Repeated cisplatin treatments inhibit gastrointestinal motility and induces baroreflex changes and mechanical hyperalgesia in rats.

Cisplatin is a chemotherapy agent known for its neurotoxicity. We evaluated the effect of cisplatin on the gastric emptying (GE), gastrointestinal (GI) transit of liquid, baroreflex function, thermal, and mechanical withdrawal latencies in rats. Cisplatin increased the GE of liquid with doses ≥ 2 mg.kg(-1) by 59.7-77.4%. This GE delay was not present two weeks after the treatment with five doses of cisplatin at 1 mg.kg(-1). Cisplatin also enhanced baroreflex gain possibly by increasing sympathetic activity. Our results demonstrated that cisplatin (2-10 mg.kg(-1)) causes autonomic neuropathy with GI and baroreflex changes and mechanical but not thermal hyperalgesia in rats.

Spinal cord transection modifies ileal fluid and electrolyte transport in rats.

Spinal cord injury (SCI) is associated with severe autonomic changes, including inhibition of gastrointestinal (GI) motility. GI motility changes are known to affect electrolytes transport and these changes have not been adequately studied after SCI. We studied the ileal permeability to fluid and electrolytes in rats submitted to experimental spinal cord transection (SCT), between T4 and T5, throughout the first week after SCT. SCT increased ileal secretion of Na+ (P<0.05) and decreased the Cl(-) absorption during the first week post SCI (P<0.05). Water transport was also significantly altered, leading to increased water secretion following the Na+ gradient. Ileal secretion of K+ was significantly increased 1 and 7 days after spinal cord injury. To our knowledge, the present findings are the first direct evidence that SCT alters ileal electrolyte transport in rats. Further studies are necessary to evaluate the mechanisms involved in this phenomenon.

1.8 cineole decreases gastric compliance in anesthetized rats.

PURPOSE: To study the effect of 1,8 cineole components of the essential oil of Croton nepetaefolius--plant of North-East of Brasil, used in the popular medicine for riots of the gastrointestinal tract--on the motor behavior of the gut of Wistar rats. METHODS: Used 16 male animals under jejun of 24h weighing 300-350 g. The effect of 1.8 cineole (1 or 3mg/Kg) on gastric compliance had been lead in anaesthetized rats. The variations of the gastric volume (GV), had been measured by plethysmography, while AP, HR and CVP had been monitored continuously by a digital system of data acquisition. RESULTS: Observe reduction of the GV, which was significant on 30, 40, 50 and 60 min after treatment (2.0 +/- 0.1; 1.9 +/- 0.1; 1.8 +/- 0.1 and 1.7 +/- 0.1mL, versus 2.1 +/- 0.2mL). The AP presented significant fall after the administration of 1.8 cineole, remaining thus during 60min of monitorization (87.9 +/- 7.7; 87.6 +/- 7.1; 87.9 +/- 6.4; 87.8 +/- 5.7; 86.0 +/- 5.5 and 87.7 +/- 6.0mmHg, respectively versus 94.4 +/- 6.2 mmHg), as well as the HR (366.3 +/- 13.4; 361.7 +/- 11.5; 357.3 +/- 10.4; 353.0 +/- 10.4; 348.3 +/- 11.1 and 350.4 +/- 13.7bpm, respectively versus 395.2 +/- 11.1bpm). The CVP did not suffer significant variations after treatment. CONCLUSION: Observe the 1.8 cineole reduces the gastric compliance in anaesthetized rats besides presenting effect hypotensor and bradycardia; probably for direct action on the gastrointestinal and vascular smooth muscle and moduling the autonomic nervous system.

Inhibitory effect of sildenafil on rat duodenal contractility in vitro: putative cGMP involvement.

1. Sildenafil citrate (Viagratrade mark; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activity in vitro. 2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic effect on acetylcholine (ACh)-induced phasic contractions, with an IC50 value of 26.7 micromol/L (95% confidence interval (CI) 2.0-55.3 micromol/L). 3. Sildenafil also relaxed the carbamylcholine (CCh)-induced sustained contraction with an IC(50) of 16.2 micromol/L (95% CI 9.5-27.6 micromol/L). Sildenafil produced significant additional relaxation of 25.2 +/- 8.1% of the CCh-induced contraction, beyond basal tone. 4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC50 of 9.6 micromol/L (95% CI 5.7-16.2 micromol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC50 values of 91.6 micromol/L (95% CI 46.0-182.2 micromol/L) and 78.5 micromol/L (95% CI 37.1-166.3 micromol/L), respectively. 5. In preparations treated previously with methylene blue (10 micromol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L), the EC50 values for the sildenafil effect were significantly increased to 39.0 micromol/L (95% CI 23.9-63.4 micromol/L) and 43.8 micromol/L (95% CI 24.5-78.3 micromol/L), respectively. These values were significantly greater than those obtained with sildenafil alone. 6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segments in vitro. The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation.

Sildenafil, a phosphodiesterase-5 inhibitor, delays gastric emptying and gastrointestinal transit of liquid in awake rats.

We studied the effect of sildenafil on gastric emptying (GE) and gastrointestinal (GI) transit in awake rats. After cervical vessel cannulation and 24 hr of fasting, the animals received an intravenous (IV) injection of sildenafil (4 mg/kg) or vehicle. Next they were gavage fed (1.5 ml) with a test meal (phenol red in 5% glucose solution, 0.5 mg/ml) and sacrificed 10, 20, or 30 min later. Experimental and control subsets consisted of 5-10 rats. Gastric and proximal, medial, and distal small intestine dye retentions (GDR and IDR, respectively) were obtained by spectrophotometry. Data were compared by ANOVA and Student-Newman-Keuls test. In sildenafil-treated animals, GDR increased (P < 0.05) by 20.3%, 46.9%, and 55,5% while medial IDR decreased (P < 0.05) by 35.1%, 43.4%, and 41.6%, respectively, at 10, 20, and 30-min intervals. Proximal and distal IDR values did not change in sildenafil-treated animals. Mean arterial pressure (MAP) decreased 25% (P < 0.05) right after sildenafil administration but normalized afterwards while in controls MAP remained unchanged. In conclusion, sildenafil delays GE and GI transit of a liquid meal while transiently decreases MAP in awake rats.

Gastric emptying and gastrointestinal transit of liquid in awake rats is delayed after acute myocardial infarction.

The outcome of acute myocardial infarction (AMI) on gastrointestinal motor behavior was assessed in awake rats. Under anesthesia, they were submitted to thoracotomy followed or not by occlusion of the left coronary artery. Next day, they were gavage fed (1.5 ml) with phenol red in 5% glucose solution and sacrificed 10, 20, or 30 min later. Each subset consisted of 7 to 19 animals. Dye recovery in the stomach, proximal, mid, and distal small intestine was obtained by spectrophotometry. Infarcted left ventricle plus septum area was about 48.9 +/- 2.8, 55.1 +/- 6.7, and 54.1 +/- 8.1% (respectively, for 10-, 20-, and 30-min subsets). AMI increased gastric dye retention by 25.5, 51.3, and 65.1% (respectively, for 10-, 20-, and 30-min subsets), while it decreased mid small intestine retention at 30 min (45.3%) as well as distal retention at 10 min (90.5%) and 20 min (90%). A positive correlation (rS = 0.64) was found between infarcted area and gastric retention values at 10 min. AMI also increased (P < 0.05) central venous pressure values in all subsets (3.8 +/- 0.2 vs. -2.1 +/- 1.5, 1.4 +/- 0.1 vs. 0.5 +/- 0.2, and 1.6 +/- 0.4 vs. -0.2 +/- 0.3 cm H2O), while it decreased (P < 0.05) mean arterial pressure (95.0 +/- 2.6 vs. 110.0 +/- 3.9 and 106.0 +/- 2.0 vs. 113.0 +/- 3.0 mm Hg, respectively, at 10 and 30 min), and increased (P < 0.05) the 10-min heart rate values (429.6 +/- 11.3 vs. 374.0 +/- 19.8 bpm). Omeprazole pretreatment did not alter this phenomenon. In another group of rats, cardiac chemoreflex stimulation by i.v. phenylbiguanide increased gastric dye retention by 51.1%. In conclusion, AMI delays the gastric emptying and gastrointestinal transit of liquid in awake rats.

1.8 cineole decreases gastric compliance in anesthetized rats

PURPOSE: To study the effect of 1,8 cineoleee components of the essencial oil of Croton nepetaefolius - plant of North-East of Brasil, used in the popular medicine for riots of the gastrointestinal tract - on the motor behavior of the gut of Wistar rats. METHODS: Used 16 male animals under jejun of 24h weighing 300-350g. The effect of 1.8 cineoleee (1 or 3mg/Kg) on gastric compliance had been lead in anaesthetized rats. The variations of the gastric volume (GV), had been measured by plethysmography, while AP, HR and CVP had been monitored continuously by a digital system of data acquisition. RESULTS: Observe reduction of the GV, which was significant on 30, 40, 50 and 60min after treatment (2.0±0.1; 1.9±0.1; 1.8±0.1 and 1.7±0.1mL, versus 2.1±0.2mL). The AP presented significant fall after the administration of 1.8 cineoleee, remaining thus during 60min of monitorization (87.9±7.7; 87.6±7.1; 87.9±6.4; 87.8±5.7; 86.0±5.5 and 87.7±6.0mmHg, respectively versus 94.4±6.2 mmHg), as well as the HR (366.3±13.4; 361.7±11.5; 357.3±10.4; 353.0±10.4; 348.3±11.1 and 350.4±13.7bpm, respectively versus 395.2±11.1bpm). The CVP did not suffer significant variations after treatment. CONCLUSION: Observe the 1.8 cineoleee reduces the gastric compliance in anaesthetized rats besides presenting effect hipotensor and bradicardic; probably for direct action on the gastrointestinal and vascular smooth muscel and moduling the autonomic nervous system.

OBJETIVO: Estudar o efeito do 1.8 cineol, componente do Cróton nepetaefolius (planta do Nordeste) comumente usada na medicina popular para distúrbios do trato gastrintestinal (TGI), sobre o comportamento motor do TGI de ratos Wistar anestesiados. MÉTODOS: Utilizamos 16 animais machos, pesando entre 300 a 350g. Os estudos de complacência gástrica foram conduzidos em animais sob jejum de 24h. As variações do volume gástrico (VG), foram medidas por pletismografia, enquanto a PA, FC e PVC foram monitoradas continuamente por um sistema digital de aquisição de dados. RESULTADOS: Observamos diminuição do VG, o qual foi significativo aos 30, 40, 50 e 60min após o tratamento com 1.8 cineol quando comparado ao perído basal (2,0±0,1; 1,9±0,1; 1,8±0,1 e 1,7±0,1mL, vs 2,1±0,2mL). A PA apresentou queda significativa após a administração de 1.8 cineol, mantendo-se assim durante os 60min de monitoração (87,9±7,7; 87,6±7,1; 87,9±6,4; 87,8±5,7; 86,0±5,5 e 87,7±6,0mmHg, respectivamente vs 94,4±6,2; mmHg), bem como a FC (366,3±13,4; 361,7±11,5; 357,3±10,4; 353,0±10,4; 348,3±11,1 e 350,4±13,7bpm respectivamente vs 395,2±11,1bpm). Já a PVC não sofreu variações significativas durante após o tratamento. CONCLUSÃO: O 1.8 cineol diminui a complacência gástrica em ratos anestesiados além de apresentar efeitos hipotensor e bradicárdico; provavelmente por ação direta sobre a musculatura lisa gastrintestinal e vascular e modulação do sistema nervoso autônomo.

Complicaçöes clínicas de injúrias medulares / Medical complications of spinal injuries

Lesöes medulares säo eventos catastróficos inesperados que acomentem anualmente milhares de indivíduos de todas as faixas etárias, determinando complicaçöes clínicas que persistiräo pelo restane de suas vidas. Com a melhoria da qualidade do atendimento , espera-se que em serviços especializados 94 por cento dos pacientes sobrevivam ao primeiro internamento hospitalar. O aumento da sobrevida, além da grande incidência de múltiplas complicaçöes (muitas delas restritas a tal grupo de pacientes, tais como hiperreflexia autonômica), aponta para a necessidade de uma maior divulgaçäo das peculiaridades fisiopatológicas a fim de possibilitar uma melhoria no manejo de tais pacientes. O objetivo do presente trabalho é revisar as complicaçöes clínicas imediatas e tardias das lesöes medulares