Cerebral blood flow effects of acute intravenous heroin administration.

We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.

Improved coronary vasodilatatory capacity by H.E.L.P. apheresis: comparing initial and chronic treatment.

Hypercholesterolemia impairs endothelial function and subsequently decreases coronary vasodilatatory capacity. We examined the quantitative effects of one single LDL apheresis on vasodilatatory capacity. Using N-13 ammonia as a tracer for dynamic quantitative positron emission tomography (PET), mean myocardial perfusion measurements were carried out before and 20 h later after LDL apheresis, both under resting conditions and after pharmacological vasodilatation with dipyridamole. LDL apheresis was carried out using the heparin induced extracorporeal LDL precipitation (H.E.L.P.) procedure. We examined 47 patients (12 women and 35 men), with angiographically-proven coronary artery disease. All of them suffered from hypercholesterolemia. Of the patients, 35 received a chronic weekly H.E.L.P. procedure (group A), while H.E.L.P. procedure treatment was started for the first time in 12 patients, who were subsequently enrolled in a chronic apheresis program (group B). H.E.L.P. apheresis was combined with cholesterol lowering drugs in all patients. Both groups underwent positron emission tomography twice (prior to LDL apheresis and 20 h later). In group A, LDL cholesterol levels decreased from 175 +/- 50 mg/dL to 60 +/- 21 mg/dL immediately after H.E.L.P. (77 +/- 25 mg/dL before the second PET). Corresponding values for fibrinogen levels were 287 +/- 75 mg/dL to 102 +/- 29 mg/dL (155 +/- 52 mg/dL), minimal coronary resistance dropped from 0.56 +/- 0.20 to 0.44 +/- 0.17 mm Hg x 100 g x min/mL (P < 0.0001). Plasma viscosity decreased by 7.8%. In group B, LDL cholesterol decreased from 187 +/- 45 mg/dL to 75 +/- 27 mg/dL (85 +/- 29 mg/dL) and fibrinogen from 348 +/- 65 mg/dL to 126 +/- 38 mg/dL (168 +/- 45 mg/dL). Minimal coronary resistance was reduced from 0.61 +/- 0.23 to 0.53 +/- 0.19 mm Hg x 100 g x min/mL (P < 0.01). Plasma viscosity was observed to decrease by 7.6%. The strong LDL drop in patients under chronic H.E.L.P. treatment has a significant impact on coronary vasodilatatory capacity within 20 h leading to an improved overall cardiac perfusion. Nearly the same effect can be seen in patients after their first H.E.L.P. treatment.

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease.

PURPOSE: The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation. METHODS: The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6+/-1.8 months after atorvastatin therapy, ( 13)N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine > or =2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF. RESULTS: LDL cholesterol decreased after atorvastatin therapy from 186+/-43 mg/dl to 101+/-26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy. CONCLUSION: The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.

Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block.

OBJECTIVE: In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO(2)) and blood flow (MBF) are missing. METHODS: We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1+/-7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7+/-7.9%). Global and regional MVO(2) as well as MBF were determined from a dynamic (11)C-acetate positron emission tomography (PET) study. RESULTS: Global MVO(2) and MBF were lower in the DCM group with LBBB than in the control group (P<0.05). Regionally, the LBBB group revealed a higher (P<0.05) MVO(2) and MBF in the lateral wall than in the other walls. The control group did not show significant differences between the myocardial walls and demonstrated a smaller variability of the parameters. CONCLUSION: DCM patients with LBBB exhibit a more heterogeneous distribution of MVO(2) and MBF among the myocardial walls than DCM patients without LBBB. Due to the LBBB associated electromechanical alterations, the highest regional values of MVO(2) and MBF are found in the lateral wall.

18F-FDG PET for detecting myocardial viability: validation of 3D data acquisition.

UNLABELLED: (18)F-FDG PET is an important diagnostic tool for detecting myocardial viability in patients with coronary artery disease. In combination with perfusion scanning, (18)F-FDG PET allows differentiation between reversibly and irreversibly damaged myocardium and selection of patients likely to benefit from revascularization. Viability PET is usually performed in two-dimensional (2D) mode. Taking into account the rising number of three-dimensional (3D)-only scanners, a validation of 3D acquisition is required. METHODS: Twenty-one patients with coronary artery disease referred for (18)F-FDG PET underwent an imaging protocol of nongated 2D (2D-NG) and gated 2D (2D-G) acquisitions for 15 min each, followed by 3D gated acquisitions for 10 min (3D-10) and 5 min (3D-5), using an ECAT Exact HR+ scanner. Results were analyzed using a 20-segment polar map in terms of activity concentration (Bq/mL), viability (50% uptake threshold), regional activity distribution, visual assessment of viability based on a 3-point rating scale, and left ventricular ejection fraction. RESULTS: Activity concentration measured in each segment with 2D-G, 3D-10, and 3D-5 showed a good linear correlation with 2D-NG. Quantitative viability assessment with 3D-5 gave a sensitivity of 84% and a specificity of 98%, compared with 2D-NG. No differences in regional activity distribution and visual viability assessment were found between the various protocols. Left ventricular ejection fractions obtained with 3D-10 and 3D-5 showed a good linear correlation with those measured with 2D-G. CONCLUSION: An ECG-gated 3D imaging protocol gave results comparable to those of 2D acquisition with regard to absolute and regional myocardial activity distribution, left ventricular function, and visual viability assessment. Sensitivity for viability assessment with a 50% uptake threshold was significantly less with 3D, but specificity was maintained. This protocol delivers a clinical performance nearly equivalent to that of 2D acquisition.

Effect of cardiac resynchronization therapy on global and regional oxygen consumption and myocardial blood flow in patients with non-ischaemic and ischaemic cardiomyopathy.

AIMS: We studied the effects of cardiac resynchronization therapy (CRT) on global and regional myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) in non-ischaemic (NICM) and ischaemic dilated cardiomyopathy (ICM). METHODS AND RESULTS: Thirty-one NICM and 11 ICM patients, all of them acute responders, were investigated. MVO2 and MBF were obtained by 11C-acetate PET before and after 4 months of CRT. In NICM global MVO2 and MBF did not change during CRT, while the rate pressure product (RPP) normalized MVO2 increased (P=0.03). Before CRT regional MVO2 and MBF were highest in the lateral wall and lowest in the septum. Under therapy, MVO2 and MBF decreased in the lateral wall (P=0.045) and increased in the septum (P=0.045) resulting in a more uniform distribution. In ICM, global MVO2, MBF, and RPP did not change under CRT. Regional MVO2 and MBF showed no significant changes but a similar tendency in the lateral and septal wall to that in NICM. CONCLUSION: CRT induces changes of MVO2 and MBF on a regional level with a more uniform distribution between the myocardial walls and improved ventricular efficiency in NICM. Based on the investigated parameters, CRT appears to be more effective in NICM than in ICM.

Diminished GABA(A) receptor-binding capacity and a DNA base substitution in a patient with treatment-resistant depression and anxiety.

In this report, we describe the case of a caucasian male patient, aged 42 years, suffering from severe treatment-resistant generalized anxiety disorder with panic attacks and from severe major depression, for which he was treated with a course of electroconvulsive therapy. During electroconvulsive treatment, anesthesia was difficult to induce with etomidate and, once, propofol. Bispectral indices recordings (assessing the depth of anesthesia) revealed a much shorter duration of loss of responsiveness compared to a control patient receiving also a course of electroconvulsive therapy. Since GABA receptor-mediated regulation of cortical excitability is important with respect to general anesthesia, we investigated the density of GABA(A) receptors with (123)I-iomazenil SPECT and found a clearly diminished binding of the radiotracer in the right frontal and orbitotemporal regions compared to the recordings in a 38-year-old healthy male control. Genetic analysis of the exons 7 and 8 of the GABRB1-3 genes coding for the beta1-3 subunits of the GABA(A) receptors revealed a silent G to A substitution in the third position of amino acid 257 of the beta1-subunit. To our knowledge, this is the first report of a link between insensitivity to anesthetic agents and altered GABA(A) receptor function in a clinical case. Whereas reduced GABA(A) receptor-binding capacity has been investigated in anxiety disorders, this has not been the case in depressive disorders. This case illustrates how clinical observations in psychiatry can prompt investigation by modern techniques and potentially link clinics and basic sciences. No conclusion can, however, be made about casual links in this single case [corrected].

Myocardial perfusion after transcutaneous/percutaneous myocardial laser revascularization.

The effectiveness of transcutaneous and percutaneous myocardial laser revascularization in patients with endstage coronary artery disease and angina refractory to pharmacological therapy has been proved by various studies. Angiogenesis associated with an improvement of microcirculation and myocardial perfusion may be responsible for the reduction of angina and the improved physical performance. Myocardial perfusion studies published so far are compared to our own results utilizing positron emission tomography before and after percutaneous myocardial laser revascularization.