Tomasz Kameczura, MD, PhD

1. The use of direct heart hypothermia by METcooler reduces microvascular obstruction and left ventricular systolic function impairment in animal experimental model of myocardial infarction - ongoing study - Tomasz Kameczura, MD, PhD

2. Introduction The reduction of heart damage and improvement of patient outcomes are the main goals in the treatment of myocardial infarction. Crucial to both are effective reperfusion (PCI) in the shortest possible time and the use of appropriate pharmacological treatment (antiplatelet therapy)

3. Introduction The slowdown of myocardial metabolism seems to be possible third way, which may decrease the deleterious impact of ischemia. The use of direct heart hypothermia (DHH) to reduce myocardial metabolic activity is a very promising method for minimizing left ventricle damage and improving patient prognosis.

4. Introduction Current recommendations on therapeutic hypothermia, issued by European Resuscitation Council, point to the scope of 12–24 hours of maintaining hypothermia in the period after resuscitation.

5. Mildtherapeutichypothermia and nowadaysproblems avoidance of risk of increase of the so called reflective (rebound) intracranial pressure • Respirator: • Pneumonias No patientconciousnes Only iv drugaministration Intubation: - Mechanicalcomplications Onlyparenteralfoodadministration Systemic iv antybiotic Pharmacologicalcoma Neuro-mascularplaque depolarizingagents Source: NEJM.org

6. METcooler (metabolism+cooling) DirectHeartHypothermia(DHH) • DHH is: • easy • performed locally • only local aneshesia • no patient sedation (patient aware) • no neuro-muscular depolarizing agents • antybiotic locally • regular solid food • cost effectivness

7. DHH studyprotocol • Methods: • Approval of the local ethics committee. 20 domestic swine (Polish Landrace Pig), 10 (SG) and 10 (CG). All subjects were sequentially given analgesia, sedation, intubation and respiratory therapy • Arterial access (right or left femoral artery using 6F arterial introducer (Balton, Poland)), then the coronarography is performed using guiding catheter JR3.5 6F (Medtronic, USA) and contrast media Omnipaque 350 mg I/ml (GE Healthcare AS, Norway). Infarction is caused by balloon catheter (BC)(Maverick Monorail PTCA Dilatation Catheter 2.5-4.0x12-15 mm) (Boston Scientific, USA) inflation for 45 minutes in the LAD (target prox /mid LAD with a diameter of 2.5-4.0 mm, behind DG1).

8. DHH study protocol • After 45 minutes, the BC is removed from the LAD. The animal is observed and monitored (if necessary appropriate medication is given as well as cardio-pulmonary resuscitation procedures are done). 48 hours latter, an MRI (GE 1.5 T)/(ECHO) is performed with assessment of left ventricle ejection fraction (LVEF) and quantitative assessment of microvascular obstruction (MO). Next procedure implies performing of two staining. • First staining performed on living animal (intra-aortic injection of 200 ml 1% solution of Evans blue). Second staining performed after heart preparation, removal of atrias and valvular aparatus, then cooling for 2 hours in temperature of -20C, then cut the ventricles muscle along the long axis to pieces of thickness of 5 mm. In sequence, pieces are incubated in 1% solution of trifenyltetrazolin (2,3,5-Triphenyl tetrazolium chloride, TTC) in temperature of 37C for 20 minutes. The next step in the study protocol is fixing scraps in 10% solution of formalin and photographed.

9. DHH study protocol • After weighting stained areas (AAR – area at risk, IA – infarct area) become measured using the planimetric method. Similarly in the SG, the coronary angiography an then LAD occlusion is performed. After removal of BC from the LAD, a “dry” puncture of the pericardium (after local analgesia, under fluoroscopy and ECG control), thru-the-needle introduction of two hydrophilic guide wire’s to pericardial space. Then removing the needle and by using a guide’s like a rail separate introduction of two 5-7F arterial sheets (Balton, Poland)) is performed, following by a 12-hour procedure of direct hypothermia (DHH, METcooler) of the heart using closed circuit with saline cooled to 30 ° C. 48 hours post-POBA, there is an MRI/echo evaluation made in the CG (MRI CG2) with estimations of EF and MO. Then all the above mentioned staining procedures are repeated as in the control group.

10. „Dry” pericardiocenthesis 1 3 4 2

11. Coronarography and POBA LAD

12. Staining

13. EF SG– 40,75%(SD+/-9.2) vs. EF CG-32% (SD+/-8,8) up of 21.56%IA SG– 6,7g(SD+/-0,71)vs. IA CG-7,4g (SD+/-0,85) down of 10.44%AAR SG– 9,8g(SD+/-1,46) vs. AAR CG-13,7g(SD+/-1,82) down of 25.25%all p<0.001 Preliminaryresults

14. Conclusion Direct heart hypothermia (DHH) method by METcooler in acute experimental heart ischemia is a viable and safe method in an animal model. Dry pericardial puncture and lowering the temperature in the pericardial sac by applying a closed refrigerant circuit are relatively simple procedures that can be performed if necessary in a regular ER or cardiology department. Preliminary results demonstrate that the DHH may be considered in the future as an additional method to reduce cardiac damage in the course of myocardial infarction

15. MVO – Microvascular Obstruction

16. Thank you for your attention…