Acute Myocardial Infarction Reduces Respiration in Rat Cardiac Fibers, despite Adipose Tissue Mesenchymal Stromal Cell Transplant

Adipose-derived mesenchymal stromal cell (AD-MSC) administration improves cardiac function after acute myocardial infarction (AMI). Although the mechanisms underlying this effect remain to be elucidated, the reversal of the mitochondrial dysfunction may be associated with AMI recovery. Here, we analyzed the alterations in the respiratory capacity of cardiomyocytes in the infarcted zone (IZ) and the border zone (BZ) and evaluated if mitochondrial function improved in cardiomyocytes after AD-MSC transplantation. Female rats were subjected to AMI by permanent left anterior descending coronary (LAD) ligation and were then treated with AD-MSCs or PBS in the border zone (BZ). Cardiac fibers were analyzed 24 hours (necrotic phase) and 8 days (fibrotic phase) after AMI for mitochondrial respiration, citrate synthase (CS) activity, F0F1-ATPase activity, and transmission electron microscopy (TEM). High-resolution respirometry of permeabilized cardiac fibers showed that AMI reduced numerous mitochondrial respiration parameters in cardiac tissue, including phosphorylating and nonphosphorylating conditions, respiration coupled to ATP synthesis, and maximal respiratory capacity. CS decreased in IZ and BZ at the necrotic phase, whereas it recovered in BZ and continued to drop in IZ over time when compared to Sham. Exogenous cytochrome c doubled respiration at the necrotic phase in IZ. F0F1-ATPase activity decreased in the BZ and, to more extent, in IZ in both phases. Transmission electron microscopy showed disorganized mitochondrial cristae structure, which was more accentuated in IZ but also important in BZ. All these alterations in mitochondrial respiration were still present in the group treated with AD-MSC. In conclusion, AMI led to mitochondrial dysfunction with oxidative phosphorylation disorders, and AD-MSC improved CS temporarily but was not able to avoid alterations in mitochondria function over time.

Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria

Fatty acids are the main respiratory substrates important for cardiac function, and their oxidation is altered during various chronic disorders. We investigated the mechanism of fatty acid–oxidation-induced changes and their relations with mitochondrial morphology and ADP/ATP carrier conformation on the kinetics of the regulation of mitochondrial respiration in rat skinned cardiac fibers. Saturated and unsaturated, activated and not activated, long and medium chain, fatty acids similarly decreased the apparent KmADP. Addition of 5% dextran T-70 to mimic the oncotic pressure of the cellular cytoplasm markedly increased the low apparent KmADP value of mitochondria in cardiac fibers respiring on palmitoyl-l-carnitine or octanoyl-l-carnitine, but did not affect the high apparent KmADP of mitochondria respiring on pyruvate and malate. Electron microscopy revealed that palmitoyl-l-carnitine oxidation-induced changes in the mitochondrial ultrastructure (preventable by dextran) are similar to those induced by carboxyatractyloside. Our data suggest that a fatty acid oxidation-induced conformational change of the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier (M-state to C-state, condensed to orthodox mitochondria) may affect the oxidative phosphorylation affinity for ADP.

The method of determining the number of excited efferent cardiac fibers in the vagus nerve of a cat

Objective: Developing method of determination the number of excited efferent cardiac fibers in the cervical region of the vagus nerve of a cat by estimating the area of the glow in the high-frequency electromagnetic field inside the nerve. Materials and methods: The observations were carried out on cats in conditions of superficial (27 cats) or deep anesthesia (13 cats out of 27) and irritation of the vagus nerve with electrical impulses (14 cats out of 27). The right vagus nerve on cat’s neck was allocated and cut at the level of the lower edge of thyroid cartilage. The central end was inserted into a glass tube. Before the cut end in the transverse plane, a scanner from the unit, which creates a high-frequency electromagnetic field was installed. The glow from the scanner were recorded by a video camera through the microscope. At the same time, the ECG was recorded. Based on the ECG signal, for the processing we took the centers of glow related to the heart rhythm. The results were processed in the "STATISTIKA 6.0" program. Results: In superficial anesthesia, the number of excitable efferent fibers was 350 or 70.0% of the available ones. In case of deep anesthesia, 193 or 38.6% accordingly. In case of nerve stimulation above the transection site all available efferent fibers have been excitable. Conclusions: Results of this work suggest a way to identify and determine the number of excitable efferent cardiac fibers in the vagus nerve and their localization on the cross section of the central end of the nerve from the area of luminescence in high-frequency electric field.

Histopathological study of different organs of charles foster strain rat under the exposure of Pueraria tuberosa

ObjectiveThe present study was undertaken to investigate the safe doses of Pueraria tuberosa water extract (PTWE) on different organs.MethodologyHaematoxylin and eosin staining was used to study the morphological alterations in heart, intestine, testis, adrenal gland and spleen. Followed the OECD guidelines 407 of repeated toxicity with respect to the selection of dose and days for different organs. The selected doses of PTWE were 250, 500, 1000 and 2000 mg/kg bw and the durations selected were 7, 14, 21 and 28 days.ResultAccording to the obtained results, we have found no any types of adverse alteration in cardiac fibers of the heart, size and shapes in crypts and villi of intestine, semeniferous tubules and spermatozoa count were normal in testis, all three zones of adrenal gland were normally identified and no any adverse sign of pulps in spleen was seen in all treated groups of PTWEConclusionThere was no any types of adverse morphological alteration found in any organs. The drug PTWE are safe at 1000 mg/kg bw upto 28 days and 2000 mg/ kg bw upto 21 days respectively.