Artificial hyperventilation normalizes haemodynamics and arterial oxygen content in hypoxic rats

Abstract

Introduction: Although humans are capable of enduring critically low levels of oxygen, many hypoxaemic patients die despite aggressive therapies. Mimicking the physiological hyperventilation necessary to survive extreme hypoxic conditions could minimize the derangements caused by acute hypoxic-hypoxia. The objective of this study was to measure the haemodynamic-biochemical response to artificially induced hyperventilation in hypoxic rats.

Material and methods: Twenty-four deeply anaesthetized and mechanically ventilated rats were allocated to 3 groups: control (n = 5, FiO2 = 1); hypoxic spontaneously hyperventilating (n = 10, FiO2 = 0.08); and hypoxic artificially induced hyperventilation (n = 9, targeting PaCO2 = 10 mm Hg, FiO2 = 0.08). We compared the spontaneously and artificially hyperventilating groups. P-values < 0.01 were considered statistically significant. Mean arterial pressure (MAP) and serum chemistry were measured for 180 minutes.

Results: The control group remained stable throughout the experiment. The hypoxic groups developed profound hypotension after the decrease in FiO2. However, the artificially induced hyperventilated rats recovered their MAP to levels higher than the spontaneously hyperventilating group (117.1 ± 17.2 vs. 68.1 ± 16.0, P = 0.0048). In regard to the biochemical derangements, even though the serum lactate and PaO2 were not different among the hypoxic groups, the artificially hyperventilated group achieved significantly higher SaO2 (94.3 ± 3.6 vs. 58.6 ± 9.6, P = 0.005), pH (7.87 ± 0.04 vs. 7.50 ± 0.13, P = 0.005), and CaO2 (17.7 ± 2.6 vs. 10.2 ± 1.3, P = 0.005) at 180 minutes.

Conclusions: Artificially induced hyperventilation led to the correction of arterial oxygen content, severe serum chemistry, and haemodynamic derangements. These findings may represent a novel rescue manoeuvre and serve as a bridge to a permanent form of support, but should be further studied before being translated to the clinical setting.

Keywords: artificial respiration; critical illness; hyperventilation.; hypocapnia; hypoxia; respiratory insufficiency.

FIGURE 1

Artificially induced hyperventilation in hypoxic rats. A) Flowchart of the studied groups. Studied rats were deeply anaesthetized and mechanically ventilated for 3 hours. No muscle relaxants were used in any of the study groups. During the first hour of the experiment, all the rats were ventilated at an FiO₂ of 1 to achieve steady state. Then the rats were randomly allocated to 3 different groups. The control group (n = 5, green) that was mechanically ventilated at an FiO₂ of 1, the hypoxic spontaneously hyperventilating group (HSH, n = 10, blue) that was mechanically ventilated at an FiO₂ of 0.08, and the hypoxic artificially induced hyperventilation group (HAIH, n = 9, red) that was mechanically ventilated at an FiO₂ of 0.08 with a respiratory rate targeting a PaCO₂ of 10 mm Hg. B) Mean arterial pressure (MAP) in the studied groups at different time points. MAP for each group is presented at 10-minute intervals throughout the 3-hour experiment period. The data is represented as mean, and the standard error is shown at 120 and 180 minutes. Differences among the HAIH and HSH groups were calculated with the Wilcoxon rank-sum test. Statistical significance was accepted as P < 0.01. During the first hour of the study there were no differences in MAP among the 3 groups. At the end of the steady-state period, the MAP of the HSH and HAIH groups rapidly fell. However, after the acclimatization process driven by the hyperventilation, the HAIH group increased the MAP. At 120 and 180 minutes, the HAIH group had a significantly higher MAP (P < 0.005) than the HSH group

FIGURE 2

Arterial blood gas results in rat groups at different time points. Arterial blood gases were measured at 60 minutes, 120 minutes, and 180 minutes during the experimental period in all rats. The data is presented in box-and-whisker plots. Whiskers depict the minimum and maximum values. The green boxes represent control rats, which were consistently ventilated throughout the experiment at an FiO₂ of 1. The red boxes represent the hypoxic artificially induced hyperventilation (HAIH) group, which were ventilated during the first 60 minutes at an FiO₂ of 1 and after that at an FiO₂ of 0.08, with a respiratory rate titrated targeting a PaCO₂ of 10 mm Hg. The blue boxes represent the hypoxic spontaneously hyperventilating group (HSH) group, which were ventilated during the first 60 minutes at an FiO₂ of 1 and after that at an FiO₂ of 0.08 without modification in respiratory rate. Differences among the HAIH and HSH groups were calculated with the Wilcoxon rank-sum test. Statistical significance was accepted as P < 0.01. A) The partial pressure of arterial oxygen was significantly higher for the HAIH at 120 minutes and had a tendency towards significance at 180 minutes (P = 0.013). B) The pH was significantly higher in the HAIH rats at 120 and 180 minutes (P = 0.005, P = 0.005). C) The partial pressure of arterial carbon dioxide was lower in the HAIH group (P = 0.005, P = 0.005)

FIGURE 3

Selected laboratory results in rat groups at different time points. Laboratory data were measured at 60, 120, and 180 minutes. The data are presented in box-and-whisker plots. Whiskers depict the minimum and maximum values. The green boxes represent the values of the control rats, which were consistently ventilated throughout the experiment at an FiO₂ of 1. The red boxes represent the values of the hypoxic artificially induced hyperventilation (HAIH) rats, which were ventilated during the first 60 minutes at an FiO₂ of 1 and then at an FiO2 of 0.08, with a respiratory rate titrated targeting a PaCO₂ of 10 mm Hg. The blue boxes represent the values of the hypoxic spontaneously hyperventilating (HSH) rats, which were ventilated during the first 60 minutes at an FiO2 of 1 and after that at an FiO₂ of 0.08 with no modification in respiratory rate. Differences among the HAIH and HSH groups were calculated with the Wilcoxon rank-sum test. Statistical significance was accepted as P < 0.01. A) Arterial oxygen saturation (SaO₂) was significantly higher in the HAIH group at 120 and 180 minutes (P = 0.005, P = 0.005). B) Arterial oxygen concentration (CaO2) was significantly higher in the HAIH group at 120 and 180 minutes (P = 0.005, P = 0.005). C) Serum glucose levels (mg dL^-1) was significantly higher in the HAIH group at 180 minutes (P = 0.007). d) Serum lactate was lower in the HAIH group at 120 and 180 minutes, but not statistically significant (P = 0.021, P = 0.039)