Mechanism of improvement in pulmonary gas exchange during growth in awake piglets.

Previous studies have shown a lower arterial PO2 (PaO2) in infants and young animals than in adults. To investigate the mechanism of this impairment of gas exchange we studied 13 piglets from 12 to 65 days of age. Two days after instrumentation we measured the distribution of ventilation-perfusion ratios (VA/Q) by use of the multiple inert gas technique on awake animals. We showed that PaO2 is lower in young animals, increasing from 72 +/- 11.5 Torr before 2 wk to 102 Torr at 2 mo. This hypoxemia is due to an enlarged alveolar-arterial O2 pressure difference that significantly decreases with age. This impairment in gas exchange is not due to shunting (0.6 +/- 1.3%). Mean dead space (36 +/- 11%) was not related to age. Mean modes of perfusion and ventilation did not differ significantly between age groups. However, the dispersion of perfusion as expressed by its logSD decreased significantly with age, whereas dispersion of ventilation remained constant. Furthermore, in the young animals only, a significant difference was evidenced between measured alveolar-arterial PO2 gradient and the value predicted by the inert gas model. We therefore conclude that the impairment of gas exchange in piglets is due to two mechanisms: VA/Q mismatch and diffusion limitation for O2.

Improvement of gas exchange during inhibition of hypoxic pulmonary vasoconstriction by nitrendipine in piglets.

To determine how nitrendipine (N), a calcium antagonist, interferes with haemodynamics and gas exchange during hypoxia, we studied 12 piglets (4-6 weeks, 4.3-9.0 kg) anaesthetized with pentobarbital (20 mg.kg-1 i.p.). Haemodynamics, blood gases and multiple inert gas elimination were measured at the end of three consecutive 30 min periods of spontaneous breathing: room air (RA), 11-12% FIO2 (H) and 11-12% FIO2 with a randomly selected infusion of N (3 micrograms.kg-1.min-1) (HN) or the carrier solution (HP) (6 animals in each group). Pulmonary vascular resistance (Rpv) doubled from 8.7 +/- 2.8 mmHg.min-1.1-1 in RA to 19.5 +/- 10.0 (mean +/- SD) in H while PaO2 fell from 83 +/- 8.3 mmHg to 28.7 +/- 5.2. With N, Rpv fell back to room air value: 8.7 +/- 2.0 (p less than 0.02; comparison H and HN), while PaO2 rose from 29.3 +/- 6.3 mmHg in H to 46.1 +/- 6.1 HN (p less than 0.001) and PaCO2 fell from 33.8 +/- 10 to 23.9 +/- 3.7 mmHg. There was a small non-significant rise in VE. Haemodynamics and blood gases of the placebo group were not statistically different in H and HP. No extrapulmonary shunting was evidenced during any experimental period. The perfusion to lung zones with VA/Q lower than 0.005 rose from 1.1 +/- 2.1% in RA to 8.9 +/- 5.7% in H, but no further increase was obtained with N: 5.1 +/- 2.5%. Overall VA/Q matching did not deteriorate with N during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic sodium cyanate treatment induces "hypoxia-like" effects in rats.

Three weeks of sodium cyanate (NaCNO) intraperitoneal treatment in rats (n = 15) induced high hemoglobin O2 affinity, i.e., low PO2 at 50% hemoglobin saturation (P50), 20.5 +/- 1.4 Torr, in comparison with the mean control values, 34.5 +/- 1.6 Torr (n = 15). NaCNO rats showed a reduction in mean body weight, 376 +/- 27 g, in comparison with controls, 423 +/- 23 g (P less than 0.001). Despite arterial O2 partial pressure (PaO2) within normal limits NaCNO-treated rats had a higher systolic right ventricular pressure (SRVP), 33.7 +/- 3.1 Torr, in comparison with control value, 29.0 +/- 2.5 Torr (P less than 0.001). Right ventricle weights were significantly increased (P less than 0.001). After 60 min of an hypoxic challenge (fractional concentration of inspired O2 = 0.10) NaCNO-treated rats increased SRVP of only 7 +/- 4% compared with 46 +/- 9% in the control animals. Inducing high hemoglobin affinity in rats (n = 10; 6 wk NaCNO treatment) resulted in increases in hematocrit ratio and hemoglobin concentration (P less than 0.001). The characteristics of the red blood cell (RBC) itself changed; values of mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration being significantly increased (P less than 0.001) when compared with mean control values. The count of nucleated RBC's appeared to be significantly higher from the 2nd wk of NaCNO treatment. Chronic NaCNO treatment was demonstrated to exert "hypoxia-like" effects since it induced prevention of normal growth, polycythemia, pulmonary hypertension, right ventricular hypertrophy, and blunted pulmonary pressor response to acute hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological effects of high-P50 erythrocyte transfusion on piglets.

Rightward shifts of the O2 dissociation curve (ODC) were experimentally obtained in lysed and resealed erythrocytes following encapsulation of inositol hexaphosphate (IHP). This continuous lysing and resealing procedure led to in vitro P50 (Po2 at 50% hemoglobin saturation) increases up to 80 Torr (pH, 7.40; Pco2, 40 Torr; temp, 37 degrees C) for both human and pig erythrocytes. The Hill number of the transformed blood decreased when IHP was fixed on the hemoglobin, but the sigmoid shape of the ODC was maintained. The O2 hemoglobin binding capacity and the mean corpuscular hemoglobin content were found unchanged by the experimental procedure in human and pig erythrocytes. Isovolumic exchange transfusion of high-P50 erythrocytes in anesthetized and ambient air-ventilated piglets (n = 6) led to substantial in vivo P50 increases (range, 8-19 Torr). The rightward shift of the ODC was concomitant with an increase of the arterial Po2 and of the arteriovenous O2 content difference, 19 and 59% respectively above their control values. The mixed-venous Po2 (PVO2) remained unchanged. The cardiac output was shown to be inversely related to the P50 value. In spite of the O2-transport reduction (37%), O2 consumption was maintained due to enhanced O2 extraction.

Induced low P50 in anesthetized rats: blood gas, circulatory and metabolic adjustments.

In anesthetized, normoxic or hypoxic rats the hemodynamic, metabolic and O2 transport characteristics following exchange transfusion with human erythrocytes containing a high O2 affinity hemoglobin (Hemoglobin Creteil, beta 89 Ser----Asp) have been studied. The in vivo oxygen partial pressure at 50% oxygen hemoglobin saturation (P50) decreased from 37.4 +/- 2.1 to 12.7 +/- 0.7 mm Hg; the arterial oxygen tension was reduced significantly from 109.9 +/- 7.7 to 87.3 +/- 12.0 mm Hg. There was a decrease in right ventricular partial pressure of oxygen (PvO2), (P less than 0.001), oxygen consumption (VO2), (P less than 0.001), arterio-venous difference, (P less than 0.001), and peripheral vascular resistance index, (P less than 0.01). Exchange transfusion with normal rat blood (P50 = 37.2 +/- 2.4 mm Hg) or with 2,3-diphosphoglycerate-enriched human red blood cells (P50 = 34.7 +/- 2.2 mm Hg), did not modify these variables in normoxic rats. In hypoxia, the reduction in P50 was associated with a further decrease in PvO2 an increase in serum lactate concentration and a VO2 decrease.

Po2 temperature blood factor for blood gas apparatus.

PO2 temperature formulae supplied by manufacturers on automatic blood gas apparatus, PO2 corr. = PO2 37 degrees C X 10F X delta T were studied and compared to the experimental determination of the delta log PO2/delta T ratio (Hérigault et al. [10]). Acid-base status at 37 degrees C appeared to have a measurable influence on the PO2 temperature factor; alkalosis increased the delta log PO2/delta T ratio, and the contrary was found for acidosis in comparison with normal acid-base status at 37 degrees C. For the same PO2, measured at 37 degrees C, all the proposed formulae of commercial blood gas automatic apparatus did not give the same temperature corrected PO2. The observed difference between the corrected PO2 may be important and greater than the precision of the initial measurement. To correct the measured PO2 for temperature, a relationship between delta log PO2/delta T and PO2 is proposed, between PO2 zero and PO2 180 mmHg, which takes into account measured pH and PO2 values at 37 degrees C:delta log PO2/delta T = [(-0.35 pH + 0.658) X 10(-4) X PO2] + 0.035.

Determination of the PO2 temperature blood factor from oxygen dissociation curves.

The variation with saturation of the temperature coefficient of PO2 in human blood (delta log PO2/delta T) was determined by continuous recording of the oxygen dissociation curve (ODC), at 37 degrees C and 25 degrees C, on the same blood samples. PCO2 and pH were held constant through an ODC run, and PCO2 was reduced at 25 degrees C to the value measured by anaerobic cooling of the same sample. delta log PO2/delta T was calculated from isosaturation points on the 37 and 25 degrees C curves. The temperature coefficient was also computed as an independent check on this method by determination of the effects of temperature (25, 30, 37 and 40 degrees C) on hemoglobin ligand interaction: fixed acid Bohr effect (delta log PO2/delta pH), carbamino-formation (delta log PO2/delta log PCO2) and hemoglobin oxygen affinity. The values of delta log PO2/delta T ratio obtained from the two different approaches were found to be in good agreement. The coefficient decreased when [H+] concentration was increased. A linear relationship between the Bohr factor and the temperature was found: delta log PO2/delta pH = 0.00267 T-0.520 (r = 0.85; n = 40) At 25 degrees C, the carbamino-formation was one order of magnitude lower than at 37 degrees C. Acid-base state and saturation value appeared to be major determinant factors for the temperature correction coefficient to be applied to blood PO2 values measured at standard (37 degrees C) temperature.

Consequences of an acute increase in P50 in anaesthetized guinea pigs.

In anaesthetized guinea pigs, ventilated with ambient air, the peripheral haemodynamics and oxygen transport characteristics have been studied following a blood exchange transfusion with rat erythrocytes suspended in guinea pig plasma. Since the rat haemoglobin exhibited a lower oxygen affinity than guinea pig haemoglobin, the oxygen partial pressure at 50% of oxygen haemoglobin saturation (P50) increased from 25.2 +/- 1.1 to 37.2 +/- 0.9 mm Hg (n = 10). This increase in P50 was accompanied by a significant increase in arterial oxygen partial pressure (PaO2) and in arterio-venous difference (AVDO2). Cardiac output (Q) was decreased significantly, but oxygen consumption (VO2) remained within control values. The increase in P50 was associated with a venous oxygen partial pressure (P-VO2) which remained constant but an increase in blood lactate concentration was observed. Control exchange transfusion with fresh guinea pig blood had no effect on acid-base status, on oxygen transport, or on peripheral resistance. The sudden reduction in haemoglobin oxygen affinity induced an increase in peripheral resistance with a decrease in cardiac output, the arterial systemic pressure being maintained. These results suggested that an acute decrease in haemoglobin oxygen affinity was compensated for by a simultaneous diminution of overall tissue blood flow and reduction of capillary recruitment.

Effects of chronic changes in hemoglobin-O2 affinity in rats.

We have assessed the characteristics of oxygen transport following chronic intraperitoneal administration of sodium cyanate (NaCNO, 90 mg/kg; P50 decreased), o-iodosodium benzoate (OISB, 300 mg/kg; P50 increased), or sodium chloride (NaCl; P50 unchanged) to rats at a rate of 5 times/wk for 16 wk. At the end of this period, the animals were exposed to a low inspired O2 concentration and were subjected to exercise stress. Hill's n50 at pH 6.90-7.60, hematocrit, and the saturation dependency of the Bohr effect (PCO2 constant) were altered by NaCNO only. Cyanate-treated rats gained less weight, probably due to a toxic side effect of the drug. Hypoxemia-induced lactatemia was greatest with a high P50 (OISB). Physical effort (swimming) was tolerated poorly at normal arterial PO2 when P50 was low (NaCNO). Although a left-shifted curve appears beneficial when FIO2 is reduced, reasons for the physiological advantage may be the result of other characteristics of the O2 dissociation curve, not P50 alone.