Morphodynamic analysis of the role of leukocytes in the microcirculation disorder of the cerebral cortex

The aim of this work was to establish the reasons for the disturbances of microcirculation (no reflow) during various kinds of oxygen starvation of the brain. Using contact optics and video-recording, direct observations were performed and leukocyte and erythrocyte displacement was monitored in the blood vessels of rat cerebral cortex in vivo in normoxia, during the development of various kinds of oxygen deficiency up to the terminal periods of life of an organism. In normoxia leukocytes were shown to decelerate erythrocyte movement in capillaries and to cause the irregularity of the capillary blood flow. Using the color videofilm recording it was shown that at deep stages of brain oxygen deficiency the disturbances of microcirculation up to its complete cessation were explained by the occlusion of venous microvessels as a result of massive adhesion of leukocytes to the inner surface of venules and the smallest veins. The co-adhesion of leukocytes was also found to take place. The latter leads to the formation of large leukocyte aggregates in venous vessels, results in "no reflow" effect. Leukocyte aggregates in veins block the venous outflow from the brain and may become the immediate cause of organism death as a result of disruption of circulation and oxygen deficiency.     

Role for the cholecystokinin-A receptor in fever: a study of a mutant rat strain and a pharmacological analysis

The involvement of the cholecystokinin (CCK)-A receptor in fever was studied. The polyphasic febrile responses to lipopolysaccharide (LPS; 10 μg kg⁻¹, i.v. ) were compared between wild-type Long-Evans (LE) rats and the CCK-A-receptor-deficient Otsuka LE Tokushima Fatty (OLETF) rats. The response of the wild-type rats was biphasic, which is typical for LE rats. Phases 1 and 2 of the response of the OLETF rats were similar to those of the LE rats, but the OLETF rats also developed a robust phase 3. This late enhancement of the febrile response could reflect either the absence of the A receptor per se or a secondary trait of the mutant strain. To distinguish between these possibilities, we conducted a pharmacological analysis. We studied whether the normally low phase 3 of LE rats can be enhanced by a CCK-A-receptor antagonist, sodium lorglumide (4.3 μg kg⁻¹ min⁻¹, 120 min, i.v. ), and whether the normally high phase 3 of Wistar rats can be attenuated by a CCK-A receptor agonist, sulphated CCK-8 (up to 0.17 μg kg⁻¹ min⁻¹, 120 min, i.v. ). The dose of sodium lorglumide used was sufficient to increase food intake (to block satiety), but it did not affect the fever response. In both febrile and afebrile rats, CCK-8 induced dose-dependent skin vasodilatation and decreased body temperature, but it failed to produce any effects specific for phase 3. We conclude that the exaggeration of phase 3 in OLETF rats reflects a secondary trait of this strain and not the lack of the CCK-A receptor per se . None of the three known phases of the febrile response of rats to LPS requires the CCK-A receptor.     

Insulin cardioplegia for elective coronary bypass surgery

BACKGROUND: Improved methods of myocardial preservation are required to reduce the morbidity and mortality of coronary bypass surgery for high-risk subgroups. Metabolic stimulation with insulin, glucose solutions, or both has been proposed as a method to preserve the ischemic myocardium. We performed a prospective, double-blind, randomized trial to evaluate the effects of insulin and glucose as cardioplegic additives when used as part of a tepid continuous blood cardioplegic strategy. METHODS: We randomized 56 male patients undergoing elective isolated coronary bypass surgery to 1 of 4 cardioplegic groups containing either 42 or 84 mmol/L glucose with or without 10 IU/L of insulin. Perioperative assessments of myocardial metabolism and left ventricular function were performed. RESULTS: Insulin-enhanced cardioplegia was associated with beneficial effects on both myocardial metabolic and functional recovery after cardioplegic arrest. Insulin's effect was independent of the ambient glucose concentration. CONCLUSIONS: Cardioplegic formulations containing a 42 mmol/L concentration of glucose and a 10 IU/L concentration of insulin provide significant benefit to patients undergoing isolated coronary bypass surgery. The clinical effect of these formulations will need to be assessed in high-risk subgroups of patients, such as those with unstable angina, recent myocardial infarction, or poor left ventricular function.     

Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl‐2 and Bcl‐xL antisense treatment

The original article to which this Erratum refers was published in International Journal of Cancer (2003) 106(2) 160–166