Anatomical vertebral artery hypoplasia and insufficiency impairs dynamic blood flow regulation

Recent studies have suggested that vertebral artery (VA) hypoplasia is a predisposing factor for posterior cerebral stroke. We examined whether anatomical vertebrobasilar ischemia, i.e., unilateral VA hypoplasia and insufficiency, impairs dynamic blood flow regulation. Twenty‐eight female subjects were divided into three groups by defined criteria: (i) unilateral VA hypoplasia (n = 8), (ii) VA insufficiency (n = 6), and (iii) control (n = 14). Hypoplastic VA criterion was VA blood flow of 40 ml min^?1, whereas VA insufficiency criterion was net (left + right) VA blood flow of 100 ml min^?1 or less. We evaluated left, right, and net VA blood flows by ultrasonography during hypercapnia, normocapnia, and hypocapnia to evaluate VA CO₂ reactivity. The unilateral VA hypoplasia group showed lower CO₂ reactivity at hypoplastic VA than at non‐hypoplastic VA (2·65 ± 0·58 versus 3·00 ± 0·48% per mmHg, P = 0·027) and net VA CO₂ reactivity was preserved (Unilateral VA hypoplasia, 2·95 ± 0·48 versus Control, 2·93 ± 0·42% per mmHg, P = 0·992). However, the VA insufficiency group showed a lower net VA CO₂ reactivity compared to the control (2·29 ± 0·55 versus 2·93 ± 0·42% per mmHg, P = 0·032) and the unilateral VA hypoplasia (P = 0·046). VA hypoplasia reduced CO₂ reactivity, although non‐hypoplastic VA may compensate this regulatory limitation. In subjects with VA insufficiency, lowered CO₂ reactivity at the both VA could not preserve normal net VA CO₂ reactivity. These findings provide a possible physiological mechanism for the increased risk of posterior cerebral stroke in subjects with VA hypoplasia and insufficiency.     

The effect of phenylephrine on arterial and venous cerebral blood flow in healthy subjects

Aim: Sympathetic regulation of the cerebral circulation remains controversial. Although intravenous phenylephrine (PE) infusion reduces the near‐infrared spectroscopy (NIRS)‐determined measure of frontal lobe oxygenation (S_cO₂) and increases middle cerebral artery mean blood velocity (MCA V_mean), suggesting α‐adrenergic‐mediated cerebral vasoconstriction, this remains unconfirmed by evaluation of arterial and venous cerebral blood flow. Methods: We determined S_cO₂, MCA V_mean, and right internal carotid artery (ICA) and internal jugular venous (IJV) blood flow (duplex ultrasound) during infusion of PE in eight supine young healthy men [26 (3) years, 177 (7) cm and 74 (8) kg; mean (SD)]. Results: Compared with saline, during infusion of PE, mean arterial pressure increased 26 ± 3% (mean ± SE) and MCA V_mean by 4·8 ± 1·9% (P<0·05), while S_cO₂ decreased by 13·7 ± 3·7% (P<0·05) with no significant changes in the arterial oxygen or carbon dioxide tensions. ICA blood flow did not change significantly in response to PE administration (351 ± 12 versus 373 ± 21 ml min^?1; P = 0·236), while IJV blood flow increased (443 ± 57 versus 507 ± 58 ml min^?1; P = 0·023). Conclusions: These findings confirm that PE induces a reduction in S_cO₂ measured by NIRS and causes an increase in MCA V_mean indicative of cerebral arterial vasoconstriction, although ICA was preserved and IJV increased. These results suggest that a decrease in S_cO₂ during infusion of PE reflects an altered cerebral contribution of arterial versus venous blood to the NIRS signal, although we cannot rule out that an effect of PE on skin blood flow is important.     

Middle cerebral artery blood flow velocity in response to lower body positive pressure

Lower body positive pressure (LBPP) has been used in the treatment of haemorrhagic shock and in offsetting g‐force induced fluid shifts. However, the middle cerebral artery blood flow velocity (MCAv) response to supine LBPP is unknown. Fifteen healthy volunteers (mean ± SD: age, 26 ± 5 year; body mass, 79 ± 10 kg; height, 174 ± 9 cm) completed 5 minutes of 20 and 40 mm Hg LBPP, in a randomized order, separated by 5 minutes rest (baseline). Beat‐to‐beat MCAv and blood pressure, partial pressure of end‐tidal carbon dioxide (P_ETCO₂) and heart rate were recorded and presented as the change from the preceding baseline. All measures were similar between baseline periods (all P>0·30). Mean arterial pressure (MAP) increased by 7 ± 6 (8 ± 7%) and 13 ± 7 mm Hg (19 ± 11%) from baseline during 20 and 40 mm Hg (P<0·01), respectively. The greater MAP increase at 40 mm Hg (P<0·01 versus 20 mm Hg) was mediated via a greater increase in total peripheral resistance (P<0·01), with heart rate, cardiac output (Model flow) and P_ETCO₂ remaining unchanged (all P>0·05) throughout. MCAv increased from baseline by 3 ± 4 cm s^?1 (5 ± 5%) during 20 mm Hg (P = 0·003), whilst no change (P = 0·18) was observed during 40 mm Hg. Our results indicate a divergent response, in that 20 mm Hg LBPP‐induced modest increases in both MCAv and MAP, yet no change in MCAv was observed at the higher LBPP of 40 mm Hg despite a further increase in MAP.     

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50–75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43·6 ml per 100 g min^?1, 5·5 l min^?1 and 2·7 l min^?1 m^?2, respectively, in males, and 53·4 ml per 100 g min^?1, 4·3 l min^?1 and 2·4 l min^?1 m^?2, respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r² = 0·22, P = 0·008) and furthermore lower in males than in females (8·6% versus 12·5%, P = 0·003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender‐related inverse association of increased low‐to‐high‐frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender‐related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease.     

Effect of propofol and thiopentone on regional blood flow in brain and peripheral tissues during normoxia and hypoxia in the dog

Summary. The effect of propofol and thiopentone on cerebral (CBF), myocardial (MBF), muscular, and arterial hepatic blood flow was assessed with radiolabeled microspheres in 12 chronically instrumented dogs, six given propofol and six thiopentone. Tissue blood flows were measured in the awake animal, after 30 min of normoxic anaesthesia (room air), and after 30 min of hypoxic anaesthesia using a mixture of 10% O₂ and 3% CO₂ in nitrogen. The decrease in CBF from awake to normoxic anaesthesia was similar with propofol and thiopentone (propofol: 77 ±8 to 38±3 ml min^-1 100 g^-1, P<0.01; thiopentone: 66±3 to 33±2 ml min^-1 100 g^-1, P<0.01). During hypoxia, CBF rose moderately in the two groups (respectively + 19% and +28%, P<0.05). The MBF increased in propofol and thiopentone groups after 30 min of anaesthesia with air (propofol: 97 ±23 to 137 ± 15 ml min^-1 100 g^-1; thiopentone: 82 ±7 to 141 ± 10 ml min^-1 100 g^-1) and increased still more during hypoxia. The increase in MBF was related to an increase in heart rate and blood pressure. The quadriceps blood flow decreased during anaesthesia in normoxia and in hypoxia. The diaphragmatic blood flow increased with thiopentone under hypoxia. The hepatic arterial blood flow was unchanged. It is concluded that the effects of propofol on regional blood flows are very similar to those of thiopentone.     

Feasibility of intercostal blood flow measurement by echo-Doppler technique in healthy subjects

Intercostal artery blood flow supplies the external and internal intercostal muscles, which are inspiratory and expiratory muscles. Intercostal blood flow measured by the echo-Doppler (ED) technique has not previously been reported in humans. This study describes the feasibility of this measurement during free and loaded breathing in healthy subjects. Systolic, diastolic and mean blood flows were measured in the eighth dorsal intercostal space during free and loaded breathing using the ED technique. Flows were calculated as the product of the artery intraluminal surface and blood velocity. Ten healthy subjects (42 ± 13·6 years) were included. Integrated electromyogram (iEMG), arterial pressure, cardiac frequency and breathing pattern were also recorded. Mean blood flows were 3·5 ± 1·2 ml min⁻¹ at rest, 6 ± 2·6 ml min⁻¹ while breathing through a combined inspiratory and expiratory resistance and 4·0 ± 1·3 ml min⁻¹ 1 min after unloading. Diastolic blood flow was about one-third the systolic blood flow. The changes in blood flows were consistent with those in iEMG. No change in mean blood flow was observed between inspiration and expiration, suggesting a balance in the perfusion of external and internal muscles during breathing. In conclusion, ED is a feasible technique for non-invasive, real-time measurement of intercostal blood flow in humans. In healthy subjects, mean blood flow appeared tightly matched to iEMG activity. This technique may provide a way to assess the vascular adaptations induced by diseases in which respiratory work is increased or cardiac blood flow altered.     

The relationship between exercise‐induced muscle fatigue,arterial blood flow and muscle perfusion after 56 days local muscle unloading

In the light of the dynamic nature of habitual plantar flexor activity, we utilized an incremental isokinetic exercise test (IIET) to assess the work‐related power deficit (WoRPD) as a measure for exercise‐induced muscle fatigue before and after prolonged calf muscle unloading and in relation to arterial blood flow and muscle perfusion. Eleven male subjects (31 ± 6 years) wore the HEPHAISTOS unloading orthosis unilaterally for 56 days. It allows habitual ambulation while greatly reducing plantar flexor activity and torque production. Endpoint measurements encompassed arterial blood flow, measured in the femoral artery using Doppler ultrasound, oxygenation of the soleus muscle assessed by near‐infrared spectroscopy, lactate concentrations determined in capillary blood and muscle activity using soleus muscle surface electromyography. Furthermore, soleus muscle biopsies were taken to investigate morphological muscle changes. After the intervention, maximal isokinetic torque was reduced by 23·4 ± 8·2% (P<0·001) and soleus fibre size was reduced by 8·5 ± 13% (P = 0·016). However, WoRPD remained unaffected as indicated by an unchanged loss of relative plantar flexor power between pre‐ and postexperiments (P = 0·88). Blood flow, tissue oxygenation, lactate concentrations and EMG median frequency kinematics during the exercise test were comparable before and after the intervention, whereas the increase of RMS in response to IIET was less following the intervention (P = 0·03). In conclusion, following submaximal isokinetic muscle work exercise‐induced muscle fatigue is unaffected after prolonged local muscle unloading. The observation that arterial blood flow was maintained may underlie the unchanged fatigability.     

Effect of renal denervation on coronary flow reserve in patients with resistant hypertension

Renal denervation (RDN) is a potential modality in the treatment of patients with resistant hypertension (RH) and has shown beneficial effect on a variety of cardiovascular surrogate markers. Coronary flow reserve, as assessed by transthoracic Doppler echocardiography (TDE‐CFR) is impaired in patients with hypertension and is an independent predictor of cardiac morbidity. However, data on the effect of RDN on TDE‐CFR are scarce. The main objective of this study was to assess the effect of RDN on TDE‐CFR. Twenty‐six consecutive patients with RH (9 female and 17 male; mean age 62 ± 8 years; mean number of antihypertensive drugs 4·2 ± 1·6) underwent bilateral RDN. CFR was assessed at baseline and 6 months after intervention. Mean flow velocity was measured in the left anterior descending artery by transthoracic Doppler echocardiography at baseline and during adenosine infusion (TDE‐CFR). Systolic office blood pressure was reduced at follow‐up (174 ± 24 versus 162 ± 27 mmHG; P = 0·01). Mean systolic ambulatory blood pressure decreased from 151 ± 21 to 147 ± 18 (P = 0·17). TDE‐CFR remained unchanged 6 months after intervention (2·7 ± 0·6 versus 2·7 ± 0·7; P = 0·67). In conclusion, renal denervation was not associated with any changes in regard to coronary flow reserve at 6‐month follow‐up.     

Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis

Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4‐h intravenous infusion of LPS (total dose: 2 ng kg^?1). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh‐cuff deflation‐induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh‐cuff deflation caused a MAP reduction of 16 (13–20) % at baseline and 18 (16–20) % after LPS, while the MAP reduction was 12 (11–13) % in patients (P<0·05 versus volunteers at baseline; P<0·01 versus volunteers after LPS). The corresponding RoR values increased from 0·46 (0·31–0·49) s^?1 at baseline to 0·58 (0·36–0·74) s^?1 after LPS (P<0·05) in healthy volunteers, whereas they were similar to values observed in patients [0·43 (0·36–0·52) s^?1; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh‐cuff deflation failed to induce sufficient MAP reductions in patients.     

Forearm metabolism during infusion of adrenaline: comparison of the dominant and non‐dominant arm

Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain‐gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured by the local ¹³³Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a‐v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0·3 nmol kg^?1 min^?1. No difference in the metabolic information obtained in the fasting state could be demonstrated. During infusion of adrenaline, blood flow and lactate output increased significantly more in the non‐dominant arm (8·12 ± 1·24 versus 6·45 ± 1·19 ml 100 g^?1 min^?1) and (2·99 ± 0·60 versus 1·83 ± 0·43 μmol 100 g^?1 min^?1). Adrenaline induced a significant increase in oxygen uptake in the non‐dominant forearm (baseline period: 4·98 ± 0·72 μmol 100 g^?1 min^?1; adrenaline period: 6·63 ± 0·62 μmol 100 g^?1 min^?1) while there was no increase in the dominant forearm (baseline period: 5·69 ± 1·03 μmol 100 g^?1 min^?1; adrenaline period: 4·94 ± 0·84 μmol 100 g^?1 min^?1). It is concluded that the two forearms do not respond equally to adrenaline stimulation. Thus, when comparing results from different studies, it is necessary to know which arm was examined.     

Differential effects of age on large artery stiffness and minimal vascular resistance in normotensive and mildly hypertensive individuals

Large artery stiffness and small artery structural changes are both cardiovascular risk factors. Arterial stiffness increases with age and blood pressure (BP), but it is unclear in which way large artery pulse wave velocity (PWV) and peripheral vascular resistance are related and whether age has any influence. In a cross‐sectional study, PWV and forearm minimum vascular resistance (R_min) was compared with emphasis on the impact of age. Normotensive (n = 53) and untreated hypertensive (n = 23) subjects were included based on 24‐h BP measurements. Age ranged from 21 to 79 years with an even distribution from each age decade. PWV was assessed using tonometry. Forearm R_min was measured by venous occlusion plethysmography at maximal vasodilatation induced by 10 min of ischaemia in combination with skin heating and hand grip exercise. In both normotensive and hypertensive subjects, PWV correlated significantly with age and BP. Based on median age, both groups were assigned into two equally large subgroups. Normotensive older (66 ± 7 years) and younger (35 ± 10 years) persons had different carotid‐femoral PWV (7·9 ± 1·8 versus 5·7 ± 0·9 m/s, P<0·01), but similar R_min values (3·7 ± 0·9 versus 3·6 ± 1·2 mmHg/ml/min/100 ml). Hypertensive older (63 ± 6 years) and younger (40 ± 10 years) also had different PWV (8·0 ± 1·5 versus 6·7 ± 1·1 m/s, P<0·05), but the older had lower R_min (3·1 ± 0·8 versus 4·7 ± 2·2 mmHg/ml/min/100 ml, P<0·05). In a regression analysis adjusting for age, BP, gender and heart rate, no correlation was seen between PWV and R_min. The data suggest that age differentially affects PWV and R_min and that BP can increase in older persons without affecting R_min.     

Effects of walking with blood flow restriction on limb venous compliance in elderly subjects

Venous compliance declines with age and improves with chronic endurance exercise. KAATSU, an exercise combined with blood flow restriction (BFR), is a unique training method for promoting muscle hypertrophy and strength gains by using low‐intensity resistance exercises or walking. This method also induces pooling of venous blood in the legs. Therefore, we hypothesized that slow walking with BFR may affect limb venous compliance and examined the influence of 6 weeks of walking with BFR on venous compliance in older women. Sixteen women aged 59–78 years were partially randomized into either a slow walking with BFR group (n = 9, BFR walk group) or a non‐exercising control group (n = 7, control group). The BFR walk group performed 20‐min treadmill slow walking (67 m min^?1), 5 days per week for 6 weeks. Before (pre) and after (post) those 6 weeks, venous properties were assessed using strain gauge venous occlusion plethysmography. After 6 weeks, leg venous compliance increased significantly in the BFR walk group (pre: 0·0518 ± 0·0084, post: 0·0619 ± 0·0150 ml 100 ml^?1 mmHg^?1, P<0·05), and maximal venous outflow (MVO) at 80 mmHg also increased significantly after the BFR walk group trained for 6 weeks (pre: 55·3 ± 15·6, post: 67·1 ± 18·9 ml 100 ml^?1 min^?1, P<0·01), but no significant differences were observed in venous compliance and MVO in the control group. In addition, there was no significant change in arm compliance in the BFR walk group. In conclusion, this study provides the first evidence that 6 weeks of walking exercise with BFR may improve limb venous compliance in untrained elder female subjects.     

The effect of dobutamine infusion on splanchnic blood flow and oxygen transport in patients with acute pancreatitis

Objectives: To measure the blood flow distribution and oxygen transport in pancreatitis and to evaluate the regional effects of increased systemic blood flow. Design: Nonrandomized controlled trial. Setting: A general intensive care unit in a tertiary care center. Patients: 10 patients with pancreatitis requiring mechanical ventilation were studied after fluid resuscitation, and for the response to dobutamine, the patients served as their own controls. For the baseline, 11 patients scheduled for elective abdominal surgery served as a control group. Interventions: Systemic and regional hemodynamics were measured after fluid resuscitation to predefined hemodynamic endpoints. In patients with pancreatitis, the measurement was repeated after cardiac output had been increased by at least 25 % by dobutamine. Measurements and results: Hepatosplanchnic blood flow was estimated using regional catheterization and the dye dilution method. In patients with pancreatitis, the cardiac index did not differ from that of the control group (3.9 ± 0.8 vs 4.1 ± 0.7 l · min^–1· m^–2;NS). Accordingly, there was no difference in the splanchnic blood flow (1.1 ± 0.4 vs 1.2 ± 0.5 l · min^–1· m^–2;NS). Systemic and splanchnic oxygen consumption was increased in patients with pancreatitis (179 ± 25 vs 147 ± 27 ml · min^–1· m^–2, p < 0.05 and 68 ± 15 vs 49 ± 19 ml · min^–1· m^–2, p < 0.05), and systemic and splanchnic oxygen extraction was higher (0.34 ± 0.08 vs23 ± 0.05, p < 0.01 and 0.46 ± 0.18 vs 0.28 ± 0.08, p < 0.05, respectively). Dobutamine had inconsistent effects on splanchnic blood flow: in individual patients, splanchnic blood flow even decreased substantially. Conclusions: In severe pancreatitis, oxygen consumption is increased in the splanchnic region; increased splanchnic oxygen demand is not always met by adequately increased blood flow. Increasing the systemic blood flow with dobutamine does not improve perfusion in the splanchnic bed. Received: 24 September 1996 Accepted: 5 May 1997     

Evidence of diminished coronary flow in pulmonary hypertension ‐ explaining angina pectoris in this patient group?

Background: Many patients with pulmonary hypertension (PH) have symptoms of angina without evidence of occlusive coronary artery disease. For the first time, this study addresses the influence of progressively increasing pulmonary artery pressure (PAP) on left anterior descending artery flow in a rat model of PH. The role of pulmonary artery dilatation, septal wall motion abnormality, cardiac output or diastolic blood pressure in determining coronary blood flow (CBF) during PH was determined. Methods: Pulmonary hypertension was induced in 6‐week‐old female nude rats (n = 44) using monocrotaline. Animals underwent right heart catheterization and echocardiography, and blood pressure measurement was taken at baseline, 21 and 35 days. Results: A total of 103 echocardiographic studies were carried out at three fixed time points in rats with variable PAP. CBF decreased from 46·6 ± 14·3 to 24·7 ± 12·3 cm s^?1 (P<0·001) over time. Pulmonary artery diameter increased from 2·30 ± 0·19 to 2·83 ± 0·30 mm (P<0·001), and left ventricular (LV) cardiac output decreased from 143 ± 23 to 78 ± 30 ml min^?1 (P<0·001). Using observed solution estimates of 0·00170 (P = 0·0005) and ?1·75 (P = 0·006) for these variables, we calculated that CBF increased by 5·90 cm s^?1 (15·6%, CI: 14·5–17·1%) or decreased by ?4·86 cm s^?1 (?12·9%, CI: ?14·1–11·9%) for every standard deviation increase in LV cardiac output or pulmonary artery diameter, respectively. CBF decreased significantly with increasing PAP. Pulmonary artery diameter and LV cardiac output appear to be independent determinants of coronary flow in PH. Conclusions: Coronary flow reduction in murine PH has potential to be clinically meaningful and should therefore further studied in a clinical trial.     

Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise

The association between muscle oxygen uptake (VO₂) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one‐legged knee‐extension exercise at variable intensities using positron emission tomography and a‐v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI‐1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI‐2). Muscle perfusion and O₂ delivery during HI‐1 (26 ± 5 and 5·4 ± 1·0 ml 100 g^?1 min^?1) and HI‐2 (28 ± 4 and 5·8 ± 0·7 ml 100 g^?1 min^?1) were similar, but both were higher (P<0·01) than during LOW (15 ± 3 and 3·0 ± 0·6 ml 100 g^?1 min^?1). Muscle VO₂ was also higher during both HI workloads (HI‐1 3·3 ± 0·4 and HI‐2 4·1 ± 0·6 ml 100 g^?1 min^?1) than LOW (1·4 ± 0·4 ml 100 g^?1 min^?1; P<0·01) and 25% higher during HI‐2 than HI‐1 (P<0·05). O₂ extraction was higher during HI workloads (HI‐1 62 ± 7 and HI‐2 70 ± 7%) than LOW (45 ± 8%; P<0·01). O₂ extraction tended to be higher (P = 0·08) during HI‐2 when compared to HI‐1. Perfusion was less heterogeneous (P<0·05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one‐legged knee‐extension exercise at variable intensities, skeletal muscle perfusion and O₂ delivery are unchanged between high‐intensity workloads, whereas muscle VO₂ is increased during the second high‐intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O₂ delivery and uptake. We propose that the excess muscle VO₂ during the second high‐intensity workload is derived from working muscle cells.     

Standardized intermittent static exercise increases peritendinous blood flow in human leg

Alteration in tendinous and peritendinous blood flow during and after exercise is suggested to contribute to the development of Achilles tendon injury and inflammation. In the present study a method for evaluating the influence of standardized workload on peritendinous flow is presented. The radioactive isotope xenon-133 was injected just ventrally to the Achilles tendon 5 cm proximal to the tendon's insertion on the calcaneus. The disappearance of ¹³³Xe was used to determine blood flow during intermittent static exercise of the calf muscle (1·5 s exercise/1·5 s rest) for 30 min at a workload equivalent to individual body weight (1 BW) in six healthy volunteers around both Achilles tendons (n = 12). During intermittent static exercise, blood flow was increased from 1·8 ± 0·3 ml 100 g tissue^?1 min^?1 (mean value and SEM) (rest) to 6·1 ± 1·3 ml 100 g tissue^?1 min^?1 (exercise) (P<0·05). The exercise induced an average increase in blood flow (3·4-fold) equivalent to results previously obtained during regular dynamic heel raises (P>0·05). It is concluded that the method is well suited to study the influence of standardized workload on the physiology and pathophysiology of the tissue around the Achilles tendon in humans.     

Inert gas rebreathing: the effect of haemoglobin based pulmonary shunt flow correction on the accuracy of cardiac output measurements in clinical practice

Background: Cardiac output (CO) is an important cardiac parameter, however its determination is difficult in clinical routine. Non‐invasive inert gas rebreathing (IGR) measurements yielded promising results in recent studies. It directly measures pulmonary blood flow (PBF) which equals CO in absence of significant pulmonary shunt flow (Q_S). A reliable shunt correction requiring the haemoglobin concentration (c_Hb) as only value to be entered manually has been implemented. Therefore, the aim of the study was to evaluate the effect of various approaches to Q_S correction on the accuracy of IGR. Methods: Cardiac output determined by cardiac magnetic resonance imaging (CMR) served as reference values. The data was analysed in four groups: PBF without correcting for Q_S (group A), shunt correction using the patients’ individual c_Hb values (group B), a fixed standard c_Hb of 14·0 g dl^?1 (group C) and a gender‐adapted standard c_Hb for male (15·0 g dl^?1) and female (13·5 g dl^?1) probands each (group D). Results: 147 patients were analysed. Mean CO_CMR was 5·2 ± 1·4 l min^?1, mean CO_IGR was 4·8 ± 1·3 l min^?1 in group A, 5·1 ± 1·3 in group B, 5·1 ± 1·3 l min^?1 in group C and 5·1 ± 1·4 l min^?1 in group D. The accuracy in group A (mean bias 0·5 ± 1·1 l min^?1) was significantly lower as compared to groups B, C and D (0·1 ± 1·1 l min^?1; P<0·01). Conclusion: IGR allows a reliable non‐invasive determination of CO. Since PBF significantly increased the measurement bias, shunt correction should always be applied. A fixed c_Hb of 14·0 g dl^?1 can be used for both genders if the exact c_Hb value is not known. Nevertheless, the individual value should be used if any possible.     

Simultaneous quantification of myocardial perfusion,oxidative metabolism,cardiac efficiency and pump function at rest and during supine bicycle exercise using 1‐11C‐acetate PET – a pilot study

Background: PET using 1‐¹¹C‐acetate (ACE‐PET) applied at rest is used for measuring absolute myocardial blood flow (MBF) and oxidative metabolic rate (k_mono). We evaluated the feasibility of quantitative ACE‐PET during exercise. Methods: Five endurance athletes underwent dynamic PET scanning at rest and during supine bicycle stress. Exercise was maintained at a workload of 120 Watt for 17 min. The rate‐pressure product (RPP) was recorded repeatedly. MBF, k_mono in left (LV) and right (RV) ventricular wall, cardiac output (CO), cardiac efficiency and a lung uptake value reflecting left heart diastolic pressures were calculated from the PET data using previously validated models. Results: MBF increased from 0·71 ± 0·17 to 2·48 ± 0·25 ml min^?1 per ml, LV‐k_mono from 0·050 ± 0·005 to 0·146 ± 0·021 min^?1, RV‐k_mono from 0·023 + 0·006 to 0·087 + 0·014 min^‐1, RPP from 4·7 ± 0·8 to 13·2 ± 1·4 mmHg × min^?1 × 10³ and Cardiac Output from 5·2 ± 1·1 to 12·3 ± 1·2 l min ^?1 (all P < 0·001). Cardiac efficiency was unchanged (P = 0·99). Lung uptake decreased from 1·1 ± 0·2 to 0·6 ± 0·1 ml g^?1 (P < 0·001). Discussion: A number of important parameters related to cardiac function can be quantified non‐invasively and simultaneously with a short scanning protocol during steady state supine bicycling. This might open up new opportunities for studies of the integrated cardiac physiology in health and early asymptomatic disease.     

Tympanic membrane temperature decreases during head up tilt: relation to frontal lobe oxygenation and middle cerebral artery mean blood flow velocity

Introduction: Changes in blood flow influence temperature of surrounding tissues. Since the internal carotid artery (ICA) and internal jugular vein (IJV) neighbor the tympanic membrane, changes in their blood flow most likely determine changes in tympanic membrane temperature (TMT). We sought to evaluate the relationship between changes during a head-up tilt (HUT) induced reduction in cerebral blood flow (CBF) and TMT.

Methods: Ten male subjects (age 19–28 years) underwent 50° HUT until presyncope. A non-contact infrared sensor in the ear canal targeted the tympanic membrane. Changes in CBF were monitored by transcranial Doppler which determined the mean blood flow velocity in the middle cerebral artery (MCA V_mean) and by near infrared spectroscopy assessed frontal lobe oxygenation (S_cO₂), while skin blood flow (SkBF) was evaluated by laser Doppler flowmetry.

Results: During HUT, TMT decreased by 0.6?°C (median; range 0.2 to 1.6?°C) related to a decrease in MCA V_mean (51.0?±?6.7 to 34.3?±?5.8?cm/sec (mean?±?SD); r?=?0.518, p?=?.002) and S_cO₂ (78.6?±?5.4% to 69.0?±?5.7%; r?=?0.352, p?=?.043), but not to SkBF (120?±?78 to 69?±?37 PU; r?=?0.245, p?=?.142).

Conclusion: During an orthostatic challenge TMT decreases and the decrease is related to a reduction in CBF as indicated by MCA V_mean and S_cO₂, but not to SkBF. We consider TMT holds potential for non-invasive assessment of changes in cerebral perfusion.     

Glucose turnover and intima media thickness of internal carotid artery in type 2 diabetes offspring

Background First‐degree offspring (OFF) of type 2 diabetic (T2DM) patients bear a ~40% lifetime risk of developing T2DM. They are insulin resistant and carry a risk of premature atherosclerosis, the extent of which can be estimated by intima media thickness (IMT) of the carotid artery (CA). Thus, this study examines parameters of glucose and lipid metabolism, insulin sensitivity, beta cell function (BCF) and IMT with their interrelationships in middle‐aged OFF. Materials and methods T2DM‐OFF (n = 18, 14f/4m, 45·6 ± 2·1 years, BMI: 26 ± 1 kg m^?2) were compared with 18 matching humans without a family history of diabetes (CON; 14f/4m, 44·5 ± 2·1 years, BMI: 24 ± 1 kg m^?2; each P > 0·30), all with normal glucose tolerance as tested by three‐hour (75 g) oral glucose tolerance tests (OGTT). Two‐hour hyperinsulinaemic (40 mU min^?1·m^?2)isoglycaemic clamp tests were performed with simultaneous measurement of endogenous glucose (D‐[6,6‐²H₂]glucose) production (EGP). IMT [internal (ICA), common CA, and bulb] were measured sonographically. BCF was assessed by Adaptation Index (AI). Results Before and during OGTT, both groups were similar in plasma glucose, insulin, C‐peptide and free fatty acids (FFA), whereas OFF showed ~30% lower (P < 0·03) fasting plasma triglycerides before OGTT. During hyperinsulinaemic clamps, insulin sensitivity was ~38% lower (P < 0·03) in OFF who showed higher plasma FFA (44 ± 9 µmol L^?1) than CON (26 ± 3 µmol L^?1, P < 0·05) after 90 min. EGP was similar in both groups. OFF had 38% (P < 0·007) reduced AI. ICA‐IMT was ~18% higher in OFF (P < 0·002), but did not correlate with insulin sensitivity. Conclusion The data obtained show middle‐aged T2DM‐OFF with normal glucose tolerance displaying reduced total insulin sensitivity and impaired beta cell function, which relates to impaired insulin‐dependent suppression of plasma FFA and increased ICA‐IMT.