Unilateral Perfusion Research Articles

Patterns of postictal cerebral blood flow in temporal lobe epilepsy

We used single-photon emission computed tomography (SPECT) to study postictal cerebral blood flow (CBF) in 51 patients with temporal lobe epilepsy. There were 78 seizures studied, 77 by early postictal injection of Tc-99m HMPAO (delay from seizure onset = 4.3 +/- 4.5 min) and one by ictal injection. Increased focal temporal lobe uptake, predominantly confined to the anteromesial region, was present in 83% and declined rapidly over 5 minutes. Reduced activity in the lateral temporal lobe accompanied the mesial increase in 80% of studies, extending over much of the ipsilateral hemisphere and closely associated with the degree and extent of postictal EEG slow waves. These patterns enabled correct seizure localization by blinded analysis in 69% (31/45) of the patients with a unilateral EEG focus. The remainder showed bilateral or no changes. One of six patients with bitemporal EEG foci had unilateral perfusion changes. The positive predictive value for the correct localization of a unilateral focus by postictal SPECT was 97% (31/32). Postictal CBF imaging with SPECT can be used to support noninvasive electrographic localization and may decrease the need for invasive electrode studies.

Renal toxicity of antineoplastic agents

Most of the drugs currently used in the treatment of cancer are highly cytotoxic and possess relatively low therapeutic selectivity. Given the major role of the kidney in the excretion of these drugs or their metabolites, it is perhaps surprising that clinically significant nephrotoxicity occurs with a limited number of drugs. Adriamycin induces a nephrotic syndrome in rats characterized by severe acute glomerular injury and sustained proteinuria. Tubular lesions subsequently develop, and the formation of tubular casts with resulting interstitial changes is accompanied by the appearance of glomerulosclerosis. Although the mechanism of adriamycin-induced nephrotoxicity is not known, it has been suggested that redox cycling may contribute to this toxicity by enhancing membrane lipid peroxidation, resulting in damage to kidney endoplasmic reticulum and mitochondrial membranes [l]. Mitocycin C is another redox-cycling drug with a cytotoxic mechanism of action that is very different from adriamycin. A hemolytic uremic syndrome of unknown pathogenesis has been reported in some patients treated with mitomycin C; this syndrome has been reproduced in’a unilateral perfusion study in the rat [2]. Nephrotoxicity has been reported for the nitrosoureas in both clinical and laboratory studies. Methyl-CCNU administered as a single, high dose produces acute proximal tubular necrosis in the rat; impaired tubular transport was evident 1 h after drug treatment. Proteinuria and decreased urine-concentrating ability accompanied necrosis of the papillary collecting ducts l-6 days later. Low-dose treatment resulted in a delayed-onset chronic progressive nephropathy involving polyuria, enzymuria, and decreased urine-concentrating ability [3,4]. Several lines of evidence point to the

Assessing Utility of Single Photon Emission Computed Tomography (SPECT) Scan in Alzheimer Disease

Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score greater than 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS less than or equal to 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS less than 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances.

Favorable outcome of neonatal aortic thrombosis and renovascular hypertension

Fifteen children with renovascular hypertension as a result of aortic thrombosis were followed for a mean of 26 months (range 5 to 58 months) to determine outcome. As neonates, all patients had hypertension and elevated plasma renin activity. Of 11 patients studied with radionuclide renography and scintigraphy, 10 had abnormal renal blood flow; three had complete absence of unilateral perfusion. On follow-up examination all children were normotensive; five children ages 5 to 24 months required antihypertensive medication. Of 15 children, 14 had normal statural growth; all had normal serum creatinine, plasma renin activity, and calculated glomerular filtration rate values. Patients with complete absence of renal perfusion unilaterally remained functionally anephric; children with less severe perfusion deficits had improved perfusion as shown by radionuclide renography and scintigraphy. We believe that many patients with aortic thrombosis and renovascular hypertension who have had aggressive antihypertensive therapy in the neonatal period will have good renal function and increased perfusion to the affected kidney 2 years later.

Tetrahydropapaveroline and salsolinol alter 45Ca2+ efflux within perfused hippocampus of unrestrained rats.

The kinetics of 45Ca2+ efflux were examined at circumscribed sites in the perfused hippocampus of the freely moving rat with either one of two tetrahydroisoquinoline (TIQ) products, tetrahydropapaveroline (THP) or salsolinol. Guide tubes for unilateral push-pull perfusion were implanted stereotaxically to rest just above sites within the dorsal hippocampus. Upon recovery from surgery, a tissue site in the hippocampus was prelabeled with 1.0 microliter of 45Ca2+ (2.0 microCi) injected through the indwelling guide tube. After 16-20 hr had elapsed, successive push-pull perfusions of the site were carried out with an artificial cerebrospinal fluid (CSF), at 5.0 min intervals and at a rate of 20 microliters/min, in order to obtain a control washout curve of declining radioactivity. On the fifth of a series of 5.0 min perfusions, either THP or salsolinol was added to the perfusion medium in a concentration of 10 or 100 ng/microliters. Then the hippocampal site was perfused again with control CSF for the collection of an additional three samples. Although THP in both of the test concentrations generally augmented the efflux of 45Ca2+, the temporal course and magnitude of the enhancement depended on the anatomical site of the perfusion. In the more rostral hippocampal planes of AP 3.0 and AP 4.0, THP caused a delayed efflux of the cation, after the perfusion of THP had been discontinued, in nearly half of the loci reactive to the TIQ. Similarly, salsolinol enhanced significantly the efflux of 45Ca2+ in a concentration-dependent manner during the interval of its perfusion within the hippocampal plane of AP 3.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of laser treatment on respiratory function in malignant narrowing of the central airways.

Twenty patients with inoperable carcinoma in the trachea or a main bronchus were investigated before and one and 10 days after treatment with a carbon dioxide laser. Patients were assessed by spirometry, maximum flow-volume loops, and a visual analogue score of breathlessness on a scale from 0 (not at all breathless) to 100 (very breathless). At day 10 mean FEV1 had improved from 51.9% to 62.6% of predicted (p less than 0.02) and mean peak expiratory flow (PEF) from 45.3% to 53.1% of the predicted value (p less than 0.05). Improvements in maximum inspiratory and expiratory flows at 50% vital capacity were not significant but the breathlessness score decreased from a mean of 49.1 to 35.3 (p less than 0.01). Improvements in breathlessness were significantly correlated with increases in FEV1 and PEF. Thirteen of the 20 patients had unilateral tumours with partial or complete occlusion of the main bronchus; in these perfusion and ventilation were assessed by radioisotope scans before and 10 days after treatment. Seven of the 13 patients showed an increase in perfusion of the affected lung after treatment but the improvement was small, with a mean increase in unilateral perfusion in the 13 patients of 2.4% of the total counts. Four patients with no perfusion of the affected side showed no significant improvement after laser treatment. Changes in ventilation scans were similar to those in perfusion. It is concluded that laser treatment improves airway function and dyspnoea in malignant narrowing of central airways and that in unilateral obstruction such treatment results, at best, in a small increase in the contribution of the affected lung to perfusion.

Effect of lung resection on regional lung function assessed by133Xe radiospirometry

The regional lung function of 39 patients, 19 with lung cancer and 20 with a non-malignant condition, was studied radiospirometrically before partial lung resection and 2, 6, and 12 months postoperatively. Dynamic spirometry was also performed at each stage. Initially, the postoperative reduction of total FEV1 was 19% and of VC 18%. There was 26% reduction of unilateral ventilation, 34% of perfusion and 30% of VC at two months post-operatively. At six months there was significant improvement in all parameters, whereas at twelve months there was no further notable change with the exception of total VC. At twelve months the reduction of FEV1 was 14% and of VC 8%. The unilateral perfusion was reduced 30%, ventilation 19%, and VC 17%. The .V/.Q ratio was 1.00 preoperatively and 1.11 12 months post-operatively. The results show that the final reduction of both unilateral and total function caused by partial lung resection is smaller than would be expected considering the anatomical extent of the operation. However, the .V/.Q mismatch ensuing from the operation may increase the functional impairment. Lung function appears to become stabilized at its permanent postoperative level during the first six months after operation.

Use of isolated perfused lung in determining pulmonary disposition and potential toxicological significance of inhaled environmental pollutants

Recent interest in the investigation of the effect of environmental pollutants on the nonrespiratory and respiratory functions of the lung has stimulated the refinement and application of the technique of perfusing isolated intact lung preparations from suitable experimental animals in toxicological and biochemical studies. Available techniques include perfusion with whole blood or constituted perfusion media via pulmonary artery while maintaining ventilation with alternating negative or positive pressure. Viable, ventilating lung preparations can be maintained for 3 h. Such preparations have been employed for studies of uptake, metabolism and disposition of intratracheally or vascularly administered endogenous or exogenous chemicals. Recent development in unilateral or split-lung perfusion preparations will undoubtedly further enhance the application of these techniques in the study of the interactions of endogenous and exogenous substances in the lung tissue. Isolated, perfused split-lung preparations are particularly suited to investigate early toxic effects of inhaled pollutants in an attempt to gain insight into underlying mechanisms that lead to lung injury. Areas in which intact perfused lungs have been employed extensively with notable success include uptake, metabolism and disposition of toxic chemicals. These preparations have been used to study the effects of gases such as SO2, NO2, O3 and CO on lung metabolism. Perfused lung preparations have been particularly useful in demonstrating pulmonary activation of toxic chemicals and in the demonstration of specific effects on the lung after chronic administration of chemicals. Areas which have not been actively investigated include the uptake and disposition of gases or vapors, effects of toxic chemicals on respiratory and nonrespiratory functions of the lung and alteration in the hemodynamics of the pulmonary circulation in the presence of interacting chemical or physical agents. It should be technically feasible to adapt the perfused lung preparations for such investigations, and interest in this area will continue.

Vasoactive intestinal polypeptide and the canine cerebral circulation.

A potential role for cerebrovascular nerves containing vasoactive intestinal polypeptide (VIP) was examined in 24 anesthetized, ventilated dogs. Cerebral blood flow (CBF) was measured by either the cerebral venous outflow or microsphere method. Plasma VIP concentration was measured by radioimmunoassay. Hypercapnia (5% and 10% CO2) and hypoxia (7% O2) produced significant increases in cerebral venous outflow, but had no affect on arterial or cerebral venous VIP concentrations. Measurements of VIP in cerebrospinal fluid (CSF) made during 5% and 8% CO2 breathing also were not different from control values. VIP produced large dose-dependent increases in common carotid artery and temporalis muscle blood flow when injected or infused intraarterially; however, VIP had no effect on total or regional cerebral blood flow (rCBF) within the brain when administered in a similar manner. Unilateral perfusion of the cerebral ventricles with VIP produced significant increases (range: 11-80%) in rCBF. These data are consistent with the possibility that local release of VIP from perivascular nerve endings could affect CBF. The unresponsiveness of canine cerebral vessels to blood-borne VIP may be due to the blood-brain barrier, since VIP dilates cerebral vessels when the barrier is bypassed by intraventricular infusion. These studies do not support the hypothesis that CBF changes induced during hypercapnia or hypoxia are mediated by VIP.

Decreased Lung Perfusion Due to Broncholithiasis

Two patients each with symptoms of an endobronchial lesion showed decreased unilateral lung perfusion upon radionuclide imaging. Chest films were normal except for hilar lymph node calcifications. Bronchography and tomography revealed compression and obstruction of the bronchial tree by the calcified lymph nodes, accounting for the patients' symptoms. Incomplete bronchial obstruction or collateral air drift accounted for the normal appearance of the lungs on the PA chest films.

UNILATERAL LUNG FUNCTION

MARION, J. M.; ALDERSON, P. O.; LEFRAK, S. S.; SENIOR, R. M.; JACOBS, M. H. Author Information

Unilateral Lung Function: Comparison of the Lateral Position Test with Radionuclide Ventilation-Perfusion Studies

Twenty-seven patients underwent studies of unilateral lung function by the lateral-position test (LPT) and by computer-analyzed radionuclide imaging of ventilation and perfusion. The patients were divided into two groups, symmetric or asymmetric, on the basis of the physical examination of the chest and the chest radiograph. In patients with symmetry, the estimate of unilateral lung function by the LPT and isotopic estimates for unilateral lung volume, unilateral distribution of tidal volume, and unilateral perfusion, agreed within 2 percent, 4 percent, and 3 percent, respectively. In patients with asymmetry, the differences were 9 percent, 8 percent, and 13 percent. In settings of marked unilateral ventilation-perfusion imbalance, the LPT primarily reflected ventilation. Prediction of unilateral ventilatory function based upon the LPT and spirometric measurements agreed closely with unilateral ventilation determined isotopically by 133xenon, even in the presence of chronic obstructive lung disease. Our results confirm that the LPT provides valid information about unilateral lung function.

Unilateral Absent Perfusion of the Lung

Common 1. Bronchogenic Carcinoma1 Less Common Pulmonary embolism' Parenchymal or pleural disease, severe1 Congenital heart disease, after shunting procedure1 After pneumonectomy1 Rare Hyperlucent lung syndrome1 Stenosis of pulmonary artery, hypoplasia, or agenesis of the lung or pulmonary artery2,3 Endobronchial foreign body4,5 Pulmonary veno-occlusive disease6 Bronchial adenoma7 (The Gamut approach to roentgenologic diagnosis has been applied to nuclear medicine [L.E. Holder et al, unpublished data]. Though scintiscan abnormalities are often less specific than roentgenographic changes, the method has proved useful.) Diagnosis Bronchogenic carcinoma. Comment The patient was a 73-year-old man with a chronic cough who had been a two-pack-per-day cigarette smoker for many years. The chest roentgenogram (Fig 1) was taken when he complained of coughing up a few flecks of blood. Hemoptysis continued, and one month later a perfusion lung scan with macroaggregated iodinated I 131 serum albumin was obtained

Chemically induced choreiform activity: Antagonism by GABA and EEG patterns

Relative potencies were determined for several agents capable of inducing choreiform activity when applied unilaterally to the striatum of unanesthetized rats. Picrotoxinin, 2.59 × 10 −10 moles 10 μ l , was followed in order of decreasing potency by d-tubocurarine, alcuronium, carbachol, bicuculline, and thiosemicarbazide. The involuntary movements induced by d-tubocurarine were blocked by intrastriatal infusions of either γ-aminobutyric acid or glutamic acid but not by glycine, aspartic, acid or homocysteic acid. The blocking actions of glutamic acid were attenuated by the presence of allylglycine, a glutamic acid decarboxylase inhibitor. Similarly, striatal infusions of glutamic acid reduced or blocked the choreiform activity induced by picrotoxinin, carbachol, alcuronium, or thiosemicarbazide.. The EEG patterns following intrastriatal d-tubocurarine in unanesthetized, immobilized rats were characterized by large cortical potentials, 0.5–1.5 mv, with a frequency of 0.5/sec. This activity was interrupted every 30–90 sec by episodes of seizurelike activity, lasting 5–10 sec. Unilateral perfusion of the cat caudate nucleus, using a push-pull cannula and Locke's solution containing d-tubocurarine, 1–2 mg/ml, produced large rhythmic discharges in both cerebral cortices and the caudate nucleus. In most animals, this discharge pattern was interrupted periodically by seizure-like activity. Gamma-aminobutyric acid (GABA), added to the perfusion fluid, did not antagonize the effects of d-tubocurarine on the EEG. These results suggest that the involuntary movements induced by d-tubocurarine in the rat may be due to GABA-receptor blockade in the striatum or an increased dopamine release resulting from GABA-receptor blockade. These conclusions are consistent not only with the long-held theory that human hyperkinetic disorders are the result of an increased dopaminergic activity in the basal ganglia, but also with the more recent finding of an abnormally low GABA content in the basal ganglia of patients with Huntington's chorea. Although the EEG changes induced in rats and cats by d-tubocurarine are not consistent with clinical EEG data in Huntington's chorea, the apparent biochemical, behavioral, and pharmacological correlates between this model and hyperkinetic syndromes in man may suggest some common neurochemical denominator.

Quantitative comparison of 99mTc-iron hydroxide aggregates and 133Xe pulmonary perfusion, and importance of sensitivity-corrected gamma-camera data

Unilateral and four-quadrant regional pulmonary perfusion fractions were quantitatively compared for 99mTc-iron hydroxide aggregates and superior-vena-cavally administered 133Xe in 23 patients with chronic obstructive lung disease and a “coin” lesion, using a gamma camera/PDP-8/1 system. 99mTc and 133Xe perfusion fractions were equivalent (±0.03), with correlation coefficient ≥0·9. Unilateral 99mTc perfusion fractions, measured only with the camera operated in divided mode, were insignificantly different from computer-processed 133Xe fractions. Correction of camera data for non-uniform sensitivity response was not necessary for determination of unilateral or four-quadrant perfusion fractions, but may be important in determining absolute 133Xe clearance half-times. Simple static 99mTc-iron hydroxide aggregates imaging was as accurate as dynamic 133Xe studies for routine clinical estimation of unilateral or four-quadrant pulmonary perfusion.

AN EXTRACORPOREAL CIRCUIT FOR UNILATERAL BRAIN PERFUSION AND COOLING.

AN EXTRACORPOREAL CIRCUIT FOR UNILATERAL BRAIN PERFUSION AND COOLING.

Excretion of Krebs cycle acids in relation to the cycle's function in avian kidney

In the chicken, unilateral renal portal perfusion with certain intermediates of the Krebs cycle (notably sodium α-ketoglutarate, succinate, and fumarate) increased excretion of other cycle acids, particularly citrate and α-ketoglutarate. These were excreted at a much higher rate from the ipsilateral kidney. This phenomenon was even more striking during infusion of sodium pyruvate with one-seventh the amount of sodium fumarate, α-ketoglutarate, or oxaloacetate. This resembles the catalytic, or "sparking" effect of these same dicarboxylic acids on pyruvate oxidation by the Krebs cycle in certain tissues, a resemblance strengthened by the fact that this sparked excretion of cycle acids is blocked by sodium malonate or ammonium salts which also block the effect in tissues. These observations are discussed in terms of 1) the possible renal tubular synthesis and secretion of these cycle acids from their infused precursors, and 2) the increased excretion of citrate and α-ketoglutarate in alkalosis.