Hemorrhagic Transformation: Influence of occlusion duration, infarct size and tissue plasminogen activator in experimental stroke
Introduction: The availability of reperfusion therapy for acute ischemic stroke patients has made the causes and significance of hemorrhagic transformation an area of intense interest and controversy. Methods: Seventy-four male Wistar rats underwent temporary middle cerebral artery occlusion (MCAO) of between 1 and 6 hours. Twenty-two animals received 10 mg/kg of tissue plasminogen activator (tPA), infused over 20 minutes, starting 5 minutes before reperfusion. At 18–24 hours, the animals were sacrificed and tissue collected for analysis. The presence of grossly observable hemorrhagic transformation (HT)was recorded and total ischemic lesion area was quantified using image analysis software (Zeiss - KS 300). Stepwise logistic regression was used to quantify the important contributors to HT development. Results: Thirty animals developed HT. The development of HT was significantly associated with occlusion duration (p=0.0004),with every hour of delay increasing the risk of HT by 1.9. The times associated with 25%,50% and 75% HT were 2.5, 4 and 5.5.hours, respectively. Infarct size (sum of lesion areas) was also signficantly associated with HT (p=0.02) but in the step wise regression, neither infarct size nor tPA contributed significantly to the model. The overall predictive value of the model was 77% but it was higher (81%) when predicting no HT. Conclusions: Duration of occlusion is a more important predictor of HT than either the infarct size or the presence of tPA in temporary MCAO in the rat. Duration of occlusion most closely predicts the degree of damage to the vasculature necessary for the development of HT.