Cardiac Function In Rabbits Research Articles

Улучшение функции сердца у кроликов с хронической сердечной недостаточностью под действием метилина

To study effects of intravenous infusion of a cardioprotective drug metilin, developed at the "National Medical Research Center of Cardiology" on indices of cardiac function in rabbits in vivo after prolonged administration of doxorubicin. Animals of the experimental group were intravenously injected with doxorubicin (2 mg / kg once a week) for 8 weeks, animals of the control group received the same volume of saline. Myocardial damage was characterized by an increase in concentration of malondialdehyde (MDA), troponin (TnI) and MB-fraction of creatine kinase (CK-MB) in venous blood and by disturbances in the left ventricle (LV) structure at morphological examination. Metilin effects on cardiac function were assessed by echocardiography and LV catheterization by the Millar catheter tip pressure transducer. Doxorubicin administration led to a decrease of the body mass of animals, an increase of the plasma concentration of cardiac markers CK-MB and TnI, lipid peroxidation (LPO) product MDA in venous blood, and pronounced disturbances in the structure of LV fibers and microvessels. At the same time, a significant decrease of myocardial contractility indices was observed. Manifestations of this decrease were increase of the end-diastolic and end-systolic dimensions (EDD and ESD, respectively), and decreases in the shortening fraction and ejection fraction (SF and EF, respectively) compared to baseline values. These changes indicated development of chronic heart failure (CHF) in animals of the experimental group. Against this background, intravenous infusion of metilin significantly increased SF and EF, but did not affect the heart rate. Beneficial effects of metilin on the indices of cardiac contractility and relaxation were maintained after the infusion was stopped. Noteworthy, metilin exerted greater influence on cardiac function of rabbits with CHF compared to control animals that did not receive doxorubicin. The obtained results indicate the potential of metilin to reduce LV dysfunction during chemotherapy with doxorubicin.

Effects of different doses of simvastatin on connective tissue growth factor and osteoprotegerin of immature rabbits with chronic heart failure

Objective To observe the effects of different doses of simvastatin on immature rabbit models of chronic heart failure(CHF) and to explore the mechanism of simvastatin in the rabbits with CHF. Methods Sixty male immature rabbits were randomly divided into 5 groups: control(CON) group, CHF group, small-dose simvastatin(SD-SIM) group, medium-dose simvastatin(MD-SIM) group, and the high-dose simvastatin(HD-SIM) group, 12 cases in each group.The models of CHF were established by injecting adriamycin(ADR) via the auricular vein of rabbits.In the first injection of ADR, simvastatin tablets [concentration of 0.3, 1.5, 3.0 mg/(kg·d), respectively] were given to the rabbits by intragastric administration for SD-SIM, MD-SIM, and HD-SIM models.The general conditions of immature rabbits in experiment group were evaluated.Hemodynamic data were detected.HE staining was used to observe structure of myocardial cells.The plasma level of osteoprotegerin(OPG) was measured by enzyme-linked immunosorbent assay (ELISA). The expression of connective tissue growth factor(CTGF) was evaluated by immunohistochemical assay. Results 1.In CON group, the rabbits were all alive; in CHF, SD-SIM, MD-SIM and HD-SIM groups, most immature rabbits had skinchapped, unhaired and sluggish with hyperkeratosis, diet reduction, and losing weight.Overall survival rate was 76.7%.2.Hemodynamic data indicated that the + dp/dtmax, -dp/dtmax and the left ventricular systolic pressure (LVSP) in the SD-SIM, HD-SIM and CHF groups dropped significantly compared with the CON group (all P<0.05). There was a remarkable increase in the SD-SIM, HD-SIM and MD-SIM groups compared with CHF group (all P<0.01); and there was a remarkable drop in the cardiac function of the SD-SIM and HD-SIM groups compared with MD-SIM group (P<0.05).3.Compared with the CON group, CTGF and OPG expression in the SD-SIM, MD-SIM, HD-SIM and CHF groups increased significantly (P<0.01), while the expression in the SD-SIM, MD-SIM and HD-SIM groups decreased significantly compared with that of the CHF group (P< 0.05). Compared with the MD-SIM group, the expression of CTGF and OPG in the SD-SIM and HD-SIM groups increased significantly (P<0.05). Conclusions Simvastatin can improve cardiac function of rabbits with CHF significantly, and the effect on MD-SIM group is the best.The mechanism of simvastatin may depress the expressions of CTGF and OPG.CTGF and OPG can predict CHF. Key words: Simvastatin; Chronic heart failure; Connective tissue growth factor; Osteoprotegerin

Cardiotoxicity in rabbits after a low-level exposure to diazinon, propoxur, and chlorpyrifos.

Lethal cardiac complications leading to death and various arrhythmias have been reported after organophosphate and/or carbamate poisonings. The present study focuses on the long-term effects of repeated low-level exposure to diazinon, propoxur, and chlorpyrifos (CPF) on cardiac function in rabbits. The yearly based experimental scheme of exposure consisted of two oral administration periods, lasting 3 months and 1 month each, interrupted by an 8-month washout period (total duration 12 months). At the end of the experimental scheme, the rabbits underwent an echocardiographic evaluation under sedation, after which they were killed and the tissue and serum samples were collected. A mild localized cardiotoxic effect was established by echocardiography for the three pesticides tested. Severe histological alterations were identified, especially in the diazinon-treated animals in agreement with increased persistence of this pesticide established in the cardiac tissue. In addition, all pesticides tested increased the oxidative stress and oxidative modifications in the genomic DNA content of the cardiac tissues, each one following a distinct mechanism.

Effects of right stellate ganglion block on expression of .BETA.3-adrenoceptor in rabbits with heart failure

Objective To evaluate the effects of the right stellate ganglion block on the expression of β3adrenoceptor (β3-AR) in rabbits with heart failure.Methods Forty-eight Japanese white rabbits of both sexes,weighing 2.5-3.0 kg,were randomly divided into 3 groups (n =16 each):sham operation group (group S),heart failure group (group HF) and right stellate ganglion block group (group RSGB).Heart failure was induced by occlusion of left anterior descending branch of coronary artery and confirmed by ultrasonic cardiography 4 weeks later.A PE-10 catheter was inserted into the right stellate ganglion for administration of drugs.0.25％ bupivacaine 2 ml was injected through the catheter once a day for 2 weeks in group RSGB,while the equal volume of normal saline was injected instead of bupivacaine in S and HF groups.The left ventricular end-diastolic diameter (LVEDD),left ventricular end-systolic diameter (LVESD),ejection fraction (EF) and left ventricular fractional shortening (LVFS) were measured at 1 day before ligation (T0),before catheter insertion (T1),before 8th administration (T2),and 1 day after the last administration (T3).Eight rabbits were sacrificed at T1 and T3 in each group and myocardial specimens were obtained from the apex of the left ventricle for determination of the expression of β3-AR by Western blot.Results Compared with group S,the LVEDD and LVESD were significantly enlarged and LVEF and LVFS were decreased at T1-3,and the expression of β3-AR was up-regulated at T1,3 in groups HF and RSGB (P ＜ 0.05).Compared with group HF,the LVEDD and LVESD were significantly decreased,LVEF and LVFS were increased,and the expression of β3-AR was significantly down-regulated at T3 in group RSGB (P ＜ 0.05).Conclusion The right stellate ganglion block can improve the cardiac function of rabbits with heart failure through down-regulating the expression of β3-AR in myocardium. Key words: Stellate ganglion ; Nerve block ; Heart failure ; Heart function tests; Receptors, adrenergic, beta-3

Effects of different fluids on cardiac function of rabbits with thermal burn-induced shock

Objective To study the effects of different fluids on on cardiac function of rabbits with thermal burn-induced shock Methods 40 rabbits were randomly divided into four groups,group Ⅰ:control group (without thermal injury),group Ⅱ:0.9％ NaC1 solution,group Ⅲ:lactated Ringer's solution,group Ⅳ:acetated Ringer's injection.The infusion rate was 0.33 ml/kg/％(area percentage of heat injury)/h in 4 h when the thermal injury of rabbit body surface area was 25％ to 30％.Cardiac function were measured in each group by working heart preparation in vitro model.Results Cardiac output(CO)[ (85±9),(90±9),(102±11),(103±10),(99±10),(101±11) ml/min],dp/dt[(1 200±110),(1 350±125),(1 210±100),(1 200±115),(1 150±120),(1 000±95) mmHg/s (1 mm Hg=0.133 kPa)],-dp/dt[(1 000±95),(1 150±100),(1 110±105),(1 100±110),(1 050±105),(1 000±100) mm Hg/s]in group Ⅱ were significantly lower than those in group Ⅰ (P＜0.05,P＜0.01 ),and these parameters were improved in group Ⅲ,but could not return to the levels in group.The parameters in group Ⅳ were similar to those in group Ⅰ (P＞0.05).Stroke work [ (21.2±2.3 ),(23.3±2.1),(27.2±2.3),(26.3±2.4),(26.1±3.2),(25.1±2.3) Q·mm Hg·bpm-1] and aortic peak systolic pressure[(55±4),(54±4),(56±4),(55±4),(53±4),(53±5) mm Hg] in group Ⅱ were significantly lower than those of group Ⅰ (P＜0.05,P＜0.01) while these parameters in group Ⅲ and Ⅳ were not different,compared to those of group. Conclusions Compound electrolyte solution infusion can improve cardiac function of rabbits with thermal burn-induced shock. Key words: Acetated ringer's injection; Lactated ringer's injection; Cardiac function; Rabbit

E0143 In vivo study of adenvirus mediated transgenic HIF-1α and its protective effects on cardiac function in experimental myocardial infarction

Hypoxia inducible factor-1α (HIF-1α) plays important roles in the regulation of transcriptional responses to hypoxia. In this study, the expression of HIF-1α gene and its downstream gene vascular endothelial growth...

NADPH oxidase inhibition ameliorates cardiac dysfunction in rabbits with heart failure

Increased NADPH oxidase activity is found in both experimental and clinical HF. Here, we investigated the effects and mechanisms of NADPH oxidase inhibition on cardiac function in rabbits with HF. HF was induced by combined volume and pressure overload. Rabbits with HF or sham operation were randomized to orally receive apocynin, an inhibitor of NADPH oxidase (15 mg per day) or placebo for 8 weeks. Echocardiography was performed to examine the cardiac function and structure of the rabbits. Cardiac fibrosis was evaluated by masson's trichrome staining. The transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) expression were measured by real-time PCR. The expression of SERCA2a and phospholamban (PLB) was detected by reverse transcription-polymerase chain reaction and Western Blot. SERCA2a activity was evaluated by measuring the Pi liberated from ATP hydrolysis. Rabbits with HF exhibited cardiac dysfunction and fibrosis. These changes were associated with significant increases in myocardial NADPH oxidase activity and oxidative stress. Compared with sham-operated rabbits, the TGF-β, CTGF, MMP-2, and MMP-9 mRNA expression significantly increased, the expression of SERCA2a and PLB dramatically decreased, and the SERCA2a activity was lower in HF rabbits. Apocynin reduced NADPH oxidase activity and oxidative stress, decreased TGF-β, CTGF, MMP-2, and MMP-9 expression, attenuated cardiac fibrosis, increased SERCA2a and PLB expression, restored SERCA2a activity, and thereby ameliorated cardiac dysfunction. Thus, chronic NADPH oxidase inhibition ameliorated cardiac dysfunction by decreasing cardiac fibrosis and preserving SERCA2a expression and activity.

Effects of electric stimulations applied during absolute refractory period on cardiac function of rabbits with heart failure

The effects of electric currents applied during absolute refractory period (ARP) on the cardiac function of rabbits with heart failure due to myocardial infarction (MI), and the safety of this method were investigated. Thirty rabbits were randomly assigned equally to 3 groups: sham-operated group, LV-anterior wall cardiac contractility modulation (LV-CCM) group, and septum-CCM (S-CCM) group. A thoracotomy was performed on all the rabbits. Electric pulses were delivered during the ARP on the anterior wall of left ventricle in CCM group and in the septum in S-CCM group, respectively. The left ventricular systolic pressure (LVSP) and maximum positive left ventricular pressure change (+dp/dt(max)), heart rates, ventricular tachycardia, ventricular fibrillation were observed. It was found that, as compared with the baseline, LVSP, and +dp/dtmax were significantly increased, on average, by 15.2% and 19.5% in LV-CCM group (P<0.05), and by 8.5% and 10.8% in S-CCM group (P<0.05). LVEDP was significantly decreased and -dp/dt(max) increased both in LV-CCM group and S-CCM group (P<0.05). CCM had no effect on heart rate and induced no arrhythmia in short time. It is concluded that electric currents delivered during the ARP could significantly enhance the contractility of myocardium safely, suggesting that CCM stimulation is a novel potent method for contractility modulation.

Effects of the combination α_2-adrenergic receptor agonist and k-opioid receptor agonist on post-resuscitation cardiac function in rabbits

Objective To investigate the effects of α_2-adrenergic receptor agonist and k-opioid receptor agonist jointly used on hemodynamics and B-type natriuretic peptide in rabbits,and to explore the effective methods for lessensing post-resuscitation myocardial dysfunction.Method After the establishment of cardiopulmonary resuscitation (CPR) model in rabbits, 30 rabbits were randomly divided into 5 groups, namely epinephrine group(E), vasopressin group(V), U50488H group(U), mivazerol group(M) and mivazerol + U50488H group(M + U). Hemodynamics and B-type natriuretic peptide were examined before ventricular fibrillation and in the early stage of post CPR (30-240 min). Statistical analysis was performed with ANOVA techniques. Results (1)MAP,peak - dp/dt and peak + dp/dt in M + U group were significantly higher than those in other groups, and the increase of LVEDP was less than that in other groups (P<0.05).(2)The concentration of BNP in M + U group was significantly decreased than that in other groups (P <0.01 or P <0.05). Conclusions The α_2-adrenergic receptor agonist (mivazerol) and k-opioid receptor agonist used together can improve post CPR hemodynamics and reduce the concentration of B-type natriuretic peptide, lessening the post CPR myocardial dysfunction. Key words: α_2-Adrenergic receptor; k-Opioid receptor; Agonist; Ventricular fibrillation; Cardiopulmonary resuscitation; Post-resuscition myocardial dysfunction; Hemodynamics; B-type natriuretic peptide

Experimental study on the influence of electroacupuncture on cardiac sympathetic nerve activity and cardiac function in acute myocardial ischemia rabbits

Objective To observe the influence of electroacupuncture (EA) of different Yuan-Primary acupoints on cardiac sympathetic nerve activity (CSNA) and cardiac function in rabbits with acute myocardial ischemia (AMI), and to understand the interaction mechanisms of cardiac sympathetic nerve in adjusting acute myocardial ischemia.

ULTRASOUND‐MEDIATED MICROBUBBLE DESTRUCTION ENHANCES THE EFFICACY OF BONE MARROW MESENCHYMAL STEM CELL TRANSPLANTATION AND CARDIAC FUNCTION

1. Application of ultrasound (US) to intravascular microbubble (MB) contrast agents causes small capillary ruptures. The purpose of the present study was to examine the effects of US-mediated MB destruction on bone marrow mesenchymal stem cell (BMSC) transplantation into the infarcted myocardium and to evaluate whether this approach could improve cardiac function. 2. Ultrasound was applied to the anterior chest of rabbits after intravenous injection of MB followed by infusion of BMSC. There were four groups investigated: (i) a control group, in which neither US nor MB were used prior to infusion of BMSC; (ii) one group subjected to US alone prior to infusion of BMSC; (iii) another group injected with MB prior to infusion of BMSC; and (iv) a group in which US was applied to MB prior to the infusion of BMSC. Cardiac function was evaluated by echocardiography 24 h and 4 weeks after cell transplantation. All rabbits were killed to enable histological and immunochemical examination. 3. Echocardiography 24 h after infusion of BMSC indicated no difference in cardiac function between any of the groups, as assessed by left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVDD), left ventricular systolic diameter (LVSD) and fractional shortening (FS%; all P > 0.05). However, 4 weeks after BMSC transplantation, there was a significant improvement in LVEF in the group subjected to US plus MB compared with the control, US alone and MB alone groups (59.5 +/- 3.5, 52.5 +/- 5.5, 52.8 +/- 5.2 and 51.1 +/- 3.5%, respectively; all P < 0.05). In addition, treatment with US plus MB significantly reduced LVDD and LVSD and increased capillary density in the infarcted area. 4. In conslusion, the results of the present study indicate that using US-mediated MB destruction prior to BMSC transplantation into the infarcted myocardium improves the effectiveness of cardiac cell therapy and cardiac function in rabbits.

Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction

Adipose-derived stem cells (ADSCs) are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function. ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscoves modified dulbeccos medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs (UASCs, n = 14), 5-azacytidine-pretreated ADSCs (AASCs, n = 13), or phosphate buffer saline (n = 13) were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation. ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak +dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak +dP/dt values than did UASC-implanted hearts. ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for augmenting myogenesis. Transplantation of 5-azacytidine-treated ADSCs into the myocardial scar was more efficient than that of untreated ADSCs in preservation of cardiac function.

Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet.

Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function. We examined the effects of cholesterol feeding (0.5%) on cardiac function in rabbits. After 10 weeks, both systolic shortening and diastolic relaxation rates were impaired without any change in aortic pressure or ventricular hypertrophy. However, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2 mRNA levels were reduced within 4 days after initiation of cholesterol feeding. After this effect, SERCA-2 protein and SERCA-mediated Ca uptake into sarcoplasmic reticulum vesicles were impaired, and the ratio of MHC-beta to MHC-alpha mRNA increased 5-fold. Suppression of the SERCA-2 message correlated temporally with enrichment of the cardiac sarcolemma with cholesterol. These data demonstrate that dietary hypercholesterolemia induces a "cholesterol cardiomyopathy" characterized by systolic and diastolic dysfunction. These alterations were independent of vascular disease and demonstrate a dietary link to cardiac dysfunction.

Taurine on the cardiac function in rabbits with chronic aortic regurgitation : K. Yamauchi, J. Azuma, N. Awata, H. Ohta, K. Ogura, A. Sawamura, H. Harada, S. Kishimoto. Third Department of Internal Medicine, Osaka University Medical School, Osaka, Japan

Taurine on the cardiac function in rabbits with chronic aortic regurgitation : K. Yamauchi, J. Azuma, N. Awata, H. Ohta, K. Ogura, A. Sawamura, H. Harada, S. Kishimoto. Third Department of Internal Medicine, Osaka University Medical School, Osaka, Japan

The effect of prolonged treatment with oxyfedrine on intracellular potentials and on other features of cardiac function in rabbits and guinea-pigs.

1. Previous work in acute experiments has shown that the main pharmacological action of oxyfedrine is stimulation of beta-adrenoceptors, yet there have been clinical reports that the drug is beneficial in the treatment of angina pectoris.2. In the present experiments rabbits and guinea-pigs were treated for several weeks with daily i.p. injections of oxyfedrine.3. A daily dosage of 15 mg/kg oxyfedrine had no effect on growth rate for 4 weeks, but thereafter the growth rate of treated animals fell below that of controls.4. The heart weights of the treated animals, expressed as a percentage of body weight, were significantly lower than those of controls.5. Measurement of intracellular potentials in hearts taken from treated rabbits showed that the main effects were a reduction in the maximum rate of depolarization and a prolongation of the plateau of the action potential.6. Guinea-pigs treated for 6 weeks with 15 mg/kg oxyfedrine daily i.p. were protected to some extent from the toxic effect of ouabain infused intravenously.