Administration of low and high doses of heparin causes changes in plasma non-esterified fatty acid concentration in merino and terminal sired lambs

Abstract

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.