Airway pressure release ventilation reduces the increase in bronchoalveolar lavage fluid high-mobility group box-1 levels and lung water in experimental acute respiratory distress syndrome induced by lung lavage.

BACKGROUND AND OBJECTIVE: Airway pressure release ventilation (APRV) may provide better alveolar recruitment at a lower peak airway pressure than conventional mechanical ventilation (CMV) and, therefore, decrease the risk of barotrauma in patients with acute lung injury and acute respiratory distress syndrome. The present study compared the effects of APRV with low tidal volume ventilation (LTV) and CMV on the ongoing response in lung injury induced by whole lung lavage. METHODS: Lung injury was induced by whole lung lavage. Twenty-one Japanese white rabbits were randomized to receive CMV (tidal volume 10 ml kg, positive end-expiratory pressure 3 cmH2O), LTV (tidal volume 6 ml kg, positive end-expiratory pressure 10 cmH2O), or APRV (Phigh 20 cmH2O, Plow 5 cmH2O). After 4 h of treatment, the lungs and heart were excised en bloc. The left lung was lavaged, and high-mobility group box-1 (HMGB1) levels were measured in the lavage. The right lung was analysed histologically and its wet-to-dry weight ratio was calculated. RESULTS: PaO2 was decreased after the induction of lung injury, but the values were significantly higher in the APRV and LTV groups after treatment than in the CMV group. Serum HMGB1 levels did not change before and after lung injury; however, bronchoalveolar lavage fluid HMGB1 levels were significantly increased at the end of the experiment (266.8 +/- 47.9 in the CMV group, 137.4 +/- 23.4 in the LTV group, and 91.2 +/- 5.4 ng ml in the APRV group). The bronchoalveolar lavage fluid HMGB1 levels after experiment were significantly lower in the APRV group than in the CMV and LTV groups (P < 0.0001 and P = 0.0391, respectively). Wet-to-dry weight ratios were also lowest in the APRV group. CONCLUSION: APRV reduces bronchoalveolar lavage fluid HMGB1 levels and lung water and it preserves oxygenation and systemic blood pressure in experimental acute respiratory distress syndrome. The results suggest that APRV could be as protective for acute respiratory distress syndrome as LTV with positive end-expiratory pressure.

Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons.

BACKGROUND: Triptans, 5-HT(1B/ID) agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca(2+) channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca(2+) channels are not yet documented. RESULTS: In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca(2+) channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba(2+) currents I(Ba) passing through Ca(2+) channels. Zolmitriptan (0.1-100 microM) reduced the size of IBa in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT(1B/1D) antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca(2+) channel blockers inhibited the inhibitory action of zolmitriptan on I(Ba), compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT(1B/1D) receptor linked to G(i/o) pathway. CONCLUSION: It is concluded that this zolmitriptan inhibition of HVA Ca(2+) channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.