MiWEndo: Evaluation of a Microwave Colonoscopy Algorithm for Early Colorectal Cancer Detection in Ex Vivo Human Colon Models.

This study assesses the efficacy of detecting colorectal cancer precursors or polyps in an ex vivo human colon model with a microwave colonoscopy algorithm. Nowadays, 22% of polyps go undetected with conventional colonoscopy, and the risk of cancer after a negative colonoscopy can be up to 7.9%. We developed a microwave colonoscopy device that consists of a cylindrical ring-shaped switchable microwave antenna array that can be attached to the tip of a conventional colonoscope as an accessory. The accessory is connected to an external unit that allows successive measurements of the colon and processes the measurements with a microwave imaging algorithm. An acoustic signal is generated when a polyp is detected. Fifteen ex vivo freshly excised human colons with cancer (n = 12) or polyps (n = 3) were examined with the microwave-assisted colonoscopy system simulating a real colonoscopy exploration. After the experiment, the dielectric properties of the specimens were measured with a coaxial probe and the samples underwent a pathology analysis. The results show that all the neoplasms were detected with a sensitivity of 100% and specificity of 87.4%.

Possible mineral contributions to the diet and health of wild chimpanzees in three East African forests.

We present new data on the ingestion of minerals from termite mound soil by East African chimpanzees (Pan troglodytes schweinfurthii) living in the Budongo Forest Reserve, Uganda, the Gombe National Park and the Mahale Mountains National Park, Tanzania. Termite mound soil is here shown to be a rich source of minerals, containing high concentrations of iron and aluminum. Termite mound soil is not, however, a source of sodium. The concentrations of iron and aluminum are the highest yet found in any of the mineral sources consumed. Levels of manganese and copper, though not so high as for iron and aluminum, are also higher than in other dietary sources. We focus on the contribution of termite mound soil to other known sources of mineral elements consumed by these apes, and compare the mineral content of termite soil with that of control forest soil, decaying wood, clay, and the normal plant-based chimpanzee diet at Budongo. Samples obtained from Mahale Mountains National Park and Gombe National Park, both in Tanzania, show similar mineral distribution across sources. We suggest three distinct but related mechanisms by which minerals may come to be concentrated in the above-mentioned sources, serving as potentially important sources of essential minerals in the chimpanzee diet.

Scars on plants sourced for termite fishing tools by chimpanzees: Towards an archaeology of the perishable.

Chimpanzees are well-studied, but raw material acquisition for tool use is still poorly understood as sources are difficult to trace. This study pioneers the use of information that can be gleaned from plant scars made by chimpanzees while they source vegetation parts to manufacture termite fishing tools. Source plant species, raw material types and locations relative to targeted termite mounds were recorded for populations at Gombe, Issa, and Mahale in western Tanzania. Recovered bark, twig, and vine tools were traced to 29 plant species, while grass sources were indeterminable. Bark extraction scars remained detectable for months, and thus possibly for as long as the plant is alive, while twig and vine scars preserved for a few weeks only. Scars preserve better than tools, given that twice as many plant species could be linked to the former than to the latter. Some source species were exploited across all sites for the same type of tool material, while two species were sourced for different types. Compared to apes at Gombe and Mahale, Issa chimpanzees carried material from twice as far away, perhaps because the Issa habitat is more open and dry, which entails greater distances between suitable raw material sources and targeted mounds. Site-specific tools were based on different raw materials, in two cases sourced from the same species, which could suggest learned preferences for particular tool material. "Archaeology of the perishable" as pioneered in this study broadens the methodological approach of the wider field of primate archaeology to include reconstructions of past animal behavior associated with the production of plant based tools.

Raw material procurement for termite fishing tools by wild chimpanzees in the Issa valley, Western Tanzania.

OBJECTIVES: Chimpanzee termite fishing has been studied for decades, yet the selective processes preceding the manufacture of fishing tools remain largely unexplored. We investigate raw material selection and potential evidence of forward planning in the chimpanzees of Issa valley, western Tanzania. MATERIALS AND METHODS: Using traditional archaeological methods, we surveyed the location of plants from where chimpanzees sourced raw material to manufacture termite fishing tools, relative to targeted mounds. We measured raw material abundance to test for availability and selection. Statistics included Chi-Squared, two-tailed Wilcoxon, and Kruskall-Wallace tests. RESULTS: Issa chimpanzees manufactured extraction tools only from bark, despite availability of other suitable materials (e.g., twigs), and selected particular plant species as raw material sources, which they often also exploit for food. Most plants were sourced 1-16 m away from the mound, with a maximum of 33 m. The line of sight from the targeted mound was obscured for a quarter of these plants. DISCUSSION: The exclusive use of bark tools despite availability of other suitable materials indicates a possible cultural preference. The fact that Issa chimpanzees select specific plant species and travel some distance to source them suggests some degree of selectivity and, potentially, forward planning. Our results have implications for the reconstruction of early hominin behaviors, particularly with regard to the use of perishable tools, which remain archaeologically invisible.

Sustained myrmecophagy in Nigerian chimpanzees: Preferred or fallback food?

OBJECTIVE: At some sites across Africa, chimpanzees consume army ants, often aided by plant tools, although consumption frequencies vary greatly. Other populations do not eat these insects at all, despite apparent abundance. The relative importance of this type of myrmecophagy for chimpanzee diet therefore remains unclear. We investigate if army ants constitute a preferred food or a fallback resource for chimpanzees at Gashaka, Nigeria, where army ants are consumed much more frequently than elsewhere. METHODS: Long-term records on temporal variation of climate and availability of fruit as the chimpanzees' preferred food are compared with rates of recovered army ant dipping wands and army ant remains in feces. RESULTS: Despite strict seasonality of rainfall and fruit abundance, myrmecophagy does not negatively correlate with fruit availability. Instead, army ant eating is sustained year round at high levels, with 44% of feces containing remains. CONCLUSIONS: Results contradict the fallback hypothesis and support the hypothesis that ants are a preferred food. Nevertheless, compared with fruit, ant-meals can normally provide only negligible amounts of nutrients. At Gashaka, however, nutritional yield may be significant, given that ant-dipping sessions provide on average 13 mg of dry weight to a chimpanzee. The species exclusively eaten here, Dorylus rubellus, might be particularly aggressive, thus resulting in greater harvesting success than elsewhere. Army ants may hence serve as a diet supplement or complement in terms of macro- or micronutrients.

Primate archaeology 3.0.

The new field of primate archaeology investigates the technological behavior and material record of nonhuman primates, providing valuable comparative data on our understanding of human technological evolution. Yet, paralleling hominin archaeology, the field is largely biased toward the analysis of lithic artifacts. While valuable comparative data have been gained through an examination of extant nonhuman primate tool use and its archaeological record, focusing on this one single aspect provides limited insights. It is therefore necessary to explore to what extent other non-technological activities, such as non-tool aided feeding, traveling, social behaviors or ritual displays, leave traces that could be detected in the archaeological record. Here we propose four new areas of investigation which we believe have been largely overlooked by primate archaeology and that are crucial to uncovering the full archaeological potential of the primate behavioral repertoire, including that of our own: (1) Plant technology; (2) Archaeology beyond technology; (3) Landscape archaeology; and (4) Primate cultural heritage. We discuss each theme in the context of the latest developments and challenges, as well as propose future directions. Developing a more "inclusive" primate archaeology will not only benefit the study of primate evolution in its own right but will aid conservation efforts by increasing our understanding of changes in primate-environment interactions over time.

Apes finding ants: Predator-prey dynamics in a chimpanzee habitat in Nigeria.

Some chimpanzee populations prey upon army ants, usually with stick tools. However, how their prey's subterranean nesting and nomadic lifestyle influence the apes' harvesting success is still poorly understood. This is particularly true for chimpanzees (Pan troglodytes ellioti) at Gashaka/Nigeria, which consume army ants (Dorylus rubellus) with much higher frequency than at other sites. We assessed various harvesting and search options theoretically available to the apes. For this, we reconstructed annual consumption patterns from feces and compared the physical characteristics of exploited ant nests with those that were not targeted. Repeated exploitation of a discovered nest is viable only in the short term, as disturbed colonies soon moved to a new site. Moreover, monitoring previously occupied nest cavities is uneconomical, as ants hardly ever re-used them. Thus, the apes have to detect new nests regularly, although colony density is relatively low (1 colony/1.3 ha). Surprisingly, visual search cues seem to be of limited importance because the probability of a nest being exploited was independent of its conspicuousness (presence of excavated soil piles, concealing leaf-litter or vegetation). However, chimpanzees preferentially targeted nests in forests or at the base of food trees, that is, where the apes spend relatively more time and/or where ant colony density is highest. Taken together, our findings suggest that, instead of employing a search strategy based on visual cues or spatial memory, chimpanzee predation on army ants contains a considerable opportunistic element.

Preclinical Evaluation of a Microwave-Based Accessory Device for Colonoscopy in an In Vivo Porcine Model with Colorectal Polyps.

BACKGROUND AND AIMS: Colonoscopy is currently the most effective way of detecting colorectal cancer and removing polyps, but it has some drawbacks and can miss up to 22% of polyps. Microwave imaging has the potential to provide a 360° view of the colon and addresses some of the limitations of conventional colonoscopy. This study evaluates the feasibility of a microwave-based colonoscopy in an in vivo porcine model. METHODS: A prototype device with microwave antennas attached to a conventional endoscope was tested on four healthy pigs and three gene-targeted pigs with mutations in the adenomatous polyposis coli gene. The first four animals were used to evaluate safety and maneuverability and compatibility with endoscopic tools. The ability to detect polyps was tested in a series of three gene-targeted pigs. RESULTS: the microwave-based device did not affect endoscopic vision or cause any adverse events such as deep mural injuries. The microwave system was stable during the procedures, and the detection algorithm showed a maximum detection signal for adenomas compared with healthy mucosa. CONCLUSIONS: Microwave-based colonoscopy is feasible and safe in a preclinical model, and it has the potential to improve polyp detection. Further investigations are required to assess the device's efficacy in humans.

Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome.

Down syndrome (DS) is characterized by the trisomy of chromosome 21 and by cognitive deficits that have been related to neuronal morphological alterations in humans, as well as in animal models. The gene encoding for amyloid precursor protein (APP) is present in autosome 21, and its overexpression in DS has been linked to neuronal dysfunction, cognitive deficit, and Alzheimer's disease-like dementia. In particular, the neuronal ability to extend processes and branching is affected. Current evidence suggests that APP could also regulate neurite growth through its role in the actin cytoskeleton, in part by influencing p21-activated kinase (PAK) activity. The latter effect is carried out by an increased abundance of the caspase cleavage-released carboxy-terminal C31 fragment. In this work, using a neuronal cell line named CTb, which derived from the cerebral cortex of a trisomy 16 mouse, an animal model of human DS, we observed an overexpression of APP, elevated caspase activity, augmented cleavage of the C-terminal fragment of APP, and increased PAK1 phosphorylation. Morphometric analyses showed that inhibition of PAK1 activity with FRAX486 increased the average length of the neurites, the number of crossings per Sholl ring, the formation of new processes, and stimulated the loss of processes. Considering our results, we propose that PAK hyperphosphorylation impairs neurite outgrowth and remodeling in the cellular model of DS, and therefore we suggest that PAK1 may be a potential pharmacological target.

Obtaining raw material: plants as tool sources for Nigerian chimpanzees.

We investigated the acquisition of plant materials from which Nigerian chimpanzees manufacture wooden tools to harvest insects and honey from nests of army ants, honey bees and stingless bees. Slender trunks of juvenile trees and branches are most commonly used, and bendable vines rarely, probably reflecting the need to work with relatively sturdy tools to extract resources. While several tools are sometimes sourced from the same plant, there is also evidence for a depletion effect, as multiple tool sources at the same site are often spaced several metres apart. Identified tool sources belong to 27 species of at least 13 families. Honey-gathering implements are often chewed upon by chimpanzees. Interestingly, twigs of the most commonly used honey-gathering species possess antibacterial propensities and are favoured by Nigerians as chewing sticks. This suggests that extractive tools might possess associated medicinal or stimulatory properties. We do not know if chimpanzees actively select specific plant parts or species as we cannot compare observed with expected frequencies. Nevertheless, about three quarters of tools are picked from plants more than 6 m away from the extraction site, potentially indicating some degree of forward planning.

Microwave-Based Colonoscopy: Preclinical Evaluation in an Ex Vivo Human Colon Model.

INTRODUCTION: Microwave imaging can obtain 360° anatomical and functional images of the colon representing the existing contrast in dielectric properties between different tissues. Microwaves are safe (nonionizing) and have the potential of reducing the visualization problems of conventional colonoscopy. This study assessed the efficacy of a microwave-based colonoscopy device to detect neoplastic lesions in an ex vivo human colon model. METHODS: Fresh surgically excised colorectal specimens containing cancer or polyps were fixed to a 3D positioning system, and the accessory device was introduced horizontally inside the ex vivo colon lumen and moved along it simulating a real colonoscopy exploration. Measurements of the colon were taken every 4 mm with the microwave-based colonoscopy device and processed with a microwave imaging algorithm. RESULTS: 14 ex vivo human colorectal specimens with carcinomas (n = 11) or adenomas with high grade dysplasia (n = 3) were examined with a microwave-based device. Using a detection threshold of 2.79 for the dielectric property contrast, all lesions were detected without false positives or false negatives. CONCLUSIONS: This study demonstrates the use of a microwave-based device to be used as an accessory of a standard colonoscope to detect neoplastic lesions in surgically excised colorectal specimens.

Hepatosplanchnic vasoregulation and oxygen consumption during selective aortic blood flow reduction and reperfusion.

BACKGROUND: Several studies have shown that the distribution of cardiac output to the intra-abdominal organs may vary during low-flow states. In this study, we developed an experimental model to selectively reduce the abdominal aortic blood flow in order to assess the initial impact of selective hepatosplanchnic hypoperfusion on regional blood flow redistribution. METHODS: Eight anesthetized and mechanically ventilated mongrel dogs were subjected to aortic blood flow reduction with an occluder in a stepwise manner by 50% and 100% for 45 min. After the ischemic period, the occluder was released, and animals were observed for an additional 45 min. Systemic hemodynamics were evaluated through a Swan-Ganz and arterial catheters, and gastrointestinal tract perfusion was evaluated by portal vein and hepatic arterial blood flows measurements (ultrasonic flowprobe). Intestinal O2-derived variables, intestinal mucosal (tonometric)-arterial and tonometric-(end-tidal-carbon-dioxide) gradients (Dt-apCO2 and Dt-EtpCO2) were also calculated. RESULTS: No significant changes in systemic and regional oxygen consumption were observed during the 50% reduction of aortic blood flow. On the other hand, both microregional pCO2 gradients (Dt-apCO2 e Dt-EtpCO2) showed a significant increase during this period. Aortic occlusion was associated with a marked reduction of systemic and regional oxygen delivery and consumption. During the reperfusion, no significant improvement in the tonometry-based pCO2 gradients was observed, in spite of the partial reestablishment of blood flow to the hepatosplanchnic territory. CONCLUSION: During selective intra-abdominal low-flow, a proportional reduction in the splanchnic and hepatic blood flows occurs. A selective reduction of approximately 50% in splanchnic oxygen delivery was not associated with significant changes in macroregional markers of hypoperfusion. In this situation, tonometry-based pCO2 gradients can be used for the assessment of hepatosplanchnic perfusion and histologic changes.

Short-term effects of hydroxyethylstarch resuscitation on systemic and regional hemodynamics and metabolism in a brain-dead canine model.

BACKGROUND: Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. METHODS: Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33 mL/kg), and HES (6%HES 450/0.7, 17 mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. RESULTS: Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. CONCLUSION: Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions.

Regional blood flow distribution and oxygen metabolism during mesenteric ischemia and congestion.

BACKGROUND: Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. METHODS: Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. RESULTS: SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-a)pCO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. CONCLUSIONS: SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection.

In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

Fluid replacement with hypertonic or isotonic solutions guided by mixed venous oxygen saturation in experimental hypodynamic sepsis.

BACKGROUND: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoncotic solution would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. METHODS: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. RESULTS: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. CONCLUSIONS: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death.

BACKGROUND: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. MATERIAL/METHODS: Ten dogs (21.3+/-0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without any additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. RESULTS: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0+/-0.2 vs. 2.8+/-2.8 L/min) and PVBF (687+/-114 vs. 623+/-130 ml/min) was observed, whereas HABF (277+/-33 vs. 134+/-28 ml/min, p<0.005) remained lower than baseline values. CONCLUSIONS: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.

Cultural variation between neighbouring communities of chimpanzees at Gombe, Tanzania.

Comparative animal studies have revealed the existence of inter-group differences in socially learned behaviours - so-called cultural variations. However, most research has drawn on geographically and thus environmentally separated populations, rendering it difficult to exclude genetic or ecological influences. To circumvent this problem, the behaviour of neighbouring groups from the same population can be juxtaposed - an approach which in wild chimpanzees (Pan troglodytes) has revealed cultural differences in the use of nut-cracking and ant-dipping tools. Here I apply archaeological methods to extend this approach to compare the qualities of termite fishing tools used by wild chimpanzees by comparing the neighbouring Kasekela and Mitumba communities at Gombe Stream National Park, Tanzania. While no identifiable differences existed between the available plant species and associated vegetal components, members of the Kasekela community selected a larger array of raw materials and manufactured significantly longer and wider tools compared with the Mitumba community. Thus, cultural knowledge is reflected in differentiated behaviour on a small spatial scale. This study emphasizes the use of archaeological methods to identify cultural variation among living chimpanzee communities, adding to the growing research operating within the new field of Primate Archaeology.

Early restoration of cocaine-induced splanchnic hypoperfusion in anesthetized dogs.

Although cardiovascular effects of cocaine have been well studied, little is known about its effects on splanchnic perfusion. We studied systemic and regional hemodynamic effects of acute cocaine intoxication in dogs under volatile anesthesia. Mechanically ventilated beagle dogs, randomized at 1.5% halothane (n = 7) or 2.25% sevoflurane (n = 7) anesthesia, received an intravenous bolus of cocaine (12 mg/kg over 5 min) followed by 0.22 mg/kg/min infusion over 30 min. They were observed for 60 min thereafter. Cardiac index (CI), heart rate (HR), mean arterial pressure (MAP), portal blood flow (PBF), gastric PCO(2) (gas tonometry), blood gases, and lactate and cocaine levels were assessed. Cocaine bolus promoted significant reductions in CI (~50%), HR (~20%), MAP (~20%), and PBF (~50%), accompanied by increase in systemic and splanchnic oxygen extractions and in gastric mucosal-arterial PCO(2) gradient. Those changes were maintained during cocaine infusion and returned to baseline values parallel to plasmatic cocaine clearance. Unlike other shock states, regional parameters, including gastric mucosal-arterial PCO(2) gradient, were restored before systemic variables. A possible local vasodilatory effect of volatile agents could play a role in this phenomenon. Cocaine infusion in anesthetized animals promoted marked systemic and regional hemodynamic derangement, which was rapidly reversible with decay of cocaine plasmatic concentration.