Perflubron emulsion prevents PMN activation and improves myocardial functional recovery after cold ischemia and reperfusion.
BACKGROUND
In cardiopulmonary bypass, extracorporeal circulation activates neutrophils, which contribute to ischemia reperfusion injury and postoperative myocardial dysfunction. Perfluorocarbons (PFCs) are compounds that dissolve oxygen and have anti-inflammatory and neutrophil-stabilizing properties. We hypothesized that perflubron emulsion (PFE), a PFC, would attenuate neutrophil activation during simulated extracorporeal circulation (SECC) and would preserve myocardial functional recovery during reperfusion after cold ischemia.


METHODS
In a SECC, diluted blood was circulated for 120 min and subsequently used to reperfuse isolated rat hearts after 2 h of cold (12 degrees C) ischemia. Three groups were studied: noncirculated control; SECC/no additive; and SECC/PFE added. In control and SECC/no additive groups, whole blood was diluted 1:1 with plasmalyte. SECC/PFE blood was diluted 1:1 with plasmalyte and PFE (0.075 mL/mL diluted whole blood). Blood counts and neutrophil activation experiments were performed before and after 120 min of SECC. Reperfusion was accomplished using a modified Langendorff preparation. Left ventricular developed pressure, dP/dt, and coronary flow were measured at 10, 15, and 20 min of reperfusion.


RESULTS
After 120 min SECC, neutrophil activation was significantly reduced in the SECC/PFE group compared to the SECC/no additive group (38.1 +/- 2.3% versus 51.7 +/- 1.0%, P < 0.05). Compared to cold ischemic hearts reperfused with fresh, non-recirculated blood, left ventricular developed pressure and dP/dt were significantly impaired in the cold ischemic hearts reperfused with SECC/no additive blood (P < 0.05). In contrast, myocardial functional recovery was not impaired in the hearts reperfused with SECC/PFE blood.


CONCLUSIONS
SECC-induced neutrophil activation was attenuated with Perflubron treatment. In addition, the progressive impairment in myocardial functional recovery after cold ischemia was significantly improved with treatment. PFE has clinical potential to limit neutrophil-mediated reperfusion injury following cold ischemia.
Gale
Stephen C
SC
Department of Surgery, University of Texas Medical School at Houston, University of Texas Health Sciences Center at Houston, Houston, Texas 77030, USA . scgalemd@yahoo.com <scgalemd@yahoo.com>
Gorman
Grace D
GD
Copeland
Jack G
JG
McDonagh
Paul F
PF
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003080:Cold Temperature; D003326:Coronary Circulation; D005112:Extracorporeal Circulation; D005466:Fluorocarbons / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D006842:Hydrocarbons, Brominated; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; C003072:perflubron