Abstract 554: Intravenous Administration of Immunoglobulin Attenuates Myocardial Reperfusion Injury and Improves Left Ventricular Remodeling
Background: Intravenous administration of immunoglobulin (IVIG) is known to have an anti-inflammatory effect through blocking of Fc receptor, inhibition of complements, and proinflammatory cytokines. We sought to determine the effect of IVIG on ischemia reperfusion (I/R) injury and subsequent left ventricular (LV) remodeling.
Methods: Wister rats underwent 30-minute left coronary artery occlusion. Rats were treated with IVIG (0.4g/kg, MI-IG, n=9) or saline (MI-C, n=9) 30 min before ischemia. Sham-operated rats were served as controls (n=5). Myocardial contrast echocardiography using intravenous Levovist was performed an hour after reperfusion. After hemodynamic study using transducer-tipped catheter and echocardiography 24 hours after reperfusion, the hearts were excised and the infarct size was determined by TTC staining. Another set of rats (n=6 for each group) underwent hemodynamic and echocardiographic studies 10 days after I/R to assess LV remodeling. Real time RT-PCR was performed to assess the mRNA expression in the risk area.
Results: MI-IG group had higher peak contrast intensity in the area at the risk an hour after I/R compared with MI-C (p=0.03). Maximum LV dP/dt 24 hours after I/R was higher in MI-IG than that in MI-C (6184±840 vs. 4638±427mmHg/s, p=0.01), although the infarct size and LV ejection fraction 24 hours after I/R were similar between the 2 groups. Ten days after I/R, maximum LV dP/dt tended to be higher (7538±511 vs. 6726±894mmHg/s, p=0.05) and LV ejection fraction was greater (71±2% vs. 56±9%, p=0.009) in MI-IG than those in MI-C. The myocardial mRNA expression of ICAM-1 (55% reduction, p=0.04), MCP-1 (68% reduction, p=0.03), MIP-1alpha (65% reduction, p=0.04), interleukin-1beta (31% reduction, p=0.03) and iNOS (58% reduction, p=0.03) 24 hours after I/R were lower in MI-IG than those in MI-C. The mRNA expression of matrix metalloproteinase (MMP)-9 24 hours after I/R and MMP-2 10 days after I/R tended to be lower in MI-IG than those in MI-C.
Conclusions: IVIG pretreatment before I/R resulted in less incidence of reperfusion injury and improved LV function, through inhibition of microcirculatory disturbance and inflammatory response. IVIG may be effective as an adjunctive therapy to reperfusion for acute myocardial ischemia.