Article

Investigating Treatment with Therapeutic Hypothermia for Ischaemia of the Heart / Mechanical Left Ventricular Unloading and Therapeutic Hypothermia

Abstract

Published online:

Citation:Interventional Cardiology Review 2021;16(Suppl 2):12–3.

Support: The development of this supplement was funded by Abiomed.

Open access:

This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

Dr Kloner’s two decades of research demonstrate that therapeutic hypothermia (TH) reduces myocardial damage in the setting of acute MI. Topical cooling of the heart to a target a temperature <35°C prior to ischaemia or coronary occlusion, followed by reperfusion, or opening of a coronary artery, significantly decreased infarct size in rabbits and sheep.1,2 Mild regional hypothermia prior to ischaemia also preserved metabolic activity in the ischaemic or occluded area by retention of adenosine triphosphate stores, glycogen stores and creatine phosphate.3

TH after ischaemia onset also reduced infarct size in rabbits and rats if administered immediately prior to reperfusion.4–6 TH induction by intracoronary injection of chilled saline prior to reperfusion limits the no-reflow or microvascular obstruction (MVO) area of the infarct.6 TH initiated after reperfusion also substantially reduced the extent of no-reflow, but did not decrease infarct size.7,8

TH using a non-invasive convective-immersion cooling ThermoSuit produced a similar cardioprotective decrease in no reflow, cardiac scar length and infarct size of ischaemic animals.9,10 TH also assisted healing after MI, with increased infarcted wall thickness, decreased inflammatory gene expression and improved left ventricular (LV) fractional shortening and ejection fraction.11 TH also improved long-term survival and blunted inflammation in rats exposed to haemorrhagic shock.12

Dr Kloner concluded his talk with a summary of TH clinical studies. Few have been successful due to difficulties decreasing temperature to a sufficient degree, delaying conventional therapy.

Four clinical studies demonstrated that TH reperfusion with a target temperature of <35°C prior to reperfusion decreases infarct size and MVO in patients with ST-segment elevation MI (STEMI).13–16

Dr Ishikawa proposes TH in combination with LV mechanical unloading as a treatment for STEMI patients. TH, during the 30-minute period of LV unloading prior to reperfusion, as recommended by the STEMI-Door-to-Unload pilot clinical trial, could enhance the impact of both treatments.17 A meta-analysis of preclinical studies from around the world over the past 40 years established that mechanical unloading reduces infarct size.18 Mechanical LV unloading decreases pressure–volume area, reducing myocardial oxygen consumption (MVO2) for mechanical work, whereas MVO2 for non-mechanical work remains unchanged.19 TH improves myocardial energy efficiency by decreasing heart rate and MVO2 for non-mechanical work.20,21 LV unloading stabilises haemodynamics and prevents lung congestion through increased blood flow, mitigating TH complications of increased arrhythmia and impaired diastolic function.22,23 Combination therapy may also limit reperfusion injury by LV unloading-mediated reduction in wall stress and TH-mediated decrease in myocardial temperature. The appropriate TH method of cooling, administration timeline and potential side-effects of combined therapy, such as thrombogenesis, should be determined in future clinical studies.

References

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