The Effect of Nimodipine on the Evolution of Human Cerebral Infarction Studied by PET

Abstract

Summary: Fourteen patients were studied by positron emission tomography (PET) within 48 h of onset of a hemispheric ischemic stroke and again 7 days later. After the first set of PET scans, the patients were randomized to receive either nimodipine (n = 7) or a carrier solution (n = 7) by intravenous infusion. The infusions were main tained until the end of the second PET studies. CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), CMR02, and CMRglc were measured each time. These metabolic and perfusion measurements were per formed by standard methods. A surface map of each met abolic and perfusion measurement in the cortical mantle was generated by interpolating between the available slices. The various surface maps representing the physi ological characteristics determined in the same or subse quent studies were aligned so that all data sets could be analyzed identically using an array of square regions of interest (ROIs). The functional status of each ROI was recorded at the two intervals following the cerebrovascu- 523 lar accident to characterize the evolution of the infarct, penumbra, and normal brain regions. We presumed the ischemic penumbra to be cortical regions in the proximity of the infarct and perfused at CBF values between 12 and 18 ml/loo g/min on the first PET scan, while densely isch emic regions had CBF of <12 nlllOO glmin and normally perfused brain> 18 ml/loo g/min. In the densely ischemic zone, CBF increased more in the nimodipine-treated group than in the carrier group. As well, in this region nimodipine reversed the decline in CMR02 noted in the carrier group, the difference in the changes being signif icant. In the penumbra zone, comparable trends were noted in OER and CMR02 but the difference in the changes between the two groups did not reach statistical significance. Changes in CMRglc and CBV were compa rable between the two groups in both cortical regions.

Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia.

“…Early intervention after ischemia also seems to increase the chance of an effect being shown with postischemic nimodipine in both animals and humans. 39 The weak neuroprotective effect in global ischemia seen individually with either NMDA antagonists or calcium channel blockers did not reach statistical significance in all brain regions in the present study. If the two groups treated with a single drug had been the only treatment groups done, they would have been significantly different on comparison with the untreated controls.…”

“…Similar to the pattern of results emerging with MK-801, investigations using nimodipine are more decidedly positive in focal ischemia than in global ischemia. Also, both animal 14 - 38 and human 39 studies finding significant benefit have tended to use continuous intravenous nimodipine infusion, as we did in the present study. Early intervention after ischemia also seems to increase the chance of an effect being shown with postischemic nimodipine in both animals and humans.…”

Quantitative T2 Values Predict Time From Symptom Onset in Acute Stroke Patients

“…1,2 The existence and extent of this tissue at risk for infarction is known to be time-variant and constantly changing. 3,4 Up-to-date therapy decisions are based on rigid time windows instead of tissue pathophysiology and individual reaction of brain parenchyma to acute ischemia. Nevertheless, time plays an important role even for compensatory mechanisms, and especially for the interpretation of tissue pathophysiology, which is, after all, also time-dependent.…”

Which Targets Are Relevant for Therapy of Acute Ischemic Stroke?

“…26 Within the boundaries of the final infarcts outlined on the 3-dimensional coregistered MR images 2 to 3 weeks after the stroke, 3 compartments were identified according to their perfusional state early after symptoms onset: critically hypoperfused tissue, penumbral tissue, and tissue with sufficient perfusion (Figure 1). …”