PPARγ Agonist Pioglitazone Prevents Hypoxia-induced Cardiac Dysfunction by Reprogramming Glucose Metabolism.

The heart relies on various defense mechanisms, including metabolic plasticity, to maintain its normal structure and function under high-altitude hypoxia. Pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ), sensitizes insulin, which in turn regulates blood glucose levels. However, its preventive effects against hypoxia-induced cardiac dysfunction at high altitudes have not been reported. In this study, pioglitazone effectively prevented cardiac dysfunction in hypoxic mice for 4 weeks, independent of its effects on insulin sensitivity. In vitro experiments demonstrated that pioglitazone enhanced the contractility of primary cardiomyocytes and reduced the risk of QT interval prolongation under hypoxic conditions. Additionally, pioglitazone promoted cardiac glucose metabolic reprogramming by increasing glycolytic capacity; enhancing glucose oxidation, electron transfer, and oxidative phosphorylation processes; and reducing mitochondrial reactive ROS production, which ultimately maintained mitochondrial membrane potential and ATP production in cardiomyocytes under hypoxic conditions. Notably, as a PPARγ agonist, pioglitazone promoted hypoxia-inducible factor 1α (HIF-1α) expression in hypoxic myocardium. Moreover, KC7F2, a HIF-1α inhibitor, disrupted the reprogramming of cardiac glucose metabolism and reduced cardiac function in pioglitazone-treated mice under hypoxic conditions. In conclusion, pioglitazone effectively prevented high-altitude hypoxia-induced cardiac dysfunction by reprogramming cardiac glucose metabolism.

Clinical Application of Proximal Arch Cannulation in the Surgical Treatment of Acute Type I Aortic Dissection.

Objective The goal is to determine the best location for inserting a catheter into the aortic arch of patients with a certain type of aortic dissection (DeBakey type I) by analyzing images of the patient's aortic arch before surgery. This analysis will take into account the shape and structure of the patient's aortic arch to find the most optimal location for cannulation. Methods A retrospective analysis was conducted on 100 patients with acute DeBakey type I aortic dissection diagnosed between January 2021 and February 2023, utilizing the Carestream medical imaging software Image Suite V4 (New York, USA). The study included 67 cases that underwent surgery and 33 cases that did not. The study aimed to evaluate the optimal intubation position on the patient's aortic arch by analyzing the true and false lumen classification, true and false lumen area, and hematoma thickness on the patient's aortic arch, as observed in the aortic computed tomography angiography (CTA) conducted upon admission. Results The vascular axis analysis showed a significant difference in the true lumen area among the three regions that were examined (P < 0.001). Zone 1 had a larger true lumen area of 6.40 ± 2.71 cm2 compared to zone 2 with 5.75 ± 2.13 cm2 and zone 3 with 4.85 ± 1.70 cm2, as determined by statistical analysis. In addition, the statistical analysis of hematoma thickness in the three regions where cannulation can be performed revealed a significant difference among the three groups (P = 0.027). Further analysis showed that there was no significant difference between zone 1 and zone 2 (P = 1.000), a significant difference between zone 1 and zone 3 (P < 0.046), and no significant difference between zone 2 and zone 3 (P = 0.080). The difference between zone 1 false lumen thickness of 1.55 ± 0.51 cm and zone 3 false lumen thickness of 1.33 ± 0.55 cm was found to be small. Conclusion Cannulation of the aortic arch is a common strategy used in cardiac surgery. Accurate cannulation is critical to the success of the procedure. The use of CTA provides valuable guidance for the cannulation procedure. A thorough examination of CTA and precise measurement of relevant parameters can help guide the surgeon to determine the optimal cannulation site. The study found that zone 1 of the aortic arch has the largest area and is the most suitable for cannulation, in accordance with the physiological characteristics and surgical practices of a surgeon. Furthermore, cannulation of the aortic arch has been found to be a safe and effective strategy for cannulation. Overall, careful examination of CTA and accurate measurement of relevant parameters can have a significant guiding effect on the cannulation of the aortic arch, which can lead to improved outcomes in cardiac surgery.