Reperfusion half-life: a novel pharmacodynamic measure of thrombolytic activity.
OBJECTIVE
We hypothesized that the probability of reperfusion can be modeled by an exponential decay (ie, half-life) function and that this reperfusion half-life is decreased by thrombolytic treatment.


METHODS
Serial perfusion MRI scans were evaluated for evidence of reperfusion in intravenous tissue plasminogen activator-treated (n=45) and untreated (n=103) patients. The cumulative probability of reperfusion for each group was fit with exponential decay functions. The resulting reperfusion half-life (ie, the time it takes half the sample to reperfuse) was calculated.


RESULTS
In untreated patients, a monoexponential decay function fit the data well (R(2)=0.95) with a half-life of 29.1 hours. In tissue plasminogen activator-treated patients, the data were best fit with a biexponential decay function (R(2)=0.99) that had a fast and a slow component. The fast component is attributable to tissue plasminogen activator therapy and has a half-life of 0.71 hours, whereas the slow component was similar to that of the untreated group. Approximately 3.5 hours after the start of treatment, the effect of tissue plasminogen activator on the probability of reperfusion was negligible.


CONCLUSIONS
The probability of reperfusion can be well described by the reperfusion half-life. Determination of the fast component reperfusion half-life may be an approach to compare the relative potency of different thrombolytic agents.
Merino
José G
JG
Latour
Lawrence L
LL
An
Li
L
Hsia
Amie W
AW
Kang
Dong-Wha
DW
Warach
Steven
S
D000368:Aged; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011336:Probability; D011446:Prospective Studies; D015424:Reperfusion; D020521:Stroke / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D010959:Tissue Plasminogen Activator