Abstract
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. Cardiovasc Endocrinol 1:4-12
Original language | English (US) |
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Pages (from-to) | 4-12 |
Number of pages | 9 |
Journal | Cardiovascular Endocrinology |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - Mar 2012 |
Keywords
- BNP
- CD-NP
- Ischemia-reperfusion injury
- Myocardial infarction
- Porcine
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrine and Autonomic Systems
- Cardiology and Cardiovascular Medicine