Microfibrillar collagen model of canine cerebral infarction.

Abstract

A new canine model of focal cerebral ischemia has been developed employing intravascular delivery of microfibrillar collagen via femoral catheterization. In 13 dogs, dose-effect studies showed neurologic deficits (ranging from mild hemiparesis to death) related to the dose of microfibrillar collagen delivered. In another 10 dogs, 0.5 ml of 60 mg/ml microfibrillar collagen was injected into the common carotid artery; neurologic assessment over 48 hours revealed a survivable stroke syndrome in seven dogs, death at 40 hours in one dog and at less than 12 hours in another, and no clinical effect in one dog. The eight surviving dogs were sacrificed at 48 hours; nine of the 10 dogs had middle cerebral artery distribution infarcts (two grossly hemorrhagic and five grossly nonhemorrhagic) on histologic examination. Angiography in three dogs demonstrated no significant major vascular occlusion. All seven dogs with survivable strokes demonstrated a dense hemiparesis at 24 hours that improved to ambulatory status at 48 hours. The use of microfibrillar collagen to produce middle cerebral artery strokes in dogs provides a new opportunity to study cerebral ischemia without surgery involving the cervical or cranial vasculature. Dogs have larger brains than other common animal models and thus are more amenable to study with imaging modalities. A model with a measurable but survivable insult provides an opportunity for short- and long-term clinical follow-up and for the investigation of therapeutic interventions.