Protective effects of trehalose preconditioning on cardiac and coronary endothelial function through eNOS signaling pathway in a rat model of ischemia-reperfusion injury.

Coronary endothelial dysfunction is a major cause of ischemia-reperfusion (I/R) injury. Trehalose, a natural disaccharide, has been reported to ameliorate endothelial dysfunction during aging by activating endothelial nitric oxide synthase (eNOS); however, its role in I/R injury is unknown. This study evaluated the effects of trehalose preconditioning on cardiac and coronary endothelial function after I/R. Langendorff-perfused rat hearts underwent 30 min of global ischemia followed by 80 min of reperfusion with or without trehalose preconditioning. Rate pressure product (RPP) and coronary flow (CF) were measured during reperfusion. Perivascular edema was assessed by hematoxylin and eosin staining. Myocardial oxidative stress and apoptosis were evaluated by immunohistochemistry and TUNEL staining, respectively. eNOS dimerization was determined by western blotting. An eNOS inhibitor was used to examine the role of eNOS. Trehalose preconditioning showed a higher recovery rate after I/R as indicated by high RPP (control vs. trehalose, 28 ± 6% vs. 46 ± 9%; P = 0.017, Cohen's d = 2.3) and CF values (35 ± 10% vs. 55 ± 9%; P = 0.025, d = 1.7). Furthermore, trehalose preconditioning reduced perivascular edema, myocardial oxidative stress, and apoptosis. The eNOS dimerization ratio was increased by trehalose (1.2 ± 0.2 vs. 1.6 ± 0.2; P = 0.023, d = 2.1), which was associated with the recovery of RPP and CF. These effects of trehalose were abolished by the eNOS inhibitor. Trehalose preconditioning showed protective effects on cardiac and coronary endothelial function after I/R through the eNOS signaling pathway.

Trehalose preconditioning for transient global myocardial ischemia in rats.

Autophagy is an intracellular pathway that degrades unnecessary proteins and organelles and provides energy substrates during cellular ischemic conditions. Although pharmacological myocardial preconditioning with an autophagy inducer has been reported to protect cells against ischemic reperfusion (I/R), the effects of preconditioning using naturally occurring substances are still unknown. We aimed to examine whether autophagic preconditioning with trehalose improves cardiac function after myocardial stunning by global ischemia in rats. Rat hearts were perfused by oxygenized Krebs Henseleit (KH) solution in Langendorff system. Ten rats were randomized into the following two groups according to the perfusates during the preconditioning: control (KH solution only, n = 5) and trehalose (KH + 2% trehalose, n = 5). After the 35-min preconditioning period and subsequent 20 min of global ischemia, the hearts were reperfused for 60 min. Cardiac function was assessed during the reperfusion. To evaluate autophagy, myocardial protein expression of microtubule-associated protein light chain 3 (LC3) II was evaluated by western blotting. During I/R, a systolic functional parameter, maximum dP/dt was significantly higher; meanwhile, coronary flow tended to be higher in the trehalose group than in the control group. Myocardial LC3-II expression after preconditioning was higher in the trehalose group than in the control group and decreased to the control level after I/R. In conclusion, in a rat model of global myocardial ischemia, trehalose preconditioning improved cardiac function during I/R. Further studies would be needed to identify the mechanism and effects of trehalose preconditioning.

[Coronary Artery Bypass Grafting in an Elderly Patient with Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery].

We report a case of a 73-year-old woman who was diagnosed with anomalous origin of the left coronary artery(LCA) from the pulmonary artery(ALCAPA) by coronary angiography. Drug stress myocardial perfusion scintigraphy demonstrated myocardial ischemia in the left anterior descending coronary artery (LAD) region. She underwent single coronary artery bypass grafting to LAD using left internal thoracic artery (LITA) and direct closure of the origin of the anomalous LCA. Postoperative coronary catheterization revealed a patent graft showing no residual shunt from the pulmonary artery into the left coronary artery. Myocardial scintigraphy proved improvement of the ischemia. In general, once ALCAPA is diagnosed, early surgical intervention is recommended. However, since there are few reports regarding surgical treatment for ALCAPA in elderly patients, the optimal treatment strategy is not completely established. Therefore careful long-term follow-up is mandatory.