Effects of a prophylactic or therapeutic application of perflubron emulsion on myocardial ischaemia-reperfusion injury in rats.
OBJECTIVE
The efficacy of administering a perfluorochemical-based oxygen therapeutic such as perflubron emulsion (Oxygen) 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.


CONCLUSIONS
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.
University Hospital, Knappschaftskrankenhaus Bochum Langendreer, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Bochum. rempf@anaesthesia.de
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C
Rempf
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Standl
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Gottschalk
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Freitag
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Ritter
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Lang
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Tuszynski
M A
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Burmeister
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000503:physiopathology; D053904:DNA Breaks, Single-Stranded; D004655:Emulsions; D005466:Fluorocarbons / Q000494:pharmacology* / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006842:Hydrocarbons, Brominated; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D015996:Survival Rate
D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; C003072:perflubron