A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia.
The purpose of this study was to test if HBOC-201, a hemoglobin-based oxygen-carrying solution, can decrease infarct size (or Inf) during acute, severe myocardial ischemia and reperfusion. To test the impact of HBOC-201 on infarct size, ischemia was produced in 18 dogs by coronary stenosis to achieve 80-95% flow reduction for 195 min along with pacing 10% above the spontaneous heart rate, followed by 180 min of reperfusion. Animals were randomized to intravenous infusion of HBOC-201 (1 g/kg) (n=6), normal saline (NS) (n=6), or phenylephrine (Phe) (n=6, as a control for the increased blood pressure seen with HBOC-201), given 15 min after the start of ischemia. Amount of infarct was quantified as the ratio between area at risk (AAR) and Inf after Evans blue and 2,3,5-triphenyltetrazolium chloride staining. Hearts were divided into five layers from base (layer A) to apex (layer E) and photographed for digital image analysis of AAR and Inf. Regional myocardial function (RMF) was also measured after 60 min of ischemia and 15 min of reperfusion. Inf/AAR was significantly reduced after HBOC-201 therapy (4.4+/-2.2%) vs. NS (26.0+/-3.6%) and Phe (25.7+/-4.1%) (both, P<0.05). RMF after reperfusion was restored to 92% of baseline with HBOC-201 compared with 11% of baseline after NS (P<0.05) and 49% after Phe (P=not significant). HBOC-201 administration after induction of severe myocardial ischemia by acute coronary stenosis reduces infarct size and improves myocardial viability.
George
Isaac
I
Department of Surgery, Division of Cardiothoracic Surgery, Columbia University College of Physicians and Surgeons, New York, NY, and The Jack H. Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, NY 10962, USA.
Yi
Geng-Hua
GH
Schulman
Allison R
AR
Morrow
Brad T
BT
Cheng
Yanping
Y
Gu
Anguo
A
Zhang
Geping
G
Oz
Mehmet C
MC
Burkhoff
Daniel
D
Wang
Jie
J
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D023921:Coronary Stenosis / Q000150:complications; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology
D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201