What is the role of cardiac PET in patients with ischaemic heart disease and significant left ventricular dysfunction?
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Humans↗
Biomedical subjects
G R Sutherland
Publications and source records attributed to G R Sutherland.
Doppler myocardial imaging in the assessment of regional myocardial function in longitudinal direction pre- and post-PTCA.
AIMS: Doppler myocardial imaging is potentially a sensitive tool to assess regional myocardial velocities pre- and post-percutaneous transluminal coronary angioplasty (PTCA) as a marker of contractility to evaluate short- to medium-term information on functional myocardial recovery following the release of ischaemia. METHODS: Thirty patients with single vessel disease were studied to assess regional myocardial peak systolic velocity, systolic velocity time integral and mitral valve plane excursion in longitudinal direction one day pre-, one day post- and 3 months post-PTCA. The patients were assigned to group A with coronary stenoses >70% and group B with stenoses < 70%. RESULTS: In group A pre-PTCA the ischaemic segments showed a significantly lower peak systolic velocity and velocity time integral compared with the values one day after PTCA (5.8 +/- 1.4 vs 7.7 +/- 1.4cm.s(-1); 1.06 +/- 0.22 vs 1.23 +/-0.28cm;P< 0.03). In contrast, mitral valve plane excursion in this group remained unchanged after PTCA for both the ischaemic and non-ischaemic left ventricular wall. In group B no changes of these parameters and no differences in mitral valve plane excursion of the ischaemic and the non-ischaemic left ventricular wall could be seen. CONCLUSION: With Doppler myocardial imaging it was possible to quantify a number of indices which changed due to the successful release of ischaemia.
Angioplasty, Balloon, Coronary↗
Changes in systolic and postsystolic wall thickening during acute coronary occlusion and reperfusion in closed-chest pigs: Implications for the assessment of regional myocardial function.
The aim of the study was to characterize the impact of short-lived total coronary occlusions in closed-chest pigs on radial wall thickening within the "at-risk" myocardial segment by using gray-scale M-mode echocardiography. Twelve pigs underwent a series of 20-second total circumflex coronary artery occlusions with an angioplasty balloon. Myocardial thickening/thinning indexes were continuously monitored before ischemia, during ischemia, and on reperfusion by high-resolution M-mode recordings of the posterior wall obtained from parasternal views. The timing of regional events was compared with global systolic time intervals derived from the color Doppler myocardial imaging velocity data. Each occlusion induced a rapid decrease in end-systolic thickening (epsilon(ES)), closely paralleled by an increase in postsystolic thickening in the ischemic segment. After 20 seconds of ischemia, epsilon(ES) decreased by -86% and postsystolic thickening increased by +100%, whereas maximal thickening decreased only by -34% in comparison with preocclusion values. All wall thickening parameters returned to baseline after 15 seconds of reperfusion. During acute total ischemia in a closed-chest animal model, the changes in regional myocardial function were best characterized by the combined analysis of systolic and postsystolic thickening abnormalities and by their respective timings relative to global cardiac events markers.
Angioplasty, Balloon, Coronary↗
Quantification of the spectrum of changes in regional myocardial function during acute ischemia in closed chest pigs: an ultrasonic strain rate and strain study.
The objectives of this study were to define the spectrum of regional myocardial function changes during acute ischemia in closed chest animals by using newly developed ultrasonic strain rate and strain indexes derived from regional color Doppler myocardial imaging (CDMI) velocity data. Myocardial ischemia was induced in 18 pigs either with acute total 20-second occlusions (group 1, n = 12) or graded hypoperfusion (40 to 0 mL/min, group 2, n = 6) of the circumflex coronary artery. In addition, a dobutamine challenge (5 to 10 microg/kg per minute) was performed during sustained subtotal ischemia (10 mL/min) in group 2. CDMI acquisitions with parasternal views monitored the myocardial posterior wall function. Regional radial strain rate and strain (epsilon(r)) were measured for systole, isovolumic relaxation, early diastole, and atrial filling, respectively. During total and graded ischemia, epsilon(r) profiles were consistently modified, showing a delayed onset and a decrease in regional systolic thickening as well as increased postsystolic thickening. Radial strain rate and epsilon(r) indexes decreased consistently during systole and early diastole and increased during isovolumic relaxation. End-systolic epsilon(r) could differentiate total ischemia from severe hypoperfusion (10 mL/min), decreasing from 32% +/- 8% to 16% +/- 5% (versus 60% +/- 10% at baseline). During dobutamine infusion (10 microg/kg per minute), end-systolic epsilon(r) tended to decrease from 27% +/- 5% to 18% +/- 11%, whereas postsystolic thickening increased by 2-fold (P <.05). The combined analysis of regional deformation characteristics and global cardiac event timing derived from CDMI data can identify and quantify regional function changes induced by experimental acute ischemia in closed chest pigs. This would appear to be a potentially promising new noninvasive approach to the clinical evaluation of ischemia-induced changes in segmental myocardial function.
Animals↗
Does atrioventricular ring motion always distinguish constriction from restriction? A Doppler myocardial imaging study.
Constrictive pericarditis and restrictive cardiomyopathy can be difficult to differentiate on clinical examination. Cardiac ultrasonography is increasingly being used as the noninvasive method of choice for confirming the specific morphologic and hemodynamic abnormalities associated with either condition. Interrogation of atrioventricular valve plane motion by Doppler myocardial imaging (DMI) has been suggested as a valuable new approach that can help differentiate one from the other. We report the color DMI, pulsed DMI, and strain rate findings in 2 cases of constrictive pericarditis in which consideration of the annular motion pattern alone would not have allowed such differentiation.
Cardiomyopathy, Restrictive↗
Age-dependent changes in regional diastolic function evaluated by color Doppler myocardial imaging: a comparison with pulsed Doppler indexes of global function.
The goals of this study were to evaluate possible normal age-related changes in regional myocardial relaxation as detected by color Doppler myocardial imaging (CDMI) velocities and to compare the extent of any such changes with age-induced changes in global diastolic function. In 80 healthy subjects (aged 21 to 72 years, equally subdivided by decades) the mitral flow velocities in early diastole (E) and atrial contraction (A) were recorded as were the velocities of left ventricular (LV) motion of early (EDV) and late diastole (LDV) in the 16 standard LV segments, and their ratios were calculated. In healthy persons younger than 40 years, all segments showed an EDV/LDV ratio > 1, whereas in healthy persons aged 40 years or older the mean EDV of all segments decreased, and the mean LDV increased, resulting in a significant decrease of the mean EDV/LDV ratio with age. Values of EDV/LDV ratios were higher than E/A ratios (P <.0001), but their changes with age correlated well with each other (r = 0.805). With increasing age, an EDV/LDV ratio <1 was observed more often in basal segments (P <.001, compared with mid and apical segments) and less often in segments of anteroseptal and posterior walls viewed from the parasternal window. The presence of >50% segments with an EDV/LDV ratio <1 was associated with an E/A ratio <1. Regional diastolic function indexes as evaluated by CDMI changed with increasing age in a heterogeneous way and influenced global diastolic function parameters.
Adult↗
Intraoperative magnetic resonance imaging for skull base surgery.
OBJECTIVES/HYPOTHESIS: Skull base surgery has evolved over the past several decades. Major improvements in the imaging of skull base pathology led to better target localization and better surgical planning. The objectives of this study were to assess the use of intraoperative magnetic resonance (MR) imaging in the management of a series of patients with skull base pathology. We hypothesized that high-quality intraoperative MR imaging would have an impact on surgery in this patient group. STUDY DESIGN: Prospective, non-randomized, cohort study. METHODS: Thirty-one patients with skull base lesions underwent surgery in a 1.5-Tesla intraoperative MR suite. The concepts of a moving magnet, high magnetic field strength, and radiofrequency coil design are presented. RESULTS: Eleven of 31 patients had the course of surgery significantly altered by the information acquired from the images obtained during surgery. CONCLUSIONS: Intraoperative MR imaging is a valuable adjunct to skull base surgery. One third of patients had altered surgery as a result of this adjunct. Intraoperative MR imaging is of particular value in the treatment of pituitary adenomas and benign skull base tumors.
Adenoma↗
Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits.
OBJECT: Cerebral revascularization with saphenous vein (SV) conduits is used in the management of hard-to-treat lesions that require deliberate arterial occlusion and in selected patients with occlusive vascular disease. Endothelial dysfunction is thought to contribute to acute perioperative vasospasm and chronic graft atherosclerosis. In the present study the authors examined the contribution of the potent vasoconstrictor endothelin-1 (ET-1) to endothelial dysfunction in human SVs. METHODS: The effects of an ET(A/B) receptor antagonist (bosentan), an ET(A) receptor antagonist (BQ-123), and an ET(B) receptor antagonist (BQ-788) on in vitro endothelium-dependent and -independent responses were studied in human SVs. Vascular segments were obtained in 34 patients who had undergone revascularization procedures, and isometric dose-response curves (DRCs) were constructed using the isolated tissue bath procedure as follows: 1) cumulative DRCs to norepinephrine; and 2) DRCs to acetylcholine (ACh) and sodium nitroprusside in the absence and presence of bosentan, BQ-123, or BQ-788. Maximal vasodilatory responses and sensitivity were compared between groups. In the presence of bosentan (Experiment 1) and BQ-123 or BQ-788 (Experiment 2), ACh responses were significantly augmented (percent maximum relaxation values: 7+/-2 [control] compared with 17+/-3 [bosentan], p < 0.002 [Experiment 1]; and 12+/-2 [control] compared with 29+/-2 [BQ-123] and 25+/-2 [BQ-788], p < 0.003 and p < 0.002, respectively [Experiment 2]). The sensitivity of SVs to ACh was unaffected by treatment. These beneficial effects were specific for the endothelium. CONCLUSIONS: Blockade of ET receptors significantly improves endothelial function in SVs. Furthermore, these effects appear to be independently and maximally mediated by antagonism of either ET(A) or ET(B) receptors. Interventions aimed at improving endothelial function may serve to counter perioperative vasospasm and impede atherosclerosis in SVs used for revascularization procedures.
Aged↗
Improvement of endothelial function in insulin-resistant carotid arteries treated with pravastatin.
OBJECT: Insulin resistance and hypertension are independent risk factors for stroke. Endothelial dysfunction in response to risk factors and carotid artery (CA) disease are important in the pathogenesis of stroke. Pravastatin may have cholesterol-independent pleiotropic effects. In the present study the authors examined the effects of short-course pravastatin treatment on endothelial function in CAs obtained in control and insulin-resistant rats with fructose-induced hypertension. METHODS: Thirty rats were divided into two experimental groups, in which 14 were fed a regular diet and 16 were fed a fructose-enriched diet for 3 weeks. The rats were then divided into four groups: control, pravastatin-treated control, fructose-fed, and pravastatin-treated fructose-fed. Pravastatin was administered (20 mg/kg/day) for 2 weeks. Excretion of the urinary nitric oxide (NO) metabolite nitrite (NO2-) was also assayed. The CAs from all rats were subsequently removed and assessed for endothelium-dependent and -independent vascular reactivity in vitro. The rats in the fructose-fed group were insulin resistant, hyperinsulinemic, and hypertensive relative to the rats in the control and pravastatin-treated control groups and exhibited diminished endothelium-dependent vasomotion and urinary NO2- excretion (p < 0.05), with preserved endothelium-independent vasomotion. Strikingly, pravastatin treatment restored endothelium-dependent vasomotion and urinary NO2- excretion in rats in the fructose-fed pravastatin-treated relative to the fructose-fed group (p < 0.05). CONCLUSIONS: The authors report, for the first time, that pravastatin restores endothelial function in CAs from insulin-resistant rats with fructose-induced hypertension. These beneficial effects were ascribed to direct, cholesterol-independent vascular effects of pravastatin and are likely the result of augmentation of NO production. These data provide impetus for further investigation of nonlipid-lowering indications for pravastatin therapy in the prevention and treatment of CA disease.
Animals↗
Transoral resection of axial lesions augmented by intraoperative magnetic resonance imaging. Report of three cases.
Transoral decompression of the cervicomedullary junction may be compromised by a narrow corridor in which surgery is performed, and thus the adequacy of surgical decompression/resection may be difficult to determine. This is problematic as the presence of spinal instrumentation may obscure the accuracy of postoperative radiological assessment, or the patient may require reoperation. The authors describe three patients in whom high-field intraoperative magnetic resonance (MR) images were acquired at various stages during the transoral resection of C-2 disease that had caused craniocervical junction compression. All three patients harbored different lesions involving the cervicomedullary junction: one each of plasmacytoma and metastatic breast carcinoma involving the odontoid process and C-2 vertebral body, and basilar invagination with a Chiari I malformation. All patients presented with progressive myelopathy. Surgical planning MR imaging studies performed after the induction of anesthesia demonstrated the lesion and its relationship to the planned surgical corridor. Transoral exposure was achieved through placement of a Crockard retractor system. In one case the soft palate was divided. Interdissection MR imaging revealed that adequate decompression had been achieved in all cases. The two patients with carcinoma required placement of posterior instrumentation for stabilization. Planned suboccipital decompression and placement of instrumentation were averted in the third case as the intraoperative MR images demonstrated that excellent decompression had been achieved. Intraoperatively acquired MR images were instrumental in determining the adequacy of the decompressive surgery. In one of the three cases, examination of the images led the authors to change the planned surgical procedure. Importantly, the acquisition of intraoperative MR images did not adversely affect operating time or neurosurgical techniques, including instrumentation requirements.
Aged↗
Understanding and managing ischemic stroke.
Transient or permanent focal brain injury following acute thromboembolic occlusion develops from a complex cascade of pathophysiological events. The processes of excitotoxicity, peri-infarct depolarisation, inflammation, and apoptosis within the ischemic penumbra are proposed. While the translation of therapeutic agents from the animal models to human clinical trials have been disappointing, there remains an atmosphere of optimism as a result of the development of new diagnostic and therapeutic approaches, which include physiological, as opposed to pharmacological, intervention. This article provides an insight into the understanding of cerebral ischemia, together with current and future treatment strategies.
Animals↗
Neurosurgical suite of the future. III.
The neurosurgical suite of the future will continue to incorporate developing technologies so that lesion localization, surgical dissection, electrode placement, and cell/drug delivery will be optimized. In this article it was shown that MR technology can be placed into a neurosurgical operating room and used as a surgical adjunct in such a way that surgical, anesthetic, and nursing techniques are not [figure: see text] compromised. Essential to the success was the high magnetic field strength and system mobility. It is now hypothesized that MR technology, coupled to advances in molecular therapies, endovascular techniques, and transplantation, will continue to improve neurosurgical outcome not only for benign pathology but also malignant neoplastic and degenerative CNS disorders. Although these technologies are intriguing and ultimately will improve neurosurgical outcome, it is likely that for the foreseeable future, neurosurgery will continue to require sound clinical judgment and surgical dexterity.
Adolescent↗
CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy.
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, idiopathic partial epilepsy characterized by clusters of motor seizures occurring in sleep. We describe a mutation of the beta2 subunit of the nicotinic acetylcholine receptor, effecting a V287M substitution within the M2 domain. The mutation, in an evolutionary conserved region of CHRNB2, is associated with ADNFLE in a Scottish family. Functional receptors with the V287M mutation are highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. CHRNB2 is a new gene for idiopathic epilepsy, the second acetylcholine receptor subunit implicated in ADNFLE.
Acetylcholine↗
No evidence for association of 5-HT2A receptor polymorphism with suicide.
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Alleles↗
Molecular cloning and chromosomal mapping of a novel five-span transmembrane protein gene, M83.
In an attempt to identify novel transmembrane molecules expressed on hematopoietic cells, we identified a novel transmembrane protein gene, M83. Cloning of the full-length cDNAs of human and mouse M83 revealed that M83 encodes a type I transmembrane protein with a region containing five hydrophobic segments within the C-terminal part of the protein, suggesting that M83 is a five-span transmembrane molecule. The M83 protein was expressed on the cell surface as a glycosylated protein with a molecular mass of 84 kDa. The M83 gene was localized to human chromosome 16p13.3, mouse chromosome 17B1, and rat chromosome 10q12.3 distal. In human, M83 mRNA was highly expressed in placenta, pancreas, and lymphohematopoietic tissues including peripheral blood, spleen, and bone marrow. Among hematopoietic cells, it was highly expressed in resting T lymphocytes and was downregulated by cell activation, suggestive of its biological role related to the T cell resting status.
Amino Acid Sequence↗
Quantitation of left-ventricular asynergy by cardiac ultrasound.
The clinical evaluation of regional delays in myocardial motion (myocardial asynchrony) has proved problematic, yet it remains an important functional parameter to evaluate. Prior attempts to quantify regional asynergy have met with limited success, often thwarted by the low temporal resolution of imaging-system data acquisition. If a delay in onset of motion of 30-40 msec is clinically important to measure, then data acquisition at frame rates of 50-100 per second is required. This is out of the current temporal resolution of angiographic, nuclear, or magnetic resonance studies. Only cardiac ultrasound can currently achieve the necessary frame rates. Furthermore, quantitative studies into the accuracy with which a trained observer can identify computed regional myocardial asynchrony in a left-ventricular 2-dimensional (2-D) image have shown that regional delays of < 80 msec are not normally recognized in a moving image. This may be improved to 60 msec when either training is undertaken or comparative image review is used. However, this is still out of the temporal resolution required in clinical practice. Thus, visual interpretation of asynchrony is not sufficiently accurate. Two ultrasound data sets based on either integrated backscatter or Doppler myocardial imaging data may provide the solution. Doppler myocardial imaging is a new ultrasound technique which, in either its pulsed or color Doppler format, can achieve the required temporal resolution (with temporal resolutions of 8 msec and 16 msec, respectively). In contrast, color Doppler myocardial imaging, in its curved M-mode format, can display the timing of events during the cardiac cycle for all in-plane myocardial segments. This should allow the quantitation of regional delay for all systolic and diastolic events. Potentially, asynchrony due to regional ischemia, bundle branch block, ventricular premature beats, and ventricular preexcitation could all be identified and the degree of delay quantified. This overview will aim to establish the potential role of these new ultrasound methodologies in the recognition and quantitation of left-ventricular asynergy and how they might best be introduced into clinical practice.
Echocardiography↗
Human and mouse homologues of the Drosophila melanogaster tweety (tty) gene: a novel gene family encoding predicted transmembrane proteins.
We have cloned cDNA for TTYH1, a human homologue of the Drosophila melanogaster tweety (tty) gene. The 450-residue predicted protein shows 27% amino acid sequence identity (51% similarity) to the Drosophila protein, which contains an additional C-terminal repetitive region. A second Drosophila homologue exhibits 42% identity (65% similarity) to the tty protein. Mouse (Ttyh1), macaque, and Caenorhabditis elegans homologues were also identified, and the complete coding sequence for the mouse gene was determined. The mouse protein is 91% identical to the human protein. Hydrophobicity analysis of the tty-related proteins indicates that they represent a new family of membrane proteins with five potential membrane-spanning regions. The yeast FTR1 and FTH1 iron transporter proteins and the mammalian neurotensin receptors 1 and 2 have a similar hydrophobicity profile, although there is no detectable sequence homology to the tty-related proteins. This suggests that the tweety-related proteins could be involved in transport of iron or other divalent cations or alternatively that they may be membrane-bound receptors. TTYH1 was mapped to chromosome 19q13.4 by FISH and by radiation hybrid mapping using the Stanford G3 panel.
Amino Acid Sequence↗
6-Aminonicotinamide inhibition of the pentose phosphate pathway in rat neocortex.
6-Aminonicotinamide (6-AN) is thought to inhibit the pentose phosphate pathway (PPP) since large increases in 6-phosphogluconate are observed following its administration. Immediately following 45 min i.v. infusion of [2-(13)C]glucose to controls and 6-AN-treated (50 mg/kg i.p. given 4 h previously) Sprague-Dawley rats (n = 5 for both groups), metabolism was arrested using freeze-funnel fixation. Chloroform-methanol-water neocortical extracts from animals administered with 6-AN demonstrated elevated levels of 6-phosphogluconate and 6-phosphoglucono-delta-lactone, both of which demonstrated labeling through metabolism of [2-(13)C]glucose. Comparison of the C-2 and C-3 lactate positions using 1H NMR spectroscopy showed that the fraction of glucose metabolized through the PPP is unchanged by 6-AN (14+/-0.6% vs 14+/-0.3% in control animals). It is hypothesized that as the PPP is inhibited by metabolites of 6-AN in the neocortex, glycolysis is inhibited in a proportionate manner through an inhibitory effect on phosphoglucose isomerase by 6-phosphogluconate and/or 6-phosphoglucono-delta-lactone.
6-Aminonicotinamide↗