Cyclosporine-induced coronary artery constriction--dissociation between thromboxane release and coronary vasospasm

Autor: Gerhard Walker, Hans-Joachim Kraemer, Harald Tillmanns, Werner Haberbosch, Markus Feussner, Ruediger C. Braun-Dullaeus, Heike Hopmann, Friedrich Grimminger
Rok vydání: 1999
Předmět:
Male
Thromboxane
Vasodilator Agents
Receptors
Thromboxane
Coronary Vasospasm
Blood Pressure
Polyethylene Glycols
Thromboxane receptor
Thromboxane A2
chemistry.chemical_compound
Nitroglycerin
Heart Rate
Vasoconstrictor Agents
Prostanoic Acids
Heart
Calcium Channel Blockers
Coronary Vessels
medicine.anatomical_structure
Anesthesia
Cardiology
Cyclosporine
Pharmaceutical Vehicles
Cardiology and Cardiovascular Medicine
Perfusion
Immunosuppressive Agents
medicine.drug
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Nifedipine
6-Ketoprostaglandin F1 alpha
Internal medicine
Coronary Circulation
medicine
Animals
Cyclooxygenase Inhibitors
Nitric Oxide Donors
Rats
Wistar
Transplantation
Aspirin
business.industry
Myocardium
Prostanoid
medicine.disease
Myocardial Contraction
Rats
Coronary arteries
Thromboxane B2
chemistry
Coronary vasospasm
Surgery
Endothelium
Vascular
business
Zdroj: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 18(4)
ISSN: 1053-2498
Popis: Cyclosporine influences vascular tone, including that of coronary arteries. But its effect on myocardial prostanoid release, which may contribute to a drug-induced coronary and/or myocardial dysfunction, remains unknown. We used the isolated perfused rat heart to study the effect of cyclosporine on both the mechanical function parameters and myocardial prostanoid release into the effluent by ELISA. Cyclosporine (5 microM) induced an increase of perfusion pressure from 40 +/- 3 to 73 +/- 4 mm Hg within 60 minutes (p0.001), reflecting an increase of coronary tone. Cyclosporine did not affect heart rate but contractility (+dp/dtmax) tended to decrease, although not significantly. The drug's effect on coronary tone was rapidly reversible upon withdrawal. Cyclosporine perfusion resulted in an increase of thromboxane B2 liberation from 236 +/- 150 to 1321 +/- 354 pg/ml effluent (p0.001), whereas the 6-keto-prostaglandin F1 alpha release was unaffected. The vehicle cremophor did not change any of these parameters. Neither inhibition of myocardial prostanoid formation with acetylsalicylic acid nor thromboxane receptor blockade prevented the cyclosporine-induced increase of perfusion pressure. However, perfusion with nitroglycerin or the voltage-sensitive calcium channel antagonist nifedipine in addition to cyclosporine were able to prevent the increase of perfusion pressure. This is the first time it has been demonstrated that cyclosporine induces an acute release of the prostanoid thromboxane within the myocardium. Despite the resulting imbalance in favor of the vasoconstrictive prostanoid, a dependency of the cyclosporine-induced increase of coronary tone on this imbalance was excluded. Conversely, nitric oxide donation or calcium channel blockade were able to prevent the negative effect of the drug on coronary tone, supporting the concept of endothelium-dependent and/or myogenic mechanism of cyclosporine toxicity on the coronary vascular bed.
Databáze: OpenAIRE
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