Kousholt, Birgitte S.7; Larsen, Jens Kjærgaard Rolighed8; Bisgaard, Line Stattau5; Burnett Jr., John C.6; Hasenkam, J. Michael7; Gøtze, Jens Peter7
1 Department of Clinical Medicine - Department of Thoracic and Cardiovascular Surgery T, Department of Clinical Medicine, Health, Aarhus University2 Faculty Secretariat, The Faculty of Health Sciences, Health, Aarhus University3 Department of Clinical Medicine - Cardiovascular Research Unit, Department of Clinical Medicine, Health, Aarhus University4 Department of Clinical Medicine, Health, Aarhus University5 Institut for Klinisk Medicin6 Cardiorenal Research Laboratory, The Mayo Clinic, Minnesota7 Department of Clinical Medicine, Health, Aarhus University8 Department of Clinical Medicine - Department of Thoracic and Cardiovascular Surgery T, Department of Clinical Medicine, Health, Aarhus University
Aim: The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia–reperfusion damage. Materials and methods: The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect was determined by assessment of intracellular caspase activity and troponin T release from cultured HL-1 cells subjected to short-term hypoxia–reperfusion. Cardiac effects were further examined in pigs (n=25) that had been subjected to 1 h of regional cardiac ischemia, followed by 3 h of reperfusion. Results: HL-1 cardiomyocytes responded to exogenous BNP with increased cGMP activity (∼3-fold, P=0.0037) and hypoxia–reperfusion with increased vascular endothelial growth factor and BNPmRNA contents (2.3- and 2.5-fold, respectively, P<0.0001) and caspase activity (2.9-fold, P=0.03), but without a decrease in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (∼15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared with controls (P=0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P=0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P=0.0015 and 0.0019), and were associated with improved RNA integrity in the ischemic left ventricular region (P<0.05). Conclusion: We report that natriuretic peptide infusion in vivo reduces cardiomyocyte injury in acute ischemia–reperfusion, possibly through indirect mechanisms (e.g. increased diuresis and vasodilation). The results suggest a role for natriuretic peptide therapy in human cardiac ischemia.
Cardiovascular Endocrinology, 2012, Vol 1, Issue 1, p. 4-12