Until recently Evans Blue (T-1 824) was the dye that had been used most extensively in indicator dilution studies and found to possess the desired characteristics of relative non-toxicity and confinement to the intravascular space. However, the use of this dye imposes certain limitations, the chief being that the total dosage of dye administered must be kept small, due to the blue coloration imparted to the skin of the patient and the toxic effects of large doses. Because of these limitations of Evans Blue, several other dyes have recentiy been proposed as suitable for indicator dilution studies. Among these are Indigo Carmine (Lacy et al., 1955), Bromsulphalein (Wassen, 1956;Mellette et al., 1958), the tricarbrocyanine dyes, "Cardio green" (Fox et al., 1957) and "Rie 1743" (Kramer and Ziegenrucker, 1957), and the blue triphenylmethane dyes (Davis et al., 1958). These dyes are, however, rapidly removed from the circulation by extravascular diffusion and rapid hepatic clearance. This seriously compromises the standardization of the response of an ear oximeter, for direct arterial standa.rdization at the time of the inscription of the curve is essential for quantitative analysis. Coomassie Blue was developed largely in an effort to overcome these difficulties and the purpose of this work was to assess the value of the dye in clinical practice.
METHODSFollowing extensive animal trials, the harmlessness of the dye was established by cautiously increasing intravenous administration in ourselves and later in patients whose condition justified dye studies. The dye was given in amounts ranging from 20 to 1000 mg. per injection to a maximum total dosage in one subject of 2000 mg. Subjective effects, together with any changes in pulse rate or blood pressure, were noted subsequent to the injection in all patients.To determine ii vitro colorimetric decay of the dye, samples of blood were taken five minutes after its intravenous injection. After centrifuging, the plasma was stored in two fractions, one at room temperature and one at 00 C. The dye was extracted from the plasma at 1, 2, 3, 4, 8, 12, and 24 hours after withdrawal.The rate of in vivo colorimetric degradation of the dye was studied in the plasma at intravenous dose levels of 25, 50, 75, and 100 mg. Six patients were studied at each level of dosage and blood samples were taken for extraction and estimation of the dye at 5, 10, 20, 30, 40, 60, 90, 120, 180, and 240 minutes after injection.Loss of the dye from the circulation was studied by measuring the pulmonary clearance (pulmonary arterial-brachial arterial difference), the hepatic clearance (brachial arterial-hepatic venous difference) and arm clearance (brachial arterial-axillary venous difference). Synchronous samples for extraction were taken from the respective vessels at various plasma levels of the dye. In those patients to whom the dye was given in large amounts, urine was collected fractionally during the succeeding 24 hours and extracted to measure the renal excretion of the unchanged dye and its meta...