The association of coronary flow changes and inflammatory indices to ischaemia–reperfusion microvascular damage and left ventricular remodelling

Abstract

The aim of this study was to investigate the effect of coronary flow (CF) changes and inflammatory indices on myocardial microcirculation--assessed by myocardial contrast echocardiography (MCE)--and on left ventricular remodelling, in an experimental ischaemia-reperfusion model. In 15 pigs, weighing 30 +/- 5 kg, ligation of the left anterior descending (LAD) coronary artery was performed, followed by reperfusion for 120 min. Peak, mean, duration and volume of systolic and diastolic components of CF distal to the LAD ligation were measured using a butterfly flowmeter and their ratio was calculated. The following two-dimensional echocardiography indices of LV geometry/function were measured from the apical four-chamber view: LV end-systolic (ESD) and end-diastolic (EDD) dimension long- (Ls, Ld) and short-axis (Ss, Sd) and their ratio (Ld/Sd, Ls/Ss, defined as the sphericity index). Interleukin (IL) 1beta, 6, 10 and tumour necrosis factor (TNF) were measured in samples obtained from the LV cavity and coronary sinus. A 0.5 ml/min injection slow bolus over 30 s of SonoVue was made into the left ventricle (LV) in order to assess myocardial perfusion by MCE. Standard apical four-chamber views were digitally acquired and stored for off-line analysis using the Echofit system. The peak intensity (Ac) of the microbubbles at the apex, distally to ligation, was normalised with respect to the peak intensity of the microbubbles in the LV cavity. All parameters were recorded at baseline, immediately after ligation and at 5, 15, 30, 60, 120 min during reperfusion. The percentage changes of CF indices, echocardiographic parameters, interleukins and Ac between baseline and reperfusion were calculated. Mean systolic CF, systolic volume, peak and mean diastolic flow (MDF) changes and epicardial mean CF, Ld/Sd, Ls/Ss changes and coronary sinus IL-6 (IL-6 cs) were inversely correlated with Ac changes during reperfusion. At 5 and 15 min of reperfusion (hyperaemic phase), the greatest median increase of mean diastolic (172% and 86%), and mean systolic CF (713% and 344%) and the greatest reduction of Ac (-41% at 5 min) compared to baseline (P < 0.05) were observed. The maximum increase of IL-6 cs (40%) was detected at 120 min. ROC analysis showed that of all examined echocardiography indices an increase of mean diastolic CF > 22% was the best predictor of a >25% reduction of Ac with 76% sensitivity and 65% specificity (area 71%, CI 54%-85%, P = 0.02). In addition an >32% increase of IL-6 at 120 min of reperfusion predicted a >25% reduction of Ac with a 76% sensitivity and 65% specificity (area 71% CI 61%-97%, P = 0.01). Changes of mean diastolic CF and IL-6 cs are associated with alterations in myocardial microvascular integrity after ischaemia-reperfusion and may be used as a predictor of myocardial dysfunction.