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Carbicarb (Na2CO3 0.33 molar NaHCO3 0.33 molar), a mixture formulated to avoid the objections to sodium bicarbonate therapy, has been compared with 1 mol/L NaHCO3 and 1 mol/L NaCl in the treatment of mixed respiratory and metabolic acidosis (pH 7.17) produced by asphyxia in rats. In clinically appropriate doses, intravenous NaHCO3 raised arterial pH only 0.03 unit, elevated arterial carbon dioxide pressure, and doubled lactate concentration. With Carbicarb, the pH rise was three times as great and the blood lactate level was unchanged. The new drug should be effective in treating the acidosis of cardiopulmonary failure without raising blood carbon dioxide pressure or lactate levels and at lower sodium doses than required for NaHCO3.

Steady state estimates of the pulmonary diffusing capacity for carbon monoxide (DLCO) require measurement of the uptake and the average alveolar partial pressure of carbon monoxide (PACO). The expired alveolar sample obtained by different experimental methods and/or breathing patterns rarely represents the actual PACO. It is widely accepted that nonuniform distribution of ventilation, diffusion and perfusion causes discrepancies in the measurement of diffusing capacity. tan additional source of error in choosing PACO arises in the sampling time chosen by the experimental method. A theoretical study of a ramp-with-pause and a square breathing pattern demonstrates that the sample-time error exists even in the homogeneous lung. The study shows for the homogeneous lung that the correct fractional concentration of alveolar carbon monoxide (FAV) occurs at a time (TAV), one-half of a breathing period after the effective inspiration time (TI) for the two very different breathing patterns. TI is well-defined in relation to any breathing pattern which can be approximated by ramps and pauses. If TAV and the sample time chosen by the experimental method are known, then the measured DLCO can be corrected to the actual diffusing capacity (DL). The theory agrees with experimental results and computer simulations of inhomogeneous lungs from the literature. This agreement suggests that the theory for the homogeneous lung is also relevant to the inhomogeneous lung.

The effects of sodium bicarbonate and a bicarbonate-carbonate mixture on expired CO2 and the volume of distribution of bicarbonate were studied in eight anesthetized, paralyzed, and ventilated dogs made acidotic with HCl (5 mmol/kg) infused over 90 min. Both sodium bicarbonate and Carbicarb resulted in systemic alkalinization and comparable increases in the serum bicarbonate at 50 min (7.07 +/- 0.91 vs. 7.99 +/- 0.77, respectively; P = NS). Sodium bicarbonate infusion resulted in an increase in CO2 excretion that accounted for a fractional CO2 excretion of 0.20 +/- 0.09, whereas infusion of a bicarbonate-carbonate mixture resulted in a fractional CO2 excretion of -0.06 +/- 0.09 (P less than 0.01). The uncorrected volume of distribution of bicarbonate after sodium bicarbonate infusion was higher than that seen with the bicarbonate-carbonate mixture (0.60 +/- 0.07 vs. 0.34 +/- 0.03 l/kg; P less than 0.01). However, when the volume of bicarbonate distribution was corrected for expired CO2, there was no difference between treatment with sodium bicarbonate and the bicarbonate-carbonate mixture (0.44 +/- 0.07 vs. 0.38 +/- 0.04 l/kg; P = NS). These data demonstrate that, in this animal model of acidosis, sodium bicarbonate treatment of systemic acidosis is accompanied by a generation of a considerable amount of CO2, whereas treatment with a bicarbonate-carbonate mixture is not. This suggests that in states of impaired ventilation, a bicarbonate-carbonate mixture may offer more efficient systemic alkalinization and may be associated with less CO2 generation than sodium bicarbonate.

The effects of iv sodium bicarbonate (NaHCO3) and Carbicarb, an experimental buffer, were compared in a rat model of lactic acidosis induced by controlled hemorrhage and asphyxia. Although both NaHCO3 and Carbicarb were effective at alkalinizing the arterial blood in this model, NaHCO3 administration resulted in a rise in PaCO2 where Carbicarb did not (+9 +/- 2 vs. +2 +/- 2 torr at 2 min after infusion, p less than .01). Moreover, NaHCO3 resulted in a small decrease in intracellular brain pH as measured with P-31 nuclear magnetic resonance where Carbicarb afforded intracellular brain alkalinization (-0.03 +/- 0.01 vs. +0.08 +/- 0.02 pH units at 2 min, p less than .01). If these data are confirmed clinically, Carbicarb may offer advantages over NaHCO3 under conditions of fixed or limited ventilation.

High-frequency oscillation (HFO) minimizes tidal volume. To investigate whether ventilation can proceed when tidal movement (volume) is eliminated, a nondistensible physical model of interconnected chambers was constructed. During HFO, ventilation was related to pressure waveform characteristics recorded within the separate chambers. Ventilation increased up to a critical frequency related to the time constant of the system. Beyond this frequency, ventilation dropped off rapidly.

Steady state estimates of the pulmonary diffusing capacity for carbon monoxide require measurement of the uptake and the average partial pressure of CO in the lung. The expired alveolar sample obtained by different experimental methods and/or breathing patterns rarely represents the actural average alveolar partial pressure. This error in choosing the correct alveolar sample arises in the sampling time chosen by the experimental method. The time (TAV) at which the correct alveolar sample (FAV) is obtained occurs one-half of a breathing period after the effective inspiration time. If TAV and the sample time chosen by the experimental method are known then the measured diffusing capacity can be corrected to the actual diffusing capacity.