Abstract

The selection of anesthetic agent is important in preclinical studies, since each agent affects the systemic hemodynamics in different ways. For that reason, we hypothesized that different anesthetic agents will result in different vaginal hemodynamic response and temperature during sexual arousal, in an animal model. To validate the hypothesis, animal experiments were performed using female rats with two anesthetic agents widely used in preclinical studies: ketamine and isoflurane. Our previously developed near-infrared-spectroscopy-based probe was used to measure the changes of oxyhemoglobin (OHb), deoxyhemoglobin (RHb), and total hemoglobin (THb) concentrations along with temperature from the animal vaginal wall. As a control, saline was administered to both isoflurane- and ketamine-anesthetized animals, and did not show any significant changes in OHb, RHb, THb, or temperature. However, an administration of apomorphine (APO, 80 μg/kg) induced increases of OHb (63 ± 28 μM/DPF), RHb (35 ± 20 μM/DPF), and THb (98 ± 49 μM/DPF) in ketamine-anesthetized animals, while decreases of OHb (52 ± 76 μM/DPF) and THb (38 ± 30 μM/DPF) and an increase of RHb (28 ± 51 μM/DPF) were found in isoflurane-anesthetized animals. The vaginal temperature decreased from the baseline in both ketamine-(0.42°C) and isoflurane-(1.22°C)anesthetized animals. These results confirmed our hypothesis, and suggest that a preclinical study monitoring hemodynamic responses under anesthesia should employ an appropriate anesthetic agent for the study.

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  1. L. J. Teppema and S. BabyAnesthetics and control of breathingRespir. Physiol. Neurobiol.20111778092
  2. J. M. Cederholm, K. E. Froud, A. C. Y. Wong, M. Ko, A. F. Ryan, and G. D. HousleyDifferential actions of isoflurane and ketamine-based anaesthetics on cochlear function in the mouseHear. Res.20122927179
  3. N. J. Michelson and T. D. Y. KozaiIsoflurane and ketamine differentially influence spontaneous and evoked laminar electrophysiology in mouse V1J. Neurophysiol.201812022322245
  4. F. A. Guarraci, C. M. F. Gonzalez, D. Lucero, P. D. Womble, H. Abdel-Rahim, J. DeVore, M. N. Kunkel, E. Quadlander, M. Stinnett, and J. Boyette-DavisThe effects of ketamine on sexual behavior, anxiety, and locomotion in female ratsPharmacol. Biochem. Behav.20181653644
  5. F. Giuliano, J. Allard, S. Compagnie, L. Alexandre, S. Droupy, and J. BernabeVaginal physiological changes in a model of sexual arousal in anesthetized ratsAm. J. Physiol. Regul. Integr. Comp. Physiol.2001281R140R149
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  13. S. Caruso, C. Agnello, G. Intelisano, M. Farina, L. D. Mari, and A. CianciPlacebo-controlled study on efficacy and safety of daily apomorphine SL intake in premenopausal women affected by hypoactive sexual desire disorder and sexual arousal disorderUrology200463955959
  14. N. Prause, J. Barela, V. Roberts, and C. GrahamInstructions to rate genital vasocongestion increases genital and self-reported sexual arousal but not coherence between genital and self-reported sexual arousalJ. Sex. Med.20131022192231
  15. C. Henson, H. B. Rubin, and D. E. HensonWomen’s sexual arousal concurrently assessed by three genital measuresArch. Sex. Behav.19798459469
  16. P. Lavoisier, R. Aloui, M. H. Schmidt, and A. WatrelotClitoral blood flow increases following vaginal pressure stimulationArch. Sex. Behav.1995243745
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  18. C.-F. Yang, M. Y.-C. Chen, T.-I. Chen, and C.-F. ChengDose-dependent effects of isoflurane on cardiovascular function in ratsTzu-Chi Med. J.201426119122
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  20. R. Matika, M. Ibrahim, and A. PatwardhanThe importance of body temperature: an anesthesiologist’s perspectiveTemperature20174912
  21. R. E. ChipkinEffects of D1 and D2 antagonists on basal and apomorphine decreased body temperature in mice and ratsPharmacol. Biochem. Behav.198830683686
  22. A. KurzEffects of anaesthesia on thermoregulationCurr. Anaesth. Crit. Care.2001127278
  23. E. I. EgerThe pharmacology of isofluraneBr. J. Anaesth.19845671S99S
  24. M. JohnstoneThe cardiovascular effects of ketamine in manAnaesthesia197631873882
  25. L. Tian, S. A. Hires, T. Mao, D. Huber, M. E. Chiappe, S. H. Chalasani, L. Petreanu, J. Akerboom, S. A. McKinney, E. R. Schreiter, C. I. Bargmann, V. Jayaraman, K. Svoboda, and L. L. LoogerImaging neural activity in worms, flies and mice with improved GCaMP calcium indicatorsNat. Methods.20096875881
  26. W. Peng, X. Xia, M. Yi, G. Huang, Z. Zhang, G. Iannetti, and L. HuBrain oscillations reflecting pain-related behavior in freely moving ratsPain2018159106118
  27. J. S. Taube, R. U. Muller, and J. B. RanckHead-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysisJ. Neurosci.199010420435

Other (27)

L. J. Teppema and S. BabyAnesthetics and control of breathingRespir. Physiol. Neurobiol.20111778092

J. M. Cederholm, K. E. Froud, A. C. Y. Wong, M. Ko, A. F. Ryan, and G. D. HousleyDifferential actions of isoflurane and ketamine-based anaesthetics on cochlear function in the mouseHear. Res.20122927179

N. J. Michelson and T. D. Y. KozaiIsoflurane and ketamine differentially influence spontaneous and evoked laminar electrophysiology in mouse V1J. Neurophysiol.201812022322245

F. A. Guarraci, C. M. F. Gonzalez, D. Lucero, P. D. Womble, H. Abdel-Rahim, J. DeVore, M. N. Kunkel, E. Quadlander, M. Stinnett, and J. Boyette-DavisThe effects of ketamine on sexual behavior, anxiety, and locomotion in female ratsPharmacol. Biochem. Behav.20181653644

F. Giuliano, J. Allard, S. Compagnie, L. Alexandre, S. Droupy, and J. BernabeVaginal physiological changes in a model of sexual arousal in anesthetized ratsAm. J. Physiol. Regul. Integr. Comp. Physiol.2001281R140R149

M. Intaglietta, P. C. Johnson, and R. M. WinslowMicrovascular and tissue oxygen distributionCardiovasc. Res.199632632643

H. Jeong, M. Seong, H.-S. Lee, K. Park, S. Moon, and J. G. KimDesign of an optical probe to monitor vaginal hemodynamics during sexual arousalSensors2019192129

T. F. Al-Shaiji, M. Banakhar, and M. M. HassounaPelvic electrical neuromodulation for the treatment of overactive bladder symptomsAdv. Urol.20112011757454

R. Baid and R. AgarwalFlibanserin: A controversial drug for female hypoactive sexual desire disorderInd. Psychiatry J.201827154157

J. E. Altwein and F. U. KeulerOral treatment of erectile dysfunction with apomorphine SLUrol. Int.200167257263

K. J. Allahdadi, R. C. A. Tostes, and R. C. WebbFemale sexual dysfunction: therapeutic options and experimental challengesCardiovasc. Hematol. Agents Med. Chem.20097260269

T. Tarcan, M. B. Siroky, K. Park, I. Goldstein, and K. M. AzadzoiSystemic administration of apomorphine improves the hemodynamic mechanism of clitoral and vaginal engorgement in the rabbitInt. J. Impot. Res.200012235240

S. Caruso, C. Agnello, G. Intelisano, M. Farina, L. D. Mari, and A. CianciPlacebo-controlled study on efficacy and safety of daily apomorphine SL intake in premenopausal women affected by hypoactive sexual desire disorder and sexual arousal disorderUrology200463955959

N. Prause, J. Barela, V. Roberts, and C. GrahamInstructions to rate genital vasocongestion increases genital and self-reported sexual arousal but not coherence between genital and self-reported sexual arousalJ. Sex. Med.20131022192231

C. Henson, H. B. Rubin, and D. E. HensonWomen’s sexual arousal concurrently assessed by three genital measuresArch. Sex. Behav.19798459469

P. Lavoisier, R. Aloui, M. H. Schmidt, and A. WatrelotClitoral blood flow increases following vaginal pressure stimulationArch. Sex. Behav.1995243745

R. J. LevinThe physiology of sexual arousal in the human female: a recreational and procreational synthesisArch. Sex. Behav.20023405411

C.-F. Yang, M. Y.-C. Chen, T.-I. Chen, and C.-F. ChengDose-dependent effects of isoflurane on cardiovascular function in ratsTzu-Chi Med. J.201426119122

T. M. Kukkonen, Y. M. Binik, R. Amsel, and S. CarrierPhysiology: Thermography as a physiological measure of sexual arousal in both men and womenJ. Sex. Med.2007493105

R. Matika, M. Ibrahim, and A. PatwardhanThe importance of body temperature: an anesthesiologist’s perspectiveTemperature20174912

R. E. ChipkinEffects of D1 and D2 antagonists on basal and apomorphine decreased body temperature in mice and ratsPharmacol. Biochem. Behav.198830683686

A. KurzEffects of anaesthesia on thermoregulationCurr. Anaesth. Crit. Care.2001127278

E. I. EgerThe pharmacology of isofluraneBr. J. Anaesth.19845671S99S

M. JohnstoneThe cardiovascular effects of ketamine in manAnaesthesia197631873882

L. Tian, S. A. Hires, T. Mao, D. Huber, M. E. Chiappe, S. H. Chalasani, L. Petreanu, J. Akerboom, S. A. McKinney, E. R. Schreiter, C. I. Bargmann, V. Jayaraman, K. Svoboda, and L. L. LoogerImaging neural activity in worms, flies and mice with improved GCaMP calcium indicatorsNat. Methods.20096875881

W. Peng, X. Xia, M. Yi, G. Huang, Z. Zhang, G. Iannetti, and L. HuBrain oscillations reflecting pain-related behavior in freely moving ratsPain2018159106118

J. S. Taube, R. U. Muller, and J. B. RanckHead-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysisJ. Neurosci.199010420435

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