piperidines and Hypocapnia

End tidal carbon dioxide (ETCO(2)) in non-intubated patients can be monitored using either sidestream or flow-through capnometry [Yamamori et al., J Clin Monit Comput 22(3):209-220, 2008]. The hypothesis of this validation study is that, flow-through capnometry will yield a more accurate estimate of ETCO(2) than sidestream capnometry when evaluated in a bench study during low tidal volumes and high oxygen administration via nasal cannula. Secondarily, when ETCO(2) from each is compared to arterial CO(2) (PaCO(2)) during a study in which healthy, non-intubated volunteers are tested under normocapnic, hypocapnic and hypercapnic conditions, the flow-through capnometer will resemble PaCO(2) more closely than the sidestream capnometer. This will be especially true during periods of lower minute ventilation and high oxygen flow rates via mask in non-intubated, remifentanil sedated, healthy volunteers whose physiologic deadspace is small.. The performance of a flow-through (cap-ONE, Nihon Kohden, Tokyo, Japan) and a sidestream (Microcap Smart CapnoLine Plus, Oridion Inc., Needham, MA) capnometer were compared in a bench study and a volunteer trial. A bench study evaluated ETCO(2) accuracy using waveforms generated via mechanical lungs during low tidal volumes and high oxygen flow rates. A volunteer study compared the ETCO(2) for each capnometer against PaCO(2) during sedation in which 8 l O(2) was delivered via mask rather than the nasal cannula.. In the bench study, the flow-through capnometer gave slightly higher values of ETCO(2) during high-flow oxygen and no discernable differences during variable tidal volumes. Bland and Altman plots comparing ETCO(2) to PaCO(2) showed essentially equal performance between the two capnometers in the volunteers.. Within a wide limit of agreement between the volunteer and bench study, flow-through and sidestream capnometry performed equally well during bench testing and in non-intubated, sedated patients.

Topics: Adolescent; Adult; Capnography; Carbon Dioxide; Computer Systems; Exhalation; Female; Humans; Hypercapnia; Hypnotics and Sedatives; Hypocapnia; Male; Monitoring, Physiologic; Oxygen; Piperidines; Remifentanil; Unconsciousness; Young Adult

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by a nitric oxide (NO) synthase inhibitor, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. N(G)-monomethyl-L-arginine monoacetate (L-NMMA; 0.1 mM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension that was maintained for 2-2.5 h even following L-NMMA washout. L-NMMA challenge in normal solution (25 mM NaHCO(3); pH 7. 42; pCO(2) 36.9) also induced near maximal tension, although the tension was maintained for only 25 min (mean). Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp (PD145065), homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp (BQ610), and N-cis-2, 6-dimethyl-piperidinocarbonyl L-gamma-MeLeu-D-Trp (COOCH(3))-Nle (BQ788; 1-3 microM), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively, completely relaxed the tension that resulted from L-NMMA challenge in hypocapnic or isocapnic alkaline solution. These results demonstrate that constriction due to hypocapnia in vitro can be triggered by an NO synthase inhibitor and is endothelin-1 mediated. Additionally, alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction.

Topics: Acetylcholine; Alkalies; Alkalosis; Animals; Basilar Artery; Carbon Dioxide; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Enzyme Inhibitors; Hypocapnia; In Vitro Techniques; Male; Oligopeptides; omega-N-Methylarginine; Papaverine; Piperidines; Rabbits; Receptor, Endothelin A; Receptor, Endothelin B; Solutions; Vasoconstriction; Vasodilation; Vasodilator Agents

We recently concluded that constriction of basilar artery due to respiration-induced hypocapnia in rabbits with acute metabolic alkalosis and accompanying compensatory hypercapnia was independent of NO and K(ATP) channels. Based on reports that endothelin-1-mediated hypocapnic constriction of the rabbit basilar artery in vitro, we further investigated whether the respiration-induced hypocapnic constriction was endothelin-1 mediated. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. The ET(A) plus ET(B) receptor antagonist, PD145065 (1 microM), and the selective ET(A) receptor antagonist, BQ610 (3 microM), completely relaxed the hypocapnic constriction, as determined in a cranial window. Unexpectedly, the ET(B) receptor antagonists, BQ788 and RES-701-1 (3 microM), relaxed the constriction by 72.1+/-2.8% (4) and 77.2+/-8.7% (5), respectively (means+/-S.E. (n)). To investigate whether the large magnitudes of relaxation to both ET(A) and ET(B) receptor antagonists were due to nonselectivity of the antagonists, the effects of the antagonists on the constriction to exogenous endothelin-1 were evaluated. BQ610, BQ788, and RES-701-1 relaxed the 3-5 nM endothelin-1 constriction by only 64.3+/-7.6% (4), 43.5+/-8.5% (5), and 26.7+/-4.8% (3) (means+/-S.E. (n)), respectively, consistent with the selective blocking action of these antagonists. To investigate whether the greater magnitude of BQ610, BQ788, and RES-701-1 relaxation of hypocapnic constricted versus exogenous endothelin-1-constricted vessels was due to differences between constriction elicited by endogenous versus exogenous endothelin-1, the effects of the endothelin receptor antagonists on constriction to isocapnic alkaline suffusate were evaluated. PD145065 (1 microM) and 0.1 mM phosphoramidon, an endothelin-converting enzyme inhibitor, inhibited the constriction to isocapnic alkaline suffusate by 83.8+/-7.8% (6) and 74.3+/-9.7% (8) (means+/-S.E. (n)), respectively, consistent with the endothelin-1 dependency of the constriction. BQ610, BQ788, and RES-701-1 relaxed the isocapnic alkaline suffusate constriction by 74.9+/-6.7% (5), 65.5+/-6.4% (5), and 78.0+/-6.5% (4) (means+/-S.E. (n)), respectively. Thus, the relaxation profile to the selective endothelin receptor antagonists in isocapnic alkaline constricted vessels more closely approximated the relaxation profile observed in hypocapnic constricted as compared to endothelin-1-constricted vessels. Hypocapnia did not alter the

Topics: Alkalosis; Animals; Basilar Artery; Blood Gas Analysis; Carbon Dioxide; Endothelins; Hydrogen-Ion Concentration; Hypercapnia; Hypocapnia; Oligopeptides; Peptides, Cyclic; Piperidines; Rabbits; Receptors, Endothelin; Vasoconstriction