Intermittent walking: a potential treatment for older people with postprandial hypotension.

BACKGROUND: Exercise has been proposed as a possible treatment for postprandial hypotension (PPH), yet, its use has not been extensively investigated. This study aimed to determine the effects of intermittent walking on blood pressure (BP) and heart rate (HR) following ingestion of a glucose drink in older people with PPH. METHODS: Thirteen persons with PPH were recruited and studied on 2 randomized days (control, intervention). On both study days, participants ingested 200 mL of water containing 50 g glucose, followed by ambulatory BP and HR monitoring 6 minutely for 60 minutes, then 15 minutely until 120 minutes. On the intervention day, participants walked at their usual pace for 30 m every 30 minutes for 120 minutes. RESULTS: On the control day, significant falls in systolic blood pressure (SBP) (P < .005) and diastolic blood pressure (DBP) (P = .016) were demonstrated between t = 0-120 minutes. On the intervention day, over the same period, there was no significant fall in SBP (P = .520), however, DBP still fell significantly (P = .045). There was a statistically significant difference (P = .005) for the area under the curve for the change in SBP from baseline for the study days but not DBP (P = .716). There was no significant change in HR (control: P = .854; intervention, P = .168) nor between the area under the curve (P = .798) for the change in HR from baseline for the study days. CONCLUSIONS: This study suggests that in older people with PPH, intermittent walking at a usual pace attenuates the fall in SBP after ingestion of a glucose drink.

Effects of varying the inter-meal interval on relationships between antral area, gut hormones and energy intake following a nutrient drink in healthy lean humans.

The aim of this study was to determine: (i) the effects of varying the inter-meal interval on subsequent energy intake, and (ii) temporal relationships between postprandial changes in antral area and gastrointestinal hormone concentrations with energy intake. 16 healthy lean participants (10 M, 6 F) were studied on 4 occasions in randomized fashion. Participants consumed 500ml of water 180min ("control"), or 500ml of a mixed-nutrient drink (750kcal) 30 ("EI-30"), 90 ("EI-90") or 180 ("EI-180") min, prior to a cold, buffet-style meal, from which energy intake was quantified. Antral area was measured using 2D-ultrasound, perceptions of hunger and fullness were scored using visual analogue scales, and blood samples collected at regular intervals for analysis of plasma cholecystokinin (CCK), peptide YY (PYY) and ghrelin concentrations. All nutrient drinks increased antral area, stimulated CCK and PYY, and suppressed ghrelin and energy intake (EI-30: -367±69, EI-90: -291±69, EI-180: -219±72kcal, P<0.05, for all), compared with control. Energy intake was related directly to the length of the inter-meal interval (R=0.33, P<0.01), such that as the inter-meal interval increased, energy intake increased. There was a strong relationship between antral area (R=-0.76, P<0.001), and weaker relationships between CCK (R=-0.36, P<0.01) and PYY (R=-0.34, P<0.01), with the inter-meal interval. In conclusion, energy intake increased as the inter-meal interval increased. This was associated with temporal changes in gastric content (antral area) and plasma gut hormone concentrations.

Comparative effects of variations in duodenal glucose load on glycemic, insulinemic, and incretin responses in healthy young and older subjects.

CONTEXT: Aging is associated with deteriorating glucose tolerance. Studies assessing glucose tolerance and subsequent insulin and incretin hormone release often fail to take into account the rate of gastric emptying when evaluating these responses. OBJECTIVE: Our objective was to determine the comparative effects of variations in the small intestinal glucose load on the glycemic, insulinemic, and incretin responses in healthy young and older subjects. MATERIALS AND METHODS: Twelve healthy young (six males, six females; age 22.2±2.3 yr) and 12 older (six males, six females; age 68.7±1.0 yr) subjects had measurements of blood glucose, serum insulin and plasma incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] and calculations of insulin resistance (homeostatic model assessment) and ß-cell function corrected for insulin sensitivity, before and during intraduodenal infusions of glucose at 1, 2, or 3 kcal/min or saline for 60 minutes. The study was double-blinded and randomized, and performed in the Discipline of Medicine at the Royal Adelaide Hospital. RESULTS: At baseline, blood glucose and serum insulin were slightly higher in the older subjects (P<0.001), whereas GLP-1 and GIP were comparable between groups. In both groups, the glycemic, insulinemic, and GLP-1 responses were dependent on the duodenal glucose load in a nonlinear fashion (P<0.001). The glycemic response was greater (P<0.001) in the older subjects, whereas GLP-1 and GIP responses were comparable between groups. The older subjects were more insulin resistant (P<0.001) and had impaired ß-cell function, particularly at higher glucose loads (P<0.05). CONCLUSION: When glucose is infused into the small intestine at equal rates in healthy young and older subjects, GLP-1 and GIP responses are comparable, indicating that impaired incretin secretion does not account for age-related glucose intolerance.

Effects of variations in duodenal glucose load on blood pressure, heart rate, superior mesenteric artery blood flow and plasma noradrenaline in healthy young and older subjects.

PPH (postprandial hypotension), leading to increased morbidity and mortality, is an important clinical problem, particularly in the elderly and individuals with autonomic dysfunction. The magnitude of the postprandial fall in BP (blood pressure) appears to be dependent on the rate of nutrient entry into the small intestine and may be related to changes in splanchnic blood flow and sympathetic nerve activity. We aimed at determining the comparative effects of different ID (intraduodenal) glucose loads on BP, HR (heart rate), SMA (superior mesenteric artery) flow and vascular conductance and plasma NA (noradrenaline) in 'young' and 'older' subjects. A total of 12 'young' (six male and six female; age, 22.2±2.3 years) and 12 'older' (six male and six female; age, 68.7±1.0 years) subjects, the latter who have been studied previously [Vanis, Gentilcore, Rayner, Wishart, Horowitz, Feinle-Bisset and Jones (2011) Am. J. Physiol. Regul. Integr. Comp. Physiol., 300, R1524-R1531], had measurements of BP, HR, SMA flow and plasma NA before, and during, ID infusions of glucose at 1, 2 or 3 kcal/min ('G1', 'G2' and 'G3') (where 1 kcal≈4.184 J), or 'S' (saline) for 60 min. In 'young' subjects, there was no change in BP during any of the four infusions. In contrast, in 'older' subjects, SBP (systolic BP) fell during 'G2', and 'G3' (P<0.005 for both), but not during 'S' or 'G1'. In 'young' and 'older' subjects HR increased during 'G2' (P<0.05) and 'G3' (P<0.001), a response that was greater (P<0.05) in the young, but not during 'S' or 'G1'. The rise in SMA flow and vascular conductance in response to ID glucose were load-dependent in both 'young' and 'older' subjects (P<0.001 for all), with no difference between them. Plasma NA rose in response to 'G2' and 'G3' (P<0.05) in the young, but in 'G3' (P<0.05) only in the 'older' subjects, with no difference between them. Hence, in response to small intestinal glucose infusions at 1, 2 and 3 kcal/min, 'older', but not 'young', subjects exhibit a comparable fall in BP in response to the two higher glucose loads, which may reflect an inadequate, compensatory, rise in HR, in the 'older' subjects, but not a greater increase in SMA conductance.

Effects of variations in intragastric volume on blood pressure and splanchnic blood flow during intraduodenal glucose infusion in healthy older subjects.

The postprandial reduction in blood pressure (BP) is triggered by the interaction of nutrients with the small intestine and associated with an increase in splanchnic blood flow. Gastric distension may attenuate the postprandial fall in BP. The aim of this study was to determine the effects of differences in intragastric volume, including distension at a low (100 ml) volume, on BP and superior mesenteric artery (SMA) blood flow responses to intraduodenal glucose in healthy older subjects. BP and heart rate (HR; automated device), SMA blood flow (Doppler ultrasound), mesenteric vascular resistance (MVR), and plasma norepinephrine of nine male subjects (65-75 yr old) were measured after an overnight fast on 4 separate days in random order. On each day, subjects were intubated with a nasoduodenal catheter, incorporating a duodenal infusion port, and orally with a second catheter, incorporating a barostat bag, positioned in the fundus. Each subject received a 60-min (t = 0-60 min) intraduodenal glucose infusion (3 kcal/min) and gastric distension at a volume of 1) 0 ml (V0), 2) 100 ml (V100), 3) 300 ml (V300), or 4) 500 ml (V500). Systolic BP fell (P < 0.05) during V0, but not during V100, V300, or V500. In contrast, HR (P < 0.01) and SMA blood flow (P < 0.001) increased and MVR decreased (P < 0.05) comparably on all 4 days. Plasma norepinephrine rose (P < 0.01) in response to intraduodenal glucose, with no difference between the four treatments. There was a relationship between the areas under the curve for the change in systolic BP from baseline with intragastric volume (r = 0.60, P < 0.001). In conclusion, low-volume (≤100 ml) gastric distension has the capacity to abolish the fall in BP induced by intraduodenal glucose in healthy older subjects without affecting SMA blood flow or MVR. These observations support the concept that nonnutrient gastric distension prior to a meal has potential therapeutic applications in the management of postprandial hypotension.

The alpha (α)-glucosidase inhibitor, acarbose, attenuates the blood pressure and splanchnic blood flow responses to intraduodenal sucrose in older adults.

BACKGROUND: Postprandial hypotension is an important problem in the elderly and may be triggered by the increase in splanchnic blood flow induced by a meal. Acarbose attenuates the fall in blood pressure (BP) induced by oral sucrose and may be useful in the management of postprandial hypotension. It is not known whether the effect of acarbose on postprandial BP reflects slowing of gastric emptying and/or carbohydrate absorption nor whether acarbose affects splanchnic blood flow. We examined the effects of intraduodenal (ID) acarbose on the BP, heart rate, superior mesenteric artery (SMA) flow, and glycemic and insulin responses to ID sucrose in older participants--this approach excluded any "gastric" effect of acarbose. METHODS: Eight healthy participants (four male and four female, age 66-77 years) received an ID infusion of sucrose (~6 kcal/min), with or without acarbose (100 mg), over 60 minutes. BP, heart rate, SMA flow, blood glucose, and serum insulin were measured. RESULTS: Acarbose markedly attenuated the falls in systolic (p < .01) and diastolic (p < .05) BP and rises in heart rate (p < .05), SMA flow (p < .05), blood glucose (p < .01), and serum insulin (p < .05). The maximum fall in systolic BP and peak SMA flow was inversely related on the control day (r(2) = -.53, p < .05) but not with acarbose (r(2) = .03, p = .70). CONCLUSIONS: We conclude that in healthy older participants receiving ID sucrose, (a) acarbose markedly attenuates the hypotensive response by slowing carbohydrate absorption and attenuating the rise in splanchnic blood flow and (b) the fall in BP is related to the concomitant increase in SMA flow.

The oligosaccharide α-cyclodextrin has modest effects to slow gastric emptying and modify the glycaemic response to sucrose in healthy older adults.

In healthy older subjects, the glycaemic response to carbohydrate-containing meals is dependent on gastric emptying and intestinal absorption; when the latter is slowed, the magnitude of the rise in glucose is attenuated. The oligosaccharide α-cyclodextrin has been reported to diminish the glycaemic response to starch in young adults; this effect has been attributed to the inhibition of pancreatic amylase. We examined the effects of α-cyclodextrin on gastric emptying of, and the glycaemic and insulinaemic responses to, oral sucrose in healthy older subjects; as sucrose is hydrolysed by intestinal disaccharides, any effect(s) of α-cyclodextrin would not be attributable to amylase inhibition. A total of ten subjects (seven males and three females, age 68-76 years) were studied on 2 d. Gastric emptying, blood glucose and serum insulin were measured after ingestion of a 300 ml drink containing 100 g sucrose, labelled with (99m)Tc-sulphur colloid, with or without 10 g α-cyclodextrin. Gastric emptying was slowed slightly by α-cyclodextrin; this effect was evident between 135 and 195 min and was associated with a slight increase (P < 0·05) in distal stomach retention. After α-cyclodextrin, blood glucose was slightly less (P < 0·05) at 60 min, and serum insulin was less (P < 0·0005) at 90 and 120 min. There was no difference in the incremental areas under the curve (iAUC) for blood glucose, but there was a trend for the iAUC for serum insulin to be lower (P = 0·09) after α-cyclodextrin. We conclude that in a dose of 10 g, α-cyclodextrin has modest effects to slow gastric emptying of, and modify the glycaemic and insulinaemic responses to, oral sucrose, probably due to delayed intestinal carbohydrate absorption.

Effects of small intestinal glucose load on blood pressure, splanchnic blood flow, glycemia, and GLP-1 release in healthy older subjects.

Postprandial hypotension is an important problem, particularly in the elderly. The fall in blood pressure is dependent on small intestinal glucose delivery and, possibly, changes in splanchnic blood flow, the release of glucagon-like peptide-1 (GLP-1), and sympathetic nerve activity. We aimed to determine in healthy older subjects, the effects of variations in small intestinal glucose load on blood pressure, superior mesenteric artery flow, GLP-1, and noradrenaline. Twelve subjects (6 male, 6 female; ages 65-76 yr) were studied on four separate occasions, in double-blind, randomized order. On each day, subjects were intubated via an anesthetized nostril, with a nasoduodenal catheter, and received an intraduodenal infusion of either saline (0.9%) or glucose at a rate of 1, 2, or 3 kcal/min (G1, G2, G3, respectively), for 60 min (t = 0-60 min). Between t = 0 and 60 min, there were falls in systolic and diastolic blood pressure following G2 and G3 (P = 0.003 and P < 0.001, respectively), but no change during saline or G1. Superior mesenteric artery flow increased slightly during G1 (P = 0.01) and substantially during G2 (P < 0.001) and G3 (P < 0.001), but not during saline. The GLP-1 response to G3 was much greater (P < 0.001) than to G2 and G1. Noradrenaline increased (P < 0.05) only during G3. In conclusion, in healthy older subjects the duodenal glucose load needs to be > 1 kcal/min to elicit a significant fall in blood pressure, while the response may be maximal when the rate is 2 kcal/min. These observations have implications for the therapeutic strategies to manage postprandial hypotension by modulating gastric emptying.

Orlistat accentuates the fat-induced fall in blood pressure in older adults.

Postprandial hypotension may be influenced by the digestion of fat. The aim of the present study was to evaluate the hypothesis that products of fat digestion mediate the hypotensive response to fat. In part A of the study, nine healthy older subjects were studied on three separate occasions in randomised order. Blood pressure, heart rate (HR), plasma TAG and gastric emptying were measured following the ingestion of equivolaemic drinks: (1) 300 ml of high-fat drink (88 % fat); (2) fat drink mixed with 120 mg orlistat (lipase inhibitor); (3) water (control). In part B of the study, ten healthy older subjects were studied on two separate occasions. Blood pressure, HR, plasma TAG and superior mesenteric artery flow were measured during 90 min intraduodenal infusions of 10 % intralipid (2·7 ml/min), with and without 120 mg orlistat. Oral fat ingestion was associated with decreases in systolic and diastolic blood pressures (both P = 0·0001) that were greater when orlistat was co-administered (both P < 0·05), and an increase in HR (P = 0·0001) that was inhibited by orlistat co-administration (P < 0·03). Gastric emptying was slowed by oral fat digestion, and orlistat administration inhibited this slowing (P < 0·04). Intraduodenal fat infusion was not associated with changes in blood pressure but increased HR (P < 0·0001), an effect attenuated by orlistat (P < 0·05). In conclusion, orlistat potentiates the hypotensive response to oral fat in older adults, possibly as a result of faster gastric emptying of fat. The results do not support a role for fat digestion in lowering blood pressure.

Comparative effects of glucose and xylose on blood pressure, gastric emptying and incretin hormones in healthy older subjects.

Postprandial hypotension is an important disorder for which current management is suboptimal. In healthy older subjects, oral and small-intestinal glucose administration decreases blood pressure (BP), and the magnitude of the reduction is dependent on the rate of glucose entry into the small intestine and, possibly, the release of glucagon-like peptide-1 (GLP-1). There is little information about the effects of other carbohydrates, particularly those poorly absorbed, on BP. The aim of the present study was to compare the effects of drinks containing xylose, glucose or water alone on BP, gastric emptying (GE), incretin hormone secretion, glycaemia and insulinaemia in healthy older subjects. A total of eight healthy older subjects (aged 65-75 years) had simultaneous measurements of BP (DINAMAP), GE (three-dimensional ultrasound), blood glucose, serum insulin, GLP-1 and glucose-dependent insulinotropic peptide (GIP), on three separate occasions, in a double-blind, randomised order. On each day, subjects consumed a 300 ml drink of water, glucose (50 g) or d-xylose (50 g). Glucose (P = 0·02), but not xylose (P = 0·63), was associated with a fall in BP. There was no difference in the GE of glucose and xylose (P = 0·47); both emptied slower than water (P < 0·001). Xylose had minimal effects on blood glucose, serum insulin or serum GIP, but was more potent than glucose in stimulating GLP-1 (P = 0·002). In conclusion, in healthy older subjects, xylose empties from the stomach at the same rate as glucose, but has no effect on BP, possibly because it is a potent stimulus for GLP-1 release. Xylose may be considered as an alternative sweetener to glucose in the management of postprandial hypotension.

Effects of gastric distension on blood pressure and superior mesenteric artery blood flow responses to intraduodenal glucose in healthy older subjects.

Postprandial hypotension occurs frequently and is associated with increased morbidity. Gastric distension may attenuate the postprandial fall in blood pressure (BP). Using a barostat, we sought to determine the effects of gastric distension on BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow responses to intraduodenal glucose in eight (6 men, 2 women) healthy older (65-75 yr old) subjects. BP and HR were measured using an automated device and SMA blood flow was measured using Doppler ultrasound on 4 days in random order. SMA blood flow was calculated using the radius of the SMA and time-averaged mean velocity. Subjects were intubated with a nasoduodenal catheter incorporating a duodenal infusion port. On 2 of the 4 days, they were intubated orally with a second catheter, incorporating a barostat bag, positioned in the fundus and set at 8 mmHg above minimal distending pressure. Each subject received a 60-min (0-60 min) intraduodenal infusion of glucose (3 kcal/min) or saline (0.9%); therefore, the four study conditions were as follows: intraduodenal glucose + barostat (glucose + distension), intraduodenal saline + barostat (saline + distension), intraduodenal glucose (glucose), and intraduodenal saline (saline). Systolic and diastolic BP fell during glucose compared with saline (P = 0.05 and P = 0.003, respectively) and glucose + distension (P = 0.01 and P = 0.05, respectively) and increased during saline + distension compared with saline (P = 0.04 and P = 0.006, respectively). The maximum changes in systolic BP were -14 +/- 5, +11 +/- 2, -3 +/- 4, and +15 +/- 3 mmHg for glucose, saline, glucose + distension, and saline + distension, respectively. There was an increase in HR during glucose and glucose + distension (maximum rise = 14 +/- 2 and 14 +/- 3 beats/min, respectively), but not during saline or saline + distension. SMA blood flow increased during glucose and glucose + distension (2,388 +/- 365 and 1,673 +/- 187 ml/min, respectively), but not during saline, and tended to decrease during saline + distension (821 +/- 115 and 864 +/- 116 ml/min, respectively). In conclusion, gastric distension has the capacity to abolish the fall in BP and attenuate the rise in SMA blood flow induced by intraduodenal glucose in healthy older subjects.

Effects of the phases of the menstrual cycle on gastric emptying, glycemia, plasma GLP-1 and insulin, and energy intake in healthy lean women.

There is evidence that the menstrual cycle affects appetite, such that energy intake is lower during the follicular compared with the luteal phase. Gastric emptying influences energy intake, glycemia, and plasma glucagon-like peptide-1 (GLP-1), insulin, and cholecystokinin (CCK) release. We hypothesized that 1) gastric emptying of a glucose drink is slower, and glycemia, plasma hormones, hunger, and energy intake are less, during the follicular compared with the luteal phase; 2) the reduction in the latter parameters during the follicular phase are related to slower gastric emptying; and 3) these parameters are reproducible when assessed twice within a particular phase of the menstrual cycle. Nine healthy, lean women were studied on three separate occasions: twice during the follicular phase (days 6-12) and once during the luteal phase (days 18-24). Following consumption of a 300-ml glucose drink (0.17 g/ml), gastric emptying, blood glucose, plasma hormone concentrations, and hunger were measured for 90 min, after which energy intake at a buffet meal was quantified. During the follicular phase, gastric emptying was slower (P < 0.05), and blood glucose (P < 0.01), plasma GLP-1 and insulin (P < 0.05), hunger (P < 0.01), and energy intake (P < 0.05) were lower compared with the luteal phase, with no differences for CCK or between the two follicular phase visits. There were inverse relationships between energy intake, blood glucose, and plasma GLP-1 and insulin concentrations with the amount of glucose drink remaining in the stomach at t = 90 min (r < -0.6, P < 0.05). In conclusion, in healthy women 1) gastric emptying of glucose is slower, and glycemia, plasma GLP-1 and insulin, hunger, and energy intake are less during the follicular compared with the luteal phase; 2) energy intake, glycemia, and plasma GLP-1 and insulin are related to gastric emptying; and 3) these parameters are reproducible when assessed twice during the follicular phase.

Comparative effects of oral and intraduodenal glucose on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects.

Postprandial hypotension occurs frequently, particularly in the elderly. The magnitude of the fall in blood pressure (BP) and rise in heart rate (HR) in response to enteral glucose are greater when gastric emptying (GE) or small intestinal infusion are more rapid. Meal ingestion is associated with an increase in splanchnic blood flow. In contrast, gastric distension may attenuate the postprandial fall in BP. The aims of this study were to evaluate, in older subjects, the comparative effects of intraduodenal glucose infusion, at a rate similar to GE of oral glucose, on BP, HR, superior mesenteric artery (SMA) flow, and blood glucose. Eight healthy subjects (5 men, 3 women, age 66-75 yr) were studied on two occasions. On day 1, each subject ingested 300 ml of water containing 75 g glucose. GE was quantified by three-dimensional ultrasonography between time t = 0-120 min, and the rate of emptying (kcal/min) was calculated. On day 2, glucose was infused intraduodenally at the same rate as that on day 1. On both days, BP, HR, SMA flow, and blood glucose were measured. The mean GE of oral glucose was 1.3 +/- 0.1 kcal/min. Systolic BP (P < 0.01), SMA flow (P < 0.05), and blood glucose (P < 0.01) were greater and HR less (P < 0.01) after oral, compared with intraduodenal, glucose. There were comparable falls in diastolic BP during the study days (P < 0.01 for both). We conclude that the magnitude of the fall in systolic BP and rise in HR are less after oral, compared with intraduodenal, glucose, presumably reflecting the "protective" effect of gastric distension.

Reproducibility of energy intake, gastric emptying, blood glucose, plasma insulin and cholecystokinin responses in healthy young males.

Gastric emptying, as well as intragastric meal distribution, and gastrointestinal hormones, including cholecystokinin (CCK), play an important role in appetite regulation. The evaluation of gastrointestinal factors regulating food intake is commonly performed in healthy, lean, young male participants. It has, however, been suggested that there is a marked interindividual variability in the effects of nutrient 'preloads' on energy intake in this group. Whether there is significant intraindividual variation in acute energy intake after a nutrient preload, and, if so, how this relates to day-to-day differences in gastric emptying and gastrointestinal hormone release, is unclear. The purpose of the present paper is to evaluate the hypothesis that energy intake after a nutrient preload would be reproducible and associated with reproducible patterns of gastric emptying, intragastric distribution and gastrointestinal hormone release. Fifteen healthy men (age 25 (sem 5) years) consumed a glucose preload (50 g glucose in 300 ml water; 815 kJ) on three occasions. Gastric emptying and intragastric meal distribution (using three-dimensional ultrasound), blood glucose, plasma insulin and CCK concentrations and appetite perceptions were evaluated over 90 min, and energy intake from a cold buffet-style meal was then quantified. Energy intake was highly reproducible within individuals between visits (intraclass correlation coefficient, ri = 0.9). Gastric emptying, intragastric meal distribution, blood glucose, plasma insulin and CCK concentrations and appetite perceptions did not differ between visits (ri>0.7 for all). In healthy males, energy intake is highly reproducible, at least in the short term, and is associated with reproducible patterns of gastric emptying, glycaemia, insulinaemia and CCK release.

Gastric distension attenuates the hypotensive effect of intraduodenal glucose in healthy older subjects.

Postprandial hypotension occurs frequently, and current management is suboptimal. Recent studies suggest that the magnitude of the fall in postprandial blood pressure (BP) may be attenuated by gastric distension. The aim of this study was to determine the effect of gastric distension on the hypotensive response to intraduodenal (ID) glucose. Eight healthy subjects (5 males, 3 females, aged 65-76 years) received an ID infusion of either 1) 50 g glucose in 300 ml saline (ID glucose) over 60 min (t=0-60 min), 2) 50 g glucose in 300 ml saline over 60 min and intragastric (4) infusion of 500 ml water between t=7-10 min (IG water and ID glucose), or 3) ID saline (0.9%) infusion over 60 min and IG infusion of 500 ml water (IG water and ID saline) all followed by ID saline infusion for another 60 min (t=60-120 min) on three separate days. BP and heart rate (HR) were measured. Gastric emptying (GE) of the IG water was quantified by two-dimensional ultrasonography. Between t=0-60 min, systolic and diastolic BP was greater (P<0.05 for both) with IG water and ID saline compared with IG water and ID glucose, and less (P<0.05 for both) with ID glucose compared with IG water and ID glucose. These effects were evident at relatively low IG volumes (approximately 300 ml). GE was faster with IG water and ID saline when compared with IG water and ID glucose. We conclude that, in healthy older subjects, IG administration of water markedly attenuates the hypotensive response to ID glucose, presumably as a result of gastric distension.

Effects of intraduodenal glucose, fat, and protein on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects.

BACKGROUND: Postprandial hypotension frequently occurs in the elderly. The hypotensive response to a meal is triggered by the interaction of nutrients with the small intestine; information relating to the effects of different macronutrients on blood pressure (BP) is limited and inconsistent. OBJECTIVE: The objective of the study was to determine the effects of intraduodenal glucose, fat, and protein on BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow in healthy older subjects. DESIGN: Eight subjects received intraduodenal glucose (64 g), fat (10% oil emulsion), protein (72 g whey), or saline (0.9%) at a rate of 2.7 mL/min for 90 min, followed by intraduodenal saline for 30 min. BP, HR, and SMA blood flow were measured. RESULTS: The falls in systolic BP during infusions of glucose, fat, and protein did not differ significantly (P=0.97); however, the fall occurred significantly earlier during the glucose infusion; (18+/-3.0 min) than during the fat (46+/-11.0 min; P=0.02) and protein 33+/-7 min; P=0.04) infusions. The increases in HR during glucose, fat, and protein infusions (P<0.0001 for all) did not differ significantly. SMA blood flow increased significantly after all infusions (P<0.001 for all), but the increase was significantly (P<0.05) lower after protein than after the other infusions. CONCLUSIONS: Intraduodenal glucose, fat, and protein decrease systolic BP in healthy older subjects, but the onset of the hypotensive response is earlier after glucose, and the effect of protein on SMA blood flow is less than that of the other nutrients.

Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects.

Postprandial hypotension is an important clinical problem, particularly in the elderly. 5-Hydroxytryptamine3 (5-HT3) mechanisms may be important in the regulation of splanchnic blood flow and blood pressure (BP), and in mediating the effects of small intestinal nutrients on gastrointestinal motility. The aims of this study were to evaluate the effects of the 5-HT3 antagonist granisetron on the BP, heart rate (HR), and antropyloroduodenal (APD) motility responses to intraduodenal glucose in healthy older subjects. Ten subjects (5 male, 5 female, aged 65-76 yr) received an intraduodenal glucose infusion (3 kcal/min) for 60 min (t = 0-60 min), followed by intraduodenal saline for a further 60 min (t = 60-120 min) on 2 days. Granisetron (10 microg/kg) or control (saline) was given intravenously at t = -25 min. BP (systolic and diastolic), HR, and APD pressures were measured. Pressure waves in the duodenal channel closest ("local") to the infusion site were quantified separately. During intraduodenal glucose, there were falls in systolic and diastolic BP and a rise in HR (P < 0.0001 for all); granisetron had no effect on these responses. Granisetron suppressed the number and amplitude (P < 0.05 for both) of local duodenal pressures during intraduodenal glucose. Otherwise, the effects of intraduodenal glucose on APD motility did not differ between study days. We conclude that in healthy older subjects, 5-HT3 mechanisms modulate the local duodenal motor effects of, but not the cardiovascular responses to, small intestinal glucose.

Effects of intraduodenal glucose concentration on blood pressure and heart rate in healthy older subjects.

The aims of this study were to determine whether the hypotensive and heart rate responses to small intestinal glucose infusion are dependent on the glucose concentration. Eight healthy subjects, aged 65-78 years, were studied on 3 separate days in random order. Each subject received intraduodenal infusions of 50 g of glucose in either 300 mL (16.7%), 600 mL (8.3%), or 1200 mL (4.1%) of saline (0.9%) at a rate of 3 kcal/min for 60 minutes (t = 0-60 minutes), followed by saline (0.9%) for a further 60 minutes (t = 60-120 minutes). During the infusions, blood pressure (systolic and diastolic) and heart rate were measured every 3 minutes, and blood glucose concentrations every 15 minutes. Systolic and diastolic blood pressure fell (P < .0001), and heart rate and blood glucose increased (P = .0001 for both) over time, during all 3 infusions. Between t = -2-120 minutes, there was no difference in systolic blood pressure (P = .20), diastolic blood pressure (P = .61), or heart rate (P = .09) over the study days. There was also no significant difference in the glycemic response to the infusions. We conclude that in healthy older subjects, glucose concentration does not affect the blood pressure or heart rate responses to intraduodenal glucose and that, therefore, the magnitude of the postprandial fall in blood pressure induced by oral glucose is likely to depend primarily on the small intestinal glucose load.

Postprandial hypotension - novel insights into pathophysiology and therapeutic implications.

Postprandial hypotension is a frequent disorder, occurring in approximately 40% of nursing-home residents, and represents a major cause of morbidity and mortality. Current approaches to management are suboptimal. While it has been generally assumed that ingestion of carbohydrate has the greatest effect, the fall in blood pressure (BP) does not appear to be mediated by the consequent elevations in blood glucose and insulin. Moreover, there is evidence that fat may decrease BP to a comparable extent to carbohydrate, although onset of the response may be slower, and that the response is affected by the type of carbohydrate. It has recently been established that the rate of nutrient delivery from the stomach into the small intestine is an important determinant of the hypotensive response to carbohydrate, so that the magnitude of the fall in BP and rise in heart rate is greater when gastric emptying is relatively more rapid. In both healthy elderly subjects and patients with type 2 diabetes, the fall in BP is attenuated when gastric emptying and small intestinal carbohydrate absorption are slowed by dietary (e.g. guar) or pharmacological (e.g. acarbose) means. Conversely, gastric distension attenuates the postprandial fall in BP. Strategies for the treatment of postprandial hypotension should, therefore, potentially be directed at (i) meal composition, particularly carbohydrate type and content, (ii) slowing gastric emptying and/or small intestinal carbohydrate absorption and/or (iii) increasing postprandial gastric distension.