Focal injury to the brain or retina is a frequent complication of drug delivery to the internal carotid artery (ICA) and may be due to poor mixing of the drug with blood at the infusion site. Rhesus monkeys were studied to determine whether phased drug delivery during diastole from a modified pulsatile angiographic injector would improve drug mixing in vivo. A radiolabeled flow tracer, carbon-14-iodoantipyrine (14C-IAP), was injected into the ICA of three monkeys in 80-msec pulses, each ending at least 50 msec before the end of local diastole. Local isotope concentration in the brain was determined by quantitative autoradiography. The ratio of highest to lowest concentration was 1.86 +/- 0.26 (mean +/- standard deviation) in the frontoparietal cortex, 1.65 +/- 0.42 in the frontoparietal white matter, 1.89 +/- 0.28 in the temporal cortex, and 1.39 +/- 0.17 in the basal ganglia. These results were similar to recordings in three control animals that received intravenous 14C-IAP to demonstrate complete drug mixing (1.37 +/- 0.12, 1.41 +/- 0.11, 1.70 +/- 0.08, 1.22 +/- 0.24, respectively), and contrasted to findings in five animals which received continuous intracarotid infusions to demonstrate standard ICA drug delivery (4.54 +/- 2.07, 2.94 +/- 1.45, 5.43 +/- 3.57, 3.60 +/- 2.90, respectively). Pulsed intra-arterial infusion during diastole provides a technically simple method for improving intravascular drug mixing, and results in drug delivery to tissue capillaries that is proportional to blood flow.
Out of a total of more than 300 radiographic identifications made by one of us (JJF), there were 11 cases in which radiologic adjuncts were used because the antemortem radiographs were either miniaturized or because anatomical landmarks could not be clearly discerned. The techniques used included slide projection (two cases), photographic enlargement and enhancement (two cases), digitization (three cases), and digitization with computer enhancement (three cases), commercial digitization (one case). In a 12th case, where identification was made by comparison of antemortem and postmortem film X-rays, the films were digitized as a further evaluation of a commercial system. This is the first reported use of these techniques.
Drug streaming has been implicated in the development of focal necrotic lesions in perfused tissues following intracarotid chemotherapy of brain tumors at low infusion rates. The narrow infusate path characteristic of streaming within laminar blood flow is not observed at high infusion rates such as are typical in contrast injection for angiography. By periodically pulsing the infusate at a high rate, the mechanisms of rapid mixing can be exploited while retaining the practicality of low average infusion rates. This in vitro study demonstrates the effects of the pulse-controlling parameters and the catheter characteristics and placement on mixing effectiveness. An internal carotid artery model including eight cerebral branches was infused with dye through various indwelling catheters, and individual branch effluents were collected and analyzed spectrophotometrically for dye concentration. While catheter placement dominates the factors that control infusate distribution, judicious selection of the pulse parameters can alleviate that dependence. A primary advantage is gained by phasing the pulse to occur during that period of the cardiac cycle when the blood flow is lowest at the injection site. The data clearly showed that diastole-phased pulsed infusions are highly effective in producing a uniform infusate distribution at low average infusion rates.
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