Ischemia and reperfusion injury: prevention of pulmonary hypertension and leukosequestration following lower limb ischemia

Ischemia is a common clinical event with potentially serious consequences. The major part of tissue damage occurs upon reperfusion and is mediated by activated neutrophils. Ischemia reperfusion injury is manifested by oedema and increased microvascular permeability. This study tested cardiopulmonary functions following 2 h of lower limb ischemia. Anesthetized dogs were randomized into three groups: nonischemic sham dogs ( n = 4), ischemic control dogs ( n = 8) and ischemic dogs pretreated with prostaglandin (PG)E 1 ( n = 8). In control animals, mean pulmonary artery pressure (mPAP) increased 1 min after declamping from 13.37 ± 2.61 mmHg to 16.88 ± 3.68 mm Hg ( P < 0.05). Pulmonary microvascular pressure (Pmv) increased within 1 minute of reperfusion from 7.71 ± 1.87 mm Hg to 10.54 ± 3.71 mm Hg ( P < 0.05). These changes are consistent with increased lung microvascular permeability. White blood cell count fell slightly but not significantly and lung histology showed leukosequestration in alveoli of 171 ± 22 polymorphonuclear leukocyte (PMN) 10 high powered fields (HPF) in the ischemic control group compared with 121 ± 56 PMN 10 HPF in the sham group ( P < 0.05). Systemic arterial pressure, cardiac output, central venous pressure and pulmonary artery wedge pressure were unaffected. In animals pretreated with PGE 1, mPAP and Pmv were unchanged during reperfusion. Lung histologic findings appeared normal and leukosequestration was not observed. PMN counts in alveoli showed 95 ± 26 PMN 10 HPF , lower than in ischemic control animals ( P < 0.05). These data indicate that lower limb ischemia during reperfusion leads to pulmonary hypertension and leukosequestration. PGE 1 infusion is effective in limiting ischemia reperfusion injury.