Changes In Forearm Vascular Resistance Research Articles

Increased Pre- and Post-Meal Free Fatty Acid Levels in Black, Obese Adolescents.

Black adolescents are at increased risk of cardiometabolic disease but have lower fasting triglyceride, which is usually associated with decreased risk. No one has studied racial differences in triglycerides or free fatty acids (FFAs) after a high-fat meal. Oral glucose tolerance testing was used to assess insulin secretion, sensitivity, and disposition index (DI). Endothelial function, triglycerides, FFA, c-reactive protein, interleukin 6 (IL6), and adiponectin were measured both pre- and 3 hr postprandially (McDonald's Big Breakfast(®) and 12 ounce Sprite(®)) in obese adolescents (10-13 years, 9 black and 7 white). Endothelial function was assessed using reactive hyperemic changes in forearm vascular resistance (FVR). Oral glucose tolerance test (OGTT) showed no difference in insulin sensitivity, but blacks tended to have (P = 0.08) higher insulin secretion and had increased DI (P = 0.003). After a high-fat meal, triglycerides increased in both groups (P < 0.001), tended to be lower in blacks compared with whites preprandially (64 ± 33 mg/dL vs 110 ± 80, P = 0.064), and was lower postprandially (112 ± 63 vs 188 ± 112, P = 0.039). Pre- and postprandial FFA (Black: 0.58 ± 0.15 and 0.39 ± 0.18 vs. white: 0.44 ± 0.14 and 0.26 ± 0.06, P = 0.020) and adiponectin (P = 0.002) were increased in blacks. FFA decreased in both groups postprandially (P = 0.002). IL6 increased after the meal (P = 0.022). Endothelial function decreased postprandially (P < 0.02), but this was due to a decrease in preocclusion FVR. These results indicate that differences in fat metabolism are present in both black and white obese adolescents. How these differences explain higher rates of cardiometabolic disease in blacks is unclear.

Endothelial dysfunction and negative emotions in adolescent girls.

Endothelial dysfunction predicts adult cardiovascular disorder and may be associated with negative emotions in adolescents. This study was conducted to determine if hopelessness, hostility, and depressive, anxiety, or conduct disorders were associated with compromised endothelial function and whether those associations were mediated by health risk behaviors. Endothelial function, assessed through brachial artery reactive hyperemia, was measured in a psychopathology enriched sample of 60 15-18-year-old girls. The correlations between hopelessness, hostility, and depressive, anxiety, or conduct disorders and the percent change in forearm vascular resistance (PCFVR) were measured. Possible mediation effects of health risk behaviors were tested. Hopelessness was negatively associated with PCFVR, controlling for race and body mass index. Conduct disorder without any anxiety disorder was associated with better endothelial function. The other negative emotions were not associated with PCFVR. Risky health behaviors were associated with conduct disorder and hopelessness, but not with PCFVR, so there was no evidence of mediation. The main finding was that hopelessness in adolescent girls was associated with endothelial dysfunction. This may indicate that when present, hopelessness places a girl at risk for later cardiovascular disease, whether she has a psychiatric disorder or not. Possible mechanisms for this finding are examined and the surprising finding that conduct disorder is associated with better endothelial function is also discussed. Suggestions for future research are presented.

Ascorbic acid blocks hyperglycemic impairment of endothelial function in adolescents with type 1 diabetes

To determine whether acute ascorbic acid infusions alter the effect of hyperglycemia on endothelial function in adolescents with type 1 diabetes. The forearm blood flow (FBF) reactive hyperemic response to 5 min of upper arm occlusion was studied in eight adolescents with type 1 diabetes during euglycemic and hyperglycemic insulin clamp (40 mU/m2/min) with and without ascorbic acid infusion (3 mg/min). The ratio of post- to preocclusion FBF decreased during hyperglycemia without ascorbic acid (p = 0.013), but did not change during hyperglycemia with ascorbic acid. The changes during hyperglycemia were different between the two studies (p = 0.038). Similar results were found when the percent change in forearm vascular resistance following occlusion was assessed. These results indicate that antioxidant treatment with ascorbic acid blocks acute hyperglycemic impairment of endothelial function in adolescents with type 1 diabetes.

Hyperglycemia Increases Muscle Blood Flow and Alters Endothelial Function in Adolescents with Type 1 Diabetes

Alterations of blood flow and endothelial function precede development of complications in type 1 diabetes. The effects of hyperglycemia on vascular function in early type 1 diabetes are poorly understood. To investigate the effect of hyperglycemia on forearm vascular resistance (FVR) and endothelial function in adolescents with type 1 diabetes, FVR was measured before and after 5 minutes of upper arm arterial occlusion using venous occlusion plethysmography in (1) fasted state, (2) euglycemic state (~90 mg/dL; using 40 mU/m2/min insulin infusion), and (3) hyperglycemic state (~200 mg/dL) in 11 adolescents with type 1 diabetes. Endothelial function was assessed by the change in FVR following occlusion. Seven subjects returned for a repeat study with hyperglycemia replaced by euglycemia. Preocclusion FVR decreased from euglycemia to hyperglycemia (P = 0.003). Postocclusion fall in FVR during hyperglycemia was less than during euglycemia (P = 0.002). These findings were not reproduced when hyperglycemia was replaced with a second euglycemia. These results demonstrate that acute hyperglycemia causes vasodilation and alters endothelial function in adolescents with type 1 diabetes. In addition they have implications for future studies of endothelial function in type 1 diabetes and provide insight into the etiology of macrovascular and microvascular complications of type 1 diabetes.

Do Changes In Vastus Lateralis Muscle Oxygenation Reflect The Leg Vascular Response To Sympathetic Stimulation?

Changes in local muscle oxygenation, measured by near-infrared spectroscopy (NIRS), have been used to assess the vascular response to sympathetic stimulation. Changes in muscle oxygenation have been shown to reflect changes in forearm vascular resistance. If such a relationship existed in the leg, NIRS derived muscle oxygenation could potentially be used as an index of the vascular response to sympathetic stimulation during large muscle mass dynamic exercise in humans. PURPOSE: To determine whether changes in vastus lateralis muscle oxygenation reflect changes in femoral vascular resistance during sympathetic stimulation. METHODS: Healthy, male volunteers (mean ± SD; Age: 25 ± 3 yrs; Height: 175 ± 4 cm; Body Mass: 76 ± 13 kg; n=6) performed a cold-pressor test (CPT) on 3 separate occasions with at least 24 hours between tests. After a 5 min supine baseline period, subjects placed their hand in ice water (-1°C) for 5 min, followed by a 5 min recovery period. Mean arterial pressure (MAP) was calculated on a beat-by-beat basis from the blood pressure waveform using finger photoplethysmography (Finometer; Finapres Medical Systems). Femoral artery blood flow was measured continuously via Doppler ultrasound (Vivid-I; GE Medical). Femoral vascular resistance (FVR; mmHg·mL·min-1) was calculated. Vastus lateralis muscle oxygenation (Tissue oxygenation index (TOI); %) was determined by NIRS (Hamamatsu Photonics, NIRO 200). CPT trials were time-aligned and averaged and the peak response of each variable was calculated as a percent change from the supine baseline value. Differences between the peak changes in TOI and FVR were determined by T-test, whereas the relationship between variables was determined by Pearson Product correlation. RESULTS: The peak decrease in TOI (13 ± 5 %) was significantly lower (p<0.001) than the peak increase in FVR (133 ± 73%). Additionally, the change in TOI was not correlated with the change in FVR (r=0.275, p=0.60). CONCLUSION: These data indicate that the changes in vastus lateralis muscle oxygenation do not reflect the leg vascular response to sympathetic stimulation. Supported by NSERC, Canada.

Angiotensin II contributes to the increased baseline leg vascular resistance in spinal cord-injured individuals

Spinal cord-injured (SCI) individuals demonstrate an increased baseline leg vascular resistance (LVR). In addition, despite the lack of sympathetic control, an increase in LVR is observed during orthostatic challenges. On the basis of the vasoconstrictive characteristics of angiotensin II, we examined the hypothesis that angiotensin II contributes to the LVR at baseline and during head-up tilt (HUT) in SCI individuals. Supine baseline leg and forearm blood flow were measured using venous occlusion plethysmography and leg blood flow during 30° HUT using duplex ultrasound. Measurements were performed before and 4 h after an angiotensin II antagonist (irbesartan, 150 mg) administered in eight SCI individuals and eight age-matched and sex-matched able-bodied controls. Vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. Angiotensin II blockade significantly decreased baseline LVR in SCI individuals (P = 0.02) but not in controls, whereas no changes in forearm vascular resistance were found in both groups. Angiotensin II blockade did not alter the increase in LVR during HUT in SCI individuals nor in controls. Our results indicate that angiotensin II contributes to the increased baseline LVR in SCI individuals. As angiotensin II does not contribute to forearm vascular resistance, the contribution to LVR may relate to the extreme inactivity of the legs in SCI individuals. Angiotensin II does not contribute to the increase in LVR during HUT in SCI individuals nor in controls.

Sympathetic nerve damage as a potential cause of lymphoedema after axillary dissection for breast cancer

The physiological disturbances leading to lymphoedema after breast cancer surgery are poorly understood. Damage to sympathetic nerves during axillary lymph node dissection (ALND), leading to increased capillary fluid filtration, was investigated as a possible contributory factor. The integrity of the upper limb sympathetic nervous system was tested in 36 patients before, and 3 and 12 months after ALND. Forearm vascular resistance (FVR), calculated from forearm blood flow and mean systemic arterial pressure, was measured before and after exposure to lower-body negative pressure. Forearm venous compliance was measured using (99m)Tc-labelled autologous erythrocytes and radionuclide plethysmography before and after cold water immersion of the feet. There were clear changes in FVR and venous compliance in response to sympathetic stimulation but no differences attributable to surgery or between the nine patients who developed lymphoedema and the 27 who did not; nor were there differences between the two arms. There was a trend towards lower preoperative FVR in patients who developed lymphoedema. Lymphoedema is not the result of sympathetic nerve damage sustained during ALND. Preoperative FVR may help predict who will get lymphoedema following this surgery.

Local vasoconstriction in spinal cord-injured and able-bodied individuals

Local vasoconstriction plays an important role in maintaining blood pressure in spinal cord-injured individuals (SCI). We aimed to unravel the mechanisms of local vasoconstriction [venoarteriolar reflex (VAR) and myogenic response] using both limb dependency and cuff inflation in SCI and compare these with control subjects. Limb blood flow was measured in 11 male SCI (age: 24-55 yr old) and 9 male controls (age: 23-56 yr old) using venous occlusion plethysmography in forearm and calf during three levels of 1) limb dependency, and 2) cuff inflation. During limb dependency, vasoconstriction relies on both the VAR and the myogenic response. During cuff inflation, the decrease in blood flow is caused by the VAR and by a decrease in arteriovenous pressure difference, whereas the myogenic response does not play a role. At the highest level of leg dependency, the percent increase in calf vascular resistance (mean arterial pressure/calf blood flow) was more pronounced in SCI than in controls (SCI 186 +/- 53%; controls 51 +/- 17%; P = 0.032). In contrast, during cuff inflation, no differences were found between SCI and controls (SCI 17 +/- 17%; controls 14 +/- 10%). Percent changes in forearm vascular resistance in response to either forearm dependency or forearm cuff inflation were equal in both groups. Thus local vasoconstriction during dependency of the paralyzed leg in SCI is enhanced. The contribution of the VAR to local vasoconstriction does not differ between the groups, since no differences between groups existed for cuff inflation. Therefore, the augmented local vasoconstriction in SCI during leg dependency relies, most likely, on the myogenic response.

10 Insulin Response to Glucose Predicts Endothelial Dysfunction in Adolescence

Background: Insulin resistance is known to affect endothelial function in adults leading to cardiovascular disease. It is important to assess adolescent changes during puberty and how they relate to carbohydrate and insulin physiology. Design/Methods: Strain gauge plethysmography and radial arterial tonometry were used to determine the percent change in forearm vascular resistance (mean arterial pressure/forearm blood flow; reactive hyperemia; RH) following 5 min of upper arm vascular occlusion after overnight fast in 14 healthy Caucasians (age 14.3±2.0 years; BMI 19.8±3.0 kg/m2; mean SD) the frequently sampled intravenous glucose tolerance test, IVGTT, and minimum model were used to assess insulin sensitivity (SI), glucose effectiveness (SG) and acute insulin response to glucose (AIRG). Results: The RH was negatively correlated with AIRG (r=-0.74, p=0.022) and tended to positively correlate with log disposition index (AIRGxSI) (r=0.62, p=0.056) (figure 1). No relations between RH and SG or SI. Conclusions: These results demonstrate that Caucasian adolescents with a high acute insulin response have poorer endothelial function. Thus high insulin levels may impair endothelial function and increase risk of cardiovascular disease. The relationship between DI and RH suggest that even in adolescence there is a close relationship between risk for type 2 diabetes and cardiovascular disease.

The effect of warmth or/and vitamin E supplementation on forearm blood flow and forearm vascular resistance in sickle cell and non sickle cell anaemia subjects

The effects of warmth stimulation and/or supplementation with vitamin E (300 mg/day for 6 weeks) on forearm blood flow (FBF) and forearm vascular resistance (FVR) were measured in 8 sickle cell anaemia (SCA) (mean age = 22.8 + 0.8 years) and 11 non sickle cell anaemia (NSCA) subjects (mean age = 23.2 + 1.1 years) of both sexes. Warmth stimulation was induced by immersing the left foot in warm water at 400C for 2 minutes. Forearm blood flow was measured with the venous occlusion plethysmography method. Warmth increased FBF (p <0.01 in each group) and reduced FVR (p <0.05) in NSCA subjects. The change in FBF was greater (p < 0.05) in the NSCA subjects than in the SCA subjects. Supplementation with vitamin E reduced systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) (p < 0.001 in each case) in the NSCA subjects but had little or no effect on the SCA subjects. Vitamin E increased FBF in NSCA subjects (p < 0.05) and SCA subjects (p < 0.01) and decreased FVR in both groups (p < 0.05 in NSCA and p < 0.01 in SCA subjects). The change in FVR seen in the NSCA subjects was less (p < 0.01) than the change in SCA subjects. After supplementation with vitamin E, warmth further decreased SBP (p < 0.01 in each group) and FVR (p < 0.01 in each case) and increased FBF in both groups (p < 0.01 respectively). The changes caused by warmth after vitamin E supplementation on the blood pressure parameters, FBF and FVR were similar in the two groups of subjects.

Sympathoadrenal imbalance before neurocardiogenic syncope

Neurocardiogenic syncope is the most common cause of acute loss of consciousness in adults. The present study attempted to identify neuroendocrine and hemodynamic changes before syncope that could therefore play a pathophysiologic role. Twenty-five patients referred for chronic orthostatic intolerance had plasma catecholamines measured serially; 21 patients during tilt-table testing (evoking syncope in 13) and 4 others with spontaneous syncope while supine. Forearm blood flow was measured by impedance plethysmography. All 12 patients with blood sampled before tilt-induced syncope had progressive, marked increases in plasma epinephrine levels (mean 11 times baseline, p <0.0001) before syncope. Simultaneously obtained norepinephrine levels increased to a much smaller extent than did epinephrine levels (“sympathoadrenal imbalance”). In the same patients, forearm vascular resistance decreased by 21% before syncope. Proportionate changes in forearm vascular resistance before syncope correlated negatively with those in the epinephrine:norepinephrine ratio (r = −0.75, p = 0.005). Patients without syncope had forearm vasoconstriction and no sympathoadrenal imbalance during tilt. Patients with syncope while supine also had sympathoadrenal imbalance before loss of consciousness. Sympathoadrenal imbalance precedes tilt-evoked and spontaneous neurocardiogenic syncope and correlates with concurrent skeletal muscle vasodilation. Sympathoadrenal imbalance may contribute to hemodynamic derangements precipitating neurocardiogenic syncope.

Vascular responsiveness to brachial artery infusions of phenylephrine during isoflurane and desflurane anesthesia.

Compared with equi-minimum alveolar anesthetic concentration (MAC) isoflurane, desflurane is associated with greater levels of sympathetic nerve activity in humans but similar reductions in blood pressure. To explore these divergent effects, we evaluated vascular alpha(1)-adrenoceptor responses in the human forearm during isoflurane and desflurane anesthesia to determine if alpha(1)-adrenoceptor responses were more substantially attenuated during desflurane administration. Bilateral forearm venous occlusion plethysmography was used to examine arterial blood flow and to determine changes in forearm vascular resistance during brachial artery infusions of saline and phenylephrine (0.2, 0.4, 0.8, and 1.6 microg/min) in 22 conscious subjects and during anesthesia with 0.65 and 1.3 MAC isoflurane or desflurane. Infusion of phenylephrine into the brachial artery increased the forearm vascular resistance in a dose-dependent manner. The arterial response to phenylephrine was significantly attenuated by 0.65 and 1.3 MAC desflurane and similarly attenuated during 1.3 MAC isoflurane (P < 0.05). Impaired arterial alpha(1)-adrenoceptor responsiveness occurred during desflurane. However, this effect was statistically similar (P > 0.05) to the impaired responses during isoflurane. Blood pressure decreases during volatile anesthesia may be, in part, caused by decreased alpha(1)-adrenoceptor responsiveness. alpha-receptors on blood vessels regulate constriction and dilation and therefore modulate blood pressure. This research indicates that vasoconstriction via the alpha(1)-receptor vascular response is impaired during isoflurane and desflurane anesthesia.

Cardiovascular Responses to Lower Body Negative Pressure in the Elderly: Role of Reduced Leg Compliance

Background: It is warranted to test the hypothesis that the orthostatic tolerance does not diminish in the aging process per se in healthy individuals. Objective: The purpose of the present study was to examine the effects of aging on cardiovascular response and baroreflex sensitivity during lower body negative pressure (LBNP) with a special reference to leg compliance. Methods: Fifteen healthy old male subjects [mean age 68.2 ± (SE) 0.8 years] and 22 young male subjects [mean age 21.4 ± (SE) 0.3 years] underwent a 21-min bout of ramped LBNP (from 0 to –60 mm Hg, 10 mm Hg each for 3 min). Heart rate (HR), blood pressure, stroke volume (SV), forearm blood flow, and leg volume were measured throughout the experimental period. The arterial baroreflex sensitivity was calculated from spontaneous changes in beat-to-beat arterial pressure and HR during LBNP. Results: The leg compliance was lower, and the orthostatic tolerance index was higher in old than in young participants. The LBNP-associated increases in leg volume and HR and the decreases in SV were lower in old subjects, suggesting that the reduction of venous return was less in magnitude in old subjects during LBNP. The baseline value of baroreflex sensitivity evaluated by the sequence analysis was smaller, and no LBNP-related change was observed in old subjects, whereas a gradual LBNP-related reduction was observed in young subjects. The slope of regression between ΔSV and change in forearm vascular resistance during LBNP was identical in both age groups. Conclusions: We conclude that: (1) aging per se does not increase the intolerance to orthostatic stress induced by LBNP; (2) a low magnitude of venous return reduction during LBNP contributes to a higher tolerance in the old because of lower leg compliance, and (3) the sensitivity of baroreflex control of the HR is attenuated in the old; however, there is no deterioration of the sensitivity of the peripheral vasoconstriction during LBNP.

Abnormal neurovascular control during exercise is linked to heart failure severity.

The purpose of this study was to determine if abnormalities of sympathetic neural and vascular control are present in mild and/or severe heart failure (HF) and to determine the underlying afferent mechanisms. Patients with severe HF, mild HF, and age-matched controls were studied. Muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) in the nonexercising arm were measured during mild and moderate static handgrip. MSNA during moderate handgrip was higher at baseline and throughout exercise in severe HF vs. mild HF (peak MSNA 67 +/- 3 vs. 54 +/- 3 bursts/min, P < 0.0001) and higher in mild HF vs. controls (33 +/- 3 bursts/min, P < 0.0001), but the change in MSNA was not different between the groups. The change in FVR was not significantly different between the three groups during static exercise. During isolation of muscle metaboreceptors, MSNA and blood pressure remained elevated in normal controls and mild HF but not in severe HF. During mild handgrip, the increase in MSNA was exaggerated in severe HF vs. controls and mild HF, in whom MSNA did not increase. In summary, the increase in MSNA during static exercise in severe HF appears to be attributable to exaggerated central command or muscle mechanoreceptor control, not muscle metaboreceptor control.

Correlation between apolipoprotein B and endothelin-1-induced vasoconstriction in humans

Low-density lipoprotein (LDL) concentrations have been linked to altered responses to endogenous vasodilators and vasoconstrictors. We evaluated retrospectively the relationship between LDL and vasoconstrictor (endothelin-1, phenylephrine) responsiveness of the forearm vasculature in 15 elderly healthy volunteers with apolipoprotein B and LDL levels in the normal range. In contrast to phenylephrine, changes in forearm vascular resistance induced by endothelin-1 were correlated with apolipoprotein B, LDL, and total cholesterol concentrations in women but not in men. These findings might suggest that lipids may increase vascular tone through both impaired endothelial vasodilation and increased vasoconstriction to endothelin-1 at least in women.

Forearm vascular responses during orthostatic stress in control subjects and patients with posturally related syncope.

The aim of this study was to compare the changes in forearm vascular resistance that occurred during orthostatic stress in asymptomatic volunteer subjects with those in patients with posturally related syncope. The authors hoped firstly that it would indicate the importance of vasoconstriction in the maintenance of blood pressure, and secondly that it might have diagnostic value if there were differences between symptomatic patients and asymptomatic volunteers. Twelve volunteers and 67 patients with unexplained syncope were classified as early or late fainters, based on their endurance of a test of combined head-up tilting and lower-body suction. Responses of vascular resistance were assessed from the ratio of arterial blood pressure (Finapres) to brachial artery blood velocity (Doppler). Changes in vascular resistance were greater in volunteers at all stages of the procedure than in patients. There was, however, no significant difference between the responses of early and late-fainting volunteers. These results demonstrate the importance of vasoconstriction in the resistance to posturally related syncope, and they indicate that assessments of responses of vascular resistance may improve the accuracy of the diagnosis.

Orthostatic blood pressure changes and arterial baroreflex sensitivity in elderly subjects.

orthostatic hypotension in elderly people is often attributed to diminished afferent baroreflex sensitivity, but this has not been demonstrated. We examined the hypothesis that postural change in blood pressure is related to baroreflex sensitivity, independent of the confounding effect of baseline blood pressure. we studied 25 active, untreated elderly subjects free of postural symptoms (mean age 70 +/- 1 years): 16 with hypertension (clinic blood pressure 194 +/- 6/98 + 3 mmHg) and nine normotensive controls (clinic blood pressure 134 + 3/77 + 3 mmHg). We assessed baroreflex sensitivity from the heart rate and blood pressure responses to the Valsalva manoeuvre and a pressor and depressor stimulus (bolus phenylephrine injection or sodium nitroprusside infusion respectively). Subjects were then passively tilted to 60 degrees and maximum changes in systolic blood pressure, heart rate, forearm blood flow and forearm vascular resistance recorded. maximum change in systolic blood pressure with head-up tilt was correlated with supine systolic blood pressure (r = 0.60, P = 0.001). Maximum change in systolic blood pressure with orthostasis was greater in the hypertensive subjects (45 +/- 4 mmHg versus 29 +/- 6, P = 0.04) and the heart rate increment was less (16 +/- 2 bpm versus 24 +/- 4, P = 0.02). The increase in forearm vascular resistance with tilt was similar in the two groups (47 +/- 11 versus 38 +/- 7 units, P = 0.52). All three methods of assessing baroreflex sensitivity showed a reduction in the hypertensive subjects (all P < or = 0.02). Lower values of baroreflex sensitivity were related to greater falls in systolic blood pressure with tilt, after adjustment for the baseline level of systolic blood pressure. we found a relationship between baroreflex sensitivity and the systolic blood pressure fall with orthostasis, even after adjustment for prevailing systolic blood pressure. Despite equivalent changes in forearm vascular resistance with tilt, greater falls in systolic blood pressure were seen in hypertensive subjects than in normotensive controls, due in part to an inadequate baroreflex-mediated heart rate response. The postural fall in blood pressure often observed in elderly hypertensive subjects may be related to the reduced baroreflex sensitivity seen in this condition.

Hyperglycemia Without Hyperinsulinemia Produces Both Sympathetic Neural Activation and Vasodilation in Normal Humans

To explore the effects of the acute induction of hyperglycemia on sympathetic activity and vascular function we studied eight normal control subjects (28 ± 3 years of age). Muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) were measured before (5.4 ± 0.2 mmol/L) and during systemic infusion of 20% dextrose with octreotide (250 μg/h) and low dose insulin (4 mU·m −2·min −1) with 60 min of hyperglycemia (venous plasma glucose, 12.5 ± 0.6 mmol/L). To control for the effects of hyperosmolarity and volume infusion subjects returned for two control studies with equal volume 20% mannitol and 0.2% saline infusions instead of dextrose infusion. The increase in MSNA during hyperglycemia (178 ± 48 units) was significantly greater than the increase during mannitol (69 ± 46 units, p < 0.001) or during 0.2% saline (28 ± 28 units, p < 0.001). The decreases in FVR after 60 min of hyperglycemia 20 ± 4 units, p = 0.002 and mannitol 13 ± 4 units, p = 0.033 were significantly greater than the decrease during saline (0.1 ± 4 units). The changes in FVR during hyperglycemia and mannitol did not differ. Acute hyperglycemia causes sympathoexcitation and peripheral vasodilation. The vascular effect may be mediated by increased osmolar load.

Age, splanchnic vasoconstriction, and heat stress during tilting.

During upright tilting, blood is translocated to the dependent veins of the legs and compensatory circulatory adjustments are necessary to maintain arterial pressure. For examination of the effect of age on these responses, seven young (23 +/- 1 yr) and seven older (70 +/- 3 yr) men were head-up tilted to 60 degrees in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Qc; acetylene rebreathing technique), central venous pressure (CVP), blood pressures, forearm blood flow (venous occlusion plethysmography), splanchnic and renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to tilting in the thermoneutral condition, CVP and stroke volume decreased to a greater extent in the young men, but HR increased more, such that the fall in Qc was similar between the two groups in the upright posture. The rise in splanchnic vascular resistance (SVR) was greater in the older men, but the young men increased forearm vascular resistance (FVR) to a greater extent than the older men. The fall in Qc during combined heat stress and tilting was greater in the young compared with older men. Only four of the young men versus six of the older men were able to finish the second tilt without becoming presyncopal. In summary, the older men relied on a greater increase in SVR to compensate for a reduced ability to constrict the skin and muscle circulations (as determined by changes in FVR) during head-up tilting.

Diastolic ventricular interaction: a possible mechanism for abnormal vascular responses during volume unloading in heart failure.

Baroreflex dysfunction is common in chronic heart failure and contributes to the associated sympathoexcitation. Baroreceptor activity normally decreases during volume unloading, causing an increase in sympathetic outflow and resulting in forearm vasoconstriction. Some heart failure patients develop attenuated vasoconstriction or paradoxical vasodilation. The mechanism for this is unknown. We have recently demonstrated diastolic ventricular interaction in some patients with chronic heart failure as evidenced by increases in left ventricular (LV) end-diastolic volume in association with decreases in right ventricular (RV) volume during volume unloading. We reasoned that such an increase in LV volume, by increasing LV mechanoreceptor activity, would decrease sympathetic outflow and could therefore explain the abnormal vascular responses seen in such patients. We assessed changes in forearm vascular resistance (FVR) during application of -20 and -30 mm Hg lower-body negative pressure (LBNP) in 24 patients with chronic heart failure and 16 control subjects. Changes in LV and RV end-diastolic volumes were assessed during -30 mm Hg LBNP in all heart failure patients. Diastolic ventricular interaction was demonstrated in 12 patients as evidenced by increases in LV end-diastolic volume in association with decreases in RV end-diastolic volume during LBNP. Changes in FVR during LBNP (-20 and -30 mm Hg) were markedly attenuated in these 12 patients (-1.6+/-11.2 and -0.9+/-12.5 U) compared with both the remaining patients (11.9+/-10.0 and 17.0+/-12.3 U) and the control subjects (16.5+/-9.5 and 23.1+/-13.9 U) (P<.01 for both comparisons at each level of LBNP). FVR decreased in 5 of these 12 patients during -30 mm Hg LBNP, a response seen in none of the remaining patients (P=.01). Diastolic ventricular interaction in patients with chronic heart failure is associated with attenuated forearm vasoconstriction or paradoxical vasodilation during LBNP. This may explain the apparent derangement in baroreflex control of sympathetic outflow during acute volume unloading in heart failure.