Cardiac Function In Rat Model Research Articles

Mitochondrial Transfer Induced by Adipose-Derived Mesenchymal Stem Cell Transplantation Improves Cardiac Function in Rat Models of Ischemic Cardiomyopathy

Although mesenchymal stem cell transplantation has been successful in the treatment of ischemic cardiomyopathy, the underlying mechanisms remain unclear. Herein, we investigated whether mitochondrial transfer could explain the success of cell therapy in ischemic cardiomyopathy. Mitochondrial transfer in co-cultures of human adipose-derived mesenchymal stem cells and rat cardiomyocytes maintained under hypoxic conditions was examined. Functional recovery was monitored in a rat model of myocardial infarction following human adipose-derived mesenchymal stem cell transplantation. We observed mitochondrial transfer in vitro, which required the formation of cell-to-cell contacts and synergistically enhanced energy metabolism. Rat cardiomyocytes exhibited mitochondrial transfer 3 days following human adipose-derived mesenchymal stem cell transplantation to the ischemic heart surface post-myocardial infarction. We detected donor mitochondrial DNA in the recipient myocardium concomitant with a significant improvement in cardiac function. Mitochondrial transfer is vital for successful cell transplantation therapies and improves treatment outcomes in ischemic cardiomyopathy.

Epac-Rap1-activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction.

Rap1, a member of Ras superfamily of small GTP-binding proteins, is involved in cardiovascular biology in numerous ways. It is an evolutionary conserved regulator of adhesion, polarity, differentiation and growth. Our aim was to analyze Rap1-activated rat bone marrow mesenchymal stem cells (MSCs) for their potential role in adhesion and cardiac differentiation. Myocardial infarction (MI) was produced in Sprague Dawley (SD) rats through occlusion of the left anterior descending coronary artery. MSCs were treated with 8-pCPT-2'-O-Me-cAMP (CPT) to activate Rap1. Normal (untreated) and CPT-treated MSCs were transplanted through intramyocardial injection in respective groups. Cardiac function was assessed by echocardiography at 2 and 4weeks after cell transplantation. Histological analysis was performed to observe changes at tissue level. Homing of CPT-treated MSCs was significantly (***P<.001) higher as compared to normal MSCs in the infarcted hearts. This may be due to increase in the gene expression of some of the cell adhesion molecules as evident by qRT-PCR analysis. Significant (***P<.001) improvement in the restoration of heart function in terms of left ventricular diastolic and systolic internal diameters (LVIDd, LVIDs), % ejection fraction, % fraction shortening and end-systolic and end-diastolic volumes were observed in CPT-treated MSCs as compared to the MI model. Histological analyses showed significant (***P<.001) reduction in scar formation in the CPT-treated group. Differentiation of treated MSCs into functional cardiomyocytes was evident through immunohistochemical staining. LV wall thickness was also preserved significantly (***P<.001). Blood vessel formation was more pronounced in CPT-treated group although both cell therapy groups showed significant increase as compared to MI model. Our findings showed that pharmacological activation of Epac-Rap1 improves cardiac function through better survival, adhesion and differentiation of transplanted cells. Transplantation of these MSCs in the infarct area restored functional myocardium.

Effects of aerobic exercise on antioxidants in rat models with cardiomyopathy

Objective: In this study, we aimed to test the hypothesis that aerobic exercise might exert its cardio-protective effect by preventing oxidative stress and improving cardiac function in rat models with doxorubicin-induced cardiomyopathy. Design: Randomized controlled trial. Methods: We randomly divided experimental rats into four groups: the normal group was used as a non-cardiomyopathy normal control (n=10); the control group included non-aerobic exercise after doxorubicin-induced cardiomyopathy (n=10); the experimental group I included aerobic exercise (3 m/min) after doxorubicin-induced cardiomyopathy (n=10); and experimental group II included aerobic exercise (8 m/min) after doxorubicin-induced cardiomyopathy. Rats in the treadmill training groups underwent treadmill training, which began at 2 weeks after the first intraperitoneal injection. At the end of the exercise period, we determined the heart weight change for each rat. Changes in the levels of oxidative stress enzymes (superoxide dismutase [SOD], thiobarbituric acid-reactive substances [TBARS], and catalase) in the cardiac tissue of rats from all four groups were examined at the end of the experiment. Results: Significant cardiac myocyte injury and increase in myocardial TBARS concomitant with a reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Significant cardiac tissue and increase in myocardial TBARS along with reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Oxidative parameters were significantly improved in the aerobic exercise groups compared with the control group. Conclusions: These findings indicate that aerobic exercise effectively prevents oxidative stress in rat models with cardiomyopathy.

Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM). Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg−1·day−1 (TXL-H, n = 9) or 0.15 g·kg−1·day−1 (TXL-L, n = 10) of tongxinluo, or normal saline at the same volume (DCM-C, n = 10) intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n = 9). After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD) increased in the TXL-H group compared with the DCM-C group (all P < 0.01). Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r = −0.683, P < 0.05), MVD and LVEF (r = 0.895, P < 0.05), and MVD and CVF (r = −0.798, P < 0.05). It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.

Q50, an Iron-Chelating and Zinc-Complexing Agent, Improves Cardiac Function in Rat Models of Ischemia/Reperfusion-Induced Myocardial Injury

Reperfusion of ischemic myocardium may contribute to substantial cardiac tissue damage, but the addition of iron chelators, zinc or zinc complexes has been shown to prevent heart from reperfusion injury. We investigated the possible beneficial effects of an iron-chelating and zinc-complexing agent, Q50, in rat models of ischemia/reperfusion (I/R)-induced myocardial infarction and on global reversible myocardial I/R injury after heart transplantation. Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24h reperfusion. Vehicle or Q50 (10 mg/kg, IV) were given 5 min before reperfusion. In a heart transplantation model, donor rats received vehicle or Q50 (30 mg/kg, IV) 1h before the onset of ischemia. In myocardial infarcted rats, increased left ventricular end-systolic and end-diastolic volumes were significantly decreased by Q50 post treatment as compared with the sham group. Moreover, in I/R rat hearts, the decreased dP/dtmax and load-independent contractility parameters were significantly increased after Q50. However, Q50 treatment did not reduce infarct size or have any effect on increased plasma cardiac troponin-T-levels. In the rat model of heart transplantation, 1h after reperfusion, decreased left ventricular systolic pressure, dP/dt(max), dP/dt(min) and myocardial ATP content were significantly increased and myocardial protein expression of superoxide dismutase-1 was upregulated after Q50 treatment. In 2 experimental models of I/R, administration of Q50 improved myocardial function. Its mechanisms of action implicate in part the restoration of myocardial high-energy phosphates and upregulation of antioxidant enzymes.

Marrow-derived MSCs and atorvastatin improve cardiac function in rat model of AMI

Objective Both atorvastatin and cell-based therapy were reportedly beneficial to ventricular function after acute myocardial infarction (AMI). In this study, we sought to study the synergistic effects of marrow-derived mesenchymal stromal cells (MSCs) and atorvastatin in a rat model of AMI. Methods To create a rat model of AMI, left anterior descending artery (LAD) ligations were performed on 40 Sprague–Dawley (SD) rats. After the establishment of AMI, animals were randomly divided into 4 groups to receive variant treatments: control, MSCs only, atorvastatin only, and MSCs plus atorvastatin, with 10 animals in each group. Results Four weeks following the treatments, the hemodynamic testing showed significant functional improvement in animals that received MSCs plus atorvastatin compared with controls, MSCs or atorvastatin only treated animals. Histological analysis showed more MSCs were present in animals receiving combination therapy than in animals which received MSCs alone. Vessel density was higher in animals receiving combination therapy than in other groups. Discussion These results suggest that either atorvastatin or MSCs cannot individually improve ventricular function significantly. However, atorvastatin synergistically enhanced the beneficial effects of MSCs in the treatment of AMI.

In vivo assessment of resting and catecholamine stimulated cardiac function in rat models of low and high aerobic running capacity

Our laboratory has previously identified inbred rat strains divergent for aerobic running capacity (ARC); low performing Buffalo (BUF) and high performing DA rats. Subsequent studies of isolated DA and BUF hearts showed a strong correlation between ARC and cardiac output (CO). In the present study, we tested the hypotheses that 1) there is increased in vivo basal LV function in DA compared with BUF rats and 2) the cardiac response to catecholamine stress is increased in DA vs. BUF rats. A high‐fidelity microtip pressure‐volume catheter was used to examine cardiac function in intact male BUF (n=13) and DA (n=12) rats at rest and during dobutamine infusion. Resting DA hearts outperformed BUF hearts as evidenced by a significantly higher cardiac output (39±2 vs 63±6 mL/min, P&lt;0.05) and contractility index (136±4 vs 154±7 mmHg2/sec, P&lt;0.05). Following dobutamine infusion (10μg/kg/min), CO was significantly greater in DA compared to BUF rats (50±2 vs 92±9 mL/min, P&lt;0.05). DA rats showed a greater increase in stroke volume whereas BUF rats displayed a greater increase in heart rate following dobutamine infusion (Figure). We conclude that cardiac function is greater at rest in DA compared to BUF rats, and that DA and BUF hearts differ in their response to catecholamine stress.This work was supported by NIH grant HL67276 (GTC) and a Medical Student Research Fellowship from The University of Toledo College of Medicine (EEM).

Carvedilol improved the mortality and the reduction in cardiac function in rat models of adriamycin-induced cardiomyopathy

Carvedilol improved the mortality and the reduction in cardiac function in rat models of adriamycin-induced cardiomyopathy

Systolic time intervals as indicators for cardiac function in rat models for heart failure

Measurement of the pre-ejection period (PEP) can give valuable information on myocardial function in rats. Depressed cardiac function is accompanied by prolongation of PEP, which shortens when cardiac function improves. Left ventricular ejection time (LVET) may be shortened with ageing in spontaneously hypertensive rats.