Effects of hemorrhage on intramural blood flow distribution, villous tissue osmolality and fluid and electrolyte transport in the cat small intestine

The hemodynamic response in the parallel-coupled vascular sections of the cat small intestine were studied before, during and after a two hour period of hemorrhage (about 30 per cent of estimated blood volume). Fluid and electrolyte transport and villous tissue osmolality were also measured. Biopsies for histology were taken at the end of all experiments. The animals were divided in two groups, undamaged and damaged, according to the degree of mucosal damage observed. 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 flows. Total intestinal blood flow was lower in the damaged as compared to the undamaged group during hypovolemia. No difference in absorptive site blood flow was observed between the two groups during hypovolemia. Furthermore, no decrease of red blood cell flow in the "villi" was recorded in either group after hemorrhage. Consequently, mucosal lesions developed despite an unchanged oxygen transport capacity to the villi. The pathophysiology of the mucosal lesions is briefly discussed. Net fluid and sodium absorption was after hemorrhage increased in the undamaged group reflecting a decrease in the tissue to lumen transport of sodium. After retransfusion net fluid and sodium absorption returned to control. In the damaged group, however, net fluid and sodium absorption was decreased after hemorrhage. The increased rate of fluid and electrolyte transport observed in the undamaged small intestine after hemorrhage, is proposed to be an important mechanism for fluid replacement after hemorrhage.     

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.     

Effects of cholera toxin on villous tissue osmolality and fluid and electrolyte transport in the small intestine of the cat

The effects of cholera toxin on tissue osmolality and on net transport rates of water, sodium, chloride and potassium as well as on unidirectional fluxes of water and sodium were studied in vivo. In all experiments the toxin caused a net secretion of water, sodium, chloride and potassium. The unidirectional sodium transport from tissue to lumen was increased while the flux in the opposite direction was reduced 180 min after cholera toxin instillation. Cholera toxin produced only a small reduction in the villous tissue hyperosmolality, created by the intestinal countercurrent exchanger. This reduction was far too small to explain the observed net secretion of fluid and solutes induced by the cholera toxin. Other mechanisms underlying the cholera secretion are discussed.     

Blood flow distribution, lymph flow, villus tissue osmolality and fluid and electrolyte transport after exposing the cat small intestine to sodium deoxycholate

The effect of luminal perfusion of a dihydroxy bile salt (sodium deoxycholate) on net fluid transport, intestinal haemodynamics, lymph flow, electrolyte transport and villus tissue osmolality was studied in cat jejunum. Furthermore, the effects of hexamethonium and tetrodotoxin, two drugs influencing nervous activity, were investigated. Concomitant to net fluid secretion, the bile salt increased mucosal blood flow whereas capillary filtration coefficient and lymph flow remained unchanged. Net sodium and chloride transport changed from absorption to secretion. The change of sodium transport was due to both an increased flux from tissue to lumen and a reduced flux in the opposite direction. Villus tissue hyperosmolality was reduced. None of the effects on intestinal haemodynamics correlated with the change in net fluid transport. Furthermore, hexamethonium and tetrodotoxin inhibited the secretion of fluid and electrolytes without influencing the induced changes in intestinal haemodynamics. It is concluded that the bile salt induces intestinal fluid secretion by stimulating an active secretory process in the crypts via enteric nerves. A minor part of the total change in net fluid transport may be due to a reduced uptake in the villi.     

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.     

Villous tissue osmolality,water and electrolyte transport in the cat small intestine at varying luminal osmolalities

Villous tissue osmolality and net transport for water, sodium, potassium and chloride were determined in the feline small intestine when exposing the mucosa to solutions with different mannitol concentrations (0, 100, 315 and 600 mmol/l). Tissue osmolality at the villous tip varied with luminal osmolality. At the villous base, on the other hand, tissue osmolality remained around the plasma osmolality regardless of the osniolality of the luminal fluid. Transport rates for water were affected in the way predicted from the lumen to tissue osmolality difference. A net flux from tissue to lumen was always recorded for the studied electrolytes. The hydraulic conductivity (L_p) of the intestinal epithelium with dilated intercellular spaces was estimated from the present results to be around 30times10–¹² cm xs^-1xPa^-1. When the intercellular spaces were collapsed L_p was estimated to be 15times10–¹² cmxs^-1xPa^-l.     

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.     

The effect of splanchnic nerve stimulation and neuropeptide Y on cholera secretion and release of vasoactive intestinal polypeptide in the feline small intestine

The effect of sympathetic nerve stimulation and intra-arterial infusion of neuropeptide Y (NPY) on net fluid secretion and release of vasoactive intestinal polypeptide (VIP) was studied in the cat small intestine during a secretion due to cholera toxin. Activation of the splanchnic nerves (4 Hz, 5 ms, 5 V) decreased net fluid secretion to 57 +/- 10% of control. Concomitantly, the release of VIP was reduced to less than 50%. Furthermore, close i.a. infusion of NPY (estimated increase in plasma concentration 75 nmol l-1) reduced the net fluid secretion and VIP release to 27 +/- 5 and 28 +/- 4% of the pre-stimulatory value. The correlation between the decrease in net fluid secretion and reduction in VIP release showed a strong positive correlation (r = 0.83). These results strongly indicate that the antisecretory effect of sympathetic nerve stimulation during cholera diarrhoea is mediated by inhibition of secretory VIP neurons in the intestinal mucosa. A similar mechanism is also proposed for the intravascularly administered NPY.     

Antisecretory effect of splanchnic nerve stimulation on choleratoxin-induced secretion in the cat, an effect mediated at the crypts

The experiments were performed on cats anaesthetized with alpha-chloralose. Segments of the small intestine were perfused with sodium-free hypotonic choline-mannitol solution and intestinal net fluid transport was recorded with a volumetric technique. The content of sodium and chloride in the lamina propria of the small intestinal villus was measured with an electron microprobe in freeze-dried paraffin embedded tissue. In absorbing control intestine, there was an even distribution of electrolytes along the villi. Sympathetic nerve stimulation (5 Hz, 5 ms, 5 V) did not significantly affect electrolyte distribution and net fluid transport. Intestinal secretion was elicited by pretreatment of the intestine with cholera toxin. The concentration of sodium and chloride was elevated in the apical third of the villi in intestines during the secretion since secreted sodium from the crypts was reabsorbed into the villi. Sympathetic nerve stimulation decreased the cholera secretion significantly in intestines pretreated with cholera-toxin. Furthermore, the apical gradients of sodium and chloride in the villi, caused by the reabsorbed sodium and chloride, disappeared during sympathetic nerve stimulation. It is concluded that, in the used experimental model, the antisecretory effect of sympathetic nerve stimulation was caused by inhibition of crypt secretion and not by augmented villus absorption.     

The importance of nervous and humoral factors in the control of vascular resistance, blood flow distribution and net fluid absorption in the cat small intestine during hemorrhage

The influence of preganglionic (splanchnic) and postganglionic (periarterial) denervation of the cat small intestine on the changes in blood flow and net fluid absorption elicited by hemorrhage was investigated. The compiled data from a previous report indicate that hemorrhage induces a vasoconstriction and a redistribution of blood flow towards the absorptive part of the mucosa. The vasoconstriction was unaffected by a total postganglionic denervation whereas after a preganglionic denervation both the vasoconstriction and the redistribution of blood flow were abolished. We have also shown earlier that hemorrhage induced an increase in net fluid absorption as long as no ischemic mucosal lesions developed. This increase was reduced by postganglionic denervation, and was reversed into a small decrease after preganglionic denervation. On the basis of these findings it is proposed that the increase in vascular resistance, the redistribution of blood flow towards the absorptive part of the mucosa as well as the increase in net fluid absorption observed after hemorrhage all are effects mainly mediated via the splanchnic nerves. Furthermore, humoral factors are of major importance for the increase in vascular resistance observed after hemorrhage. The increase in net fluid absorption was shown to be induced both by direct nervous and by humoral factors.     

Intramural blood flow distribution in the small intestine of the cat studied by carbon monoxide uptake and 85krypton elimination

Carbon monoxide (CO) uptake from the feline small intestine was measured to investigate if it could be used to determine blood flow in the superficial parts of the intestinal mucosa. Several observations were made that substantiated this proposal: 1) Lowering P_CO in the intestinal lumen from 100 to 70 kPa did not influence the rate of CO absorption during “resting” blood flow conditions, while the same reduction of lumen P_CO resulted in a decreased rate of CO uptake during isoprenaline induced vasodilatation. These observations suggest that CO uptake was flow limited during “rest” and diffusion limited during vasodilation. 2) Lowering perfusion pressure or totally occluding the intestinal vascular supply markedly reduced the rate of CO uptake. 3) The diffusion distance for CO into the tissue was calculated to be 75–225 μm, i. e. CO mainly diffused into the villous tissue. 4) The flow values calculated from the CO measurements were of the same order of magnitude as earlier reported with other techniques (microspheres, indicator dilution method). It was concluded that CO absorption mainly reflected villous blood flow during “resting” and low intestinal blood flow. Total blood flow (venous drop recorder) and muscle layer blood flow (⁸⁵Kr elimination) were measured simultaneously to CO uptake. From these determinations “resting” blood flow distribution in the small intestine was calculated.     

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.     

Effect of renal nerve stimulation, renal blood flow and adrenergic blockade on plasma renin activity in the cat

1. The effect of electrical stimulation of the distal cut ends of the renal nerves of unilaterally nephrectomized, anaesthetized cats was studied. Using stimulation parameters of 15 pulses per second (pps), 15 V and 0.2 msec duration, there was an immediate sharp drop in renal blood flow, as determined by an electromagnetic flowmeter, which was maintained for about 2 min. Flow gradually returned to control values over approximately the next 10 min in spite of continued stimulation for up to 30 min.2. Plasma renin activity (PRA) increased markedly after 10 min of stimulation but 20 min later fell towards pre-stimulation values whether stimulation was maintained or not.3. Phentolamine, an alpha-adrenergic-receptor antagonist, abolished both the blood flow and PRA responses to a 10 min period of renal nerve stimulation.4. When the renal artery was constricted in order to produce blood flow changes similar to those found with renal nerve stimulation, the rise in PRA was similar to that observed with renal stimulation.5. In phentolamine-blocked animals, renal artery constriction, as described, produced the same effect on PRA as was observed with renal nerve stimulation.6. Propranolol, a beta-adrenergic-receptor antagonist, did not block the blood flow response to renal nerve stimulation, but did block the rise in PRA normally associated with renal nerve stimulation.7. It is suggested that the effect of renal nerve stimulation on PRA is mediated, primarily, by changes in renal blood flow and that one of the steps leading to renin release following stimulation is sensitive to propranolol. This step must be distal to the effect on vascular smooth muscle.     

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.     

Effects of vasoactive intestinal polypeptide on blood flow,motility and fluid transport in the gastrointestinal tract of the cat

The effect of close intraarterial infusions of vasoactive intestinal polypeptide (VIP) on gastric motility, intestinal fluid transport and colonic motility were studied in the cat. Regional blood flow was also followed in all experiments. In the stomach VIP produced a gastric relaxation and a blood flow increase. The motility response was similar to that observed when eliciting the vago-vagal reflex relaxation by distending the esophagus. In the small intestine a hyperemia and a decrease of net water uptake was observed. When infusing small amounts of VIP a decrease of net water uptake was seen without any change of intestinal blood flow. Large amounts of VIP produced a transient secretory state in the small intestine. In the colon a hyperemia was seen immediately upon starting the infusion of the drug. After 2–3 min of infusion a contraction of the colon was apparent. The administration of atropine to the animal did not significantly affect any of the responses produced by VIP. The results are discussed in relation to VIP as a possible neurotransmitter in the gastrointestinal tract.