Limitation of myocardial reperfusion injury by intravenous perfluorochemicals. Role of neutrophil activation.
Neutrophil activation and infiltration into the ischemic myocardium after reperfusion may limit the amount of salvageable myocardium (reperfusion injury). The effects of intravenous perfluorochemicals (Fluosol-DA) on infarct size, ventricular contractility, and neutrophil function were assessed in an occlusion-reperfusion canine model. Closed-chest dogs were subjected to 90 minutes of left anterior descending artery occlusion followed by 24 hours of reperfusion. Animals were randomized to receive either Fluosol-DA (FDA, n = 8) or Ringer's lactate (CONT, n = 10) intravenously over 30 minutes just before left anterior descending artery reperfusion. Neutrophil demargination and infiltration into the myocardium were assessed in vivo with In111. Neutrophil chemotaxis, superoxide radical production, and lysozyme degranulation were evaluated ex vivo at baseline, 1 hour after occlusion, and 1 hour after reperfusion. Perfluorochemicals significantly reduced infarct size expressed as percent of area at risk (FDA, 7 +/- 4%; CONT, 24 +/- 6%; p less than 0.01). This was associated with positive wall motion in the jeopardized zone of Fluosol-DA animals compared with dyskinesis in control animals (FDA, +4.4 +/- 2.1%; CONT, -1.1 +/- 1.5%; p less than 0.05). Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cells in the Fluosol-DA animals. Myocardial blood flow was greater in the ischemic endocardium of Fluosol-DA animals 1 hour after reperfusion (FDA, 1.23 +/- 0.21; CONT, 0.62 +/- 0.08 ml/g/min; p less than 0.01). Neutrophil demargination and infiltration into the ischemic myocardium was reduced in the animals treated with Fluosol-DA. (FDA, 2.5 +/- 0.7 x 10(3); CONT, 14.1 +/- 2.7 x 10(3) neutrophils/g; p less than 0.01). Neutrophil chemotaxis and lysozyme release were also markedly suppressed in the Fluosol-DA groups ex vivo. These results show that intravenous Fluosol-DA significantly reduces reperfusion injury with greater salvage of myocardium and improved left ventricular function. The chief mechanism of action of Fluosol-DA appears to be the suppression of neutrophil function.
Bajaj
A K
AK
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Cobb
M A
MA
Virmani
R
R
Gay
J C
JC
Light
R T
RT
Forman
M B
MB
D000818:Animals; D001802:Blood Substitutes / Q000627:therapeutic use*; D002634:Chemotaxis, Leukocyte; D004285:Dogs; D004338:Drug Combinations / Q000627:therapeutic use; D005260:Female; D005466:Fluorocarbons / Q000627:therapeutic use*; D005609:Free Radicals; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008297:Male; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects*; D011897:Random Allocation; D000077325:Ringer's Lactate; D013481:Superoxides / Q000378:metabolism
D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D005609:Free Radicals; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D013481:Superoxides; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination