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Mild hypothermia markedly reduces ischemia related coronary t-PA release.

vanderPals, Jesper LU ; Götberg, Matthias LU ; Olivecrona, Göran LU ; Brogren, Helen; Jern, Sverker and Erlinge, David LU (2010) In Journal of Thrombosis and Thrombolysis 29(3). p.289-295
Abstract
In experimentally induced myocardial ischemia, mild hypothermia (33-35 degrees C) has a robust cardioprotective effect. Tissue plasminogen activator (t-PA) is a profibrinolytic enzyme that is released from the vascular endothelial cells in response to ischemia and other injurious stimuli. t-PA has also been found to have proinflammatory properties that could contribute to reperfusion injury. We postulated that hypothermia could attenuate t-PA release in the setting of myocardial ischemia. Sixteen 25-30 kg pigs were anesthetized and a temperature of 37 degrees C was established using an intravascular cooling/warming catheter. The pigs were then randomized to hypothermia (34 degrees C) or control (37 degrees C). A doppler flow wire was... (More)
In experimentally induced myocardial ischemia, mild hypothermia (33-35 degrees C) has a robust cardioprotective effect. Tissue plasminogen activator (t-PA) is a profibrinolytic enzyme that is released from the vascular endothelial cells in response to ischemia and other injurious stimuli. t-PA has also been found to have proinflammatory properties that could contribute to reperfusion injury. We postulated that hypothermia could attenuate t-PA release in the setting of myocardial ischemia. Sixteen 25-30 kg pigs were anesthetized and a temperature of 37 degrees C was established using an intravascular cooling/warming catheter. The pigs were then randomized to hypothermia (34 degrees C) or control (37 degrees C). A doppler flow wire was placed distal to a percutaneous coronary intervention balloon positioned immediately distal to the first diagonal branch of the left anterior descending artery (LAD). The LAD was then occluded for 10 min in all pigs. Coronary blood flow and t-PA was measured before, during and after ischemia/reperfusion. t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus. Net t-PA release over the coronary bed was calculated by subtraction of arterial values from coronary sinus values. An estimate of differences in total t-PA release was calculated by multiplying net t-PA release with the relative increase in flow compared to baseline, measured in relative units consisting of ((ng/ml - ng/ml) x (cm/s/cm/s)). There was no observed difference in t-PA levels in peripheral arterial samples. As shown previously, net t-PA release increased during reperfusion. Hypothermia significantly inhibited the increase in t-PA release during reperfusion (peak value 9.44 +/- 4.34 ng/ml vs. 0.79 +/- 0.45 ng/ml, P = 0.02). The effect was even more prominent when an estimation of total t-PA release was performed with mean peak value in the control group 26-fold higher than in the hypothermia group (69.74 +/- 33.86 units vs. 2.62 +/- 1.10 units, P = 0.01). Mild hypothermia markedly reduces ischemia related coronary tissue plasminogen activator release. The reduction of t-PA release may contribute to the cardioprotective effect of hypothermia. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ischemia, t-PA, Hypothermia
in
Journal of Thrombosis and Thrombolysis
volume
29
issue
3
pages
289 - 295
publisher
Springer
external identifiers
  • wos:000275555100005
  • pmid:19499190
  • scopus:77957963540
ISSN
1573-742X
DOI
10.1007/s11239-009-0350-2
language
English
LU publication?
yes
id
3ca06857-b4c2-45c8-af39-7113fb9fba3f (old id 1434465)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19499190?dopt=Abstract
date added to LUP
2009-07-02 15:28:08
date last changed
2018-05-29 11:47:15
@article{3ca06857-b4c2-45c8-af39-7113fb9fba3f,
  abstract     = {In experimentally induced myocardial ischemia, mild hypothermia (33-35 degrees C) has a robust cardioprotective effect. Tissue plasminogen activator (t-PA) is a profibrinolytic enzyme that is released from the vascular endothelial cells in response to ischemia and other injurious stimuli. t-PA has also been found to have proinflammatory properties that could contribute to reperfusion injury. We postulated that hypothermia could attenuate t-PA release in the setting of myocardial ischemia. Sixteen 25-30 kg pigs were anesthetized and a temperature of 37 degrees C was established using an intravascular cooling/warming catheter. The pigs were then randomized to hypothermia (34 degrees C) or control (37 degrees C). A doppler flow wire was placed distal to a percutaneous coronary intervention balloon positioned immediately distal to the first diagonal branch of the left anterior descending artery (LAD). The LAD was then occluded for 10 min in all pigs. Coronary blood flow and t-PA was measured before, during and after ischemia/reperfusion. t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus. Net t-PA release over the coronary bed was calculated by subtraction of arterial values from coronary sinus values. An estimate of differences in total t-PA release was calculated by multiplying net t-PA release with the relative increase in flow compared to baseline, measured in relative units consisting of ((ng/ml - ng/ml) x (cm/s/cm/s)). There was no observed difference in t-PA levels in peripheral arterial samples. As shown previously, net t-PA release increased during reperfusion. Hypothermia significantly inhibited the increase in t-PA release during reperfusion (peak value 9.44 +/- 4.34 ng/ml vs. 0.79 +/- 0.45 ng/ml, P = 0.02). The effect was even more prominent when an estimation of total t-PA release was performed with mean peak value in the control group 26-fold higher than in the hypothermia group (69.74 +/- 33.86 units vs. 2.62 +/- 1.10 units, P = 0.01). Mild hypothermia markedly reduces ischemia related coronary tissue plasminogen activator release. The reduction of t-PA release may contribute to the cardioprotective effect of hypothermia.},
  author       = {vanderPals, Jesper and Götberg, Matthias and Olivecrona, Göran and Brogren, Helen and Jern, Sverker and Erlinge, David},
  issn         = {1573-742X},
  keyword      = {Ischemia,t-PA,Hypothermia},
  language     = {eng},
  number       = {3},
  pages        = {289--295},
  publisher    = {Springer},
  series       = {Journal of Thrombosis and Thrombolysis},
  title        = {Mild hypothermia markedly reduces ischemia related coronary t-PA release.},
  url          = {http://dx.doi.org/10.1007/s11239-009-0350-2},
  volume       = {29},
  year         = {2010},
}