Proof-of-concept trial to evaluate haemoglobin based oxygen therapeutics in elective percutaneous coronary revascularisation. Rationale, protocol design and haemodynamic results

To test the hypothesis that intracoronary infusion of pre-oxygenated HBOC-201 during brief, total coronary artery occlusion would preserve left ventricular function.Immediately following a successful PCI, the target coronary artery was occluded without ("dry occlusion")--or with--infusion of pre-oxygenated HBOC-201 distal to the stent via the guidewire shaft of an over-the-wire balloon for up to three minutes at an infusion rate of 48 ml/min. A cross-over design was applied. Early signs of myocardial ischaemia were evaluated by left ventricular pressure-volume loops and intracoronary ECG. A 12-lead Holter ECG was activated before the PCI and deactivated four hours after the study period. Primary endpoints were change in left ventricular relaxation indices and in the sum of ST segment deviations.None of the measured parameters differed significantly from their respective baseline values during HBOC-201 infusion. By contrast, ejection fraction (EF), cardiac output (CO) and minimal rate of LV pressure change (dP/dTMIN) decreased significantly and the end diastolic pressure (EDP) and time constant of relaxation increased significantly during dry occlusions (P<0.05). The end diastolic pressure-volume relationship (EDPVR) at the fixed pressure level of 30 mmHg (V30), an index of myocardial compliance, reflected greater myocardial stiffness during dry occlusions compared to occlusions with HBOC-201 infusion.Intracoronary infusion of oxygenated HBOC-201 is capable of preserving left ventricular function, likely through maintenance of myocardial oxygenation. It is hypothesised, that in an acute setting, HBOC-201 could serve as an oxygen bridge to reperfusion by PCI extending the "golden" time period during which permanent myocardial damage is unlikely.