Background. This study was designed to test the hypothesis that the potassium channel opener pinacidil (Pin) as a pretreatment (PT) agent or additive to St. Thomas' solution (StT) could enhance myocardial protection. Methods. In a parabiotic rabbit Langendorff model, 36 hearts underwent global normothermic ischemia (1 hour) followed by reperfusion (30 minutes). Cardioplegia (50 mL, every 20 minutes) consisted of: StT; PinPT/StT, where Pin PT preceded StT arrest; Pin alone; Pin in StT (Pin/StT); and Pin in low potassium StT. Systolic function after reperfusion (percent recovery of developed pressure) and compliance (diastolic slope from pressure-volume relationship) were measured. Results. There was no significant difference between StT and PinPT/StT in percent recovery of developed pressure (51.54% ± 3.5%, 42.17% ± 4.0%, respectively) or compliance. Likewise, no significant differences occurred between Pin, StT, Pin/StT, and Pin in low potassium StT in percent recovery of developed pressure (58.99% ± 4.8%, 51.54% ± 3.5%, 53.09% ± 3.2%, 66.43% ± 7.3%, respectively) or compliance. Conclusions. Pin is as effective a cardioplegic agent as StT; however, its use as a pretreatment or additive to traditional and Pin in low potassium StT provided no additional benefit in functional recovery. (C) 2000 by The Society of Thoracic Surgeons.