Peritoneal Dialysate Effluent During Peritonitis Induces Human Cardiomyocyte Apoptosis and Express Matrix Metalloproteinases-9

Cardiovascular event and infection are the first and second leading causes of death in the peritoneal dialysis (PD) populations (Parfrey and Foley, 1999; Go et al., 2004; Schiffrin et al., 2007; USRDS, 2008); both events are closely related. PD-related peritonitis is the crucial infection in PD patients (Aslam et al., 2006; Bender et al., 2006). Peritoneal toxin should be absorbed to the systemic circulation and might induce cardiotoxicity. After an episode of severe infection in dialysis patients, risk of death from cardiovascular events is increased sevenfold for 6 months and continues to rise for up to 48 months (Ishani et al., 2005; Bender et al., 2006). It has been considered to play a significant role in up to one sixth of patient deaths occurring during the course of PD therapy (Fried et al., 1996). In 41.5% of patients with peritonitis-related mortality, immediate cause of death was a cardiovascular event (Pe ́ rez Fontan et al., 2005). Clinical findings indicate that a peritonitis episode may culminate in cardiovascular event (Fried et al., 1996; Bender et al., 2006): high incidence of peritonitis is accompanied by greater risk of death (Maiorca et al., 1993; Fried et al., 1996; Piraino, 1998), and cardiovascular events contribute to risk of peritonitis-related death in patients undergoing PD (Digenis et al., 1990; Firanek et al., 1991; Lupo et al., 1994). However, the possible mechanisms connecting PD-related peritonitis and cardiac mortality have not been addressed. Growing evidence implicates cardiomyocyte apoptosis as a mechanism contributing to various types of heart disease (Olivetti et al., 1997; Haunstetter and Izumo, 1998; Narula et al., 1999). Cardiomyocyte apoptosis could result in a loss of contractile tissue, compensatory hypertrophy of myocardial cells, reparative fibrosis, and heart failure. In animal models, endotoxin (Natanson et al., 1989; Ramana et al., 2006), exotoxin (Natanson et al., 1989; Sibelius et al., 2000), and inflammatory mediator (Mann, 1999) play important roles in cardiomyocyte apoptosis. In PD patients with infectious peritonitis, expression of inflammatory mediators and cytokines increase in PD effluent (PDE) and correlate with treatment outcome (Lai et al., 2000; Wang and Lin, 2005). Yet there are no data on effects of peritonitis PD effluent (PPDE) on cardiomyocytes viability and apoptosis. Bcl-2 protein family members are the best characterized proteins that are directly involved in the regulation of apoptosis (Cory and Adams, 2002). Bcl-2 and its closest homologues,