A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia

Abstract

. A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia. Am J Physiol Heart Circ Physiol 291: H1126 -H1137, 2006. First published April 14, 2006 doi:10.1152/ajpheart.00076.2006.-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 ϭ 6), normal saline (NS) (n ϭ 6), or phenylephrine (Phe) (n ϭ 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 Ϯ 2.2%) vs. NS (26.0 Ϯ 3.6%) and Phe (25.7 Ϯ 4.1%) (both, P Ͻ 0.05). RMF after reperfusion was restored to 92% of baseline with HBOC-201 compared with 11% of baseline after NS (P Ͻ 0.05) and 49% after Phe (P ϭ not significant). HBOC-201 administration after induction of severe myocardial ischemia by acute coronary stenosis reduces infarct size and improves myocardial viability.coronary; blood; nitric oxide inhibitor OVER 600,000 people die each year in the United States from complications of ischemic heart disease, including acute myocardial infarction (AMI), congestive heart failure (CHF), and fatal arrhythmias (22), and its treatment continues to challenge the medical community. With an estimated 1.1 million new cases of AMI each year, the burden on the health care system and society is enormous (2). The need for improved myocardial protection after acute ischemia is paramount. Despite a vast array of therapies that reportedly attenuate ischemiareperfusion injury, clinical application of these therapies has been meager and disappointing (22). The trend for earlier percutaneous revascularization (PCI) has helped to improve outcomes (11). However, the problems of contractile dysfunction during acute ischemia, expansion of infarct size (or Inf), and reperfusion injury have largely remained unaddressed and are more complex than simply restoring flow. In addition, the logistical requirements for early PCI, such as trained interventional cardiologists, specialized equipment, and transport time to treatment, limit its use as an immediate treatment for patients with AMI. Thus a noninvasive cardioprotective strategy that can be applied in a prehospital ...

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Angiotensin-Converting Enzyme Inhibitor Captopril Reverses the Adverse Cardiovascular Effects of Polymerized Hemoglobin

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