A model for evaluation of artificial oxygen carriers regarding circulation, respiration and metabolism in anesthetized spontaneously breathing guinea pigs

Abstract

The evaluation of artificial oxygen carriers requires experiments with suitable animals. Many investigators do this with the classical laboratory animal, the rat, but it has a quite different oxygen pressure of half saturation (p50 = 36mmHg) from that of humans (26mmHg). It was demonstrated that induced changes of the p50 value in animals provokes substantial changes in important cardiovascular parameters. Therefore, we decided to develop a guinea pig model for evaluation of artificial oxygen carriers, because it has a p50 of about 24 mmHg that is very similar to that of man. We found an anesthesia combination using fentanyl/droperidol/urethane to be very suitable for the narcosis, because important cardiovascular and respiratory parameters remain normal. Our model allows assessment of arterial pressure, oxygen uptake, carbon dioxide release, cardiac output, total peripheral resistance, shock index, blood lactate level, and, in particular, it allows to different/ate the oxygen transport in blood. We evaluated two hemoglobin-based oxygen carriers: bovine and porcine hemoglobin polymerized with glutaraldehyde in isoncotic solution (n = 3). Control experiments (n = 4) were done with an isotonic albumin solution. The protocol comprised a so-called exchange phase (I) with different degrees of hemodilution and a so-called time phase (II), an observation period with a hematocrit of 10% over about 3 hours. In the control group substantial changes in mean arterial pressure, total peripheral resistance, shock index, oxygen uptake and of blood lactate level were seen. All these effects were prevented by the artificial oxygen carriers tested. The carriers prove to be very effective, as small quantities in blood effectively restored these parameters, presumably via synergetic effects. Moreover, the experiments clearly revealed the limitation of hemodilution, at least in guinea pigs: below a hematocrit of 20% all parameters mentioned above changed significantly. The animal model presented prove to be appropriate for the evaluation of artificial oxygen carriers.