Nicorandil decreases postischemic actin oxidation.

This study examined the hypothesis that preconditioning can decrease postischemic oxidative protein damage. Isolated rat hearts were subjected to 25 min of normothermic global ischemia followed by 45 min of reperfusion. These were compared with hearts pretreated with 20 microM nicorandil or preconditioned with two cycles of ischemia. Changes in the high energy phosphates, ATP and phosphocreatine, were followed using (31)P-NMR spectroscopy. Protein carbonyls were assessed using an immunoblot technique. Postischemic hemodynamic function and high energy phosphates recovered to significantly (p <.05) higher levels in nicorandil-treated and ischemic preconditioned hearts as compared to controls. Postischemic protein carbonyl formation was highest in control reperfused hearts but reduced to intermediate between control and preischemic hearts by ischemic preconditioning and virtually prevented by nicorandil pretreatment, with a prominent band at 43 kDa significantly affected (p <.05). Based on immunoshift and immunoprecipitation studies, this band was identified as a mixture of actin isoforms. These studies support the conclusion that nicorandil diminishes protein oxidative damage in general, and specifically actin oxidation, which in the presence of improved supply of high energy phosphates, leads to enhanced postischemic contractile function.

New solution for prolonged myocardial preservation for transplantation.

BACKGROUND: A solution for prolonged cold storage of the heart has been developed. The Jerusalem-Cape Town Solution (JCT) is an "intracellular" type cardioplegic solution and is formulated to (1) minimize hypothermic-induced cell swelling, (2) diminish intracellular acidosis, (3) prevent the expansion of the interstitial space during the reperfusion, (4) protect against oxygen free radical injury during early reperfusion, and (5) provide substrates for regenerating high-energy phosphates. METHODS: With a Langendorff model, rat hearts were subjected to 15 minutes of perfusion with Krebs-Henseleit, 10 minutes of cardioplegic infusion and 20 hours of cold storage (5 degrees to 6 degrees C). Hearts were reperfused for 60 minutes and hemodynamic recovery was assessed. The hearts were assigned to three groups (eight hearts in each), according to the cardioplegic solution used: group 1, JCT; group 2, Bretschneider's HTK cardioplegic solution; and group 3 University of Wisconsin cold storage solution. RESULTS: After 60 minutes of reperfusion, the recovery of the coronary artery flow in group 1 (JCT) was significantly better than in group 2, and slightly better than in group 3 (64% +/- 8.9%, 47.2% +/- 11.6%, 52.5% +/- 19.9%, mean +/- SD, respectively; group 1 versus group 2, p < 0.01). The recovery of the left ventricular developed pressure (LVDP) was significantly better in group 1 compared with group 2 and group 3 (60.2% +/- 14.5%, 41.1% +/- 12.6% and 36.5% +/- 10.1%, respectively; p < 0.01). The recovery of the heart contractility expressed by the product of LVDP and the heart rate (LVDP x heart rate) was significantly higher in group 1 than in group 2 and group 3 (47.5% +/- 3.4%, 23.6% +/- 9.6%, and 28.7% +/- 8.3%, respectively, p < 0.001). In hearts stored for 12 hours in JCT or HTK, the recovery of the heart contractility did not differ significantly (73.4% +/- 12.7% or 70.8% +/- 30.8%, respectively). Modified reperfusion aimed to improve postischemic heart recovery did not bring significant changes in cardiac mechanical function but resulted in an increase in postischemic coronary artery flow recovery in hearts reperfused with amino acid-enriched buffer. CONCLUSIONS: The JCT solution is effective (as well as HTK) in preserving the ischemic hearts for up to 12 hours. It is superior to HTK or University of Wisconsin solution at 20 hours of isolated ischemic storage.

New experimental technique to study blood cardioplegia in the isolated, perfused rat heart.

Blood cardioplegia has been extensively studied clinically and in the large animal experimental model. We describe here a modification of the original Langendorff technique to study continuous warm blood cardioplegia in the isolated, perfused rat heart. The excised heart is mounted on the perfusion apparatus and perfused with Krebs-Henseleit buffer. Prearrest hemodynamics are recorded. The shed blood in the mediastinal cavity (8 to 12 mL) is collected, filtered, and reconstituted into cardioplegic solution (hematocrit, 0.20; K+, 15 mmol/L). Hearts are arrested and maintained at 37 degrees C by continuous recirculation of blood cardioplegia for 1 hour. The blood cardioplegia system consists of a Silastic tubing oxygenator, peristaltic pump, and two filters (40 microns pore size). The heart is reperfused with Krebs-Henseleit solution, and postarrest hemodynamics are recorded. Percentage recovery of peak left ventricular pressure, heart rate, and coronary flow were 98.5 +/- 3.1, 102 +/- 4.2, and 98.5 +/- 4.5 (mean +/- standard error of the mean; n = 6), respectively. Myocardial oxygen consumption during arrest was 57 microL.min-1.g-1 dry wt, which is 10% of the myocardial oxygen consumption of a beating heart in in-vivo and ex-vivo models. These results suggest the feasibility of studying blood cardioplegia in the isolated, perfused rat heart model under controlled conditions. Continuous warm blood cardioplegic arrest provided excellent myocardial protection for 1 hour in this model.