SAFETY AND FEASIBILITY OF INTRACORONARY HYPOTHERMIA IN ACUTE MYOCARDIAL INFARCTION (SINTAMI)

In acute myocardial infarction, early restoration of epicardial and myocardial
blood flow is of paramount importance to limit infarction size and create
optimum conditions for favourable long-term outcome.
Currently, restoration of epicardial blood flow is preferably obtained by
primary percutaneous coronary intervention (PPCI). After opening the occluded
artery, the reperfusion process itself also causes damage to the myocardium,
the so called *reperfusion injury.* Therapeutic hypothermia, i.e. the cooling
of damaged tissue, is thought to attenuate this reperfusion injury.
Animal studies have shown that the induction of hypothermia before reperfusion
of an acute coronary occlusion reduces infarct size. Previous studies in
humans, however, have not been able to confirm this effect, which is mainly
believed due to the fact that therapeutic temperature was not reached before
reperfusion in the majority of the patients. Furthermore, in these studies it
was intended to induce whole body hypothermia, which may lead to systemic
reactions such as shivering and an enhanced adrenergic state. We aimed to
evaluate the safety and feasibility of rapidly induced intracoronary
hypothermia by selective intracoronary infusion of cold saline before and after
reperfusion in patients with acute myocardial infarction.

To evaluate the feasibility and safety of selective intracoronary hypothermia
in acute myocardial infarction

Pilot study in which the safety and feasibility of an intervention is
evaluated.

Additional to the routine percutaneous coronary interrvention, the procedures
for the study include:
- insertion of temperature wire (PW)
- Insertion of over-the-wire balloon (OTW)
- Inflating balloon (4 atm.)
- removal of guide wire
- start hypothermia (10 min.):
- induction: NaCl room temperature degrees Celsius, at a flow rate of 40
ml/min.,
- Continuous monitoring of distal coronary temperature by the PW
- Deflating balloon after 10 min. of hypothermia during occlusion
Reperfusion occurs, but no stent is placed yet
- Continuing hypothermia (10 min): NaCl room temperature degrees Celsius, 40
ml/min. on an open coronary artery

The initial procedure will be the emergent coronary angiography identical to
the first part of a regular PPCI and implantation of stents. There are no
associated risks with that part of the procedure.
In patients eligible for the study, thereafter, the additional intracoronary
hypothermia is administered with measurements of physiologic parameters.
Equipment and drugs used in this part of the exam are not different from
standard equipment. The procedure is prolonged by 20 minutes. There is a
moderate load of saline, i.e. 1000 a 1200 ml. We do not anticipate any adverse
effect.
Several animal studies indicated no risks of moderate hypothermia.[6-8]
Additionally, there were even benefits observed concerning safety such as less
arrhythmia.[5]
In human studies no additional risks, such as hemodynamic instability or
arrhythmias, were noted during systemic hypothermia.[9-12] All the clinical
studies used a cooling method in which the whole body was cooled off. We
postulate that these cooling methods carry much higher risks and patient
discomfort such as shivering compared to the selective intracoronary
hypothermia in which systemic hypothermia symptoms probably will not occur.
Finally and importantly, in the Catharina hospital Eindhoven we already
performed several studies in which saline at room temperature was infused
intracoronary in a similar rate as in this study, both in stable patient. (n =
88) [13] and patients with acute myocardial infarction (n=20). (Wijnbergen et
al. study performed presently METC nr M11-1158) Except rapidly transient
conductive disturbances in three patients, not any adverse effect was noted.