Role of adenosine 5 '-triphosphate in vasospasm after subarachnoid hemorrhage: Human investigations

OBJECTIVE: Adenosine 5'-triphosphate (ATP) is a vasoactive compound found i n high concentrations inside erythrocytes. This compound may contribute to vasospasm after subarachnoid hemorrhage (SAH). We assessed the hypothesis t hat ATP contributes to vasospasm in humans. METHODS: ATP and hemoglobin concentrations were measured in cerebrospinal f luid (CSF) from humans with SAH and in blood incubated in vitro. The vasoac tivity of the human CSF samples and of fractionated (fractions with molecul ar weight greater than or less than 10 kDa) and unfractionated blood incuba ted in vitro was assessed by application of samples to canine basilar arter y segments under isometric tension. RESULTS: ATP in human CSF declined within 72 hours of SAH to concentrations too low to contract cerebral arteries. Vasoactivity of human CSF correlate d with the concentration of hemoglobin. The vasoactivity of incubated eryth rocyte hemolysates remained high despite a decline in ATP concentrations. F ractionation of incubated erythrocyte hemolysates showed that for incubatio n periods up to 7 days, all vasoactivity was in a fraction of molecular wei ght greater than 10 kDa. CONCLUSION: ATP is unlikely to contribute to vasospasm because the concentr ations in CSF after SAH in humans are not high enough to cause vasospasm af ter 72 hours. The vasoactivity of erythrocyte hemolysate is not related to the ATP or ferrous hemoglobin content but may be related to the total hemog lobin content. Therefore, ATP is unlikely to be a major cause of clinically significant delayed vasospasm.