Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008, 152(1):79-82 | DOI: 10.5507/bp.2008.012

CHANGES IN BIOMECHANICAL PARAMETERS DURING HEART PERFUSION AND AFTER MIDAZOLAM PRE-MEDICATION – EXPERIMENTAL PILOT STUDY

Lenka Bartosikovaa, Jiri Necasa, Tomas Bartosikb, Petr Franac, Martin Pavlikb
a Department of Physiology, Faculty of Medicine and Dentistry, Palacky University, 775 15 Olomouc, Czech Republic
b Department of Anaesthesiology and Intensive Care, St. Anne',s University Hospital Brno, Czech Republic
c 2nd Department of Internal Medicine, St. Anne',s University Hospital Brno, Czech Republic

Background: Midazolam is a frequently used benzodiazepine in anaesthesiology and intensive care.

Aim: The aim of pilot study was to monitor its effect during heart perfusion in the laboratory rat.

Methods: The same groups of animals (n = 10). The 1st group was treated with midazolam in a dose of 0.5mg/kg i.p. The 2nd group was a placebo. After i.p. administration of heparine injection of 500 IU dose, the hearts were excised and perfused (modified Langendorf's method). Working schedule: stabilization/ischaemia/reperfusion proceed at intervals of 20/30/60 min. Monitored parameters in isolated heart: left ventricle pressure (LVP), end-diastolic pressure (LVEDP), contractility (+dP/dtmax).

Results: The treated hearts showed improved postischemic recovery, reaching LVP values of 92 ± 6 % at the end of the reperfusion, placebo only 61 ± 7 %. In placebo hearts LVEDP rose from 10.0 ± 0.5 mmHg to 43 ± 4 mmHg after, in treated animals only about 25 mmHg. The treated hearts improved +dP/dtmax recovery during reperfusion to 91 ± 8 %. These values were significantly greater than those obtained from the placebo hearts.

Conclusions: Positive changes in monitored parameters were found in this experimental pilot study. We conclude that the administration of midazolam in laboratory rats has a cardioprotective potential against ischemia-reperfusion induced injury.

Keywords: Heart ischemia-reperfusion, Midazolam

Received: February 15, 2008; Accepted: April 25, 2008; Published: June 1, 2008  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Bartosikova, L., Necas, J., Bartosik, T., Frana, P., & Pavlik, M. (2008). CHANGES IN BIOMECHANICAL PARAMETERS DURING HEART PERFUSION AND AFTER MIDAZOLAM PRE-MEDICATION – EXPERIMENTAL PILOT STUDY. Biomedical papers, 152(1), 79-82. doi: 10.5507/bp.2008.012
Download citation

References

  1. Walser A, Zenchoff G, Fryer RI. Quinazolines and 1.4-benzodiazepines. 75.7-hydroxyaminobenzodiazepines and derivatives. J Med Chem 1976; 19:1378-81. DOI: 10.1021/jm00234a005 Go to original source... Go to PubMed...
  2. Skerritt JH, Johnston GA. Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol 1983; 89:193-98. DOI: 10.1016/0014-2999(83)90494-6 Go to original source... Go to PubMed...
  3. Isojärvi JI, Tokola RA. Benzodiazepines in the treatment of epilepsy in people with intellectual disability. J Intellect Disabil Res 1998; 42:80-92.
  4. Garratt JC, Gent JP, Feely M, Haigh JR. Can benzodiazepines be classifi ed by characterising their anticonvulsant tolerance-inducing potential? Eur J Pharmacol 1988; 145:75-80. DOI: 10.1016/0014-2999(88)90351-2 Go to original source... Go to PubMed...
  5. Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C. Eff ects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci 2007; 103:201-6. DOI: 10.1254/jphs.FP0061173 Go to original source... Go to PubMed...
  6. Kozlovski VI, Vdovichenko VP, Chlopicki S, Malci SS, Praliyev ZD, Zcilkibayev OT. Antiarrhytmic profi le and endothelial action of novel decanhydroquinoline derivatives. Pol J Pharmacol 2004; 56:767-74.
  7. Yellon DM, Downey JM. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 2003; 83:1113-51. Go to original source... Go to PubMed...
  8. Vaage J, Valen G. Preconditioning and cardiac surgery. Ann Thorac Surg 2003; 75:S709-14. DOI: 10.1016/S0003-4975(02)04696-9 Go to original source... Go to PubMed...
  9. Mullenheim J, Ebel D, Bauer M, Otto F, Heinen A, Frassdorf J, Preckel B, Schlack W. Sevofl urane confers additional cardioprotection after ischemic late preconditioning in rabbits. Anesthesiology 2003; 99:624-31. DOI: 10.1097/00000542-200309000-00017 Go to original source... Go to PubMed...
  10. Zaugg M, Lucchinetti E, Uecker M, Pasch T, Schaubb MC. Anaesthetic and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms. Br J Anaesth 2003; 91:551-65. DOI: 10.1093/bja/aeg205 Go to original source... Go to PubMed...
  11. Schlack W, Hollmann M, Stunneck J, Thämer V. Eff ect of halothane on myocardial reoxygenation injury in the isolated rat heart. Br J Anaesth 1996; 76:860-67. Go to original source... Go to PubMed...
  12. Preckel B, Schlack W. Eff ect of anesthetic on ischemia-reperfusion injury of the heart. In: Vincent JL, ed. Yearbook of intensive care and emergency medicine. Berlin: Springer; 2002. Go to original source...
  13. Oguchi T, Kashimoto S, Yamaguchi T, Nakamara T, Kumazawa T. Comparative eff ects of halothane, anfl urane, isofl urane and sevofl urane on function and metabolism in the ischemic rat heart. Br J Anaesth 1995; 74:569-75. Go to original source... Go to PubMed...
  14. Szekely A, Heindl B, Zahler S, Conzen PF, Becker BF. Nonuniform behavior of intravenous anesthetics on postischemic adhesion of neutrophils in the guinea pig heart. Anesth Analg 2000; 90:1293- 1300. Go to original source... Go to PubMed...
  15. Buljubasic N, Marijic J, Berczi V, Supan DF, Kampine JP, Bosnjak ZJ. Diff erential eff ects of ethomidate, propofol, and midazolam on calcium and potassium channel currents in canine myocardial cells. Anesthesiology 1996; 85:1092-99. Go to original source... Go to PubMed...
  16. Galley HF, Dubbels AM, Webster NR. The eff ect of midazolam and propofol on interleukin-8 from human polymorphonuclear leucocytes. Anesth Analg 1998; 86:1289-93. Go to original source... Go to PubMed...
  17. Nishina K, Akamatsu H, Mikawa K, Shiga M, Maekawa N, Obara H, Niwa Y. The inhibitory eff ects of thiopental, midazolam and ketamine on human neutrophil functions. Anesth Analg 1998; 86:159-65. Go to original source... Go to PubMed...
  18. Nonaka A, Kashimoto S, Imamura M, Furuya A, Kumazawa T. Mechanism of the negative inotropic eff ect of midazolam and diazepam in cultured foetal mouse cardiac myocytes. Eur J Anaesthesiol 1997; 14:481-87. Go to original source... Go to PubMed...
  19. Anholt RR, De Sousa EB, Oster-Granite ML, Snyder SH. Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body section of neonatal rats. J Pharmacol Exp Ther 1985; 233:517-26. Go to PubMed...
  20. De Sousa EB, Anholt RR, Murphy KMM, Snyder SH, Kuhar MJ. Peripheral-type benzodiazepine receptors in endocrine organs: autoradiographic localization in rat pituitary, adrenal, and testis. Endocrinology 1985; 116:567-73. Go to original source... Go to PubMed...
  21. Gavish M, Katz Y, Bar-Ami S, Weizman R. Biochemical, physiological and pathological aspects of the PBR. J Neurochem 1992; 58:1589-1601. Go to original source... Go to PubMed...
  22. McEnery MW, Snowman AM, Trifi letti RR, Snyder SH. Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. Proc Natl Acad Sci USA 1992; 89:3170-74. Go to original source... Go to PubMed...
  23. Liazun EJ, Delmas P, Shire D, Ferrara P. Topological analysis of the peripheral benzodiazepine receptor in yeast mitochondrial membranes supports a fi ve-transmembrane structure. J Biol Chem 1998; 273:2146-52. Go to original source... Go to PubMed...
  24. Li J, Wang J, Zeng Y. Peripheral benzodiazepine receptor ligand, PK 11195 induces mitochondria cytochrome c release and dissipation of mitochondria potential via induction of mitochondria permeability transition. Eur J Pharmacol 2007; 560:117-22. Go to original source... Go to PubMed...
  25. Bono F, Lamarche I, Prabonnaud V, Le Fur G, Herbert JM. Peripheral benzodiazepine receptor agonists exhibit potent antiapoptotic activities. Biochem Biophys Res Commun 1999; 265:457-61. Go to original source... Go to PubMed...
  26. Leducq N, Bono F, Sulpice T, Vin V, Janiak P, Le Fur G, O´Connor SE, Herbert JM. Role of peripheral benzodiazepine receptors in mitochondrial, cellular and cardiac damage induced by oxidative stress and ischemia-reperfusion. J Pharmacol Exp Ther 2003; 306:828- 37. Go to original source... Go to PubMed...
  27. Galiegue S, Tinel N, Casellas P. The peripheral benzodiazepine receptor: a promising therapeutic drug target. Curr Med Chem 2003; 10:1563-72. Go to original source... Go to PubMed...
  28. Semba K, Adachi N, Arai T. Facilitation of serotogenic activity and amnesia in rats caused by intravenous anesthetics. Anesthesiology 2005; 102:616-23. Go to original source... Go to PubMed...
  29. Veselis RA, Reinsel RA, Feshchenko VA, Wronski M. The comparative amnestic eff ects of midazolam, propofol, thiopental, and fentanyl at equisedative concentrations. Anesthesiology 1997; 87:749-64. Go to original source... Go to PubMed...
  30. Malagon I, Hogenbirk K, Pelt J, Hazekamp MG, Bovill JG. Eff ect of three diff erent anaesthetic agents on the postoperative production of cardiac troponin T in pediatric cardiac surgery. Brit J Anaesth 2005; 94:805-9. Go to original source... Go to PubMed...
  31. Szekely A, Heindl B, Zahler S, Conzen PF, Becker BF. Nonuniform behaviour of intravenous anesthetics on postischemic adhesion of neutrophils in the guinea pig heart. Anesth Analg 2000; 90:1293- 1300. Go to original source... Go to PubMed...
  32. Nishina K, Akamatsu H, Mikawa K. The inhibitory eff ect of thiopental, midazolam and ketamine on human neutrophil functios. Anesth Analg 1998; 86:159-65. Go to original source... Go to PubMed...
  33. Papaioannou V, Dragoumanis CH. Molecular mechanisms of cell adaptation to hypoxia and the role of ischemic and anesthetic preconditioning. Greek Eur J Perioperative Med 2007; 5:1-10.
  34. Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Garcia C, Schaub MC. Diff erential eff ects of anesthetics on mitochondrial KATP channel activity and cardiomyocyte protection. Anesthesiology 2002; 97:15-23. Go to original source... Go to PubMed...
  35. Shryock JC, Belardinelli L. Adenosine and adenosine receptors in the cardiovascular system: Biochemistry, physiology, and pharmacology. Am J Cardiol 1997; 79:2-10. Go to original source... Go to PubMed...
  36. Mullane K. Acadesine: The prototype adenosine regulating agent for reducing myocardial ischaemic injury. Cardivasc Res 1993; 27:43-7. Go to original source... Go to PubMed...
  37. Barker PH, Chanachan AS. Inhibition of adenosine accumulation into guinea pig ventricle by benzodiazepines. Eur J Pharmacol 1982; 78:241-44. Go to original source... Go to PubMed...
  38. Kenakin TP. The potentiation of cardiac responses to adenosine by benzodiazepines. J Pharmacol Exp Ther 1982; 222:752-58. Go to PubMed...
  39. Seubert CN, Morey TE, Martynyuk AE, Cucchiara RF, Dennis DM. Midazolam selectively potentiates the A2A- but not A1- receptor-mediated effects of adenosine. Anesthesiology 2000; 92:567-77. Go to original source... Go to PubMed...