Cortical Nicotinamide Adenine Dinucleotide (NADH) Kinetics in Patients Undergoing Extracranial-Intracranial Bypass

Abstract

Nicotinamide adenine dinucleotide (NADH) kinetics were measured in 76 cortical areas in 26 patients with transient ischemic attacks (TIAs) undergoing extracranial-intracranial bypass. Direct cortical stimulation was utilized to induce changes in surface fluorescence corresponding to a brief oxidation and reduction of mitochondrial NADH. Preoperative studies of cerebral blood flow in gray matter ((CBF)g) demonstrated normal perfusion in 11 patients and ischemic changes ((CBF)g < 43.5 ml/100 g/minute) in 15 patients. In 30 normally perfused areas within the craniotomy, the mean half-time for reduction (t½(red)) of cortical NAD was 21.5 ± 2.6 seconds. In 39 ischemic areas, the mean t½(red) was 5.6 ± 1.2 seconds. These rapid reduction rates were associated with supernormal overshoots of the base line indicative of a transient oxygen debt. Kinetic responses could not be elicited from 7 areas adjacent to foci of decreased attenuation on computed tomography. Bypass resulted in normalization of the t½(red) in 24 of 28 areas of ischemia. The dependence of NADH kinetics on blood flow through the graft was demonstrated in 15 of 19 areas of mild ischemia by the reapplication of a clip to the donor artery. It is concluded that persistent reversible abnormalities of cortical mitochondrial metabolism exist in a significant number of patients with a history of TIAs who are suitable candidates for bypass surgery. In such patients bypass may effectively augment the nutrient supply to meet the bioenergetic demands associated with increased electrophysiological activity.