Changes in regional brain perfusion during functional brain activation: comparison of [(64)Cu]-PTSM with [(14)C]-Iodoantipyrine.

A dilemma in behavioral brain mapping is that conventional techniques immobilize the subject, extinguishing all but the simplest behaviors. This is avoided if brain activation is imaged after completion of the behavior and tissue capture of the tracer. A single-pass flow tracer proposed for positron emission tomography (PET) is a radiolabeled copper(II) complex of pyruvaldehyde bis(N(4)-methylthiosemicarbazone), [Cu(64)]-PTSM. [Cu(64)]-PTSM reaches steady-state cerebral distribution more rapidly than the metabolic tracer [(18)F]-fluorodeoxyglucose, allowing imaging with substantially greater temporal resolution. Using dual-label autoradiography, this study compares the relative regional cerebral blood flow tracer distribution (CBF-TR) of [(64)Cu]-PTSM to that of the classic perfusion tracer [(14)C]-iodoantipyrine in a rat model during treadmill walking. Rats were exposed to continuous walking on a treadmill and compared to quiescent controls. [(64)Cu]-PTSM was bolus injected (iv) after 1 min, followed by a 5-minute uptake and subsequent bolus injection of [(14)C]-iodoantipyrine. CBF-TR was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping, as well as by region-of-interest analysis. A high homology was found between the [(64)Cu]-PTSM and [(14)C]-iodoantipyrine patterns of cerebral activation in cortical and subcortical regions. For white matter, however, [(64)Cu]-PTSM showed lower perfusion than [(14)Cu]-iodoantipyrine. [(64)Cu]-PTSM is a useful tracer for functional brain mapping in freely-moving subjects. Its application in conjunction with PET promises to increase our understanding of the neural circuitry of behaviors dependent on locomotion.

Changes in brain functional activation during resting and locomotor states after unilateral nigrostriatal damage in rats.

To evaluate functional neuronal compensation after partial damage to the nigrostriatal system, we lesioned rats unilaterally in the striatum with 6-hydroxydopamine. Five weeks later, cerebral perfusion was mapped at rest or during treadmill walking using [(14)C]-iodoantipyrine. Regional CBF-related tissue radioactivity (CBF-TR) was quantified by autoradiography and analyzed by statistical parametric mapping and region-of- interest analysis. Lesions were confirmed by tyrosine hydroxylase immunohistochemistry and changes in rotational locomotor activity. Functional compensations were bilateral and differed at rest and during treadmill walking. Consistent with the classic view of striatopallidal connections, CBF-TR of lesioned compared to sham-lesioned rats increased in the ipsilateral subthalamic nucleus (STN) and internal globus pallidus, and decreased in the striatum and external globus pallidus. Contrary to the classic view, CBF-TR increased in the ipsilateral ventral lateral, ventral anterior thalamus and motor cortex, as well as in the central medial thalamus, midline cerebellum, and contralateral STN. During walking, perfusion decreased in lesioned compared to sham-lesioned rats across the ipsilateral striato-pallidal-thalamic-cortical motor circuit. Compensatory increases were seen bilaterally in the ventromedial thalamus and red nucleus, in the contralateral STN, anterior substantia nigra, subiculum, motor cortex, and in midline cerebellum. Enhanced recruitment of associative sensory areas was noted cortically and subcortically. Future models of compensatory changes after nigrostriatal damage need to address the effects of increased neural activity by residual dopaminergic neurons, interhemispheric interactions and differences between resting and locomotor states. Identification of sites at which functional compensation occurs may define useful future targets for neurorehabilitative or neurorestorative interventions in Parkinson's disease.

Mapping cerebral blood flow changes during auditory-cued conditioned fear in the nontethered, nonrestrained rat.

Conditioned fear (CF) is one of the most frequently used behavioral paradigms; however, little work has mapped changes in cerebral perfusion during CF in the rat-the species which has dominated CF research. Adult rats carrying an implanted minipump were exposed to a tone (controls, n = 8) or a tone conditioned in association with footshocks (CS group, n = 9). During reexposure to the tone 24 h later, animals were injected intravenously by remote activation with [14C]-iodoantipyrine using the pump. Significant group differences in regional CBF-related tissue radioactivity (CBF-TR) were determined by region-of-interest analysis of brain autoradiographs, as well as in the reconstructed, three-dimensional brain by statistical parametric mapping (SPM). CS animals demonstrated significantly greater, fear-enhanced increases in CBF-TR in auditory cortex than controls. The lateral amygdala was activated, whereas the basolateral/basomedial and central amygdala were deactivated. In the hippocampus and medial prefrontal cortex, CBF-TR increased significantly ventrally but not dorsally. Significant activations were noted in medial striatum and the thalamic midline and intralaminar nuclei. However, the ventrolateral/dorsolateral striatum and its afferents from motor and somatosensory cortex were deactivated, consistent with the behavioral immobility seen during CF. Significant activations were also noted in the lateral septum, periaqueductal gray, and deep mesencephalic nucleus/tegmental tract. Our results show that auditory stimuli endowed with aversive properties through conditioning result in significant redistribution of cerebral perfusion. SPM is a useful tool in the brain mapping of complex rodent behaviors, in particular the changes in activation patterns in limbic, thalamic, motor, and cortical circuits during CF.

Solitary plasmacytoma of the sternum: surgical resection with long-term follow-up.

Two patients with solitary plasmacytoma of the sternum were treated with primary surgical resection. Good long-term results were obtained. There is no long-term documentation that primary radiotherapy alone is the treatment of choice for solitary plasmacytomas. An individualized approach is warranted, especially when there is an isolated bulky lesion involving the chest wall.

Upper dorsal sympathectomy.

Over a 20 year period, 60 patients underwent 76 procedures for upper dorsal sympathectomy, usually with a transaxillary approach but occasionally with an anterior approach. Procedures in male patients and in those that were carried out on the right side were most frequent. There were few simultaneous procedures. The extent of sympathectomy included resection of the lower half of the stellate ganglion through the fourth thoracic ganglion. The results were satisfying for patients with vasospastic disorders and hyperhidrosis and quite acceptable for those with causalgia and vaso-occlusive disorders. Complication rates and the incidence of postoperative Horner's syndrome were low. There were prominent differences in results among the various age groups. In addition, female patients and those with bilateral procedures had less favorable results. Factors that did not appear to affect results included technique of surgical approach, extent of sympathectomy, presence of Horner's syndrome, or the addition of other procedures. Current indications for upper dorsal sympathectomy include cases of Raynaud's and Buerger's diseases refractory to drug therapy, causalgia, vaso-occlusive disorders, and hyperhidrosis.

Technique and value of operative arteriography in coronary artery bypass operations.

In an attempt to make evaluation of coronary artery bypass more meaningful, operative coronary arteriography has been used to aid in defining more precisely the technical aspects of the operation at a time when corrective measures can be carried out. Arteriography is performed following the completion of distal bypass graft anastomoses, whether saphenous vein or internal mammary artery (IMA) bypasses are used. Cut films are exposed at the rate of 2 to 4 frames per second and are evaluated for showing (1) status of anastomosis, (2) status of runoff, (3) lesions undetected preoperatively, and (4) any problems with the bypass conduit. A total of 934 vessels (including 107 IMA grafts) have been visualized in 535 patients. Some form of technical revision was necessary in nine instances. The use of this technique during intraoperative balloon dilatation, in conjunction with and to extend the benefits of conventional bypass, is currently being evaluated.

Aneurysm of the descending thoracic aorta: replacement with the use of a shunt or bypass.

The optimal method of protecting the spinal cord and viscera during the resection of aneurysms of the descending thoracic aorta is controversial, and some surgeons have recently abandoned shunting and bypass techniques. We are concerned that this may not be the safest approach in most surgeon's hands and have reviewed our experience with a consecutive series of these aneurysms, all of which were done with either bypass or a shunt. Between 1965 and 1976, we performed 23 aneurysm replacements with femorofemoral bypass. From 1976 to 1980, we used the Gott shunt in 12 aneurysm operations. Atherosclerotic, traumatic, and dissecting aneurysms were all presented. Nineteen operations were elective and 16 were urgent. Three patients died in the hospital, for an 8.6% operative mortality. There were no cases of paraplegia in the entire series of 35 operations. The actuarial 5 year survival rate (including operative deaths) is 79%. We conclude that when the appropriate surgical technique of aneurysm replacement is combined with a shunt or bypass, an acceptable operative mortality and a very low incidence of paraplegia can be obtained.

Dynamic behavior of prosthetic aortic tissue valves as viewed by high-speed cinematography.

Using a valve testing apparatus of our own design and with a high-speed (600 to 800 frames per second) 16 mm movie camera, films were made of Hancock porcine, Carpentier-Edwards porcine, and Ionescu-Shiley bovine pericardial valves mounted in the aortic position and cycled under physiological conditions at 72 to 100 beats per minute. Fresh and explanted valves were observed using saline or 36.5% glycerol as the pumping solution. When fresh valves were studied using saline solution as the pumpint fluid, the Hancock and Carpentier-Edwards porcine valves showed high-frequency leaflet vibration, which increased in frequency with higher cycling rates. Abnormal leaflet motion was decreased when glycerol was used as the blood analogue. The Ionescu-Shiley bovine pericardial valve did not show abnormal leaflet motion under these conditions. Conclusions drawn from tissue valve testing studies that use excessively high pulsing rates and pressures (accelerated testing) and saline or water as pumping solutions cannot be transposed to predict the fate of tissue valves in a clinical setting.

Some comments on heart valve testing and other observations.

Testing of cardiac valve prostheses has been conducted primarily to ascertain flow patterns, fatigue, and thrombogenicity. The authors present their observations on valve dynamics, strain factors, and clinical correlations resulting from extensive experience in testing valve prostheses. They emphasize the need to retest valves that have undergone even minor modification.

Hydrogen-induced microelectronic capacitor failure in pacemakers.

Ceramic chip capacitors used in hybrid microelectronics for cardiac pacemakers are usually highly reliable. However, under certain conditions of capacitor construction, capacitor materials, mounting techniques, and environmental conditions, high failure rates may occur. A specific example is presented in which a ceramic capacitor used in an implanted pacemaker delaminated and failed approximately 30 days after being implanted. The failed capacitor caused a pulse rate rise, but due to circuit design techniques, the rate increase was limited to an acceptable value. The capacitor that failed was from an isolated lot of capacitors that was manufactured using pure palladium plates. The circuit containing this capacitor was hermetically sealed within a titanium case by welding. During the welding, a small amount of hydrogen was released from the titanium which, over a period of 2 to 4 weeks, was absorbed by the palladium plates in the capacitor. By absorbing the hydrogen, the palladium plates exhibit a volumetric expansion of sufficient magnitude to crack and delaminate the capacitor to the point of failure. Subsequently, the recurrence of this failure mode has been avoided by using capacitors containing special palladium alloys that cannot absorb hydrogen. This phenomenon is of interest to pacemaker designers since mercury batteries used in conventional pacemakers generate large amounts of hydrogen and potentially may be responsible for complications when used in conjunction with capacitors containing palladium.

Thoracic outlet compression. Application of positional arteriographic and nerve conduction studies.

Positional arteriography has not proved to be of significant assistance in the evaluation of patients with thoracic outlet compression and should be reserved for those patients presenting with an obvious arterial problem such as aneurysm, obstruction, or embolic phenomena. Positional ulnar nerve conduction times were positive in 88 per cent of all patients operated on for thoracic outlet compression. Patients with normal neutral and elevated velocities through the outlet should be approached cautiously from a surgical standpoint. We believe that positional ulnar nerve conduction times are a desirable addition to the diagnostic armamentarium of the physician evaluating the patient presenting with symptoms and signs of the thoracic outlet compression syndrome.

In vivo strain measurements of a prosthetic aortic valve.

Up to the present, stress forces on prosthetic heart valves have been studied primarily in an in vitro state and have been derived with a fair amount of estimation. Because of the practical and clinical implications, such as forces that may cause fabric wear or material deterioration, we felt that in vivo determination would be worthy of investigation. A microminiature strain gauge was secured to each leg of a non-cloth-covered prosthetic aortic valve and connected to a dual-beam oscilloscope. Strain measurements were first determined in a pulse duplicator with a blood analogue solution and physiological pressures and flow. The valve was also implanted into a dog in the subcoronary position and strain again measured. In vivo strain was found to be approximately 57 per cent of strain on a prosthetic aortic valve, in vitro, under the conditions of this experiment. This represents the first time that strain and force on a prosthetic aortic valve have been determined directly in the intact animal.