Robustness of arterial blood gas analysis for assessment of respiratory safety pharmacology in rats

Whiteside, Garth T.; Hummel, Michele; Boulet, Jamie; Beyenhof, Jessica D.; Strenkowski, Bryan; John, Janet Dell; Knappenberger, Terri; Maselli, Harry; Koetzner, Lee

doi:10.1016/j.vascn.2015.11.001

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…The basal pH in both groups was significantly different from post-infusion. The changes in pH, pCO 2, and HCO 3 observed in our study are associated with anesthesia since the respiratory depression of inhalation anesthesia produces slight hypoxia and hypercapnia, caused to respiratory acidosis 35 , 36 .…”

Section: Discussionsupporting

confidence: 49%

Preliminary evaluation of the safety and efficacy of glucose solution infusion through the hepatic artery on irreversible electroporation focusing

Sarreshtehdari

Burdı́o

López-Alonso

et al. 2023

Sci Rep

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Due to electrical features of the tissue, such as impedance, which have a significant impact on irreversible electroporation (IRE) function, the administration of glucose solution 5% (GS5%) through the hepatic artery would focus IRE on scattered liver tumors. By creating a differential impedance between healthy and tumor tissue. This study aimed to determine the effects of the GS5% protocol on healthy liver tissue and its safety. 21 male Athymic nude rats Hsd: RH-Foxn1mu were used in the study. Animals were split into two groups. In group 1, a continuous infusion through the gastroduodenal artery of GS5% was performed to measure the impedance with a dose of 0.008 mL/g for 16 min. In group 2, the animals were divided into two subgroups for infusions of GS5%. Group 2.1, at 0.008 mL/g for 16 min. Group 2.2 at 0.03 mL/g for 4 min. Blood samples were collected after anesthesia has been induced. The second sample, after catheterization of the artery, and the third after the GS5% infusion. All the animals were sacrificed to collect histological samples. The survival rate during the experiment was 100%. A considerable impact on the impedance of the tissue was noticed, on average up to 4.31 times more than the baseline, and no side effects were observed after GS5% infusion. In conclusion, impedance alteration by Glucose solution infusion may focus IRE on tumor tissue and decrease IRE’s effects on healthy tissue.

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Section: Discussionsupporting

confidence: 49%

Preliminary evaluation of the safety and efficacy of glucose solution infusion through the hepatic artery on irreversible electroporation focusing

Sarreshtehdari

Burdı́o

López-Alonso

et al. 2023

Sci Rep

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“…Among these are that it might diminish morphine's undesirable side effects. These include tolerance and dependence (Cowan and Macfarlane, 1975;Nozaki et al, 1975;Hasanein et al, 2015;Salmanzadeh et al, 2017), inhibition of gastrointestinal motility (Niwa et al, 2002;Gallantine and Meert, 2008), and respiratory depression (Emery et al, 2016;Whiteside et al, 2016). These preceding reports show that these adverse effects of morphine are dose dependent, and that the doses of morphine used in the present studies in combination with CRAs are sufficiently low that they would have the possibility of obviating the development of at least some of these adverse effects.…”

Section: Discussionmentioning

confidence: 63%

Coadministration of Chemokine Receptor Antagonists with Morphine Potentiates Morphine’s Analgesic Effect on Incisional Pain in Rats

Inan

Eisenstein

Watson

et al. 2018

J Pharmacol Exp Ther

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Crossdesensitization between opioid and chemokine receptors and involvement of chemokines in pain modulation are well established. We investigated if coadministration of chemokine receptor antagonists (CRAs) with morphine would enhance the analgesic potency of morphine on incisional pain in rats. Animals underwent incisional surgery on the left hind paw and pain responses were evaluated using von Frey filaments at various time points postsurgery between 15 and 360 minutes and daily between 24 and 72 hours. Dose-response curves for morphine, maraviroc (a CCR5 antagonist), and AMD3100 (a CXCR4 antagonist) alone were established. While morphine significantly reduced pain in a time-and dose-dependent manner, maraviroc and AMD3100 had no effect by themselves. Coadministration of either maraviroc or AMD3100 with morphine significantly increased morphine's analgesic effect on incisional pain, shifting the dose-response curve to the left 2.3and 1.8-fold, respectively. Coadministration of both CRAs with morphine significantly shifted further the morphine doseresponse curve to the left 3.3-fold. The effect of treatments on mRNA levels in the draining popliteal lymph node for a panel of chemokines and cytokines showed that message for many of these mediators was upregulated by the incision, and the combination of morphine with the CRAs markedly downregulated them. The data show that combining morphine with CRAs potentiates morphine's analgesic effect on incisional pain. Thus, the same analgesic effect of morphine alone can be achieved with lower doses of morphine when combined with CRAs. Using morphine in lower doses could reduce unwanted side effects and possibly block development of tolerance and dependence.

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“…Oxycodone depresses respiration in man (Leino et al, ; Chang et al, ) and in rodents (Kuo et al, ; Whiteside et al, ). In the present experiments, we have characterized the respiratory depressant effects of oxycodone in mice.…”

Section: Introductionmentioning

confidence: 99%

Oxycodone‐induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition

Hill

Dewey

Kelly

et al. 2018

British J Pharmacology

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BACKGROUND AND PURPOSEOxycodone, a prescription opioid, is a major drug of abuse, especially in the USA, and contributes significantly to opioid overdose deaths each year. Overdose deaths result primarily from respiratory depression. We have studied respiratory depression by oxycodone and have characterized how tolerance develops on prolonged exposure to the drug. We have investigated the role of PKC in maintaining tolerance and have examined whether ethanol or pregabalin reverses oxycodoneinduced tolerance. EXPERIMENTAL APPROACHRespiration was measured in male CD-1 mice by whole-body plethysmography. Mice were preinjected with oxycodone then implanted with mini-pumps (s.c.) delivering 20, 45 or 120 mg·kg À1 ·day À1 oxycodone for 6 days and subsequently challenged with oxycodone (3 mg·kg À1 , i.p.) or morphine (10 mg·kg À1 , i.p.) to assess the level of tolerance. KEY RESULTSOxycodone-treated mice developed tolerance to oxycodone and cross tolerance to morphine-induced respiratory depression. Tolerance was less with 20 mg·kg À1 ·day À1 than with 45 or 120 mg·kg À1 ·day À1 oxycodone treatment. At doses that do not depress respiration, ethanol (0.3 g·kg À1 ), pregabalin (20 mg·kg À1 ) and calphostin C (45 μg·kg À1 ) all reversed oxycodone-induced tolerance resulting in significant respiratory depression. Reversal of tolerance was less in mice treated with oxycodone (120-mg·kg À1 ·day À1 ). In mice receiving ethanol and calphostin C or ethanol and pregabalin, there was no greater reversal of tolerance than seen with either drug alone. CONCLUSION AND IMPLICATIONSThese data suggest that oxycodone-induced tolerance is mediated by PKC and that reversal of tolerance by ethanol or pregabalin may be a contributory factor in oxycodone overdose deaths. Abbreviation NorBNI, norbinaltorphimineBritish Journal of

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Robustness of arterial blood gas analysis for assessment of respiratory safety pharmacology in rats

Cited by 7 publications

References 29 publications

Preliminary evaluation of the safety and efficacy of glucose solution infusion through the hepatic artery on irreversible electroporation focusing

Preliminary evaluation of the safety and efficacy of glucose solution infusion through the hepatic artery on irreversible electroporation focusing

Coadministration of Chemokine Receptor Antagonists with Morphine Potentiates Morphine’s Analgesic Effect on Incisional Pain in Rats

Oxycodone‐induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition

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