Compartmental vascular changes in dogs after nephrectomy, DOCA, and saline: effect of nifedipine

Hypertension (mean arterial pressure, (MAP) 131 +/- 3 mmHg) developed in 18 dogs 4 weeks after left nephrectomy, deoxycorticosterone acetate (DOCA), 5 mg/kg sc twice weekly), and 0.5% NaCl drinking solution. This can be compared with MAP (95 +/- 7 mmHg) of 13 dogs with nephrectomy alone and MAP (86 +/- 4 mmHg) of dogs without nephrectomy. The two-compartment model of the circulation revealed no differences in systemic vascular compliance, compartmental compliance, or flow distribution to the compartments. However, the time constant for venous return for the compartment with the rapid time constant was increased from 0.05 +/- 0.004 min in control animals to 0.07 +/- 0.006 min in the nephrectomy alone group and 0.09 +/- 0.008 min in the hypertensive group (p less than 0.001), as a result of an increase in venous resistance. Arteriolar resistance in this compartment was also increased in the hypertensive animals, as was the mean circulatory filling pressure and overall resistance to venous return. Nifedipine (0.025-0.05 mg/kg) reduced MAP by 15% in the nephrectomy alone group and by 22% in the hypertensive group, with reduction in arteriolar resistance only in the fast time constant compartment. In the slow time constant compartment, arteriolar resistance was increased by more than 100% and flow decreased by more than 50% after nifedipine. Unilateral nephrectomy, DOCA, plus NaCl resulted in hypertension by increasing arteriolar resistance in a vascular compartment with a fast time constant for venous return. Nifedipine countered this effect by inducing arteriolar vasodilation in this compartment. In addition, nifedipine reduced the mean circulatory filling pressure and overall resistance to venous return.     

Influence of positive airway pressure on the pressure gradient for venous return in humans.

To study the effect of positive airway pressure (Paw) on the pressure gradient for venous return [the difference between mean systemic filling pressure (Pms) and right atrial pressure (Pra)], we investigated 10 patients during general anesthesia for implantation of defibrillator devices. Paw was varied under apnea from 0 to 15 cmH(2)O, which increased Pra from 7.3 +/- 3.1 to 10.0 +/- 2.3 mmHg and decreased left ventricular stroke volume by 23 +/- 22%. Episodes of ventricular fibrillation, induced for defibrillator testing, were performed during 0- and 15-cmH(2)O Paw to measure Pms (value of Pra 7.5 s after onset of circulatory arrest). Positive Paw increased Pms from 10.2 +/- 3.5 to 12.7 +/- 3.2 mmHg, and thus the pressure gradient for venous return (Pms - Pra) remained unchanged. Echocardiography did not reveal signs of vascular collapse of the inferior and superior vena cava due to lung expansion. In conclusion, we demonstrated that positive Paw equally increases Pra and Pms in humans and alters venous return without changes in the pressure gradient (Pms - Pra).     

Effect of positive pressure on venous return in volume-loaded cardiac surgical patients.

The hemodynamic effects of increases in airway pressure (Paw) are related in part to Paw-induced increases in right atrial pressure (Pra), the downstream pressure for venous return, thus decreasing the pressure gradient for venous return. However, numerous animal and clinical studies have shown that venous return is often sustained during ventilation with positive end-expiratory pressure (PEEP). Potentially, PEEP-induced diaphragmatic descent increases abdominal pressure (Pabd). We hypothesized that an increase in Paw induced by PEEP would minimally alter venous return because the associated increase in Pra would be partially offset by a concomitant increase in Pabd. Thus we studied the acute effects of graded increases of Paw on Pra, Pabd, and cardiac output by application of inspiratory-hold maneuvers in sedated and paralyzed humans. Forty-two patients were studied in the intensive care unit after coronary artery bypass surgery during hemodynamically stable, fluid-resuscitated conditions. Paw was progressively increased in steps of 2 to 4 cmH(2)O from 0 to 20 cmH(2)O in sequential 25-s inspiratory-hold maneuvers. Right ventricular (RV) cardiac output (CO(td)) and RV ejection fraction (EF(rv)) were measured at 5 s into the inspiratory-hold maneuver by the thermodilution technique. RV end-diastolic volume and stroke volume were calculated from EF(rv) and heart rate data, and Pra was measured from the pulmonary artery catheter. Pabd was estimated as bladder pressure. We found that, although increasing Paw progressively increased Pra, neither CO(td) nor RV end-diastolic volume changed. The ratio of change (Delta) in Paw to Delta Pra was 0.32 +/- 0.20. The ratio of Delta Pra to Delta CO(td) was 0.05 +/- 00.15 l x min(-1) x mmHg(-1). However, Pabd increased such that the ratio of Delta Pra to Delta Pabd was 0.73 +/- 0.36, meaning that most of the increase in Pra was reflected in increases in Pabd. We conclude that, in hemodynamically stable fluid-resuscitated postoperative surgical patients, inspiratory-hold maneuvers with increases in Paw of up to 20 cmH(2)O have minimal effects on cardiac output, primarily because of an in-phase-associated pressurization of the abdominal compartment associated with compression of the liver and squeezing of the lungs.     

Blood flow measurement from plethysmographic pulse waves without venous occlusion

An air plethysmograph with a sensitive phototransducer was constructed so that plethysmographic volume-change pulsations could be displayed in detail without using venous occlusion. Software was developed to allow analysis of the pulses using a modification of the backward extrapolation technique. This allowed calculation of the forward arterial blood flow and noninvasive derivation of the resting arterial flow waveform. There is good reproducibility of the technique, with 8% variability between pairs of measurements at rest and 4% variability after hand exercise. Direct comparison made with blood flows measured by venous occlusion plethysmography showed good average agreement. The mean blood flow for venous occlusion (rest and exercise) was 0.76 +/- 0.07 mL/beat (mean +/- SEM), and the mean blood flow for backward extrapolation (rest and exercise) was 0.74 +/- 0.09 mL/beat (mean +/- SEM). This corresponds to 3.86 +/- 0.36 mL/min/100 mL and 3.76 +/- 0.46 mL/min/100 mL, respectively. Important assumptions when using this method are that venous return is constant and that forward arterial flow is over before the end of the cardiac cycle.     

Blood flow to the placenta and lower body in the growth-retarded guinea pig fetus

Blood flow to the placenta and lower body of control and growth retarded (IUGR) guinea pig fetuses was measured between 60-64 days of pregnancy by the microsphere technique. Further information about the hepatic blood supply and its interlobular distribution was obtained by injecting microspheres into the umbilical vein and a branch of the portal vein. Liver weight was reduced by 60% in IUGR fetuses from 5.0 +/- 0.2 to 2.0 +/- 0.1 g, compared to a decrease in body weight of 50% from 91.6 +/- 3.0 to 45.4 +/- 2.6 g. In addition, there was a proportionately greater reduction in the size of the right liver lobe. Umbilical blood flow was 10.8 +/- 1.0 ml min-1 in control fetuses and 4.9 +/- 1.2 ml.min-1 in IUGR fetuses, whilst blood flow in the portal vein was reduced from 1.4 +/- 0.1 to 0.8 +/- 0.3 ml min-1 and that in the hepatic artery from 0.6 +/- 0.1 to 0.3 +/- 0.1 ml.min-1. Since ductus venosus flow was absent or negligible, the umbilical venous return accounted for greater than 80% of the hepatic blood supply in both control and IUGR fetuses. Blood flows were, however, unequally distributed between the liver lobes. The right lobe was supplied mainly by the portal vein in IUGR fetuses as well as the controls, and received less than 6% of the umbilical venous return. No significant change occurred in total liver perfusion, which was 2.8 +/- 0.2 ml min-1 per g in control fetuses and 2.6 +/- 0.4 ml min-1 per g in IUGR fetuses. It is therefore suggested that a high rate of liver metabolism is maintained in IUGR, but by a smaller tissue mass, and that the rate of umbilical blood flow may be one factor determining the size of the liver. The relatively greater reduction in size of the right lobe in IUGR is probably the result of poor oxygenation of the portal venous blood.     

Decreased skeletal muscle pump activity in patients with postural tachycardia syndrome and low peripheral blood flow

Standing translocates thoracic blood volume into the dependent body. The skeletal muscle pump participates in preventing orthostatic intolerance by enhancing venous return. We investigated the hypothesis that skeletal muscle pump function is impaired in postural tachycardia (POTS) associated with low calf blood flow (low-flow POTS) and depends in general on muscle blood flow. We compared 12 subjects that have low-flow POTS with 10 controls and 7 patients that have POTS and normal calf blood flow using strain-gauge plethysmography to measure peripheral blood flow, venous capacitance, and calf muscle pump function. Blood volume was estimated by dye dilution. We found that calf circumference was reduced in low-flow POTS (32 +/- 1 vs. 39 +/- 3 and 43 +/- 3 cm) and, compared with controls and POTS patients with normal blood flow, is related to the reduced fraction of calf venous capacity emptied during voluntary muscle contraction (ejection fraction, 0.52 +/- 0.07 vs. 0.76 +/- 0.07 and 0.80 +/- 0.06). We found that blood flow was linearly correlated (r(p) = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 +/- 0.3 in low-flow POTS vs. 2.6 +/- 0.5 in controls (P = 0.17) and 2.4 +/- 0.7 in normal-flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and thereby impair the upright ejective ability of the skeletal muscle pump and further contribute to overall reduced blood flow and orthostatic intolerance in these patients.     

Effect of synthetic physalaemin on splanchnic circulation in dogs

Physalaemin has been reported as one of the most potent vasodilator and hypotensive peptides (1-4). In spite of these studies, however, the effect of the peptide on splanchnic circulation is not known precisely. In the present study, the effect of synthetic physalaemin on superior mesenteric arterial blood flow, portal venous blood flow and pancreatic capillary blood flow was investigated in dogs. Dose dependent increases of superior mesenteric arterial blood flow and portal venous blood flow were induced in response to physalaemin (0.1-10.0 ng/kg). Superior mesenteric arterial blood flow and portal venous blood flow attained maximal increases of 77 +/- 8.9% and 70 +/- 8.6%, respectively, at a dose of 5 ng/kg. Physalaemin caused a dose-related decrease in systemic arterial blood pressure. Pancreatic capillary blood flow did not show significant change with the administration of physalaemin. These data suggest that physalaemin may play some physiological roles in the regulation of splanchnic circulation.     

Peripheral vascular resistance increases after termination of obstructive apneas.

The mechanisms by which obstructive apneas produce intermittent surges in arterial pressure remain poorly defined. To determine whether termination of obstructive apneas produce peripheral vasoconstriction, we assessed forearm blood flow during and after obstructive events in sleeping patients experiencing spontaneous upper airway obstructions. In all subjects, heart rate was monitored with an electrocardiogram and blood pressure was monitored continuously with digital plethysmography. In 10 patients (protocol 1), we used forearm plethysmography to assess forearm blood flow, from which we calculated forearm vascular resistance by performing venous occlusions during and after obstructive episodes. In an additional four subjects, we used simultaneous Doppler and B-mode images of the brachial artery to measure blood velocity and arterial diameter, from which we calculated brachial flow continuously during spontaneous apneas (protocol 2). In protocol 1, forearm vascular resistance increased 71% after apnea termination (29.3 +/- 15.4 to 49.8 +/- 26.5 resistance units, P < 0.05) with all patients showing an increase in resistance. In protocol 2, brachial resistance increased at apnea termination in all subjects (219.8 +/- 22.2 to 358.3 +/- 46.1 mmHg x l(-1) x min; P = 0.01). We conclude that termination of obstructive apneas is associated with peripheral vasoconstriction.     

Effects of calcium channel-blocker tokolysis on the foetal circulation

The Ca++-antagonist nifedipine has been successfully employed in the treatment of non-gravid hypertension, and was found to inhibit uterine contractions in the perimenstrual period, as well as during premature labour in animal models. The use of antihypertensive drugs in pregnancy introduces the possibility of iatrogenic foetal distress. It has been established that nifedipine crosses the placental barrier in the sheep and causes a fall in mean arterial pressure and tachycardia in both the ewe and the foetus. This paper examines the effects of nifedipine on the foetus when administered to the pregnant ewe. Catheters and electrodes were implanted by surgical procedures in 15 ewes and foetal lambs between days 118 and 122 of gestation. The redistribution of foetal blood flow was measured by the radioactive microsphere injection technique. The infusion of nifedipine caused a 9% increase in the combined ventricular output (CVO) from 446 to 509 ml/min/kg in the foetus. Foetal lung blood flow increased from 29 +/- 6 to 69 +/- 14 ml/min/kg while figures for the skeletal muscle flow were 109 +/- 34 and 141 +/- 41.6 ml/min/kg. Heart and brain blood flow, expressed as percentages of CVO showed variations of 4.3 and 5.6 per cent, respectively. Blood flow in the gut, placental membranes, skin, kidney and spleen was reduced. The present results show that nifedipine, in addition to its known effects causes a redistribution of the foetal circulation.     

Analysis of venous flow transients for estimation of vascular resistance, compliance, and blood flow distribution

We analysed venous flow transients using a long venous circuit and right heart bypass in 17 dogs after a rapid decrease in atrial pressure. A biphase curve was obtained which we decomposed into a two-compartment model, one with a fast time constant for venous return (0.069 min) and 52% of total circulating flow (Q), and one with a slower time constant (0.456 min) and 48% of Q. Subsequently, separate drainage from splanchnic and peripheral beds (with the renal venous return in the peripheral bed drainage) allowed comparison of time constants and venous outflow in these beds. The sum of the venous outflow volumes over time during separate drainage was indistinguishable from the single biphasic venous outflow volume curve over time observed with a long circuit and single reservoir. The fast time constant of the biphasic curve was not different from that determined by separate drainage from the peripheral circulation. The slow time constant of the single biphasic curve of 0.456 min was hybrid of two time constants, 0.216 min in the splanchnic bed and 0.862 min in the peripheral bed. Separate drainage from peripheral and splanchnic vascular beds demonstrated that the peripheral bed constituted 70% of venous outflow in the fast time constant compartment using Caldini's technique, whereas the splanchnic bed constituted 63% of venous outflow in the slow time constant compartment. It is concluded that, although Caldini's technique demonstrates biphasic venous flow transients, neither the fast nor the slow time constant compartments resolved from this analysis represent a particular anatomical region or vascular bed.     

Theoretical analysis of the noncardiac limits to maximum exercise

When right atrial pressure (Pra) is greater than zero (atmospheric pressure), cardiac output is determined by the intersection of two functions, cardiac function and return function, which is used here to mean the determinants of venous return. When Pra < or = 0, flow is only determined by circuit function. The objective of this analysis was to determine the potential changes in return function that need to occur to allow the maximum cardiac output during exercise when Pra < or = 0 or is constant. The analysis expands on the model of Green and Jackman and includes the effects of changes in circuit parameters, including venous resistance, changes in capacitance, and muscle contractions. The analysis is based on the model of the circulation proposed by Permutt and co-workers, which assumes that the systemic circulation has two lumped compliant regions in parallel with independent inflow and outflow resistances. Changes in total flow in this model can come about by changes in the distribution of flow between the regions, recruitment of unstressed vascular volume, and changes in the regional venous resistances. The data for the analysis are from previous animal studies and are normalized to a 70-kg man. The major conclusions are that, to achieve the high cardiac output that occurs at peak exercise, there need to be marked changes in the distribution of blood flow, recruitment of unstressed volume, and the venous resistance draining vascular beds. A consequence of the increase in peripheral flow is a marked increase in pressure in the veins of the working muscle. Muscle contractions are potentially a very important mechanism for transiently decreasing this pressure and preventing excessive filtration of plasma during exercise.     

Venous occlusion plethysmography reduces arterial diameter and flow velocity

The measurement of peripheral blood flow by plethysmography assumes that the cuff pressure required for venous occlusion does not decrease arterial inflow. However, studies in five normal subjects suggested that calf blood flow measured with a plethysmograph was less than arterial inflow calculated from Doppler velocity measurements. We hypothesized that the pressure required for venous occlusion may have decreased arterial velocity. Further studies revealed that systolic diameter of the superficial femoral artery under a thigh cuff decreased from 7.7 +/- 0.4 to 5.6 +/- 0.7 mm (P less than 0.05) when the inflation pressure was increased from 0 to 40 mmHg. Cuff inflation to 40 mmHg also reduced mean velocity 38% in the common femoral artery and 47% in the popliteal artery. Inflation of a cuff on the arm reduced mean velocity in the radial artery 22% at 20 mmHg, 26% at 40 mmHg, and 33% at 60 mmHg. We conclude that inflation of a cuff on an extremity to low pressures for venous occlusion also caused a reduction in arterial diameter and flow velocity.     

Relationship between blood flow and steroidogenesis in the rabbit corpus luteum

Blood flow in the corpus luteum of the pseudopregnant rabbit was measured with tracer-labelled microspheres before and at 1 and 3 h after saline treatment (N = 8) or after inhibition of progesterone synthesis with aminoglutethimide (N = 10). Before treatment luteal blood flow (29.5 +/- 3.9 ml/min.g-1 (mean +/- s.e.m.] was much higher than blood flow to other tissues (ovarian stroma = 2.9 +/- 0.6; uterus = 0.5 +/- 0.1; adrenal gland = 2.6 +/- 0.2 ml/min.g-1). Aminoglutethimide reduced serum progesterone by 60% within 1 h but luteal blood flow was unchanged (26.2 +/- 3.5 ml/min.g-1). At 3 h after aminoglutethimide, serum progesterone remained low and luteal blood flow was slightly reduced to 22.5 +/- 3.4 ml/min.g-1. This reduction was associated with a significant decline in mean arterial blood pressure which resulted in luteal vascular resistance being unaltered by aminoglutethimide treatment. Further analysis of these data indicated that serum progesterone concentration was not significantly correlated with blood flow to the corpora lutea or with blood flow to other tissues. In contrast, mean arterial blood pressure was highly correlated with blood flow to the corpus luteum (r = 0.80; P less than 0.001) but not to the ovarian stroma (r = 0.04), or adrenal gland (r = 0.06). These results indicate that luteal blood flow is not acutely responsive to changes in luteal progesterone production and suggest that luteal blood flow changes passively with changes in arterial blood pressure.     

Erythrocyte deformability and segmental pulmonary vascular resistance: osmolarity and heat treatment

The site and nature of change in resistance to blood flow in canine left lung lobe preparation after changes in blood viscosity were assessed by using the arterial and venous occlusion (AVO) technique and the vascular pressure-flow relationship. Blood viscosity was changed by erythrocyte (RBC) shrinkage and swelling with hypertonic and hypotonic NaCl solutions and by RBC membrane rigidification with heat treatment (49 degrees C for 1 h). The results show that although all three methods of changing blood viscosity increased the pulmonary vascular resistance (PVR) by 15-50%, the site and nature of the change in PVR were different in each case. The AVO data showed that the increase in PVR with heat treatment of RBC's was due entirely (100%) to increased resistance of the middle microvascular segment, whereas deviation from normal osmolarity potentiated the resistance in arterial, middle, and venous segments. By examining the effect of osmolarity in plasma-perfused lobes, it was possible to separate the increase in PVR due to changes in RBC deformability from those due to other factors. The increase in arterial and venous resistances with hypertonic solution was attributed in part (approximately 50%) to factors other than RBC's; however, the increase in middle resistance was entirely due to RBC crenation. The increase in arterial and venous resistances with hypotonic solutions was small and was apparently caused by factors other than RBC swelling, whereas the increase in middle resistance was partially (approximately 50%) due to RBC swelling and partially to other factors (e.g., endothelial cell hydration).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchial vasodilation by histamine in sheep: characterization of receptor subtype.

Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased vasodilator responsiveness to BRL 34915 in spontaneously hypertensive versus normotensive rats: contrast with nifedipine

The blood pressure-lowering potency and activity of BRL 34915, a new vasodilator and putative stimulator of potassium efflux from vascular smooth muscle, was investigated in conscious spontaneously hypertensive rats (SHR) and normotensive rats (NTR) after intravenous administration and compared with that of the calcium channel blocker, nifedipine. In SHR, BRL 34915 (3-100 micrograms/kg) or nifedipine (10-3000 micrograms/kg) produced similar reductions in mean arterial pressure of 58 +/- 3% and 55 +/- 3%, respectively. BRL 34915 (ED30% = 13.8 micrograms/kg) was 15.3 times more potent than nifedipine (ED30% = 207 micrograms/kg) in SHR. In contrast, only a 1.7-fold difference in potency was observed in NTR between BRL 34915 (ED30% = 123 micrograms/kg) and nifedipine (ED30% = 182 micrograms/kg). The potency ratio (ED30% NTR/ED30% SHR) for BRL 34915 was 8.83 whereas nifedipine had a ratio of 0.88, reflecting the greater responsiveness of the SHR to BRL 34915. Systemic hemodynamics were monitored in anesthetized SHR and NTR to determine the basis for the reductions in blood pressure. BRL 34915 (3-100 micrograms/kg iv) lowered mean arterial pressure in both groups solely by decreasing total peripheral vascular resistance, since no changes in cardiac output were observed. Relaxation responses were also obtained in phenylephrine-contracted isolated aortic strips from both strains of rat to ascertain whether differences in responsiveness existed at this level of the vasculature. No significant difference in the potency of BRL 34915 (3-10 microM) as a vasodilator was found in aortas from SHR or NTR. These results indicate that, unlike nifedipine, BRL 34915 is a more potent vasodepressor agent in SHR than in NTR and suggests that the potassium efflux stimulator may preferentially relax resistance vessels in the hypertensive rat.     

Long-lasting vasoconstriction and efficient regional extraction of endothelin-1 in human splanchnic and renal tissues

Six healthy subjects were given endothelin-1, intravenously in a dose of 4 pmol.kg-1.min-1 for 20 min. Blood samples were drawn from arterial, hepatic and renal vein catheters for determinations of splanchnic and renal blood flows and the extraction of endothelin-1 in these vascular beds. Intravenous infusion of endothelin-1 increased the mean arterial blood pressure by 6.8 +/- 2.0 mm Hg (p less than 0.05) and reduced splanchnic and renal blood flows by 34% (p less than 0.005) and 26% (p less than 0.001) respectively. Return to basal flow values occurred after about 1 hr for the splanchnic and 3 hrs for the renal blood flow. The fractional extractions of endothelin-1-like immunoreactivity corresponded to 75 +/- 2% and 60 +/- 2% in the splanchnic and renal vascular beds, respectively. The disappearance curve in plasma and two half-lives of 1.4 +/- 0.1 min and 35 +/- 2.8 min respectively.     

Attenuated hepatosplanchnic uptake of lactate during intense exercise in humans.

We evaluated whether the increase in blood lactate with intense exercise is influenced by a low hepatosplanchnic blood flow as assessed by indocyanine green dye elimination and blood sampling from an artery and the hepatic vein in eight men. The hepatosplanchnic blood flow decreased from a resting value of 1.6 +/- 0.1 to 0.7 +/- 0.1 (SE) l/min during exercise. Yet the hepatosplanchnic O2 uptake increased from 67 +/- 3 to 93 +/- 13 ml/min, and the output of glucose increased from 1.1 +/- 0.1 to 2.1 +/- 0.3 mmol/min (P < 0.05). Even at the lowest hepatosplanchnic venous hemoglobin O2 saturation during exercise of 6%, the average concentration of glucose in arterial blood was maintained close to the resting level (5.2 +/- 0.2 vs. 5.5 +/- 0.2 mmol/l), whereas the difference between arterial and hepatic venous blood glucose increased to a maximum of 22 mmol/l. In arterial blood, the concentration of lactate increased from 1.1 +/- 0.2 to 6.0 +/- 1.0 mmol/l, and the hepatosplanchnic uptake of lactate was elevated from 0.4 +/- 0.06 to 1.0 +/- 0.05 mmol/min during exercise (P < 0.05). However, when the hepatosplanchnic venous hemoglobin O2 saturation became low, the arterial and hepatosplanchnic venous blood lactate difference approached zero. Even with a marked reduction in its blood flow, exercise did not challenge the ability of the liver to maintain blood glucose homeostasis. However, it appeared that the contribution of the Cori cycle decreased, and the accumulation of lactate in blood became influenced by the reduced hepatosplanchnic blood flow.     

Local vascular responses affecting blood flow in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.     

Contribution of prostaglandins to the dilation that follows isometric forearm contraction in human subjects: effects of aspirin and hyperoxia.

In 11 healthy volunteers, we evaluated, in a double-blind crossover study, whether the vasodilation that follows isometric contraction is mediated by prostaglandins (PGs) and/or is O2 dependent. Subjects performed isometric handgrip for 2 min at 60% maximal voluntary contraction (MVC), after pretreatment with placebo or aspirin (600 mg orally), when breathing air or 40% O2. Forearm blood flow was measured in the dominant forearm by venous occlusion plethysmography. Arterial blood pressure was also recorded, allowing calculation of forearm vascular conductance (FVC; forearm blood flow/arterial blood pressure). During air breathing, aspirin significantly reduced the increase in FVC that followed contraction at 60% MVC: from a baseline of 0.09 +/- 0.011 [mean +/- SE, conductance units (CU)], the peak value was reduced from 0.24 +/- 0.03 to 0.14 +/- 0.01 CU. Breathing 40% O2 similarly reduced the increase in FVC relative to that evoked when breathing air; the peak value was 0.24 +/- 0.03 vs. 0.15 +/- 0.02 CU. However, after aspirin, breathing 40% O2 had no further effect on the contraction-evoked increase in FVC (the peak value was 0.15 +/- 0.02 vs. 0.16 +/- 0.02 CU). Thus the present study indicates that prostaglandins make a substantial contribution to the peak of the vasodilation that follows isometric contraction of forearm muscles at 60% MVC. Given that hyperoxia similarly reduced the vasodilation and attenuated the effect of aspirin, we propose that the stimulus for prostaglandin synthesis and release is hypoxia of the endothelium.