**6.1 Pharmacological**

Prevention of PH represents a promising strategy to prevent RV failure, its most important consequence after cardiac surgery. To date, very few studies have addressed this issue and one of the potential avenues constitutes the prevention of the pulmonary reperfusion syndrome. In this regard, both iPGI2 (Fortier et al., 2004) and inhaled milrinone (Lamarche et al., 2005) have been demonstrated to prevent CPB-induced endothelial dysfunction, in an animal model. A pilot randomized controlled trial (RCT) conducted by Hache *et al.* (Hache et al., 2003) in patients with preoperative PH concluded that iPGI2 was superior to placebo in reducing PH and was also associated with lower requirements for vasoactive support.

A pilot RCT was conducted on the administration of inhaled milrinone before CPB in 21 patients, all undergoing valvular surgeries (Denault et al., 2010b). Procedures consisted of 14 complex surgeries and 5 reoperations. The study included a total of 8 males and 13 females with a mean age of 70±6.3 years old and a mean Parsonnet Score of 32±9. Inhaled milrinone (*n*=10) significantly reduced mean SPAP, which decreased from 66±20 mmHg (pre-CPB) to 46±20 mmHg (after CPB) (p<0.001). In contrast, SPAP remained unchanged in the control group (*n*=11) and no significant differences between groups were observed in decreased systemic arterial pressures.

A retrospective study reporting the preliminary experience on the use of inhaled milrinone at the Montreal Heart Institute was conducted in 70 high risk patients with a mean Parsonnet Score of 27±14 (Bernstein & Parsonnet, 2000; Lamarche et al., 2007). Results were compared to those of a control group with similar baseline characteristics. In conclusion, the administration of inhaled milrinone prior to CPB (*n*=30) was associated with a lower chance of CPB re-initiation (9 *vs* 1; p=0.021) and lower postoperative PAP. Further studies (# NCT00819377) are underway to determine the efficacy of this approach.

## **6.2 Non-pharmacological**

In addition to therapeutic approaches to the prevention of PH, the choice of type and size of aortic prosthetic valve may be a very important factor. As previously discussed, it has been shown that, if the EOA of the aortic valve is too small relative to body size, the so-called PPM, the intraoperative and long-term mortality will increase (Milano et al., 2001; Rao et al., 2000; Pibarot & Dumesnil, 2000; Blais et al., 2003; Ruel et al., 2004; Pibarot & Dumesnil, 2006; Tasca et al., 2006; Kulik et al., 2006). Hence, prevention of PPM may contribute to reducing PH after cardiac surgery and facilitate separation from CPB. This includes strategies such as the implantation of a prosthesis with better performance (stentless bioprosthesis, new generation bileaflet mechanical valve, new generation supra-annular stented bioprosthetic valve) or enlargement of the aortic root (Fig. **9**) in order to accommodate a larger prosthesis. On the other hand, some strategies used to prevent PPM are complex and may even increase the risk of difficult weaning from CPB extending the duration of the surgical procedure and consequently, CPB duration. Unfortunately, in some cases, the drawbacks of using alternative procedures may supercede the benefits of avoiding PPM. Therefore, the establishment of accurate criteria for a better assessment of the benefit-risk ratio with respect to the prevention of PPM is essential. In the case of mitral valve PPM, the best option would be to favor mitral valve repair rather than replacement. However, mitral valve repair may not be possible in a significant number of patients, which limits the options when compared to aortic valve replacement (Magne et al., 2007).
