Hemodynamic effects of combined sildenafil and L-arginine during acute pulmonary embolism-induced pulmonary hypertension.
ABSTRACT Sildenafil attenuates acute pulmonary embolism-induced pulmonary hypertension. However, the hemodynamic effects of sildenafil in combination with other vasodilators during acute pulmonary embolism have not been examined yet. In the present study, we examined the hemodynamic effects of combined sildenafil (0.25 mg/kg, i.v.) and L-arginine (100, 200, 500, and 1000 mg/kg/h, i.v.) in an anesthetized dog model of acute pulmonary embolism. Plasma nitrite/nitrate (NO(x)) and cGMP concentrations were determined using an ozone-based chemiluminescence assay and a commercial enzyme immunoassay, respectively. We found that L-arginine alone did not attenuate acute pulmonary embolism-induced pulmonary hypertension. However, significant decreases in mean pulmonary artery pressure were observed 30, 45, 60, and 75 min after the administration of sildenafil alone or after the combined administration of sildenafil and L-arginine (all P < 0.05). No significant differences among groups were observed in the respiratory parameters. While L-arginine significantly increased NO(x) concentrations, cGMP concentrations increased only when sildenafil was administered (all P < 0.05). These results suggest that while sildenafil attenuates acute pulmonary embolism-induced pulmonary hypertension, L-arginine does not enhance the beneficial hemodynamic effects of sildenafil. In addition, these findings suggest that stimulation of NO synthesis with L-arginine during acute pulmonary embolism does not produce beneficial effects.
Article: Pulmonary thromboembolism.[show abstract] [hide abstract]
ABSTRACT: To review the pathophysiology, clinical signs, diagnosis, and treatment of pulmonary thromboembolism (PTE) in small animals. Human and veterinary clinical studies, reviews, texts, and recent research in canine and feline PTE diagnosis and thromboembolic therapeutics. In humans, clinical probability assessment and point-of-care D-dimer-based algorithms are widely used. Computed tomography pulmonary angiography is the gold standard for PTE diagnosis in humans. Echocardiography is increasingly used for bedside assessment of affected patients. In low-risk human patients anticoagulants alone are recommended while patients with cardiogenic shock are treated with thrombolytics followed by anticoagulation. PTE is associated with numerous predisposing conditions causing hypercoagulability, blood flow stasis, or endothelial injury. Identifying at-risk patients is key to diagnosis in small animals. Thromboelastography provides a method for identifying hypercoagulable patients. Computed tomography pulmonary angiography may replace selective pulmonary angiography as the imaging technique of choice for PTE diagnosis. PTE therapy consists of supportive treatment combined with appropriate, individualized thromboembolic pharmacotherapy for acute treatment and chronic management. Thrombolytic therapy for PTE remains controversial but may be indicated in hemodynamically unstable acute PTE. Thromboprophylaxis in specific conditions is rational although evidence of efficacy is limited. Prognosis depends upon degree of cardiopulmonary compromise and patient response to therapy. Mortality rates in small animals are unknown. New diagnostic techniques and advances in therapy offer significant potential for improvements in the identification and treatment of PTE in small animals. Further study must be directed to validating new diagnostic modalities and evaluating therapeutic regimes.Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001). 03/2009; 19(1):30-52.