title: Hypothermia in cardiogenic shock reduces systemic t-PA release.
abstract: Therapeutic hypothermia has been found to improve hemodynamic and metabolic parameters in cardiogenic shock. Tissue plasminogen activator (t-PA) is a pro-thrombolytic enzyme, which also possesses pro-inflammatory properties. Interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) are pro-inflammatory cytokines; interleukin 10 (IL-10) and transforming growth factor beta 1 (TGF-β1) are anti-inflammatory cytokines. The aim of this experiment was to investigate the mechanism behind the protective effect of therapeutic hypothermia in cardiogenic shock. This was done by studying the effect of hypothermia on basal t-PA levels, peripheral t-PA release, and on the inflammatory response. Cardiogenic shock was induced by inflation of an angioplasty balloon in the proximal left anterior descending artery for 40 min in 16 pigs, followed by 110 min of reperfusion. The animals were randomized to hypothermia (33°C, n = 8), or normothermia (n = 8) at reperfusion. Hemodynamic parameters were continuously monitored. Plasma was sampled every 30 min for analysis of blood-gases and t-PA, and for analysis of inflammatory markers at baseline and at the end of the experiment. t-PA, IL-6 and TGF-β1 increased during cardiogenic shock. Apart from favourably affecting hemodynamic and metabolic variables, hypothermia was found to reduce basal arterial and venous t-PA levels, and to inhibit the release of t-PA from the peripheral vascular bed. Hypothermia did not alter the inflammatory response. In conclusion, mild hypothermia improves hemodynamic and metabolic parameters in cardiogenic shock. This is associated with a reduction in basal t-PA levels and t-PA release from the peripheral vascular bed, but not with an altered inflammatory response.
authors.affiliation: Department of Cardiology, Skåne University Hospital, Lund University, 221 85, Lund, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: van der Pals
authors.forename: Michael I
authors.initials: MI
authors.lastname: Götberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Götberg
authors.forename: Lillemor Mattsson
authors.initials: LM
authors.lastname: Hultén
authors.forename: Mia
authors.initials: M
authors.lastname: Magnusson
authors.forename: Sverker
authors.initials: S
authors.lastname: Jern
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D005260:Female; D006439:Hemodynamics; D007036:Hypothermia, Induced; D008297:Male; D012770:Shock, Cardiogenic / Q000097:blood*; D013552:Swine; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood*
chemical_list: D016207:Cytokines; D010959:Tissue Plasminogen Activator