Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size

Matthias Götberg, Goran K Olivecrona, Henrik Engblom, Martin Ugander, Jesper van der Pals, Einar Heiberg, Håkan Arheden, David Erlinge, Matthias Götberg, Goran K Olivecrona, Henrik Engblom, Martin Ugander, Jesper van der Pals, Einar Heiberg, Håkan Arheden, David Erlinge

Abstract

Background: The aim of this study was to evaluate the combination of a rapid intravenous infusion of cold saline and endovascular hypothermia in a closed chest pig infarct model.

Methods: Pigs were randomized to pre-reperfusion hypothermia (n = 7), post-reperfusion hypothermia (n = 7) or normothermia (n = 5). A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min. Hypothermia was started after 25 min of ischemia or immediately after reperfusion by infusion of 1000 ml of 4 degrees C saline and endovascular hypothermia. Area at risk was evaluated by in vivo SPECT. Infarct size was evaluated by ex vivo MRI.

Results: Pre-reperfusion hypothermia reduced infarct size/area at risk by 43% (46 +/- 8%) compared to post-reperfusion hypothermia (80 +/- 6%, p < 0.05) and by 39% compared to normothermia (75 +/- 5%, p < 0.05). Pre-reperfusion hypothermia infarctions were patchier in appearance with scattered islands of viable myocardium. Pre-reperfusion hypothermia abolished (0%, p < 0.001), and post-reperfusion hypothermia significantly reduced microvascular obstruction (10.3 +/- 5%; p < 0.05), compared to normothermia: (30.2 +/- 5%).

Conclusion: Rapid hypothermia with cold saline and endovascular cooling before reperfusion reduces myocardial infarct size and microvascular obstruction. A novel finding is that hypothermia at the onset of reperfusion reduces microvascular obstruction without reducing myocardial infarct size. Intravenous administration of cold saline combined with endovascular hypothermia provides a method for a rapid induction of hypothermia suggesting a potential clinical application.

Figures

Figure 1
Figure 1
Protocol for induction of hypothermia. In the pre-reperfusion group, hypothermia was started after 25 min of ischemia (15 min before reperfusion) and in the post-reperfusion group, hypothermia was started immediately after reperfusion. The normothermic group was maintained at 38.0°C.
Figure 2
Figure 2
Core body temperature (esophageal) measurements in the different groups. The combination of infusion of cold saline with endovascular cooling caused a rapid reduction in core body temperature. Data are expressed as mean ± SEM.
Figure 3
Figure 3
(a) Size of area at risk (AAR) by SPECT. There was no difference in AAR between the different groups. (b) Infarct size (IS) measured by ex-vivo MRI as a percentage of area at risk (AAR) by SPECT in the two groups. Pre-reperfusion hypothermia causes a 43% relative reduction in infarct size compared to post-reperfusion hypothermia and by 39% compared to normothermia. (c) Infarct size (IS) measured by ex vivo MRI, expressed as a percentage of the left ventricular mass. (d) Microvascular obstruction measured by ex vivo MRI, expressed as a percentage of the infarct size. Pre-reperfusion hypothermia totally abolished microvascular obstruction. Post-reperfusion hypothermia significantly decreased the extent of micovascular obstruction compared to normothermia. (* = p < 0.05, ** = p < 0.01, *** = p < 0.001). Data are expressed as mean ± SEM.
Figure 4
Figure 4
This figure illustrates the visual comparison between typical examples from the respective groups. The bottom row shows the area at risk measured by SPECT shown in a bull' eye plot of the left ventricle. The top row illustrates the region of infarction from ex vivo MRI. White lines denote the slice position of the two ex vivo MRI slices in relation to each other. Note the patchy pattern of the myocardial infarction in the MRI image from the pre-reperfusion hypothermia group. In the MRI images from the post-reperfusion hypothermia group and most notably, the normothermia group, hypointense zones of microvascular obstruction are seen within the area of infarction.

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