Proof-of-concept trial to evaluate haemoglobin based oxygen therapeutics in elective percutaneous coronary
Emanuele Meliga1, Pascal Vranckx, Evelyn Regar
1Department of Interventional Cardiology, Thoraxcenter, Erasmus MC, University Medical Centre Rotterdam, The Netherlands.
Insights
Intracoronary infusion of oxygenated hemoglobin-based oxygen carrier (HBOC-201) during coronary artery occlusion preserved left ventricular function. This HBOC-201 infusion acted as an oxygen bridge, preventing myocardial damage during percutaneous coronary intervention (PCI).
Area of Science:
- Cardiology
- Biomedical Engineering
- Pharmacology
Background:
- Percutaneous coronary intervention (PCI) can lead to brief periods of coronary artery occlusion.
- Maintaining myocardial oxygenation during these occlusions is crucial for preserving left ventricular function.
- Current methods for oxygen delivery during PCI are limited.
Purpose of the Study:
- To evaluate the efficacy of intracoronary infusion of pre-oxygenated hemoglobin-based oxygen carrier (HBOC-201) in preserving left ventricular function during brief coronary artery occlusion.
- To test the hypothesis that HBOC-201 infusion can prevent myocardial ischemia and dysfunction.
Main Methods:
- A cross-over study design was employed in patients undergoing successful PCI.
- Coronary arteries were occluded for up to three minutes, either without (dry occlusion) or with intracoronary infusion of HBOC-201.
- Left ventricular pressure-volume loops, intracoronary ECG, and Holter ECG were used to assess myocardial ischemia and function.
Main Results:
- Intracoronary HBOC-201 infusion maintained left ventricular ejection fraction, cardiac output, and relaxation indices.
- Dry occlusions led to significant decreases in ejection fraction, cardiac output, and relaxation, with increased end-diastolic pressure and myocardial stiffness.
- No significant changes in measured parameters were observed during HBOC-201 infusion compared to baseline.
Conclusions:
- Intracoronary HBOC-201 infusion effectively preserves left ventricular function during brief coronary artery occlusion.
- HBOC-201 likely maintains myocardial oxygenation, acting as an oxygen bridge to reperfusion.
- This approach may extend the time window for successful PCI and reduce permanent myocardial damage.
Aims:
To test the hypothesis that intracoronary infusion of pre-oxygenated HBOC-201 during brief, total coronary artery occlusion would preserve left ventricular function.
Methods:
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.
Results:
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.
Conclusions:
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.
