Abstract：
INTRODUCTION:Mouse models of chronic heart failure (HF) have been widely used in HF research. However, the current HF models most often use the C57BL/6 mouse strain and do not show the clinically relevant characteristics of pulmonary congestion. In this study, we developed a robust mouse model of HF in the BALB/c mouse strain, exhibiting pulmonary edema and pleural effusion, and we validated the model using the standard pharmacological therapies in patients with chronic HF and reduced ejection fraction (HFrEF) or acute decompensated HF. METHODS:After induction of myocardial infarction (MI) by permanent ligation of the left coronary artery in BALB/c mice, the cardiac function, pulmonary congestion, disease biomarkers, and survival were evaluated using the angiotensin converting enzyme inhibitor enalapril or the loop diuretic furosemide. Enalapril was administered 4 weeks post-MI for 6 weeks or furosemide was given 10 weeks post-MI for 4 days, when pulmonary congestion was evident. RESULTS:Compared to sham controls, MI mice developed systolic dysfunction, exhibited lung weight increase at 4 weeks, and progressively developed pleural effusion (60% of the animals) at 10 weeks. Compared to the vehicle, enalapril significantly reduced the lung weight and pleural effusion, preserved systolic function, and improved survival. Furthermore, furosemide completely abolished the pleural effusion. Enalapril or furosemide also reduced the plasma brain natriuretic peptide concentration. DISCUSSION:The post-MI HF in BALB/c mice shows reproducible and robust pulmonary congestion and may be a clinically relevant model for novel drug testing for treatment in patients with HFrEF or acute decompensated HF.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Ma X,Tannu S,Allocco J,Pan J,Dipiero J,Wong Pdoi
10.1016/j.vascn.2019.02.001subject
Has Abstractpub_date
2019-01-01 00:00:00pages
78-86eissn
1056-8719issn
1873-488Xpii
S1056-8719(18)30803-7journal_volume
96pub_type
杂志文章abstract：:In this article we review the value and utility of the minipig as an animal model in regulatory toxicity testing. Our review is based on detailed consideration of the comparative biology of the minipig, and of the practical features of toxicity testing in the minipig. The minipig presents a favourable profile as a non...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2010.05.009
更新日期：2010-11-01 00:00:00
abstract：:For the rapid assay of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) in the mouse brain, we developed a simple method using isocratic HPLC with coulometric detection. This method permits NE and MHPG assay within 5 min in one chromatographic run. Within-run coefficients of variati...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(94)90060-4
更新日期：1994-10-01 00:00:00
abstract：:A method for determination of cis-diaminedichloroplatinum (II) (cisplatin) in ultrafiltered plasma, cell, and tumour samples is described. Cisplatin separation was carried out on a reversed-phase column using methanol-acetonitrile-water as the mobile phase. The flow rate was maintained constant at 1.6 mL/min and analy...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2005.06.005
更新日期：2005-11-01 00:00:00
abstract：INTRODUCTION:In recent years, the anesthetized guinea pig has been used increasingly to evaluate the cardiovascular effects of drug-candidate molecules during lead optimization prior to conducting longer, more resource intensive safety pharmacology and toxicology studies. The aim of these studies was to evaluate the co...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2013.04.010
更新日期：2013-07-01 00:00:00
abstract：:A comparison is made of four rat aortic preparations, that is, single ring, spiral strip, zig-zag strip, and multiple-ring, on the basis of the responses to norepinephrine (NE) and acetylcholine (ACh). The single ring preparation was suitable under isometric, but not under isotonic conditions, because of the small iso...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(96)00023-8
更新日期：1996-06-01 00:00:00
abstract：:The application of microdialysis technique for the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of probe performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investiga...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(00)00117-9
更新日期：2000-11-01 00:00:00
abstract：:The majority of articles published in J Pharmacol Tox Methods describe new approaches, or modifications to those established (Curtis, 2006). However, even established methods have their limitations. It is part of the practice of research to troubleshoot: to identify methodological weaknesses and correct them. This pro...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 社论
doi：10.1016/j.vascn.2010.02.013
更新日期：2010-03-01 00:00:00
abstract：INTRODUCTION:Recent EU/US pediatric legislation and FDA/EMEA guidelines recognize the potential differences in safety profiles of drugs in adults versus young patients. Hence safety studies are recommended to investigate key functional domains of e.g. the developing CNS. METHODS:Selected psychoactive stimulants (caffe...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2008.06.001
更新日期：2008-09-01 00:00:00
abstract：INTRODUCTION:The aim of this work was to compare the suitability of different pharmacodynamic models for PK-PD modeling of verapamil cardiovascular effects in aortic coarctated rats (ACo), a model of renovascular hypertension. METHODS:A "shunt" microdialysis probe was inserted in a carotid artery of anaesthetized sham...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2008.03.002
更新日期：2008-05-01 00:00:00
abstract：INTRODUCTION:MEKK1 is a 196-kDa serine-threonine kinase activated in response to a variety of stimuli, including EGF, lysophosphatidic acid, osmotic stress, UV light, and microtubule toxins. However, there are few reports about the expression level of MEKK1 in cancers. METHODS:In this report, a direct competitive ELIS...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2004.08.004
更新日期：2005-03-01 00:00:00
abstract：INTRODUCTION:Drug-induced QT interval prolongation has been one of the critical issues for developing new chemical entities and pharmaceutical companies need to evaluate the risk early in the development stage. At such stage, guinea pigs are appropriate due to their small size requiring only small amounts of test drugs...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2006.11.002
更新日期：2007-05-01 00:00:00
abstract：INTRODUCTION:RL-14 cells, human fetal ventricular cardiomyocytes, are a commercially available cell line that has been established from non-proliferating primary cultures derived from human fetal heart tissue. However, the expression of different drug metabolizing enzymes (DMEs) in RL-14 cells has not been elucidated y...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.11.005
更新日期：2015-01-01 00:00:00
abstract：:The objective of this research is to determine whether the administration of a complete soft food formula to sub-lethal irradiated animals from three different transgenic mouse strains over a period of 21 consecutive days will have a significant impact on the clinical signs, and the general survival rate of the animal...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.12.003
更新日期：2015-01-01 00:00:00
abstract：:Escherichia coli produces a heat-stable (STa) enterotoxin that belongs to a family of peptides that mediate several diarrheal diseases, including traveler's diarrhea and epidemic diarrhea in infants and newborns. The STa enterotoxin consists of 18 or 19 amino acids and is encoded by genes specified on a transposon. In...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/1056-8719(92)90049-7
更新日期：1992-09-01 00:00:00
abstract：INTRODUCTION:Regulatory guidelines recommend the use of conscious, unrestrained animals for comprehensive cardiovascular safety assessment of a new therapeutic agent. Cardiovascular safety pharmacology studies normally use internal telemetry (surgical implants) in free-moving animals to monitor key ECG endpoints, like ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2009.04.196
更新日期：2009-07-01 00:00:00
abstract：:Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2016.03.002
更新日期：2016-09-01 00:00:00
abstract：INTRODUCTION:A variety of in vitro tests to replace the Draize test have been developed; however, there is no available method for assessing the full spectrum of Globally Harmonized System (GHS) categories. Human cornea-like three-dimensional (3D) reconstructed tissue models are the most promising in vitro systems. The...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2018.02.007
更新日期：2018-01-01 00:00:00
abstract：:Induction of acute myocardial infarction in the rat is an established model for studying effects of therapeutic interventions. Images of sections of the rat left ventricle, stained with nitroblue tetrazolium, were digitized and several parameters estimated by dedicated software on an image analyzer (IBAS 2.0). The met...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(95)00019-e
更新日期：1995-08-01 00:00:00
abstract：:Evaluation of the myocardial relaxation has become important in the last years. An impaired relaxation may precede contractile dysfunctions and even cause heart failure. To treat this impaired lusitropism it is necessary to properly assess the lusitropic state of the heart and understand how drugs affect the cellular ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/1056-8719(94)90011-6
更新日期：1994-09-01 00:00:00
abstract：INTRODUCTION:The evaluation of drug's cytotoxicity is a crucial step in the development of new pharmacological compounds. 31P NMR can be a tool for toxicological screening, as it enables the study of drugs' cytotoxicity and their effect on cell energy metabolism in a real-time, in a non- invasive and non-destructive wa...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2018.11.004
更新日期：2019-01-01 00:00:00
abstract：:In many circumstances, rapid information is required about the effects of drugs on neurotransmitter release in brain, and a common method used is measurement of radiolabelled release from superfused brain slices or synaptosomes in vitro. However, the method requires expensive equipment and is not readily adapted to th...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(97)00010-5
更新日期：1997-04-01 00:00:00
abstract：INTRODUCTION:Affymetrix oligonucleotide microarrays are widely used in basic and applied research (Lander, E.S., (1999). Array of hope. Nature Genetics 21, 3-4; Lockhart, D.J. & Winzeler, E.A. (2000) Genomics, gene expression and DNA arrays. Nature 405, 827-836.) The need for a significant amount of starting RNA has li...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2005.02.004
更新日期：2006-03-01 00:00:00
abstract：INTRODUCTION:The aim of this investigation was to evaluate methods for increasing Caco-2 cell throughput for assessing drug intestinal absorption. The use of 6-, 12-, and 24-well membranes and the effect of membrane size on permeability and the integrity of the Caco-2 cell monolayer were assessed. In an effort to optim...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(01)00161-7
更新日期：2001-07-01 00:00:00
abstract：:Two methods of measuring body temperature were compared in common marmosets. Subcutaneous temperatures were measured remotely via previously implanted subcutaneous microchips (Plexx BV, IPTT-100) prior to measurement of rectal temperature using a conventional rectal probe. Marmosets were treated with saline or the bra...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(98)00030-6
更新日期：1998-07-01 00:00:00
abstract：:The use of 3H-paroxetine as a ligand for quantitative autoradiography of serotonin (5-HT) transport sites was optimized, and the distribution of 3H-paroxetine binding sites in rat brain was studied. Under the conditions described, 3H-paroxetine binding in forebrain sections was of high affinity and saturable, with a K...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(92)90043-z
更新日期：1992-07-01 00:00:00
abstract：:The origins of safety pharmacology are grounded upon observations that organ functions (like organ structures) can be toxicological targets in humans exposed to novel therapeutic agents, and that drug effects on organ functions (unlike organ structures) are not readily detected by standard toxicological testing. Safet...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2004.02.007
更新日期：2004-05-01 00:00:00
abstract：:There is a need for short-term, reliable and reproducible animal model of chronic pancreatitis (CP) in small animals like mice. This study was aimed to establish the 9 exposures of cerulein-induced CP in mice. Repeated intraperitoneal cerulein injections were performed at 6 consecutive doses (50 μg/kg)/day, 3 days a w...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2019.01.002
更新日期：2019-01-01 00:00:00
abstract：INTRODUCTION:Inhalation of antigen in atopic asthma induces early (EAR) and late asthmatic responses (LARs), inflammatory cell infiltration and airways hyperresponsiveness (AHR). Previously, we have established a protocol of sensitisation and subsequent ovalbumin (Ova) inhalation challenge in guinea-pigs which induced ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.10.007
更新日期：2015-03-01 00:00:00
abstract：:Seizures are amongst the most frequent neurological issues encountered in pre-clinical safety testing. The objective was to characterize EEG morphologies and premonitory signs in drug-induced seizures in preclinical species. A comparative (inter-species) retrospective analysis for drug-induced seizures recorded by vid...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2019.106611
更新日期：2019-01-01 00:00:00
abstract：:Lipid peroxidation is a major consequence of oxidative stress and an important cause of neuronal damage in ischaemic injuries and neurodegenerative disorders such as Parkinson's disease. Recent research has focused on the development of antioxidant drugs which may delay or minimize neurodegeneration. Rapid and reliabl...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(98)00022-7
更新日期：1998-04-01 00:00:00
