Biomaterial Database

Dose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated heart. 2010

Theofilos M Kolettis, and Konstantinos Kontaras, and Ioannis Spartinos, and Christos Maniotis, and Varnavas Varnavas, and Michael Koutouzis, and Iordanis Mourouzis, and Apostolos Papalois, and Constantinos Pantos, and Zenon S Kyriakides

Department of Cardiology, University of Ioannina, Ioannina, Greece.

OBJECTIVE Sildenafil may be beneficial during myocardial ischaemia/reperfusion, but this effect may be dose-dependent, accounting for previous conflicting results. We have explored the effects of two acute and one chronic administration regimen on left ventricular function. METHODS The study was conducted on 36 Wistar rats (290 +/- 7 g). Sildenafil was administered 30 min before ischaemia at a low (0.7 mg/kg, n= 8) or high (1.4 mg/kg, n= 8)dosage. The chronic treatment arm (n= 8) consisted of two daily injections of sildenafil (0.7 mg/kg) for three weeks. The control group was formed by 12 rats. Ischaemic contracture, post-ischaemic recovery and hypercontracture were measured in isolated, Langendorff-perfused preparations. RESULTS Ischaemic contracture tended to be lower after high-dose sildenafil, while remaining unchanged after low-dose or chronic sildenafil administration. Compared with controls (62.9 +/- 2.0% of baseline developed pressure), post-ischaemic recovery was higher (P= 0.0069) after low dose (75.1 +/- 2.4%), unchanged (P= 0.13) after high dose (69.1 +/- 2.1%), but lower (P < 0.001) after chronic (42.9 +/- 4.5%) sildenafil administration. Compared with controls (71.8 +/- 3.9 mmHg), hypercontracture was higher (P= 0.0052) after chronic sildenafil administration (89.5 +/- 4.1 mmHg), but similar after acute low dose (65.7 +/- 3.3 mmHg, P= 0.33) or high dose (67.1 +/- 4.7 mmHg, P= 0.43). CONCLUSIONS The effects of sildenafil after ischaemia/reperfusion were strongly dose-dependent. Beneficial actions on left ventricular function were evident after acute pretreatment with a low dosage, but were lost after doubling the dose. Chronic sildenafil administration deteriorated left ventricular function during ischaemia and reperfusion.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010726	Phosphodiesterase Inhibitors	Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.	Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011687	Purines	A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D011897	Random Allocation	A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.	Randomization,Allocation, Random
D002316	Cardiotonic Agents	Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).	Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D000068677	Sildenafil Citrate	A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION.	1-((3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine citrate,Acetildenafil,Desmethyl Sildenafil,Desmethylsildenafil,Homosildenafil,Hydroxyhomosildenafil,NCX-911,Revatio,Sildenafil,Sildenafil Lactate,Sildenafil Nitrate,UK 92480-10,UK-92,480-10,Viagra,Citrate, Sildenafil,Lactate, Sildenafil,NCX 911,NCX911,Nitrate, Sildenafil,Sildenafil, Desmethyl,UK 92,480 10,UK 92480 10,UK 9248010
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia