Effects of hydroxocobalamin on carboxyhemoglobin measured under physiologic and pathologic conditions.

CONTEXT: Pre-hospital administration of hydroxocobalamin (B12a) is used for empiric treatment of cyanide poisoning because cyanide poisoning is difficult to identify and requires immediate treatment. B12a interferes with the accuracy of several blood laboratory tests. This study aimed to explore how B12a affects carboxyhemoglobin (COHb) measurements in human blood at both physiologic and pathologic COHb levels. METHODS: Several clinically relevant concentrations of B12a were added to human blood samples containing physiologic (∼ 3%) and pathologic (30% and 50%) COHb levels. We then measured the COHb levels of the samples using two different co-oximeters, the Radiometer ABL 700 and the Rapidpoint 500, and compared to their actual baseline COHb levels. RESULTS: B12a had minimal effects on the COHb measured at both physiologic and pathologic levels when measured on the Radiometer. In contrast, the Rapidpoint B12a caused a dose-dependent decrease in the COHb measured, especially of pathologic COHb levels (∼ 30 and 50%). CONCLUSION: The magnitude of B12a interference on measured COHb is dependent upon the specific co-oximeter used, the actual COHb level and the serum B12a concentration. These errors may potentially influence clinical decision making and thus affect patient outcomes. Our findings emphasize the importance of measuring COHb levels on blood samples collected prior to B12a administration.

Role of lipid packing in the activity of phospholipase C-delta1 as determined by hydrostatic pressure measurements.

Previous studies with phospholipid monolayers revealed a large decrease in the activity of phosphoinositide-specific phospholipase C-delta(1) (PLC-delta(1)) which catalyses the hydrolysis of PtdIns(4, 5)P(2) as lateral pressure is applied to the membrane. If stress on the membrane is the sole inhibitor of PLC-delta(1) activity, the enzyme must penetrate the membrane surface to engage its substrate. To test the effect on PLC-delta(1) activity of lipid packing in the absence of a directional stress, we examined the effects of increasing hydrostatic pressure on enzymic activity. We find that, in contrast with monolayer studies, increasing lipid packing by hydrostatic pressure does not affect membrane binding and increases enzymic activity by 90% in going from atmospheric pressure to 10(8) Pa (approx. 1000 atm). The increase in activity could be accounted for mainly by electrostriction of water around the multiply-charged product. Our results show that when there is no net stress on the monolayer, lipid packing does not alter PLC-delta(1) activity, possibly because penetration of the enzyme into the membrane surface is shallow. We suggest that, in biological membranes, the activity of this and possibly other interfacial proteins is independent of headgroup packing.