Context The anticoagulant properties of heparin have led to the routine use of heparinised saline flushes to prevent thrombus formation and to prolong the patency of indwelling cannulas. However, limited work exists on very low-dose heparin used to retain cannula patency for the purpose of repeated blood sampling for metabolic studies. Of particular interest is whether low-dose heparin will cause increases in plasma non-esterified fatty acid (NEFA) concentration. This is most relevant in metabolic studies involving repeated sampling, as this may erroneously elevate apparent plasma NEFA concentrations. Aims The objective of the present study was to evaluate the impacts of low- and high-dose heparin administration on plasma NEFA response in lambs. Methods In total, 14 merino (3 female, 4 wether) and terminal (4 female, 3 wether) sired lambs were selected from the Katanning, Western Australia, site of the Meat and Livestock Australia genetic resource flock All lambs were subjected to the following three treatments: low heparin (0.25 mL, 250 IU), high heparin (1 mL, 1000 IU) or control (1 mL of 0.9% NaCl saline), with each challenge being randomly allocated over 1.5 days. Blood samples were collected at the following time points: –30, –15, –10, –5, 0, 2.5, 5, 10, 15, 20, 30, 45, 60, 90, 120, 125 and 130 min relative to the administration of the challenge (Time 0) and tested for NEFA concentration. A derived exponential function was fitted to the raw data, enabling the plasma NEFA concentration response curve to be modelled at different time pointspre- and post-challenge, using the area under curve (AUC), maximum concentration and return to basal concentration, to quantify the NEFA response. Results Heparin-challenge dose had a significant (P < 0.01) impact on peak NEFA response at 10 min following challenge administration (NEFA AUC10), with the values after high-heparin challenge (1.03 ± 0.086 mmol/L per 10 min) being ~25% higher (P < 0.05) than those after the low-heparin challenge (0.78 ± 0.086 mmol/L per 10 min). The NEFA AUC10 values with low-dose heparin and high-dose heparin were 0.76 units and 1.02 units higher than those with the saline treatment (0.02 ± 0.086 mmol/L per 10 min; P < 0.01). Heparin-challenge dose also had a significant impact on the maximum NEFA concentration (P < 0.05). The high-heparin challenge (0.32 ± 0.057 mmol/L) had 20% higher maximum NEFA concentrations than the low-heparin challenge (0.26 ± 0.057 mmol/L). Both high and low heparin-challenge groups had maximum NEFA concentrations that were 72% and 36% higher respectively, than for the saline-challenge (0.19 ± 0.057 mmol/L) group. NEFA returned to basal concentrations by 60 min for both challenges, although the high heparin-challenge group demonstrated a slower rate of return (P < 0.05). Conclusions High and low doses of heparin caused an increase in plasma NEFA response as measured by AUC10 and maximum NEFA concentration, but returned to basal concentrations within 1 h. Implications Results indicated that heparin as an anticoagulant should be avoided where frequent blood samples are required within intervals of less than 1 h. However, for repeated sampling at intervals greater than 1 h, judicious flushing with heparinised saline is unlikely to have an impact on plasma NEFA concentrations.

中文翻译：

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给予低剂量和高剂量的肝素会导致美利奴羊和终产羔羊的血浆非酯化脂肪酸浓度发生变化

背景 肝素的抗凝特性导致常规使用肝素盐水冲洗以防止血栓形成并延长留置插管的通畅性。然而，用于保持插管通畅的极低剂量肝素的工作有限，以用于代谢研究的重复采血。特别令人感兴趣的是低剂量肝素是否会导致血浆非酯化脂肪酸 (NEFA) 浓度增加。这在涉及重复采样的代谢研究中最为相关，因为这可能会错误地提高表观血浆 NEFA 浓度。目的 本研究的目的是评估低剂量和高剂量肝素给药对羔羊血浆 NEFA 反应的影响。方法 总共 14 条美利奴羊（3 只雌性，4 条天气）和终端（4 只雌性，3 只) 公羊羔选自西澳大利亚州卡坦宁，澳大利亚肉类和畜牧业遗传资源群的所在地 所有羔羊均接受以下三种处理：低肝素 (0.25 mL, 250 IU)、高肝素 (1 mL, 1000 IU）或对照（1 mL 0.9% NaCl 盐水），每次挑战随机分配超过 1.5 天。在以下时间点收集血样：–30、–15、–10、–5、0、2.5、5、10、15、20、30、45、60、90、120、125 和 130 分钟，相对于攻击的管理（时间 0）并测试 NEFA 浓度。衍生的指数函数拟合原始数据，使血浆 NEFA 浓度响应曲线能够在攻击前和攻击后的不同时间点建模，使用曲线下面积 (AUC)、最大浓度和恢复到基础浓度，来量化 NEFA 的反应。结果 肝素激发剂量对激发给药后 10 分钟的峰值 NEFA 反应（NEFA AUC10）有显着影响（P < 0.01），高肝素激发后的值（1.03 ± 0.086 mmol/L 每 10 分钟）为比低肝素攻击后的那些高 25% (P < 0.05) (0.78 ± 0.086 mmol/L 每 10 分钟)。低剂量肝素和高剂量肝素的 NEFA AUC10 值比生理盐水治疗高 0.76 个单位和 1.02 个单位（0.02 ± 0.086 mmol/L 每 10 分钟；P < 0.01）。肝素激发剂量也对最大 NEFA 浓度有显着影响 (P < 0.05)。高肝素挑战 (0.32 ± 0.057 mmol/L) 的最大 NEFA 浓度比低肝素挑战 (0.26 ± 0.057 mmol/L) 高 20%。高和低肝素攻击组的最大 NEFA 浓度分别比生理盐水攻击组 (0.19 ± 0.057 mmol/L) 高 72% 和 36%。NEFA 在 60 分钟后恢复到两种挑战的基础浓度，尽管高肝素挑战组表现出较慢的恢复率 (P < 0.05)。结论 根据 AUC10 和最大 NEFA 浓度测量，高剂量和低剂量肝素导致血浆 NEFA 反应增加，但在 1 小时内恢复到基础浓度。影响 结果表明，如果需要在少于 1 小时的时间间隔内频繁采集血液样本，则应避免使用肝素作为抗凝剂。然而，对于间隔大于 1 小时的重复采样，用肝素盐水进行明智的冲洗不太可能对血浆 NEFA 浓度产生影响。