Hydroxytyrosol Protects against Myocardial Ischemia/Reperfusion Injury through a PI3K/Akt-Dependent Mechanism.

OBJECTIVE: To investigate the effects and mechanisms of hydroxytyrosol (HT) during the pathogenesis of myocardial ischemia reperfusion (I/R) in rat hearts. METHODS: The rats were randomized into five groups: sham group, I/R group, HT+I/R group, HT+LY294002+I/R group, and LY+I/R group. Myocardial infarct size, markers of oxidative stress, extent of myocardial apoptosis, echocardiographically assessed cardiac function, and expression of Akt and GSK 3ß were measured in each group. RESULTS: Prereperfusion administration of HT was associated with a significantly smaller area of myocardial infarction and remarkably decreased level of myocardial apoptosis and necrosis, as evidenced by a lower apoptotic index, reduced cleaved caspase-3, and the serum activities of lactate dehydrogenase and creatinine kinase MB. Moreover, HT also attenuated the impairment of cardiac systolic function. However, cotreatment with LY294002 and HT completely abolished the above cardioprotective effects of HT. A subsequent mechanistic study revealed that the cardioprotective effects of HT during the process of I/R of the myocardium were dependent on the activation of the Akt/GSK3ß pathway. CONCLUSION: Pretreatment with HT may have antiapoptotic and cardioprotective effects against myocardial I/R injury, and these effects seem to be related to the activation of the Akt/GSK3ß pathway in the myocardium.

The role of p38 MAPK in acute paraquat-induced lung injury in rats.

CONTEXT: Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium dichloride) is highly toxic and accounts for a large proportion of the herbicide poisonings seen in clinic. The major cause of mortality is respiratory failure. The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway coordinates various cellular stress responses that have been shown to participate in the pathogenesis of PQ-induced lung injury. OBJECTIVE: To evaluate the effect of the specific p38 MAPK inhibitor SB203580 on PQ-induced lung injury and cytokine secretion. METHODS: In groups of 24, rats were treated with PQ, PQ and SB203580 (SB + PQ), SB203580 alone (SB) or normal saline (control group). Six rats from each group were euthanized at 1, 3, 5 or 7 d. Pathology of lung specimens was scored through hematoxylin and eosin staining. Edema in the lung was quantified from wet-to-dry weight ratios. p38 and p-p38MAPK proteins were measured via electrochemiluminescent Western blots. tumor necrosis factor (TNF)-alpha and interleukin-1 beta (IL-1ß) concentrations in lung specimens and bronchoalveolar lavage fluid (BALF) were quantified via enzyme-linked immunosorbent assay. RESULTS: The mortality rate of the SB + PQ group (16.7%) was significantly lower than that of the PQ group (33.3%; p < 0.05). The PQ group had significantly higher pulmonary histology scores, wet-to-dry weight ratios and phosphorylated p-p38 MAPK levels, as well as higher IL-1ß and TNF-alpha levels in BALF and lung tissues, that did the SB + PQ and control groups (p < 0.05, all). CONCLUSION: The data suggest that the p38 MAPK signaling pathway has an important role in regulating the production of IL-1ß and TNF-alpha in PQ-induced lung injury in rats.

Reversible cardiogenic shock caused by atrioventricular junctional rhythm after percutaneous coronary intervention.

An 82-year-old female patient undergoing cardiogenic shock caused by atrioventricular junctional rhythm immediately after percutaneous coronary intervention (PCI) is described. Pharmacotherapy was invalid, and subsequent application of atrial pacing reversed the cardiogenic shock. PCI-related injury of sinuatrial nodal artery leading to acute atrial contractility loss, accompanied by atrioventricular junctional arrhythmia, was diagnosed. We recommend that preoperative risk evaluation be required for multi-risk patients. Likewise, emergent measures should to be established in advance. This case reminds us that atrial pacing can be an optimal management technique once cardiogenic shock has occurred.