Biomedical subjects

Eric Chou

Publications and source records attributed to Eric Chou.

4 recordsLinked to original sources

PubMed2006

Sildenafil and vardenafil but not nitroglycerin limit myocardial infarction through opening of mitochondrial K(ATP) channels when administered at reperfusion following ischemia in rabbits.

Phosphodiesterase-5 (PDE-5) inhibitors including sildenafil and vardenafil induce powerful preconditioning-like cardioprotective effect against ischemia/reperfusion injury through opening of mitochondrial K(ATP) channels in the heart. The goal of these studies was to demonstrate the protective effect of sildenafil and vardenafil on reperfusion injury and to compare it with the antianginal vasodilator nitroglycerin (NTG). In addition, we determined the role of mitochondrial K(ATP) channels in protection. Adult male New Zealand white rabbits were anesthetized and subjected to ischemia by 30 min of coronary artery occlusion followed by 3 h of reperfusion. Seven groups were studied. 1-Controls; 2-Sildenafil (total dose: 0.71 mg/kg; i.v.) infused for 65 min starting 5 min before reperfusion; 3-Sildenafil+5-hydroxydecanoate (5-HD, blocker of mitochondrial K(ATP) channel, total dose: 5 mg/kg) administered as 2 bolus injections; 4-Vardenafil (total dose: 0.014 mg/kg; iv) administered as in group 2; 5-Vardenafil+5-HD administered as in group 3; 6-5-HD administered as two bolus injections and 7-Nitroglycerin (NTG, total dose: 2 microg kg(-1) min(-1)) administered as in group 2. Infarct size was reduced in sildenafil (19.19+/-1.3%) as well as vardenafil (17.0+/-2.0%) treated groups as compared to controls (33.8+/-1.7%). However, NTG failed to confer similar cardioprotection (31.5+/-0.8%). 5-HD blocked the cardioprotective effects of sildenafil and vardenafil as shown by an increase in infarct size (34.0+/-1.1% and 28.3+/-1.9%, respectively). Both sildenafil and vardenafil protect the ischemic myocardium against reperfusion injury through a mechanism dependent on mitochondrial K(ATP) channel opening.

Animals↗

PubMed2006

Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding.

Dual antiplatelet therapy of aspirin and a thienopyridine is the standard of care following coronary stenting. Patients who are on chronic warfarin therapy and receive a coronary stent need to be treated with the triple therapy of aspirin, clopidogrel and warfarin; however, the bleeding risk in these patients is unknown. To evaluate the bleeding risk in patients requiring chronic warfarin therapy and undergoing stent implantation, we compared 107 consecutive patients on chronic warfarin therapy who underwent coronary stenting and were discharged on aspirin, clopidogrel and warfarin to 107 contemporary patients who were treated with aspirin and clopidogrel. We evaluated their bleeding history before and after coronary stenting. Major bleeding was defined as bleeding that was significantly disabling, intraocular or requiring at least 2 units of blood transfusion. Minor bleeding was defined as other bleeding that led to interruption of the medications. Patients on triple therapy were younger and more likely to have hypertension. This group had significantly higher major bleeding (6.6% vs. 0%; p = 0.03) and minor bleeding (14.9% vs. 3.8%; p = 0.01) compared with the dual antiplatelet therapy group. In the triple therapy group, the international normalized ratio or aspirin dosage did not influence the bleeding risk. In patients requiring warfarin therapy, the addition of dual antiplatelet therapy is associated with an approximately 7% major bleeding risk. Thus, novel regimens are needed to reduce the bleeding risk.

Aged↗

PubMed2005

Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications.

The phosphodiesterase type-5 (PDE5) inhibitor, sildenafil, is the first drug developed for treatment of erectile dysfunction in patients. Experimental data in animals show that sildenafil has a preconditioning-like cardioprotective effect against ischemia/reperfusion injury in the intact heart. Mechanistic studies suggest that sildenafil exerts cardioprotection through NO generated from eNOS/iNOS, activation of protein kinase C/ERK signaling and opening of mitochondrial ATP-sensitive potassium channels. Additional studies show that the drug attenuates cell death resulting from necrosis and apoptosis, and increases the Bcl2/Bax ratio through NO signaling in adult cardiomyocytes. Emerging new data also suggest that sildenafil may be used clinically for treatment of pulmonary arterial hypertension and endothelial dysfunction. Future demonstration of the cardioprotective effect in patients with the relatively safe and effective FDA-approved PDE5 inhibitors such as sildenafil could have an enormous impact on bringing the long-studied phenomenon of ischemic and pharmacologic preconditioning to the clinical forefront.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

Sildenafil citrate (viagra) induces cardioprotective effects after ischemia/reperfusion injury in infant rabbits.

Infants undergoing surgery for congenital heart disease are at risk for myocardial ischemia during cardiopulmonary bypass, circulatory arrest, or low-flow states. The purpose of this study was to demonstrate the effects of sildenafil, a selective phosphodiesterase-5 (PDE-5) inhibitor on myocardial functional improvement and infarct size reduction during ischemia/reperfusion injury in infant rabbits. Infant rabbits (aged 8 wk) were treated with sildenafil citrate (0.7 mg/kg i.v.) or normal saline 30 min before sustained ischemia for 30 min and reperfusion for 3 h. Transesophageal echocardiography (TEE) was used to assess left ventricular cardiac output (LVCO) and aortic velocity time integral (VTI). After ischemia/reperfusion, risk area was demarcated by Evan's blue dye and infarct size determined by computer morphometry of triphenyltetrazolium chloride-stained sections. The sildenafil-treated group had preservation and elevation in LVCO (143% of baseline, p < 0.05) and an elevated aortic VTI (145% of baseline, p < 0.05) after 30 min of ischemia compared with the control group LVCO (72% of baseline, p < 0.05) and aortic VTI (73% of baseline, p < 0.05). This is a statistically significant increase in LVCO and aortic VTI in the sildenafil group compared with controls (n = 6/group, p < 0.05). The sildenafil-treated group had significant reduction in infarct size (15.5 +/- 1.2 versus 33 +/- 2.3 in the saline group, % risk area, mean +/- SEM, n = 10-15/group, p < 0.05). For the first time, we have shown that sildenafil citrate promotes myocardial protection in infant rabbits as evidenced by postischemic preservation and elevation in LVCO and aortic VTI and reduction in infarct size.

3',5'-Cyclic-GMP Phosphodiesterases↗