scholarly journals Cardiotoxic effects of pavetamine extracted from Pavetta harborii in the rat

Author(s):  
L. Hay ◽  
R.A. Schultz ◽  
P.J. Schutte

Previous studies have shown that crude extracts from Pavetta harborii as well as dried plant material have cardiotoxic effects on rats and sheep that can lead to heart failure. The active component has since been isolated and identified. This substance has been named pavetamine. The aim of this study was to determine whether pavetamine has cardiotoxic effects similar to those seen in previous reports, when administered to rats intraperitoneally. Sprague Dawley rats received two doses, initially 4 mg / kg and then 3 mg / kg pavetamine respectively and were monitored for 35 days before cardiodynamic parameters were measured by inserting a fluid-filled catheter into the left ventricle via the right carotid artery. These values were compared to those of control rats that had received only saline. Pavetamine significantly reduced systolic function and body mass in the treated rats, which indicates that it has the potential to induce heart failure in this animal model.

2019 ◽  
Vol 35 (07) ◽  
pp. 499-504 ◽  
Author(s):  
Xiaoliang Yin ◽  
Gengfan Ye ◽  
Jun Lu ◽  
Lijun Wang ◽  
Peng Qi ◽  
...  

Background End-to-end, end-to-side, and side-to-side microvascular anastomoses are the main types of vascular bypass grafting used in microsurgery and neurosurgery. Currently, there has been no animal model available for practicing all three anastomoses in one operation. The aim of this study was to develop a novel animal model that utilizes the rat abdominal aorta (AA), common iliac arteries (CIAs), and the median sacral artery (MSA) for practicing these three types of anastomosis. Methods Eight adult Sprague–Dawley rats were anesthetized and then laparotomized. The AA, MSA, and bilateral CIAs were exposed and separated from the surrounding tissues. The length and diameter of each artery were measured. The relatively long segment of the AA without major branches was selected to perform end-to-end anastomosis. One side of the CIAs (or AA) and MSA were used for end-to-side anastomosis. The bilateral CIAs were applied to a side-to-side and another end-to-side anastomosis. Results Anatomical dissection of the AA, CIAs, and MSA was successfully performed on eight Sprague–Dawley rats; four arterial-to-arterial anastomoses were possible for each animal. The AA trunk between the left renal artery and right iliolumbar arteries was 15.60 ± 0.76 mm in length, 1.59 ± 0.15 mm in diameter, for an end-to-end anastomosis. The left CIA was 1.06 ± 0.08 mm in diameter, for an end-to-side anastomosis with the right CIA. The MSA was 0.78 ± 0.07 mm in diameter, for another end-to-side anastomosis with the right CIA or AA. After finishing end-to-side anastomosis in the proximal part of bilateral CIAs, the distal portion was juxtaposed for an average length of 5.6 ± 0.25 mm, for a side-to-side anastomosis. Conclusion This model can comprehensively and effectively simulate anastomosis used in revascularization procedures and can provide more opportunities for surgical education, which may lead to more routine use in microvascular anastomosis training.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Agnieszka Wsol ◽  
Kaja Kasarello ◽  
Marek Kuch ◽  
Kamila Gala ◽  
Agnieszka Cudnoch-Jedrzejewska

Aim.The present study was designed to test the hypothesis that the development of postinfarction heart failure is associated with a change of activity of the intracardiac oxytocinergic system.Methods.Experiments were performed on male Sprague-Dawley rats subjected to myocardial infarction or sham surgery. Four weeks after the surgery, blood samples were collected and the samples of the left ventricle (LV) and right ventricle (RV) were harvested for evaluation of the mRNA expression (RT-PCR) of oxytocin (OT), oxytocin receptor (OTR), natriuretic peptides, and the level of OT and OTR protein (ELISA). The concentration of N-terminal B-type natriuretic peptide was measured to determine the presence of heart failure.Results.Plasma NT-proBNP concentration was higher in the infarcted rats. In the infarcted rats, the expression of OT mRNA and the OT protein level were higher in the RV. There were no significant differences between infarcted and noninfarcted rats in the expression of OT mRNA and in the OT protein level in the fragments of the LV. In both the left and the right ventricles, OTR mRNA expression was lower but the level of OTR protein was higher in the infarcted rats.Conclusions.In the present study, we indicate that postinfarction heart failure is associated with an increased activity of the intracardiac oxytocinergic system.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.


Author(s):  
Yun-Hee Kim ◽  
Sung-Uk Choi ◽  
Jung-Min Youn ◽  
Seung-Ha Cha ◽  
Hyeon-Ju Shin ◽  
...  

BACKGROUND: The prevention of rheologic alterations in erythrocytes may be important for reducing sepsis-associated morbidity and mortality. Remote ischemic preconditioning (RIPC) has been shown to prevent tissue damage caused by severe ischemia and mortality resulting from sepsis. However, the effect of RIPC on erythrocytes in sepsis is yet to be determined. OBJECTIVE: To investigate the effect of RIPC on rheologic alterations in erythrocytes in sepsis. METHODS: Thirty male Sprague-Dawley rats were used in this study. An endotoxin-induced sepsis model was established by intraperitoneally injecting 20 mg/kg LPS (LPS group). RIPC was induced in the right hind limb using a tourniquet, with three 10-minute of ischemia and 10 min of reperfusion cycles immediately before the injection of LPS (RIPC/LPS group) or phosphate-buffered saline (RIPC group). The aggregation index (AI), time to half-maximal aggregation (T1/2), and maximal elongation index (EImax) of the erythrocytes were measured 8 h after injection. RESULTS: The AI, T1/2, and EImax values in the LPS and RIPC/LPS groups differed significantly from those in the RIPC group, but there were no differences between the values in the LPS and RIPC/LPS groups. CONCLUSIONS: RIPC did not prevent rheologic alterations in erythrocytes in the rat model of LPS-induced endotoxemia.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Majos ◽  
A Kraska ◽  
I Kowalik ◽  
E Smolis-Bak ◽  
H Szwed ◽  
...  

Abstract Background Assessment of the right ventricle (RV) in heart failure (HF) is challenging and requires applicable methods and parameters. Atrial fibrillation (AF) is a common and clinically significant arrhythmia in 30–50% of HF patients. Assessment of the RV function in patients with AF is problematic. Still little is known about RV function in HF and AF patients. The aim of the study was to assess RV function in HF with focus on AF patients. Methods Patients with HF of ischemic etiology, NYHA II-III, LVEF ≤40%, with AF and sinus rhythm (SR), underwent two- and three- dimensional echocardiography (2DE and 3DE) for assessment of the RV with use of multiple parameters. The RV was examined for: linear dimensions, end-diastolic and end-systolic areas adjusted to body surface area (RV EDA and RV ESA/BSA) and end-diastolic and end-systolic volumes adjusted to lean body mass (RV EDV and RV ESV/LBM) to reflect volume overload and in terms of right ventricular pressure (RVSP) as an index of pressure overload. RV systolic function was assessed with 2DE: tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RV FAC), tricuspid lateral annular systolic velocity (s') and 3DE parameters: right ventricular ejection fraction (RVEF) and free wall right ventricular longitudinal strain (FW RVLS). Also, TAPSE/RVSP parameter was included. Results The study included 126 patients: 94 with AF and 32 with SR. Within the AF group 28 patients were treated medically, 41 had RV pacing (pacemaker or an implantable cardioverter-defibrillator, ICD) and 25 had cardiac resynchronisation therapy (CRT). In comparison with SR group AF patients had: larger RV inflow tract dimension (4.49±0.85 vs. 3.95±0.72 cm; p=0.0017), RV EDA/BSA (12.7±3.9 vs. 11.1±3.0 cm2/m2; p=0.0358) and RV ESA/BSA (8.0±3.0 vs. 6.7±2.4 cm2/m2; p=0.0226). Similarly, patients with AF had greater RV volumes in 3DE than patients with SR: RV EDV/LBM (1.82±0.60 vs. 1.61±0.38ml/kg, p=0.0267) and RV ESV/LBM (1.11±0.40 ml/kg vs. 0.81±0.28, p<0,0001). Also, in patients with AF right ventricular systolic pressure (RVSP) was higher (40.8±10.2 vs. 34.0±8.1 mmHg, p=0,0010). No differences in TAPSE and RVFAC were found but the relation TAPSE/RVSP was higher in AF than in SR group (0.51±0.21 vs. 0.65±0.24 cm/mmHg; p=0.0046). Also, in AF patients in comparison to SR group some parameters had worse values: s' (9.7±2.31 vs. 12.1±3.83, p=0.014), RVEF (37.2±7.3 vs. 48.2±7.5, p<0.0001 and FW RVLS (−18.3±4.6 vs. −23.9±4.23%, p<0,0001). Within the AF group no significant differences in studied variables depending on RV pacing or CRT were found. Conclusions Larger volumes and higher pressure overload of the RV were observed in patients with AF in comparison to SR. Systolic function of the RV seems to be more depressed in AF compared to SR patients with systolic heart failure. Further research in larger groups is required to identify the most applicable and valuable methods of RV evaluation.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michele Ciccarelli ◽  
Giuseppe Rengo ◽  
Kurt Chuprun ◽  
Gaetano Santulli ◽  
Bruno Trimarco ◽  
...  

The beta adrenergic receptor (βAR) kinase, GRK2, is upregulated and participates to the evolution of heart failure (HF) through downregulation and desensitization of βARs. Recent studies showed that this molecule affects insulin signaling and reduce glucose uptake in hepatocytes and adipocytes. We hypothesized that in HF, GRK2 reduces cardiac performance also through inhibition of cardiac glucose metabolism. In 12 week old Sprague/Dawley rats, we measured cardiac glucose uptake by PET 3 days, 3 and 6 weeks after myocardial infarction (MI). Function and cardiac dimensions were measured by echocardiography. We observed that glucose uptake was reduced in animal post-MI at 3 and 6 weeks respect to healthy animals (3 rd week: 1.3±0.22 vs 2.1±0.3; 6 th week: 1±0.1 vs 2.4±0.2, ml/min/g, p<0.05). No difference was observed in glucose uptake acutely after surgery. Echo showed cardiac dilation and reduced function at 6 weeks (LVD: 9.2± 0.3 vs 7.2± 0.4 mm; EF: 42%±1.1 vs 66%±2.2, p<0.05, Sham vs MI). To inhibit GRK2 in the heart during post-ischemic HF, we delivered the GRK2 inhibitor βARKct by adeno-associated type 6 virus (AAV6) to the left ventricle before induction of the MI. As a control we treated rats with AAV6 encoding for the green fluorescent protein (GFP). Cardiac dilation and function were preserved after 6 weeks post MI in AAV6 βARKct respect to AAV6GFP rats (LVD: 7.73 ±0.25 vs 9.9 ±0.8 mm; EF: 55%±2.25 vs 44%±2, p<0.05). Glucose uptake was better preserved in AAV6βARKct rats after 3 and 6 weeks post MI respect to AAV6GFP group (3rd week: 2.3±0.3 vs 1.2±0.2; 6th week: 1.8±0.2 vs 1.1±0.05, ml/min/g, p<0.05). Since Akt mediates most of the anabolic effects of insulin in cells, we evaluated the effects of GRK2 overexpression by adenovirus (ADGRK2) in neonatal cardiomyocytes (NRVMs) on Akt phosphorylation later on insulin stimulation (ins, 10 – 6 M). As control we induced overexpression of GFP by adenovirus (ADGFP). We observed reduced activation of Akt in presence of GRK2 overexpression as compared to the ADGFP treated cells (1.2±0.2- vs. 3.5±0.4- fold activation over basal, p<0.05). Our data show that post MI, impaired glucose extraction precedes development of HF, and that early GRK2 inhibition prevents impaired myocardial glucose uptake and HF development.


2021 ◽  
Vol 14 ◽  
Author(s):  
Xue-jia Li ◽  
Fei Zhu ◽  
Bo Li ◽  
Dong Zhang ◽  
Cheng-Wei Liang

Introduction: Osteoarthritis (OA) is a dominant cause of morbidity and disability. As a chronic disease, its etiological risk factors and most therapies at present, are empirical and symptomatic. Regenerating gene 4 (Reg4) is involved in cell growth, survival, regeneration, adhesion, and resistance to apoptosis, which are partially thought to be the pathogenic mechanisms of OA. However, the proper role of Reg4 in OA is still unknown. Methods: In this study, a consecutive administration of rhReg4 was applied to normal Sprague-Dawley rats or rats after OA induction. Histological changes and chondrocyte proliferation in the articular cartilage were measured. Results: We found that RhReg4 promotes chondrocyte proliferation in normal rats, and RhReg4 attenuated the severity of OA in rats by promoting chondrocytes’ proliferation in OA rats. Conclusion: In conclusion, recombinant human regenerating gene 4 (rhReg4) attenuates the severity of osteoarthritis in OA animal models and may be used as a new method for the treatment of osteoarthritis.


1985 ◽  
Vol 248 (1) ◽  
pp. E70-E74 ◽  
Author(s):  
R. A. Bennett ◽  
P. C. Colony ◽  
J. L. Addison ◽  
D. E. Rannels

The effects of adrenalectomy, with and without subsequent glucocorticoid replacement therapy, on postpneumonectomy compensatory lung growth in the rat were investigated. Male Sprague-Dawley rats (200-230 g) were subjected to no operation (UNOP), left pneumonectomy (PNX), or PNX preceded by bilateral adrenalectomy 5 days earlier (ADX/PNX). At 14 days post-PNX, when compensatory lung growth is normally complete in 200-g rats, right lung (RL) dry weights of PNX (263 +/- 6 mg, n = 26) and ADX/PNX (334 +/- 13 mg, n = 25) rats were increased 58 and 101%, respectively, relative to UNOP controls (166 +/- 5 mg, n = 10). Increases in total DNA, RNA, and protein in the right lungs of PNX and ADX/PNX rats occurred in proportion to RL dry mass. The increase in all parameters examined in PNX and ADX/PNX rats at 7 days post-PNX was half that at 14 days, indicating linear lung growth in both treatment groups. The stimulatory effect of ADX on lung growth was blocked by hydrocortisone acetate (HCA), administered intraperitoneally in daily doses of 5 mg/kg, beginning on the day of PNX. The RL dry weights of HCA-treated ADX/PNX rats (241 +/- 7 mg, n = 10) did not differ significantly from the corresponding value in PNX rats (270 +/- 14 mg, n = 7). The lower RL weights in the HCA-treated rats resulted from an inhibition of cell division, as evidenced by the total RL DNA content, which was similar to that in PNX animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Surgery Today ◽  
2020 ◽  
Author(s):  
Yuhi Suzuki ◽  
Masayoshi Yamamoto ◽  
Kosuke Sugiyama ◽  
Toshiya Akai ◽  
Katsunori Suzuki ◽  
...  

Abstract Purpose To investigate the utility of the device for evaluating intestinal oxygenation and viability using an animal model. Methods Sprague–Dawley rats underwent laparotomy under general anesthesia, and the blood vessels in the terminal ileum were clamped to create ischemia. We measured the regional tissue oxygenation saturation (rSO2) using an oximeter after 1, 3, and 6 h of vessel clamping. Ischemic tissue damage was assessed using a histological score. The intestine was reperfused after each clamping period, and intestinal rSO2 and survival rate were evaluated. Results When reperfusion was performed at 1 and 3 h after ischemia, rSO2 increased after 10 min, and it improved to the same level as for normal intestine after 1 h; all rats survived for 1 week. In contrast, after 6 h of ischemia, rSO2 did not increase after reperfusion, and all animals died within 2 days. The histological scores increased after 1 h of reperfusion, with longer clamping periods. Conclusion A finger-mounted tissue oximeter could evaluate intestinal ischemia and the viability, which is thus considered to be a promising result for future clinical application.


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