Kinetic analysis of a short infusion of 7.5% saline/6% dextran or 0.9% saline accurately predicts the effects of a longer infusion of the same volume (7.5% saline/6% dextran) or of a larger volume (0.9% saline).

After hemorrhage, blood volume is partially restored by transcapillary refill, a process of spontaneous compensatory intravascular volume expansion that we hypothesized would be inhibited by anesthesia. Six chronically instrumented sheep were subjected to four randomly ordered experiments while conscious or during anesthesia with isoflurane. After plasma volume measurement (indocyanine green), 15% or 45% of the blood volume was withdrawn. To quantify transcapillary refill, mass balance and kinetic calculations utilized repeated measurements of hemoglobin concentration, assuming that transcapillary refill would dilute hemoglobin concentration. After 15% hemorrhage, mean arterial blood pressure remained stable in both conscious and isoflurane-anesthetized sheep (normotensive hemorrhage) but decreased after 45% hemorrhage (hypotensive hemorrhage). After either normotensive or hypotensive hemorrhage, transcapillary refill occurred more rapidly during the first 40 min than during the next 140 min (P < 0.001). In conscious sheep, at 180 min, 57% and 42% of the bled volume had been restored after normotensive and hypotensive hemorrhage, respectively, in contrast to only 13% and 27% (P < 0.001) in isoflurane-anesthetized sheep. A novel kinetic model implicated hemodynamic factors in rapid, early transcapillary refill and decreased plasma oncotic pressure in subsequent slower filling. We conclude that isoflurane inhibits transcapillary refill after both normotensive and hypotensive hemorrhage in sheep.

It was previously postulated on the basis of clinical data that the cardiovascular sequelae of extracorporeal whole-body hyperthermia (e-WBH), i.e., hypotension (which requires catecholamine support) results in unique nephrotoxicity in combination with select chemotherapeutic agents. In an attempt to explain this phenomenon, we mimicked e-WBH physiological conditions in a rat model. Animals were treated with and without ifosfamide (IFO) and/or carboplatin (CBDCA) at 37 degrees C or 41.5-41.8 degrees C, with blood pressure monitoring and catecholamine support comparable to the clinical setting. Ex vivo post-treatment data (24 h) from artificially perfused kidneys (i.e., histology, urine volume, perfusion rate, glomerular filtration rate, and the reabsorption of sodium, glucose, and water) demonstrated unique toxicity including proximal tubular necrosis for the combination of WBH and IFO, for WBH and CBDCA and for WBH and IFO plus CBDCA, but not for IFO and CBDCA without WBH. These data, considered together with results derived from a subsequent clinical trial and the laboratory work of others were consistent with the hypothesis.

In contrast to our hypothesis, severe acute hypoproteinemia does not reduce plasma volume expansion in response to 50 mL/min 0.9% saline infusion in nonspleenectomized sheep when compared with the resultant plasma volume expansion after a 50 mL/min of 0.9% infusion in the euproteinemic state.

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