Increased flow rate and papaverine increase K+ exchange in perfused rat hind-limb skeletal muscle.

This study tested the hypothesis that increases in perfusate flow rate result in increased rates of unidirectional and net K+ transport in rat hind-limb skeletal muscle at rest. Ten neurally and vascularly isolated hind limbs, with arterial and venous catheters placed proximal to the popliteal region, were perfused for 10-min periods at flow rates (presented in a random order) of 0.27, 0.42, 0.63, 0.84, or 1.05 mL x min(-1) x g(-1). Potassium extraction and unidirectional K+ influx were determined using 42K, and arterial perfusion pressure was measured continuously. Increases in flow rate resulted in decreases in K+ extraction and increases in unidirectional K+ influx, unidirectional K+ efflux, and net K+ efflux. The increases in K+ flux were associated with increases in oxygen uptake, glucose uptake, and lactate release. In separate experiments (n = 5), the vasodilator papaverine (10(-4) M) did not further vasodilate the vasculature of resting hind limbs, suggesting that the hind limbs in this preparation were fully vasodilated. Papaverine, at constant flow, resulted in a nearly 1.5-fold increase in K+ extraction, a doubling of unidirectional K+ influx, and increases in unidirectional K+ efflux and net K+ efflux. It is concluded that physiological increases in flow rate result in increases in K+ transport in isolated, perfused rat hind-limb skeletal muscle. Furthermore, papaverine appeared to induce an increase in skeletal muscle membrane permeability to K+.     

Is flow in subpleural region typical of the rest of the lung? A study using laser-Doppler flowmetry.

The microcirculation in the subpleural region of the lung is thought to be physiologically typical of the entire vasculature. To investigate this issue, an in situ blood-perfused dog lung lobe (500 ml/min) was prepared and the blood flow in the subpleural region (Qs) was monitored with laser-Doppler flowmetry (LDF). The flow rates into and out of the lobe were monitored with in-line flow probes, and the arterial and venous pressures were recorded from side ports in the cannulas. The LDF signal measures flow in arbitrary units over a region less than 2 mm deep and 1 mm2. The LDF signal was independent of site of measurement and was linearly proportional to total flow rate (r2 greater than 0.9), suggesting that during baseline conditions Qs behaves similarly to, although not necessarily the same as, blood flow in the rest of the lung. However, if the vasculature is constricted by serotonin (arterial constriction) or by histamine (venous constriction), Qs decreases significantly relative to total flow. In fact, in some cases Qs approached zero during vasoconstriction, despite the fact that total flow was maintained constant and the pulmonary arterial pressure became elevated. Reduction in Qs most likely reflects a redistribution from the subpleural to the central regions of the lung. The results of this study suggest that LDF is a useful tool for monitoring flow in the subpleural region of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral chemoreceptor modulation of the pulmonary vasculature in the cat.

The present study was undertaken to determine whether stimulation of the carotid and aortic bodies (cb and ab) could affect the pulmonary vasculature. Our hypothesis was that each promoted vasodilation and thus could modulate the pulmonary vasoconstrictor response to hypoxia. The experimental design of the first set of experiments took advantage of the facts that 1) the ab, but not the cb, increases its neural output in response to CO, whereas both respond to a decreased arterial PO2 (hypoxic hypoxia, HH) and 2) the aortic nerves in cats are easily transected. Hence, both cb and ab sent neural activity to the brain stem when the intact cat was exposed to 10% O2 in N2. Only the ab sent information during CO hypoxia (COH intact). Only the cb did so during HH in the cat in which the aortic nerves had been transected, removing the aortic body (HH abr); neither ab nor cb did so during COH abr. Fifteen anesthetized paralyzed artificially ventilated cats were fit with catheters in the femoral artery and vein, right and left atria, left ventricle, and pulmonary artery and with an aortic flow probe. In the HH intact and HH abr conditions, there was a significant rise in cardiac output, whereas pulmonary arterial pressure (Ppa) rose initially but then leveled off while cardiac output continued to rise. During the 15-min exposure to HH, pulmonary vascular resistance [PVR = (Ppa - Pla)/cardiac output, where Pla is left atrial pressure] rose initially and then decreased significantly at 2-3 min. In response to COH, PVR showed only a significant decrease. In the second set of experiments, seven cats were instrumented as above and had loops placed in the common carotid arteries for selectively perfusing the cbs. In response to a brief infusion of venous blood mixed with 0.3-0.5 micrograms NaCN, which selectively stimulated only the cb, aortic flow remained relatively constant while heart rate and Ppa - alveolar pressure difference decreased significantly; so also did PVR. These data are consistent with the hypothesis that stimulation of the ab and cb singly or together can provoke a significant pulmonary vasodilation in the anesthetized paralyzed artificially ventilated cat.     

Hemodynamic effects of blood loss during a passive response to a stressor in the conscious rabbit

In the conscious rabbit, exposure to an air jet stressor increases arterial pressure, heart rate, and cardiac output. During hemorrhage, air jet exposure extends the blood loss necessary to produce hypotension. It is possible that this enhanced defense of arterial pressure is a general characteristic of stressors. However, some stressors such as oscillation (OSC), although they increase arterial pressure, do not change heart rate or cardiac output. The cardiovascular changes during OSC resemble those seen during freezing behavior. In the present study, our hypothesis was that, unlike air jet, OSC would not affect defense of arterial blood pressure during blood loss. Male New Zealand White rabbits were chronically prepared with arterial and venous catheters and Doppler flow probes. We removed venous blood until mean arterial pressure decreased to 40 mmHg. We repeated the experiment in each rabbit on separate days in the presence and absence (SHAM) of OSC. Compared with SHAM, OSC increased arterial pressure 14 +/- 1 mmHg, central venous pressure 3.3 +/- 0.4 mmHg, and hindquarter blood flow 34 +/- 4% while decreasing mesenteric conductance 32 +/- 3% and not changing heart rate or cardiac output. During normotensive hemorrhage, OSC enhanced hindquarter and renal vasoconstriction. Contrary to our hypothesis, OSC (23.5 +/- 0.6 ml/kg) increased the blood loss necessary to produce hypotension compared with SHAM (16.8 +/- 0.6 ml/kg). In nine rabbits, OSC prevented hypotension even after a blood loss of 27 ml/kg. Thus a stressful stimulus that resulted in cardiovascular changes similar to those seen during freezing behavior enhanced defense of arterial pressure during hemorrhage.     

Atrial natriuretic peptide (ANP) does not inhibit the basal vascular tone present in the in situ blood-perfused dog gracilis muscle

This study evaluated the effects of rat ANP(5-28) infusion into the blood-perfused dog gracilis muscle at concentrations ranging from 30 to 10,000 pg/ml. The vasculature of gracilis muscles from anesthetized beagle dogs was isolated and pump-perfused at constant flow with blood utilizing an extracorporeal circuit. Maximal vasodilatory capacity was determined by adenosine injection. ANP was infused into the arterial circuit to produce increasing arterial blood concentrations. Each infusion lasted 10 min. Systemic arterial pressure, central venous pressure, cardiac output and heart rate did not change during ANP infusion into the gracilis vasculature. ANP at arterial blood concentrations up to 10,000 pg/ml did not produce significant vasodilation although the vasculature showed pronounced vasodilation in response to adenosine. In vitro experiments showed that ANP had much less vasorelaxant activity in dog femoral artery and saphenous vein than in rabbit aorta. Therefore, rat ANP(5-28) at concentrations within and well above physiological and pharmacological ranges does not inhibit the basal vascular tone present in the innervated, blood-perfused dog gracilis muscle in situ.     

Adaptation of small intestinal membrane transport processes during diabetes mellitus in rats

Intestinal amino acid and glucose transport is increased in various disease states and physiological circumstances. This enhancement is generally due to an increase in transport capacity (Vmax) without a change in carrier affinity (KD). Furthermore, the increase in transport capacity is too large to be attributed, in most cases, to simple intestinal hypertrophy. In the streptozotocin-treated chronically diabetic rat model, specific binding indicated an enhanced total number of glucose carriers in the small intestine compared with controls. Furthermore, autoradiography reveals that specific phlorizin (i.e., glucose) binding extends into the intervillous region of the intestine, while in age-matched controls binding is confined to the villous tip. These studies suggest that during experimental diabetes mellitus in rats, enhanced intestinal nutrient absorption may occur as a consequence of recruitment of carriers into previously nontransporting enterocytes. This review looks at ways in which this alteration may be influenced, and examines the expression of various isoforms of Na-K ATPase during streptozocin-induced diabetes mellitus.     

Prostacyclin production with serotonin, increased flow, or elevated venous pressure in dog lung

The lung may release prostacyclin (PGI2) in response to humoral or mechanical stimuli. We measured 6 keto-PGF1 alpha as an index of PGI2 production during serotonin (5-HT) infusion, elevated venous pressure (Pv), or increased blood flow (Q) in the isolated canine lower left lung lobe (LLL). Lobar vascular resistance (LVR) was partitioned into arterial (Ra), middle (Rm), and venous (Rv) components by arterial and venous occlusions. The infusion of 55-210 micrograms/min 5-HT (n = 9) was associated with concomitant increases in PGI2 production and dose-related increases in pulmonary arterial pressure (Pa) and LVR. 5-HT increased Ra at each infusion rate, whereas Rm was not changed and Rv was increased only at the highest infusion rate. When Pa was increased by stepwise elevations in Pv from 3.7 to 19.1 cmH2O (n = 8) or by increases in Q from 250 to 507 ml/min (n = 5) to match the Pa increase observed during 5-HT infusion, PGI2 production was not altered. Increases in Pv reduced LVR largely by decreasing Ra, whereas increases in Q reduced LVR without changing Ra, Rm, or Rv. Infusion of 5-HT when Pa was held constant by reduction in blood flow (n = 6) did not increase PGI2. Thus infusion of 5-HT at a normal blood flow rate increased PGI2 formation in the isolated blood-perfused dog lung lobe. The results also suggest that sustained mechanical effects related to increased venous pressure or elevated blood flow are not associated with a sustained elevation of PGI2 formation.     

Differential effects of venous stasis and arterial insufficiency on tissue oxygenation in myocutaneous island flaps: an experimental study in pigs.

The supply, consumption, and tissue tension of oxygen were studied in experimental bilateral myocutaneous island flaps in five control pigs and in eight pigs during progressive 1-hour intervals of flap ischemia. Progressive ischemia was obtained by partial to complete clamping of the artery in one flap, producing arterial insufficiency, and simultaneous clamping of the vein in the other flap, producing venous stasis. Blood flow was reduced to 50, 25, and 0 percent of baseline. In the arterial insufficiency flaps, the oxygen tension in subcutaneous tissue, muscle, and venous outflow was significantly reduced once blood flow was reduced to 50 percent of baseline. Oxygen consumption during partial vessel occlusion was lower in the venous stasis flaps than in the arterial insufficiency flaps when blood flow was reduced to 25 percent of baseline, suggesting either that cellular metabolism is reduced in the venous stasis flaps or that the oxygen which is delivered is unavailable for the cells. Increased presence of tissue fluid in the venous stasis flap inhibits the diffusion of oxygen through the interstitial tissue, and this may explain the lower oxygen consumption. During 3 hours of reperfusion, increased blood flow was observed in the arterial insufficiency flaps, whereas blood flow in the venous stasis flaps was sluggish. The arterial insufficiency flaps recovered more rapidly than the venous stasis flaps during the first hour of reperfusion, judged by the rate of increase in oxygen tension and the higher venous oxygen tension. Oxygen tension increased more rapidly in muscle than in subcutaneous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Localization of biotransformational enzymes along the crypt-villus axis of the rat intestine. Evaluation of two cell isolation procedures

Rat intestinal epithelial cells were isolated by EDTA-chelation, combined with gentle shaking (modified Weiser procedure) or with strong longitudinal vibration (Harrison/Webster procedure). Both methods yield large numbers of viable cells and are relatively easy to use. Electronmicroscopical and biochemical data indicate that cell fractions from different levels of the villous region can be obtained only by the modified Weiser procedure. When strong mechanical forces are involved (Harrison-Webster procedure) the villus epithelium is released according to an all-or-nothing process. The biotransformational capacity of cell fractions, obtained from different levels of the villi by the modified Weiser procedure, was investigated. It was shown that the rate of metabolism of 7-ethoxycoumarin and 1-naphthol was substantially higher in lower villous cells than in cells isolated from the upper villous region. O-Deethylation of 7-ethoxycoumarin decreases from 145 +/- 13 pmole/min mg cell protein (72 +/- 4% conjugated) in lower villous cells to 62 +/- 12 pmole/min mg cell protein (37 +/- 6% conjugated) in tip cells. Glucuronidation of 1-naphthol decreased from 495 +/- 23 pmole/min mg cell protein (lower villous cells) to 137 +/- 13 pmole/min mg cell protein (tip cells).     

Nature and distribution of vascular resistance in hypoxic pig lungs

We used the vascular occlusion technique in pig lungs isolated in situ to describe the effects of hypoxia on the distribution of vascular resistance and to determine whether the resistive elements defined by this technique behaved as ohmic or Starling resistors during changes in flow at constant outflow pressure, changes in outflow pressure at constant flow, and reversal of flow. During normoxia, the largest pressure gradient occurred across the middle compliant region of the vasculature (delta Pm). The major effect of hypoxia was to increase delta Pm and the gradient across the relatively noncompliant arterial region (delta Pa). The gradient across the noncompliant venous region (delta Pv) changed only slightly, if at all. Both delta Pa and delta Pv increased with flow but delta Pm decreased. The pressure at the arterial end of the middle region was independent of flow and, when outflow pressure was increased, did not increase until the outflow pressure of the middle region exceeded 8.9 Torr during normoxia and 18.8 Torr during hypoxia. Backward perfusion increased the total pressure gradient across the lung, mainly because of an increase in delta Pm. These results can be explained by a model in which the arterial and venous regions are represented by ohmic resistors and the middle region is represented by a Starling resistor in series and proximal to an ohmic resistor. In terms of this model, hypoxia exerted its major effects by increasing the critical pressure provided by the Starling resistor of the middle region and the ohmic resistance of the arterial region.     

Arterial system of the gill of the lobster,Homarus americanus

Three-dimensional architecture of the branchial artery and venous vasculature of Homarus americanus was studied by the method of corrosion cast or styrene cracking and by scanning electron microscopy. Four arteries, the epibranchial (EA) and hypobranchial arteries (HA) on the septal wall of the afferent and efferent vessels, respectively, and two lateral canal arteries (LCA), each in one of the paired lateral canals, run parallel to the gill axis. The EA directs dendroid branches to the spongy tissue in the afferent vessel wall far from the efferent, supplying oxygen to the otherwise oxygen-depleted tissue. The HA distributes the filament arteriole (FA) into the central channel of individual middle filaments via the LCA. The FA opens halfway at a position where the channel narrows. Thus, it is likely that venous hemolymph in the central channel flows from base to tip in the direction in which arterial hemolymph from the FA flows. This and the anatomy of venous vasculature suggest three probable patterns of perfusion from afferent to efferent vessels: double serial circulation via the outer and inner filaments and novel routes both through the middle filament, i.e., single circulation via the afferent and efferent channels of this filament and double serial circulation via the outer filament and then the central channel of the middle. On the basis of the physics of flow and known physiological data, we propose that switching of these routes that involves independently functional multiple double serial circulations can play an important role in controlling efficiency of gas exchange, particularly during hypoxia. J Morphol. 233:165–181, 1997. © 1997 Wiley-Liss, Inc.     

Metabolic and myogenic factors in local regulation of the microcirculation.

Patterns of flow were recorded from individual capillaries of mesentery and muscle during autoregulation and reactive hyperemia. In cat mesentery at normal arterial pressure capillary blood flow was often periodic in nature. When arterial pressure was reduced periodicity was abolished and in certain cases mean flow increased. Elevation of venous pressure at this time caused restoration of flow periodicity and simultaneously a large fall in mean flow. Vasomotion and autoregulation in mesentery appear to be dependent on intravascular pressure per se. In cat sartorius muscle substantial increase in flow was seen in most capillaries during reactive hyperemia. In certain capillaries the pattern resembled the gross flow pattern while others showed a brief hyperemia and then a period of flow arrest that is presumably due to a strong precapillary vasoconstriction. The latter response is suggestive of a myogenic control while the former may be due to accumulation of metabolites. In frog pectoralis muscle reactive hyperemia was very prolonged in comparison to cat sartorius muscle. The general pattern of flow was consistent with the notion of a strong metabolic control mechanism. The three tissues studied provide examples of strong myogenic, strong metabolic, and combined metabolic and myogenic control of the microcirculation.     

Orthostasis fails to produce active limb venoconstriction in adolescents.

Orthostasis is characterized by translocation of blood from the upper body and thorax into dependent venous structures. Although active splanchnic venoconstriction is known to occur, active limb venoconstriction remains controversial. Based on prior work, we initially hypothesized that active venoconstriction does occur in the extremities during orthostasis in response to baroreflex activation. We investigated this hypothesis in the arms and legs of 11 healthy volunteers, aged 13-19 yr, using venous occlusion strain gauge plethysmography to obtain the forearm and calf blood flows and to compute the capacitance vessel volume-pressure compliance relation. Subjects were studied supine and at -10, +20, and +35 degrees to load the baroreflexes. With +20 degrees of tilt, blood flow decreased and limb arterial resistance increased significantly (P < 0.05) compared with supine. With +35 degrees of tilt, blood flow decreased, limb arterial resistance increased, and heart rate increased, indicating parasympathetic withdrawal and sympathetic activation with arterial vasoconstriction. The volume-pressure relation was unchanged by orthostatic maneuvers. The results suggest that active venoconstriction in the limbs is not important to mild orthostatic response.     

Morphofunctional reorganization of the kidneys in lymphatic outflow disturbance

In 115 Wistar male rats structures and rates of tissue blood flow have been studied in the cortical and medullary renal substance histologically, polarographically (estimation of the volumetric tissue blood flow by hydrogen clearance). Systemic arterial (peritoneal aorta), venous (caudal vena cava) and lymphatic (renal lymph nodes) pressures have been measured, normal and after ligation of the thoracic duct at early (1-3 days), middle (1 month) and late (2-3 months) periods. In 1-3 days edema and dystrophy of the renal parenchyma, decrease of the blood flow rate in the cortical and its increase in the renal medullary substance, as well as a sharp elevation of pressure in the lymph nodes are observed. In 1 month of the experiment together with dystrophy and edema moderate sclerosis, decreasing blood flow rate in the cortical and medullary substance are noted. Increase of the systemic arterial and venous pressure and decreasing pressure in the lymph nodes, as well as a sharp increase of the renal nodes mass are revealed. In 2-3 months of the experiment, together with sclerosis of the renal parenchyma, elevated blood flow rate is observed in the kidneys and decreasing pressure in the lymph nodes up to its initial value takes place.     

Histamine H3 receptors modulate reactive hyperemia in rat gut.

Reactive hyperemia (RH) is an abrupt blood flow increase following release from mechanical occlusion of an artery, with restoration of intra-arterial pressure. The mechanism of this postocclusion increase in blood flow in the gut is multifactorial. Relaxation of intestinal resistance vessels, observed during RH, may involve myogenic, metabolic, hormonal and neurogenic factors. Evidence exists that histamine is an important endogenous mediator of various functions of the gut, including blood flow. The vascular effects of histamine in the intestinal circulation are due its agonistic action on histamine H1, H2 and H3 receptors. In the present study the hypothesis was tested that peripheral histamine H3 receptors are involved in the mediation of RH in the intestinal circulation. In anesthetized rats, anterior mesenteric artery blood flow (MBF) was determined with ultrasonic Doppler flowmeter, and arterial pressure (AP) was determined with a transducer. The increase in the volume of blood accumulating during RH (RH-volume), the peak increase of arterial blood flow (RH-peak response) and the duration of the hyperemia (RH-duration) were used to quantify RH after occluding the anterior mesenteric artery for 30, 60 and 120 s. Hyperemia parameters were determined before and after administration of the selective histamine H3 receptor antagonist clobenpropit. Pretreatment with clobenpropit was without any effect on control MBF and AP but significantly reduced most of RH responses. These findings support the hypothesis that histamine H3 receptors do not play any role in the control of intestinal vasculature at basal conditions but these receptors participate in the intestinal hyperemic reaction in response to complete temporal intestinal ischemia.     

Epinephrine induces tissue perfusion deficit in porcine endotoxin shock: evaluation by regional CO(2) content gradients and lactate-to-pyruvate ratios

Epinephrine is widely used as a vasoconstrictor or inotrope in shock, although it may typically induce or augment lactic acidosis. Ongoing debate addresses the question of whether hyperlactatemia per se is a sign of tissue perfusion deficit or aerobic glycolysis. We wanted to test the hypothesis that epinephrine has selective detrimental effects on visceral perfusion and metabolism. We performed rigorous regional venous blood gas analyses as well as intraperitoneal microdialysis. We used a mathematical model to calculate regional arteriovenous CO(2) content gradients and estimated the magnitude of the Haldane effect in a porcine model of prolonged hypotensive shock induced by endotoxin infusion (mean arterial blood pressure < 60 mmHg). Subsequently, vasopressors (epinephrine or norepinephrine) were administered and adjusted to maintain systemic mean arterial pressure > 70 mmHg for 4 h. Epinephrine caused systemic hyperlactatemia and acidosis. Importantly, both systemic and regional venous lactate-to-pyruvate ratios increased. Epinephrine was associated with decreasing portal blood flow despite apparently maintained total splanchnic blood flow. Epinephrine increased gastric venous-to-arterial Pco(2) gradients and CO(2) content gradients with decreasing magnitude of the Haldane effect, and the regional gastric respiratory quotient remained higher after epinephrine as opposed to norepinephrine infusion. In addition, epinephrine induced intraperitoneal lactate and glycerol release. We did not observe these adverse hemodynamic or metabolic changes related to norepinephrine with the same arterial pressure goal. We conclude that high CO(2) content gradients with decreasing magnitude of the Haldane effect pinpoint the most pronounced perfusion deficiency to the gastric wall when epinephrine, as opposed to norepinephrine, is used in experimental endotoxin shock.     

Gastric and intestinal release of vasoactive intestinal polypeptide in the milk-fed lamb

Vasoactive intestinal polypeptide (VIP) has been proposed as the neurotransmitter of the atropine-resistant relaxation of gastric structures in the lamb. To examine this proposal VIP concentrations in plasma from arterial, gastric venous and intestinal venous blood were measured in healthy conscious lambs before, during and after teasing with, and sucking of milk. Basal arterial plasma VIP concentrations were undetectable (less than 3 pmol/l) and remained so during and after feeding. Before feeding VIP was detected in only 2 of 12 gastric venous plasma samples (5 and 13 pmol/l). During teasing with food there were increments in VIP of 19 +/- 4 pmol/l and during feeding of 27 +/- 5 pmol/l. VIP concentration in gastric venous plasma rapidly returned to fasting levels after cessation of sucking. In contrast VIP in the intestinal venous plasma did not rise during teasing or upon commencement of sucking but a peak increment of 34 +/- 6 pmol/l occurred at 5 min after cessation of feeding. The results are consistent with the hypotheses that VIP is released in anticipation of and during sucking from inhibitory neurones involved in relaxation of gastric structures and that intestinal release of VIP is a consequence of entry of digesta into the small intestine.     

Reductions in cardiac output in hypoxic young pigs: systemic and regional perfusion and oxygen metabolism

We tested the hypotheses that, in hypoxic young pigs, reductionsin cardiac output restrict systemic oxygen transport to a greaterextent than does hypoxia alone and that compensatory responses to thisrestriction are more effective in higher than in lower priorityvasculatures. To study this, 10- to 14-day-old instrumented awakehypoxic (arterial oxygen tension = 39 Torr) pigs were exposed toreduced venous return by inflation of a right atrial balloon-tipped catheter. Blood flow was measured withradionuclide-labeled microspheres, and oxygen metabolism was determinedwith arterial and venous oxygen contents from appropriate vessels.Hypoxia resulted in a reduction in oxygen tension; increases in cardiacoutput and perfusion to brain (72% over baseline), heart, adrenalglands, and liver without reductions to other organs except for thespleen; reductions in systemic and intestinal oxygen delivery; andincreases in systemic and intestinal oxygen extraction without changesin systemic, cerebral, or intestinal oxygen uptake. Duringhypoxia, decreasing venous return was associated with increases inarterial lactic acid concentration and central venous pressure;attenuation of the hypoxia-related increase in cardiac output;sustained increases in brain (72% over baseline) and heart perfusion;reductions in lung (bronchial artery), pancreatic, renal, splenic, andintestinal (50% below baseline) perfusion; decreases insystemic and gastrointestinal oxygen delivery; sustained increases insystemic and intestinal oxygen extraction; and decreases in intestinaloxygen uptake, without changes in cerebral oxygenmetabolism. We conclude that when venous return to theheart is reduced in hypoxic young pigs, the hypoxia-related increase incardiac output was attenuated and the relative reduction in cardiacoutput was associated with preserved cerebral oxygen uptake andcompromised intestinal oxygen uptake. Regional responses to hypoxiacombined with relative reductions in cardiac output differ from that ofhypoxia alone, with the greatest effects on lower priority organs suchas the gastrointestinal tract.

     

Notch signalling in healthy and diseased vasculature

Notch signalling is an evolutionarily highly conserved signalling mechanism governing differentiation and regulating homeostasis in many tissues. In this review, we discuss recent advances in our understanding of the roles that Notch signalling plays in the vasculature. We describe how Notch signalling regulates different steps during the genesis and remodelling of blood vessels (vasculogenesis and angiogenesis), including critical roles in assigning arterial and venous identities to the emerging blood vessels and regulation of their branching. We then proceed to discuss how experimental perturbation of Notch signalling in the vasculature later in development affects vascular homeostasis. In this review, we also describe how dysregulated Notch signalling, as a consequence of direct mutations of genes in the Notch pathway or aberrant Notch signalling output, contributes to various types of vascular disease, including CADASIL, Snedden syndrome and pulmonary arterial hypertension. Finally, we point out some of the current knowledge gaps and identify remaining challenges in understanding the role of Notch in the vasculature, which need to be addressed to pave the way for Notch-based therapies to cure or ameliorate vascular disease.     

The influence of congestion and ischemia on survival of an experimental vascular pedicle island flap

We investigated the relationship between the survival rate of experimental rat pedicle island flaps and mild vascular insufficiency, using a flap designed to induce constant distant necrosis. To eliminate individual variation, the vasculature of each flap was evaluated by injecting dye prior to ligating either or both of the pedicle vessels. Seventy-five male Wistar rats divided into four groups were used. Six of the rats died, so 69 rats were evaluated. Statistically, the dye distance of each group was the same. In the control group of 29 rats, survival length was directly proportional to dye distance. Although the mean values of the survival length minus the dye distance of each flap (delta S.L.) in the venous inadequacy group were not different from those of the control group, there was significant difference between the mean values of the arterial insufficiency and the venous inadequacy plus arterial insufficiency groups and those of the control group. In the pedicle island flap, mild venous inadequacy was less responsible for necrosis when the arterial inflow was sufficient. However, when the arterial inflow was impaired, even mild venous inadequacy affected flap survival.