Cerebral haemodynamics during the Mueller manoeuvre in humans

Voluntary negative intra‐thoracic pressure (Mueller manoeuvre) is known to reduce arterial blood pressure (ABP). To investigate changes in cerebral blood flow velocity (CBFV) during 15 s Mueller manoeuvres at –30 mmHg intra‐thoracic pressure, 27 young (aged 21–31 years, group A) and 11 older (52–64 years, group B) healthy adults were studied using transcranial Doppler and non‐invasive ABP measurement (Finapres). After closely following the initial ABP drop, CBFV showed an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased significantly to below baseline. While ABP declined further until the end of the manoeuvre, CBFV increased in group A 4·7 s (2·4–8·5) (median and range) and in group B 5·7 s (4·1–7·2) after the onset of the CBFV decrease. Critical closing pressure (CCP), calculated for each cardiac cycle from the dynamic pressure–flow relationship (DPFR), indicated a reduction of intra‐cranial pressure during the first half of the strain. DPFR‐related estimation of cerebrovascular resistance provided a more physiological response than the conventional cerebrovascular resistance quotient ABP/CBFV, and decreased about 1·5 s before the observed CBFV increase. A modification of the previously described dynamic auto‐regulation index ROR correlated significantly with CO₂ reactivity values (r=0·61, P=0·001). In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect dynamic cerebral auto‐regulation and may provide an estimate of dynamic cerebral auto‐regulation capacity. In older adults, the maximal dynamic auto‐regulatory response seems to be unchanged, but the onset of reaction is slightly delayed.     

Long‐term changes in dynamic cerebral autoregulation: a 10 years follow up study

This study takes a novel approach to describing time‐related changes in dynamic cerebral autoregulation (dCA). It is well‐recognized that dCA exhibits both intra‐ and inter‐ subject variability, and this study seeks to characterize the extent to which intra‐subject variability occurs after a significant period of time by studying the same subjects 10 years apart, thus eliminating inter‐subject variability as a source of error. Ten healthy subjects were identified in 1998 and followed up in 2008. On each visit they underwent simultaneous recordings of right middle cerebral artery cerebral blood flow velocity (RMCA CBFV), blood pressure and heart rate. Data were analysed in the frequency domain using transfer function analysis and in the time domain using CBFV step response, from which the autoregulatory index (ARI) was calculated. Ten subjects of mean age 35·5 (range 24–51) years in 1998 (seven male) were studied. There was a significant fall in ARI from 1998–2008 (ΔARI = 1·1, P = 0·021), along with a significant rise in coherence in 2008 (at 0·05 Hz, P = 0·018). Difference in mean step response between 1998 and 2008 was also significant (P = 0·045). This is the first study to assess dCA in the same subjects 10 years apart, providing a novel opportunity to assess intra‐subject variation in dCA after a long time period has elapsed. A fall in frequency and time domain parameters was observed. This is important, and needs to be considered in future studies assessing long‐term changes in dCA, particularly given the body evidence which suggests that dCA is unaffected by ageing.     

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.     

Pulmonary capillary blood flow by partial CO2 rebreathing: importance of the regularity of the respiratory pattern

The partial CO₂ rebreathing technique has been shown to be a reliable non‐invasive method for measurement of pulmonary capillary blood flow (Q˙_c), but experience with this technique has been limited to controlled mechanical ventilation. In this study, we evaluated this technique during spontaneous and oriented ventilation in nine subjects without known cardiopulmonary disease. Subjects underwent 10 consecutive (Q˙_c) measurements with both spontaneous and oriented ventilation. Breath‐by‐breath gas exchange was measured and (Q˙_c) was calculated from changes in CO₂ elimination and P_ETCO₂, which were achieved by sudden increase of the apparatus deadspace (rebreathing period). An exponential curve was fitted to the P_ETCO₂ values in the rebreathing period in order to estimate P_ETCO₂ at equilibrium. We found that mean (Q˙_c) values were not influenced by the ventilation pattern (P=0·51), but that the intra‐individual variability with oriented ventilation (median=16·0%) was significantly lower than with spontaneous ventilation (median=31·8%, P=0·039). Accordingly, the curve fitting for rebreathing P_ETCO₂ rise failed in 4·4% of measurements with oriented ventilation vs. 18·9% of measurements with spontaneous ventilation (P=0·039). Our results suggest that the performance of the partial CO₂ rebreathing technique is adversely affected by spontaneous ventilation and, consequently, that this method should be reserved for patients with regular respiratory patterns.     

Effect of the H1 blocker d-chlorpheniramine on cerebral blood flow in the conscious dog during normocapnic hypoxia

The mechanism causing cerebral vasodilatation during hypoxia remains unclear. A role for histamine is suspected because H₂ receptor-blocking drugs blunt the hypoxia-induced increase in cerebral blood flow (CBF). Moreover, in vitro blockade of H₁ receptors by chlorpheniramine decreases the vasodilatation of cerebral arteries that is induced by histamine. The present study tested the hypothesis that an H₁ receptor blocker (d-chlorpheniramine) would have a similar effect in vivo during hypoxia. Isocapnic hypoxia (inspired oxygen fraction, FIO ₂ = 0·10; inspired carbon dioxide fraction, FICO ₂ = 0·035) was induced in 16 conscious dogs randomly divided into two groups: eight dogs received saline intravenously (controls) at time 0 (normoxia) and after 2 h and 4 h hypoxia, and the other eight dogs received d-chlorpheniramine intravenously (0·5 mg kg^?1) to block the H₁ receptors. Regional CBF was measured by the radioactive microspheres technique 15 min after each injection of d-chlorpheniramine or saline. In the control group, CBF increased during hypoxia in all regions of the brain. In the d-chlorpheniramine group, total CBF increased similarly after 2 h of hypoxia. After 4 h of hypoxia, the increase was limited, especially in the pons, cerebral peduncles, hippocampus, hypothalamus, thalamus, and occipital lobes (six out of 12 studied regions). It is concluded that the H₁ blocker d-chlorpheniramine did not strongly inhibit the increase in CBF during hypoxia. After cumulative doses, however, as in the fourth hour of hypoxia, the increase in total CBF was limited.     

Cytogenetic patterns in multiple myeloma after a phase of preceding MGUS

Background Presenting the same histological diagnosis, multiple myeloma (MM) shows a large genomic variety, resulting in variable times of overall survival. Materials and methods To investigate major cytogenetic categories (any 14q‐translocation, t(11;14), t(4;14), 13q‐deletions, 17p‐deletions) and their clinical consequences in MM after a pre‐existing monoclonal gammopathy (MM post‐MGUS), we performed a comparative analysis of 41 patients with MM post‐MGUS and 287 patients with unknown prior history MM (U‐MM). Results In MM post‐MGUS, a t(11;14) was found to be more frequent than in U‐MM (24% vs. 14%) and it was associated with significantly shortened survival (24 months vs. 70 months in U‐MM; P = 0·01). MM post‐MGUS was further characterized by a higher frequency of 13q‐deletions only (absence of all other specific abnormalities; 28% vs. 12% in U‐MM; P = 0·02). A 13q‐deletion only was an indicator of long survival in MM post‐MGUS (median not yet reached) as opposed to U‐MM (median survival, 29 months; P = 0·001). 17p‐deletions were infrequent in MM post‐MGUS (3% vs. 16% in U‐MM; P = 0·04). Survival times for patients with t(4;14) and/or 17p‐deletions and other abnormalities were similar in both MM patient cohorts. Conclusions Our data suggest that t(11;14) and 13q‐deletions have distinct prognostic implications in the context of MM post‐MGUS.     

Reproducibility of blood oxygen level‐dependent signal changes with end‐tidal carbon dioxide alterations

Hypercapnia has been utilized as a stimulus to elicit changes in cerebral blood flow (CBF). However, in many instances it has been delivered in a non‐controlled method that is often difficult to reproduce. The purpose of this study was to examine the within‐ and between‐visit reproducibility of blood oxygen level‐dependent (BOLD) signal changes to an iso‐oxic square wave alteration in end‐tidal carbon dioxide partial pressure (P_etCO₂). Two 3‐Tesla (3T) MRI scans were performed on the same visit, with two square wave alterations administered per scan. The protocol was repeated on a separate visit with minimum of 3 days between scanning sessions. P_etCO₂ was altered to stimulate changes in cerebral vascular reactivity (CVR), while P_etO₂ was held constant. Eleven subjects (six females; mean age 26·5 ± 5·7 years) completed the full testing protocol. Excellent within‐visit square wave reproducibility (ICC > 0·75) was observed. Similarly, square waves were reproducible between scanning sessions (ICC > 0·7). This study demonstrates BOLD signal changes in response to alterations in P_etCO₂ are reproducible both within‐ and between‐visit MRI scans.     

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.     

Ultrasound measurements of carotid intima–media thickness by two semi‐automated analysis systems

Increased carotid intima–media thickness (cIMT) is associated with an increased risk of cardiac events and stroke. Several semi‐automated edge‐detection techniques for measuring cIMT are used for research and in clinical practice. Our aim was to compare two currently available semi‐automated techniques for the measurement of cIMT. Carotid ultrasound recordings were obtained from 99 subjects (mean age 54·4 ± 8·9 years, range 33–69) without known cardiovascular diseases using a General Electric (GE) Vivid 7 ultrasound scanner, 8‐MHz transducer. The far‐wall cIMT was evaluated 1–2 cm proximal to the carotid bulb. Three diastolic images (ECG R‐wave) from the left and three images from the right common carotid arteries were analysed using GE and Artery Measurement System (AMS) semi‐automated softwares. Mean systolic and diastolic blood pressures were 120 ± 13 and 76 ± 8 mmHg, respectively. The cIMT_mean (left + right)/2 by GE and cIMT_mean (left + right)/2 AMS were highly correlated (r = 0·92, P<0·001). Higher values were measured by GE (0·72 ± 0·12 mm) compared with AMS (0·69 ± 0·12 mm), and this was significant (P<0·001). The coefficients of variation for the intra‐observer variability of cIMT_mean (left + right)/2 were 1·0% (GE) and 2·2% (AMS). cIMT_mean measured by GE's semi‐automated edge‐detection method correlated well with that measured by AMS. However, there were small but significant systematic differences between the cIMT_mean values measured by the two techniques. Thus, the use of only one type of measurement program seems favourable in follow‐up studies and when evaluating treatment effects.     

A comparison of head motion and prefrontal haemodynamics during upright and recumbent cycling exercise

The aim of this observational study was to compare head motion and prefrontal haemodynamics during exercise using three commercial cycling ergometers. Participants (n = 12) completed an incremental exercise test to exhaustion during upright, recumbent and semi‐recumbent cycling. Head motion (using accelerometry), physiological data (oxygen uptake, end‐tidal carbon dioxide [P_ETCO₂] and heart rate) and changes in prefrontal haemodynamics (oxygenation, deoxygenation and blood volume using near infrared spectroscopy [NIRS]) were recorded. Despite no difference in oxygen uptake and heart rate, head motion was higher and P_ETCO₂ was lower during upright cycling at maximal exercise (P<0·05). Analyses of covariance (covariates: head motion P>0·05; P_ETCO₂, P<0·01) revealed that prefrontal oxygenation was higher during semi‐recumbent than recumbent cycling and deoxygenation and blood volume were higher during upright than recumbent and semi‐recumbent cycling (respectively; P<0·05). This work highlights the robustness of the utility of NIRS to head motion and describes the potential postural effects upon the prefrontal haemodynamic response during upright and recumbent cycling exercise.     

MMP-9 haplotypes and carotid artery atherosclerosis: an association study introducing a novel multicolour multiplex RealTime PCR protocol

Background Among other matrix metalloproteinases (MMPs), gelatinase B (MMP‐9) is discussed to be associated with the pathogenesis of vascular diseases. Two single nucleotide polymorphisms (SNPs) of the MMP‐9 gene, C‐1562T in the promoter region and a G/A transition in exon 6 (R + 279Q), have been addressed in previous association studies which, however, produced conflicting results. Material and methods A novel multiplex RealTime PCR protocol for the fast and simultaneous detection of both polymorphisms is presented, which was used for genotyping 1737 participants of a prospective study investigating genetic factors influencing the progression of atherosclerosis. Results Haplotype analysis revealed –1562C/+279Q as the major haplotype in this population. Allelic distribution of the C‐1562T polymorphism was consistent with data published for similar cohorts; however, we found that R + 279Q allelic distribution appears to vary significantly among Caucasian populations. Considering clinical data available from 1487 participants, we found significant associations between the presence of atherosclerotic plaque and the CA‐haplotype in men (P = 0·028, phi = 0·08), and between the AG variant of exon 6 and common carotid artery intima‐media thickness (CIMT) in women (P = 0·004, Eta² = 0·019). Conclusions In summary, our results demonstrate associations of MMP‐9 genotypes with different stages of carotid atherosclerosis.     

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.     

Ventilation–perfusion inequality and carbon dioxide sensitivity in hypoxaemic chronic obstructive pulmonary disease (COPD) and effects of 6 months of long‐term oxygen treatment (LTOT)

The aim of our study was to find out how blood gas disturbances in stable, eucapnic, severe chronic obstructive pulmonary disease (COPD) patients with an arterial oxygen tension (PaO₂) value of 7·7 (6·1–8·4) kPa are affected by ventilation–perfusion (V_A/Q) relationships and carbon dioxide (CO₂) sensitivity and how these parameters are influenced by 6 months of long‐term oxygen treatment (LTOT). V_A/Q ratios were measured using the multiple inert gas elimination technique (MIGET). Mouth occlusion pressure 0·1 s after onset of inspiration (Pi0·1) and minute ventilation (V_E) were measured to assess respiratory drive response (ΔPi0·1/ΔPCO₂) and hypercapnic ventilatory response (HCVR) to CO₂ rebreathing. At the start of LTOT, a normal median respiratory drive response level of 1·2 (0·2–2·3) cm H₂O/kPa and a low median HCVR as compared with healthy individuals (P<0·001) were found. However, 7·9 (0–29·8)% of the V_E, was directed towards hypoperfused lung areas. The dispersion of ventilation (log SDV; 0·47–1·76), and the dispersion of perfusion (log SDQ; 0·66–1·07) were wider than normal. The PaO₂ level correlated inversely with mean V_A/Q ratio for ventilation (V mean) and shunt. The PaCO₂ level correlated inversely with HCVR and vital capacity. After 6 months of LTOT, no significant changes in daytime blood gas levels, CO₂‐sensitivity or V_A/Q ratios were found. V_E tended to be reduced by 1·0 l min^–1. Conclusions: An elevated V mean and probably shunting are important contributing factors for the reduced PaO₂ and hypercapnic ventilatory response is a major determinant of PaCO₂ in eucapnic stable hypoxaemic COPD. Six months of LTOT does not affect blood gases, CO₂ sensitivity or ventilation–perfusion relationships.     

Dynamic cerebral autoregulation and cerebrovascular reactivity: a comparative study in lacunar infarct patients

The major purpose of this study was to simultaneously evaluate dCA before and shortly after cerebral vasodilatation evoked by infusion of acetazolamide (ACZ). It was questioned if and to what degree dCA was changed after ACZ infusion. Using 15 mg kg(-1) ACZ infusion cerebrovascular reactivity (CVR) was assessed in 29 first ever lacunar stroke patients (19 M/10 F). During the CVR-test, the electrocardiogram, non-invasive finger arterial blood pressure (ABP) and middle cerebral artery blood flow velocity (CBFV) were recorded. DCA based on spontaneous blood pressure variations was evaluated in 24 subjects by linear transfer function analysis. Squared coherence, gain and phase angle in the frequency range of autoregulation (0.04-0.16 Hz) were compared before and after ACZ infusion. After ACZ infusion, median phase angle decreased significantly (p < 0.005 Wilcoxon) to 0.77 rad compared to a pre-test baseline value of 1.05 rad, indicating less efficient dCA due to ACZ. However, post-test phase values are still mostly within the normal range. Poor and statistically non-significant correlations were found between CVR and absolute dCA phase angle. It can be concluded that CVR testing with body weight adjusted infusion of ACZ lowers dCA performance but by no means exhausts dCA, suggesting that in this way maximal CVR is not determined. Characterizing dCA based on transfer function analysis of ABP to CBFV needs no provocation and adverse patient effects are minimal. The poor correlation between CVR and dCA phase angle supports an interpretation that CVR and dCA study different mechanisms of cerebrovascular control.     

An 18oxygen inhalation method for determination of total body formation of nitric oxide in humans

The formation of nitric oxide (NO) and the subsequent conversion of the NO formed into nitrate require molecular oxygen. Based on this fact, we have recently developed a method using inhalation of the stable oxygen isotope, i.e. ¹⁸O₂, to determine total formation of NO in small laboratory animals. The method has now been further developed to be applicable also in humans. Five healthy awake male subjects inhaled a gas mixture of unlabelled and 18-labelled oxygen (approximate ratio 4:1) in nitrogen from a closed breathing system equipped with eliminators for carbon dioxide and water vapour. The ratio of unlabelled to 18-labelled oxygen, as well as the total oxygen concentration during the inhalation, were monitored. Venous blood samples were taken before and after the inhalation for analysis of unlabelled and ¹⁸O-labelled nitrate by gas chromatography/mass spectrometry. The procedure was repeated with the same protocol on a later occasion, during ongoing treatment with the NO synthesis inhibitor N^G-monomethyl- L -arginine ( L -NMMA). The average nitrate level in plasma in the absence of L -NMMA was 26 μmol l^–1. The rate of total synthesis of NO was estimated to be 0·38 ± 0·06 μmol kg^–1 h^–1, corresponding to a total body formation of 600–700 μmol/24 h in an adult male. Infusion of L -NMMA caused an increase in mean arterial blood pressure from 86 ± 4 to 99 ± 5 mmHg (P<0·05). The average plasma level of nitrate during infusion of L -NMMA was 24 μmol l^–1. NO formation during infusion of L -NMMA was 0·17 ± 0·03 μmol kg^–1 h^–1, i.e. significantly (P<0·05) lower than in the absence of L -NMMA. We suggest that the described method allows direct determination of total NO formation in man. The method may be useful in the study of various experimental and pathophysiological conditions affecting NO formation.     

Influence of arterial wave reflection on carotid blood pressure and intima‐media thickness in older endurance trained men and women with pre‐hypertension

Increased carotid intima‐media thickness (IMT) with aging is a significant predictor of mortality. Older endurance trained (ET) individuals have lower carotid artery stiffness but similar carotid IMT when compared to sedentary (SED) age‐matched peers. The purpose of this study was to examine the contribution of arterial wave reflections to carotid hemodynamics and IMT in older ET and SED with pre‐hypertension. Subjects consisted of endurance‐trained master athletes and age‐matched sedentary controls (mean age 67 years). Carotid artery Beta‐stiffness index and IMT was assessed with ultrasonography. Carotid pressure and augmented pressure from wave reflections (obtained from pulse contour analysis) was measured with applanation tonometry. Carotid systolic blood pressure (SBP) and IMT were not different between groups (P>0·05). Carotid stiffness was significantly lower in ET versus SED (7·3 ± 0·8 versus 9·9 ± 0·6, P<0·05). Augmented pressure was significantly greater in ET versus SED (17·7 ± 1·6 versus 13·3 ± 1·5 mmHg, P<0·05). When adjusting for differences in resting heart rate, there were no group differences in augmented pressure. In conclusion, older ET persons with pre‐hypertension have reduced carotid artery stiffness, but similar carotid SBP and carotid IMT when compared to SED. The lack of change in carotid SBP and IMT in older ET may be related to the inability of chronic exercise training to reduce bradycardia‐related augmented pressure from wave reflections with aging.     

Relationship between peak cardiac pumping capability and indices of cardio-respiratory fitness in healthy individuals

Cardiac power output (CPO) is a unique and direct measure of overall cardiac function (i.e. cardiac pumping capability) that integrates both flow‐ and pressure‐generating capacities of the heart. The present study assessed the relationship between peak exercise CPO and selected indices of cardio‐respiratory fitness. Thirty‐seven healthy adults (23 men and 14 women) performed an incremental exercise test to volitional fatigue using the Bruce protocol with gas exchange and ventilatory measurements. Following a 40‐min recovery, the subjects performed a constant maximum workload exercise test at or above 95% of maximal oxygen consumption. Cardiac output was measured using the exponential CO₂ rebreathing method. The CPO, expressed in W, was calculated as the product of the mean arterial blood pressure and cardiac output. At peak exercise, CPO was well correlated with cardiac output (r = 0·92, P<0·01), stroke volume (r = 0·90, P<0·01) and peak oxygen consumption (r = 0·77, P<0·01). The coefficient of correlation was moderate between CPO and anaerobic threshold (r = 0·47, P<0·01), oxygen pulse (r = 0·57, P<0·01), minute ventilation (r = 0·53, P<0·01) and carbon dioxide production (r = 0·56, P<0·01). Small but significant relationship was found between peak CPO and peak heart rate (r = 0·23, P<0·05). These findings suggest that only peak cardiac output and stroke volume truly reflect CPO. Other indices of cardio‐respiratory fitness such as oxygen consumption, anaerobic threshold, oxygen pulse, minute ventilation, carbon dioxide production and heart rate should not be used as surrogates for overall cardiac function and pumping capability of the heart.     

Left ventricular diastolic function is enhanced after peak exercise in endurance‐trained adolescents as well as in their non‐trained controls

The aims of the study were to explore the temporal change of cardiac function after peak exercise in adolescents, and to investigate how these functional changes relate to maximal oxygen uptake (VO_2max). The cohort consisted of 27 endurance‐trained adolescents aged 13–19 years, and 27 controls individually matched by age and gender. Standard echocardiography and colour tissue Doppler were performed at rest, and immediately after as well as 15 min after a maximal cardio pulmonary exercise test (CPET) on a treadmill. The changes in systolic and diastolic parameters after exercise compared to baseline were similar in both groups. The septal E/e′‐ratio increased immediately after exercise in both the active and the control groups (from 9·2 to 11·0; P<0·001, and from 8·7 to 10·2; P = 0·008, respectively). In a comparison between the two groups after CPET, the septal E/e′‐ratio was higher in the active group both immediately after exercise and 15 min later compared to the control group (P = 0·007 and P = 0·006, respectively). We demonstrated a positive correlation between VO_2max and cardiac function including LVEF and E/e′ immediately after CPET, but the strongest correlation was found between VO_2max and LVEDV (r = 0·67, P<0·001) as well as septal E/e′ (r = 0·34, P = 0·013). Enhanced diastolic function was found in both groups, but this was more pronounced in active adolescents. The cardiac functional response to exercise, in terms of LVEF and E/e′, correlates with the increase in VO₂ uptake. These findings in trained as well as un‐trained teenagers have practical implications when assessing cardiac function.     

Grading of dynamic cerebral autoregulation without blood pressure recordings: a simple Doppler-based method

Transcranial Doppler sonography allows for noninvasive assessment of dynamic cerebral autoregulation. A wider clinical use of this approach has been hampered by the need for continuous arterial blood pressure (ABP) measurements. We describe a new method of a pure Doppler signal based estimation of dynamic autoregulation using heart rate (HR) and cerebral blood flow velocity (CBFV) information. The phase between these two signals was assessed from 0.1 Hz oscillations induced by regular breathing. We compared this new approach with the standard method (phase between ABP and CBFV oscillations) in 93 patients with unilateral severe carotid artery obstruction. On a group level, the phase HR-CBFV differed significantly between ipsi- and contralateral sides (p = 0.024) and correlated significantly with the standard phase ABP-CBFV (r = 0.369, p < 0.001). The proposed method can, thus, detect impaired dynamic autoregulation in occlusive carotid artery disease using a single Doppler probe.     

Intracellular pH,intrauterine growth and the insulin resistance syndrome

Defects of both sodium–hydrogen exchange (NHE) and sodium–lithium countertransport (SLC) have been described in subjects at increased risk of coronary heart disease (CHD). Sodium transport is linked to the regulation of cell volume, intracellular pH and cell growth, which may explain aspects of this association. However, impaired growth in early life is also linked to adult CHD, and ‘programmed’ alterations of cell behaviour are postulated to be responsible for this. In this study, therefore, we examined whether NHE or SLC in adults are predicted by anthropometric measures at birth, as well as being associated with insulin resistance syndrome (IRS) variables in adulthood. Red cell SLC was measured in 26 adults, and NHE in dermal fibroblasts from another 15 subjects characterized anthropometrically at birth. SLC activity correlated with LDL cholesterol, triglycerides and urate (r=0·42 – 0·49; 0·05 > P>0·01), but not birth anthropometry. NHE V_max correlated with plasma insulin (r=0·80; P<0·001), but birth weight was unrelated to V_max, K_m or Hill coefficient for H⁺_i. However, pH_i correlated with birth weight (r=0·74; P=0·002), insulin sensitivity (r=0·52; P<0·05), fasting glucose (r=–0·52; P<0·05) 2 h insulin (r=0·51; P<0·05) 2 h glucose (r=–0·54; P<0·05). In conclusion, red cell SLC is related to IRS variables, but not with birth weight measures. In contrast, low intracellular pH_i is related to both low birth weight and adult insulin resistance, suggesting it might be a ‘programmed’ cell phenotype, although this is not apparently explained by altered NHE kinetics.