Cyclophosphamide protects against myocardial ischemia/reperfusion injury in rats: One of the therapeutic targets is high sensitivity C-reactive protein

Abstract

Cyclophosphamide has a role of decreasing high-sensitivity C-reactive protein in the treatment of autoimmune disorders. The effect of cyclophosphasmide on high-sensitivity C-reactive protein was investigated in myocardial ischemia/reperfusion rat. Open-chest rats were submitted to 30 minutes of ischemia and followed for 3, 12, or 24 hours of reperfusion. All 72 rats survived and were divided into sham, ischemia/reperfusion (I/R) and cyclophosphamide groups, and each group included 3 time-point subgroups (3, 12, and 24 hours; n = 8 for each subgroup). Cyclophosphamide (0.75 g/m(2)) or saline was intraperitoneally administrated in the cyclophosphamide or I/R group. A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure, left ventricular end-diastolic pressure, and maximum rate of rise or fall of left ventricular pressure. In the end, blood was collected for detection of high-sensitivity C-reactive protein, and hearts were harvested for histopathologic assessment and infarct size determination. Compared with the I/R group, rats treated with cyclophosphamide showed a significant recovery in myocardial function with improved left ventricular systolic pressure (88.27 +/- 3.78 vs 68.62 +/- 3.78 mm Hg at 3 hours, 92.04 +/- 3.77 vs 63.74 +/- 4.87 mm Hg at 12 hours, and 90.41 +/- 3.98 vs 64.21 +/- 4.88 mm Hg at 24 hours; P < .05, respectively). Left ventricular end-diastolic pressure and maximum rate of rise or fall of left ventricular pressure also had similar trends. Infarct size was reduced (26.1% +/- 0.4% vs 40.4% +/- 0.4% at 3 hours, 21.6% +/- 0.4% vs 49.9% +/- 0.4% at 12 hours, and 21.6% +/- 0.4% vs 40.0% +/- 0.4% at 24 hours; P < .01, respectively). Histopathologic damage score was attenuated (1.83 +/- 0.14 vs 2.17 +/- 0.14 at 3 hours, 2.33 +/- 0.14 vs 3.17 +/- 0.14 at 12 hours, and 2.83 +/- 0.14 vs 3.83 +/- 0.14 at 24 hours; P < .01, respectively). Plasma high-sensitivity C-reactive protein concentration was significantly reduced (29.28 +/- 0.51 vs 32.26 +/- 0.51 ng/mL at 3 hours, 29.06 +/- 0.50 vs 31.8 +/- 0.51 ng/mL at 12 hours, and 28.61 +/- 0.51 vs 31.86 +/- 0.51 ng/mL at 24 h; P < .01, respectively). Cyclophosphamide protects myocardial ischemia/reperfusion injury in the rat with a decrease in plasma concentration of high-sensitivity C-reactive protein.