{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T10:14:36Z","timestamp":1766398476944,"version":"3.48.0"},"reference-count":21,"publisher":"IMR Press","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HSF"],"abstract":"Background: Papaverine (Paveron N\u2122 Linden Arzneimittel Vertrieb GmbH, Germany) is a widely used agent for preventing spasm in mammary artery preparations. The question addressed in this study is whether the intraluminal administration of papaverine can result in detectable absorption of the drug into the systemic arterial circulation.Methods: In 15 patients (age 65 \u00b1 6 years; body mass index 28.9 \u00b1 3.7), an internal mammary artery (IMA) was prepared during coronary artery bypass grafting (CABG). A maximum of 3 mL of a 1 mg\/1 mL diluted papaverine solution was injected intravascularly (intraluminally) for spasm prophylaxis. The IMA was closed proximally and distally with bulldog clamps. Blood samples were taken immediately after administration (T1), after 20 minutes (T2), and at the end of the operation (T3). Samples were measured in a liquid chromatography--tandem mass spectrometry (LC-MS\/MS) system consisting of a binary pump from Agilent (Waldbronn, Germany) coupled to a high-throughput screening (HTS) PAL injection system (CTC, Zwingen, Switzerland) and a tandem mass spectrometer (API 4000, AB Sciex, Darmstadt, Germany). Papaverine was analyzed in positive mode using an electrospray ion source. Quantitation was performed using Analyst 1.5 software (AB Sciex, Darmstadt, Germany).Results: The newly developed LC-MS\/MS method was successfully established for the detection of papaverine in plasma samples. The highest plasma papaverine levels were determined at time point T1 (mean 54.7 \u00b1 39 ng\/mL, range 16.6-179 ng\/mL). The concentration was already halved 20 minutes after administration (T2) (mean 23.3 \u00b1 2 ng\/mL, range 4.6-118 ng\/mL). Because of the short half-life and the hemodilution in the extracorporeal circulation, at the end of the operation papaverine (T3) had already fallen to just above the limit of detection (mean 4.1 \u00b1 3.9 ng\/mL, range 1.3-16.9 ng\/mL). At time point T1, a significant negative correlation was determined between plasma levels and systemic diastolic, but not systolic, blood pressure.Conclusion: Papaverine was successfully determined systemically in plasma by LC-MS\/MS after intraluminal administration in the IMA. Systemic circulatory effects are dependent on the detected quantity. Group size and the absence of a control group are considerable limitations.<\/jats:p>","DOI":"10.1532\/hsf98.2013201","type":"journal-article","created":{"date-parts":[[2013,11,11]],"date-time":"2013-11-11T21:17:22Z","timestamp":1384204642000},"page":"E266-E270","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics of Intraluminally Administered Serum Papaverine for Spasm Prophylaxis of the Internal Mammary Artery"],"prefix":"10.31083","volume":"16","author":[{"given":"Arndt-Holger","family":"Kiessling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deniss","family":"Romasku","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres","family":"Beiras-Fernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nerea","family":"Ferreir\u00f3s","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Labocha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Moritz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ardawan Julian","family":"Rastan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2013,11,11]]},"reference":[{"key":"1","doi-asserted-by":"crossref","DOI":"10.1532\/HSF98.20061166","article-title":"Effects of pretreatment with different topical vasodilators on blood flow in the internal mammary artery: a prospective randomized study","volume":"10","author":"B. 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Goldman","year":"1982","journal-title":"J Thorac Cardiovasc Surg"},{"key":"8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1055\/s-0030-1271191","article-title":"Cardiac surgery in Germany during 2010: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery","volume":"59","author":"J. Gummert","year":"2011","journal-title":"Thorac Cardiovasc Surg"},{"key":"9","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1159\/000177372","article-title":"Endothelium-dependent and endothelium-independent flow regulation in coronary vascular regions supplied by arterial and venous bypass grafts","volume":"88","author":"A. Hartmann","year":"1997","journal-title":"Cardiology"},{"key":"10","unstructured":"Hazardous Substances Data Bank (HSDB). 2002. Papaverine. http:\/\/toxnet.nlm.nih.gov\/cgi-bin\/sis\/search\/f?.\/temp\/~Vp56q5:1<\/a>"},{"key":"11","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/S0022-5223(94)70420-1","article-title":"Pharmacologic dilatation of the internal mammary artery during coronary bypass grafting","volume":"107","author":"G. He","year":"1994","journal-title":"J Thorac Cardiovasc Surg"},{"key":"12","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/00045391-199504000-00007","article-title":"Hemodynamic responses to papaverine: do nitric oxide, cyclic GMP, or calcium mediate the vasodilation?","volume":"2","author":"J. Jahr","year":"1995","journal-title":"Am J Ther"},{"key":"13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0022-5223(19)34463-0","article-title":"Preparation of the internal mammary artery graft. Which is the best method?","volume":"98","author":"N. Mills","year":"1989","journal-title":"J Thorac Cardiovasc Surg"},{"key":"14","first-page":"632","article-title":"Preparations of internal mammary arteries for coronary bypass with intraluminal papaverine","volume":"16","author":"N. Mills","year":"1975","journal-title":"J Cardiovasc Surg"},{"key":"15","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0003-4975(97)00291-9","article-title":"Prevention of internal thoracic artery spasm","volume":"64","author":"A. Mulay","year":"1997","journal-title":"Ann Thorac Surg"},{"key":"16","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/S1010-7940(99)00308-5","article-title":"Preparation of the internal thoracic artery by vasodilator drugs: is it really necessary? A randomized double-blind placebo-controlled clinical study","volume":"16","author":"M. Nili","year":"1999","journal-title":"Eur J Cardiothorac Surg"},{"key":"17","first-page":"384","article-title":"Off-pump coronary artery bypass grafting. 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