Discussion

These results indicate that whilst VLDL can act as a substrate for heart at physiological concentrations, its efficacy as a cardiac substrate is significantly improved if the VLDL is synthesised by a liver previously subjected to endotoxic stimulation—a greater proportion of the TAG is assimilated and then oxidised, and under certain dosage conditions less is esterified into myocardial tissue lipid whilst hydraulic work and cardiac output are doubled. This effect may be partly due to increased LPL activity although the mechanism for the endotoxic VLDL-induced translocation of myocardial LPL to its active endothelial site is uncertain. One report4 suggests that the composition of VLDL may change during systemic E.coli sepsis with proportionately increased NEFA and TAG compared to apoprotein content in VLDL particles from septic rats. Such a modification of VLDL particle composition may explain the change in LPL activity since TAG and

Figure 3. Effect of VLDL on LPL activity in perfused working rat heart. Hearts from endotoxic or control rats were perfused with VLDL from control (VLDL-C) or endotoxic (VLDL-LPS) rat liver perfusions; some control hearts were perfused with oleate (NEFA). Results are means ± SEM for n = 6-10 experiments. *P < 0.05, **P < 0.01, ***P < 0.001 VLDL compared to NEFA, "P < 0.05 control VLDL compared to endotoxic VLDL.

Heart: control control control LPS

Perfusate: NEFA VLDL-C VLDL-LPS VLDL-LPS

Figure 3. Effect of VLDL on LPL activity in perfused working rat heart. Hearts from endotoxic or control rats were perfused with VLDL from control (VLDL-C) or endotoxic (VLDL-LPS) rat liver perfusions; some control hearts were perfused with oleate (NEFA). Results are means ± SEM for n = 6-10 experiments. *P < 0.05, **P < 0.01, ***P < 0.001 VLDL compared to NEFA, "P < 0.05 control VLDL compared to endotoxic VLDL.

NEFA are known to modulate cardiac LPL activity,16 and the increased TAG content of VLDL may render it a better substrate for LPL. Glucose was present as a co-substrate but its rate of utilisation was not measured in these experiments. The mechanism whereby endotoxaemia induces increased TAG content of VLDL is unknown but may be related to the increased hepatic lipogenesis.3 An alternative pathway for VLDL access into the cardiomyocyte is through the VLDL-receptor8 which binds apo-E as well as LPL; this may account for quantitatively important amounts of VLDL-TAG uptake under certain conditions but Tripp et al.9 noted decreased hepatic VLDL-apo-E synthesis during systemic sepsis suggesting that this pathway is unlikely to be increased during endotoxi-naemia. These results support the hypothesis that excessive, abnormal VLDL produced by the liver during systemic sepsis/endotoxinaemia may be destined for the heart.

Support was provided by the Wellcome Trust, the British Journal of Anaesthesia and Oxford Cardiac Surgical Sciences.

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