Ultrasound assessment of heart remodelling affected by therapeutic hypothermia and MSC on myocardial infarction model

Abstract

Background. Late seeking medical advice, limited number of cardiac surgery hospitals and conservative treatment, which does not seem to be always efficacious, trigger the search for new, more effective mode therapy of acute myocardial infarction (MI). Recently, mesenchymal stromal cells (MSCs) have come into sharp focus of scientists due to the prospects for clinical use. On the other hand, multicenter studies have proved that therapeutic hypothermia (TH) has neuro- and cardioprotective effects, and it is administered as one of the urgent methods in providing primary health care. Purpose. Providing and analyzing ultrasonography (US) of rat hearts with experimental MI in order to determine the nature of heart remodelling under combined use of TH and introducing allogeneic MSCs. Materials and methods. The study involved 90 outbred white rats weighing 240–270 g. Myocardial infarction was reproduced by ligating the descending branch of the left coronary artery on the border of the upper and middle third of the vessel. Therapeutic hypothermia was performed in a cold chamber, 60 minutes long. The local skin temperature of the neck area was maintained at +4 оC, while the rectal and tympanic temperature decreased to + 25 оC. A suspension of allogeneic cryopreserved MSCs of the placenta with a concentration of 1.2 × × 106 cells/ml was administered once intravenously through v. saphena magna. Heart sonography was carried out by means of «Сономед 500» («СПЕКТРОМЕД», Russia) ultrasound scanner in B- and M-mode using a linear sensor 7.5L38 with frequency of 7.5 MHz. Results and discussion. The control group with experimental MI showed significantly suppressed function of the left ventricle (LV). It resulted in decreasing stroke volume (SV) and cardiac output (CO) and on the whole indicated reduced ejection fraction (EF) to 46.04 %, that was 35 % less than the corresponding normal range. According to the values of relative wall thickness (RWT) and left ventricular mass (LVM) on day 7 and day 30 after ligating the left coronary artery, LV remodelling was proceeding via eccentric mode of LV alteration. Therapeutic hypothermia was not able to completely stop the pathophysiological processes associated with coronary ligation. EF was not significantly different from the control group, and was 51.08 ± ± 2.68 %. On day 7 of the experiment, heart remodelling in this group was proceeding according to the normal geometry model, and on day 30 – according to the eccentric model. In spite of the volume overload causing post-infarction extension of the left ventricular cavity, in the group with applying MSCs, on day 7 there was a compensatory increase of the stroke volume, 1.8 times over compared to the group with normal range values and 2.3 over compared to the control group. The ejection fraction was 17 % less than the normal range, but statistically significantly higher than the corresponding indicator of the control group of this observation period. Heart remodelling after applying allogeneic MSCs associated with MI at all stages of observation was proceeding by eccentric LV hypertrophy. Аfter therapeutic hypothermia and applying MSCs associated with experimental myocardial infarction on day 7 and day 30, the group recorded the best values of echo params of LV anatomical structures, indicating no dilatation along with occuring moderate myocardial hypertrophy. The ejection fraction showed the best outcome, i. e. 58.78 %, while LV remodelling was minimal, occurring according to normal heart geometry. Conclusions. Applying echocardiography in rats is a very informative diagnosis method which makes it possible to describe the type of structural and functional remodelling of the myocardium associated infarction at early and late observation stages. The ultrasound study showed that the closest to the normal range was the group of animals exposed to therapeutic hypothermia and MSC transplantation. According to LVM and RWT values, in the rats of that group on day 7 and day 30 of the experiment, LV remodelling was characterized by normal geometry.

Keywords

• experimental myocardial infarction, ultrasound, therapeutic hypothermia, mesenchymal stromal cells.