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Ischemia/reperfusion (I/R), a phenomenon that is associated with conditions such as organ transplantation, trauma, vascular disease, and stroke, involves the recruitment of activated and adherent leukocytes that subsequently mediate tissue injury. Endothelial cell adhesion molecules such as P-selectin mediate I/R-induced leukocyte recruitment and allow the adherent leukocytes to damage the vascular wall and parenchymal cells. This study examines the influence of dypiridamole (persantine) on hemorrhagic shock (H/S)-induced P-selectin expression. H/S was induced in C57BL/6 mice by withdrawing blood to drop the mean arterial blood pressure to 30 to 35 mm Hg for 45 minutes. The mice were resuscitated by infusing the shed blood and Ringer's lactate (50% shed blood volume). In vivo P-selectin expression was determined using a dual monoclonal antibody technique in the heart, lung, liver, kidneys, stomach, small bowel, and colon of a control group, a hemorrhagic shock group, and a hemorrhagic shock group that was pretreated with Persantine (Boehringer, Ingelheim, Ingelheim, Germany). H/S significantly (P0.01) increased P-selectin expression in all regional vascular beds of untreated mice. Persantine treatment largely prevented the H/S-induced P-selectin expression in the same vascular beds. Persantine significantly attenuates the upregulation of P-selectin in the hemorrhagic shock model.

Ischemic preconditioning has been shown to protect some tissues from ischemia/reperfusion (I/R) injury. Adenosine is believed to play an important role by attenuating leukocyte-endothelial cell adhesive interactions. Dipyridamole increases adenosine bioavailability. The purpose of this study was to evaluate the effects of mechanical (MPC) and pharmacological preconditioning (PPC) on leukocyte endothelial cell interaction in hepatic I/R injury.C57BL6 mice were subjected to 30 min of ischemia to the left lobe of the liver. Groups tested at 30 min, 2, 5, 12, and 24 hr of reperfusion had 1) sham laparotomy (n = 10, 2) I/R (n = 25), 3) ischemic preconditioning with 5 min of ischemia and 10 min reperfusion before I/R (n = 25), and 4) (PPC) with dipyridamole (n = 25). Intravital microscopic examination was used to assess leukocyte/endothelial cell adhesion. Blood was drawn for leukocyte counts and liver function tests.A significant decrease in leukocyte rolling was observed at 30-min and 5-hr reperfusion intervals in the PPC and ischemic preconditioning groups compared with the I/R group. A significant decrease in leukocyte saltation was also observed in the PPC and MPC groups at 2, 5, and 12 hr of reperfusion when compared with the I/R group. aspartate aminotransferase was significantly decreased in the 5-hr preconditioning groups. There was not a significant decrease in the white blood cell count because of PPC or MPC vs. I/R CONCLUSIONS: Preconditioning decreases endothelial/ leukocyte interaction and reduces liver damage as measured by aspartate aminotransferase. These data prove that IPC and PPC provide some degree of hepatic protection in I/R injury.

Mechanisms of injury in hepatic ischemia/reperfusion injury are poorly defined. Leukocytes are thought to be important in the final mechanism of hepatic damage. We intend to show the time course of abnormal leukocyte activity in the liver after ischemia/reperfusion (I/R) injury. Left lobar hepatic ischemia was induced for 20 min in anesthetized C57B1-6 mice. Measurements were taken at control, reperfusion, and matching sham times (no ischemia) of 2, 5, 12, and 24 h. Measurements were taken using rhodamine and fluorescein enhanced intravital microscopy. Post sinusoidal venules were evaluated for numbers of rolling leukocytes, leukocyte saltation, and leukocyte velocity. Data are expressed as number of rolling leukocytes per 100 microns venule length (2 min). Statistical analysis was by ANOVA. The number of rolling leukocytes at 5, 12, and 24 h of reperfusion (p0.001) was significantly higher than control and sham-operated animals. Leukocyte velocities were significantly slower in the 12 h I/R group when compared to sham animals (p0.001). These data show that there are definable and quantifiable changes in leukocyte kinetics in the liver after ischemia/reperfusion. These changes, which lasted for 24 h, are likely due to upregulation of various endothelial cell adhesion molecules. Delineation of these mechanisms may be important in disease states such as shock, sepsis, and hepatic transplantation.

Rats gathered pellets from the tops of 15.5-cm-tall poles. In a matrix of poles, bait was located on the tops of poles arranged in either a square (Experiment 1) or linear (Experiment 2) configuration. The specific locations of baited poles varied unpredictably from trial to trial. The data show that the rats' choices were controlled by the spatial configuration of baited locations. This indicates that the rats represented the geometric pattern formed by the locations of food.

In 6 experiments, the performance of male rats in a 12-arm radial maze was examined. The focus of study was the extent to which the spatial location of individual baited maze arms was determined before the rat was exposed to the extramaze visual cues corresponding to the arm, and thereby guided the rat toward the location of baited arms. Such spatial guidance of choice behavior implies a spatially organized cognitive representation of maze arms (i.e., a cognitive map). A higher level of spatial guidance was found when visual access to extramaze cues was restricted than when it was unrestricted. There was no evidence of a difference between the level of spatial guidance in the context of working memory performance and reference memory performance. Some evidence that intramaze cues contributed to microchoice guidance was found. However, spatial guidance, under at least some conditions, is best explained in terms of cognitive mapping.

Mesenteric hypoperfusion may be responsible for alterations in gut mucosa leading to necrotizing enterocolitis. Platelet-activating factor (PAF) and cocaine have been implicated in the etiology of necrotizing enterocolitis. We have demonstrated direct toxic effects of these compounds in vitro, but the in vivo mechanism of bowel damage is unknown. Newborn piglets (3.0 +/- 0.3 kg) had physiologic parameters (electrocardiogram, blood pressure, pulse, and central venous pressure) continuously monitored as well as Doppler probe recordings of superior mesenteric artery flow (Qsma). Aortic flow with calculation of cardiac index, and systemic and mesenteric vascular resistances (SVR and MVR) were also determined. Group 1 (N = 8) received PAF (0.5 microgram/kg). Groups 2 (N = 8) and 3 (N = 8) received high (17 mg/kg) and low (9 mg/kg) doses of cocaine, respectively. Each subject served as its own control. Histology demonstrated edema or early mucosal hemorrhage in all groups. PAF caused a third-degree atrioventricular block of short duration and a prolonged decrease of the cardiac index, but only a brief elevation of SVR and MVR. The cocaine groups had a sustained increase of SVR and MVR associated with a decrease of cardiac index. The decrease of Qsma paralleled the changes of MVR in each subject. These data show that both PAF and cocaine induce mesenteric ischemia. The effect of PAF is of short duration and mainly related to its cardiotoxic effects resulting in low Qsma. Cocaine causes an increase in MVR with prolonged depression of mesenteric flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Fifteen rats performed in a standard radial-arm maze task (Experiment 1) and in a modified task with a set of forced choices and a 15-min retention interval prior to completion of the maze (Experiment 2). In addition to the standard measure of choice in the radial-arm maze, orientation toward arms was measured and considered to constitute go-no-go "microchoice" decisions. Rats investigated but rejected many arms. A model of choice was developed in which it was assumed that choice decisions about arms were made independently and that microchoices were not selectively guided toward baited arms. The model performed nearly as well as the rats. These results place important limitations on the theory that choice behavior in the radial-arm maze is guided by a cognitive map.

Pigeons were trained to match color and line orientation element or compound samples in a symbolic matching-to-sample task. In subsequent test sessions with element and compound samples, there was an initial superiority of element matching for the element-trained group and of compound matching for the compound-trained group. This difference persisted over the course of 100 test sessions for the element-trained group, whereas element- and compound-matching accuracy converged for the compound-trained group. In a second experiment, in which sample duration was manipulated, element-matching accuracy was superior to compound-matching accuracy for both groups. Thus, element-matching accuracy was superior to compound-matching accuracy under conditions that rule out generalization decrement and training history as explanations. The data are interpreted as supporting the view that the dimensions of visual compound stimuli compete for a limited cognitive resource.

Extract Auto-immune, haemolytic anacmias (AHA) of man (Dacie, 1963) and domestiicated animals (Schalm, 1965; Farrelly et al., 1966; Lapras and Oudar, 1971) are classified either as idiopathic or secondary to an underlying disease process (Pirofsky, 1969). In both categories antibodies active against the indivual's own erythrocytes are formed. These auto-antibodies are of two types being either warm or cold-acting. Warm-acting antibodies are most effective at 37°C, belong to the IgG class of immunoglobulins, and are incomplete in that, generally, they do not cause autohaemagglutination. Coldacting, or cryopathic, antibodies show maximum activitv at 4°C, are of the IgM immunoglobulin class and are capable of effecting autohaemagglutination. The two types of antibodies also differ in their prevalence. In man warm-acting antibodies occur infrequently and are always pathological (Dacie, 1963) while low titres of cold antibodies occur in most normal sera (Finland et al., 1945; Ellenhorn and Weiner, 195...