ORIGINAL ARTICLESDifferent cardiac tissue plasminogen activator release patterns by local stimulation of the endothelium and sympathetic nerves in pigsAspelin, Trudea; Eriksen, Mortenb; Ilebekk, Arnfinnb; Björkman, Jan-Arnec; Lyberg, TorsteinaAuthor Information aDepartment of Medical Biochemistry, Oslo University Hospital, Ullevål bInstitute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway cAstraZeneca R&D, Mölndal, Sweden Correspondence to Trude Aspelin, IEMF, Bygg 7, 4.etg, Oslo Universitetssykehus, Ullevål, Kirkeveien 166, Post box 4956 Nydalen, 0424 Oslo, Norway E-mail: [email protected] Received 24 April, 2012 Accepted 6 July, 2012 Blood Coagulation & Fibrinolysis: December 2012 - Volume 23 - Issue 8 - p 714-722 doi: 10.1097/MBC.0b013e328357d388 Buy Metrics Abstract Myocardial ischemia induces cardiac tissue plasminogen activator (tPA) release, declining by repeated periods of ischemia. However, the mechanisms and cellular sources are unknown. Sympathetic nerve stimulation (SS) and bradykinin (BK), an endogenous inducer of endothelial tPA release, may play roles, potentially involving different sources or mechanisms revealed by different release patterns. Therefore, we compared the cardiac tPA release patterns during repeated coronary BK infusions and SS, both with an ensuing period of local myocardial ischemia/reperfusion (I/R). Nine pigs were subjected to four periods of coronary BK infusion (4 min) and another nine animals to four periods of SS (4 min). Finally, 10 min of I/R was induced in both groups. The single-peaked BK-induced tPA release declined toward baseline by repeated infusions, but tPA release reappeared during I/R. In contrast, total tPA release during repeated SS and subsequent I/R was more stable, and SS-induced total tPA and norepinephrine (NE) releases were strongly correlated. Surprisingly, the instantaneous SS-induced tPA release was biphasic with a stable first peak, and a second peak declining toward baseline by repeated stimulations. The fluctuations in cardiac release of plasminogen activator inhibitor-1 and the endogenous BK inhibitor angiotensin-converting enzyme, could not explain the diverging tPA release patterns. Different tPA release patterns were demonstrated during SS and BK stimulation, as well as diverging responses to repeated stimulations and subsequent I/R. This study demonstrates strong association between tPA and NE during SS and possibly two different sources or mechanisms for SS-induced tPA release. © 2012 Lippincott Williams & Wilkins, Inc.