Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation.
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 degrees C) hyperkalemic cardioplegia (n=8) or cardioplegia where hyperkalemia was substituted with 1.2 mM adenosine (n=8). After 1h of cold ischemic arrest, coronary blood flow was monitored for the following 2h. The LAD artery was then explanted, and cylindrical rings were mounted for isometric tension recordings in organ chambers. Vessels were preconstricted with U46610 (Thromboxane A(2) 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
Invivo: The adenosine group had, as distinct from the hyperkalemic group, a significantly increased coronary blood flow index 1h 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. Invitro: 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).


CONCLUSIONS
Adenosine instead of supranormal potassium in cold crystalloid cardioplegia increases postcardioplegic myocardial blood flow and preserves EDHF-dependent vasodilation.
Department of Cardiothoracic and Vascular Surgery, University Hospital of North Norway and Institute of Clinical Medicine, University of Tromsø, Norway. oyvind.jakobsen@fagmed.uit.no
Oyvind
O
Jakobsen
Thor A
TA
Stenberg
Ole
O
Losvik
Sveinung
S
Ekse
Dag G
DG
Sørlie
Lars M
LM
Ytrebø
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D002314:Cardioplegic Solutions / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006324:Heart Arrest, Induced / Q000379:methods; D006439:Hemodynamics; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D011188:Potassium / Q000494:pharmacology*; D011897:Random Allocation; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001685:Biological Factors; D002314:Cardioplegic Solutions; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D000241:Adenosine; D011188:Potassium