Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 µg/kg (5 doses, N = 10), 100 µg/kg (2, 3, 4 and 5 doses, N = 49) or 150 µg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 µg/kg significantly decreased GE by 31-59 percent and GI transit by 55-93 percent. The effect of 5 doses of vincristine (150 µg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 µg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 µg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 µg/kg or after 3-5 doses of 150 µg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.

Variations in gastric compliance induced by acute blood volume changes in anesthetized rats

The impact of acute volume imbalances on gastric volume (GV) was studied in anesthetized rats (250-300 g). After cervical and femoral vessel cannulation, a balloon catheter was positioned in the proximal stomach. The opposite end of the catheter was connected to a barostat with an electronic sensor coupled to a plethysmometer. A standard ionic solution was used to fill the balloon (about 3.0 ml) and the communicating vessel system, and to raise the reservoir liquid level 4 cm above the animals' xiphoid appendix. Due to constant barostat pressure, GV values were considered to represent the gastric compliance index. All animals were monitored for 90 min. After a basal interval, they were randomly assigned to normovolemic, hypervolemic, hypovolemic or restored protocols. Data were compared by ANOVA followed by Bonferroni's test. Mean arterial pressure (MAP), central venous pressure (CVP) and GV values did not change in normovolemic animals (N = 5). Hypervolemic animals (N = 12) were transfused at 0.5 ml/min with a suspension of red blood cells in Ringer-lactate solution with albumin (12.5 ml/kg), which reduced GV values by 11.3 percent (P<0.05). Hypovolemic rats (N = 12) were bled up to 10 ml/kg, a procedure that increased GV values by 15.8 percent (P<0.05). In the restored group (N = 12), shed blood replacement brought GV values back to basal levels in bled animals (P>0.05). MAP and CVP values increased (P<0.05) after hypervolemia but decreased (P<0.05) with hypovolemia. In conclusion, blood volume level modulates gastric compliance, turning the stomach into an adjustable reservoir, which could be part of the homeostatic process to balance blood volume

Os grandes ensaios terapêuticos em arritmias ventriculares e sua repercussäo na terapêutica farmacológica antiarrítmica / Great trials with antiarrhytmic drugs on treatment of ventricular arrythmias and their impact on modern pharmacology therapy

As arritmias ventriculares têm sido objeto de numerosos estudos multicêntricos nos últimos vinte anos. Os resultados desses estudos modificaram näo só as opçöes terapêuticas atuais, como também motivaram a elaboraçäo de novos ensaios terapêuticos. A populaçäo de coronarianos após o infarto do miocárdio tem sido a mais amplamente estudada. As drogas da classe II foram as únicas que realmente preveniram a mortalidade total em infartados sem taquiarritmias ventriculares sustentadas prévias. Já as drogas da classe I, apesar de serem potentes supressoras de ectopias ventriculares, näo demonstraram reduçäo da mortalidade. No CAST, em um acompanhamento médio de 10 meses, a mortalidade foo maior no grupo tratado (7,7 por cento) que o placebo (3 por cento). Metanálises realizadas com drogas dessa classe mostraram mortalidade maior no grupo tratado (5,6 por cento) que no placebo (4,9 por cento). Quando comparada com o placebi, a amiodarona promoveu uma reduçäo de 33 'por cento' no risco de morte por arritmia no CAMIAT, que acompanhou por 2 anos pacientes infartados com arritmia ventricular complexa. Entretanto a reduçäo da mortalidade total de 18 'por cento' näo foi considerada estatisticamente significante. No EMIAT, comparada com o placebo, a amiodarona tampouco reduziu a mortalidade total em infartados portadores de disfunçäo ventriuclar esquerda. Durante 2 anos de acompanhamento em portadores de miocardiopatia, o GESICA revelou menor mortalidade total em uma populaçäo com apenas 39 'por cento' de coronarianos, 1,2 grupo tratado com a amiodarona. A reduçäo de risco foi de 28 'por cento', quando comparada com o grupo controle. O STAT-CHF näo demostrou reduçäo da mortalidade total em miocardiopatas (71 por cento de coronarianos) comparando o placebo (42 por cento) com a amiodarona (39 por cento) durante um acompanhamento de 2 anos. No grupo de pacientes que sobreviveram à fibrilaçäo ventricular, o CASCADE demonstrou menor mortalidade no grupo tratado impiricamente com a amiodarona quando comparado a drogas da classe I guiadas pelo Holter ou pelo estudo eletrofisiológico. Comparando o D,L sotalol com drogas classe I, o ESVEM demonstrou menor incidência de recorrência da taquicardia ventricular sustentada e menor mortalidade quando comparado com seis drogas da classe I em três anos de acompanhamento. O sucesso da amiodarona e do sotalol no controle das taquicardias sustentadas foi atribuído à combinaçäo da açÝo classe III com a ß - bloqueadora presente nas duas

Effects of acute volemic changes on jejunal compliance in dogs

1. Jejunal compliance (deltaV/deltaP) was calculated from the intraluminal pressures measured in anesthetized dogs in an in situ upper jejunal pouch (40-50-ml capcity) with intraluminal volumes of 10, 20, 30, 40 and 50 ml of fisotonic saline. 2. Measurements were made in the same animal during and after acute sequential alterations of the extracellular fluid (ECF) volume obtained by: a) acute intravenous (iv) infusion of isotonic saline, b) acute hemorrhage, and c) reinfusion of isotonic saline. 3. Expansion of the ECF volume caused a significant, reversible downward shift of the compliance curve, i.e., the jejunal pouch became less receptive to liquid distension. After saline infusion was discontinued, complicance gradually returned to control levels. 4. Acute loss a substantial volume of blood after ECF expansion gradually shifted the complicance curve upwards to levels significantly diferent from control, indicating that retraction of the ECF volume made the jejunal pouch more receptive to liquid distension. 5. Reinfusion of bled animals with saline rather than autologous blood also induced a significant decrease in jejunal complicance to below control levels. 6. The jejunal pouch as a suitable preparation for monitoring in vivo modifications of compliance induced by acute changes in ECF volume, especially when it was nearly "half-full" (i.e., filled with 20 ml), suggesting a critical relationship between the volume capacity of the pouch and its fluid content. 7. These results suggest that the modulation of the jejunal portion os small intestine compliance is involved in the processes that balance the ECF volume during acute life-threatening situations such as accidental hyperhydration or hemorrhage

Acute changes in extracellular fluid volume modify the antroduodenal flow of saline in dogs: a possible physiological role

The antroduodenal (AD) flow of saline was measured in anesthetized dogs following two different protocols of acute changes in extracellular fluid (ECF) volume, ECF expansion by in infusion of saline before or after hemorrhage decreased the AD flow; conversely, hemorrhage before or after expansion increased flow. These alternating modifications in the AD flow are independent of the sequence of volemic changes and may constitue part of the homeostatic responses of the gut to confront life-thratening situations such as accidental hyperhydration or hemorrhage