Quantitative stress echocardiography in coronary artery disease using contrast-based myocardial blood flow measurements: prospective comparison with coronary angiography

AIM: To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml x min(-1) x g(-1)) measurements can detect coronary artery disease in humans. METHODS: 48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 microg x kg(-1) x min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography. RESULTS: Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml x min(-1) x g(-1) and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>or=75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml x min(-1) x g(-1) and 2.54 (1.03), respectively, and decreased linearly (r2 = 0.21 and r2 = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR <1.94 detected >or=50% stenosis with 89% sensitivity and 92% specificity. CONCLUSION: Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.

General anesthesia with sevoflurane decreases myocardial blood volume and hyperemic blood flow in healthy humans

BACKGROUND Preservation of myocardial perfusion during general anesthesia is likely important in patients at risk for perioperative cardiac complications. Data related to the influence of general anesthesia on the normal myocardial circulation are limited. In this study, we investigated myocardial microcirculatory responses to pharmacological vasodilation and sympathetic stimulation during general anesthesia with sevoflurane in healthy humans immediately before surgical stimulation. METHODS Six female and 7 male subjects (mean age 43 years, range 28-61) were studied at baseline while awake and during the administration of 1 minimum alveolar concentration sevoflurane. Using myocardial contrast echocardiography, myocardial blood flow (MBF) and microcirculatory variables were assessed at rest, during adenosine-induced hyperemia, and after cold pressor test-induced sympathetic stimulation. MBF was calculated from the relative myocardial blood volume multiplied by its exchange frequency (β) divided by myocardial tissue density (ρT), which was set at 1.05 g·mL(-1). RESULTS During sevoflurane anesthesia, MBF at rest was similar to baseline values (1.05 ± 0.28 vs 1.05 ± 0.32 mL·min(-1)·g(-1); P = 0.98; 95% confidence interval [CI], -0.18 to 0.18). Myocardial blood volume decreased (P = 0.0044; 95% CI, 0.01-0.04) while its exchange frequency (β) increased under sevoflurane anesthesia when compared with baseline. In contrast, hyperemic MBF was reduced during anesthesia compared with baseline (2.25 ± 0.5 vs 3.53 ± 0.7 mL·min(-1)·g(-1); P = 0.0003; 95% CI, 0.72-1.84). Sympathetic stimulation during sevoflurane anesthesia resulted in a similar MBF compared to baseline (1.53 ± 0.53 and 1.55 ± 0.49 mL·min(-1)·g(-1); P = 0.74; 95% CI, -0.47 to 0.35). CONCLUSIONS In otherwise healthy subjects who are not subjected to surgical stimulation, MBF at rest and after sympathetic stimulation is preserved during sevoflurane anesthesia despite a decrease in myocardial blood volume. However, sevoflurane anesthesia reduces hyperemic MBF, and thus MBF reserve, in these subjects.

Association of individual resting state EEG alpha frequency and cerebral blood flow

Cognitive task performance differs considerably between individuals. Besides cognitive capacities, attention might be a source of such differences. The individual's EEG alpha frequency (IAF) is a putative marker of the subject's state of arousal and attention, and was found to be associated with task performance and cognitive capacities. However, little is known about the metabolic substrate (i.e. the network) underlying IAF. Here we aimed to identify this network. Correlation of IAF with regional Cerebral Blood Flow (rCBF) in fifteen young healthy subjects revealed a network of brain areas that are associated with the modulation of attention and preparedness for external input, which are relevant for task execution. We hypothesize that subjects with higher IAF have pre-activated task-relevant networks and thus are both more efficient in the task-execution, and show a reduced fMRI-BOLD response to the stimulus, not because the absolute amount of activation is smaller, but because the additional activation by processing of external input is limited due to the higher baseline.

Right ventricular absolute myocardial blood flow in complex congenital heart disease

A consequence in patients with d-transposition of the great arteries (d-TGA) and tetralogy of Fallot (TOF) is right ventricular hypertrophy (RVH) and right ventricular failure. Myocardial contrast echocardiography (MCE) permits the determination of the myocardial microvascular density reflected by the relative myocardial blood volume (rBV; ml/ml). This study was conducted to elucidate the relationship between RVH and myocardial microvascular changes by quantitative MCE in patients with d-TGA and TOF.

Resting state cerebral blood flow and objective motor activity reveal basal ganglia dysfunction in schizophrenia

Reduced motor activity has been reported in schizophrenia and was associated with subtype, psychopathology and medication. Still, little is known about the neurobiology of motor retardation. To identify neural correlates of motor activity, resting state cerebral blood flow (CBF) was correlated with objective motor activity of the same day. Participants comprised 11 schizophrenia patients and 14 controls who underwent magnetic resonance imaging with arterial spin labeling and wrist actigraphy. Patients had reduced activity levels and reduced perfusion of the left parahippocampal gyrus, left middle temporal gyrus, right thalamus, and right prefrontal cortex. In controls, but not in schizophrenia, CBF was correlated with activity in the right thalamic ventral anterior (VA) nucleus, a key module within basal ganglia-cortical motor circuits. In contrast, only in schizophrenia patients positive correlations of CBF and motor activity were found in bilateral prefrontal areas and in the right rostral cingulate motor area (rCMA). Grey matter volume correlated with motor activity only in the left posterior cingulate cortex of the patients. The findings suggest that basal ganglia motor control is impaired in schizophrenia. In addition, CBF of cortical areas critical for motor control was associated with volitional motor behavior, which may be a compensatory mechanism for basal ganglia dysfunction.

Intussusceptive angiogenesis: pillars against the blood flow

Adaptation of vascular networks to functional demands needs vessel growth, vessel regression and vascular remodelling. Biomechanical forces resulting from blood flow play a key role in these processes. It is well-known that metabolic stimuli, mechanical forces and flow patterns can affect gene expression and remodelling of vascular networks in different ways. For instance, in the sprouting type of angiogenesis related to hypoxia, there is no blood flow in the rising capillary sprout. In contrast, it has been shown that an increase of wall shear stress initiates the splitting type of angiogenesis in skeletal muscle. Otherwise, during development, both sprouting and intussusception act in parallel in building the vascular network, although with differences in spatiotemporal distribution. Thereby, in addition to regulatory molecules, flow dynamics support the patterning and remodelling of the rising vascular tree. Herewith, we present an overview of angiogenic processes with respect to intussusceptive angiogenesis as related to local haemodynamics.

Hypotension during fluid-restricted abdominal surgery: effects of norepinephrine treatment on regional and microcirculatory blood flow in the intestinal tract

Vasopressors, such as norepinephrine, are frequently used to treat perioperative hypotension. Increasing perfusion pressure with norepinephrine may increase blood flow in regions at risk. However, the resulting vasoconstriction could deteriorate microcirculatory blood flow in the intestinal tract and kidneys. This animal study was designed to investigate the effects of treating perioperative hypotension with norepinephrine during laparotomy with low fluid volume replacement.

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Outer skull landmark-based coordinates for measurement of cerebral blood flow and intracranial pressure in rabbits

Despite the increased use of intracranial neuromonitoring during experimental subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are lacking. This study evaluates the safety and reliability of using outer skull landmarks to identify locations for placement of cerebral blood flow (CBF) and intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was performed in 17 rabbits using an extracranial-intracranial shunt model. ICP probes were placed in the frontal lobe and compared to measurements recorded from the olfactory bulb. CBF probes were placed in various locations in the frontal cortex anterior to the coronary suture. Insertion depth, relation to the ventricular system, and ideal placement location were determined by post-mortem examination. ICP recordings at the time of SAH from the frontal lobe did not differ significantly from those obtained from the right olfactory bulb. Ideal coordinates for intraparenchymal CBF probes in the left and right frontal lobe were found to be located 4.6±0.9 and 4.5±1.2 anterior to the bregma, 4.7±0.7mm and 4.7±0.5mm parasagittal, and at depths of 4±0.5mm and 3.9±0.5mm, respectively. The results demonstrate that the presented coordinates based on skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes in rabbit brains without the use of a stereotactic frame.

Postoperative splanchnic blood flow redistribution in response to fluid challenges in the presence and absence of endotoxemia in a porcine model

We hypothesized that fluid administration may increase regional splanchnic perfusion after abdominal surgery-even in the absence of a cardiac stroke volume (SV) increase and independent of accompanying endotoxemia. Sixteen anesthetized pigs underwent abdominal surgery with flow probe fitting around splanchnic vessels and carotid arteries. They were randomized to continuous placebo or endotoxin infusion, and when clinical signs of hypovolemia (mean arterial pressure, <60 mmHg; heart rate, >100 beats · min(-1); urine production, <0.5 mL · kg(-1) · h(-1); arterial lactate concentration, >2 mmol · L(-1)) and/or low pulmonary artery occlusion pressure (target 5-8 mmHg) were present, they received repeated boli of colloids (50 mL) as long as SV increased 10% or greater. Stroke volume and regional blood flows were monitored 2 min before and 30 min after fluid challenges. Of 132 fluid challenges, 45 (34%) resulted in an SV increase of 10% or greater, whereas 82 (62%) resulted in an increase of 10% or greater in one or more of the abdominal flows (P < 0.001). During blood flow redistribution, celiac trunk (19% of all measurements) and hepatic artery flow (15%) most often decreased, whereas portal vein (10%) and carotid artery (7%) flow decreased less frequently (P = 0.015, between regions). In control animals, celiac trunk (30% vs. 9%, P = 0.004) and hepatic artery (25% vs. 11%, P = 0.040) flow decreased more often than in endotoxin-infused pigs. Accordingly, blood flow redistribution is a common phenomenon in the postoperative period and is only marginally influenced by endotoxemia. Fluid management based on SV changes may not be useful for improving regional abdominal perfusion.

Anterior knee pain after total knee arthroplasty: does it correlate with patellar blood flow?

Total knee arthroplasty (TKA) disturbs patellar blood flow, an unintended accompaniment to TKA that may be a cause of postoperative anterior knee pain. We examine whether disrupted patellar blood flow correlates with anterior knee pain following TKA.

[Blood flow assessment with magnetic resonance imaging after 1.9 μm diode laser assisted arterial micronastomoses]

The most important factor for successful free-flap transfer and replantations is a well-executed anastomosis. The aim of this study is to assess blood flow after laser assisted arterial microanastomosis (LAMA) using a 1.9 μm diode laser.

Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

Cerebral blood flow identifies responders to transcranial magnetic stimulation in auditory verbal hallucinations

Auditory hallucinations comprise a critical domain of psychopathology in schizophrenia. Repetitive transcranial magnetic stimulation (TMS) has shown promise as an intervention with both positive and negative reports. The aim of this study was to test resting-brain perfusion before treatment as a possible biological marker of response to repetitive TMS. Twenty-four medicated patients underwent resting-brain perfusion magnetic resonance imaging with arterial spin labeling (ASL) before 10 days of repetitive TMS treatment. Response was defined as a reduction in the hallucination change scale of at least 50%. Responders (n=9) were robustly differentiated from nonresponders (n=15) to repetitive TMS by the higher regional cerebral blood flow (CBF) in the left superior temporal gyrus (STG) (P<0.05, corrected) before treatment. Resting-brain perfusion in the left STG predicted the response to repetitive TMS in this study sample, suggesting this parameter as a possible bio-marker of response in patients with schizophrenia and auditory hallucinations. Being noninvasive and relatively easy to use, resting perfusion measurement before treatment might be a clinically relevant way to identify possible responders and nonresponders to repetitive TMS.

Reduced Cerebral Blood Flow Within the Default-Mode Network and Within Total Gray Matter in Major Depression

The default-mode network (DMN) was shown to have aberrant blood oxygenation-level-dependent (BOLD) activity in major depressive disorder (MDD). While BOLD is a relative measure of neural activity, cerebral blood flow (CBF) is an absolute measure. Resting-state CBF alterations have been reported in MDD. However, the association of baseline CBF and CBF fluctuations is unclear in MDD. Therefore, the aim was to investigate the CBF within the DMN in MDD, applying a strictly data-driven approach. In 22 MDD patients and 22 matched healthy controls, CBF was acquired using arterial spin labeling (ASL) at rest. A concatenated independent component analysis was performed to identify the DMN within the ASL data. The perfusion of the DMN and its nodes was quantified and compared between groups. The DMN was identified in both groups with high spatial similarity. Absolute CBF values within the DMN were reduced in MDD patients (p<0.001). However, after controlling for whole-brain gray matter CBF and age, the group difference vanished. In patients, depression severity was correlated with reduced perfusion in the DMN in the posterior cingulate cortex and the right inferior parietal lobe. Hypoperfusion within the DMN in MDD is not specific to the DMN. Still, depression severity was linked to DMN node perfusion, supporting a role of the DMN in depression pathobiology. The finding has implications for the interpretation of BOLD functional magnetic resonance imaging data in MDD.