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Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs

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Abstract

The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg−1·min−1 for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg−1·min−1 was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg−1·min−1 was −20±11% (P<0.01) and −60±16% (P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg−1·min−1 increased Cl a maximum of 11±13% (P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg−1·min−1 showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg−1·min−1, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment of hypertension during halothane anesthesia in clinical practice.

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References

  1. Turlapaty P, Vary R, Kaplan JA (1989) Nicardipine, a new intravenous calcium antagonist: a review of its pharmacology, pharmacokinetics, and perioperative applications. J Cardiothorac Anesth 3:344–355

    Article  PubMed  CAS  Google Scholar 

  2. Kashiwabara T, Nakajima S, Izawa T, Fukushima H, Nishikori K (1991) Characteristics of KRN2391, a novel vasodilator, compared with those of cromakalim, pinacidil and nifedipine in rat aorta. Eur J Pharmacol 196:1–7

    Article  PubMed  CAS  Google Scholar 

  3. Ogawa N, Jinno Y, Kaneta S, Harada H, Fukata Y, Fukushima H (1993) Hemodynamic profile of KRN2391, a novel vasodilator, in anesthetized dogs. J Cardiovasc Pharmacol 21:874–882

    PubMed  CAS  Google Scholar 

  4. Ogawa N, Kaneta S, Jinno Y, Kasai H, Nishikori K, Fukushima H (1992) Comparative cardiovascular effects of KRN2391 and other coronary vasodilators in anesthetized open-chest dogs. Arch Int Pharmacodyn Ther 318:36–46

    PubMed  CAS  Google Scholar 

  5. Buljubasic N, Rusch NJ, Marijic J, Kampine JP, Bosnjak ZJ (1992) Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells. Anesthesiology 76:990–998

    PubMed  CAS  Google Scholar 

  6. Kaneta S, Jinno Y, Harada K, Ohta H, Ogawa N, Nishikori K (1990) Cardiohaemodynamic effect of KRN2391, a novel vasodilator, in anesthetized dogs. Jpn J Pharmacol 52 [Suppl 1]:314

    Google Scholar 

  7. Biscoe TJ, Miller RA (1964) The effect of halothane on carotid sinus baroreceptor activity. J Physiol (Lond) 173:24–37

    CAS  Google Scholar 

  8. Price HL, Price ML, Morse HT (1965) Effects of cyclopropane, halothane and procaine on the vasomotor “center” of the dog. Anesthesiology 26:55–60

    PubMed  CAS  Google Scholar 

  9. Seagard IL, Hopp FA, Donegan JH, Kalbfleisch JH, Kampine JP (1982) Halothane and the carotid sinus reflex: evidence for multiple sites of action. Anesthesiology 57:191–202

    PubMed  CAS  Google Scholar 

  10. Lynch C III, Vogel S, Sperelakis N (1981) Halothane depression of myocardial slow action potentials. Anesthesiology 55:360–368

    PubMed  CAS  Google Scholar 

  11. Jinno Y, Kaneta S, Ohta H, Fukushima H, Izawa T, Ogawa N (1993) Inotropic and chronotropic effects of KRN2391, a novel vasodilator, on isolated guinea-pig atria. Asia Pacific J Pharmacol 8:23–27

    CAS  Google Scholar 

  12. Todd MM, Morris PJ, Moss J, Philbin DM (1982) Hemodynamic consequences of abrupt withdrawal of nitroprusside or nitroglycerin following induced hypotension. Anesth Analg 61:261–266

    Article  PubMed  CAS  Google Scholar 

  13. Gotanda K, Yokoyama H, Satoh K, Taira N (1989) Cardiohemodynamic effects of cromakalim and pinacidil, potassiumchannel openers, in the dog, special reference to venous return. Cardiovasc Drugs Ther 3:507–515

    Article  PubMed  CAS  Google Scholar 

  14. Kokubun M, Taira N, Hashimoto K (1974) Cardiohemodynamic effects of nitroglycerin and several vasodilators. Jpn Heart J 15:126–144

    PubMed  CAS  Google Scholar 

  15. Sakai K, Shiraki Y, Nabata H (1981) Cardiovascular effects of a new coronary vasodilator N-(2-hydroxyethyl)nicotinamide nitrate (SG-75): comparison with nitroglycerin and diltiazem. J Cardiovasc Pharmacol 3:139–150

    Article  PubMed  CAS  Google Scholar 

  16. Leier CV, Huss P, Magorien RD, Unverferth DV (1983) Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure. Circulation 67:817–822

    PubMed  CAS  Google Scholar 

  17. Sutton SC, Fung H-L (1983) Effect of dosage regimen on the development of tolerance to nitroglycerin in rats. J Cardiovasc Pharmacol 5:1086–1092

    PubMed  CAS  Google Scholar 

  18. Unger P, Leone A, Degre S, Berkenboom G (1991) Tolerance to intravenous nitrates. J Cardiovasc Pharmacol 17 [Suppl 3]:S300-S303

    Article  Google Scholar 

  19. Kaneta S, Jinno Y, Harada K, Fukushima H, Ogawa N (1992) Tolerance to the increase in coronary blood flow induced by KRN2391. Arch Int Pharmacodyn Ther 318:21–35

    PubMed  CAS  Google Scholar 

  20. Khambatta HJ, Stone JG, Khan E (1979) Hypertension during anesthesia on discontinuation of sodium nitroprusside-induced hypotension. Anesthesiology 51:127–130

    PubMed  CAS  Google Scholar 

  21. Packer M, Meller J, Medina N, Gorlin R, Herman MV (1979) Rebound hemodynamic events after the abrupt withdrawal of nitroprusside in patients with severe chronic heart failure. N Engl J Med 301:1193–1197

    Article  PubMed  CAS  Google Scholar 

  22. Kapur PA, Bloor BC, Flacke WE, Olewein SK (1984) Comparison of cardiovascular responses to verapamil during enflurane, isoflurane, or halothane anesthesia in the dog. Anesthesiology 61:156–160

    PubMed  CAS  Google Scholar 

  23. Hysing ES, Chelly JE, Doursout M-F, Hartley C, Merin RG (1986) Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. III. nicardipine and isoflurane. Anesthesiology 65:385–391

    Article  PubMed  CAS  Google Scholar 

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Takeda, S., Inada, Y., Ozawa, Y. et al. Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs. J Anesth 9, 176–181 (1995). https://doi.org/10.1007/BF02479852

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  • DOI: https://doi.org/10.1007/BF02479852

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