Dataset Information

Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis.

ABSTRACT: 1. In a recent in vivo study, liriodenine, an aporphine alkaloid, has been identified as a prominent anti-arrhythmic agent that can prevent rats' sudden deaths, even at the dose as low as 10(-7) g kg(-1). The aim of this study was to determine whether liriodenine at its effective anti-arrhythmic dose of 10(-7) g kg(-1) had effects on the left ventricular (LV)-arterial coupling in Wistar rats. 2. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (E(es)) and effective arterial volume elastance (E(a)), respectively. The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the optimality of energy transmission from the left ventricle to the arterial system. 3. Liriodenine at the dose of 10(-7) g kg(-1) showed no significant changes in basal heart rate (HR), cardiac output (CO), LV end-systolic pressure (P(es)), E(a), E(es), and Q(load). 4. By contrast, liriodenine at the dose of 10(-6) g kg(-1) produced a significant fall of 2.0% in HR and a significant rise of 5.8% in CO, but no significant change in P(es). Moreover, liriodenine administration of 10(-6) g kg(-1) to rats significantly decreased E(es) by 8.5% and E(a) by 10.6%, but did not change Q(load). 5. We conclude that liriodenine at the dose of 10(-7) g kg(-1) has no effects on the mechanical properties of the heart and the vasculature and the matching condition for the left ventricle coupled to its vasculature in rats. Even at 10 times the effective anti-arrhythmic dose, liriodenine shows no effects on the efficiency of energy transferred from the left ventricle to the arterial system.

SUBMITTER: Chang KC

PROVIDER: S-EPMC1572753 | biostudies-other | 2001 May

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Obesity increases the risk for cardiomyopathy in the absence of comorbidities. Myocardial structure is modified by dietary fatty acids. Left ventricular hypertrophy is associated with Western (WES) diet consumption, whereas intake of n-3 polyunsaturated fatty acids is associated with antihypertrophic effects. We previously observed no attenuation of left ventricular thickening after 3 months of docosahexaenoic acid (DHA) supplementation of a WES diet, compared with WES diet intake alone, in rats that had similar weight, adiposity, and insulin sensitivity to control animals. The objective of this study was to define left ventricular gene expression in these animals to determine whether diet alone was associated with a physiologic or pathologic hypertrophic response. We hypothesized that WES diet consumption would favor a pathologic or maladaptive myocardial gene expression pattern and that DHA supplementation would favor a physiologic or adaptive response. Microarray analysis identified 64 transcripts that were differentially expressed (P ? .001) within one or more treatment comparisons. Using quantitative real-time polymerase chain reaction, 29 genes with fold change at least 1.74 were successfully validated; all but 3 had similar directionality to that observed using microarray, and 2 genes, connective tissue growth factor and cathepsin M, were differentially expressed according to diet. WES blot analysis was performed on 4 proteins relevant to myocardial hypertrophy and metabolism. Acyl-CoA thioesterase 1, B-cell translocation gene 2, and carbonic anhydrase III showed directional change consistent with gene expression. Retinol saturase (all-trans-retinol 13,14-reductase), although not consistent with gene expression, was different according to diet, with increased concentrations in WES-fed rats compared with control and DHA-supplemented animals. Diet did not distinguish a transcriptome reflecting physiologic or pathologic myocardial hypertrophy; furthermore, the modest changes observed suggest that obesity and associated comorbidities may play a larger role than mere dietary fatty acid composition in development of cardiomyopathy.

Project description:BACKGROUND:Weaning post-cardiac surgery patients from mechanical ventilation (MV) poses a big challenge to these patients. Optimized left ventricular-arterial coupling (VAC) may be crucial for reducing the MV duration of these patients. However, there is no research exploring the relationship between VAC and the duration of MV. We performed this study to investigate the relationship between left ventricular-arterial coupling (VAC) and prolonged mechanical ventilation (MV) in severe post-cardiac surgery patients. METHODS:This was a single-center retrospective study of 56 severe post-cardiac surgery patients from January 2015 to December 2017 at the Department of Critical Care Medicine of Peking Union Medical College Hospital. Patients were divided into two groups according to the duration of MV (PMV group: prolonged mechanical ventilation group, MV >?6?days; Non-PMV group: non-prolonged mechanical ventilation group, MV???6?days). Hemodynamics and tissue perfusion data were collected or calculated at admission (T0) and 48?h after admission (T1) to the ICU. RESULTS:In terms of hemodynamic and tissue perfusion data, there were no differences between the two groups at admission (T0). Compared with the non-prolonged MV group after 48?h in the ICU (T1), the prolonged MV group had significantly higher values for heart rate (108?±?13 vs 97?±?12, P?=?0.018), lactate (2.42?±?1.24 vs.1.46?±?0.58, P?<?0.001), and Ea/Ees (5.93?±?1.81 vs. 4.05?±?1.20, P?<?0.001). Increased Ea/Ees (odds ratio, 7.305; 95% CI, 1.181-45.168; P?=?0.032) and lactate at T1 (odds ratio, 17.796; 95% CI, 1.377-229.988; P?=?0.027) were independently associated with prolonged MV. There was a significant relationship between Ea/EesT1 and the duration of MV (r?=?0.512, P?<?0.01). The area under the receiver operating characteristic (AUC) of the left VAC for predicting prolonged MV was 0.801, and the cutoff value for Ea/Ees was 5.12, with 65.0% sensitivity and 90.0% specificity. CONCLUSIONS:Left ventricular-arterial coupling was associated with prolonged mechanical ventilation in severe post-cardiac surgery patients. The assessment and optimization of left VAC might be helpful in reducing duration of MV in these patients.

Project description:BackgroundPatients with dilated cardiomyopathy, increased ventricular volume, pressure overload or dysynergistic ventricular contraction and relaxation are susceptible to develop serious ventricular arrhythmias (VA). These phenomena are primarily based on a theory of mechanoelectric feedback, which reflects mechanical changes that produce alterations in electrical activity. However, very few systematic studies have provided evidence of the preventive effects of artemisinin (ART) on VA in response to left ventricle (LV) afterload increases. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate expression of multiple genes by suppressing mRNAs post-transcriptionally.AimsThe aims of this study were to investigate preventive effects of ART on mechanical VA and the underling molecular mechanisms of differentially expressed miRNAs (DEMs).MethodsFor the study, 70 male Wistar rats were randomly divided into seven groups: group 1 was a control group (sham surgery); group 2 was a model group that underwent transverse aortic constriction (TAC) surgery; groups 3, 4, 5 and 6 were administered ART 75, 150, 300 and 600 mg/kg before TAC surgery, respectively; and group 7 was administered verapamil (VER) 1 mg/kg before TAC surgery. A ventricular arrhythmia score (VAS) was calculated to evaluate preventive effects of ART and VER on mechanical VA. The high throughput sequencing-based approach provided DEMs that were altered by ART pretreatment between group 2 and group 4. All predicted mRNAs of DEMs were enriched by gene ontology (GO) and Kyoto Encyclopedia annotation of Genes and Genomes (KEGG) databases. These DEMs were validated by a real time quantitative polymerase chain reaction (RT-qPCR).ResultsThe average VASs of groups 3, 4, 5, 6 and 7 were significantly reduced compared with those of group 2 (2.70 ± 0.48, 1.70 ± 0.95, 2.80 ± 0.79, 2.60 ± 0.97, 1.40 ± 0.52, vs 3.70 ± 0.67, p < 0.01, respectively). The three top GO terms were neuron projection, organ morphogenesis and protein domain specific binding. KEGG enrichment of the 16 DEMs revealed that MAPK, Wnt and Hippo signaling pathways were likely to play a substantial role in the preventive effects of ART on mechanical VA in response to LV afterload increases. All candidate DEMs with the exception of rno-miR-370-3p, rno-miR-6319, rno-miR-21-3p and rno-miR-204-5p showed high expression levels validated by RT-qPCR.ConclusionsArtemisinin could prevent mechanical VA in response to LV afterload increases. Validated DEMs could be biomarkers and therapeutic targets of ART regarding its prevention of VA induced by pressure overload. The KEGG pathway and GO annotation analyses of the target mRNAs could indicate the potential functions of candidate DEMs. These results will help to elucidate the functional and regulatory roles of candidate DEMs associated with antiarrhythmic effects of ART.

Project description:BackgroundLuhong formula (LHF)-a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd-is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis.MethodsForty-eight SD male rats were randomly assigned into six groups (n?=?8), model group, sham-operation group, perindopril group (0.036?mg/ml), LHF high doses (LHF-H, 1.44?g/mL), LHF middle doses (LHF-M, 0.72?g/mL), and LHF low doses (LHF-L, 0.36?g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-?1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-?1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope.ResultsLHF significantly lowered the rat's HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-?1, caspase-3, VEGF, and VEGFR2 expression.ConclusionLHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-?1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

Dataset Information

Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets