Myocardial protection with pinacidil cardioplegia in the blood-perfused heart.
BACKGROUND
Adenosine triphosphate-sensitive potassium-channel openers are potent vasodilators that have been found to be cardioprotective during myocardial ischemia. The potassium-channel opener pinacidil was investigated to determine its efficacy as a cardioplegic agent.


METHODS
A blood-perfused, parabiotic, isolated rabbit heart Langendorff preparation was used. Fifty-six hearts underwent 30 minutes of global normothermic ischemia after a 50-mL infusion of cardioplegia, followed by 60 minutes of reperfusion. The cardioplegia consisted of Krebs-Henseleit solution with either vehicle alone (control), 20 mmol KCl, or pinacidil (10, 50, 100, 150, or 200 mumol/L). The developed pressure was measured at baseline and after reperfusion. Coronary blood flow was measured with an in-line ultrasonic probe.


RESULTS
Pinacidil (50 mumol/L), as opposed to potassium cardioplegia, provided significantly better postischemic percentage recovery of developed pressure compared with controls (68.3% +/- 4.0% versus 44.6% +/- 5.5%; p < 0.05). The time until electrical arrest was significantly shorter in the hyperkalemic group than in all other groups. Linear end-diastolic pressure-volume relationships revealed an increase in slope after ischemia in all groups. Coronary flow after 5 minutes of reperfusion was significantly higher in both the 50-mumol/L and 100-mumol/L pinacidil groups compared with traditional hyperkalemic arrest, and this returned to baseline after 15 minutes.


CONCLUSIONS
The potassium channel opener pinacidil provided dose-dependent myocardial protection during global ischemia in the blood-perfused rabbit heart model. Potassium-channel openers are a promising class of drugs that may provide an alternative to traditional hyperkalemic cardioplegia.
Lawton
J S
JS
Department of Surgery, Medical College of Virginia, Richmond, USA.
Harrington
G C
GC
Allen
C T
CT
Hsia
P W
PW
Damiano
R J
RJ
D000818:Animals; D001769:Blood; D001794:Blood Pressure / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006324:Heart Arrest, Induced; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009926:Organ Preservation; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D013237:Stereoisomerism; D013997:Time Factors; D014325:Tromethamine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D002314:Cardioplegic Solutions; D006146:Guanidines; C074097:Krebs-Henseleit solution; D015221:Potassium Channels; D014665:Vasodilator Agents; D014325:Tromethamine; D011189:Potassium Chloride; D020110:Pinacidil; D005947:Glucose