Tetrahydrobiopterin improves cardiac and pulmonary function after cardiopulmonary bypass

Objective: Tetrahydropioterin (BH4) is an important co-factor of endogenous nitric oxide synthesis. In the present pre-clinical study, we investigated the effects of tetrahydrobiopterin on cardiac and pulmonary function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation.

Methods: Twelve anesthetized dogs, underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n=6), or terahydrobiopterin (n=6). Left ventricular end-systolic pressure volume relationship (Ees) was measured by a combined pressure-volume-conductance catheter at baseline and after 60 minutes of reperfusion. Left anterior descendent coronary blood flow (CBF) and pulmonary blood flow (PBF), endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) and alveolo-arterial O2 gradient were determined.

Results: The admimistration of tetrahydrobiopterin led to a significantly better recovery (given as percent of baseline) of Ees 76±9% vs. 46±6%, p<0.05. CBF was also significantly higher in the BH4 group (38±4 vs. 25±4, ml/min, p<0.05). While the vasodilatatory response to SNP was similar in both groups, ACH resulted in a significantly higher increase in CBF (77±6% vs. 31±5%, p<0.05) and PBF (49±7% vs. 36±6%, p<0.05) in the tetrahydrobiopterin group. Alveolo-arterial O2 gradient was significantly lower in the tetrahydrobiopterin group (80±6 vs. 43±5mmHg, p<0.05).

Conclusions: Application of tetrahydrobioterin improves myocardial, endothelial and pulmonary function after cardiopulmonary bypass with hypothermic cardiac arrest.