Anatomic considerations in therapeutic arteriogenesis for cerebral ischemia.

Arteriogenesis for Cerebral Ischemia To the Editor: The pioneering efforts in the development of therapeutic arteriogenesis for cerebral ischemia reported by Buschmann et al1 herald a new era in the field of stroke therapy. The role of collaterals in maintaining perfusion beyond the site of a proximal arterial occlusion has long been appreciated as a critical factor in reducing ischemic injury in the brain,2 analogous to observations in the coronary and peripheral circulation. Despite recent advances in therapeutic arteriogenesis of coronary and peripheral collaterals, studies of the cerebral collateral circulation have been limited. Anatomic considerations are paramount in the study of the cerebral collateral circulation. The anatomy of the cerebral collateral circulation is strikingly dissimilar to that of the coronary or peripheral circulation. Proximal collateral routes at the circle of Willis recruited at the onset of ischemia may be easily assessed with various modalities, yet the influential distal leptomeningeal collaterals that determine stroke outcome require multivessel angiography for evaluation.3,4 These proximal and distal collateral arteries or arterioles have numerous anatomic differences that influence hemodynamics and ultimately, cerebral perfusion. The hemodynamic characteristics of anterograde collateral blood flow from an adjacent proximal cerebral artery to supply distal anastomoses are also different from the hemodynamics of retrograde collateral blood flow in distal aspects of an occluded artery. Several anatomic details have been omitted in the recent report by Buschmann et al.1 Occlusion of the left carotid and bilateral vertebral arteries was used to demonstrate therapeutic arteriogenesis in the left posterior cerebral artery, yet there are no data on the contralateral posterior cerebral artery or posterior communicating arteries that supply the left posterior cerebral artery via the circle of Willis. Other “collateralized” vessels such as the anterior and middle cerebral arteries ipsilateral to the occluded carotid artery were also not described. Therapeutic arteriogenesis with granulocyte-macrophage colony-stimulating factor was demonstrated in the left posterior cerebral artery, a relatively large conductance vessel, yet arteriogenesis was not demonstrated in the distal anastomoses. These distal anastomoses are pre-existing collateral arterioles that have previously been described as “the substrates of arteriogenesis.”5 Why should arteriogenesis occur in the large conductance artery and not in the pre-existing collateral arterioles? Future studies of the cerebral collateral circulation and arteriogenesis must account for all of the specific anatomic routes that supply collateral blood flow. Each experimental model of cerebral ischemia, such as the three-vessel occlusion method, elicits collaterals with a particular anatomic configuration. Selective description of collateral recruitment leaves far more questions unanswered.