Anesthesiology
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The stability of the pulmonary blood pressure and flow response to alveolar hypoxia (hypoxic pulmonary vasoconstriction or HPV) was studied in six pentobarbital anesthetized, mechanically ventilated open-chested dogs. Aortic and left pulmonary artery blood flows; systemic and pulmonary arterial, central venous, left atrial, and airway pressures; hemoglobin; arterial and mixed venous blood gases were measured. The right lung was ventilated continuously with 100% oxygen, while the left lung was ventilated alternately with 100% O2 ( prehypoxia control phase), an hypoxic gas mixture containing 4% O2, 3% CO2, balance N2 for 4 h, or 100% O2 (post-hypoxia control phase). ⋯ The response to hypoxia was maximal by 15 min, however, QL% decreased more slowly during atelectasis, where the maximal reduction was observed by 60 min. The present study therefore demonstrated that hypoxic ventilation of the left lung yielded an immediate and sustained decrease in left lung blood flow for 4 h. The stability of the HPV response probably was accounted for by the lack of such confounding factors as respiratory alkalosis, severe systemic hypoxemia, and increased cardiac output.
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Fifteen patients undergoing thoracotomy were given 0.25 or 0.50 mg morphine intrathecally (L2-L3 or L3-L4) for an analgetic and pharmacokinetic study. Administration of morphine at the end of the operation resulted in a highly variable duration of analgesia ranging from 1-20.5 and 1-40 h for the 0.25 and 0.50 mg groups, respectively. Calculation of cumulative consumption pattern of additional analgesics given im indicated a dose-related analgesia lasting around 12 h. ⋯ For the 0.50 and 0.25 mg groups, the terminal elimination half-life in CSF was 175 +/- 9 min and 196 +/- 13 min, respectively: the volume of CSF distribution was 0.88 +/- 0.16 ml X kg-1 and 1.06 +/- 0.17 ml X kg-1, respectively: and the clearance from CSF was 2.81 +/- 0.41 microliter X kg-1 X min-1 and 3.41 +/- 0.55 microliter X kg-1 X min-1, respectively (means +/- SEM). The study indicates that the significant pharmacokinetic parameter related to the long duration of analgesia after intrathecal morphine administration probably is the high CSF concentrations found, since the rate of elimination from CSF is similar to what is reported for morphine in plasma. Furthermore, modulation of nociceptive input in the thoracic region also may be achieved by lumbar administration, but a slower onset should be anticipated.