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Substance P (SP) is known to reduce inflammatory reaction and induce mobilization of stem cells, suggesting a potential benefit of reducing ischemia-reperfusion injury and infarct size. We reported the cardio protective effect of SP in a rat and mouse model. We assessed a cardio protective effect of SP in a porcine model of acute myocardial infarction (MI).
A total of 16 pigs were randomly allocated to group 1 (substance P, n=8) and group 2 (placebo, n=8). Acute MI was induced by occlusion of the left anterior descending artery with a 3.0 mm balloon catheter for 50 minutes. Five minutes before reperfusion, substance P (5 nmol/kg) and normal saline were administered intravenously in group 1 and 2, respectively. Two-dimensional echocardiography and myocardial perfusion single photon emission computed tomography (SPECT) with technetium-99 m sestamibi were performed at 1 week and 4 weeks after the procedure to assess left ventricular (LV) function and infarct size. At 4 weeks, the pigs underwent follow-up coronary angiography and were sacrificed for histomorphometric infarct size assessment.
Baseline LV ejection fraction (LVEF), LV end-diastolic and end-systolic volumes were similar between 2 groups. LVEF at 1 week was significantly higher in group 1 than group 2 (37.9 ± 4.6% vs. 29.4 ± 3.2%, p=0.001). LVEF at 4 weeks was not different between the groups (41.1 ± 8.8% vs. 38.0 ± 4.4%, p=0.427). The number of defect segments and the magnitude of total perfusion defect on SPECT were lower in group 1, compared to group 2 at 1 week (0.5 ± 0.8 vs. 2.1 ± 2.3, p=0.118 and 15.4 ± 8.6% vs. 23.6 ± 18.5%, p=0.313, respectively) and at 4 weeks (0.5 ± 0.8 vs. 1.1 ± 1.1, p=0.197 and 13.3 ± 10.3% vs. 14.7 ± 12.0%, p=0.803, respectively). Pathologic infarct size (% LV) was significantly lower in group 1, compared to group 2 (2.4 ± 2.3% vs. 5.7 ± 2.5%, p=0.020).
In a porcine model of acute MI, substance P improved LVEF early post-MI and reduced infarct size at 4 weeks. SP might be used for prevention of IR injury in MI.