Xylazine-/diazepam-ketamine and isoflurane differentially affect hemodynamics and organ injury under hemorrhagic/traumatic shock and resuscitation in rats.

Most experimental studies on hemorrhage and trauma are performed under anesthesia. We determined the effects of three commonly used anesthetic regimens on hemodynamics and organ damage under normal and hemorrhagic/traumatic shock (HTS) conditions in rats. Animals were anesthetized with ketamine/diazepam (K/D), ketamine/xylazine (K/X), or isoflurane (ISO). Hemorrhagic/traumatic shock was induced by a midline laparotomy, bleeding to a mean arterial pressure of 30 to 35 mmHg until decompensation, followed by restrictive and adequate phases of resuscitation. The experiment was terminated 120 min after the completion of resuscitation. Under normal conditions, K/D anesthesia resulted in higher mean arterial pressure and heart rate than K/X and higher systemic vascular resistance index (SVRI) than ISO. Stroke volume was significantly lower in K/D group than in K/X and ISO groups. Under normal conditions, ISO anesthesia was accompanied by the highest cardiac index. During shock and resuscitation, heart rate remained higher in the K/D than K/X. During shock, SVRI decreased in the K/D group but increased in K/X and ISO groups. After resuscitation, SVRI was lower, and cardiac index was higher in the ISO group than in the K/D group. Despite higher shed blood volume, the rats anesthetized with ISO did not decompensate within the time frame compared with other groups. Cellular damage (plasma creatine kinase, lactate dehydrogenase, uric acid) was more pronounced with K/D compared with ISO. Histological examinations revealed frequent HTS-induced damage to adrenals, kidney, and liver of animals anesthetized with K/D and K/X but not with ISO. Anesthetics differentially affect HTS-induced hemodynamic alterations and organ injury. Thus, when interpreting data from HTS models, the individual effect of anesthetics should be considered.

Telomerase-immortalized lymphatic and blood vessel endothelial cells are functionally stable and retain their lineage specificity.

OBJECTIVE: Microvasculature plays an important role in a variety of physiological and pathological processes. The authors have previously shown that primary cultures of human microvascular endothelial cells consist of 2 distinct populations of blood vascular and lymphatic endothelial cells. These subtypes are ephemeral and lose purity through passaging. To generate reproducible in vitro and in vivo experiments stable blood and lymphatic endothelial cell lines are an essential prerequisite. METHODS: In this study they have used human telomerase gene-immortalized nontransformed human microvascular endothelial cell cloned pure cultures of blood and lymphatic endothelial cell subpopulations. Flow cytometry, immunofluorescence, Northern and Western blotting, microarray gene analysis, as well as basic functional assays were used to characterize these clones. RESULTS AND CONCLUSIONS: Immortalized blood and lymphatic subpopulations are stable and functionally specialized cell lineages that expressed pan-endothelial and cell-type-specific markers. They are excellent candidates for long-term culture studies on microvascular-related diseases.