Pitavastatin Prevents Bacterial Translocation after Nonpulsatile/Low-Pressure Blood Flow in Early Atherosclerotic Rat: Inhibition of Small Intestine Inducible Nitric Oxide Synthase

Abstract

Background: Cardiopulmonary bypass decreases intestinal mucosal blood flow because of nonpulsatile and low-pressure blood flow resulting in bacterial translocation (BT) and atherosclerosis also has peripheral blood flow deficiency. The risk of nonpulsatile and low-pressure blood flow for atherosclerotic animals and the effect of statin administration, which has pleiotropic effects, were studied. Methods: Wistar rats were divided into four groups: group N (normal diet), group C (high-cholesterol diet), group S (group C plus pitavastatin therapy), and group I [group C plus inducible nitric oxide (iNOS) inhibitor therapy]. First of all, vascular responses were measured. Then the rats underwent nonpulsatile/low-pressure blood flow in the intestine, and the serum peptidoglycan concentration as a parameter of BT, the small intestinal PO₂ ratio (intestinal PO₂/PaO₂) as a parameter of mucosal blood flow, and NO concentrations were measured before surgery (T0), at the end of 90 min of stenosis (T1), and 90 min after the release of stenosis (T2). Immunostaining for nitrotyrosine was also performed at T2. Results: Group C had vascular endothelial dysfunction without histological changes, which indicated early atherosclerosis. The serum peptidoglycan concentration increased significantly at T2 only in group C. The intestinal PO₂ ratio was decreased at T1 in all the groups, and retuned to baseline at T2 in group N and group S, but not in group C or group I. Jejunal NO only in group C was significantly higher at all time points and ileal NO production at T1 and T2. There tended to be a positive stain for nitrotyrosine along the mucosal epithelium in group C. Conclusion: In the setting of early atherosclerosis, intestinal blood flow does not only improve after nonpulsatile/low-pressure blood flow but causes BT because of a large amount of NO from high enzymatic intestinal iNOS activity, and pitavastatin treatment can prevent BT by improving both issues.

Use of Statins in Adhesive Small Bowel Obstruction

“…It did not consider the doses or types of statins that patients were taking, nor did it account for the length of time patients had been on statins. Though our aim was to explore the class effect of statins, differences in the properties of individual statin drugs have been previously described [7,24,26]. The interval between the index operation and presentation with ASBO may also be a variable of interest but was unable to be calculated due to a lack of reliable data and patients having multiple operations.…”

“…Statins may also reduce adhesions due to their antioxidant properties [23]. Moreover, statins have also been shown to reduce intestinal ischemia and reperfusion injury and decrease bacterial translocation and peritoneal inflammation [24][25][26].…”

PAMPs and DAMPs as the Bridge Between Periodontitis and Atherosclerosis: The Potential Therapeutic Targets

“…Early studies found that PGN induced the production of pro-inflammatory cytokines through TLR2 and increased the vulnerability of AS plaques (Nijhuis et al, 2004). While the vascular endothelial dysfunction appeared in rats modeled by surgery and a high-cholesterol diet, the concentration of serum PGN was significantly increased (Tsunooka et al, 2005). It has been confirmed that TLR2 is expressed in macrophages in AS lesions.…”

New Trends in the Impact of Periodontal Treatment on Early Cardiovascular Diseases Outcomes: Insights and Future Perspectives

“…In this way it enhances monocyte adhesion and chemotaxis, that lead to vascular disease PGN recognition protein-1 (PGLYRP-1) which can also recognize PGN. It should be highlighted that high levels of PGLYRP-1 are associated with vascular disease and may favor the formation of atherosclerotic plaques by modulating the overexpression of adhesion molecules [ 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ].…”