Splanchnic Blood Pooling Research Articles

Potential for Gut Peptide-Based Therapy in Postprandial Hypotension.

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.

Similar Cerebral Blood Flow and Autonomic Responses to Upright Tilt Test in Adult Patients With Different Hemodynamic Mechanisms Leading to Reflex Syncope.

Although the underlying mechanisms of reflex syncope remain under debate, there is evidence that it results from decreased cardiac output related to splanchnic blood pooling or a fall in systemic vascular resistance. The aim was to evaluate the response of cerebrovascular and autonomic variables to passive orthostatic challenge in adult patients with different mechanisms leading to reflex syncope. The study included 30 subjects (66% women, mean age 34 ± 14 years) who suffered a hemodynamic collapse during a drug-free head-up tilt test. They were categorized into three groups according to their hemodynamic cardiovascular response during the head-up tilt test: (1) reduced cardiac output (patients, n = 10), (2) reduced systemic vascular resistance (patients, n = 10), and (3) reduced cardiac output and systemic vascular resistance, (reduced cardiac output reduced systemic vascular resistance patients, n = 10). Cardiovascular and cerebrovascular dynamics, as well as autonomic variables, were noninvasively assessed during the head-up tilt test and median values were calculated at baseline and throughout the three phases of the tilt. At baseline, the reduced systemic vascular resistance group had lower cardiac output and higher total peripheral resistance index and a sustained increase of heart rate throughout the head-up tilt test in comparison to the other groups. Cerebrovascular dynamics and autonomic variables showed no difference among groups throughout the test. Compared with baseline, these variables had similar percentual change during the orthostatic challenge. Although different cardiovascular hemodynamic mechanisms of reflex syncope exist in adult patients, cerebrovascular hypoperfusion and autonomic modulation occur to a similar extent.

Mechanisms of Vasovagal Syncope in the Young: Reduced Systemic Vascular Resistance Versus Reduced Cardiac Output.

BackgroundSyncope is a sudden transient loss of consciousness and postural tone caused by cerebral hypoperfusion. The most common form is vasovagal syncope (VVS). Presyncopal progressive early hypotension in older VVS patients is caused by reduced cardiac output (CO); younger patients have reduced systemic vascular resistance (SVR). Using a priori criteria for reduced CO (↓CO) and SVR (↓SVR), we studied 48 recurrent young fainters comparing subgroups of VVS with VVS‐↓CO, VVS‐↓SVR, and both VVS‐↓CO&↓SVR.Methods and ResultsSubjects were studied supine and during 70‐degrere upright tilt with a Finometer to continuously measure blood pressure, CO, and SVR and impedance plethysmography to estimate thoracic, splanchnic, pelvic, and calf blood volumes, blood flows, and vascular resistances and electrocardiogram to measure heart rate and rhythm. Central blood volume was decreased in all VVS compared to control. VVS‐↓CO was associated with decreased splanchnic blood flow and increased splanchnic blood pooling compared to control. Seventy‐five percent of VVS patients had reduced SVR, including 23% who also had reduced CO. Many VVS‐↓SVR increased CO during tilt, with no difference in splanchnic pooling, caused by significant increases in splanchnic blood flow and reduced splanchnic resistance. VVS‐↓CO&↓SVR patients had splanchnic pooling comparable to VVS‐↓CO patients, but SVR comparable to VVS‐↓SVR. Splanchnic vasodilation was reduced, compared to VVS‐↓SVR, and venomotor properties were similar to control. Combined splanchnic pooling and reduced SVR produced the earliest faints among the VVS groups.ConclusionsBoth ↓CO and ↓SVR occur in young VVS patients. ↓SVR is predominant in VVS and is caused by impaired splanchnic vasoconstriction.

PP.14.06

Objective: Postprandial hypotension is a common disorder of blood pressure regulation in the elderly, associated with falls and syncope. The pathophysiological mechanism is thought to be related to impaired vascular compensation for splanchnic blood pooling after a meal. Several studies have suggested that caffeine, acarbose, and Guar gum can improve reduction of postprandial blood pressure (BP). However, these treatments may not necessarily be effective in the patients with symptomatic PPH. Recently, we first experienced the effect of Theophylline on PPH which categorized as xanthine like caffeine. In this study, we investigated the mechanism of action of Theophylline.Design and method: The case is an 92-year-old man under outpatient care for hypertension was admitted to Aoyama Hospital, Tokyo Women's Medical University, Tokyo, Japan, for the investigation and treatment of faintness after breakfast in December 2014. Ambulatory BP monitoring (ABPM) over a 24 hours period showed a decrease in systolic BP of more than 20 mmHg within 2 hours after meal, leading to the diagnosis of PPH. We performed meal test during two days hospitalization. Measurement items were blood pressure, blood test including plasma levels of glucose, insulin, noradrenaline (NA) and renin activity (PRA) before and after breakfast. At the first day, we tested in control (without Theopylline). Next day, we evaluate the effects of Theopylline on PPH. Four hundred mg of Theopylline was given at once before going to sleep at the first day Results: In control, the systolic blood pressure (SBP) decreased from 134mmHg to 97mmHg at 90 minutes after eating. Surprisingly, Theophylline maintained to the drop of SBP from 114mmHg to 97mmHg. Serum NA and PRA levels showed marked elevation under Theophylline administration. Moreover, after taking Theophylline, the patient's symptoms had disappeared Conclusions: We report a case of postprandial hypotension improved by theophylline administration. The part of mechanism may involve the effects of Theopylline as an Adenosine receptor antagonist.

Anti‐VEGFR agents ameliorate hepatic venous dysregulation/microcirculatory dysfunction, splanchnic venous pooling and ascites of NASH‐cirrhotic rat

Antivascular endothelial growth factor receptor (VEGFR) agents improve hepatic fibrosis and portal hypertension in cirrhosis. Detail interactions among recruited/activated leucocytes, hepatic angiogenesis and fibrogenesis, splanchnic blood pooling, decreased hepatic veins to fluctuated splanchnic blood volume (hepatic venous dysregulation), portal hypertensive syndrome and ascites have never explored in cirrhosis. Our study used two anti-VEGFR agents - brivanib and sorafenib - to elucidate the relationship between above abnormalities of nonalcoholic steatohepatitis (NASH)-cirrhotic rats. NASH-cirrhotic rats received 2-week brivanib, sorafenib or vehicle (NASH-cirrhotic+briv, NASH-cirrhotic+soraf and NASH-cirrhotic rats) were included for various measurements. In comparison with NASH-cirrhotic rats, significant decreased plasma VEGF, fibroblast growth factor, platelet-derived growth factor, hepatic tumour necrosis factor (TNFα), IL-1β, IL-6, IL-17 were accompanied by decreased leucocyte mass/activity ((99 m) Tc-phytate and (18) F-FDG SPECT/PET/CT scans), hepatic leucocytes recruitment/microvascular density (fluorescence-enhanced intravital microscopy) and hydroxyproline content, and increased hepatic blood flow in NASH-cirrhotic+briv and NASH-cirrhotic+soraf rats. In addition, increased hepatic microvasculatures compliance-related improved buffering effect of portal vein to acute mannitol infusion was associated with decreased circulating nitric oxide and aldosterone, plasma volume expansion (dye dilution method), splanchnic blood pooling ((99 m) Tc-RBC SPECT/PET/CT scans), peripheral hypotension, portal hypertension and ascites in brivanib and sorafenib-treated NASH-cirrhotic rats. Besides antifibrotic, antiangiogenic and portal hypertensive effects, chronic antagonism of anti-VEGFR with brivanib and sorafenib improves hepatic blood flow, hepatic venous dysregulation, inhibits leucocytes recruitment/activation, splanchnic blood pooling and ascites formation in NASH-cirrhotic rats. Thus, brivanib and sorafenib might be ideal therapeutic agents in cirrhotic patients suffering from severe haemodynamic disarrangement and ascites.

Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow.

Previous investigations have demonstrated a subset of postural tachycardia syndrome (POTS) patients characterized by normal peripheral resistance and blood volume while supine but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such "normal-flow" POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14-23 yr of age) and compared them with 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain-gauge occlusion plethysmography, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide (Pet(CO2)), and impedance plethysmographic indexes of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70 degrees. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTS(HC)) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POTS(HC) and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POTS(HC) compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTS(HC).

Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome

Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising "normal-flow POTS" patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20 degrees, 35 degrees, and 70 degrees. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels.

Postprandial middle cerebral arterial vasoconstriction in cirrhotic patients. A placebo, controlled evaluation

Background/Aims: The objective of this study was to determine whether cerebral arterial vasoconstriction occurs in relation to postprandial splanchnic blood pooling in cirrhotic patients.Methods: The pulsatility and the resistive indexes and blood flow in the middle cerebral artery were measured by magnetic resonance imaging in 21 cirrhotics and 14 controls. These measurements were repeated 30 min after ingestion of a 400 kcal liquid meal or placebo. Seven controls and 14 patients received the meal, and seven controls and seven patients received placebo.Results: In the fasting conditions, cirrhotics had a greater pulsatility index (0.81±0.10 vs. 0.67±0.05, P<0.001) and a greater resistive index (0.61±0.04 vs. 0.53±0.04, P<0.001) and a lower blood flow (127±42 ml/min vs. 167±37 ml/min, P<0.03) in the middle cerebral artery compared with controls. Meal ingestion significantly increased the pulsatility index (P<0.03) and the resistive index (P<0.01) and decreased blood flow (P<0.03) in the middle cerebral artery in cirrhotics but not in controls. In contrast, placebo ingestion had no effect on the hemodynamic parameters in the middle cerebral artery in the two groups.Conclusions: Results support the hypothesis that middle cerebral arterial vasoconstriction seen in cirrhotic patients is one of the cerebral artery's homeostatic responses to underfilling of the splanchnic arterial circulation.

A Study of the Mechanism of Postprandial Hypotension in Essential Hypertension

In order to elucidate the mechanism of blood pressure control system on patients with essential hypertension (EH), postprandial changes of blood pressure (BP), pulse rate (PR), blood sugar (BS), serum insulin (IRI), plasma norepinephrine (PNE) and renin activity (PRA) were investigated in 60 patients with EH, who were divided into following two groups: 1) 37 EH patients without diabetes mellitus (HN), and 2) 23 EH patients with diabetes mellitus (HD). Twenty-four healthy volunteers (NN) and 13 normotensive diabetic patients (ND) underwent the same study as the EH patients.Systolic and diastolic blood pressure significantly decreased in all groups after ingestion of the test meal, and the postprandial decrease in BP tended to be greater in HN and in HD compaired to their normotensive control groups (NN and ND, respectively). Prolonged hypotensive response to ingestion of the test meal was observed in hypertensive groups (HN and HD). The change in BP after ingestion of the test meal appears to be affected by aging, because the decrease in BP after ingestion of the test meal in elder subjects was greater than that in younger subjects. The decrease in BP induced by the test meal was not associated with the increase in IRI in any group. The maximum increase in PNE, PRA and IRI was followed by a maximum decrease in BP. Ingestion of the test meal induced a significant increase in PNE in two normotensive groups (NN and ND) and in HN, but not in HD. A postprandial increase in PNE was associated with an increase in IRI. Postprandial change in BP was negatively correlated to the change in PNE. An increase in PRA after ingestion of the test meal was observed only in NN. The increase in PRA was accompanied by an increase in IRI.These results suggest that the splanchnic blood pooling after ingestion of the test meal may be important for the postprandial decreases in BP, and that activation of the sympathetic nervous system as well as the renin-angiotensin system, which is probably triggered by baroreceptor stimulation and an increase in circulatory insulin, may play a crucial role in recovery of postprandial decrease in BP. It is possible that an enhanced and prolonged decrease in BP observed in older patients with EH, especially those with diabetes mellitus and hypertension may be attributed to the age-related impairment of the sympathetic nervous system and the renin-angiotensin system.

Postprandial Hypotension in Elderly Patients With Unexplained Syncope

Syncope in older patients may be caused by a variety of disorders, including hypotension, but frequently remains unexplained. Postprandial hypotension is a common disorder of blood pressure regulation in the elderly. To determine the pathogenic mechanisms and potential role of postprandial hypotension in elderly patients with otherwise unexplained syncope. We studied 16 elderly patients with unexplained syncope and nine elderly controls. Blood pressure, heart rate, forearm vascular resistance, plasma norepinephrine level, and cardiac and splanchnic blood volumes were measured before and after a 1680-kJ meal. Eight elderly patients with syncope had postprandial hypotension, with a decline in supine mean arterial blood pressure of 17 +/- 2 mm Hg after a meal (P < .001). The blood pressure remained unchanged after the meal in the other patients with syncope and the controls. In patients with postprandial hypotension, systemic vascular resistance fell after the meal, while it remained unchanged in the other groups. Heart rate and plasma norepinephrine level increased to a similar extent in all three groups. Forearm vascular resistance increased only in the control subjects. Splanchnic blood volume increased by 26% (P < .01) in patients with syncope who had postprandial hypotension and by 22% (P < .01) in control subjects. Splanchnic blood volume remained unchanged in the patients with syncope without postprandial hypotension. Postprandial hypotension may be an important causative factor in elderly patients with unexplained syncope. The evaluation of syncope in elderly patients should therefore include blood pressure measurements surrounding a meal. Elderly patients with syncope who have postprandial hypotension fail to maintain systemic vascular resistance, probably because of splanchnic blood pooling without a compensatory increase in peripheral vascular resistance.

Alternations in liver hemodynamics in an intact porcine model of endotoxin shock

Septic shock decreases preload, increases splanchnic blood pooling and edema formation, and induces hepatic dysfunction. We hypothesized that the hemodynamic effects of endotoxemic shock on the portal venous (PV) and hepatic arterial (HA) vascular beds contribute to this picture. Multipoint pressure-flow relationships were generated to evaluate the slope (resistance or conductance) and effective back pressure (Pback) in each bed in an intact porcine model of endotoxemia. Slope and Pback were determined during endotoxemia over 300 min (n = 8) and compared with sham-treated control studies (n = 5). At time (t) = 60 min, HA slope significantly decreased (P < 0.05) without a change in Pback. The HA buffer response (HABR), defined as a decrease in HA resistance produced by reduction in PV flow (Qpv), was abolished at t = 90 min. The PV Pback significantly increased without a change in PV slope. At t = 300 min, HA slope returned to baseline, and the HABR was present while PV slope and Pback increased (P < 0.05). Fractional flow (flow relative to cardiac output) was constant except for a transient increase in HA fractional flow at t = 60 min. Histological studies showed focal necrosis and hemorrhage without evidence of vasoconstriction or thrombosis. In conclusion, endotoxic shock leads to time-dependent impairment of Qpv with increased PV resistance, causing an increase in splanchnic blood pooling and subsequent decrease in venous return. The HA bed is dilated early with an absent HABR. Later an HABR is present but defined by increased HA resistance for a given Qpv.(ABSTRACT TRUNCATED AT 250 WORDS)

Postprandial hypotension: epidemiology, pathophysiology, and clinical management.

To show the clinical relevance of postprandial hypotension and to review its pathophysiology and management. Articles on postprandial hypotension were identified through MEDLINE and bibliographies of relevant articles. All articles and case reports describing meal-related hypotension in the elderly and in patients with autonomic failure. Postprandial hypotension, defined as a decrease in systolic blood pressure of 20 mm Hg or more, may result in syncope, falls, dizziness, weakness, angina pectoris, and stroke. Postprandial hypotension is distinct from and probably more common than orthostatic hypotension. Because meal-related hypotension is particularly common in older hypertensive patients, it has important implications for the evaluation and management of hypertension. The mechanism of postprandial hypotension is not fully understood. Possible contributors include inadequate sympathetic nervous system compensation for meal-induced splanchnic blood pooling; impairments in baroreflex function; inadequate postprandial increases in cardiac output; and impaired peripheral vasoconstriction, insulin-induced vasodilation, and release of vasodilatory gastrointestinal peptides. Although caffeine is often recommended as treatment for postprandial hypotension, available data do not support its use. Octreotide, a somatostatin analog, has been shown to be effective, but it is expensive and must be given parenterally. All physicians caring for elderly patients should be aware of the hypotensive effects of food intake and should consider postprandial hypotension in the evaluation of syncope, falls, dizziness, and other cerebral ischemic symptoms.

Postprandial hypotension: Microneurographic analysis and treatment with vasopressin

To clarify the mechanism of postprandial hypotension (PPH), we made microneurographic analyses of patients with PPH and 10 healthy controls by recording multi-unit vasoconstrictive impulses of muscle sympathetic nerve activity (MSNA) directly from the tibial nerve fascicles during a glucose tolerance test. Oral intake of 75 grams glucose in 225 ml of water produced significant and prolonged hypotension in all patients and an increase in MSNA in all healthy subjects. Insulin and glucose responses were not significantly correlated with arterial blood pressure reduction. PPH was prevented by an infusion of vasopressin (0.3 U/min) given before glucose intake. These results suggest that PPH is caused by the lack of sympathetic compensation for the systemic hypotensive stress of splanchnic blood pooling that occurs after food ingestion, and that prior treatment with vasopressin reduces the portal venous flow by constricting the splanchnic vessels in patients with PPH.

Equilibre acido-basique et exclusion vasculaire du foie : étude de 30 hépatectomies étendues

The acid-base disorders after hepatic vascular exclusion (HVE) were studied in 30 major liver resections. HVE included portal triad clamping and occlusion of the inferior vena cava below and above the liver, without venous shunt nor cooling. Clamping of the supra-cœliac abdominal aorta (AoC) was associated with HVE in 12 patients. HVE lasted 18 to 65 min (mean 37 min). Liver ischemia and splanchnic blood pooling resulted in metabolic acidosis and hyperlactatemia. In order to prevent this acidosis, prophylactic administration of NaHCO 3 was used during the first 19 cases. This induced significant metabolic alkalosis during HVE and the early postoperative period; increasing experience made us reduce the amount of NaHCO 3. After the release of the clamps, Pa co 2 increased 25% following HVE without AoC (p <0.001) and 53% following HVE with AoC (p <0.001). In an attempt to distinguish between the effects of the metabolic acidosis and the rise of Pa co 2 in the fall of pH which occurred after removal of the clamps, NaHCO 3 was deliberately not given in the last 11 patients. Acidosis appeared to be greater with AoC than without and mainly related to the rise of Pa co 2. A fall of Pa co 2 to its initial value was always followed by the return of pH to the normal range. This study demonstrated the human ability to correct spontaneously the acidosis which followed HVE. The need for NaHCO 3 after HVE reflected a poor haemodynamic state after major liver resection rather than a metabolic consequence of hepatic ischaemia.