Resting Blood Flow Research Articles

Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor.

In the present study, we delivered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the functional performance of the developed collateral vessels. The left femoral artery of a male Japanese White rabbit was excised to induce limb ischemia, and a section of skin was resected for culture of auto-fibroblasts. Twenty days later, the VEGF gene, bFGF gene or beta-galactosidase gene (LacZ) was adenovirally transferred to the cultured auto-fibroblasts (5x10(6) cells), and the next day, a pair of specifically infected fibroblasts (total 1x10(7) cells) was injected via the left internal iliac artery of the same rabbit. Pairs of transferred genes into the fibroblasts were as follows: LacZ/LacZ (control group), VEGF/LacZ (VEGF group), bFGF/LacZ (FGF group) and VEGF/bFGF (combination group). Twenty-eight days after cell administration, collateral development and its function were evaluated. Calf blood pressure ratio, resting blood flow of the left iliac artery and capillary density of ischemic muscle showed similar degrees of angiogenic effects in the VEGF and FGF groups, which were significantly greater than those in the control group. On the contrary, angiographic score, collateral conductance and smooth muscle cell (SMC)-positive vessel density in the FGF group were significantly greater than those in the VEGF group. In the combination group, collateral conductance showed synergistic effects, and in vivo blood flow and smooth muscle cell-positive vessel density revealed additive effects of VEGF and bFGF. These findings suggested that bFGF-induced collateral development exceeded VEGF-induced collateral development in the induction of arteriogenesis, and that combined gene delivery of VEGF and bFGF produced additive or synergistic effects of collateral development as compared with the effects induced by transfer of each gene alone.

Pathophysiology and diagnosis of hibernating myocardium in patients with post-ischemic heart failure: the contribution of PET.

Identification and treatment of hibernating myocardium (HM) lead to improvement in LV function and prognosis in patients with post-ischemic heart failure. Different techniques are used to diagnose HM: echocardiography, MRI, SPECT and PET and, in patients with moderate LV impairment, their predictive values are similar. There are few data on patients with severe LV dysfunction and heart failure in whom the greatest benefits are apparent after revascularization. Quantification of FDG uptake with PET during hyperinsulinemic euglycemic clamp is accurate in these patients with the greatest mortality risk in whom other techniques may give high false negative rates. The debate on whether resting myocardial blood flow to HM is reduced or not has stimulated new research on heart failure in patients with coronary artery disease. PET with H2(15)O or 13NH3 has been used for the absolute quantification of regional blood flow in human HM. When HM is properly identified, resting blood flow is not different from that in healthy volunteers although a reduction of approximately 20% can be demonstrated in a minority of cases. PET studies have shown that the main feature of HM is a severe impairment of coronary vasodilator reserve that improves after revascularization in parallel with LV function. Thus, the pathophysiology of HM is more complex than initially postulated. The recent evidence that repetitive ischemia in patients can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and HM are two facets of the same coin.

Exogenous nitric oxide increases basal leg glucose uptake in humans

This study addressed the role of blood flow and nitric oxide in leg glucose uptake. Seven subjects (5 men, 2 women) were studied during conditions of resting blood flow and increased blood flow, achieved by infusion of the nitric oxide (NO) donor sodium nitroprusside (SNP) into the femoral artery. Femoral arterial and venous blood samples were obtained and blood flow was determined by infusion of indocyanine green dye. SNP infusion significantly increased leg blood flow (769 ± 103 v 450 ± 65 mL · min−1 · leg−1, P < .001), but did not affect arterial (4.68 ± 0.13 mmol/L control, 4.63 ± 0.09 mmol/L SNP) or venous (4.60 ± 0.14 mmol/L control, 4.54 ± 0.10 mmol/L SNP) glucose concentrations. Glucose uptake was significantly (P < .01) higher during SNP infusion (65 ± 6 μmol · min−1 · leg−1) than during the basal period (34 ± 6 μmol · min−1 · leg−1), whereas lactate release was unaffected (rest, 45 ± 11 μmol · min−1 · leg−1; SNP, 42 ± 14 μmol · min−1 · leg−1). We conclude that blood flow and/or NO increase basal leg glucose uptake.

Cerebral blood flow and anxiety in older men: An analysis of resting anterior asymmetry and prefrontal regions

Asymmetric resting blood flow in prefrontal and hemispheric regions, assessed by single photon emission computed tomography (SPECT), was examined as a potential biological marker for enhanced trait and state anxiety in 30 older men (ages 55–81). Average and asymmetric perfusion in dorsolateral, medial, and orbital regions of the prefrontal lobes was also assessed. Results indicated a significant association between lower levels of resting dorsolateral blood flow and greater state anxiety responses to a series of stressful provocations (measured on a separate occasion). A significant curvilinear (U-shaped) relation between asymmetric dorsolateral perfusion and state anxiety was also identified; increased asymmetric blood flow favoring either the right or the left dorsolateral region related to higher levels of state anxiety. However, this association was attenuated by age and systolic blood pressure. Resting perfusion in the dorsolateral region may represent a more reliable biological marker for state anxiety than trait anxiety in older men.

EFFECTS OF 48 HOURS OF LEG SUSPENSION ON FEMORAL ARTERY VASCULAR PROPERTIES

Physical inactivity is associated with an increased risk of cardiovascular mortality. Vascular changes contributing to this increased risk are largely unknown. In order to study the effect of inactivity on vascular properties, without profound systemic effects like in bed rest and space flight, the leg suspension model was used. This model has been used successfully to study effects of inactivity on strength. However, effects on vascular properties have not been reported. PURPOSE To determine short term vascular adaptations to 48 hours of inactivity using the leg suspension model. METHODS In 6 subjects one leg was suspended for 48 hours, while subjects used crutches for walking. Before and after leg suspension foot volume (measured by water displacement) and maximal voluntary contraction (MVC) of the quadriceps muscle were determined to test effectiveness of the inactivation. Resting blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA), and the hyperemic response in the SFA after 13 minutes of arterial occlusion were measured by echo doppler ultrasound. RESULTS In the suspended leg quadriceps MVC decreased from 736 ± 123 N to 698 ± 105 N, p < 0.05 and foot volume increased from 1145 ± 114 ml to 1173 ± 117 ml, p < 0.05. CFA blood flow was unaltered (before: 238 ± 74 ml/min, after 307 ± 129 ml/min). While resting SFA blood flow was unchanged (before: 129 ± 67 ml/min, after 102 ± 53 ml/min), the hyperemic response in the SFA was markedly decreased (before: 864 ± 259 ml/min, after 584 ± 150 ml/min, p < 0.05), suggesting functional vascular adaptation to inactivity. CONCLUSION Leg suspension for a short period of 48 hours is effective in changing quadriceps muscle strength and foot volume, changes that have previously been described after 28 days of suspension. While resting CFA and SFA blood flow are not affected by 48 hours of leg suspension, the hyperemic response in the SFA is significantly diminished, suggesting fast adaptation of vascular properties to inactivity.

Validation of an Angiographic Method for Estimating Resting Blood Flow to Distal Tissue Beds in the Lower Extremities

The authors propose to validate an angiographic scoring system that estimates the resting blood flow in the lower extremities in patients with peripheral vascular disease (PVD). Twenty patients with PVD underwent lower-extremity angiography. For each patient, three readers used the proposed scheme to estimate flow within 23 separate vessel segments from the infrarenal aorta to the pedal vessels. Each reviewer scored each angiogram twice. The scheme includes not only an assessment of stenoses and occlusions but also corrections for collaterals. Flow reductions to muscles in the thigh and calf were calculated by multiplying the estimated flows in the series of vessels that lead to these regions. The consistency of the scoring scheme was assessed by calculating Pearson correlation coefficients for intra- and interobserver variability. The scoring scheme was also used to estimate the ankle-brachial index (ABI) and these estimates were compared to the known ABIs. Overall, the scoring scheme demonstrated very good intra- and interobserver agreement. Correlation coefficients were typically greater than 0.9. In general, the correlation coefficients for proximal vessels were higher than those for distal vessels. The scoring scheme also had minimal intra- and interobserver variability for estimated flows to distal tissue beds. Agreement was better for a series of vessels than it was for individual segments. The estimated ABIs correlated well with the measured ABIs in all but two cases. These outliers include one case in which the measured ABI was >1 as a result of noncompressible vessels and the estimated ABI correctly reflected PVD. In the second case, the ABI was near normal because of a patent peroneal artery and our estimated ABI was abnormally low because our estimation method failed to factor in the peroneal artery. The proposed angiography scoring system reproducibly estimated flow reductions to distal tissue beds. The authors plan to use this system as a research tool for evaluating new methods of assessing and treating PVD.

In vivo evidence of altered skeletal muscle blood flow in chronic tension-type headache.

Brain. 2002 Feb;125(Pt 2):320-326 Painful impulses from tender pericranial muscles may play a major role in the pathophysiology of chronic tension-type headache. Firm evidence for peripheral muscle pathology as a cause of muscle pain and chronic headache is still lacking. Using a microdialysis technique, we aimed to estimate in vivo blood flow and interstitial lactate concentrations in the trapezius muscle at rest and during static exercise in patients with chronic tension-type headache and in healthy subjects. We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle (on the non-dominant side) of subjects, and dialysates were collected at rest, 15 and 30 min after the start of static exercise (10% of maximal force) and 15 and 30 min after the exercise was completed. All samples were coded and analysed blind. The primary endpoints were to detect a difference between patients and controls in changes of muscle blood flow and the interstitial lactate concentration from baseline to exercise and post-exercise periods. The increase in muscle blood flow from baseline to exercise and post-exercise periods was significantly lower in patients than controls (P = 0.03). There was no difference in resting blood flow between patients and controls (P = 0.43). Resting interstitial concentration of lactate did not differ between patients (2.51 ± *T0.18 mM; mean ± standard error of the mean) and controls (2.35 ± 0.23 mM, P = 0.57). There was no difference in change in interstitial lactate from baseline to exercise and post-exercise periods between patients and controls (P = 0.38). The present study provides in vivo evidence of decreased blood flow in response to static exercise in a tender muscle in patients with chronic tension-type headache. We suggest that, because of increased excitability of neurones in the CNS, the central interpretation and response to normal sensory input are altered in patients with chronic tension-type headache. This may lead to enhanced sympathetically mediated vasoconstriction and thereby a decreased blood flow in response to static exercise. Comment: An important study which links decreased blood flow in statically exercised trapezius muscle in patients with chronic tension-type headache (CTTH) with muscle tenderness. A better understanding of the pathophysiology of CTTH may provide a clue to novel therapeutic maneuvers. DSM

Phasic coronary blood flow velocity pattern and flow reserve in the atrium: regulation of left atrial myocardial perfusion

ObjectivesThe purpose of this study was to assess rest and stress atrial coronary blood flow (CBF) velocity and flow reserve. BackgroundBecause of the limitations of the methods used until now for assessing myocardial perfusion (MP) in the small mass of atrial tissue, data are lacking for human atrial MP. MethodsSeventeen patients with suitable coronary anatomy underwent CBF velocity measurements with the use of a Doppler guide wire in the proximal left circumflex coronary artery (LCx) and left atrial circumflex branch (LACB), at baseline and after adenosine administration. All measurements were performed at resting heart rate and at 100 and 120 beats/min. ResultsCoronary blood flow velocity in the LACB showed a predominant systolic pattern in contrast to the diastolic pattern of the LCx. There was a disproportionate increase in baseline time-averaged peak coronary flow velocity (cm/s) between the LACB and LCx during the two levels of pacing-induced stress (16.8 ± 5.5 vs. 16.2 ± 5.1 at rest; 22.9 ± 7.9 vs. 18.4 ± 5.2 at 100 beats/min; and 27.1 ± 8.0 vs. 20.4 ± 5.1 at 120 beats/min; significant interaction, p < 0.001), but there were no significant differences in coronary flow reserve (CFR). ConclusionsCoronary blood flow in the left atrium is out of phase with that in the ventricular myocardium, showing a predominant systolic pattern. Although atrial and ventricular CFR show no significant differences at rest and with two levels of stress, the disproportionate increase in atrial blood flow velocity during stress indicates a peculiarity of atrial perfusion regulation.

Single photon emission computed tomography perfusion imaging for assessment of myocardial viability and management of heart failure.

In the setting of coronary artery disease, some areas of dysfunctional myocardium may realize significant improvement in function as a consequence of revascularization. These areas represent viable myocardium, encompassing a spectrum of pathophysiology ranging from chronic stunning, in which resting blood flow is preserved, to hibernating myocardium, in which resting blood flow is decreased. The accurate preoperative evaluation of viable myocardium helps identify those patients with left ventricular dysfunction who will most benefit from coronary revascularization. Of the various modalities available for viability assessment, the nuclear medicine techniques (201)Thallium and (18)Fluorodeoxyglucose positron emission tomography have emerged as the most sensitive. It has been consistently shown that in patients with a significant amount of viable myocardium, there is a substantial survival benefit in revascularization versus medical therapy. The likelihood of affecting a significant improvement decreases with time to revascularization, however, particularly in the setting of an enlarged left ventricle secondary to ventricular remodeling.

Role of K+ATP channels, endothelin A receptors, and effect of angiotensin II on blood flow in oral tissues.

K+(ATP) channels are involved in CGRP-mediated vasodilation and in the vasoconstriction induced by endothelin or angiotensin II. In this study, we examined the effects of a K+(ATP) channel antagonist and an ET(A) receptor antagonist on resting blood flow in the pulp and gingiva, and observed their role in the vasodilation induced by tooth stimulation. We also investigated whether receptors for angiotensin II exist in the pulp and gingiva. Blood flow was measured with laser-Doppler flowmetry. Under control conditions, the K+(ATP) channel antagonist and angiotensin II caused a significant drop in blood flow in both target tissues. Blocking of ET(A) receptor did not change basal blood flow. The vasodilation observed after tooth stimulation remained unchanged following blockade of K+(ATP) channels and ET(A) receptors. Analysis of the data shows that open K+(ATP) channels exist during resting conditions in the pulp and gingiva, but that CGRP seems to induce vasodilation mainly via mechanisms other than K+(ATP) channels. ET(A) and AT(1) receptors are found in the pulp and gingiva, but ET(A) receptors are not involved in modulation of a basal vascular tone in these tissues or in the vasodilation observed after tooth stimulation.

Assessment of myocardial viability in dysfunctional myocardium by resting myocardial blood flow determined with oxygen 15 water PET

Background. There is controversy about the role of decreased resting blood flow as the pathophysiologic correlate of hibernating myocardium. The aim of this study was an absolute quantification of volumetric myocardial blood flow (MBFvol) in dysfunctional myocardium with different viability conditions as defined by fluorine 18 deoxyglucose (FDG) positron emission tomography (PET) while taking into consideration the functional recovery after revascularization. The impact of MBFvol in the diagnosis of functional recovery was also investigated. Methods and Results. Forty-two patients with severe coronary artery disease and dysfunctional myocardium underwent resting oxygen 15 water PET, as well as FDG PET and technetium 99m tetrofosmin single photon emission computed tomography, all attenuation-corrected. Relative FDG and Tc-99m tetrofosmin uptake (normalized to the segment with 100% Tc-99m tetrofosmin uptake), as well as MBFvol (myocardial blood flow multiplied by the water-perfusable tissue fraction to account for the flow to the entire segment volume), were determined in 18 myocardial segments per patient. Viability in dysfunctional segments (estimated by ventriculography) with reduced Tc-99m tetrofosmin uptake of 70% or lower was classified as viable (FDG >70%, mismatch) or nonviable (FDG ≤70%, match). Fifteen patients underwent revascularization and were followed up. Mismatch segments with improved function were classified as hibernating myocardium. Mean MBFvol in viable myocardium was slightly reduced (0.60 ± 0.02 mL · min–1 · mL–1) compared with that in normokinetic myocardium (0.64 ± 0.01 mL · min–1 · mL–1) (P = .036) and was significantly higher than in nonviable myocardium (0.36 ± 0.01 mL · min–1 · mL–1) (P < .001). Receiver operating characteristic analysis confirmed an FDG uptake greater than 70% as the optimal threshold to predict functional recovery (diagnostic accuracy [ACC], 76%). MBFvol in hibernating myocardium (0.62 ± 0.04 mL · min–1 · mL–1) was not significantly reduced compared with that in normokinetic myocardium (0.66 ± 0.02 mL · min–1 · mL–1) and was significantly higher than in persistently dysfunctional myocardium (0.51 ± 0.04 mL · min–1 · mL–1) (P < .05). The ACC of MBFvol greater than 0.40 mL · min–1 · mL–1 as the threshold to predict functional recovery was 61% but did not improve the accuracy of FDG PET by itself. Conclusions. In patients with severe coronary artery disease and dysfunctional myocardium, MBFvol as determined with O-15 water differs significantly between viable and nonviable myocardium as determined by FDG PET and is not significantly reduced in hibernating compared with normokinetic myocardium. Therefore chronically reduced resting blood flow appears unlikely to be the pathophysiologic correlate of the functional state of hibernation. However, MBFvol does not improve the ACC of FDG PET by itself. (J Nucl Cardiol 2003;10:34-45)

Modulation of collateral artery growth in a porcine hindlimb ligation model using MCP-1.

For an appropriate extrapolation to patients with peripheral arterial obstructive disease, we tested the efficacy of monocyte chemoattractant protein 1 (MCP-1) treatment in a porcine hindlimb ligation model. In 40 minipigs, a femoral artery ligation was performed. Control animals were examined immediately after ligation (n = 4) or after 2 wk of intra-arterial infusion of PBS (n = 11). A second group of animals was evaluated after intra-arterial infusion of 2.0 microg/h of MCP-1 for 48 h (followed by 12 days of PBS; n = 13) or 2 wk continuously (n = 12). In the terminal experiment after 2 wk, resting flow to the leg and peripheral arterial pressures were assessed without vasodilatation. Subsequently, vascular conductance was determined by using a pump-driven extracorporal circulation during maximal vasodilatation. The results showed that resting blood flow to the hindlimb was 53% of the normal after 2 wk of infusion of PBS, compared with 81% in both MCP-1 treatment groups (P < 0.05). Collateral conductance was 645 +/- 346 ml x min(-1) x mmHg(-1) after 2 wk of infusion with PBS, compared with 1,070 +/- 530 and 1,158 +/- 535 ml x min(-1) x mmHg(-1) after 48 h and 2 wk treatment with MCP-1, respectively (P < 0.05). Modulation of the process of arteriogenesis is feasible in this large animal model via intra-arterial infusion of the Cys-Cys-chemokine MCP-1.

Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide.

To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution (N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly (P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 +/- 4 vs. 60 +/- 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially (P < 0.05) shorter in the l-NAME-treated group: 539 +/- 67 vs. 889 +/- 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.

Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation.

Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs (n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment (P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.

Augmentation of myocardial blood flow in hypertensive heart disease by angiotensin antagonists: A comparison of lisinopril and losartan

ObjectivesThe goal of this study was to compare myocardial perfusion reserve (MPR) before and after long-term treatment with lisinopril and losartan in patients with hypertension and left ventricular hypertrophy (LVH). BackgroundStudies have suggested that treatment with angiotensin-converting enzyme inhibitors (ACEIs) improves MPR in patients with hypertension by potentiating endogenous bradykinins. Because angiotensin receptor blockers (ARBs) lack a direct effect on bradykinins, we hypothesized that they may not improve MPR. MethodsWe measured pre- and post-treatment myocardial blood flow (MBF) by positron emission tomography in 17 patients (lisinopril: 9 patients, losartan: 8 patients) with hypertension and LVH at baseline and after coronary vasodilation with intravenous dipyridamole. In addition, we measured rest and hyperemic blood flow in eight normotensive controls. ResultsPost-treatment maximal coronary blood flow and MPR in the lisinopril group increased significantly compared with pretreatment values (3.5 ± 1.2 vs. 2.6 ± 1.1 ml/min/g, p = 0.02; 3.7 ± 1.1 vs. 2.4 ± 1 ml/min/g, respectively, p = 0.002, respectively). Post-treatment hyperemic flow in the patients treated with lisinopril was not significantly different from corresponding measurements in controls (3.5 ± 1.2 vs. 3.9 ± 1 ml/min/g, respectively, p = NS). In the patients treated with losartan, there was no difference between pre- and post-treatment MBF values and MPR. ConclusionsMyocardial perfusion reserve and maximal coronary flow improved in asymptomatic patients with hypertension-induced LVH after long-term treatment with lisinopril but not with losartan. Thus, ACEIs, but not ARBs, might be effective in repairing the coronary microangiopathy associated with hypertension-induced LVH.

Flow-mediated dilatation of the brachial artery in pregnancy at high altitude.

Pregnancy at high altitude has been associated with increased prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that have been associated with endothelial dysfunction. The aim of this study was to examine the effect of high altitude (4370 m above sea level) on endothelial function during pregnancy as assessed by a non-invasive method. Cross-sectional study. Two maternity units providing routine antenatal care: one at high altitude (District General Hospital--IPSS in Cerro de Pasco, Peru) and one at sea level (Instituto Materno-Perinatal in Lima, Peru). Sixty pregnant women at 6-42 weeks of gestation resident at high altitude (Cerro de Pasco, Peru, 4370 m above sea level) and 54 at sea level (Lima, Peru). Comparisons were performed also in 11 and 14 non-pregnant women at each altitude, respectively. Endothelial function was assessed by flow-mediated dilatation of the brachial artery using high-resolution ultrasound. Differences in flow mediated dilatation of the brachial artery in two groups of pregnant women, one at high altitude and one at sea level. Both at high altitude and sea level flow-mediated dilatation of the brachial artery increased in the first two trimesters to levels 32% higher than non-pregnant controls. However, in the third trimester, flow-mediated dilatation of the brachial artery was lower than non-pregnant levels. Resting vessel size increased during pregnancy by 15% compared with non-pregnant controls at term, with no difference between the two populations at high and low altitude. Pregnancy at high altitude, compared with sea level, was associated with 59% lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non-pregnant controls at high altitude compared with sea level demonstrated similar flow-mediated dilatation of the brachial artery and 40% lower resting blood flow of the brachial artery. However, the difference in reactive hyperaemia did not reach statistical significance. These data suggest that, during pregnancy at high altitude, endothelial function, as assessed by flow-mediated dilatation of the brachial artery, is not impaired.

Flow-mediated dilatation of the brachial artery in pregnancy at high altitude

Objective Pregnancy at high altitude has been associated with increased prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that have been associated with endothelial dysfunction. The aim of this study was to examine the effect of high altitude (4370 m above sea level) on endothelial function during pregnancy as assessed by a non-invasive method. Design Cross-sectional study. Setting Two maternity units providing routine antenatal care: one at high altitude (District General Hospital - IPSS in Cerro de Pasco, Peru) and one at sea level (Instituto Materno-Perinatal in Lima, Peru). Population Sixty pregnant women at 6–42 weeks of gestation resident at high altitude (Cerro de Pasco, Peru, 4370 m above sea level) and 54 at sea level (Lima, Peru). Comparisons were performed also in 11 and 14 non-pregnant women at each altitude, respectively. Methods Endothelial function was assessed by flow-mediated dilatation of the brachial artery using high-resolution ultrasound. Main outcome measures Differences in flow mediated dilatation of the brachial artery in two groups of pregnant women, one at high altitude and one at sea level. Results Both at high altitude and sea level flow-mediated dilatation of the brachial artery increased in the first two trimesters to levels 32% higher than non-pregnant controls. However, in the third trimester, flow-mediated dilatation of the brachial artery was lower than non-pregnant levels. Resting vessel size increased during pregnancy by 15% compared with non-pregnant controls at term, with no difference between the two populations at high and low altitude. Pregnancy at high altitude, compared with sea level, was associated with 59% lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non-pregnant controls at high altitude compared with sea level demonstrated similar flow-mediated dilatation of the brachial artery and 40% lower resting blood flow of the brachial artery. However, the difference in reactive hyperaemia did not reach statistical significance. Conclusion These data suggest that, during pregnancy at high altitude, endothelial function, as assessed by flow-mediated dilatation of the brachial artery, is not impaired.

Elevation in resting blood flow attenuates exercise hyperemia.

These experiments tested the hypothesis that elevating muscle blood flow before exercise would wash out vasoactive substances produced by muscle contraction and reduce the magnitude of exercise hyperemia and/or delay the response. In chronically instrumented dogs (n = 7), hindlimb blood flow was measured with chronically implanted flow probes during mild treadmill exercise. In an anesthetized preparation (n = 8), arterial and venous blood flows of a single hindlimb were obtained during 1-s tetanic contractions evoked by electrical stimulation of the cut sciatic nerve. Elevation of blood flow by intra-arterial infusion of adenosine attenuated the increase in flow during exercise and tetanic contraction by 48 and 47%, respectively. No delay was observed in the latency to peak flow. The attenuated hyperemic response to exercise or contraction is best explained by washout of vasoactive substance(s) produced by contracting muscle, but the residual response suggests that a metabolic mediator may not be the sole explanation for exercise hyperemia.

The Danish PET/depression project: clinical symptoms and cerebral blood flow. A regions-of-interest analysis.

We wanted to explore associations between clinical symptoms of depression and the blood flow to specific regions of the brain. Furthermore, we wanted to compare the regions-of-interest (ROI) method with the functions-of-interest (FOI) approach. The resting blood flow to 42 ROI in the brain was obtained with positron emission tomography (PET) imaging in 42 representative in-patients with major depression and 47 matched healthy controls. The patients had increased blood flow to hippocampus, cerebellum, anterior cingulate gyrus, and the basal ganglia. A strong negative correlation was found between the degree of psychomotor retardation of the patients and the blood flow to the dorsolateral and supraorbital prefrontal cortices. The total Hamilton score was correlated with the blood flow to the hippocampus. Our findings support the notion that depressed patients have disturbances in the loops connecting the frontal lobes, limbic system, basal ganglia, and cerebellum.

Severe energy deprivation of human hibernating myocardium as possible common pathomechanism of contractile dysfunction, structural degeneration and cell death

ObjectivesWe tested the hypothesis that severe alterations in myocardial energy metabolism play an important role in the pathophysiology of human hibernating myocardium (HHM). BackgroundIt is well established that a disturbed myocardial energy metabolism results in impairments of contractile performance, structure and viability. All of these are important characteristics of HHM. MethodsIn 16 patients with documented coronary artery disease and impaired left ventricular function, HHM was preoperatively detected by thallium-201 scintigraphy, radionuclide ventriculography and low-dose dobutamine echocardiography. These regions were validated as HHM by their recovery of contractile function three months following revascularization. During open-heart surgery, transmural biopsies were removed from the hibernating areas and analyzed both biochemically and morphologically. These findings were compared to normal human myocardium. All metabolite contents given were normalized for the degree of fibrosis (control: 9.8 ± 0.5%; HHM: 28.1 ± 3.0%; p < 0.05), providing myocellular contents. ResultsIn HHM, decreased contents (μmol/g wet weight) in adenosine triphosphate (ATP) (control: 4.17 ± 0.26; HHM: 1.72 ± 0.25; p < 0.001), creatine phosphate (5.67 ± 0.70 vs. 0.84 ± 0.13; p < 0.001) and creatine (27.6 ± 3.19 vs. 11.2 ± 1.56; p < 0.0001) were found, but contents in lactate (2.22 ± 0.26 vs. 25.38 ± 3.53; p < 0.001), purine bases (0.58 ± 0.09 vs. 1.26 ± 0.13; p < 0.001) and protons (pH units: 7.199 ± 0.01 vs. 6.59 ± 0.07; p < 0.001) were increased. Levels in adenosine diphosphate, adenosine monophosphate and inorganic phosphate remained unchanged. Energy depletion in HHM was reflected by decreases in the free energy of ATP hydrolysis and in energy charge. ConclusionsThese data confirm our hypothesis that HHM is energy-depleted myocardium, exhibiting signs of chronic reduction in resting blood flow and a downregulation of energy turnover. The alterations in energy metabolism observed may become operative in triggering and maintaining contractile dysfunction, continuous tissue degeneration and cardiomyocyte loss.