Koronare Mikroembolisation am Kaninchenmodell: Simvastatin vermindert die Inflammation und myokardiale Dysfunktion nach koronarer Mikroembolisation

Koronare Mikroembolisation am Kaninchenmodell: Simvastatin vermindert die Inflammation und myokardiale Dysfunktion nach koronarer Mikroembolisation

Coronary microembolisation in the rabbit model: Simvastatin supresses inflammation and myocardial dysfunction after coronary microembolisation

Georg Schultz

Doctoral thesis

Date of Examination: 2013-09-24

Date of issue: 2013-08-27

Advisor: Post, Heiner PD Dr.

Referee: Pieske, Burkert Prof. Dr.

Referee: Danner, Bernhard C. PD Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0001-BB35-B

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Abstract

English

Background: Coronary microembolisation (CME) frequently occurs during spontaneous coronary plaque rupture and coronary angioplasty. In experimental studies, CME induces a pronounced inflammatory response that decreases contractile function of embolized myocardium for several days. Since statins exert anti-inflammatory effects, we tested whether simvastatin (Sim) would preserve left ventricular (LV) function after CME. Methods and Results: In anaesthetized rabbits, polysterol microspheres (45 µM diameter, n=10.000-30.000) were infused into the left main coronary artery via a 3 F catheter during fluoroscopy. Animals received Sim (3 mg/kg/day p.o., n=10) or placebo (P, n=14) from 3 days before until 9 days after CME. Three animals treated with P but none treated with Sim died within 24 h after CME. Troponin T increased to a similar extent at 1 day after CME (P 3.5±1.1, Sim 3.5±1.0 ng/ml). In P, LV shortening fraction (SF, echocardiography) was decreased at day 2 after ME (32±2 vs 40±1%, p<0.05) but was preserved in Sim (40±2 vs 41±1%). SF recovered completely at 9 days after CME (P 43±2%, Sim 41±2%). At 2 days after CME, Sim also prevented LV dilatation and attenuated the decrease of LV ejection fraction. LV myocardial fibrosis was not different between P and Sim at 9 days after CME (15.3±1.5 vs 14.2±1.4 %, picrosirius red). In further animals sacrificed at 2 days after CME, Sim suppressed macrophage infiltration and tumor necrosis factor alpha expression (immunohistochemistry). Conclusion: CME induces a transient, inflammatory phase of myocardial dysfunction that can effectively be prevented by simvastatin. These data support the immediate use of statins during acute coronary syndromes.

Keywords: coronary microembolisation; simvastatin; myocardial inflammation; myocardial dysfunction; rabbits