Mild hypothermia markedly reduces ischemia related coronary t-PA release

Abstract

"Mild hypothermia markedly reduces ischemia related coronary t-PA release." Journal of thrombosis and thrombolysis, 2009 Jun 5 http://dx.doi.org/10.1007/s11239-009-0350-2Access to the published version may require journal subscription.Published with permission from: Springer Methods: 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 ten minutes 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)).Results: 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). Conclusion: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.

Hypothermia in cardiogenic shock reduces systemic t-PA release

“…Moreover, hypothermia has been shown to improve ion homeostasis, decrease free radical formation, stabilize cellular membranes and prevent intracellular acidosis [21]. It has also been shown to reduce ischemia related coronary t-PA release [28]. In the current experiment hypothermia was found to inhibit a shock-related increase in basal arterial and venous levels of t-PA and also the release of t-PA from the peripheral vascular bed.…”

“…The tissue-protective mechanism of action is multi-factorial and partly unknown [20][21][22][23][24][25][26][27]. We recently found that hypothermia reduces ischemia related coronary t-PA release, suggesting a possible role for t-PA as a mechanism for reperfusion injury that may be affected by hypothermia [28].…”

Hypothermia as a cytoprotective strategy in ischemic tissue injury

“…Like the brain, timing of hypothermia is a major concern in order to rescue the heart from ischemia. Several studies have shown salutary effects of hypothermia in cardioprotection when cooling began prior to the onset of ischemia (Hale and Kloner 1997,van der Pals et al 2009). While consistent and robust effects have been demonstrated, such a paradigm would have limited clinical utility, except in cases of prophylactic cardioprotection in high risk procedures such as aortic aneurysm repair (Coselli and LeMaire 2008) and infants with aortic coarctation and ventricular septal defect (Kanter 2007).…”