ADVANTAGES OF CONTINUOUS HYPERPOLARIZED ARREST WITH PINACIDIL OVER ST.-THOMAS-HOSPITAL SOLUTION DURING PROLONGED ISCHEMIA

Objective: The potassium channel opener, pinacidil, has been shown to be an effective cardioplegic agent over short periods of ischemia, How ever, clinical settings typically involve longer ischemic periods. Thi s study tested the hypothesis that myocardial protection with a potass ium channel opener is feasible during prolonged periods of arrest and is comparable with the traditional St. Thomas' Hospital solution. Meth ods: With a blood-perfused, isolated rabbit heart model, hearts underw ent 1 hour of global normothermic ischemia followed by 30 minutes of r eperfusion, During ischemia, three different cardioplegic solutions we re administered either intermittently by infusion every 20 minutes or as continuous low-flow cardioplegia (150 ml total volume in all groups ): (1) Krebs-Henseleit solution alone (control), (2) Krebs-Henseleit s olution + pinacidil (50 mu mol/L), or (3) St. Thomas' Hospital solutio n. Initial potassium channel opener infusions contained 5 mmol/L proca ine, Postreperfusion systolic function (percent of developed pressure) was measured. Compliance changes were integrated from the end-diastol ic pressure/volume relationships. Results: For intermittent cardiopleg ia, only St. Thomas' Hospital solution improved function (62.5% +/- 4. 0%) versus control (43.6% +/- 3.3%, p < 0.001), However, with continuo us cardioplegia, only pinacidil (75.6% +/- 4.8%) exceeded control (62. 7% +/- 2.2%, p < 0.001) and was significantly better than St. Thomas' Hospital solution. Compared with the intermittent control group, all o ther groups showed significant preservation of preischemic diastolic p roperties. Conclusions: Myocardial protection during a longer, more cl inically relevant ischemic period is feasible with a potassium channel opener only when it is given continuously. Continuous low-flow pinaci dil cardioplegia was superior to St. Thomas' Hospital solution given e ither as an intermittent or continuous infusion.