Biomedical subjects

Michael Wittkamp

Publications and source records attributed to Michael Wittkamp.

3 recordsLinked to original sources

PubMed2006

Vardenafil: a novel type 5 phosphodiesterase inhibitor reduces myocardial infarct size following ischemia/reperfusion injury via opening of mitochondrial K(ATP) channels in rabbits.

cGMP and opening of mitochondrial K(ATP) channel play an important role in preconditioning of the heart following ischemia/reperfusion (I/R) injury. We investigated the cardioprotective effect of vardenafil (VAR) (Levitra), a highly selective and biochemically potent inhibitor of phosphodiesterase-5 (PDE-5) that enhances erectile function in men through up-regulation of cGMP. Rabbits were treated with VAR (0.014 mg/kg, iv) or volume-matched saline, 30 min prior to 30 min of sustained regional ischemia followed by 3 h of reperfusion. 5-hydroxydecanoate (5-HD, 5 mg/kg, iv) or HMR 1098 (HMR, 3 mg/kg, iv), the respective blockers of mitochondrial or sarcolemmal K(ATP) channels were administered 10 min before I/R. Infarct size was measured by computer morphometry of tetrazolium stained sections. Vardenafil treatment caused decrease in mean arterial blood pressure from 93.5+/-2.6 to 82.2+/-1.5 mmHg and increase in heart rate from baseline value of 151+/-20 to 196+/-4.6 bpm (mean+/-standard error of mean (S.E.M.), P<0.05) within 5 min. The infarct size (% of risk area) was reduced from 33.8+/-1.3 in control rabbits to 14.3+/-2.2 (58% reduction, P<0.05). 5-HD abolished VAR-induced protection as demonstrated by increase in infarct size to 34.5+/-2.3 (P<0.05, N=6 per group). In contrast, HMR failed to block the protective effect of VAR (infarct size, 14.3+/-2.2 versus 16.3+/-1.0 in VAR + HMR, P>0.05). Neither inhibitors of the K(ATP) channel influenced the infarct size in the control rabbits, as shown by infarct size of 34.9+/-1.1 and 33.3+/-1.4 in animals treated with 5-HD and HMR, respectively. For the first time, we demonstrate that VAR induces protective effect against I/R injury via opening of mitochondrial K(ATP) channel. These results further support our hypothesis that the novel class of PDE-5 inhibitors induce protective effect in the ischemic heart, in addition to their well known clinical effects in the treatment of erectile dysfunction in men.

Adenosine Triphosphate↗

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

A comparison of pulmonary vein ostial anatomy by computerized tomography, echocardiography, and venography in patients with atrial fibrillation having radiofrequency catheter ablation.

Accurate assessment of pulmonary vein anatomy is important to procedures that isolate these structures in patients with atrial fibrillation. Various modalities of pulmonary vein (PV) imaging are employed in clinical practice; however, the consistency of findings among the different modalities is unknown. The purpose of this study is to compare PV ostial anatomy by 4 common imaging techniques. Twenty-four patients undergoing catheter-based PV isolation procedures for atrial fibrillation had their PV ostial anatomy determined by cardiac computerized tomography (CT) and transesophageal echocardiography (TEE) before ablation and by intracardiac echocardiography (ICE) and venography during the ablation procedure. The number and maximal dimension of the PV ostia were determined by each imaging modality. In the 24 patients, 98 PV ostia were visualized by CT, 93 by ICE, 81 by TEE, and 71 by venography. The average ostial diameters were similar between CT (1.45 +/- 0.29 cm) and ICE (1.51 +/- 0.22 cm, p = 0.066). Compared with CT or ICE, the ostial diameters were larger with venography (1.67 +/- 0.32 cm) and smaller with TEE (1.16 +/- 0.28 cm, all p <0.001). PV ostial diameters as determined by ICE were significantly correlated with CT measurements (r = 0.57, p <0.001) and venography (r = 0.52, p <0.001). Venography measures of PV diameter were correlated with measures by CT (r = 0.33, p = 0.03). TEE measures were not correlated with any other modality (all p >/=0.43). CT identifies the greatest number of PV ostia followed by ICE. Venography overestimates and TEE underestimates ostial diameters compared with CT or ICE. The PV ostial dimensions obtained by ICE, CT, and venography are all significantly correlated.

Atrial Fibrillation↗