Mohammad Anadani, MD
Ischemic reperfusion injury after flow restoration is an extensively studied but not well-understood phenomena. The prominent mechanism of reperfusion injury is a molecular (non-ischemic) cell death in the absence of circulatory disturbance. Preclinical studies demonstrated that reperfusion injury is responsible for up to 70% of the infarct volume; therefore, it can be hypothesized that restoring reperfusion with mechanical thrombectomy in humans could lead to infarct expansion and worsening ischemic injury. There is overwhelming evidence that supports the direct association between degree of reperfusion after mechanical thrombectomy with functional independence. In fact, complete reperfusion (mTIC=3) was associated with better outcome than successful but incomplete reperfusion (mTICI >=2b).1
In this study, Gauberti and colleagues underwent a post-hoc analysis of the ASTER trial to investigate the effect of complete reperfusion on early lesion growth. Patients were included in this study if they achieved complete reperfusion at the end of the procedure (defined as modified Treatment in Cerebral Ischemia score=3) and had MRI pre- and post-mechanical thrombectomy. Patients with hemorrhagic transformation (hemorrhagic infarction type 2 or any parenchymal hemorrhage) were excluded from this study. The authors measured the ischemic lesion size on DWI both before and at day 1 after endovascular treatment.
A total of 35 patients were included in this study. Mean age was 69+-14 and median NIHSS 14 (IQR 10-18). The median growth of the ischemic lesion size was +0.9ml, and only 5/35 patients had lesion growth >10 ml. Also, only one patient had a midline shift (which was used as a surrogate for brain edema).
Figure 2. Lesion growth between baseline imaging and after 1 d of stroke evolution in patients achieving modified Thrombolysis in Cerebral Infarction 3 reperfusion after mechanical thrombectomy. A, Representative magnetic resonance angiography (MRA) and diffusion-weighted imaging (DWI) in a patient before (baseline) and at d 1 after complete reperfusion. B, Ischemic lesions sizes at baseline and after 1 d of lesion evolution from all the included patients. C, Distribution of lesion growths between baseline and d 1.
This study’s findings challenge the concept of reperfusion injury that was reported in numerous preclinical studies.
The above-mentioned study has multiple limitations. First, and as acknowledged by the authors, infarct volume likely expanded in the time between imaging and revascularization; therefore, the infarct growth that was observed in this study is, at least in part, due to the delay between imaging and groin puncture. Second, the authors excluded patients with hemorrhagic transformation to allow for precise measurement of lesion size evaluation. However, hemorrhagic transformations are indeed secondary, at least in part, to reperfusion injury2 3; therefore, excluding them likely underestimated the reperfusion injury. Finally, blood pressure, which plays an important part in reperfusion injury, was not accounted for in this study.2 3
References:
- Dargazanli C, Fahed R, Blanc R, et al. Modified Thrombolysis in Cerebral Infarction 2C/Thrombolysis in Cerebral Infarction 3 Reperfusion Should Be the Aim of Mechanical Thrombectomy: Insights From the ASTER Trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). Stroke 2018;49(5):1189-96. doi: 10.1161/STROKEAHA.118.020700
- Fagan SC, Bowes MP, Lyden PD, et al. Acute hypertension promotes hemorrhagic transformation in a rabbit embolic stroke model: effect of labetalol. Exp Neurol 1998;150(1):153-8. doi: 10.1006/exnr.1997.6756
- Fenske A, Kohl J, Regli F, et al. The effect of arterial hypertension of focal ischemic edema. An experimental study. Journal of neurology 1978;219(4):241-51.
