Effect of MK-467 on organ blood flow parameters detected by contrast-enhanced ultrasound in dogs treated with dexmedetomidine.

OBJECTIVE To evaluate the dexmedetomidine-induced reduction in organ blood flow with quantitative contrast-enhanced ultrasound (CEUS) method and to observe the influence of MK-467 on such reduction. STUDY DESIGN Randomized cross-over study. ANIMALS Six adult purpose-bred laboratory beagle dogs (mean body weight 15.3 ± 1.9 kg). METHODS Contrast-enhanced ultrasound was performed on six conscious healthy laboratory beagles. The animals on separate occasions underwent three treatments: awake without any medication (CTRL), dexmedetomidine 10 μg kg(-1) (DEX) and DEX + MK-467 500 μg kg(-1) (DMK) intravenously (IV). The kidney (10-15 minutes post-treatment), spleen (25-30 minutes post-treatment), small intestine (40-45 minutes post-treatment) and liver (50-55 minutes post-treatment) were examined with CEUS. A time curve was generated and the following perfusion parameters were analysed: arrival time (AT), time to peak from injection (TTPinj), peak intensity (PI) and wash-in rate (Wi). In addition to CEUS, renal glomerular filtration rate was indirectly estimated by the rate of iohexol elimination. RESULTS AT and TTPinj were significantly higher for DEX than for CTRL in all studied organs. The same parameters were significantly higher for DEX than for DMK in the kidney, spleen and small intestine. PI was significantly lower for DEX than for CTRL or DMK in the kidney. Wi was significantly lower for DEX than for CTRL or DMK in the kidney and significantly lower than for CTRL only in the small intestine. Plasma concentration of iohexol was significantly higher after DEX than CTRL administration. CONCLUSIONS Contrast-enhanced ultrasound was effective in detecting DEX-induced changes in blood flow. MK-467 attenuated these changes. CLINICAL RELEVANCE Clinicians should consider the effects of the sedation protocol when performing CEUS. Addition of MK-467 might beneficially impact the haemodynamic function of sedation with alpha-2 adrenoceptor agonists.

[1]  F. Rossi,et al.  Safety of contrast-enhanced ultrasonography in dogs and cats: 488 cases (2002-2011). , 2013, Journal of the American Veterinary Medical Association.

[2]  O. Vainio,et al.  Plasma glucose, insulin, free fatty acids, lactate and cortisol concentrations in dexmedetomidine-sedated dogs with or without MK-467: a peripheral α-2 adrenoceptor antagonist. , 2012, Veterinary journal.

[3]  W. McDonell,et al.  Cardiopulmonary and sedative effects of the peripheral α2-adrenoceptor antagonist MK 0467 administered intravenously or intramuscularly concurrently with medetomidine in dogs. , 2012, American journal of veterinary research.

[4]  J. Wallace,et al.  Quantitative perfusion analysis of the pancreas and duodenum in healthy dogs by use of contrast-enhanced ultrasonography. , 2012, American journal of veterinary research.

[5]  O. Vainio,et al.  Effect of anaesthesia on contrast-enhanced ultrasound of the feline spleen. , 2011, Veterinary journal.

[6]  O. Vainio,et al.  The effect of contrast-enhanced ultrasound on the kidneys in eight cats. , 2011, Veterinary journal.

[7]  O. Vainio,et al.  Effects of different doses of L-659'066 on the bispectral index and clinical sedation in dogs treated with dexmedetomidine. , 2011, Veterinary anaesthesia and analgesia.

[8]  O. Vainio,et al.  The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs. , 2011, Journal of veterinary pharmacology and therapeutics.

[9]  A. Laghi,et al.  CONTRAST‐ENHANCED ULTRASONOGRAPHY OF THE SMALL BOWEL IN HEALTHY CATS , 2011, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[10]  J. Wallace,et al.  Intraoperative contrast-enhanced ultrasonography of normal canine jejunum. , 2011, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[11]  Brigitte Vollmar,et al.  Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. , 2010, World journal of gastroenterology.

[12]  O. Vainio,et al.  Quantitative contrast-enhanced ultrasonographic analysis of perfusion in the kidneys, liver, pancreas, small intestine, and mesenteric lymph nodes in healthy cats. , 2010, American journal of veterinary research.

[13]  O. Vainio,et al.  The effects of L-659,066, a peripheral α2-adrenoceptor antagonist, and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep. , 2010, Journal of veterinary pharmacology and therapeutics.

[14]  H. Saloniemi,et al.  Rapid LC-UV Analysis of Iohexol in Canine Plasma for Glomerular Filtration Rate Determination , 2010 .

[15]  M. Takiguchi,et al.  Quantitative contrast-enhanced ultrasonography of canine spleen. , 2009, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[16]  F. J. Neto,et al.  Effects of a peripheral alpha2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs. , 2008, American journal of veterinary research.

[17]  S. McCluskey,et al.  Effect of propofol on hepatic blood flow and oxygen balance in rabbits , 2008, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[18]  O. Vainio,et al.  The effects of L-659,066, a peripheral alpha2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia in dogs. , 2008, Veterinary anaesthesia and analgesia.

[19]  W. Lautt,et al.  Regulatory processes interacting to maintain hepatic blood flow constancy: Vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction , 2007, Hepatology research : the official journal of the Japan Society of Hepatology.

[20]  M. Roos,et al.  Contrast harmonic imaging of the normal canine spleen. , 2007, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[21]  J. Zagzebski,et al.  Quantitative contrast ultrasound analysis of renal perfusion in normal dogs. , 2007, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[22]  P. Barthez,et al.  Iohexol plasma clearance in healthy dogs and cats. , 2006, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[23]  Xiaoling Yu,et al.  Gray Scale Contrast Enhancement and Quantification in Different Positions of Rabbit Liver , 2006, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[24]  P. Vallone,et al.  Contrast-enhanced sonography of the spleen. , 2005, Seminars in ultrasound, CT, and MR.

[25]  P. Barthez,et al.  Simplified methods for estimation of plasma clearance of iohexol in dogs and cats. , 2006, Journal of veterinary internal medicine.

[26]  M. Kjelgaard‐Hansen,et al.  Contrast-enhanced ultrasonography in normal canine liver. Evaluation of imaging and safety parameters. , 2005, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[27]  Christian Greis,et al.  Technology overview: SonoVue (Bracco, Milan). , 2004, European radiology.

[28]  J. Listinsky,et al.  Regional variation in the alpha-adrenergic receptors in the canine resistance vessels , 1982, Naunyn-Schmiedeberg's Archives of Pharmacology.

[29]  M. Sinclair,et al.  The echocardiographic effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate. , 2003, Veterinary anaesthesia and analgesia.

[30]  M. Sinclair A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. , 2003, The Canadian veterinary journal = La revue veterinaire canadienne.

[31]  J. Zagzebski,et al.  Quantitative contrast harmonic ultrasound imaging of normal canine liver. , 2003, Veterinary Radiology & Ultrasound.

[32]  W. Braselton,et al.  Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs. , 2001, Journal of veterinary internal medicine.

[33]  S. Kaul,et al.  Quantification of renal blood flow with contrast-enhanced ultrasound. , 2001, Journal of the American College of Cardiology.

[34]  P. Talke,et al.  The effect of alpha(2) agonist-induced sedation and its reversal with an alpha(2) antagonist on organ blood flow in sheep. , 2000, Anesthesia and analgesia.

[35]  J. Llull,et al.  Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging. , 2000, Investigative radiology.

[36]  Ryan,et al.  Interaction between blood flow and motility in normal and inflamed ileum , 1999, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[37]  B. Pypendop,et al.  Hemodynamic effects of medetomidine in the dog: a dose titration study. , 1998, Veterinary surgery : VS.

[38]  C. Bryant,et al.  Characterisation of the cardiovascular pharmacology of medetomidine in the horse and sheep. , 1998, Research in veterinary science.

[39]  P. Pagel,et al.  A novel alpha 2-adrenoceptor antagonist attenuates the early, but preserves the late cardiovascular effects of intravenous dexmedetomidine in conscious dogs. , 1998, Journal of cardiothoracic and vascular anesthesia.

[40]  F. Prinzen,et al.  The Effect of Dexmedetomidine on Nutrient Organ Blood Flow , 1996, Anesthesia and analgesia.

[41]  A. Michell,et al.  Evaluation of iohexol as a marker for the clinical measurement of glomerular filtration rate in dogs. , 1996, Research in veterinary science.

[42]  P. Wouters,et al.  Hemodynamic Changes During Induction of Anesthesia with Eltanolone and Propofol in Dogs , 1995, Anesthesia and analgesia.

[43]  R. Heiene,et al.  Estimation of glomerular filtration rate in dogs with 99M-Tc-DTPA and iohexol. , 1995, Research in veterinary science.

[44]  W. Olson,et al.  Hemodynamic and analgesic effects of propofol infusion in medetomidine-premedicated dogs. , 1994, American Journal of Veterinary Research.

[45]  M. S. Langley,et al.  Propofol , 1988, Drugs.

[46]  B. Olsson,et al.  Human pharmacokinetics of iohexol. A new nonionic contrast medium. , 1983, Investigative radiology.

[47]  J. Doxey,et al.  Studies on the pre- and postjunctional activities of alpha-adrenoreceptor agonists and their cardiovascular effects in the anaesthetized rat. , 1981, Journal of autonomic pharmacology.

[48]  D. Clough,et al.  Hypotensive and sedative effects of alpha-adrenoceptor agonists: relationship to alpha 1- and alpha 2-adrenoceptor potency. , 1981, British journal of pharmacology.