Assessing the impacts of total liquid ventilation on left ventricular diastolic function in a model of neonatal respiratory distress syndrome.

BACKGROUND: Filling the lung with dense liquid perfluorocarbons during total liquid ventilation (TLV) might compress the myocardium, a plausible explanation for the instability occasionally reported with this technique. Our objective is to assess the impacts of TLV on the cardiovascular system, particularly left ventricular diastolic function, in an ovine model of neonatal respiratory distress syndrome. METHOD: Eight newborns lambs, 3.0 ± 0.4 days (3.2 ± 0.3kg) were used in this crossover experimental study. Animals were intubated, anesthetized and paralyzed. Catheters were inserted in the femoral and pulmonary arteries. A high-fidelity pressure catheter was inserted into the left ventricle. Surfactant deficiency was induced by repeated lung lavages with normal saline. TLV was then conducted for 2 hours using a liquid ventilator prototype. Thoracic echocardiography and cardiac output assessment by thermodilution were performed before and during TLV. RESULTS: Left ventricular end diastolic pressure (LVEDP) (9.3 ± 2.1 vs. 9.2 ± 2.4mmHg, p = 0.89) and dimension (1.90 ± 0.09 vs. 1.86 ± 0.12cm, p = 0.72), negative dP/dt (-2589 ± 691 vs. -3115 ± 866mmHg/s, p = 0.50) and cardiac output (436 ± 28 vs. 481 ± 59ml/kg/min, p = 0.26) were not affected by TLV initiation. Left ventricular relaxation time constant (tau) slightly increased from 21.5 ± 3.3 to 24.9 ± 3.7ms (p = 0.03). Mean arterial systemic (48 ± 6 vs. 53 ± 7mmHg, p = 0.38) and pulmonary pressures (31.3 ± 2.5 vs. 30.4 ± 2.3mmHg, p = 0.61) were stable. As expected, the inspiratory phase of liquid cycling exhibited a small but significant effect on most variables (i.e. central venous pressure +2.6 ± 0.5mmHg, p = 0.001; LVEDP +1.18 ± 0.12mmHg, p<0.001). CONCLUSIONS: TLV was well tolerated in our neonatal lamb model of severe respiratory distress syndrome and had limited impact on left ventricle diastolic function when compared to conventional mechanical ventilation.

Optimal Control of Inspired Perfluorocarbon Temperature for Ultrafast Hypothermia Induction by Total Liquid Ventilation in an Adult Patient Model.

GOAL: Recent preclinical studies have shown that therapeutic hypothermia induced in less than 30 min by total liquid ventilation (TLV) strongly improves the survival rate after cardiac arrest. When the lung is ventilated with a breathable perfluorocarbon liquid, the inspired perfluorocarbon allows us to control efficiently the cooling process of the organs. While TLV can rapidly cool animals, the cooling speed in humans remains unknown. The objective is to predict the efficiency and safety of ultrafast cooling by TLV in adult humans. METHODS: It is based on a previously published thermal model of ovines in TLV and the design of a direct optimal controller to compute the inspired perfluorocarbon temperature profile. The experimental results in an adult sheep are presented. The thermal model of sheep is subsequently projected to a human model to simulate the optimal hypothermia induction and its sensitivity to physiological parameter uncertainties. RESULTS: The results in the sheep showed that the computed inspired perfluorocarbon temperature command can avoid arterial temperature undershoot. The projection to humans revealed that mild hypothermia should be ultrafast (reached in fewer than 3 min (-72 °C/h) for the brain and 20 min (-10 °C/h) for the entire body). CONCLUSION: The projection to human model allows concluding that therapeutic hypothermia induction by TLV can be ultrafast and safe. SIGNIFICANCE: This study is the first to simulate ultrafast cooling by TLV in a human model and is a strong motivation to translate TLV to humans to improve the quality of life of postcardiac arrest patients.

Thermal Dynamics in Newborn and Juvenile Models Cooled by Total Liquid Ventilation.

BACKGROUND: Total liquid ventilation (TLV) consists in filling the lungs with a perfluorocarbon (PFC) and using a liquid ventilator to ensure a tidal volume of oxygenated, CO 2 -free and temperature-controlled PFC. Having a much higher thermal capacity than air, liquid PFCs assume that the filled lungs become an efficient heat exchanger with pulmonary circulation. OBJECTIVE: The objective of the present study was the development and validation of a parametric lumped thermal model of a subject in TLV. METHODS: The lungs were modeled as one compartment in which the control volume varied as a function of the tidal volume. The heat transfer in the body was modeled as seven parallel compartments representing organs and tissues. The thermal model of the lungs and body was validated with two groups of lambs of different ages and weights (newborn and juvenile) undergoing an ultrafast mild therapeutic hypothermia induction by TLV. RESULTS: The model error on all animals yielded a small mean error of -0.1 ±0.4  (°)C for the femoral artery and 0.0 ±0.1   (°)C for the pulmonary artery. CONCLUSION: The resulting experimental validation attests that the model provided an accurate estimation of the systemic arterial temperature and the venous return temperature. SIGNIFICANCE: This comprehensive thermal model of the lungs and body has the advantage of closely modeling the rapid thermal dynamics in TLV. The model can explain how the time to achieve mild hypothermia between newborn and juvenile lambs remained similar despite of highly different physiological and ventilatory parameters. The strength of the model is its strong relationship with the physiological parameters of the subjects, which suggests its suitability for projection to humans.

Liquid ventilator for ultrafast hypothermia induction in juvenile lambs: Preliminary results.

Total liquid ventilation (TLV) is an emerging mechanical ventilation technique. In this technique, the lungs are filled with liquid perfluorocarbons (PFC) and a liquid ventilator assures ventilation by periodically renewing a volume of oxygenated, CO2 freed and temperature controlled PFC. A huge difference between conventional mechanical ventilation and TLV relates to the fact that PFCs are about 1500 times denser than air. Thus, the PFCs filled lungs turn into an efficient heat exchanger with the circulating blood. One of the most appealing utilization of the lungs as a heat exchanger in TLV is for ultrafast induction of mild therapeutic hypothermia (MTH) for neuroprotection and cardioprotection after ischemia-reperfusion injuries. This study aimed to perform ultrafast MTH induction by TLV in animals up to 25 kg, then perform a fast post-hypothermic rewarming while maintaining proper ventilation. A thermal model of the lamb and liquid ventilator was developed to predict the dynamic and the control strategy to adopt for MTH induction. Two juvenile lambs were instrumented with temperature sensors in the femoral artery, pulmonary artery, oesophagus, right eardrum and rectum. After stabilization in conventional mechanical ventilation, TLV was initiated with ultrafast MTH induction, followed by posthypothermic rewarming. Preliminary results in the two juvenile lambs reveal that the liquid ventilator Inolivent-6.0 can induce MTH by TLV in less than 2.5 min for systemic arterial blood and in less than 10 min for venous return, esophagus and eardrum. Rectal temperature reached MTH in respectively 19.4 and 17.0 min for both lambs. Experimental results were consistent with the model predictions. Moreover, blood gas analysis exhibited that the gas exchange in the lungs was maintained adequately for the entire experiments.