The hemodynamic response to hemorrhage in tumor-bearing animals

Tumor-bearing rats submitted to hypovolemia have higher mortality rates than have non-tumor-bearing control rats. To determine the mechanisms underlying this sensitivity to hemorrhage, we studied Fischer-344 rats with subcutaneous methylcholanthrene-induced sarcoma (tumor burden, 10% body weight) to determine hematologic and blood volume alterations. Subsequently we used the same animal model in an unanesthetized condition to determine the sensitivity to hemorrhage and resuscitation, as well as vascular responsiveness to vasoactive agents. The rats were separated into two groups: control and tumor-bearing rats (TBR). Sensitivity to hemorrhage and resuscitation was determined by bleeding the conscious rats (15 ml/kg) and resuscitating them with 0.9% NaCl (45 ml/kg). Vascular responsiveness was determined after injection of varying doses of phenylephrine and nitroglycerin, with continuous measurement of mean arterial pressure (MAP). Rate of increase of MAP, maximum MAP, relative increase in MAP (maximum minus baseline), rate of recovery toward baseline MAP, and duration of the response were determined. There was a significant anemia in TBR, but blood volume was similar in both groups. Baseline MAP was significantly higher in control rats (125.3 +/- 8.1 mm Hg) compared with TBR (107.5 +/- 6.0 mm Hg). After hemorrhage, MAP in TBR reached significantly lower levels than in control rats. In addition, after saline resuscitation, MAP in TBR did not return to baseline levels, whereas MAP in control rats returned to prehemorrhage MAP. With nitroglycerin, MAP decreased to lower levels in TBR than in control rats. With phenylephrine, the maximum MAP reached was significantly higher, and the response to phenylephrine was maintained for a significantly longer period in control rats compared with TBR. We conclude that TBR are more sensitive to hypovolemic events in association with decreased oxygen-carrying capacity, profound hypotension, and altered overall vascular responsiveness to sympathetic stimuli.