Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis.
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ABSTRACT:
SUBMITTER: Chang KC
PROVIDER: S-EPMC1572753 | biostudies-other | 2001 May
REPOSITORIES: biostudies-other
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Project description:BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties. EXPERIMENTAL APPROACH: Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg x kg(-1), i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E(es), an indicator of myocardial contractility) and effective arterial volume elastance (E(a)). The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the coupling efficiency between the left ventricle and its vasculature. KEY RESULTS: There was a significant interaction between fructose and AG in their effects on E(a). Fructose loading significantly elevated E(a) and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E(es) and Q(load), and there was an interaction between fructose and AG for these two variables. Both E(es) and Q(load) exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats. CONCLUSIONS AND IMPLICATIONS: AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.
| S-EPMC2013974 | biostudies-other
Project description:Apelin plays important roles in cardiovascular homeostasis. However, its effects on the mechanoenergetics of heart failure (HF) are unavailable. We attempted to investigate the effects of apelin on the left ventricular-arterial coupling (VAC) and mechanical efficiency in rats with HF. HF was induced in rats by the ligation of the left coronary artery. The ischemic HF rats were treated with apelin or saline for 12 weeks. The sham-operated animals served as the control. The left ventricular (LV) afterload and the systolic and diastolic functions, as well as the mechanoenergetic indices were estimated from the pressure-volume loops. Myocardial fibrosis by Masson's trichrome staining, myocardial apoptosis by TUNEL, and collagen content in the aorta as well as media area in the aorta and the mesenteric arteries were determined. Our data indicated that HF rats manifested an increased arterial load (Ea), a declined systolic function (reduced ejection fraction, +dP/dtmax, end-systolic elastance, and stroke work), an abnormal diastolic function (elevated end-diastolic pressure, ?, and declined -dP/dtmax), and decreased mechanical efficiency. Apelin treatment improved those indices. Concomitantly, increased fibrosis in the LV myocardium and the aorta and enhanced apoptosis in the LV were partially restored by apelin treatment. A declined wall-to-lumen ratio in the mesenteric arteries of the untreated HF rats was further reduced in the apelin-treated group. We concluded that the rats with ischemic HF were characterized by deteriorated LV mechanoenergetics. Apelin improved mechanical efficiency, at least in part, due to the inhibiting cardiac fibrosis and apoptosis in the LV myocardium, reducing collagen deposition in the aorta and dilating the resistant artery.
| S-EPMC6604493 | biostudies-literature
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.
| S-EPMC4265552 | biostudies-literature
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.
| S-EPMC6284290 | biostudies-literature
Project description:Left ventricular hypertrophy (LVH) is associated with decreased responsiveness of renal α1-adrenoreceptors subtypes to adrenergic agonists. Nitric oxide donors are known to have antihypertrophic effects however their impact on responsiveness of renal α1-adrenoreceptors subtypes is unknown. This study investigated the impact of nitric oxide (NO) and its potential interaction with the responsiveness of renal α1-adrenoreceptors subtypes to adrenergic stimulation in rats with left ventricular hypertrophy (LVH). This study also explored the impact of NO donor on CSE expression in normal and LVH kidney. LVH was induced using isoprenaline and caffeine in drinking water for 2 weeks while NO donor (L-arginine, 1.25g/Lin drinking water) was given for 5 weeks. Intrarenal noradrenaline, phenylephrine and methoxamine responses were determined in the absence and presence of selective α1-adrenoceptor antagonists, 5- methylurapidil (5-MeU), chloroethylclonidine (CeC) and BMY 7378. Renal cortical endothelial nitric oxide synthase mRNA was upregulated 7 fold while that of cystathione γ lyase was unaltered in the NO treated LVH rats (LVH-NO) group compared to LVH group. The responsiveness of renal α1A, α1B and α1D-adrenoceptors in the low dose and high dose phases of 5-MeU, CEC and BMY7378 to adrenergic agonists was increased along with cGMP in the kidney of LVH-NO group. These findings suggest that exogenous NO precursor up-regulated the renal eNOS/NO/cGMP pathway in LVH rats and resulted in augmented α1A, α1B and α1D adrenoreceptors responsiveness to the adrenergic agonists. There is a positive interaction between H2S and NO production in normal animals but this interaction appears absent in LVH animals.
| S-EPMC5844246 | biostudies-literature
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.
| S-EPMC6304267 | biostudies-literature
Project description: Not available
| S-EPMC9314840 | biostudies-literature
Project description:We reported the RNAseq analyses of right ventricle (RV) and left ventricle (LV) in neonatal volume overload (VO) and sham-operated SD rat. VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) within 24 hours postnatally (P1). RNAseq analyses of RV and LV free wall of P7 from VO and sham-operated rat. It demonstrated that the 1806 differentially expressed genes (DEGs) between RV and LV at the neonatal stage were primarily enriched in GTPase mediating signal transduction, insulin signaling pathway and thyroid hormone signaling pathway. VO produced 3 more times DEGs in LV than RV . GO analysis of these DEGs demonstrated that in the top 150 enriched terms, the LV comparison and RV comparison shared 34 terms (22.7%) in common. These commonly enriched terms were primarily associated with GTPase mediating signal transduction. KEGG analysis of these DEGs demonstrated that in the top 30 enriched terms, the LV comparison and RV comparison shared 14 terms (46.7%) in common. And insulin signaling pathway and thyroid hormone signaling pathway are the top two enriched terms in common. Regarding the differently enriched GO terms, they were primarily associated with lipid metabolism and ion channel in RV and primarily associated nucleic acid metabolism in LV. The top two differently enriched KEGG terms were arrhythmogenic right ventricular cardiomyopathy (ARVC) and adipocytokine signaling pathway in RV while microRNAs in cancer and longevity regulating pathway in LV. These results were further confirmed by the determination of metabolites.
2022-12-15 | GSE186247 | GEO
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.
| S-EPMC7277070 | biostudies-literature
Project description:Age is the dominant risk factor for cardiovascular diseases. Understanding the coupling between the left ventricle (LV) and arterial system, termed arterial-ventricular coupling (E(A)/E(LV)), provides important mechanistic insights into the complex cardiovascular system and its changes with aging in the absence and presence of disease. E(A)/E(LV) can be indexed by the ratio of effective arterial elastance (E(A); a measure of the net arterial load exerted on the LV) to left ventricular end-systolic elastance (E(LV); a load-independent measure of left ventricular chamber performance). Age-associated alterations in arterial structure and function, including diameter, wall thickness, wall stiffness, and endothelial dysfunction, contribute to a gradual increase in resting E(A) with age. Remarkably there is a corresponding increase in resting E(LV) with age, due to alterations to LV remodeling (loss in myocyte number, increased collagen) and function. These age-adaptations at rest likely occur, at least, in response to the age-associated increase in E(A) and ensure that E(A)/E(LV) is closely maintained within a narrow range, allowing for optimal energetic efficiency at the expense of mechanical efficacy. This optimal coupling at rest is also maintained when aging is accompanied by the presence of hypertension, and obesity, despite further increases in E(A) and E(LV) in these conditions. In contrast, in heart failure patients with either reduced or preserved ejection fraction, E(A)/E(LV) at rest is impaired. During dynamic exercise, E(A)/E(LV) decreases, due to an acute mismatch between the arterial and ventricular systems as E(LV) increases disproportionate compared to E(A) (≈200 vs. 40%), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. However, with advancing age the reduction in E(A)/E(LV) during acute maximal exercise is blunted, due to a blunted increase E(LV). This impaired E(A)/E(LV) is further amplified in the presence of disease, and may explain, in part, the reduced cardiovascular functional capacity with age and disease. Thus, although increased stiffness of the arteries itself has important physiological and clinical relevance, such changes also have major implications on the heart, and vice versa, and the manner in the way they interact has important ramifications on cardiovascular function both at rest and during exercise. Examination of the alterations in arterial-ventricular coupling with aging and disease can yield mechanistic insights into the pathophysiology of these conditions and increase the effectiveness of current therapeutic interventions.
| S-EPMC3345942 | biostudies-literature