LUNG VASCULAR EFFECTS OF HIGH FREQUENCY VENTILATION

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The objective of this project is to investigate the effects of high frequency ventilation (HFV) on pulmonary vascular function. The working hypothesis is that vasoactive substances, eicosanoids and atrial natriuretic factor (ANF) are released during substances can influence cardiac output, pulmonary and systemic vascular pressures and water balance. The effects of HFV may be modulated by the conditions of ventilation, including the presence of hypoxia and hypercapnia. Initially rabbits will be experimental animals. These are the lowest order of animals which will allow us to obtain useful data on the HFV system. In terms of body and organ sizes and weights, they will approximate human infants. Subsequent data will be collected in sheep to more closely simulate conditions in the mechanically ventilated human. HFV is clinically important during anesthesia when the surgeon is competing for the airway or when he requires a motionless field. HFV is also important where blood CO2 is to be removed with the least pressure cost such as with bronchopleural fistula, pulmonary interstitial emphysema or persistent pulmonary hypertension in the newborn. No studies have been reported on the effect of HFV on the release of ANF. Also, the very few studies reported so far on the effect of HFV on the release of eicosanoids, particularly during hypoxia, have yielded conflicting results. Physiological parameters to be recorded in this project include systemic and pulmonary arterial blood pressures, pulmonary wedge pressure, left atrial pressure, heart rate, cardiac output, arterial blood gases, including pH, concentrations of eicosanoids and ANF in plasma and in lymph, airway pressure and body temperature. Cardiac output will be determined by the thermodilution technique. Cardiac catherization will also provide a measurement of pulmonary arterial pressure and pulmonary wedge pressure. Pulmonary vascular resistance will be calculated from cardiac output and the pulmonary arterial and wedge or left atrial pressures. The effect of HFV will be compared with conventional mechanical ventilation on pulmonary vascular function. We will test the effects of HFV on hypoxic pulmonary vasoconstriction and on release of endogenous modulators such as ANF. We will study the effects of acute and chronic infusion of ANF on lung vascular and airway function and on hypoxic vasoconstriction.