Mild hypothermia markedly reduces ischemia related coronary t-PA release
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In experimentally induced myocardial ischemia, mild hypothermia (33–35°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°C was established using an intravascular cooling/warming catheter. The pigs were then randomized to hypothermia (34°C) or control (37°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) × (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.
Keywordst-PA Ischemia Hypothermia
The study has been supported by the Swedish Scientific Research Council, the Swedish Heart and Lung Foundation, the Vascular Wall program (Lund University Faculty of Medicine) and Hains Foundation. David Erlinge is a holder of the Lars Werkö distinguished research fellowship from the Swedish Heart and Lung Foundation. We would like to thank Boston Scientific Cardiology, Nordic AB (Helsingborg, Sweden) for their generosity in unrestricted donations of catheters and guide wires for use in animal research and Innercool therapies Inc., San Diego, CA, USA for unrestricted loan of the Celsius Control™ cooling consol.
- 5.Rapid Intravascular Cooling in Myocardial Infarction as Adjunctive to Percutaneous Coronary Intervention (RAPID MI-ICE). www.clinicaltrials.gov
- 6.Can Hypothermia be Incorporated Into Primary Angioplasty for Heart Attack? (CHIPAHA). www.clinicaltrials.org
- 8.2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 7.5: postresuscitation support. Circulation 112(Suppl I):IV-84–IV-88, 2005. doi: 10.1161/CIRCULATIONAHA.105.166560
- 10.Wang Y, Hand AR, Wang YH et al (1998) Functional and morphologic evidence of the presence of tissue-plasminogen activator in vascular nerves: implications for a neurologic control of vessel wall fibrinolysis and rigidity. J Neurosci Res 53:443–453. doi: 10.1002/(SICI)1097-4547(19980815)53:4<443::AID-JNR6>3.0.CO;2-6 CrossRefPubMedGoogle Scholar
- 18.Witherow FN, Dawson P, Ludlam CA et al (2002) Marked bradykinin-induced tissue plasminogen activator release in patients with heart failure maintained on long-term angiotensin-converting enzyme inhibitor therapy. J Am Coll Cardiol 40:961–966. doi: 10.1016/S0735-1097(02)02061-2 CrossRefPubMedGoogle Scholar