Adjustments of hepatic and small intestine blood flow on selective vasoconstrictor fibre stimulation

FASTH, S., HULTÉN, L. & NORDGREN, S.: Adjustments of hepatic and small intestinal blood flow on selective vasoconstrictor fibre stimulation. Acta Physiol Scand 1980, 110 :343–350. Received 16 Jan. 1980. ISSN 0001–6772. Department of Surgery II, Sahlgrenska sjukhuset, University of Goteborg, Sweden. The mutual changes in hepatic and small intestinal blood flow on selective nervous stimulation of the periarterial vasoconstriction fibres, were studied in anaesthetized cats. Occlusion of the hepatic artery did not change portal blood flow, whereas occlusion of superior mesenteric blood flow caused a significant increase in hepatic arterial flow. Stimulation of the hepatic sympathetic nervous supply caused a phasic blood flow response with a marked transient peak flow reduction of hepatic arterial blood flow. The magnitude of the peak response varied with the frequency of the stimulation. Despite continuous stimulation the first phase went over into a second phase of less pronounced vasoconstriction. This “steady state” blood flow, was maintained at about 20% below the control level, irrespective of stimulation frequency. Corresponding in time with the peak vasoconstriction there was a transient increase of portal pressure. Sympathetic nerve stimulation increased portal pressure even on occlusion of the hepatic artery. Stimulation of the mesenteric sympathetic nerves evoked the characteristic transient peak vasoconstrictor response consisting of two phases, a brief intense peak resistance response followed by a second phase of less pronounced but generally well maintained constriction. Simultaneously a slight reduction of portal pressure and hepatic arterial vascular resistance was regularly seen. In contrast to the observations in the hepatic arterial circuit the magnitude of this “steady state” blood flow in the small intestine was dependent on the rate of the stimulation, however. On simultaneous stimulation of the hepatic and mesenteric sympathetic nerves the hemodynamic responses were largely the same as when these nerves were stimulated separately. The portal pressure affecting mean capillary pressure in the intestine differed, however. Small and variable pressure changes were followed by rapid return towards control and during steady state it did not differ from the prestimulatory level. This investigation was supported by grants from the Swedish Medical Research Council (No. 17X-3117), from the Faculty of Medicine, University of Goteborg, The Swedish Society of Medical Sciences, from Goteborgs Likaresallskap and Assar Gabrielsson's Fund.     

Blood flow distribution, villous tissue osmolality and fluid and electrolyte transport in the cat small intestine during regional hypotension

The hemodynamic reactions of the parallel coupled vascular circuits in the cat small intestine were studied before, during and after a two-hour period of intestinal hypotension induced by lowering the intestinal arterial inflow pressure by partially occluding the superior mesenteric artery during a continuous stimulation of the postganglionic nerves to the small intestine. Furthermore, fluid and electrolyte transport and villous tissue osmolality were measured. A histological examination of biopsies taken during and after the hypotensive period was also carried out. The animals were divided into two groups (undamaged and damaged) according to the histological appearance of the intestinal mucosa. The hemodynamic reactions were investigated with a method that made it possible to study total intestinal, absorptive site ("villous"), nonabsorptive site ("crypt") and muscle layer blood flow. Total intestinal blood flow was lower in the damaged group than in the undamaged group during the arterial hypotension. However, absorptive site blood flow was similar in the two groups. Consequently, a significantly larger fraction of blood flow was distributed to the "villi" in the damaged group. Moreover, absorptive site red blood cell flow was only slightly reduced despite the development of mucosal ulcerations. These findings are discussed in relation to the pathophysiology of the mucosal lesions. Net fluid, net sodium and net chloride absorption was unchanged in the undamaged group whereas in the damaged group a marked decrease was observed after lowering the perfusion pressure. The decrease in net sodium absorption was due to a decrease in the lumen to tissue transport of sodium. Thus, the capacity of the small intestine to absorb fluid and electrolytes is unchanged even during a marked arterial hypotension with a pronounced decrease of intestinal blood flow as long as no mucosal damage has developed.     

The effect of vagal nerve stimulation on net fluid transport in the small intestine of the cat

The effect of electrical vagal nerve stimulation on intestinal net fluid transport rate was studied in the small intestine of the cat. The splanchnic nerves were severed in all experiments. Absorption was quantified with a new gravimetric technique which made it possible to study fluid transport also during intestinal motility. The stimulation characteristics were varied to activate selectively low threshold fibres or low and high threshold fibres. The observations did not reveal any affects of low threshold stimulation on intestinal fluid transport whereas an inhibition was seen when also the high threshold fibres were stimulated. This inhibitory vagal mechanism could also be elicited after the administration of atropine. Atropine in itself increased “resting” net fluid absorption. The results speak against a role for vagal cholinergic mechanisms in the control of net fluid absorption. There seem, however, to be tonically active intramural cholinergic pathways and noncho-linergic inhibitory vagal neurons of unknown physiological significance.     

Intramural blood flows and flow distribution in the feline small intestine during arterial hypotension

The vascular reactions of the parallel-coupled vascular sections of the small intestine were studied during hypotension at two different levels of intestinal arterial inflow pressure, using a 85Kr elimination technique. The regional hypotension was accomplished by partially occluding the superior mesenteric artery with a clamp and maintained for 2 h. At the higher level (50-55 mmHg) total intestinal blood flow decreased but not to the same relative extent as blood pressure due to the autoregulatory capacity of the intestinal vascular bed. The flow autoregulation was also reflected in a decreased blood flow resistance. The distribution of blood to the muscularis and mucosa-submucosa layer, respectively, did not change significantly during or after hypotension as compared to the prehypotensive level, since the relative flow decrease was the same in the mucosa-submucosa and in themuscularis. At the lower arterial pressure level (30-35 mmHg) a more marked decrease of intestinal blood flow and flow resistance was observed as compared to the experiments performed at the 50-55 mmHg pressure level. Moreover, muscularis blood flow was relatively more decreased than blood flow in the mucosa-submucosa implying the fraction of total blood flow diverted to the muscularis was significantly decreased. Despite this redistribution of blood flow, a histological damage was apparent only in the mucosa, particularly at the villous tips.     

Fatigue effects in the cat gastrocnemius during frequency-modulated efferent stimulation

Effects of low- and high-frequency fatigue were studied on muscle dynamics in isometric conditions of the cat gastrocnemius. Fatiguing sessions consisted of 25-28 repetitions of the standard tests that included an 18-s interval of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions. The rate of the continuous part was changed in accordance with a symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10s(-1); between these phases, each lasting for 4s, the rate changed linearly within a 2-s interval. The following modes of muscle activation were applied: (i) stimulation of single filaments constituting approximately one-fifth to one-seventh of the total cross-section of the L(7) and S(1) ventral roots; (ii) the distributed stimulation of five similar filaments; and (iii) direct stimulation of muscle through bipolar wire electrodes. A relative drop in tension, the fatigue index, expressed as the ratio at the end of a fatigue session over its value at the beginning of the test, was used to quantify fatigue effects. The fatigue indices during low-rate stimulation were 0.56+/-0.03 (mean+/-S.D.) at the first phase and 0. 64+/-0.02 at the third phase, while during high-rate stimulation this parameter was only 0.32+/-0.02. The high-rate stimulation noticeably increased the mean tension during low-rate stimulation; the ratio between the reactions at the third and the first phases could be as much as two to three times greater than that at the beginning of the fatigue session. It was demonstrated that the potentiation was connected with after-effects of the rate-tension hysteresis. The hysteresis decreased with fatigue, the fatigue index for the rate-tension loop areas ranging from 0.39 to 0.52 (0.45+/-0. 05, mean+/-S.D.). The fatigue processes developed more quickly and intensively in the previously fatigued muscles: the obtained fatigue indices were 0.73+/-0.05 and 0.70+/-0.10 at the first and third phases, and 0.62+/-0.06 (mean+/-S.D.) at the second phase of stimulation, respectively. In the cases of distributed and direct stimulation applied to muscles in a fresh state, fatigue dynamics did not differ significantly from those observed during single-filament stimulation. In experiments with distributed stimulation applied to previously fatigued muscles, a powerful depression of the high-rate components was registered in several cases, which seemed to be connected with depressive effects at the level of nerve-muscle synaptic transmission.The effects of low- and high-frequency fatigue were studied in isometric conditions of muscle contraction. In addition to the well-known differentiation between low- and high-frequency fatigue effects, the complex pattern of efferent stimulation used allowed us to identify additional fatigue-related changes in the rate-tension hysteresis. This hysteresis seems to be one of the possible mechanisms directed to compensate for low-frequency fatigue in the muscle contraction.     

The effects of cholera toxin on intramural blood flow distribution and capillary hydraulic conductivity in the cat small intestine

Blood flow distribution to the mucosa-submucosa and to the muscularis in the cat small intestine was investigated with a 85Kr elimination technique before and after exposing the intestinal mucosa for 30 min to cholera enterotoxin. In all experiments the toxin induced an intestinal secretion. Concomitantly, total intestinal blood flow was increased to a level 50 per cent above control 3 h after exposure. This vasodilatation reflected a doubling of mean blood flow in the mucosa--submucosa while muscularis blood flow remained unchanged. In another series of experiments the effect of cholera toxin on intestinal capillary hydraulic conductivity was investigated by determining the capillary filtration coefficient (CFC). A slight increase in CFC was noted during the 3 h observation period but this was not more pronounced than would have been expected from the concomitant vasodilatation. It is concluded that hemodynamic changes in the intestinal mucosa may be one of the several factors that probably are involved in the pathogenesis of cholera.     

核素显像评价电刺激对健康青年人小肠运动功能影响的试验研究

目的利用放射性核素显像研究十二指肠电刺激对人小肠通过时间的影响。方法12例健康青年志愿者,男女各6例,年龄21～25岁,中位年龄23岁。在胃镜引导下留置导管至十二指肠水平部,并安置电极,将99mTc-DTPA(二乙撑三胺五乙酸)和乳果糖混合液注入导管,用单光子发射式计算机断层仪(SPECT)进行连续小肠显像。择日对受试者进行电刺激,刺激条件:频率13Hz、波宽300ms、刺激强度5mA的方波,采用上述方法进行显像。使用感兴趣区分析法,生成小肠时间-放射性曲线,计算出小肠半排时间(T50),比较刺激前后小肠半排时间的变化。结果电刺激前后小肠平均半排时间分别为(49.5±15.8)min和(29.6±10.9)min,刺激前后T50变化有统计学意义(P<0.01)。结论放射性核素显像能很好地反映小肠运动变化,十二指肠电刺激能明显加快小肠运动。     

Malignant tumors of the small intestine: a histopathologic study of 41 cases among 1,312 consecutive specimens of small intestine

There are few comprehensive studies of small intestinal malignancies. The author retrospectively reviewed 1,312 archival pathologic specimens of the small intestine in the last 10 years in our pathologic laboratory in search for malignant tumors of the small intestine. There were 22 cases (1.7%) of primary adenocarcinoma, 3 cases (0.2%) of primary squamous cell carcinoma, 6 cases (0.5%) of metastatic carcinoma, 6 cases (0.5%) of malignant lymphoma, 3 cases (0.2%) of carcinoid tumor, and 1 case (0.08%) of gastrointestinal stromal tumor (GIST). Of the 25 cases of primary adenocarcinoma and squamous cell carcinoma, 24 cases were located in the duodenum and 1 case in the ileum. The 22 cases of adenocarcinoma were classified into 7 well differentiated, 7 moderately differentiated, and 8 poorly differentiated adenocarcinomas. All the three squamous cell carcinomas were moderately differentiated ones with keratinization and intercellular bridges. In the 25 cases of carcinoma, immunoreactive p53 protein was present in 23 cases, and the Ki-67 labeling ranged from 40% to 95% with a mean of 76%. In the 6 cases of metastatic adenocarcinoma, the origin was ovary in 1 case, pancreas in 2 cases, gall bladder in 1 case, lung in 1 case, and colon in 1 case. In the 6 cases of lymphoma, 4 cases were diffuse large B-cell lymphomas and 2 cases were peripheral T-cell lymphomas. In the 3 cases of carcinoid tumor, all were typical carcinoids and immunohistochemically positive for at least one of neuroendocrine markers (chromogranin, synaptophysin, neuron specific enolase, and CD56). In the 1 case of GIST, the cell type is spindle and GIST cells were immunohistochemically positive for KIT and CD34. The histological risk was intermediate. Forty-one cases of small intestinal malignancies were reviewed histopathologically.