Cardioprotective effect of nicorandil in histidine-tryptophan-ketoglurate solution during the cold storage of isolated hearts.
We compared the efficacy of using histidine-tryptophan-ketoglurate (HTK) solution with that of University of Wisconsin (UW) solution for heart preservation in an isolated rat heart preparation. Nicorandil (NCR) exerts its action as an ATP-sensitive potassium channel opener at low extracellular potassium concentrations, and HTK solution has a low potassium concentration. Therefore, we also investigated the efficacy of using HTK solution with NCR following 12-hr preservation. Hearts isolated from male Wistar rats were mounted on a Langendorff apparatus to estimate baseline aortic flow (AF), coronary flow (CF), cardiac out-put (CO), heart rate (HR), systolic pressure (SP), aortic mean pressure, and the rate-pressure product (RPP). The hearts were divided into four groups: group 1, 8-hr storage in UW solution; groups 2 and 3, 8- or 12-hr storage in HTK solution, respectively; and group 4, 12-hr storage in HTK solution with NCR. They were arrested and stored at 4 degrees C in each preservation solution. Following storage, they were reperfused and postpreservative function was measured to assess cardiac functional recovery. Concentrations of creatine phosphokinase, troponin-T, and lactate in the coronary perfusate were measured. Frozen tissue samples from groups 3 and 4 were analyzed for adenylate content and cGMP. The myocardial water content was also measured. The recovery of AF, CF, CO, SP, and RPP in group 2 was significantly improved compared with that in group 1 (P<0.05). The recovery of AF, CF, CO and HR in group 4 was significantly better than that in group 3 (P<0.05). Creatine phosphokinase leakage in group 2 and troponin-T leakage in group 4 were significantly reduced (P<0.05 vs. groups 1 and 3, respectively). Total adenine nucleotides and the adenylate energy charge in group 4 were well sustained (P<0.05 vs. group 3). These results suggest that HTK solution is more effective than UW solution for cardiac preservation, and that NCR provides still better protection.
Gu
K
K
First Department of Surgery, Shimane Medical University, Izumo, Japan.
Kin
S
S
Saitoh
Y
Y
Nosaka
S
S
Sasaki
T
T
Yamauchi
M
M
Nakayama
K
K
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003080:Cold Temperature; D006152:Cyclic GMP / Q000032:analysis; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
C039984:Bretschneider cardioplegic solution; D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D008353:Mannitol; D011343:Procaine; D000493:Allopurinol; D011189:Potassium Chloride; D005978:Glutathione; D006152:Cyclic GMP; D005947:Glucose; D000241:Adenosine; D011887:Raffinose