K(ATP) channel opener protects neonatal rabbit heart better than St. Thomas' solution.
OBJECTIVE
Myocardial protection with ATP-sensitive potassium channel (K(ATP) channel) openers is as effective as St. Thomas' cardioplegia (StTCP) in adult rabbit hearts. This study compares the effectiveness of the K(ATP) channel opener pinacidil to StTCP in protecting neonatal rabbit hearts exposed to global ischemia.


METHODS
Seventeen neonatal rabbit hearts (7-9 days old) perfused with Krebs-Henseleit buffer (KHB) on a Langendorff apparatus underwent 90 min of normothermic ischemia. Six (ischemia control) received no pretreatment before or during ischemia. Six others (pinacidil) received a 3-min infusion of 50 microM pinacidil in KHB without StTCP at the onset of ischemia. Five others (StTCP) received a 3-min infusion of StTCP at the onset of ischemia. After 60 min of KHB reperfusion, recovery of left ventricular (LV) performance and coronary flow (CF) were measured and compared to preischemia. A paired t test was used for comparison between drug-treated and untreated groups.


RESULTS
Pinacidil-treated hearts had significantly better recovery of left ventricular developed pressure (47 +/- 3.8 mmHg vs 32 +/- 2.5 mmHg, P < 0.05), contractility (+dP/dt(max); 885.4 +/- 74 mmHg vs 643.7 +/- 65 mmHg, P < 0.05), left ventricular end diastolic pressure (10.5 +/- 0.9 mmHg vs 17.4 +/- 1.2 mmHg P < 0.05), compliance (-dP/dt(max); 994.2 +/- 86 mmHg vs 673.6 +/- 69 mmHg, P < 0.05), and CF (5.9 +/- 0.4 ml/min vs 4.2 +/- 0.2 ml/min, P < 0.05) compared to ischemic control. StTCP only improved the recovery of -dP/dt(max) (877.4 +/- 73 mmHg/s vs 673.6 +/- 69 mmHg/s, P < 0.05) and CF (5.7 +/- 0.3 ml/min vs 4.2 +/- 0.2 ml/min, P < 0.05) compared to control.


CONCLUSIONS
Pinacidil pretreatment provided superior recovery of systolic performance compared to St. Thomas' cardioplegia solution in neonatal hearts. Myocardial protection by pretreatment with the K(ATP) channel opener pinacidil may be a new strategy for myocardial protection during pediatric cardiac surgery.
Feng
Jun
J
Division of Cardiothoracic Surgery, Daughtry Department of Surgery, University of Miami School of Medicine, Miami, Florida 33101, USA.
Li
Hongling
H
Rosenkranz
Eliot R
ER
D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology*; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009926:Organ Preservation / Q000379:methods; D020110:Pinacidil / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology*; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000502:physiology
D001639:Bicarbonates; D002314:Cardioplegic Solutions; D015221:Potassium Channels; C041711:St. Thomas' Hospital cardioplegic solution; D014665:Vasodilator Agents; D012965:Sodium Chloride; D011189:Potassium Chloride; D020110:Pinacidil; D008274:Magnesium; D002122:Calcium Chloride; D011188:Potassium