Initial reperfusion with 2,3 butanedione monoxime is better than hyperkalemic reperfusion after cardioplegic arrest in isolated guinea pig hearts.

Abstract

Initial warm cardioplegic reperfusion is widely used to ameliorate cardiac reperfusion damage after cardioplegic arrest. However, undesired effects of the high potassium concentration of the cardioplegic perfusate may limit the beneficial effect of this treatment. Contraction uncoupling by a negative inotropic and vasodilating agent such as 2,3-butanedione monoxime (BDM) may be superior to warm cardioplegic reperfusion in reducing reperfusion damage. Thus, initial reperfusion with BDM was compared with hyperkalemic reperfusion (HKR) after global ischemia of Langendorff-perfused guinea pig hearts. Cardiac arrest was induced in 16 hearts using hyperkalemic Krebs' solution and hearts were stored unperfused at 37 degrees C for 40 min. Two groups were studied: HKR, initial reperfusion with 37 degrees C oxygenated hyperkalemic Krebs' for 5 min, and BDM, addition of 20 mM BDM to normokalemic Krebs' for 5 min. BDM increased reactive coronary reflow (128 +/- 8%; all data mean +/- SEM of baseline) much more than HKR treatment (65 +/- 5%). O2 consumption was reduced more by HKR (28 +/- 1%) than by BDM (42 +/- 4%), but the O2 supply/consumption ratio was higher with BDM. During perfusion with normal Krebs' solution, flow stabilized at about 75% of baseline in both groups. Post-ischemic responses to adenosine, serotonin, and nitroprusside were depressed to a similar degree in both two groups. Recovery of left ventricular developed pressure was better in BDM (69 +/- 2%) than in HKR (61 +/- 3%)-treated hearts. Reperfusion dysrhythmias were markedly reduced after BDM reperfusion. These data indicate that treatment in the initial 5-min reperfusion period with BDM is more effective than hyperkalemic reperfusion in reducing reperfusion damage.