Perflubron emulsion improves tolerance to low-flow ischemia in isolated rabbit hearts.
The efficacy of the temporary oxygen carrier perflubron emulsion (PFC) in maintaining oxygen delivery, tissue oxygenation, high-energy phosphates (HEPs), and myocardial function was investigated during low-flow ischemia. Perfusion rate, oxygen tensions, and cardiac function were measured during stabilization (5 min), controlled-flow (22 ml/min x 20 min), and low-flow (0.22 ml/min x 120 min) periods in isolated rabbit hearts. Hearts were perfused with Krebs-Henseleit (KH) solution (Control), or 10 or 20% PFC (vol/vol; n = 8 per group) 5 min before and throughout the low-flow period. Myocardial tissue was then frozen for biochemical and metabolic measurements. Myocardial oxygenation was measured at incremental flow rates by using 20% PFC (n = 4) or KH (n = 6). In PFC hearts, oxygen delivery and intramyocardial tissue Po2 were improved at all evaluated time points and flow rates, respectively (p < 0.05). In Control hearts, left ventricular end-diastolic pressure was elevated at 60, 90, and 120 min of low-flow ischemia (p < 0.05). Tissue lactate was higher (p < 0.05) and HEPs lower (p < 0.05) in Control hearts during low-flow ischemia. These results indicate that PFC treatment improves myocardial oxygenation, maintains HEPs, prevents ischemic contracture, and may increase the margin of safety during low-flow ischemia in isolated rabbit hearts.
Division of Biological Sciences, Alliance Pharmaceutical Corporation, San Diego, California 92121, USA.
J D
JD
Symons
X
X
Sun
S F
SF
Flaim
U
U
del Balzo
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D005466:Fluorocarbons / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006842:Hydrocarbons, Brominated; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism*; D011817:Rabbits
D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D010710:Phosphates; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C003072:perflubron; D010100:Oxygen