Intestinal Vascular Resistance Research Articles

Интенсивность мезентериального кровотока и степень зрелости кишечника у новорожденных группы риска по развитию некротизирующего энтероколита

Актуальность. В последние годы распространяется использование ультразвукового исследования брюшной полости для диагностики некротизирующего энтероколита (НЭК) у новорожденных. На начальных стадиях заболевания толщина стенки кишки, эхогенность и перфузия увеличиваются вследствие воспаления кишечника и отека слизистой оболочки. При прогрессировании НЭК утончение стенки кишечника, отсутствие перфузии и перистальтики превалируют и предупреждают о возможности перфорации кишечника. Это является доказательством диагностического преимущества УЗИ в отношении оценки прогрессирования НЭК. В статье представлены некоторые результаты собственного опыта использования УЗИ брюшной полости для диагностики НЭК у преждевременно рожденных детей. Цель: оценить степень зрелости кишечника и связь между допплеровскими индексами кишечной перфузии и сосудистым сопротивлением в бассейне верхней брыжеечной артерии у недоношенных новорожденных на 1–5-е сутки жизни с риском развития НЭК. Материалы и методы. В статье проведено обследование случайно выбранных 34 недоношенных детей с малой и очень малой массой тела и со сроком гестации 28–36 недель от матерей с отягощенным течением беременности. Оценивались: максимальная систолическая скорость, конечная диастолическая скорость и средняя скорость кровотока при ≥ 5 последовательных циклах сердечных сокращений. На основании этих показателей был рассчитан пульсовой индекс. Результаты. После проведенного исследования на 1–5-е сутки жизни ретроспективно новорожденные были распределены по группам в зависимости от клинических диагнозов в конце раннего неонатального периода. Новорожденные группы риска, родившиеся в асфиксии тяжелой степени, с высокими показателями сосудистого сопротивления в верхней брыжеечной артерии на 1–5-е сутки жизни, а также при толщине стенки кишки менее 1,6 мм имеют повышенный риск развития НЭК. Выводы. Выявленные высокие показатели сосудистого сопротивления в верхней брыжеечной артерии на 1–5-е сутки жизни у недоношенных детей с очень низкой массой тела и высоким риском развития НЭК помогут принимать правильные клинические решения по тактике ведения и лечения, в том числе о начале энтерального питания и расширении его объема.

Role of NO and other vascular mediators in the etiopathogenesis of necrotizing enterocolitis

The etio-pathogenesis of necrotizing enterocolitis (NEC) is complex and multifactorial. Decades of research have not identified a definite etiology. Prematurity, enteral feeding, intestinal hypoxia/ischemia, inflammation and an abnormal microbiome are potential risk factors for developing this multisystem illness. Lack of specific diagnostic and prognostic markers adds to the challenges faced in managing NEC. Vascular mediators such as Nitric oxide (NO), catecholamines and endothelin (ET) regulate neonatal intestinal vascular resistance and may influence the pathophysiology of NEC. Neonatal morbidities, medications, transfusions, an altered microbiome and breast milk feeds may influence the vasculature in various ways. Better understanding of these mediators and their role in regulation of intestinal microcirculation and pathogenesis of NEC will assist in identifying strategies in prevention and management of this devastating illness.

Serotonin-induced Hypotension is Mediated by a Decrease in Intestinal Vascular Resistance

Serotonin-induced Hypotension is Mediated by a Decrease in Intestinal Vascular Resistance

Developmental expression of eNOS in postnatal swine mesenteric artery.

Developmental changes in the expression of endothelial nitric oxide synthase (eNOS) within the mesenteric artery of swine were studied in fetal (110 days postconception/117 days total gestation) and on postnatal days 1, 3, 10, and 30. Subjects in the 1-day-old group were subdivided into fed and nonfed. Transcription of eNOS was determined by real-time PCR, protein expression was evaluated by Western blotting, and hemodynamic and oxygenation parameters were measured within in situ gut loops before and after the administration of N(G)-monomethyl-L-arginine (L-NMMA). The abundance of eNOS mRNA remained steady throughout all ages. In contrast, expression of eNOS protein was twofold greater in the 1-day-old fed subjects compared with fetal or 1-day-old nonfed subjects. eNOS protein expression remained elevated on day 3, increased on day 10, and then declined to a level similar to the day 1 nonfed group by postnatal day 30. Intestinal vascular resistance was 31% lower in the day 1 fed group when compared to the day 1 nonfed group; resistance continued to decline through day 10 but then significantly increased on day 30. We conclude that the expression of eNOS changes within the mesenteric artery during early postnatal development at a posttranscriptional level.

Use of an extracorporeal circuit to evaluate effects of intraluminal distention and decompression on the equine jejunum

To use an extracorporeal circuit to evaluate effects of intraluminal distention on the jejunum of healthy horses. 2 jejunal segments from each of 5 horses. Jejunal segments were harvested and maintained in an extracorporeal circuit. One segment was subjected to distention (intraluminal pressure, 25 cm H2O) followed by decompression, and 1 segment was maintained without distention. The influence of distention-decompression on vascular resistance was calculated. Mucosal permeability was evaluated by measuring the clearance of albumin from blood to lumen. After distention and decompression, tissue specimens were collected for histomorphologic evaluation. In addition, the contractile response of the circular smooth muscle layer was determined following incubation with 3 prokinetic agents. Intestinal vascular resistance increased during intraluminal distention and returned to baseline values after decompression. Albumin clearance rate increased after distention, compared with baseline and control values. Histologic examination of the distended segments revealed grade-1 and -2 lesions of the mucosal villus. Edema and hemorrhage were evident in the submucosa and muscular layers. Mesothelial cell loss, edema, and hemorrhage were also evident in the serosa. Mucosal surface area and villus tip height decreased and submucosal volume increased in the distended tissue. Compared with responses in control specimens, distention decreased the contractile response induced by cisapride, erythromycin, and metoclopramide. Intraluminal distention of the jejunum followed by decompression increased mucosal permeability and injury and decreased responses to prokinetic agents. Horses with intraluminal intestinal distention may have a decreased response to prokinetic agents.

Beneficial effects of low-dose prostacyclin on cat intestinal perfusion during endotoxemia as evaluated with microdialysis and oxygen transport variables.

To evaluate the effects of low-dose prostacyclin on intestinal perfusion during endotoxemia. A randomized, blinded experimental study. A university laboratory. Sixteen anesthetized cats. The animals received endotoxin by continuous intravenous infusion (0.5 mg/kg plus 0.5 mg x kg(-1) x hr(-1)) and a continuous volume replacement throughout the experiment. Four hours after the start of endotoxin, the animals were randomized to receive an infusion of either prostacyclin at a dose of 1 ng x kg(-1) x min(-1) (prostacyclin group) or vehicle (control group) during the next 4 hrs. Intestinal vascular resistance was calculated from systemic arterial pressure, central venous pressure, and superior mesenteric artery blood flow, and intestinal oxygen delivery and uptake were calculated from superior mesenteric artery and vein blood samples and blood flow. Interstitial lactate, pyruvate, glucose, and glycerol in the ileal wall were measured by using microdialysis. There were no differences in baseline values between the groups. Systemic blood pressure decreased initially but recovered and remained stable in both groups. In the control group, intestinal vascular resistance increased from 10.9 +/- 1.0 to 24.7 +/- 5.3 mm Hg x mL x min(-1) x kg(-1) (p <.05) at 8 hrs, and oxygen delivery decreased from 2.6 +/- 0.2 to 1.3 +/- 0.3 mL x min(-1) x kg(-1) (p <.05). Simultaneously, microdialysis lactate increased from 1.6 +/- 0.1 to 3.6 +/- 0.5 mmol/L (p <.05) with concomitant pyruvate increase and unchanged lactate/pyruvate ratio. Blood lactate increased and pH decreased. In the prostacyclin group at 8 hrs, intestinal vascular resistance of 6.9 +/- 0.8 mm Hg x mL x min(-1) x kg(-1) was lower and intestinal oxygen delivery of 3.2 +/- 0.3 was higher (p <.05) than in the control group at 8 hrs. Intestinal oxygen uptake of 0.54 +/- 0.10 mL x min(-1) x kg(-1) was higher than in the control group, in which oxygen uptake was 0.26 +/- 0.04 mL x min(-1) x kg(-1). Lactate, pyruvate, and pH were normalized at 8 hrs in the prostacyclin group. Low-dose prostacyclin has beneficial effects on small intestinal perfusion during endotoxemia in this experimental cat model.

Cerebral and intestinal perfusion and metabolism in normocythemic hyperviscous hypoxic newborn pigs.

We studied the effects of hypoxia on cerebral cortical and intestinal perfusion and metabolism in normocythemic hyperviscous newborn pigs. Seven pigs were made hyperviscous by an injection of cryoprecipitate, increasing viscosity from 5.8 +/- 0.9 to 9.0 +/- 1. 2 (SD) cycles/s. Six normoviscous pigs received 0.9% NaCl. Reducing the inspired O(2) decreased the arterial O(2) content (Ca(O(2))) from 9.5 +/- 1.6 to 3.6 +/- 1.3 ml O(2)/100 ml. Increases in brain and decreases in gastrointestinal blood flow at the lower Ca(O(2)) values were similar between the groups. During hypoxia, blood flow to stomach, distal intestinal mucosa, and large intestines was lower (-50, -23, and -28%, respectively) in the hyperviscous than normoviscous group. At the lower Ca(O(2)) values, cerebral cortical vascular resistance decreased in both groups and intestinal vascular resistance increased (+257%) in the hyperviscous but not in the normoviscous group. During hypoxia, systemic oxygen delivery decreased, extraction increased, and uptake did not change; cerebral cortical O(2) delivery, extraction, and uptake did not change; and intestinal O(2) delivery decreased, extraction increased, and uptake did not change in both groups. Our study demonstrated that 1) during hypoxia, increases in systemic O(2) extraction compensated for decreases in delivery and systemic uptake did not change; vasodilation sustained cerebral cortical O(2) delivery and preserved metabolism; increases in intestinal oxygen extraction offset decreases in delivery and uptake was preserved; and 2) nonpolycythemic hyperviscosity did not have a major influence on cardiovascular or metabolic responses to hypoxia, except for modest effects on intestinal resistance and perfusion to certain gastrointestinal regions. We conclude that, under normocythemic conditions, a moderate increase in viscosity does not have a major impact on hemodynamic or metabolic adjustments to hypoxia in newborn pigs.

Postnatal changes in gut hemodynamics: a possible role for substance P.

Studies were conducted in young postnatal swine to determine if substance P (SP) participates in the regulation of postnatal intestinal hemodynamics and oxygenation. SP was present in homogenates of whole intestine from postnatal swine in an age-dependent manner as follows: 1 day old and never fed, 126 +/- 35; 3 days old and fasted, 148 +/- 30; and 14 days old, 51 +/- 10 pg/mg protein (P < 0.01, 14- vs. 1- or 3-day-olds). Phenylephrine-precontracted rings of mesenteric artery from 3-day-old subjects mounted for tension recording within buffer-filled myographs demonstrated brisk relaxation in response to SP (EC50, 2 x 10(-10) M). This relaxation was eliminated by mechanical removal of the endothelium or blockade with the L-arginine analog NG-monomethyl-L-arginine (L-NMMA) and was significantly attenuated by pretreatment with N-acyl-L-Trp-3,5-bis-(trifluoromethyl) benzyl ester (NATB), a highly selective NK-1 receptor antagonist (pA2 5 x 10(-10) M). Infusion of exogenous SP into the mesenteric artery of innervated in vivo gut loops reduced intestinal vascular resistance 35% and increased tissue oxygen uptake 40% in both 3- and 14-day-old subjects. By contrast, blockade of the NK-1 receptor for SP with NATB increased intestinal vascular resistance 19% in 3-day-old subjects but only 5% in 14-day-old subjects (P < 0.01). SP-induced changes in gut vascular resistance were significantly attenuated by prior coinfusion of NATB or L-NMMA, indicating that the peptide exerted this vascular effect via theNK-1 receptor, which is linked to endothelial cell nitric oxide synthase. Both NATB and L-NMMA attenuated flow-induced dilation within pump-perfused in vitro gut loops from 3-day-old subjects. SP appears to participate in the regulation of the newborn intestinal circulation, especially during the first days after birth.

Intestinal blood flow is controlled by both feed arteries and microcirculatory resistance vessels in freely moving rats.

1. In freely moving rats, intestinal blood flow, aortic blood pressure and blood pressure at the base of mesenteric arcades were measured simultaneously so as to determine the role of feed arteries and of the microcirculation in the control of intestinal vascular resistance. Segmental resistances of feed arteries (Rfeed) and of microcirculatory vessels (Rmicro) were calculated. 2. At rest, Rfeed and Rmicro were 32 and 68%, respectively, of the total intestinal vascular resistance. 3. Injection of noradrenaline (2 micrograms i.v,) increased Rfeed by 151% and Rmicro by 243%. Angiotensin II (400 ng i.v.) did not increase Rfeed significantly, but increased Rmicro by 239%. Conversely, serotonin (15 micrograms i.v.) increased Rfeed by 414% but did not affect Rmicro significantly. 4. Spontaneous physical activity increased Rfeed by 29% and Rmicro by 39%, while sudden environmental stress increased Rfeed by 116% and Rmicro by 129%. Infused noradrenaline (1 microgram min-1 i.v.) or adrenaline (0.8 microgram min-1 i.v.) reduced intestinal flow by 21 and 16% respectively, while noradrenaline, but not adrenaline, increased intestinal resistances. 5. alpha 1-Blockade with prazosin (0.1 mg i.v.) reduced Rfeed and Rmicro by 43 and 16%, respectively. Thereafter, environmental stress decreased Rfeed by 24% while Rmicro was unaffected. Intravenous noradrenaline and adrenaline responses were attenuated. 6. We conclude that in freely moving rats, mesenteric feed arteries, as well as microcirculatory vessels, are true resistance vessels, and that both participate in the control of intestinal blood flow.

The Effects of Systemic Hypotension on Postnatal Intestinal Hemodynamics and Oxygenation

This study investigated the effect of acute systemic hypotension, induced by pericardial tamponade, on intestinal hemodynamics and oxygenation in 3- and 35-d-old swine. To delineate intrinsic versus systemic responses, the effects of tamponade were compared with those noted after isolated pressure reduction to an innervated in vivo gut loop, achieved by local arterial constriction. Younger subjects demonstrated 16 and 58% increases in vascular resistance during constriction and tamponade, respectively, whereas older subjects exhibited an increase in resistance (27%) only during tamponade. Intestinal oxygen uptake decreased approximately 30% during both constriction and tamponade in the younger group, despite the greater effect of tamponade on gut perfusion. Older subjects exhibited no change in gut oxygenation during either perturbation. In a separate series of experiments, vasopressin, phenylephrine, and angiotensin II, each an element of the systemic pressor response, were infused into in vitro gut loops from 3- and 35-d-old swine. Vasopressin caused sustained vasoconstriction in both age groups; however, phenylephrine and angiotensin II caused greater sustained increases in intestinal vascular resistance in 3- than in 35-d-old intestine. We conclude that systemic hypotension compromises intestinal perfusion to a greater extent in younger subjects, although this effect is not associated with overwhelming tissue hypoxia. The pronounced rise in gut vascular resistance in 3-d-old intestine may reflect the additive effects of intrinsic and systemic vasoactive forces engaged during acute systemic hypotension.

Cholinergic Agents Modulate Transport in the Isolated, Perfused Ileum

The mammalian small intestine is extensively innervated by cholinergic nerve fibers, including projections to the muscular and submucosal layers. This study tested the hypothesis that cholinergic agents modulate ileal transport independent of alterations in intestinal vascular resistance and motility. Ten-centimeter segments of rabbit ileum ( n = 32) were vascularly perfused ex vivo with a physiologic electrolyte solution containing red cells. The lumen was perfused with an electrolyte solution containing [ 14C]polyethylene glycol. Net fluxes of water, sodium, and chloride were calculated during three 20-min periods: basal, drug infusion, and recovery. Agents infused at a final arterial concentration of 10 -5 mole/liter included acetylcholine, atropine, and hexamethonium. Measured perfusion pressure reflected changes in vascular resistance. Recovery calculations controlled for motility effects. Acetylcholine caused significant secretion of water, sodium, and chloride ( P < 0.05). The infusion of atropine or hexamethonium alone had no effect. Atropine but not hexamethonium prevented the prosecretory effect of acetylcholine. There were no significant changes in perfusion pressure or 14C recovery for any infused agent. Acetylcholine-induced ileal secretion is (1) mediated via atropine-sensitive muscarinic cholinergic receptors, (2) independent of extraintestinal neural pathways, and (3) independent of changes in vascular resistance or motility. These data support the hypothesis that acetylcholine influences ileal transport directly, independent of alterations in vascular resistance and motility.

Vasodilator effects of desflurane and isoflurane in the feline small intestine

The influence of desflurane (DES) and isoflurane (ISO) on the intestinal vasculature was investigated in normoventilated cats (n = 10) during basal chloralose anesthesia (control). We measured heart rate, mean arterial pressure (MAP), and intestinal blood flow (optical drop flowmetry). Intestinal vascular resistance (IVR) was derived. To avoid changes in local vascular tone related to alterations in transmural pressure gradients, intestinal arterial pressure was controlled and kept constant by a variable aortic clamp. Measurements were performed during control and during the administration of DES (3.5% and 7.0% end-tidal) or ISO (0.8% and 1.6% end-tidal). Each animal was exposed to both agents, prior to and after intestinal postganglionic denervation. In the innervated intestine, both DES and ISO dose-dependently decreased IVR. At the high dose, DES (50 +/- 10% decrease in IVR) was a significantly more powerful vasodilator than ISO (37 +/- 12% decrease in IVR). In the denervated intestine, less pronounced vasodilations were produced by both DES and ISO, as compared to the innervated state, and there were, in this situation, no significant differences between agents concerning the magnitude of the vasodilation. As indicated by comparisons between the innervated versus the denervated state, both neurogenic and non-neurogenic mechanisms contributed to the vasodilator responses. The vascular relaxation at the high dose was for ISO associated with a significantly more powerful non-neurogenic vasodilation, and for DES associated with a significantly more powerful neurogenic vasodilation. This suggests that withdrawal of sympathetic neurogenic vasoconstrictor tone is more important for the vasodilation produced by DES than it is for ISO.

Development of Circulatory and Metabolic Shock Following Transient Portal Triad Occlusion

Liver ischemia is purposefully induced by portal triad occlusion (PTO) in several clinical situations including liver surgery for trauma, tumor, and transplantation. Despite significant morbidity from PTO, the hemodynamic and metabolic effects of PTO have not been evaluated relative to duration of ischemia. We investigated this using a total hepatic ischemia model. Rats received isoflurane anesthesia, carotid artery and jugular vein cannulation, and serial measurements of cardiac output (CO), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), stroke volume (SV), systemic vascular resistance (SVR), superior mesenteric artery blood flow (SMAF), intestinal vascular resistance (IVR), pH, pCO2, pO2, lactate, glucose, hematocrit (HCT), white blood cell count (WBC), and total neutrophils. Each group received 0, 15, 30, 45, or 60 min of PTO followed by 2 hr of reperfusion. All sham ischemia animals remained hemodynamically stable throughout the study. However, in the ischemic groups, there were significant time-dependent decreases in MAP, HR, CO, CVP, SV, SMAF, and pH, and increases in SVR, IVR, HCT, and lactate, while pCO2, pO2, glucose, and WBC remained stable. All of the ischemic animals survived except those that received 60 min of PTO. In this group, all of the animals survived the ischemic period; however, only one animal survived beyond 60 min of reperfusion. These data demonstrate a time-dependent circulatory and metabolic shock following PTO heralded by intestinal venous pooling and loss of intravascular fluid, and culminating in death. Careful hemodynamic monitoring and restoration of blood volume in the trauma patient may reduce morbidity and mortality.

Prolonged Use of Cyclosporine (CsA) Produces Reversible Hemodynamic and Absorptive Alterations in the Transplanted Rat Small Intestine

Cyclosporine (CsA)-induced alterations in organ blood flow (BF) and function have been studied in kidney and pancreatic transplants. In this study, we assessed the effect of prolonged CsA administration on graft tissue BF and absorption from transplanted rat small intestine (SI). Isogeneic SI transplantation was performed in Lewis rats. Animals were grouped based upon the following treatment schedules: no treatment for 1 week in group 1; 0.15 ml/kg/day im olive oil for 1 week in group 2; 0.15 ml/kg/day olive oil for 1 week and then 0.1 ml/kg/day for 5 weeks in group 3; 15 mg/kg/day im CsA for 1 week in group 4; and 15 mg/kg/day CsA for 1 week and then 10 mg/kg/day for 5 weeks in group 5. Group 6 was the same as group 5 but CsA was withdrawn for 1 week prior to assessment. Maltose absorption was measured to evaluate graft absorptive function. BF and its intramural distribution to mucosal and serosal/muscularis layers were determined using the radioactive microsphere technique. Perfusion pressure was measured to calculate vascular resistance (VR). One week of CsA of administration in group 4 resulted in a significant increase in mucosal VR (68.4 ± 15.5 versus 46.9 ± 8.7 U/g, P < 0.01) and significant decreases in mucosal BF (1.21 ± 0.25 versus 1.80 ± 0.38 ml/g/min, P < 0.01) and maltose absorption 30 min after loading (168.9 ± 21.1 versus 214.4 ± 28.4 glucose mg/dl, P < 0.01). Prolonged CsA treatment up to 6 weeks in group 5 resulted in further increases in whole intestinal VR (88.6 ± 19.1 versus 70.1 ± 12.4 U/g, P < 0.05) and decreases in whole intestinal BF (0.93 ± 0.18 versus 1.16 ± 0.18 ml/g/min, P < 0.05) and maltose absorption 39 min after loading (137.4 ± 21.3 versus 168.9 ± 21.1 glucose mg/dl) when compared with 1 week of CsA treatment in group 4. Withdrawal of CsA for 1 week after prolonged CsA treatment in group 6 resulted in restorations of VR in both mucosal and serosal/muscularis layers, BF in serosal/muscularis layer, and absorptive function to the normal ranges as shown in group 3 (P = NS). We concluded that CsA administration causes hemodynamic alterations in the intestinal vascular system and dose-dependent functional impairment which are reversible when CsA is discontinued.

Adrenergic and pressure-dependent vascular regulation in sedentary and trained rats

In this study, we determined if aerobic exercise training alters adrenergic or pressure-dependent vascular regulation in the rat hindlimb or intestine. Pressor responses to bilateral carotid artery occlusion and systemic phenylephrine (PE) infusion were not altered by training. During occlusion, peak and steady-state changes in hindlimb vascular resistance (HLR) were significantly greater in trained (24 and 13%) than in sedentary (8 and -3%) rats; a similar trend existed for intestinal vascular resistance (IR). The pressure-dependent contribution was consistent between groups (HLR: peak 55-85%, steady state 25-45%; IR: peak and steady state 40-65%). During PE infusion, increases in IR and HLR were similar between groups. The increase in HLR was substantially pressure dependent in both groups (approximately 50% at highest dose) as was the change in IR in trained rats. However, the IR response to PE was not pressure dependent in sedentary rats. The direct effects of PE were similar between sedentary and trained rats in the hindlimb but were suppressed in the intestine of trained rats compared with sedentary rats. Therefore, aerobic exercise training altered adrenergic and pressure-dependent vasoregulatory mechanisms in both skeletal muscle and intestinal tissues.

Effect of sustained mesenteric nerve stimulation on intestinal oxygenation in developing swine

The effects of sustained mesenteric nerve stimulation on intestinal oxygenation were determined in 3- and 35-day-old swine. Studies were conducted in pentobarbital-anesthetized animals during free-flow or constant-flow perfusion. Square-wave stimuli sufficient to induce maximal resistance vessel constriction were applied to postganglionic periarterial mesenteric nerves and each stimulation was sustained until measured variables reached steady state. When vascular resistance data were analyzed without data transformation, autoregulatory escape of intestinal vascular resistance was more complete in 3- than in 35-day-old animals when the escape process was complete; however, expression of these data as escape indexes revealed a similar degree of escape in both age groups. In 35-day-old animals, (a-v)O2 increased during sustained nerve stimulation under free-flow conditions; under constant-flow conditions, (a-v)O2, 86Rb extraction, and capillary permeability-surface area product were lower at completion of the escape process compared with baseline. In 3-day-old swine, these variables remained unchanged from baseline. Intestinal O2 uptake was compromised by sustained nerve stimulation, and this effect was similar in both age groups. We conclude that sustained nerve stimulation reduces intestinal oxygenation to a similar degree in 3- and 35-day-old swine. It is important to note, however, that the response of 3-day-old swine may be dissimilar from that which occurs during immediate postnatal life; indeed, the intestinal hemodynamic response of swine less than or equal to 1 day old should not be extrapolated from the response of 3-day-old animals.

Baroreflex control of jejunal blood flow and fluid transport in cats; effects of yohimbine, an alpha 2-adrenergic antagonist.

The aim of the study was to test the hypothesis that baroreceptor unloading increases jejunal fluid absorption rate via an alpha 2-adrenergic effect on electrogenic active transport. In 13 chloralose-anaesthetized cats, the carotid sinus baroreceptors were isolated and perfused with arterial blood, and we studied the effects of a graded decrease in carotid sinus pressure on intestinal vascular resistance, net fluid absorption rate and the potential difference between the intestinal lumen and the peritoneal cavity (PD). Experiments were performed in seven control animals and in six animals pretreated with yohimbine, an alpha 2-adrenergic antagonist, at a dose of 0.1 mg kg-1 i.v. Yohimbine per se had no significant effects on systemic arterial pressure, intestinal vascular resistance, net fluid absorption rate or PD. In the control animals, baroreceptor unloading induced an increase in systemic arterial pressure, intestinal vascular resistance and net fluid absorption rate, and a decrease in the PD. Yohimbine pretreatment did not significantly affect the systemic blood pressure response to baroreceptor unloading, but abolished the effect on intestinal vascular resistance and PD. After yohimbine treatment, decreases in carotid sinus pressure still enhanced net fluid absorption rate, but this response was observed in a higher range of carotid sinus pressures than in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal capillary filtration in acute and chronic portal hypertension.

The impact of acute and chronic portal hypertension on the dynamics of intestinal microvascular fluid exchange was examined in anesthetized, fasted, sham-operated control rats with normal portal pressures (CON), during acute elevations in portal pressure (APH) in control rats, and in rats in which chronic portal hypertension (CPH) was produced by calibrated stenosis of the portal vein 10 days prior to the experiments. Although intestinal blood flow and vascular resistance were not altered by APH in control rats, CPH was associated with an increased intestinal blood flow and reduced intestinal vascular resistance when compared with CON and APH. Intestinal capillary pressure and lymph flow were elevated in APH and CPH relative to control values. However, the increase in both variables was greater in CPH. The capillary filtration coefficient was elevated only in CPH. The transcapillary oncotic pressure gradient was not altered by APH or CPH. Interstitial fluid pressure was increased from -1.1 mmHg in CON to 3.9 mmHg during APH and to 5.0 mmHg in CPH. The results of this study indicate that chronic elevations in portal venous pressure produce larger increments in intestinal capillary pressure and filtration rate than do acute elevations in portal venous pressure of the same magnitude. However, the potential edemagenic effects of elevated capillary pressure in both acute and chronic portal hypertension are opposed by increases in lymph flow and interstitial fluid pressure.

Intestinal hyperemia in experimental diabetes mellitus.

Intestinal blood flows were measured using the radioactive microsphere technique in anesthetized, fasted (18-24 h) rats 4 wk after administration of streptozotocin (65 mg/kg body wt) or its vehicle. Blood flow was increased along the length of the small bowel in diabetic rats relative to normal animals. In an attempt to define the mechanisms underlying the intestinal hyperemic response to diabetes, we employed an in situ, blood perfused, isolated rat jejunum-ileum preparation. Intestinal blood flow was increased by 37%, while intestinal vascular resistance was reduced by 39% in diabetic rats relative to control animals. Cross-perfusion of control intestinal preparations with arterial blood from diabetic rats produced a 30% increase in blood flow and a 24% reduction in vascular resistance. Increasing plasma osmolarity, plasma glucose concentration, or plasma glucagon concentration in control animals to levels measured in diabetic animals produced reductions in vascular resistance that were qualitatively similar to that seen in the diabetic intestine. Intestinal vascular sensitivity to norepinephrine was assessed by constructing dose-response curves in control and diabetic animals. The mean ED50 values for norepinephrine were increased in diabetic rats relative to control animals. These results indicate that the intestinal hyperemic response in diabetes may be related to increased levels of circulating vasodilators, including hyperosmolarity and glucagon, and a reduced vascular sensitivity to norepinephrine.

Determinants of resting and passive intestinal vascular pressures in rat and rabbit.

Microvascular pressures in the intestinal arteries, submucosal arterioles, and mucosal venules were measured in rats and rabbits at rest and during maximum dilation. From these data and Doppler velocimetry measurements of relative changes in whole organ blood flow on maximum dilation, it was possible to determine to what extent microvascular pressures at rest depend on the active control and passive hemodynamic characteristics of specific vascular segments. New Zealand White rabbits (2-3 kg body wt) had a mean arterial pressure of 70-75 mmHg. However, pressures in arterioles of both species became equivalent at the second order of arteriolar branching within the bowel wall, and pressures in the smallest mucosal venules were 13.7 +/- 0.6 (SE) mmHg in rabbits and 14.9 +/- 0.3 mmHg in rats. Maximum vasodilation to approximately 300% of the control blood flow increased mucosal venule pressures approximately 10 mmHg in rats compared with approximately 4 mmHg in rabbits. The increased mucosal venule pressure during vasodilation was primarily due to increased pressures within the submucosal small arterioles, which immediately precede the villus vasculature in both species. The increased blood flow during vasodilation was due primarily to a decreased resistance of the small arteries and large arterioles, even though pressures in these larger vessels changed only approximately 10%. This situation allows a major decrease in intestinal vascular resistance to substantially increase blood flow with a minimal increase in mucosal microvascular pressures.