New NO Donor S-NO-HSA improves cardioplegic solutions

Abstract

Introduction: HTK is a commonly used cardioplegia to perform open heart surgery. Aim of this study is to evaluate the myocardial and endothelial protection of its experimental successor HTK-N in a model of an acute damaged rat heart. Subsequently, evaluation of S-NO-HSA addition to the cardioplegic solution will be performed to investigate the protective effects of the NO-Donor. Material and methods: Male Sprague Dawley rats underwent 60' LAD ligature and 120' in vivo reperfusion. Afterwards, they were randomly assigned for evaluation of hemodynamic parameters in an erythrocyte perfused isolated working heart during 45' baseline measurements, 60' of HTK [group 1; n=10], HTK-N [group 2; n=10], or S-NO-HSA enriched HTK-N [group 3; n=8] protected ice cold ischemia and 45' of postischemic reperfusion. Blood gas analyses were performed before and after global ischemia. Results: At similar infarct size, postischemic recovery of hemodynamic parameters showed minor improvements in the HTK-N group whereas it was significantly enhanced in the S-NO-HSA enriched HTK-N group: External Heart Work (HTK: 79±14% vs. HTK-N: 83±9% n.s.; HTK vs. HTK-N + S-NO-HSA: 99±12% p≤0.01), Cardiac Output (HTK: 82±13% vs. HTK-N: 87±9% n.s.; HTK vs. HTK-N + S-NO-HSA: 99±9% p≤0.01). Recovery of Coronary Flow was significantly improved in the HTK-N group (HTK: 83±17% vs. HTK-N: 99±16% p<0.05.), but further improvement was observed after S-NO-HSA addition (HTK vs. HTK-N + S-NO-HSA: 109±22% p≤0.01). Blood gas analyses showed significantly increased recovery of myocardial oxygen delivery (HTK: 81±13% vs. HTK-N: 96±9% p≤0.05; HTK vs. HTK-N + S-NO-HSA: 103±16% p≤0.05) in both groups whereas myocardial oxygen consumption (HTK: 92±7% vs. HTK-N: 97±16% n.s.; HTK vs. HTK-N + S-NO-HSA: 110±16% p≤0.05) was significantly enhanced only in the S-NO-HSA enriched group. Discussion: HTK-N improves myocardial function after protected ex vivo global ischemia compared to its clinical predecessor HTK. Further improvement was observed through S-NO-HSA enrichment. In addition, S-NO-HSA shows signs of enhanced endothelial protection. Hence, S-NO-HSA might be an interesting therapeutic option to further improve cardiac protection for acute damaged hearts.