To determine the therapeutic effect of fasciotomy+hypertonic saline flushing for crush syndrome (CS) in rats.

SD rats (weighing 250±20 g) were randomly divided into normal control group (NC group, n=10) and CS group (n=14).Rat CS model was established by compressing the buttocks and both hindlimbs with a weight of 7.5 kg for 4 h, and the presence of hematuria or anuria was defined as success of modeling.In 6 h after modeling, the fluid exuded from the compressed tissues was collected, and the contents of potassium ions (K⁺), calcium ions (Ca²⁺), myoglobin (Mb), and lactic acid (Lac) in the exudate of each group were detected.Another 63 male SD rats (weighing 250±20 g) were randomly and equally divided into blank control group (NC group), CS group, CS+fasciotomy group (CSO group), and CS+fasciotomy+difference doses of NaCl solution irrigation groups (0.9%, 3.0%, 5.0% and 7.0% NaCl, respectively).At 6 h after modeling, the renal blood flow was measured, the contents of K⁺, Ca²⁺, Mb, Lac, AST, ALT, Cr, and urea in the plasma of each group were detected, and the compressed tissues and kidney tissues were observed for pathological changes.

Detection of exudates showed the contents of K⁺, Mb, and Lac were significantly higher, while that of Ca²⁺ content was obviously decreased in the CS group than the NC group (P < 0.01).Plasma detection indicated that simple fasciotomy had no therapeutic effect, while it combined with NaCl solution flushing decreased the contents of K⁺, Mb, Lac, AST, ALT, urea and Cr, and increased the Ca²⁺ content in the blood of the CS group (P < 0.05).Laser speckle contrast imaging revealed that simple fasciotomy could not increase renal blood flow, while the combination of fasciotomy and NaCl solution flushing notably increased the renal blood flow in the CS rats (P < 0.05).In addition, the combination treatment reduced the pathological damage in the kidneys induced by CS, but fasciotomy alone had no such effect (P < 0.5).

Fasciotomy combined with hypertonic NaCl solution (3%) flushing can significantly reduce the damage caused by CS in rats.

To explore the protective effect of L-carnitine on myocardial systolic dysfunction in sepsis and its underlying mechanism.

A mouse sepsis model was established by cecal ligation and puncture (CLP). Ten-week-old male SPF-grade C57 BL/6 mice (body weight 20~30 g) were randomly divided into 5 groups via random number table: Sham group, Sepsis group, L-carnitine group, L-carnitine+Etomoxir (Eto) group, and Eto group. Echocardiography assessed cardiac function, ELISA measured serum creatine kinase isoenzyme MB (CK-MB) levels, and 72-hour survival rates were recorded to evaluate L-carnitine’s effects on cardiac function. Cardiomyocytes were isolated, and a cell microtensiometer was used to detect cardiomyocyte contractile function and calcium transients. Myocardial tissues were collected from each group, and ELISA was used to determine the contents of triglyceride (TG), free fatty acid (FFA), and adenosine triphosphate (ATP). An in vitro sepsis model was constructed by stimulating HL-1 cardiomyocytes with lipopolysaccharide (LPS) for 12 hours, which was divided into 5 groups: control (CTRL) group, LPS group, L-carnitine group, L-carnitine + Eto group, and Eto group. ELISA was used to detect the contents of TG, FFA, and ATP as well as the activity of carnitine palmitoyltransferase 1A (CPT1A) in cardiomyocytes. A cellular energy metabolism analysis system was employed to measure fatty acid oxidation capacity, and Western blot was used to detect the protein expression of CPT1A in cardiomyocytes. BODIPY-FL-C16 (green fluorescently labeled palmitic acid) was utilized to detect the distribution of fatty acids in the cytoplasm and mitochondria via immunofluorescence technology, thereby observing the ability of cells to transport fatty acids into mitochondria.

Compared with the Sham group, cardiac function was significantly impaired in the Sepsis group, as evidenced by decreased ejection fraction and mean arterial pressure (P<0.05), along with elevated levels of the cardiac injury marker CK-MB (P<0.05). Treatment with L-carnitine significantly improved myocardial function, restored blood pressure in septic mice, and increased their survival rate from 12.50% to 81.25%(P<0.05). Compared with the Sham group, the contractile function and calcium transients of acutely isolated single cardiomyocytes were significantly reduced in the Sepsis group (P<0.05), while L-carnitine treatment remarkably restored the contractile function and calcium release capacity of septic cardiomyocytes (P<0.05). Both in vivo and in vitro experiments showed that TG and FFA levels were significantly increased (P<0.05), and ATP levels was significantly decreased (P<0.05) in the Sepsis and LPS groups—effects significantly reversed by L-carnitine treatment. Compared with the CTRL group, the basal oxidation rate and maximum oxidation capacity of fatty acids in cardiomyocytes of the LPS group were significantly reduced (P<0.05), and L-carnitine treatment notably improved these indicators.Compared with the CTRL group, the expression and activity of CPT1A in cardiomyocytes of the LPS group were significantly decreased (P<0.05), while L-carnitine treatment significantly increased the expression and activity of CPT1A (P<0.05). In LPS group cardiomyocytes, green fluorescently labeled palmitic acid primarily formed numerous granular/clumpy aggregates in the cytoplasm with minimal mitochondrial colocalization. In the L-carnitine group, the green fluorescent granules in the cytoplasm of cardiomyocytes were smaller, and colocalization with mitochondria was increased. However, the L-carnitine + Eto group exhibited similar phenomena to the LPS group. In addition, both in vivo and in vitro experiments demonstrated that treatment with the CPT1A inhibitor Eto reversed the effect of L-carnitine. Compared with the L-carnitine group, the ATP content in the L-carnitine + Eto group was significantly decreased (P<0.05), while the FFA content was significantly increased (P<0.05).

L-carnitine facilitates fatty acid entry into mitochondria for β-oxidation via a CPT1A-dependent mechanism, thereby ameliorating fatty acid oxidation dysfunction in septic cardiomyocytes and improving myocardial contractile function.