Abstract 2056: BNP Expression in Ischemic Myocardium
Background: Diastolic stretch and neuroendocrine acitivation are known to induce gene expression and release of the B-type natriuretic peptide (BNP). However, it is widely unknown whether increased BNP-values found in ischemic heart disease are triggered directly by ischemic and metabolic alterations or whether they are caused indirectly by ischemia through diastolic contractures or regional wall motion abnormalities. Therefore, we investigated the BNP expression in isolated human atrial and ventricular muscle strips under conditions of metabolic stress with and without contracture.
Material and Methods: Muscle strips were isolated from human left ventricles (n=25) from patients undergoing heart transplantation due to end-stage dilated cardiomyopathy. Contractures were induced by glucose and oxygen withdrawal. In n=10 contractures were prevented by means of the calcium desensitizing agent butanedione-monoxime (BDM). The gene expression of BNP was determined in all muscle strips using rt-PCR and compared to control muscle strips contracting under physiological conditions (n=5).
Results: Withdrawal of oxygen and glucose resulted in a reduction of the systolic contractile force from 8.05±2.1 mN/mm2 to 1.45±1.34 mN/mm2. The diastolic contracture after 20 and 30 min was 8.62 and 6.13 mN/mm2, respectively. Adding BDM (30 mmol) before glucose and oxygen withdrawal completely prevented systolic contractions and diastolic contractures. The gene expression of BNP increased in the group without BDM (contracture) 71-fold after 30 min and 218-fold after 60min in comparison to control (p<0.05). In the group with a BDM-induced prevention of contractures, the BNP expression increased 65-fold after 30 min and 185-fold after 60 min in comparison control (p<0.05). There was no significant difference between the both groups.
Conclusions: The gene expression of BNP under metabolic stress is independent from BDM. These results indicate that ischemia is an autonomous mechanism for the expression of BNP and independent from mechanical alterations.