Myocardial reperfusion injury may be due to biophysical changes (e.g., endothelial cell junctional separations), as well as biochemical mechanisms (e.g.,
oxygen free radical activity).
Superoxide dismutase (SOD), a
free radical scavenger, may be effective in reducing chemical injury. Fractions of hydroxyethyl
starch (HES-Pz), a large macromolecule, have been shown to decrease microvascular permeability associated with reperfusion-induced biophysical alterations. A comparison of SOD to HES-Pz was performed using a canine model of 1-hour left anterior descending coronary artery (LAD) clamping followed by 24 hours of reperfusion. Amounts of the test
solution equal to 10% of the dog's blood volume were administered intraatrially to the animals just before release of the LAD clamp. Six dogs received
Ringer's lactate, 7 were given 600,000 IU of SOD, 13 received 6% HES-Pz, and 9 were given SOD and HES-Pz. The ratio of
infarct to area at risk was 20 +/- 3% in the control dogs receiving
Ringer's lactate, 16 +/- 4% in animals receiving SOD alone (p = NS), 6 +/- 3% in dogs receiving HES-Pz alone (p less than 0.05), and 8 +/- 3% in dogs given a combination of SOD and HES-Pz (p less than 0.05). HES-Pz alone and with SOD significantly reduced
reperfusion injury, although addition of SOD to HES-Pz did not have an additive effect. Appropriate-sized macromolecules may act by reducing
ischemia-induced microvascular permeability.