sildenafil-citrate and Heart-Arrest

MiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.. Thirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n = 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20 mg/kg L) group (n = 8), saline (SA group, n = 8); and sham operation group (sham group, n = 8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time polymerase chain reaction and ultra structural analysis were performed to evaluate myocardial injury.. Compared with the sildenafil + L-NAME and saline groups, the sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, and attenuated myocardial injury; In this study, CA pigs showed evidently increased levels of miR-155-5p and miR-145-5p, while the sildenafil treatment decreased the levels of miR-155-5p and miR-145-5p in CA pigs. In addition, the levels of eNOS was decreased in CA pigs, validating sildenafil attenuating post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.. Sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.

Topics: Animals; Cardiomyopathies; Cardiopulmonary Resuscitation; Disease Models, Animal; Heart Arrest; Hemodynamics; Male; MicroRNAs; Nitric Oxide Synthase Type III; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Swine

Topics: Antihypertensive Agents; Female; Heart Arrest; Heart Failure; Humans; Hypertension, Pulmonary; Middle Aged; Pulmonary Artery; Pulmonary Wedge Pressure; Risk Factors; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents; Ventricular Function, Left

Infarto medular y de cuerpos vertebrales cervicales tras consumo de sildenafilo.

Topics: Angiography; Bradycardia; Cardiopulmonary Resuscitation; Cervical Vertebrae; Heart Arrest; Humans; Hypotension; Infarction; Male; Middle Aged; Paresis; Sildenafil Citrate; Spinal Cord; Spinal Cord Ischemia; Sympathetic Nervous System; Vasoconstriction

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

Topics: Angiotensin II; Animals; Apoptosis; Cardiopulmonary Resuscitation; Cardiotonic Agents; Cyclic GMP; Disease Models, Animal; Gene Expression Regulation; Heart Arrest; Hemodynamics; Male; Myocardial Reperfusion Injury; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Phosphodiesterase 5 Inhibitors; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Sildenafil Citrate; Swine

Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism.. Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation.. After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na(+)-K(+)-ATPase and Ca(2+)-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively).. Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.

Topics: Animals; Animals, Newborn; Cardiopulmonary Resuscitation; Heart Arrest; Male; Metabolism; Microdialysis; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Swine

Resuscitation after cardiac arrest may lead to ischemia-reperfusion injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5 inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac transplantation model.. Sixty-one Fischer344 rats underwent syngeneic heterotopic cardiac transplantation after ischemia and ligation of the left anterior coronary artery of the heart to yield myocardial infarction (IRI + MI). Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI +MI + S). Twenty-three additional grafted animals with transplantation only served as controls with ischemia reperfusion injury (IRI). After 2 days, immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed after graft harvesting and histology.. Two days after transplantation, remote intramyocardial arteries were more preserved in IRI + MI + S as compared with IRI +MI and IRI (0.74 ± 0.14, 0.56 ± 0.23 and 0.55 ± 0.22, PSU, p < 0.05, respectively). Decreased eNOS staining confirmed the presence of developing infarction in IRI + MI and IRI + MI + S. The expression of iNOS was significantly lower during IRI + MI +S as compared with IRI + MI (0.02 ± 0.01 and 1.02 ± 0.02, FC, p < 0.05).. Administered at the onset of reperfusion and developing infarction, sildenafil has an impact on myocardial recovery after cardiac arrest and ischemia.

Topics: Animals; Aquaporins; Coronary Vessels; Disease Models, Animal; Drug Administration Schedule; Heart Arrest; Heart Transplantation; Immunohistochemistry; Injections, Subcutaneous; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Rats; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; Sildenafil Citrate; Sulfones; Time Factors; Vasodilator Agents

A 23-week-old baby, born at 26(+2) weeks, presented to the hospital with critical respiratory failure, which was impossible to stabilize. She had unstable oxygen saturations between 35% and 95%. A presumptive diagnosis of bronchopulmonary dysplasia with associated pulmonary hypertensive crisis was made. In the absence of inhaled nitric oxide, 2 oral doses of 1 mg/kg sildenafil were given, with a dramatic improvement 30 to 45 minutes later. Her oxygenation index fell from 43 to 14. She made a full recovery and was discharged from the hospital 2 weeks later.

Topics: Administration, Oral; Bronchopulmonary Dysplasia; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Arrest; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Intubation, Gastrointestinal; Oxygen; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Respiratory Insufficiency; Sildenafil Citrate; Sulfones; Vasodilator Agents

Left coronary artery arising from the right sinus of Valsalva is an uncommon congenital coronary anomaly that seems to be associated with sudden death in young patients.. We report a case of cardiac arrest in a 59-year-old patient after sexual intercourse and Sildenafil ingestion. A coronary arteriography and an angiographic computed tomography scan subsequently revealed a LCA origin from the right aortic sinus along with an intramural course of the left main stem. In addition a distal stenosis of the right coronary artery was detected. After successful resuscitation without neurological deficits coronary artery bypass surgery was performed.. To our knowledge, this is the first report demonstrating sudden cardiac arrest associated with Sildenafil ingestion in a patient with this type of coronary anomaly. The question arises, whether a cardiac screening is necessary before a Sildenafil therapy is initiated.

Topics: Coronary Vessel Anomalies; Heart Arrest; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones

The highly putrefied corpse of an 80-year-old man was found in the apartment which he had rented to a prostitute. A package of Viagra 25 was found beside the corpse and three tablets were missing. Autopsy revealed severe coronary artery sclerosis as well as signs of previous myocardial infarctions. For the detection and identification of sildenafil and three metabolites in urine and tissue samples, solid-phase extraction, LC/MS and MS/MS methods were developed. Blood was not available for toxicological analysis due to the putrefaction. For method development, urine from a volunteer who had ingested 25 mg sildenafil was collected over 8 h, and three metabolites were identified by MS/MS. These metabolites were also found in the victim's urine. These findings prove that sildenafil was taken some time prior to death, but the causality of sildenafil intake and fatal cardiac failure could not be proven, since no blood was available for analysis. However, the administration of sildenafil was contraindicated due to several previous myocardial infarctions.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Aged; Aged, 80 and over; Autopsy; Chromatography, High Pressure Liquid; Heart Arrest; Humans; Linear Models; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Spectrometry, Mass, Electrospray Ionization; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adverse Drug Reaction Reporting Systems; Aged; Canada; Erectile Dysfunction; Heart Arrest; Humans; Male; Middle Aged; Myocardial Infarction; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones