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Effects of Super-Imposed Pressure Oscillations on a Long-term Chronic Sensitized Airways Mouse Model.

The hyperconstriction of airway smooth muscle (ASM) is the main driving mechanism during an asthmatic attack. The airway lumen is reduced, resistance to airflow increases, and normal breathing becomes more difficult. The tissue contraction can be temporarily relieved by using bronchodilator drugs which induce relaxation of the constricted airways. In vitro studies indicate that relaxation of isolated, pre-contracted ASM is induced by mechanical oscillations in healthy subjects but not asthmatics. Further, short term acute asthmatic subjects respond to superimposed pressure oscillations (SIPO), generated in the range of 5 - 15 Hz, with ~50% relaxation of pre-constricted sensitized airways. Mechanical oscillations, and specifically SIPO, are not widely characterized in asthmatic models. The objective of this in vivo study is to determine the effects of a range of oscillation patterns similar to our previous acute study differing from normal breathing. Both healthy and sensitized mice were observed, with their responses to SIPO treatments measured during induced bronchoconstriction resulting from acetylcholine (ACh) challenge. SIPO- generated results were compared to data from treatments using the bronchorelaxant Isoproterenol (ISO). The study shows that SIPO in the range of 5 - 20 Hz induces relaxation in chronic sensitized airways, with significant improvements in respiratory parameters at SIPO values near 1.7 cmH2O irrespective of the frequency of generation.