Post-cardiopulmonary bypass hypoxaemia in paediatric patients undergoing congenital heart disease surgery: risk factors, features, and postoperative pulmonary complications.

BACKGROUND: Hypoxemia after cardiopulmonary bypass (CPB) is the quantifiable manifestation of pulmonary dysfunction. This retrospective study was designed to investigate the risk factors for post-cardiopulmonary bypass hypoxaemia and the features of hypoxaemia and pulmonary complications in paediatric congenital heart disease surgery involving CPB. METHODS: Data including demographics, preoperative pulmonary or cardiac parameters, and intraoperative interventions were retrospectively collected from 318 paediatric patients who underwent radical surgery with CPB for congenital heart disease. Among them, the factors that were significant by univariate analysis were screened for multivariate Cox regression. The lowest ratio of arterial oxygen tension and the inspiratory oxygen fraction (PaO2/FiO2), hypoxaemia (PaO2/FiO2 ≤ 300) insult time, duration of hypoxaemia, extubation time, and pulmonary complications were also analysed postoperatively. RESULTS: The morbidity of post-cardiopulmonary bypass hypoxaemia was 48.4% (154/318). Months (6 < months ≤ 12, 12 < months ≤ 36 and 36 < months compared with 0 ≤ months ≤ 6: HR 0.582, 95% CI 0.388-0.873; HR 0.398, 95% CI 0.251-0.632; HR 0.336, 95% CI 0.197-0.574, respectively; p < 0.01), preoperative intracardiac right-to-left shunting (HR 1.729, 95% CI 1.200-2.493, p = 0.003) and intraoperative pleural cavity entry (HR 1.582, 95% CI 1.128-2.219, p = 0.008) were identified as independent risk factors for the development of post-cardiopulmonary bypass hypoxaemia. Most hypoxaemia cases (83.8%, 129/154) occurred within 2 h, and the rate of moderate hypoxaemia (100 < PaO2/FiO2 ≤ 200) was 60.4% (93/154). CONCLUSION: The morbidity of post-cardiopulmonary bypass hypoxaemia in paediatric congenital heart disease surgery was considerably high. Most hypoxaemia cases were moderate and occurred in the early period after CPB. Scrupulous management should be employed for younger infants or children with preoperative intracardiac right-to-left shunting or intraoperative pleural cavity entry.

Y-27632, a Rho-kinase inhibitor, attenuates myocardial ischemia-reperfusion injury in rats.

The present study aimed to evaluate the cardioprotective effects of a Rho­kinase inhibitor, Y­27632, and the underlying mechanisms. A rat model of myocardial ischemia­reperfusion (I/R) injury was generated by ligation of the coronary artery, and global ischemia of isolated rat hearts was conducted using the Langendorff system. Staining with triphenyltetrazolium chloride (TTC) and hematoxylin and eosin was performed to analyze the myocardial infarct size and histopathological alterations of the I/R­induced rat heart. In addition, coronary flow, myocardial contractility and an electrocardiogram were analyzed. The effects of Y­27632 on inflammatory cytokines and cardiac enzymes in the serum were assessed by ELISA. The expression of apoptosis­ and inflammation­associated proteins was also analyzed via western blotting. Rats in the Y­27632 group exhibited alleviated myocardial I/R injury according to TTC staining and histopathological diagnosis. Additionally, Y­27632 restored the ST segment. The data of coronary flow and myocardial contractility in isolated rat hearts indicated that Y­27632 improved heart function following I/R. The levels of inflammatory cytokines and cardiac enzymes in the serum were downregulated by Y­27632. The mitogen­activated protein kinase (MAPK) and nuclear factor (NF)­κB signaling pathways were inhibited by Y­27632. Furthermore, apoptosis­associated protein expression in rats and the isolated hearts was effectively inhibited by Y­27632. In conclusion, the findings of the present study indicated that Y­27632 attenuated myocardial injury via inhibiting the activation of the MAPK and NF­κB signaling pathways; thus, apoptosis and the inflammatory response were suppressed.

Quercetin attenuates myocardial ischemia-reperfusion injury via downregulation of the HMGB1-TLR4-NF-κB signaling pathway.

The goal of this study was to assess the ability of quercetin (Qu) to protect against myocardial ischemia-reperfusion injury. Cardiac injury was assessed in the context of global ischemia of isolated hearts, coronary artery ligated rats, and H9C2 cells. Qu was shown to significantly inhibit inflammatory cytokine production in coronary artery occlusion-induced rats, isolated hearts, and H9C2 cells. Electrocardiographic analysis revealed a restoration of the ST segment to normal levels following treatment of Qu. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that Qu could significantly alleviate myocardial injury in vivo. Furthermore, ex vivo analyses showed improved recovery of heart function in response to Qu, characterized by enhanced myocardial contractility and coronary flow in isolated hearts. From a mechanistic standpoint, these effects appeared to be mediated through the HMGB1-related pathway, with expression of downstream targets significantly downregulated in rats, isolated hearts, and H9C2 cells following Qu treatment. Taken together, these data demonstrate the protective effects of Qu against myocardial injury via inhibition of the HMGB1 pathway in a myocardial ischemia-reperfusion injury (I/R) model.

Captopril inhibits calpain­mediated apoptosis of myocardial cells in diabetic rats and improves cardiac function.

To explore the effects of captopril on calpain­mediated apoptosis of myocardial cells and cardiac function in diabetic rats, 30 adult male Sprague­Dawley rats were randomly divided into three groups: Negative control (NC group), untreated diabetic rats (DM group) and diabetic rats treated with captopril (Cap group). Diabetes was induced by streptozotocin injection. Captopril was intragastrically administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups received an equivalent volume of saline. After 12 weeks of treatment, left ventricular systolic pressure (LVSP), left ventricular end­diastolic pressure (LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal rate of left ventricular pressure decrease (­dp/dtmax) and left ventricular mass index (LVMI) were measured. The levels of calpain­1, calpain­2, B­cell lymphoma (Bcl)­2, Bcl­2 associated protein X (Bax) and total caspase­3 were detected in cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed with a terminal deoxynucleotidyl transferase­mediated dUTP nick­end labeling assay. The ultrastructure of cardiac tissue was determined by transmission electron microscopy. Compared with the NC group, LVDEP and LVMI were increased, whereas LVSP, +dp/dtmax and ­dp/dtmax were decreased in the DM group. In the Cap group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and ­dp/dtmax were increased compared with the DM group. Bcl­2 protein expression was decreased, whereas the levels of calpain­1, calpain­2, Bax and total caspase­3 protein were increased in the DM group, compared with the NC group. Cap treatment increased Bcl­2 protein expression and decreased calpain­1, calpain­2, Bax and total caspase­3 protein expression compared with the DM group. Additionally, the AI was increased in the DM group compared with the NC group, and decreased in the Cap group compared with the DM group. Furthermore, ultrastructural examination demonstrated that myocardial cell injury was reduced in the Cap group compared with the DM group. Therefore, captopril improved myocardial structure and ventricular function, by inhibiting calpain­1 and calpain­2 activation, increasing Bcl­2 expression, reducing Bax expression and subsequently inhibiting caspase­3­dependent apoptosis.

Hyperlipidemia induces vascular smooth muscle cell proliferation involving Wnt/ß-catenin signaling.

Hyperlipidemia has been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. Wnt signaling pathway plays a critical role in embryonic development and cell proliferation. In this study, Sprague-Dawley rats fed with high-fat or normal diet for 12 weeks were sacrificed, and the thoracic aorta was harvested to determine wnt3a, ß-catenin, T-cell factor 4 (TCF4), and cyclin D1 expressions. VSMC proliferation within thoracic aorta and lipid accumulation within VSMCs were detected. Rat aortic VSMCs were cultured in serum from rats with hyperlipidemia or DKK-1; Wnt3a, ß-catenin, TCF4, and cyclin D1 expressions, and cell cycle distribution were determined. The findings demonstrated that increased number of VSMCs, lipid droplets, and vacuoles within thoracic aorta in the high-fat-fed group. Compared with controls, VSMCs from high-fat-fed rats showed higher mRNA expressions of wnt3a, ß-catenin, TCF4, and cyclin D1, as well as in VSMCs cultured with hyperlipidemic serum. After 24 h, VSMCs stimulated with hyperlipidemic serum showed significantly increased cell number and S-phase entry compared with cells exposed to normolipidemic serum. These effects were blocked by DKK-1. These results suggest that Wnt/ß-catenin signaling plays an important role in hyperlipidemia-induced VSMC proliferation.