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.
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cardiovascular Endocrinology |
| Vol/bind | 1 |
| Sider (fra-til) | 4-12 |
| DOI | |
| Status | Udgivet - 2012 |