Inadequate infusate/blood mixing during intra-arterial chemotherapy at low catheter infusion rates (1 ml/min) produces highly nonuniform downstream drug concentrations. Inadequate treatment of the lesion and overexposure of normal tissues may result. Studies are underway to investigate the advantage of diastolically phased, high flow rate, pulsed intra-arterial infusions in effecting uniform downstream concentrations. Triggered by the ECG, a high velocity pulse during the interval of lowest blood velocity and retriggered on successive cardiac cycles, will yield average flow rates at the desired theraeutic value. Apparatus to produce that pulsed flow and methods of in vivo evaluation of downstream concentration uniformity are being developed. Highly realistic flow studies in an accurate model of the superior carotid artery and cerebral branches have demonstrated essentially complete concentration uniformity as determined by spectrophotometric comparison of infusate dye concentrations in all downstream branches. Upon optimization of the apparatus for animal and clinical use, and determination of appropriate clinical evaluation methods, pulsed intra-arterial infusions will be used in low flow rate clinical chemotherapeutic treatments.
