Beneficial effects of diltiazem on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion

Abstract

To evaluate the beneficial effects of diltiazem on myocardial no-reflow. Twenty-four mini-swine were randomized into 3 equal groups: diltiazem-treated group subjected to 3 hours of coronary occlusion to cause acute myocardial infarction (AMI), followed by 60 minutes of reperfusion and injected with diltiazem into the coronary artery 1 minute before reperfusion, control group undergoing coronary occlusion followed by 60 minutes of reperfusion and injected with normal saline, and sham operation group. 5 minutes before AMI in all groups and 180 minutes after AMI and 60 minutes after re-perfusion in the diltiazem and control groups, hemodynamic data, such as heart rate (HR), left ventricular systolic pressure (LVSP). Left ventricular end diastolic pressure (LVEDP), +/- dp/dt(max), cardiac output (CO), and coronary blood volume (CBV) were measured. Myocardial contrast echography (MCE) was used to measure the left ventricle wall area (LVWA) and ligation area (LA) so as to calculate LA and to measure the area of no-reflow (ANR) so as to calculate ANR. 60 minutes after reperfusion thioflavin-S was injected into left ventricle so as to color the reperfused area and then the descending anterior branch was re-ligated and Evan's blue was injected into the left ventricle to color the area outside the ligation area. The heart was taken out to undergo histological examination. (1) In comparison with the values before AMI the LVSP, +/- dp/dt(max), and CO of the control group significantly declined (P < 0.05, 0.01), while the LVEDP significantly increased (P < 0.01) by the end of 3 hours after LAD occlusion; and the LVSP significantly increased and the +/- dp/dt(max) further significantly declined (both P < 0.05) 60 minutes after reperfusion. In the diltiazem group, the changes of LVSP, +/- dp/dt(max), CO, and LVEDP were the same as those in the control group after 3 hours of AMI, while the +/- dp/dt(max), CO, and LVEDP recovered significantly, more significantly than those in the control group, 60 minutes after reperfusion (all P < 0.05). (2) In the control group, the sizes of coronary ligation area (LA) measured by both MCE in vivo and histopathological evaluation were similar (P > 0.05), and the values of area of no-reflow (ANR) measured by MCE in vivo and histopathological evaluation were 78.5% and 82.3% respectively with the final necrosis area (NA) reaching 99% of the LA. There was no significant difference in LA measured by both MCE and histopathological evaluation between the control and diltiazem groups, while the values of ANR measured by both methods was significantly decreased to 19.9% and 20.6% that before AMI respectively in the diltiazem group (both P < 0.01). There was no significant difference in NA between the control and diltiazem groups (P > 0.05). The CBV of the control group was significantly declined to 45.8% and 50.6% of the baseline value respectively immediately and 60 minutes after reperfusion (both P < 0.01), while the CBV of the diltiazem group became 80.4% and 79.3% of the baseline value respectively immediately and 60 minutes after reperfusion (both P < 0.05), both significantly higher than those of the control group (both P < 0.01). Diltiazem is effective both in preventing myocardial no-reflow and improving left ventricular function, but not in reducing MI size during AMI and reperfusion.