Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: an intravital fluorescence microscopy study in pigs.
BACKGROUND
Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs.


METHODS
Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed.


RESULTS
During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination.


CONCLUSIONS
Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.
Ben Mime
Lotfi
L
Department of Cardiothoracic Surgery, University of Cologne, Cologne, Germany. Lofti.ben-mime@uk-koeln.de
Arnhold
Stefan
S
Fischer
Juergen Hartmut
JH
Addicks
Klaus
K
Rainer de Vivie
Ernst
E
Bennink
Gerardus
G
Suedkamp
Michael
M
D000818:Animals; D001783:Blood Flow Velocity; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000517:prevention & control; D002196:Capillaries / Q000187:drug effects; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000077542:Eptifibatide; D006324:Heart Arrest, Induced; D006624:Hippocampus / Q000098:blood supply; D007036:Hypothermia, Induced; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015424:Reperfusion; D013552:Swine
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077542:Eptifibatide; D010100:Oxygen