EFFECTS OF M101-AN EXTRACELLULAR HEMOGLOBIN-APPLIED DURING CARDIOPULMONARY RESUSCITATION: AN EXPERIMENTAL RODENT STUDY

Abstract

During and immediately after cardiac arrest, cerebral oxygen delivery is impaired mainly by microthrombi and cerebral vasoconstriction. This may narrow capillaries so much that it might impede the flow of red blood cells and thus oxygen transport. The aim of this proof-of-concept study was to evaluate the effect of M101, an extracellular hemoglobin-based oxygen carrier (Hemarina SA, Morlaix, France) derived from Arenicola marina , applied during cardiac arrest in a rodent model, on markers of brain inflammation, brain damage, and regional cerebral oxygen saturation. Twenty-seven Wistar rats subjected to 6 min of asystolic cardiac arrest were infused M101 (300 mg/kg) or placebo (NaCl 0.9%) concomitantly with start of cardiopulmonary resuscitation. Brain oxygenation and five biomarkers of inflammation and brain damage (from blood, cerebrospinal fluid, and homogenates from four brain regions) were measured 8 h after return of spontaneous circulation. In these 21 different measurements, M101-treated animals were not significantly different from controls except for phospho-tau only in single cerebellum regions ( P = 0.048; ANOVA of all brain regions: P = 0.004). Arterial blood pressure increased significantly only at 4 to 8 min after return of spontaneous circulation ( P < 0.001) and acidosis decreased ( P = 0.009). While M101 applied during cardiac arrest did not significantly change inflammation or brain oxygenation, the data suggest cerebral damage reduction due to hypoxic brain injury, measured by phospho-tau. Global burden of ischemia appeared reduced because acidosis was less severe. Whether postcardiac arrest infusion of M101 improves brain oxygenation is unknown and needs to be investigated.

Fig. 1

Mean blood pressure during the experiment. The blood pressure was significantly higher after return of spontaneous circulation in the M101 group (two-way repeated-measures ANOVA; P = 0.008). Within-group comparisons are statistically significant for 4 to 8 min only (P < 0.001), pre: P = 0.735, 3 min: P = 0.053, 9–15: P = 0.061. Red dots: blood pressure of animals in the M101 group, blue dots: blood pressure of animals in the control group. X axis: “M101” denotes M101 group, “plac” denotes control group. Pre denotes the time epoch from −2 min to cardiac arrest, 3 min the epoch ROSC to +3 min, 4 to 8 min the epoch +4 min to +8 min, and 9 to 15 min +9 min to +15 min.

Fig. 2

Time course of the rSO₂ measured by NIRS on the animals’ frontal head. Regional brain tissue oxygen saturation rSO₂ fell rapidly after cardiac arrest but rose during CPR and after return of spontaneous circulation to precardiac arrest levels in both groups. Data are presented as mean ± SD of the original curves (moving average at 0.25 Hz). Right, with red curve is the M101 group, left, with blue curve, the control group. All 27 animals are included.