Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-28T00:16:56.292Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of a prophylactic or therapeutic application of perflubron emulsion on myocardial ischaemia–reperfusion injury in rats

Published online by Cambridge University Press:  01 October 2008

C. Rempf ,
T. Standl ,
A. Gottschalk ,
M. Freitag ,
A. Ritter ,
E. Lang ,
S. Tuszynski  and
M. A. Burmeister
C. Rempf*
Affiliation:
University Hospital, Knappschaftskrankenhaus Bochum Langendreer, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Bochum
T. Standl
Affiliation:
Academic Hospital Solingen, Department of Anaesthesia and Critical Care Medicine, Solingen
A. Gottschalk
Affiliation:
University Hospital, Knappschaftskrankenhaus Bochum Langendreer, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Bochum
M. Freitag
Affiliation:
University Medical Center Hamburg, Department of Anaesthesiology, Hamburg
A. Ritter
Affiliation:
Asklepios Klinikum Nord, Department of Anaesthesiology, Hamburg
E. Lang
Affiliation:
University Hospital Muenster, Department of Anaesthesiology, Muenster, Germany
S. Tuszynski
Affiliation:
University Medical Center Hamburg, Department of Anaesthesiology, Hamburg
M. A. Burmeister
Affiliation:
University Medical Center Hamburg, Department of Anaesthesiology, Hamburg
*
Correspondence to: Christian Rempf, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Knappschaftskrankenhaus Bochum Langendreer, In der Schornau 23-25 44892, Bochum, Germany. E-mail: rempf@anaesthesia.de; Tel: +49 234 299 3001; Fax: +49 234 299 3009
Get access

Summary

Background and objective

The efficacy of administering a perfluorochemical-based oxygen therapeutic such as perflubron emulsion (Oxygent™) prior to ischaemia is currently unknown, although there is evidence for potential beneficial effects for the perioperative treatment in cardiac risk patients. This experimental study investigated the efficacy of perflubron emulsion in preventing reperfusion injury and myocardial infarction size after coronary ischaemia and reperfusion. The perflubron emulsion was given either in a prophylactic manner, prior to induction of myocardial ischaemia, or as a therapeutic agent given during ischaemia.

Methods

Thirty-two anaesthetized and mechanically ventilated rats were subjected to 25 min occlusion of the left coronary artery followed by 120 min reperfusion. Animals were randomized to one of four groups: Group 1 was treated with administration of 6 g kg−1 intravenous perflubron emulsion 25 min before occlusion; Group 2 received the same dose 10 min after occlusion; and Groups 3 and 4 received no perflubron emulsion. Inspired O2 (FiO2) concentration was maintained at 1.0 in Groups 1, 2 and 3 and at 0.35 in Group 4.

Results

Neither prophylactic nor therapeutic perflubron emulsion treatment reduced infarct size measurements by triphenyltetrazolium-chloride staining or severity of cardiac arrhythmias in comparison to the hyperoxic control group. However, prophylactic application of perflubron emulsion reduced areas of impaired perfusion vs. Group 3 assessed by in vivo staining with Thioflavin-S while no significant effect was seen in Groups 2 and 4 vs. 3. Density of DNA single-strand breaks in the ventricle was increased in all groups ventilated with 100% oxygen.

Conclusion

Although administration of perflubron emulsion did not reduce infarct size, areas of impaired perfusion were significantly mitigated when perflubron emulsion was administered prior to coronary occlusion. However, a high oxygen concentration may provoke DNA strand breaks during reperfusion after ischaemia. Further studies must clarify whether enhanced oxidative stress outweighs the advantage of improved areas of impaired perfusion following perflubron emulsion.

Keywords

PERFLUBRONISCHAEMIA–REPERFUSIONRATMICROCIRCULATIONHEART
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 10 , October 2008 , pp. 850 - 859
Copyright
Copyright © European Society of Anaesthesiology 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Mangano, DT, Browner, WS, Hollenberg, M et al. Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group. N Engl J Med 1990; 323: 1781–1788.Google Scholar
2.Saito, T, Unno, N, Yamamoto, N et al. Intraperitoneal administration of hyperbarically oxygenated perfluorochemical enhances preservation of intestinal mucosa against ischemia/reperfusion injury. Shock 2006; 26 (6): 620–624.Google Scholar
3.Kozhura, VL, Basarab, DA, Timkina, MI et al. Reperfusion injury after critical intestinal ischemia and its correction with perfluorochemical emulsion “perftoran”. World J Gastroentorol 2005; 11 (45): 7084–7090.Google Scholar
4.Papadimitriou, DK, Pitoulias, GA, Kotakidou, RE et al. Prolongation of the intestinal viability using oxygenated perfluorocarbon in an experimental model of acute intestinal ischemia. Eur J Vasc Endovasc Surg 2004; 28 (6): 636–641.CrossRefGoogle Scholar
5.Kwon, TH, Sun, D, Daugherty, W et al. Effect of perfluorocarbons on brain oxygenation and ischemic damage in an acute subdural hematoma model in rats. J Neurosurg 2005; 104 (4): 724–730.Google Scholar
6.Gale, SC, Gorman, GD, Copeland, JG, McDonagh, PF. Perflubrom emulsion prevents PMN activation and improves myocardial functional recovery after cold ischaemia and reperfusion. J Surg Res 2007; 138 (1): 135–140.CrossRefGoogle Scholar
7.Forman, MB, Bingham, S, Kopelman, HA et al. Reduction of infarct size with intracoronary perfluorochemical in a canine preparation of reperfusion. Circulation 1985; 71: 1060–1068.Google Scholar
8.Glogar, DH, Kloner, RA, Muller, J et al. Fluorocarbons reduce myocardial ischemic damage after coronary occlusion. Science 1981; 211: 1439–1441.Google Scholar
9.Rice, HE, Virmani, R, Hart, CL et al. Dose-dependent reduction of myocardial infarct size with the perfluorochemical Fluosol-DA. Am Heart J 1990; 120: 1039–1046.Google Scholar
10.National Research Council IoLAR. Comission of Life Science. Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academy Press, 1996.Google Scholar
11.Burmeister, MA, Rempf, C, Standl, TG et al. Effects of prophylactic or therapeutic application of bovine haemoglobin HBOC-200 on ischaemia-reperfusion injury following acute coronary ligature in rats. Br J Anaesth 2005; 95: 737–745.Google Scholar
12.Waynworth, H, Flecknell, P. Experimental and Surgical Technique in the Rat. San Diego, CA: Academic Press, 1992.Google Scholar
13.Selye, H, Bajusz, E, Grasso, S, Mendell, P. Simple techniques for the surgical occlusion of coronary vessels in the rat. Angiology 1960; 11: 398–407.Google Scholar
14.Ito, WD, Schaarschmidt, S, Klask, R et al. Infarct size measurement by triphenyltetrazolium chloride staining versus in vivo injection of propidium iodide. J Mol Cell Cardiol 1997; 29: 2169–2175.Google Scholar
15.Reffelmann, T, Kloner, RA. Microvascular reperfusion injury: rapid expansion of anatomic no reflow during reperfusion in the rabbit. Am J Physiol Heart Circ Physiol 2002; 283: H1099–H1107.CrossRefGoogle ScholarPubMed
16.Fishbein, MC, Meerbaum, S, Rit, J et al. Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. Am Heart J 1981; 101: 593–600.Google Scholar
17.Walker, MJ, Curtis, MJ, Hearse, DJ et al. The Lambeth Conventions: guidelines for the study of arrhythmia’s in ischaemia infarction, and reperfusion. Cardiovasc Res 1988; 22: 447–455.Google Scholar
18.Curtis, MJ, Walker, MJ. Quantification of arrhythmia’s using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia. Cardiovasc Res 1988; 22: 656–665.Google Scholar
19.Forman, MB, Puett, DW, Wilson, BH et al. Beneficial long-term effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model. J Am Coll Cardiol 1987; 9: 1082–1090.Google Scholar
20.Kolodgie, FD, Virmani, R, Farb, A. Limitation of no reflow injury by blood-free reperfusion with oxygenated perfluorochemical (Fluosol-DA 20%). J Am Coll Cardiol 1991; 18: 215–223.Google Scholar
21.Maxwell, MP, Hearse, DJ, Yellon, DM. Species variation in the coronary collateral circulation during regional myocardial ischaemia: a critical determinant of the rate of evolution and extent of myocardial infarction. Cardiovasc Res 1987; 21: 737–746.Google Scholar
22.Kolodgie, FD, Farb, A, Carlson, GC et al. Hyperoxic reperfusion is required to reduce infarct size after intravenous therapy with perfluorochemical (Fluosol-DA 20%) or its detergent component (poloxamer 188) in a poorly collateralized animal model. Absence of a role of polymorphonuclear leukocytes. J Am Coll Cardiol 1994; 24: 1098–1108.Google Scholar
23.Hale, SL, Hammerman, H, Kloner, RA. Effect of two perfluorocarbon emulsions on reperfusion injury after coronary artery occlusion in rabbits. Basic Res Cardiol 1995; 90: 404–409.Google Scholar
24.Forman, MB, Puett, DW, Bingham, SE et al. Preservation of endothelial cell structure and function by intracoronary perfluorochemical in a canine preparation of reperfusion. Circulation 1987; 76: 469–479.CrossRefGoogle Scholar
25.Reffelmann, T, Hale, SL, Li, G, Kloner, RA. Relationship between no reflow and infarct size as influenced by the duration of ischemia and reperfusion. Am J Physiol Heart Circ Physiol 2002; 282: H766–H772.Google Scholar
26.Janco, RL, Virmani, R, Morris, PJ, Gunter, K. Perfluorochemical blood substitutes differentially alter human monocyte procoagulant generation and oxidative metabolism. Transfusion 1985; 25: 578–582.Google Scholar
27.Carlson, RE, Schott, RJ, Buda, AJ. Neutrophil depletion fails to modify myocardial no reflow and functional recovery after coronary reperfusion. J Am Coll Cardiol 1989; 14: 1803–1813.Google Scholar
28.Saran, M, Bors, W. Direct and indirect measurements of oxygen radicals. Klin Wochenschr 1991; 69: 957–964.Google Scholar
29.Iseki, S. DNA strand breaks in rat tissues as detected by in situ nick translation. Exp Cell Res 1986; 167: 311–326.Google Scholar
30.Masuck, TM, Taylor, AR, Lough, J. Arabinosylcytosine-induced accumulation of DNA nicks in myotube nuclei detected by in situ nick translation. J Cell Physiol 1990; 144: 12–17.CrossRefGoogle ScholarPubMed
31.Didier, M, Bursztajn, S, Adamec, E et al. DNA strand breaks induced by sustained glutamate excitotoxicity in primary neuronal cultures. J Neurosci 1996; 16: 2238–2250.Google Scholar
32.Nagayama, T, Lan, J, Henshall, DC et al. Induction of oxidative DNA damage in the peri-infarct region after permanent focal cerebral ischemia. J Neurochem 2000; 75: 1716–1728.Google Scholar
33.Chen, J, Jin, K, Chen, M et al. Early detection of DNA strand breaks in the brain after transient focal ischemia: implications for the role of DNA damage in apoptosis and neuronal cell death. J Neurochem 1997; 69: 232–245.Google Scholar
34.Norbury, CJ, Hickson, ID. Cellular responses to DNA damage. Annu Rev Pharmacol Toxicol 2001; 41: 367–401.Google Scholar
35.de Murcia, G, Schreiber, V, Molinete, M et al. Structure and function of poly(ADP-ribose) polymerase. Mol Cell Biochem 1994; 138: 15–24.Google Scholar
36.Lautier, D, Lagueux, J, Thibodeau, J et al. Molecular and biochemical features of poly (ADP-ribose) metabolism. Mol Cell Biochem 1993; 122: 171–193.Google Scholar
37.Ha, HC, Snyder, SH. Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci USA 1999; 96: 13978–13982.Google Scholar
38.Miyashita, T, Reed, JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 1995; 80: 293–299.Google Scholar
39.Nelson, WG, Kastan, MB. DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways. Mol Cell Biol 1994; 14: 1815–1823.Google Scholar
40.Wall, TC, Califf, RM, Blankenship, J et al. Intravenous Fluosol in the treatment of acute myocardial infarction. Results of the Thrombolysis and Angioplasty in Myocardial Infarction 9 Trial. TAMI 9 Research Group. Circulation 1994; 90: 114–120.Google Scholar
41.Mullenheim, J, Frassdorf, J, Preckel, B et al. Ketamine, but not S(+)-ketamine, blocks ischemic preconditioning in rabbit hearts in vivo. Anesthesiology 2001; 94: 630–636.Google Scholar