Peripheral bypass-induced pulmonary and coronary vascular injury. Association with increased levels of tumor necrosis factor.

Abstract

Background. Although cardiopulmonary bypass is associated with systemic complement activation and neutrophil sequestration, it is unclear whether bypass-induced vascular injury is localized and dependent on organ ischemia. We hypothesized that other factors perhaps related to placement of a bypass circuit or to blood perfusion of a pump-oxygenator system may produce vascular injury caused by systemically circulating mediators. In dogs, we determined whether application of a systemic venoarterial bypass circuit with pump-oxygenator perfusion but without pulmonary or cardiac flow diversion (peripheral bypass) leads to vascular injury. Since several features of the postperfusion syndrome after bypass resemble sequelae of endotoxin exposure, we also measured circulating endotoxin and tumor necrosis factor levels.Methods and Results. Anesthetized dogs underwent 2 hours of exposure to a pump-oxygenator with peripheral venoarterial bypass. We used a double indicator measurement of pulmonary and coronary vascular permeability (protein leak index [PLIJ)as indexes of vascular injury. Compared with controls (n=7), the pulmonary PLI of dogs undergoing bypass (n=11) increased more than threefold (18.8±2.3 vs 63.3±7.6x 10-4 min'; P<.05) and the coronary PLI increased more than twofold (P<.05). The rate of disappearance of intravascular radiolabeled protein increased threefold after bypass (disappearance ti,2, 241±35 vs 84±15 minutes, control vs bypass; P<.05), suggesting a generalized increase in vascular permeability. Circulating endotoxin was detectable in blood samples from 8 of 8 bypass animals (range, 0.24 to 4.56 ng/mL) compared with 2 of 5 controls (P<.05). Tumor necrosis factor levels increased significantly with bypass (6.7±3.8 vs 146.7±33.6 UlmL, baseline vs bypass; P<.05) and were only slightly and nonsignificantly increased in controls (7.0+4.4 vs 18.2±5.9 U/mL; P=NS). Peak tumor necrosis factor but not peak endotoxin levels correlated with pulmonary and with coronary protein leak. As expected, circulating complement (CH50) levels decreased significantly during bypass, reflecting systemic complement activation. However, the levels correlated pooriy with the severity of vascular injury.Conclusions. We conclude that peripheral pump-oxygenator bypass causes coronary and pulmonary vascular injury that is independent of blood flow diversion and is associated with the appearance of circulating levels of endotoxin and tumor necrosis factor, which may play a role in bypass-induced vascular injury. (Circulation 1993;88:726-735 We performed studies in dogs to determine whether peripheral placement of a pump-oxygenator in a systemic venoarterial circuit (peripheral bypass) causes pulmonary and coronary vascular injury independent of blood flow diversion and whether this is associated with increases in circulating endotoxin and/or TNF. As indexes of vascular injury, pulmonary and coronary vascular protein permeability were measured with a previously described double indicator radioisotope protein leak index (PLI).28-31 We fou...

Vasomotor dysfunction after cardiac surgery

“…Increased circulating levels of tumor necrosis factor-a (TNF-a), interleukin (IL)-6, IL-8, and other cytokines liberated during CPB have been shown to directly increase the permeability of blood vessels, mediate inflammation, and increase the expression of iNOS [30,[59][60][61][62][63]. The expression of vascular endothelial growth factor (VEGF), a potent vasodilator and inducer of vascular permeability, and that of its receptor VEGFR-1 are also upregulated after cardioplegic arrest and reperfusion, resulting in increased coronary microvascular relaxation responses [64,65].…”

Vascular changes after cardiopulmonary bypass and ischemic cardiac arrest: roles of nitric oxide synthase and cyclooxygenase

“…PMN and macrophage infiltration has been documented in myocardium (28) after ischemia and cardioplegia and also in mesenteric (25) and pulmonary tissue (29) after CPB. Furthermore, increased circulating and tissue levels of tumor necrosis factor (TNF)-alpha, Il-6, Il-8, and other inflammatory cytokines liberated during and after CPB (30)(31)(32)(33) have been directly associated with the increase in permeability of blood vessels (6,30,31) and contribute to the inflammatory reaction and increased expression of inducible iNOS (34).…”

Upregulation of the Water Channel Aquaporin-4 as a Potential Cause of Postischemic Cell Swelling in a Murine Model of Myocardial Infarction

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