Modulation Of Inflow Research Articles

Successful modulation of portal inflow by somatostatin in a porcine model of small-for-size syndrome

BackgroundSomatostatin may prevent the small-for-size syndrome in subjects undergoing extended hepatectomy by decreasing portal pressure. MethodsTwenty pigs underwent 70% hepatectomy (H70 group, n = 7), 90% hepatectomy (H90 group, n = 7), or sham laparotomy (control group, n = 6). Splanchnic hemodynamics was measured before and after an intraoperative infusion of somatostatin. ResultsThe portal vein flow normalized to liver weight increased in both H70 and H90 groups (from 125 ± 42 to 342 ± 82 mL/min/100g, P = .031 and from 140 ± 46 to 530 ± 241, P = .016, respectively). The hepatic venous pressure gradient (HVPG) increased in the H90 group only (from 5.5 ± 5.8 to 13 ± 4.9 mm Hg, P = .004). Somatostatin decreased portal vein flow normalized to liver weight in both H70 and H90 groups (from 408 ± 224 to 360 ± 227 mL/min/100g, P = .031 and from 560 ± 190 to 466 ± 189 mL/min/100g, P = .016), and restored a normal HVPG in the H90 group (from 14.3 ± 4.8 to 7.7 ± 6.1 mm Hg, P = .047). ConclusionsSomatostatin restores a normal HVPG in the setting of small-for-size syndrome and can be considered as an effective pharmaceutical modality of portal inflow modulation after extended hepatectomy.

Successful modulation of portal inflow by somatostatin in a porcine model of subtotal hepatectomy

Aims: To assess the intraoperative effects of somatostatin (SM) on splanchnic hemodynamic parameters in two porcine models of extended hepatectomy. Methods: Twenty female pigs underwent surgery and were divided in 3 groups: 7 animals underwent 70% hepatectomy (H70 group), 7 underwent 90% (subtotal) hepatectomy (H90 group), and 6 underwent sham laparotomy (control group). The variations of splanchnic hemodynamic parameters (portal vein flow, PVF; hepatic artery flow, HAF; portal vein pressure, PVP; inferior vena cava pressure, IVCP; and hepatic venous pressure gradient, HVPG [defined as IVCP-PVP]) were assessed before and after infusion of SM. Flow values were normalized to the liver remnant weight. Results: The mean body and liver weights were 28,600 and 784 grams, respectively (liver-to-body ratio = 2.8%). The mean weights of the excised livers were 600 and 711 grams (71.3% and 88.6% of the whole liver), and the liver remant-to-body ratios were 0.77% and 0.33% in the H70 and in the H90 groups, respectively. A significant increase in PVF was observed after both 70% and 90% hepatectomy (+67%, p = 0.031 and +278%, p = 0.016, respectively), while HVPG significantly increased only after 90% hepatectomy (from 5.5 to 13 mmHg, p = 0.004). After intraoperative infusion of SM, PVF decreased in all 3 groups (−13% in the control group, p = 0.062; −12% in the H70 group, p = 0.031; −17% in the H90 group, p = 0.016), while HVPG significantly decreased and returned to normal value in the H90 group only (from 14.3 to 7.7 mmHg, p = 0.047). No significant changes in HAF were observed after SM infusion. Conclusions: Somatostatin reduces portal inflow and restores a normal HVPG below critical values, without changes in HAF in a porcine model of small-for-size syndrome.

Liver Volume Restoration and Hepatic Microarchitecture in Small-for-Size Syndrome.

We investigated preoperative parameters that could work as markers of liver regeneration (LR), and tried to create an algorithm for therapeutic decision-making, looking at the clinical setting of post-hepatectomy liver failure (PHLF) after major liver resection for malignancies (LRM) and of the small-for-size syndrome (SFSS) after adult-to-adult living related liver transplantation (LRLT), considering PHLF and SFSS a single clinical entity. The clinical data of 2 series of 10 consecutive patients who experienced liver-specific complications after LRLT or LRM between 2008 and 2013 were analyzed. LR was evaluated by multidetector computed tomography (MDCT) and hepatic parenchymal findings with specific re-examinations of liver biopsies. The analysis was done according to demographics, tumor characteristics, and postoperative complications occurring within 90 days of surgery and codified within the Clavien classification. A total of 13 cases of SFSS occurred in 8 LRLT recipients (61.5%) and in 5 patients after LRM (38.5%). The incidence of SFSS was significantly associated with a greater spleen volume/future remnant liver volume ratio (1.08±0.5; P=0.02) and a reduced number of hepatic tumors (0.58±0.6; P=0.04). A greater degree of LR was not associated with a lesser likelihood of developing SFSS (P=0.31). SFSS incidence and re-examination of post-operative liver biopsies differed according to the evidence of focal endothelial denudation in the portal vein and centrilobular hepatocanalicular cholestasis. We found an association between SFSS incidence and the immunohistochemical overexpression of cytological proliferation marker Ki-67 (29.3±29.8%; P=0.007), which was a significant predictor of poor post-operative survival (OR=1.12, C.I.: 1.013; 1.242). SFSS is a rare but dangerous clinical entity characterized by anarchic hepatic regeneration. We suggest focusing on early diagnosis in order to establish non-surgical modulation of the portal inflow, in conjunction with optimization of medical management.

Modulation of graft vascular inflow guided by flowmetry and manometry in liver transplantation

Survival of the partial graft after living donor liver transplantation owes much to its tremendous regenerative ability. With excellent venous outflow capacity, a graft within a wide range of graft-to-standard-liver-volume ratios can cope with portal hypertension that is common in liver transplant recipients. However, when the ratio range is exceeded, modulation of graft vascular inflow becomes necessary for graft survival. The interplay between graft-to-standard-liver-volume ratio and portal pressure, in the presence of portosystemic shunt or otherwise, requires individualized modulation of graft portal and arterial inflows. Boosting of portal inflow by shunt ligation can be guided by transonic flowmetry, whereas muting of portal inflow by splenic artery ligation can be monitored by portal electronic manometry. We describe four cases to illustrate the above. One patient had hepatic artery thrombosis resulting from splenic artery steal syndrome which was the sequela of small-for-size syndrome. Emergency splenic artery ligation and re-anastomosis of the hepatic artery successfully muted the portal inflow and boosted the hepatic arterial inflow. Another patient with portal vein thrombosis underwent thrombendvenectomy. Portal inflow was boosted with ligation of portosystemic shunt, which is often present in these patients with portal hypertension. The coexistence of splenic aneurysm and splenorenal shunt required ligation of both in the third patient. The fourth patient, with portal pressure and flow monitoring, avoided ligation of a coronary vein which became a main portal inflow after portal thrombendvenectomy. Management of graft inflow modulation guided selectively by transonic flowmetry or portal manometry was described.

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Early Modulation of Portal Graft Inflow in Adult Living Donor Liver Transplant Recipients With High Portal Inflow Detected by Intraoperative Color Doppler Ultrasound

Splenic flow clearly contributes to portal hyperperfusion in end-stage liver disease patients with hypersplenism. Early modulation of portal graft inflow can relieve the partial graft from the deleterious effects of this portal overflow. Color Doppler ultrasound may play an important role in the intraoperative detection of patients with high recipient portal inflow. Among 138 cases, portal inflow increased after liver transplantation, namely recipient portal inflow (rPVF) of 60 to 554 mL/min/100 g graft weight (mean = 156 mL/min/100 g). There were eight cases in which the rPVF was >250 mL/min/100 g graft weight. In the early period of this study, there were two patients with high portal inflow (rPVF > 250 mL/min/100 g graft) who did not undergo modulation of the portal flow. Small-for-size syndrome occurred in two patients. Later in the series, six patients underwent intraoperative splenic arterial ligation or splenectomy; only one of them displayed prolonged hyperbilirubinemia. The incidence of small-for-size syndrome between these two groups was significant (P = .048). No complication occurred related to the splenic artery ligation or the splenectomy. In conclusion, early modulation of portal graft inflow can protect the graft from portal overflow damage. Intraoperative Doppler ultrasound measurement is an optimal modality for detection of high rPVF.

Left lobe adult-to-adult living donor liver transplantation: Small grafts and hemiportocaval shunts in the prevention of small-for-size syndrome

Adult-to-adult living donor liver transplantation (AA-LDLT) has better outcomes when a graft weight to recipient weight ratio (GW/RW) > 0.8 is selected. A smaller GW/RW may result in small-for-size syndrome (SFSS). Portal inflow modulation seems to effectively prevent SFSS. Donor right hepatectomy is associated with greater morbidity and mortality than left hepatectomy. In an attempt to shift the risk away from the donor, we postulated that left lobe grafts with a GW/RW < 0.8 could be safely used with the construction of a hemiportocaval shunt (HPCS). We combined data from 2 centers and selected suitable left lobe living donor/recipient pairs. Since January 2005, 21 patients underwent AA-LDLT with left lobe grafts. Sixteen patients underwent the creation of an HPCS between the right portal vein and the inferior vena cava. The portocaval gradient (portal pressure - central venous pressure) was measured before the unclamping of the shunt and 10 minutes after unclamping. The median actual graft weight was 413 g (range = 350-670 g), and the median GW/RW was 0.67 (range = 0.5-1.0). The portocaval gradient was reduced from a median of 18 to 5 mmHg. Patient survival and graft survival at 1 year were 87% and 81%, respectively. SFSS developed in 1 patient, who required retransplantation. Two patients died at 3 and 10 months from a bile leak and fungal sepsis, respectively. The median recipient bilirubin level and INR were 1.7 mg/dL and 1.1, respectively, at 4 weeks post-transplant. One donor had a bile leak (cut surface). This is the first US series of small left lobe AA-LDLT demonstrating that the transplantation of small grafts with modulation of the portal inflow by the creation of an HPCS may prevent the development of SFSS while at the same time providing adequate liver volume. As it matures, this technique has the potential for widespread application and could positively effect donor safety, the donor pool, and waiting list times.

Sacral neuromodulation: Therapy evolution

Objectives:Sacral neuromodulation has gained increased worldwide acceptance as the standard of care in patients with refractory overactive bladder (OAB) and non-obstructive urinary retention (NOUR). This review will detail the evolution of the technology.Materials and Methods:The mechanism of action and advances in treatment, including tined lead, fluoroscopic imaging, and smaller implantable pulse generator (IPG) are reviewed. This discussion also explores expanding indications and future advances including interstitial cystitis, chronic pelvic pain, neurogenic bladder, fecal incontinence, constipation, and dysfunctional elimination syndrome in children.Results:Sacral neuromodulation (SNM) exerts its influence by modulation of sacral afferent inflow on storage and emptying reflexes. The tined lead allows for placement and stimulation to be performed in the outpatient setting under local anesthesia with mild sedation. Lead migration has been minimal and efficacy improved. The use of fluoroscopy has improved accuracy of lead placement and has led to renewed interest in bilateral percutaneous nerve evaluation (PNE). Bilateral PNE can be performed in the office setting under local anesthesia, making a trial of therapy less expensive and more attractive to patients. A smaller IPG has not only improved cosmesis, but decreased local discomfort and need for revision. The role for SNM continues to expand as clinical research identifies other applications for this therapy.Conclusions:Our understanding of SNM, as well as technological advances in therapy delivery, expands the pool of patients for which this form of therapy may prove beneficial. Less invasive instrumentation may even make this form of therapy appealing to patients without refractory symptoms.

Modeling the diurnal variation of tracer transit velocity through a subglacial channel

Tracer injections into a moulin connecting to a subglacial channel at Unteraargletscher were repeated at intervals of about two hours over two diurnal discharge cycles in August and September 2000. The pronounced hysteresis in the relationships between tracer transit velocity and proglacial discharge may be explained by adjustments of the channel cross section in response to discharge variations or alternatively by modulation of inflow from the tributary moulin into a main subglacial channel. To test these hypotheses, we employ a physically based, time‐dependent model of channelized subglacial drainage. In a series of numerical experiments, we explore the general characteristics of each mechanism before the model is applied to diurnal discharge variations measured during the tracer tests at Unteraargletscher. We found that the ability of a Röthlisberger channel to adjust its size to the prevailing hydraulic conditions can contribute to the hysteresis in the velocity‐discharge relationships. However, using plausible parameter values, R channel hydraulics alone is not satisfactory in reproducing the magnitude of observed transit velocities. The model further confirms that retardation of the tracer in the tributary moulin due to inflow modulation has major effects on transit velocities both in magnitude and timing. With appropriate assumptions on channel sinuosity and moulin size, a combination of both mechanisms can be found that is capable of reproducing the observed transit velocities.

Modulation of proprioceptive inflow when initiating a step influences postural adjustments

A synergistic inclination of the whole body towards the supporting leg is required when producing a stepping movement. It serves to shift the centre of mass towards the stance foot. While the importance of sensory information in the setting of this postural adjustment is undisputed, it is currently unknown the extent to which proprioceptive afferences (Ia) give rise to postural regulation during stepping movement when the availability of other sensory information relying on static linear acceleration (gravity) is no longer sensed in microgravity. We tested this possibility asking subjects to step forward with their eyes closed in normo- and microgravity environments. At the onset of the stepping movement, we vibrated the ankle muscles acting in the lateral direction to induce modification of the afferent inflow (Ia fibres). Vibration-evoked movement (perceived movement) was in the same direction as the forthcoming body shift towards the supporting side (current movement). A control condition was performed without vibration. In both environments, when vibration was applied, the hip shift towards the supporting side decreased. These postural modifications occurred, however, earlier in normogravity before initiating the stepping movement than in microgravity (i.e. during the completion of the stepping movement). Our results suggest that proprioceptive information induced by vibration and afferent inflow related to body movement exaggerated sense of movement. This biased perception led to the postural adjustment decrease. We propose that in both environments, proprioceptive inflow enables the subject to scale the postural adjustments, provided that body motion-induced afferences are present to activate this postural control.

Impact of a Left-Lobe Graft Without Modulation of Portal Flow in Adult-to-Adult Living Donor Liver Transplantation

In adult-to-adult living donor liver transplantation (LDLT), left-lobe grafts can sometimes be small-for-size. Although attempts have been made to prevent graft overperfusion through modulation of portal inflow, the optimal portal venous circulation for a liver graft is still unclear. Hepatic hemodynamics were analyzed with reference to graft function and outcome in 19 consecutive adult-to-adult LDLTs using left-lobe grafts without modulation of graft portal inflow. Overall mean graft volume (GV) was 398 g, which was equivalent to 37.8% of the recipient standard liver volume (SV). The GV/SV ratio was less than 40% in 13 of the 19 recipients. Overall mean recipient portal vein flow (PVF) was much higher than the left PVF in the donors. The mean portal contribution to the graft was markedly increased to 89%. Average daily volume of ascites revealed a significant correlation with portal vein pressure, and not with PVF. When PVP exceeds 25 mmHg after transplantation, modulation of portal inflow might be required in order to improve the early postoperative outcome. Although the study population was small and contained several patients suffering from tumors or metabolic disease, all 19 patients made good progress and the 1-year graft and patient survival rate were 100%. A GV/SV ratio of less than 40% or PVF of more than 260 mL/min/100 g graft weight does not contraindicate transplantation, nor is it necessarily associated with a poor outcome. Left-lobe graft LDLT is still an important treatment option for adult patients.

L/I‐5 Hemodynamics in adult‐to‐adult living donor liver transplantation: personal experience

Introduction: The interaction and modulation of inflow and outflow in adult living donor liver transplants (LDLTs) is very complex; small‐for‐size syndrome (SFSS) still represents the most dangerous complication in this regard.Methods: We measured the liver hemodynamics, in both donors and recipients, in 21 LDLTs.Measured parameters included hepatic artery flow (HAF) and portal vein flow (PVF) (ml/min/100 g ), PVF/HAF ratio (PAR) by means of transit time flowmeter, and portal vein pressure (PVP). For all recipients, we used a maximalized outflow with blanket technique (with MHV in 19). According to the results, in order to prevent SFSS, we performed either splenic artery ligation (SAL) or modified porto‐caval‐shunt (PCS) or intrarterial PGI2 + steroid infusion.Results: The median reference values in donors were as follows: HAF, 26.5 ml/min/100g; PVF, 78.5 ml/min/100g; and PAR, 2.5. At total of 5 patients underwent SAL because of GBWR ≤ 0.9; HAF decreased from 32% to 82% in 4; PVF increased from 300% to 400% in 3; PAR was &gt; 20 in 2. None of these patients developed SFSS. Two patients underwent intraarterial infusion of PGI2 + steroids over 14 days because of a PVF increase ≥ 300%, HAF decrease of 82% in 1, PAR 66 and 22, PVP &gt; 20 in 1, and impossibility of SAL. No SFSS was observed. One patient underwent a modified PCS because of PVF increase of 250%, HAF decrease of 70%, PAR 27. No complications occurred.Discusssion: Strength monitoring of liver hemodynamics at pre‐, intra‐, and posthepatic level allows specific management at the different levels in order to prevent SFSS and graft loss.

Nerve specific modulation of somatosensory inflow to cerebral cortex during submaximal sustained contraction in first dorsal interosseous muscle

Modulation of the early component (latency ∼20–30 ms) of somatosensory evoked potentials (SEPs) and that of the middle and long latency cutaneous reflexes was examined in 13 healthy volunteers during fatiguing submaximal voluntary contraction (20% maximum) of the first dorsal interosseous muscle (FDI). The SEP was evoked by stimulating the ulnar nerve (U-SEP), a mixed nerve innervating the FDI muscle, the purely cutaneous nerves of the 2nd digit (D2-SEP) and the 5th digit (D5-SEP). The cutaneous reflex was recorded concurrently with D2-SEP. The size of D2- and D5-SEP significantly decreased during fatiguing contraction as compared to rest, and the decrease in both SEPs persisted throughout fatiguing contraction. In contrast, the significant decrease in the gating of U-SEP disappeared during the latter phase of fatiguing contraction. The ratio (reflex response/background EMG) of excitatory E2 (latency ∼60–90 ms) and E3 (∼120–180 ms) responses following D2 stimulation significantly increased during the middle or latter phase of fatiguing contraction. In contrast, no significant changes in inhibitory I1 and I2 were seen. The release of the attenuation of U-SEP and a constant gating of the D2- and D5-SEP suggests that the brain selectively permits the muscular afferent inflow into the cortex during fatiguing contraction. An increase in the E2 and E3 reflex ratio of cutaneous reflexes during the later phase of fatiguing contraction most likely results from an increase in the excitability of the motor cortex.

Living Donor Liver Transplantation with Left Liver Graft

Small-for-size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year-old patient underwent to LDLT at our institution. During the anhepatic phase a porto-systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post-operative course was characterized by good graft function. Small-for-size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult-to-adult living donor liver transplantation.

Diurnal variability of subglacial drainage conditions as revealed by tracer experiments

The morphology of the drainage system of Unteraargletscher, Switzerland, and the diurnal variability of drainage conditions were investigated by conducting a series of tracer tests over a number of discharge cycles during the ablation season 2000. Dye injections into a moulin were repeated at intervals of a few hours and were accompanied by simultaneous measurements of discharge of supraglacial meltwater draining into the moulin and bulk runoff in the proglacial stream. Fast transit velocities in conjunction with low dispersion values suggest that the tracer was routed through a hydraulically efficient, channelized drainage system. However, detailed analyses reveal a large diurnal variability in terms of transit velocity and dispersion coefficient. This finding underlines the difficulty of detecting a possible drainage system evolution based on single tracer tests conducted at coarse temporal intervals. Furthermore, the obtained velocity‐discharge relationships display pronounced hysteresis. We suggest that the evolution of the cross‐sectional area of an ice‐walled conduit and the modulation of inflow at the junction of a tributary moulin to a main subglacial channel are responsible for the observed behavior.

Liver transplantation in pigs with small-for-size grafts: effect of portocaval shunt

Small-for-size livers are associated with graft dysfunction, probably due to portal hyperperfusion. Modulation of the recipient portal inflow is a new option in these cases. This article sought to analyze the effect of portocaval shunt in small-for-size liver grafts in pigs. Twelve liver transplants were performed in white pigs. The donors' mean weight was 10 kg and the recipient's mean weight was 34 kg. In all cases a standard technique was utilized. A portocaval shunt was added on the back-table in six cases. One hour after the procedure, the livers were sent for histologic examination. In all six cases without a portocaval shunt, the livers showed hemorrhagic necrosis, which was not observed in any of the six livers with a portocaval shunt. In small-for-size liver grafts in pigs, a portocaval shunt prevents hemorrhagic necrosis.

Modulation of afferent inflow during the control of balancing tasks using the lower limbs

This study investigated the control of sensory inputs during the performance of an inverted-pendulum balancing task. Experiments were conducted to examine modulation of proprioceptive inputs during balance tasks of varying difficulty. It was hypothesized that proprioceptive inputs to both spinal and cortical levels would be facilitated during a challenged balance task. In contrast, during challenged balance control, results revealed task-specific facilitation of sensory inputs to the cortex and inhibition of the spinal reflex pathway. Observations of increased transmission of proprioceptive inputs to the cortex and decreased transmission at the spinal level suggest that the cortex plays an important role in challenged balance, whereas the role for the spinal stretch reflex appears to be less important.

Mechanisms of spinal cord stimulation in neuropathic pain

The understanding of the mode of action of spinal cord stimulation (SCS) as treatment of neuropathic pain is still fragmentary. SCS evolved from the gate-control theory postulating a spinal modulation of noxious inflow, but there is little evidence that SCS influences nociceptive pain; pain relief in peripheral vascular disease and angina pectoris is presumably secondary to other SCS effects. In man, SCS may effectively abolish both continuous and evoked pain (tactile/thermal allodynia) whereas induced, acute nociceptive pain is unaffected. Recent SCS studies performed on rat models of mononeuropathy have demonstrated a preferential effect on AB fiber mediated functions, and the hyperexcitability of wide-dynamic-range dorsal horn neurons was attenuated. These effects were coupled to increased release of CABA and reduced glutamate and aspartate release in the dorsal horn. Intrathecal administration of GABA, baclofen and adenosine enhanced the SCS effect on tactile allodynia even in previously non-responsive rats. Preliminary results indicate that gabapentin may have a similar effect. GABAergic and adenosine-related mechanisms conceivably represent only examples of a number of putative receptor systems involved in SCS. Clinical trials have been initiated exploring the possibility to improve the efficacy of SCS by concomitant pharmacotherapy. [Neurol Res 2000; 22: 28S-292]