Cells In Left Ventricle Research Articles

Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of Alzheimer's disease.

Systemic organ dysfunction is one of the important issues for the patients with Alzheimer's disease (AD) and their caregivers. Recent evidences suggest that periodontitis is a possible risk factor for progression of AD and lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) which is a major periodontopathic bacteria induces cognitive impairment in mice. However, the precise relationships between the brain exposure of Pg-LPS and systemic organ dysfunction in AD patients are still undetermined. In this study, we investigated whether brain exposure of Pg-LPS induced systemic organ dysfunction in a model of AD mouse. We employed 6 (young) and 13 (middle-aged) months-old 5XFAD mice and 6 months-old littermate (LT) mice, and treated with intracerebroventricular (ICV) injection of 2 μg Pg-LPS or saline (vehicle). The animals were monitored cognitive functions (Y maze, nest building, and Morris water maze tests), motor functions (wire hang and rotarod tests), physical condition (symptom score), and blood pressure (BP). Twenty-eight days later, their organs were weighted and the organ damages were examined. Continuous ICV injection of 2 μg/day Pg-LPS increased ionized calcium binding adapter molecule-1 (Iba-1) and cluster of differentiation 3 (CD3) positive cells in periventricular area of 5XFAD mice without enhancement of cognitive impairment, amyloid β protein deposition, expressions of phosphorylated nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (COX-2). In addition, the Pg-LPS lowered the latency of rotarod test in young 5XAD mice and also reduced symptom score and weight of gastrocnemius muscle in the middle-aged animals. Moreover, the Pg-LPS induced cardiac atrophy in both young and middle-aged 5XFAD mice, and increased Iba-1 positive cells in left ventricle of the young animals. On the other hand, single ICV injection of 2 μg Pg-LPS in 5XFAD and continuous injection of 2 μg/day Pg-LPS in LT mice did not show any positive findings. Our present results demonstrated that continuous brain exposure of Pg-LPS started sarcopenia and cardiac injury without enhancing cognitive impairment in AD model mice.

Effects of regular exercise plus food restriction on left ventricular pathological remodeling in heart failure‑induced rats.

Cardiac remodeling is the main pathophysiological process leading to heart failure. Exercise and food restriction have been shown to exert some profound physiological benefits. This study investigated the effects of exercise plus food restriction (FR) on rat left ventricular remodeling. Fifty male rats were randomly divided into 5 groups. 1) Sham (saline injection), 2) ISO (isoproterenol injection), 3) FR+ ISO (8 weeks with 60 % food restriction and then isoproterenol injection), 4) E+ISO (run-in period of 4 weeks on treadmill and then isoproterenol injection), and 5) FR+E+ISO. Serum levels of creatine kinase, nitric oxide, gene expression of microtubule-associated protein 1 light chain 3-I and II, Beclin-1, Bax and Bcl2 and TUNEL staining were investigated. ISO increased the plasma CK-MB level, gene expression of Bax and TUNEL‑positive cells in left ventricle and at the same time, decreased the serum level of NO. Regular exercise plus food restriction enhanced the expression of LC3B-II, Beclin-1, Bcl2 genes and elevated LC3B-II / LC3B-Ι, while decreasing the gene expression of Bax and TUNEL‑positive cells in the left ventricle. Our results propose that exercise plus food restriction is more effective than either therapy alone for possibly preserving cardiac internal defenses against heart failure consequences and remodeling (Tab. 2, Fig. 3, Ref. 20).

High-throughput Study of Rabbit Ventricle Action Potential Populations in MI Model

Background: Electrical activity in isolated cardiomyocytes has been widely studied using patch clamping, which offers limited throughput. Using voltage- and calcium-sensitive dyes, the electrical activity, calcium dynamics and contractility profile of cells can be measured simultaneously in approximately 100 cells per heart. This feature provides further insight into the mechanisms of excitation-contraction coupling in the failing heart. Moreover, this high-throughput methodology allows the study of large cell populations in individual hearts, offering a quantitative measure of cellular and regional heterogeneity, otherwise obscured by animal variation and undersampling. Methods: Adult rabbit cardiomyocytes were isolated from the left ventricle of infarcted (MI), control (Sham), and stock rabbits, loaded with the fluorescent, voltage-sensitive dye FluoVolt® (1:6000), and plated on to 35mm glass-bottomed plates (Krebs solution at 37°C; 1.8mM CaCl2). Left ventricle cells were serially paced at 1Hz, 2Hz and 3Hz using field stimulation (2x20mm graphite electrodes; 40V, 2ms pulse width). Separately isolated cells originating from either epicardium or endocardium were paced at 2Hz. A 10s action potential train was recorded from each cell. Results: The methodology corroborates previously published work showing an increase in mean APD90 in MI at slow rates. Mean APD90 in MI (Nanimals=6, ncells=450-800) was 374±11ms, 287±4ms, and 208±4ms at 1Hz, 2Hz and 3Hz, respectively. Mean APD90 in Sham was 336±16ms, 252±6ms, 206±1ms, at 1Hz, 2Hz, and 3Hz, respectively (Mean±S.E.M). Regional analyses (Nanimals=9, ncells=554) found AP90 was shortened in the epicardium vs. the endocardium in stock (21±6ms difference) and sham animals (37±10ms), while this difference was entirely lost in MI (P=0.323). Moreover, epicardial cell populations showed consistently higher variability than endocardial cells, across all experimental groups. This technique consequently provides accurate quantification of biological variation in individual hearts and heart regions, suggesting a strong potential for drug screening assays.

Abstract P109: Spiny Mice Are Protected From Myocardial Infarction Induced Cardiac Pathophysiology

Background: Despite the advancement in drug and surgical interventions, myocardial damage and associated cardiac dysfunction lead to heart failure that remains common cause of death following myocardial infarction (MI). Spiny mice (Acomys cahirinus, SM) have been shown to possess regenerating capacity following deep tissue injury without scarring ( Nature 2013 ). This led us to investigate if this regenerative property would also be preserved in the heart. Methods and Results: Adult CD1 and SM were subject to left anterior descending coronary artery ligation or sham surgeries. Proliferative cells were identified by nuclear incorporation of 5-bromodeoxyuridine (BrdU, daily, i.p.) and injection was started from 3d post MI continued to 2wks post MI. Cardiac function was assessed using echocardiography and MRI. SM exhibited 3-fold smaller infarct size (SM-MI 18.6±3.4% vs CD1-MI 76.2±3.4%, p<0.05) and better contractility measured by ejection fraction (SM-MI 77.1±6.5 vs CD1-MI 24.6±4.6, %, p<0.05) than CD1 mice. SM showed 6-fold increase in BrdU + cells in left ventricle after MI while CD1 mice had 4-fold increase (CD1-sham 11±3.5 vs CD1-MI 44±9.1 and SM-sham 16±9.8 vs SM-MI 101.1±30.9, p<0.05). Though basal cardiac ACE2 activity was not different between CD1 and SM, MI resulted in a 16% decrease in cardiac ACE2 activity in CD1-MI mice but 20% elevation of cardiac ACE2 activity in myocardial tissue in SM-MI. Conclusions: SM are protected from ischemia induced cardiac damage and dysfunction. This involves increased proliferating cardiac cells and reduction in infarct size. Thus SM could be an ideal animal model for identification of molecular and genetic circuits involved in preservation/regeneration of cardiac function with translational implication to human MI.

Isoproterenol sensitivity of isolated cardiac myocytes from rats with monocrotaline-induced right-sided hypertrophy and heart failure

Rats treated with the alkaloid monocrotaline developed right ventricular hypertrophy with a left: right ventricle weight ratio of 1.35 ± 0.10 (mean ± s.e.m., n = 25) compared with 3.83 ± 0.40 ( n = 14) in diet-matched controls ( P < 0.001). Urine volume and sodium content were reduced and body water increased consistent with heart failure. In 10 out of 26 treated rats pleural, pericardial or peritoneal effusions were present. Urine norepinephrine content was significantly raised ( P < 0.02) but epinephrine was unchanged. Plasma norepinephrine levels were raised though not significantly. Myocytes isolated from the right ventricle had a reduced myosin Ca 2+-activated ATPase ( P < 0.05) activity and a shift towards slower V2 and V3 myosin isofroms. There was no decrease in maximum contraction amplitude with calcium or isoproterenol in either left or right ventricular cells of treated rats. Right ventricular cells from treated rats showed a reduced rate of contraction in maximum isoproterenol ( P < 0.05) and a significant rightward shift in PD 2 ( P < 0.05) representing a two-fold increase in EC50 for isoproterenol compared with right ventricular cells from control animals. There was no shift in EC50 for isoproterenol in left ventricle cells. In parallel experiments, myocytes isolated from both ventricles of rats treated with isoproterenol for one week showed a rightward shift of more than 50-fold in the isoproterenol concentration-response curve and a depressed response to maximum isoproterenol. In the rat monocrotaline model of right-sided cardiac hypertrophy and failure, changes in sensitivity to beta-adrenoceptor agonists are slight, and present only in the right ventricle. The lack of change in the left ventricle seems to suggest that this functional desensitisation is not a consequence of raised circulating catecholamines.

Experimental Studies on the Influence of Positive Acceleration upon Streaming Blood.

Experiments were carried out on rabbits. In preliminary studies, proved that the reliability of the counting red blood cells were in following order, i.e. 1. spectrophotometry by cyanhematin method 2. direct counting. 3. calculating from total Fe ions estimated and 4. colorimetry by Sahli's method. In cases of dead animals by the influence of acceleration, remarkable anemia was observed in head and the other hand, clotted blood was seen in periphery. Numbers of red cells in V. renalis decreased in left side but increased in right side. Red cells in left ventricle increased while those in right ventricle decreased. The phenomenon seemed to cause from the morphological and anatomical factors. Causes of death of animals were bleeding in parenchymatous organs by physical injury or injuries from static pressure and anemic and anoxic hypoxia in brain cortex.