The effect of the synthetic somatostatin analogue octreotide on left ventricular systolic function in an experimental model of coronary occlusion and reperfusion in rats

Background. One of the key components of post-ischemic damage is impaired myocardial contractility and changes in left ventricular geometry, characterized by a decrease in ejection fraction (EF), an increase in left ventricular (LV) volume, a drop in cardiac output (CO), and the appearance of areas of local contractility impairment. Limiting damage, preserving LV contractile function are the main goals of modern cardioprotection.

Aim: To assess the relationship between endogenous somatostatin (ES) and echocardiographic parameters during the experiment, as well as the effect of preventive administration of octreotide at doses of 20 and 40 μg/kg/day on systolic function indicators of the LV in an experimental model of prolonged coronary occlusion and reperfusion in rats.

Material and Methods. The study included 35 male Wistar rats divided into 3 series of experiments. Series 1 consisted of 12 intact animals (control group), series 2 consisted of 11 rats that were administered octreotide (Pharmstandard JSC) at a dose of 20 mcg/kg/ day for 8 days prior to coronary occlusion, and the third series consisted of 12 animals that received octreotide at a dose of 40 mcg/ kg/day for 8 days prior to coronary occlusion. The model included 45 minutes of occlusion of the left coronary artery and 120 minutes of reperfusion. The animals underwent thoracotomy at the level of the 2nd-3rd ribs, and a ligature was applied to the left descending coronary artery a few millimetres below its origin from the aorta. The duration of coronary occlusion was 45 min. After 45 min of ischaemia, the ligature was removed, and the restoration of blood flow was confirmed by the appearance of epicardial hyperaemia. The duration of reperfusion was 120 minutes. To assess systolic function and changes in ventricular geometry during the experiment, transthoracic echocardiography was performed at 20 and 90 minutes of reperfusion. End-systolic (ESV) and end-diastolic volumes (EDV), ejection fraction (EF), cardiac output (CO), stroke volume (SV) and local contractility impairment index (WMSI) were assessed. Levels of CK-MB (MB fraction of creatine phosphokinase) and endogenous somatostatin were determined by immunoassay (ELISA).

Results. Ischemic damage was confirmed by an increase in CK-MB in all series. In the control series, the ES level at 120 minutes of reperfusion increased statistically significantly compared to the baseline (p = 0.016), and a strong correlation was found between ES levels and EDV LV, CO, and SV indices at 90 minutes of reperfusion (r = 0.580; p = 0.048; r = 0.813; p = 0.001 and r = 0.879; p = 0.0001, respectively). The use of octreotide at a dose of 20 μg/kg contributed to an increase in EF by the 90th minute, but did not affect LVEF. The use of a dosage of 40 μg/kg/day led to a decrease in CK-MB levels (p = 0.018) and an improvement in the parameters of pump function and LV contractility.

Conclusion. ES concentration is associated with echocardiographic parameters reflecting LV contractile and pumping functions at the end of reperfusion, and the use of the somatostatin analogue octreotide dose-dependently reduces post-ischaemic left ventricular myocardial contractile dysfunction in ischaemic and reperfusion injury.

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