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Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation

^a Department of Cardiothoracic and Vascular Surgery, University Hospital of North Norway and Institute of Clinical Medicine, University of Tromsø, Norway
^b Department of Anesthesiology, University Hospital of North Norway and Institute of Clinical Medicine, University of Tromsø, Norway

Received 22 June 2007; received in revised form 26 September 2007; accepted 8 October 2007.

^_* Corresponding author. Address: Surgical Research Laboratory, Institute of Clinical Medicine, Faculty of Medicine, University of Tromsø, 9037 Tromsø, Norway. Tel.: +47 970 63 949; fax: +47 776 28 298. (Email: oyvind.jakobsen{at}fagmed.uit.no).

Objective: We have recently shown that adenosine instead of supranormal potassium in cold crystalloid cardioplegia improves cardioprotection. Studies indicate that hyperkalemia has unfavorable effects on vascular endothelial function. Three pathways have been identified as major vasodilatory pathways: the nitric oxide (NO) pathway, the cyclooxygenase (COX) pathway, and the endothelium-derived hyperpolarization (EDHF) pathway, where the EDHF pathway, in particular, seems susceptible to hyperkalemia. We hypothesized that adenosine cardioplegia improves postcardioplegic endothelial function. Methods: Sixteen pigs were randomized to receive either cold (6 °C) hyperkalemic cardioplegia (n = 8) or cardioplegia where hyperkalemia was substituted with 1.2 mM adenosine (n = 8). After 1 h of cold ischemic arrest, coronary blood flow was monitored for the following 2 h. The LAD artery was then explanted, and cylindrical rings were mounted for isometric tension recordings in organ chambers. Vessels were preconstricted with U46610 (Thromboxane A₂ analog) and then bradykinin-mediated relaxation was investigated. To differentiate between the vasodilatory pathways the relaxation was assessed in the absence and presence of inhibitors of the COX (indomethacin), NO (L-NAME + carboxy-PTIO), and EDHF (apamin + charybdotoxin) pathways. Results: In vivo: The adenosine group had, as distinct from the hyperkalemic group, a significantly increased coronary blood flow index 1 h after cross-clamp release (from (ml/min/100 g, mean ± SD) 50.9 ± 13.9 to 72.8 ± 21.9, p = 0.010). The difference was, however, not statistically significant between groups. In vitro: Maximal relaxation without blockers was 27.4 ± 10.1% of maximal tension in the adenosine group and 22.2 ± 7.5% in the hyperkalemic group. To investigate EDHF-dependent vasodilation the vessel rings were simultaneously treated with indomethacin, L-NAME, and carboxy-PTIO. Maximal relaxation in the hyperkalemic group was then reduced to 47.4 ± 17.4% of maximal tension, which was a significant reduction compared to the adenosine group with a maximal relaxation of 20.6 ± 8.7% (p = 0.028). Conclusion: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia increases postcardioplegic myocardial blood flow and preserves EDHF-dependent vasodilation.

Key Words: Adenosine • Cardioplegia • Cardiopulmonary bypass • Coronary flow • Endothelium • Vascular relaxation