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DOI: 10.1055/s-2007-967687
Inhibition of poly (ADP-Ribose) polymerase improves endothelial and myocardial function after brain death
Aims: Recently, it was shown that brain death (BD) leads to an systemic inflammatory reaction with subsequent cardiovascular dysfunction. As poly (ADP)-ribose polymerase (PARP) activation plays a key role in free radical induced injury in the context of systemic inflammation, we investigated the effects of PARP inhibition after BD.
Methods: We infused the PARP-inhibitor INO-1001 (1mg/kg) in 6 dogs for 1 hour starting 30 minutes after BD induction (subdural balloon). 6 vehicle treated BD animals served as controls. Coronary blood flow (CBF), endothelium-dependent vasodilatation after to acetylcholine (ACH) were assessed before and 6 hour after BD. Left ventricular pressure-volume data were measured by a combined conductance catheter and preload recruitable stroke work (PRSW) was calculated.
Results: BD induction led to an initial hyperdynamic reaction with a significant (p<0.05) increase of CBF and myocardial contractility. After 6 hours CBF decreased significantly in the control group (38.2±3.5 vs. 26.8±3.1ml/min, p<0.05), while the decrease was less pronounced in the INO-1001 group (44.8±5.4 vs. 37.0±2.2ml/min, p<0.05 vs. control). Before BD, ACH led to a similar vasodilative response in both groups (76±6 vs. 77±7%). After BD, a paradox vasoconstriction occurred after ACH in the control group, while the vasodilative response did not change in the INO-1001 group (–36±6 vs. 59±7%, p<0.05). After BD PRSW decreased in both groups, however, it was still significantly higher in the INO-1001 group (56±7 vs. 73±4 kerg, p<0.05).
Conclusion: Thus PARP-inhibition treatment prevents endothelial dysfunction and improves myocardial performance after BD.