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Role of plasminogen activator inhibitor-1 polymorphism on the development of vasoplegic syndrome associated with cardiopulmonary bypass
Critical Care volume 11, Article number: P255 (2007)
Vasoplegic syndrome (VS) after cardiac surgery with cardiopulmonary bypass (CPB) can vary from mild to severe complication and it appears with an incidence ranging between 5% and 15%. The etiology is not completely elucidated but risk factors such as temperature and duration of cardiopulmonary bypass and preoperative treatment with angiotensin-converting enzyme (ACE) inhibitors have been associated . We wanted to investigate the possible role of several genetic polymorphisms in patients with VS after elective CPB.
We performed a nested case–control study of 50 patients undergoing CPB, 27 (54%) men and 23 (46) women, mean age 66.5 (SD 9.6) years. VS was defined as systemic vascular resistance index lower than 1,600 dyn∙seg/cm5/m2 and a cardiac index greater than 2.5 l/min/m2 within the first 4 hours after surgery. We recorded data related to hemodynamic parameters at different postoperative time points, at ICU admission (0 hours), 4 and 24 hours after surgery, and the polymorphism of the following genes: plasminogen activator inhibitor-1 (PAI-1) and β-TNF + 250. In addition, 23 neutral markers were genotyped to follow genomic control strategies that would detect spurious associations due to population substructure. We used the Pearson chi-squared test and binary logistic regression. SPSS version 12.1 was used.
We observed 17 (34%) patients with vasoplegia criteria, 11 (65%) men and six (35%) women, age 67 (61–72) years. The only one associated with VS was the PAI-1 polymorphism, and its distribution in the study population was: 4G/G genotype in 10 (20%) patients, 4G/5G in 26 (52%) patients, and 5G/G in 14 (28%) patients. According to the PAI-1 polymorphism, vasoplegia criteria were found in one (5.5%) 4G/G carrier, in seven (39%) 4G/5G carriers and in 10 (55.5%) 5G/G carriers (P = 0.012) (Figure 1). The post-hoc power for PAI-1 polymorphism and vasoplegia was 0.85. After controlling for temperature, clamping time, antifibrinolytics, body mass index and ACE inhibitors, the 5G/G genotype was independently associated with vasoplegia (P = 0.017); OR: 24.6 (95% CI: 1.8–342).
The PAI-1 polymorphism (homozygous 5G/G) was independently associated with the onset of VS.
Carrel T, Englberger L, Mohacsi P, Neidhart P, Schmidli J: Low systemic vascular resistance after cardiopulmonary bypass: incidence, etiology, and clinical importance. J Card Surg 2000, 15: 347-353.
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Jimenez, J., Iribarren, J., Brouard, M. et al. Role of plasminogen activator inhibitor-1 polymorphism on the development of vasoplegic syndrome associated with cardiopulmonary bypass. Crit Care 11, P255 (2007). https://0-doi-org.brum.beds.ac.uk/10.1186/cc5415
- Cardiopulmonary Bypass
- Cardiac Index
- Binary Logistic Regression
- Resistance Index
- Systemic Vascular Resistance