Neurochemical alterations of different cerebral regions in rats with myocardial ischemia-reperfusion injury based on proton nuclear magnetic spectroscopy analysis.

BACKGROUND: Recent studies have demonstrated a complex and dynamic neural crosstalk between the heart and brain. A heart-brain interaction has been described regarding cardiac ischemia, but the cerebral metabolic mechanisms involved are unknown. METHODS: Male Sprague Dawley rats were randomly allocated into 2 groups: those receiving myocardial ischemia-reperfusion surgery (IR group, n =10) and surgical controls (Con group, n=10). These patterns of metabolic abnormalities in different brain regions were assessed using proton magnetic resonance spectroscopy (PMRS). RESULTS: Results assessed by echocardiography showed resultant cardiac dysfunction following heart ischemia-reperfusion. Compared with the control group, the altered metabolites in the IR group were taurine and choline, and differences mainly occurred in the thalamus and brainstem. CONCLUSIONS: Alterations in cerebral taurine and choline are important findings offering new avenues to explore neuroprotective strategies for myocardial ischemia-reperfusion injury. These results provide preliminary evidence for understanding the cerebral metabolic process underlying myocardial ischemia-reperfusion injury in rats.

Quantitative proteomics reveal the alterations in the spinal cord after myocardial ischemia­reperfusion injury in rats.

There is now substantial evidence that myocardial ischemia­reperfusion (IR) injury affects the spinal cord and brain, and that interactions may exist between these two systems. In the present study, the spinal cord proteomes were systematically analyzed after myocardial IR injury, in an attempt to identify the proteins involved in the processes. The myocardial IR injury rat model was first established by cross clamping the left anterior descending coronary artery for 30­min ischemia, followed by reperfusion for 2 h, which resulted in a significant histopathological and functional myocardial injury. Then using the stable isotope dimethyl labeling quantitative proteomics strategy, a total of 2,362 shared proteins with a good distribution and correlation were successfully quantified. Among these proteins, 33 were identified which were upregulated and 57 were downregulated in the spinal cord after myocardial IR injury, which were involved in various biological processes, molecular function and cellular components. Based on these proteins, the spinal cord protein interaction network regulated by IR injury, including apoptosis, microtubule dynamics, stress­activated signaling and cellular metabolism was established. These heart­spinal cord interactions help explain the apparent randomness of cardiac events and provide new insights into future novel therapies to prevent myocardial I/R injury.

Mapping Changes of Whole Brain Blood Flow in Rats with Myocardial Ischemia/Reperfusion Injury Assessed by Positron Emission Tomography.

18F-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) is the most sensitive tool for studying brain metabolism in vivo. We investigated the image patterns of 18F-FDG PET during reperfusion injury and correlated changes of whole brain blood flow utilizing a rat myocardial ischemia/reperfusion injury (MIRI) model. The results assessed by echocardiography indicated resultant cardiac dysfunction after ischemia-reperfusion in the rat heart. It was found that the average standardized uptake value (SUVaverage) of the whole brain was significantly decreased in model rats, and the glucose uptake of different brain regions including accumbens core/shell (Acb), left caudate putamen (LCPu), hippocampus (HIP), left hypothalamus (LHYP), olfactory (OLF), superior colliculus (SC), right midbrain (RMID), ventral tegmental area (VTA), inferior colliculus (IC) and left thalamus whole (LTHA) was significantly decreased in MIRI rats whereas no significant difference was found in the SUVaverage of amygdala (AMY), right CPu, RHYP, right HYP, left MID, right THA, pons and medulla oblongata (MO). These 18F-FDG PET data provide a reliable identification method for brain metabolic changes in rats with MIRI.

Alterations in amino acid levels and metabolite ratio of spinal cord in rat with myocardial ischemia-reperfusion injury by proton magnetic resonance spectroscopy.

OBJECTIVES: The mechanism behind spinal metabolites and myocardial ischemia-reperfusion (IR) injury is not well understood. Proton magnetic resonance spectroscopic analysis of spinal cord extracts provides a quick evaluation of the specific metabolic activity in rats with myocardial IR injury. We investigated the relationship between the IR-related variables and the changes in spinal metabolites. METHODS: Proton magnetic resonance spectroscopy (1H-MRS) was used to assess the spinal metabolites of adult rats with and without myocardial IR injury (n = 6 per group). Myocardial IR injury was reproduced using intermittent occlusion of the left anterior descending coronary artery. We studied the relationship between the metabolite ratio measurement and IR-related variables. All rats underwent 1H-MRS, with the ratio of interest placed in different spinal cord segments to measure levels of twelve metabolites including N-acetylaspartate (NAA), taurine (Tau), glutamate (Glu), gamma amino acid butyric acid (GABA), creatine (Cr), and myoinositol (MI), etc. Results: Rats with myocardial IR injury had higher concentration of Tau in the upper thoracic spinal cord (P < 0.05), and lower concentration of Gly and Glu in the cervical segment of the spinal cord (P < 0.05), when compared to the Control group. The ratios of glutamate/taurine (Glu/Tau), Glu/(GABA + Tau) and Glu/Total were significantly different between the IR group and the Control group in the upper thoracic spinal cord (P < 0.05). So were the ratios of Glu/(GABA + Tau) in the cervical segment (P < 0.05), and Glu/Tau and Glu/(GABA + Tau) in the lower thoracic spinal cord (P < 0.05). CONCLUSIONS: These findings suggest that myocardial IR injury may be related to spinal biochemical alterations. It is speculated that these observed changes in the levels of spinal metabolites may be involved in the pathogenesis and regulation of myocardial IR injury.

Identification of lncRNA and mRNA expression profiles in rat spinal cords at various time­points following cardiac ischemia/reperfusion.

The identification of the expression patterns of long non­coding RNAs (lncRNAs) and mRNAs in the spinal cord under normal and cardiac ischemia/reperfusion (I/R) conditions is essential for understanding the genetic mechanisms underlying the pathogenesis of cardiac I/R injury. The present study used high­throughput RNA sequencing to investigate differential gene and lncRNA expression patterns in the spinal cords of rats during I/R­induced cardiac injury. Male Sprague Dawley rats were assigned to the following groups: i) Control; ii) 2 h (2 h post­reperfusion); and iii)v0.5 h (0.5 h post­reperfusion). Further mRNA/lncRNA microarray analysis revealed that the expression profiles of lncRNA and mRNA in the spinal cords differed markedly between the control and 2 h groups, and in total 7,980 differentially expressed (>2­fold) lncRNAs (234 upregulated, 7,746 downregulated) and 3,428 mRNAs (767 upregulated, 2,661 downregulated) were identified. Reverse transcription­quantitative polymerase chain reaction analysis was performed to determine the expression patterns of several lncRNAs. The results indicated that the expression levels of lncRNA NONRATT025386 were significantly upregulated in the 2 and 0.5 h groups when compared with those in the control group, whereas the expression levels of NONRATT016113, NONRATT018298 and NONRATT018300 were elevated in the 2 h group compared with those in the control group; however, there was no statistically significant difference between the 0.5 h and control groups. Furthermore, the expression of lncRNA NONRATT002188 was significantly downregulated in the 0.5 and 2 h groups when compared with the control group. The present study determined the expression pattern of lncRNAs and mRNAs in rat spinal cords during cardiac I/R. It was suggested that lncRNAs and mRNAs from spinal cords may be novel therapeutic targets for the treatment of I/R­induced cardiac injury.

Application of animal and human PET in cardiac research.

PURPOSE OF REVIEW: After a warm-up period of imaging research, several modalities of positron emission tomography (PET) are under development for evaluating ischemic heart disease. RECENT FINDINGS: Several types of well-documented stem/progenitor PET imaging have been utilized for changes in myocardial blood flow and carbohydrate metabolism. Some recent experimental and human studies reported that these data may have beneficial effects on cardiac research. SUMMARY: Although the role of PET in the pathology of ischemic heart disease has not been sufficiently elucidated, many studies attempting imaging research of myocardial metabolism and neural regulation have been reported. Further studies are needed to better evaluate the potential of PET in evaluating ischemic heart disease.

Melanocortin-4 receptor expression in autonomic circuitry involved in gastric function.

Several studies have shown that CNS provides the regulation of gastric functions. Recent evidence indicated that the activation of melanocortin 4 receptors (MC4R) in brain nuclei played an important role in modulating gastric activity. This study was designed to assess whether MC4R signaling existed in autonomic circuitry modulated the activity of stomach by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV)-614 was injected into the ventral stomach wall in adult male MC4R-green fluorescent protein (GFP) transgenic mice (n = 5). After a survival time of 5 days, the mice were assigned to humanely sacrifice, and spinal cords and caudal brainstem were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the stomach were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML and the dorsal motor nucleus of the vagus nerve (DMV). Our findings support the hypothesis that MC4R signaling in autonomic circuitry may participate in the modulation of gastric activity by the melanocortinergic-sympathetic pathway or melanocortinergic-parasympathetic pathway.

[Hemodynamic variations during tracheal intubation with intubating laryngeal mask airway versus direct laryngoscope in hypertensive patients].

OBJECTIVE: To compare the variations of cardiovascular responses and vascular angiotensin II (AngII) in hypertensive patients during tracheal intubation with intubating laryngeal mask airway (ILMA) versus direct laryngoscope (DLS). METHODS: A total of 120 hypertensive patients undergoing abdominal surgery were randomly divided into 2 groups, i.e.intubating laryngeal mask airway (Group I) and direct laryngoscope (Group D).Variations of invasive arterial blood pressure and angiotensin II were compared between two groups before and after intubation. RESULTS: The variations of cardiovascular responses and vascular angiotensin II (AngII) during tracheal intubation used of ILMA (T4) and DLS (T4) in an instant, tracheal intubation were immediately accomplished in two groups (T5). The variations of group I were significantly lower than those of group D (P < 0.05). And statistical significance existed between two groups. CONCLUSION: Tracheal intubation with intubating laryngeal mask airway (ILMA) can significantly reduce violent cardiovascular reactions and avoid cardiovascular accidents.