinoma or inflammatory diseases, it appears that operative trauma enhances heparin release into both the pulmonary and systemic circulations, possibly through pulmonary mast cell degranulation. Thus, an episodic auto anti-coagulant effect is established during the course of surgery. Such findings may partly provide an understanding of the excessive bleeding encountered during some thoracotomies and the recognized reduced incidence of thrombo-embolic complications among thoracic surgical patients. Should an unexplained bleeding occur during the course of surgery, an excess of heparin release is recommended to be kept in mind as a possible cause.
长期以来,人们一直认为肝素是在肺和胃肠道中最常见的肥大细胞颗粒中生物合成和储存的。在炎症和创伤等刺激下,肥大细胞脱颗粒并因此释放肝素。本前瞻性研究旨在调查肺游离术中的手术创伤是否会增强肝素向肺循环和体循环的释放。
对34例行择期开胸手术的患者进行前瞻性调查和数据收集,其中19例为慢性炎症性疾病患者,15例为肺癌患者。对每位患者的四份血样进行高效液相色谱法肝素测定。样本1术前从桡动脉采集。术中肺游离后切除前,样本2从引流肺静脉采集,同时样本3从桡动脉采集。术后第二天早晨,样本4从桡动脉采集。
样本1 - 4的血清肝素水平平均pg/ml值分别为205.1(标准差±282.1)、366.0(标准差±371.7)、337.2(标准差±225.3)和250.8(标准差±282.2)。这些结果表明,术中血清肝素水平(样本2和3)显著高于术前值(样本1)(分别为P = 0.0016,P = 0.0014)。样本2(肺循环)和样本3(体循环)之间的差异不显著(P = 0.6508)。虽然术后肝素水平(样本4)高于术前值,但无统计学意义(P = 0.1340)。肺癌患者和炎症性疾病患者术前肝素水平的平均值分别为136.2(标准差±62.6)和259.4(标准差±368.3)。术中,肝素水平分别升至260.9(标准差±139.7)和449(标准差±470.7)。这些结果表明,炎症性肺病患者的肝素平均水平高于癌症患者。
在肺癌或炎症性疾病的肺手术中,手术创伤似乎会增强肝素向肺循环和体循环的释放,可能是通过肺肥大细胞脱颗粒实现的。因此,在手术过程中会产生一种间歇性的自身抗凝作用。这些发现可能部分解释了一些开胸手术中出现的出血过多以及胸外科患者血栓栓塞并发症发生率公认降低的现象。如果手术过程中出现无法解释的出血,应考虑肝素释放过多是可能的原因。