ω-Halofatty acids: A probe for mitochondrial membrane integrity

Long-chain -halofatty acids, especially -¹²³I-iodoheptadecanoic acid (IHA), are widely used clinically as radiopharmaceuticals for functional heart imaging. The metabolic interpretation of the various elimination rates, however, remains in dispute. It has been previously shown (Kloster and Stöcklin 1982) that in isolated perfused guinea-pig hearts halide diffusion from the mitochondrion to the blood is the rate-determining step of IHA pharmacokinetics in normal myocardium. We have now extended these in vitro experiments to normal and globally ischaemic isolated perfused rabbit hearts. Again, in normal hearts a single phase iodide elimination half-time (14.3±2.1 min) was observed. In hearts made globally ischaemic for 90 min, the iodide elimination was biphasic with a first fast phase (T_1/2=3.8±0.49 min) and a late slow phase (T _1/2=60.5±14.0 min). The first fast phase is attributed to iodide ion released by residual -oxidation (more rapid than in normal hearts due to damaged membranes in ischaemia), while the late slow phase is explained by -oxidation of IHA slowly released by hydrolysis of intracellular lipid stores. These data were compared with published data from investigations in patients which seem to support our interpretation.     

Measurement of myocardial fatty acid metabolism: kinetics of iodine-123 heptadecanoic acid in normal dog hearts

To define the potential of iodine-123 heptadecanoic acid (IHA) for the noninvasive assessment of myocardial fatty acid metabolism with gamma camera imaging, the influence of myocardial oxygen consumption (MVO2) and blood flow (MBF) on extraction and half-times of IHA were investigated in dogs. Following IHA injection into the left circumflex coronary artery, extraction fraction and half-times were derived from the peak and slope of the IHA time activity curve, which consisted of a vascular, early, and late phase. Single-pass extraction fraction of IHA averaged 0.53 +/- 0.11 s.d. at control and was not influenced by MVO2 and MBF. The half-time of the early phase (T = 9.3 min +/- 2.8 s.d. in controls) as well as the ratio between the size of the early and late phase increased with MVO2 (r = 0.82, r = 0.87, respectively). Thus, early phase intracellular turnover of IHA increased, yet clearance of 123I activity was slowed by augmented cardiac work. Preliminary data of HPLC and electrophoretic analysis of myocardial arterial and venous blood samples over time indicate that the early phase is characterized by a decreasing washout of IHA and a relative increase of radioiodine washout. The half-time of the late phase (T = 245 min +/- 156 s.d. at control) was not related to MVO2 and MBF. In conclusion, myocardial fatty acid metabolism cannot be measured from the half-time of the early phase but might be analyzed from the ratio between the size of the early and late phase when using IHA.     

Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: effect of decreased fatty acid oxidation on deiodination

Terminally radioiodinated fatty acid analogs are of potential use for the noninvasive delineation of regional alterations of fatty acid metabolism by gamma imaging. Since radioactivity from extracted iodine-123 heptadecanoic acid [( 123I]HDA) is released from the myocardium in form of free radioiodide (123I-) the present study was performed to determine whether deiodination of [123I]HDA is related to free fatty acid metabolism. Myocardial production of free radioiodide was measured in rat hearts in vitro and in vivo both under control conditions and after inhibition of fatty acid oxidation. In isolated rat hearts perfused at constant flow with a medium containing [123I]HDA, release of 123I- was markedly reduced during cardioplegia and pharmacologic inhibition of mitochondrial fatty acid transfer with POCA by 67% (p less than 0.005) and 72% (p less than 0.005), respectively. In fasted rats in vivo, 1 min after i.v. injection of [123I]HDA, 51 +/- 5% of myocardial radioactivity was recovered in the aqueous phase, containing free iodide, of myocardial lipid extracts. Aqueous activity was significantly decreased in fed (20 +/- 2%; p less than 0.002) and POCA pretreated (30 +/- 3.7%; p less than 0.05) animals exhibiting reduced oxidation of [14C]palmitate. Thus, deiodination of [123I]HDA was consistently reduced during inhibition of fatty acid oxidation in vitro and in vivo. The results apply to the interpretation of myocardial clearance curves of terminally radioiodinated fatty acid analogs.     

Mathematical model of the metabolism of 123I-16-iodo-9-hexadecenoic acid in an isolated rat heart. Validation by comparison with experimental measurements

The aim of the present study was to demonstrate that it is possible to estimate the intracellular metabolism of a fatty acid labelled with iodine using external radioactivity measurements. ¹²³I-16-iodo-9-hexadecenoic acid (IHA) was injected close to the coronary arteries of isolated rat hearts perfused according to the Langendorff technique. The time course of the cardiac radioactivity was measured using an INa crystal coupled to an analyser. The obtained curves were analysed using a four-compartment mathematical model, with the compartments corresponding to the vascular-IHA (O), intramyocardial free-IHA (1), esterified-IHA (2) and iodide (3) pools. Curve analysis using this model demonstrated that, as compared to substrate-free perfusion, the presence of glucose (11 mM) increased IHA storage and decreased its oxidation. These changes were enhanced by the presence of insulin. A comparison of these results with measurements of the radioactivity levels within the various cellular fractions validated our proposed mathematical model. Thus, using only a mathematical analysis of a cardiac time-activity curve, it is possible to obtain quantitative information about IHA distribution in the different intracellular metabolic pathways. This technique is potentially useful for the study of metabolic effects of ischaemia or anoxia, as well as for the study of the influence of various substrates or drugs on IHA metabolism in isolated rat hearts.     

Pulmonary clearance of 99mTc-HMPAO aerosol

The clearance rate of inhaled aerosols of a lipophilic substance, 99mTc-HMPAO (Hexamethyl propylene amine oxime) was studied and compared to that of hydrophilic substances in 6 normal volunteers and 18 patients with lung diseases. The subject in sitting position inhaled a single deep breath of 99mTc-HMPAO aerosols, and held his breath about 30 sec. Then he continued to breath aerosols again for about 3 min. Radioactivity rapidly falls down during breath holding, to about 60% of the peak value (fast phase), with T 1/2 of 3.75 +/- 2.22 sec in 6 normal volunteers. This rapid phase was not appeared in hydrophilic aerosols with 99mTc-DTPA and 99mTc-pertechnetate and in lipophilic aerosol with 123I-IMP aerosol. The clearance of residual activity of 99mTc-HMPAO was slow with T 1/2 of 17.4 +/- 4.0 min. The T 1/2 of 99mTc-DTPA, 99mTc-pertechnetate and 123I-IMP were 50.2 +/- 20.9 min, 11.4 +/- 4.3, and 62.5 +/- 20.8 min respectively. 99mTc-HMPAO may cross transcellularly using the whole alveolar surface. The clearance of aerosols in the fast phase is rapid and depend on the regional perfusion. On the other hand, hydrophilic aerosol pass by an intercellular pathway and the clearance will be diffusion limited. As conclusion, inhalation study of 99mTc-HMPAO might be a new method to evaluate perfusion following ventilation study.     

Free fatty acid scintigraphy in patients with successful thrombolysis after acute myocardial infarction

Twenty-three patients with successful intracoronary thrombolytic therapy in the acute stage of infarction underwent scintigraphy with radioiodinated heptadecanoic acid two weeks after myocardial infarction and three to 12 months later. In patients with normal or slow elimination rates in the infarct area, ejection fractions were significantly higher than in patients with fast elimination (70 +/- 6% vs 47 +/- 13%, P less than 0.05). Consequently, left ventricular damage score was lower in patients with normal and slow elimination rates (1.7 +/- 1.6 vs 4.9 +/- 2.4, P less than 0.05). Repeated scintigraphy showed normalization of the elimination rates in patients with previously slow elimination, except in one patient in whom the elimination rate remained slow, patients with fast elimination rates remained unaltered. It is concluded that scintigraphy with radioiodinated heptadecanoic acid is an appropriate method to assess myocardial viability in patients with successful thrombolytic therapy.     

Separate effects of ischemia, hypoxia, and contractility on thallium-201 kinetics in rabbit myocardium

The effects of hypoxia and ischemia, as well as altered contractility, on thallium-201 (201TI) kinetics were evaluated in 42 isolated isovolumetrically contracting rabbit hearts. In Group A, three subgroups (n = 7 each) were studied that had either normal flow and oxygenation, hypoxia and normal flow, or ischemic flow and normal perfusate oxygen content. In Group B, three subgroups (n = 7 each) were studied and all hearts had normal flow but the contractile state was either enhanced with isoproterenol or impaired by hypocalcemia. A hemoglobin-free buffer perfusate was used in all experiments and multiple timed collections of arterial and coronary sinus effluent were used to model myocardial isotope activity during 30 min of constant uptake followed by 30 min of tracer clearance. During ischemia, hypoxia and hypocalcemia peak developed pressure and peak positive and negative dP/dt were all significantly reduced when compared to normal hemodynamic parameters (p less than 0.01). As expected, isoproterenol significantly elevated these parameters (p less than 0.04). Myocardial 201TI kinetics were adequately described utilizing a bi-exponential model having a fast and slow component. Only ischemic hearts had significantly lower rate constants for 201TI uptake and clearance than normal hearts (p less than 0.001). The mean (+/- s.d.) myocardial uptake and clearance rates for 201TI (%/min) varied between 4.86 +/- 0.87 and 7.18 +/- 1.45 for the remaining groups of hearts. Therefore, myocardial 201TI kinetics appear to be dominated by coronary flow and may not reflect marked alterations in the metabolic and contractile state. These data suggest that normal 201TI uptake in impaired or hypercontractile cells, receiving normal flow, may not represent normal cellular function.     

Beta-oxidation of 1-[14C]-17-[131I]-iodoheptadecanoic acid following intracoronary injection in humans results in similar release of both tracers

Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [¹²³I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, ¹⁴CO₂ and inorganic ¹³¹I appeared nearly in parallel, with a peak time of 4–5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (¹²³I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through -oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [¹¹C]palmitic acid and [¹²³I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals.     

Influence of calcium channel inhibitors on the myocardial uptake and retention of technetium 99m N-NOET, a new myocardial perfusion imaging agent: A study on isolated perfused rat hearts

BACKGROUND: Technetium 99m N-NOET is a new myocardial perfusion imaging agent currently in phase III clinical trials in Europe. In vitro studies on newborn rat cardiomyocytes have shown that calcium inhibitors, such as verapamil or diltiazem, inhibit its cellular uptake by 40%. To determine whether such a specificity exists ex vivo, we studied the effect of verapamil, diltiazem, and nifedipine on the myocardial uptake and retention of Tc-99m N-NOET in isolated perfused rat hearts. METHODS AND RESULTS: After a 15-minute baseline period, rat hearts were perfused with 0.5 micromol/L verapamil (n = 6), 0.75 micromol/L diltiazem (n = 6), or 0.1 micromol/L nifedipine (n = 6) for 10 minutes before the injection of a bolus (40 microCi/250 microL) of the tracer. Control hearts were perfused with either 1.5 mmol/L calcium (same concentration as in the treated groups; n = 7) or 0.75 mmol/L calcium (same contractility as in the treated groups; n = 6). Myocardial activity of Tc-99m N-NOET was monitored for 30 minutes. The functional parameters of the hearts were recorded throughout the experiments. Calcium inhibitors induced a 40% to 55% decrease in maximal first derivative of left ventricular pressure (dP/dt) (0.0001相似文献   

Assessment of the neovascular permeability in glioma xenografts by dynamic T(1) MRI with Gadomer-17.

The uptake of Gadomer-17, as probed by fast dynamic T(1) measurements, was used to assess the vascular permeability surface-area product per leakage volume of tissue (k(Tofts)) of human glioma xenografts implanted in mice. With this approach we could discriminate between two types of glioma xenograft lines with a known difference in the perfused vascular architecture and degree of hypoxia. The T(1) data were analyzed according to the Tofts-Kermode compartment model. The fast-growing E102 tumor demonstrated a homogeneous distribution of the vascular permeability surface area across the tumor (mean k(Tofts) value = 0.18 +/- 0.05 min(-1)). The slowly growing E106 tumor showed a more heterogeneous pattern. Three perfused tumor areas with differences in vascular permeability surface area could be distinguished: a well-perfused periphery with high k(Tofts) values (0.24 +/- 0.04 min(-1)), perfused capillaries inside the tumor with low k(Tofts) values (0.108 +/- 0.026 min(-1)), and perfused capillaries adjacent to necrotic regions with high k(Tofts) values (0.29 +/- 0.10 min(-1)). On a different series of tumors, the hypoxic fractions were measured, and these were significantly higher in E106 tumors (0.14 +/- 0.05) compared to tumors of the E102 line (0.03 +/- 0.02).     

Efficacy of 15-(123I)-p-iodophenyl pentadecanoic acid (IPPA) in assessing myocardial metabolism in a model of reversible global ischemia

In a canine model of reversible global ischemia, the residual quantity of 123I was assessed following a bolus injection of 15-p-(123I)-iodophenyl pentadecanoic acid (123I-IPPA). This technique was used to assess changes in free fatty acid metabolism following the utilization of three cardioplegic formulations. Cardioplegic arrest was initiated with Tyers' iso-osmolar (IO) solution (Group A); IO + superoxide dismutase (SOD) (Group B) and IO + allopurinol (Group C). Pre and post operative scanning were completed with 2-5 mCi 123I-IPPA. Clearance was assessed by IPPA time activity curve analysis generating t1/2 (half lives in min) for the early and late phases of the curve. The assessment between groups demonstrated that the elimination of 123I-IPPA products (early phase) was faster from the lateral wall in groups B and C versus group A (14 +/- 12 min, 13 +/- 9 min and 24 +/- 10 min, respectively). The elimination of IPPA (late phase) was also faster from the lateral wall in groups B and C when compared to group A (240 +/- 270 min, 132 +/- 85 min and 416 +/- 238 min). Examining the changes between control and postoperative values for each area of the left ventricle within each group demonstrated no significant changes for groups B and C. Group A, however, demonstrated significantly increased t1/2 values for the lateral wall (early and late phases) and the apical wall (late phase).(ABSTRACT TRUNCATED AT 250 WORDS)     

MR microscopy of multicomponent diffusion in single neurons.

This study examines multicomponent diffusion in isolated single neurons and discusses the implications of the results for macroscopic water diffusion in tissues. L7 Aplysia neurons were isolated and analyzed using a 600 MHz Bruker wide-bore instrument with a magnetic susceptibility-matched radiofrequency microcoil. Using a biexponential fit, the apparent diffusion coefficients (ADCs) from the cytoplasm (with relative fraction) were 0.48 +/- 0.14 x 10(-3) mm2 x s(-1) (61 +/- 11%) for the fast component, and 0.034 +/- 0.017 x 10(-3) mm2 x s(-1) (32 +/- 11%) for the slow component (N = 10). Diffusion in the nucleus appears to be primarily monoexponential, but with biexponential analysis it yields 1.31 +/- 0.32 x 10(-3) mm2 x s(-1) (89 +/- 6%) for the fast component and 0.057 +/- 0.073 x 10(-3) mm2 x s(-1) (11 +/- 6%) for the slow (N = 5). The slow component in the nucleus may be explained by cytoplasmic volume averaging. These data demonstrate that water diffusion in the cytoplasm of isolated single Aplysia neurons supports a multiexponential model. The ADCs are consistent with previous measurements in the cytoplasm of single neurons and with the slow ADC measurement in perfused brain slices. These distributions may explain the multiple compartments observed in tissues, greatly aiding the development of quantitative models of MRI in whole tissues.     

Myocardial kinetics of fluorine-18 misonidazole: a marker of hypoxic myocardium

Fluoromisonidazole, a member of a class of compounds referred to as "hypoxic sensitizers," accumulates in hypoxic, viable tumor cells. We hypothesized that it might therefore accumulate also in ischemic, but non-necrotic myocardium potentially salvageable by interventional therapy. To evaluate the myocardial kinetics of [18F]fluoromisonidazole (FM), 20 isolated perfused rabbit hearts were used to characterize the uptake and binding of tracer under control conditions (n = 6), or with ischemia (flow 10% of control, n = 5), hypoxia without low flow (control flow rates with hypoxic medium, n = 5), or with reperfusion (n = 4). Myocardial retention of tracer detected externally with gamma scintillation probes after 20 min of constant [18F]FM infusion followed by 20 min of washout with nonradioactive buffer was 41 +/- 7% and 46 +/- 8% of peak activity in hearts subjected to ischemia or hypoxia, respectively, and significantly higher than in hearts subjected to either control perfusion or to ischemia followed by reperfusion (18 +/- 6 and 16 +/- 5% of peak activity, respectively, p less than 0.01). The biologic half-time of retained tracer was 40 hr in all hearts indicating essentially irreversible binding. Based on these findings, we measured uptake of [18F]FM using positron emission tomography in five dogs subjected to acute coronary occlusion. Five to thirteen millicuries of tracer were injected within 3 hr of occlusion. Within 30 min after administration of tracer, 18F accumulation in ischemic myocardium was greater than that observed in normal myocardium. The results indicate that [18F]FM accumulates in ischemic myocardium in relation to diminished tissue oxygen content and not simply because of diminished flow. Thus, this class of compounds may be potentially useful to help identify hypoxic myocardium.     

Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactatemediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid ¹⁴C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.

     

An in vivo NMR imaging determination of multiexponential Hahn T2 of normal lung

We describe the first in vivo imaging determination of normal lung tissue's multiexponential transverse magnetization decay. Normal spontaneously breathing rats were used for the measurements. To obtain motion-insensitive images, we used a modified line scan imaging technique which we call the interleaved line scan (ILS). The ILS overcomes the following difficulties associated with imaging lungs: low signal-to-noise ratio (S/N) due to lung's low proton density and short T2 decay, artifacts associated with cardiac and respiratory motion, and excessively long imaging times with conventional line scan techniques. Using the ILS, a 16-line 32-average image with an 8-s repetition time requires 4.3 min. From a series of 16 Hahn spin-echo images with echo times ranging from 16 to 90 ms, we obtained a two-component T2 decay for normal peripheral lung tissue. The measured fast and slow T2 components were 9.5 +/- 1.0 and 34 +/- 5.0 ms for the right lung and 9.0 +/- 1.5 and 32 +/- 4.5 for the left lung. The relative magnetization for the slow T2 component was 7.0 +/- 4.5% for the right lung and 10 +/- 3.0% for the left lung.     

Characteristics of extracellular sodium relaxation in perfused hearts with pathologic interventions.

Sodium spectroscopy and imaging sequences designed to emphasize fast T2 decay or the multiple quantum signal have previously demonstrated a high contrast between normal and pathologic tissue which may be due to changes in intracellular versus extracellular sodium distribution. Since alterations in the amount of signal with fast T2 decay have previously been shown to occur with changes in intracellular sodium content, this study investigated the fast T2 relaxation characteristics of extracellular sodium during pathologic interventions on nonsubmerged perfused rat hearts. T2 data on total sodium content were obtained while global ischemia (stopping all perfusate flow) and extracellular edema (due to long perfusion times) were induced in the heart. The data were fit to a biexponential, with Mf(T2f) the magnitude (time constant) of the fast component of decay. Mf increased significantly in both pathologies (to 319 +/- 26%, n = 3, of baseline for ischemia and to 527 +/- 284%, n = 3, of baseline for edema); the increase with edema was demonstrated to be due to extracellular sodium by intermittently perfusing the heart for a short period with shift reagent. When shift reagent was not used until the conclusion of the edema experiment, Mf increased to 169 +/- 35% of baseline, also due mainly to extracellular sodium. T2f did not exhibit any trends with these experiments, with values ranging from 1.7 to 5.5 ms. We believe that these results indicate that compartmental sodium content will most likely not be quantifiable in pathologic states in the heart with relaxation-based techniques. However, correlations between the pathologic state of the tissue and the sodium NMR signal obtained with pulse sequences or images that emphasize a particular aspect of relaxation may prove to be useful.     

Kinetic analysis of 99mTc-sestamibi evaluates the protective effects by ischaemic preconditioning on ischaemic myocardium in an isolated rabbit heart

OBJECTIVE: To analyse the kinetic changes of uptake, washout and retention of Tc-sestamibi in order to evaluate the protective effects and possible mechanism of ischaemic preconditioning and adenosine preconditioning on myocardium injured by ischaemia/reperfusion. METHODS: Isolated ischaemia/reperfusion rabbit heart models, as established by Langendorff, were used. Eighteen rabbit hearts perfused in Krebs-Henseleit (KH) buffer were randomly assigned to three groups: ischaemia/reperfusion (I/R, n=6), adenosine preconditioning (AD, n=6), and ischaemic preconditioning (IPC, n=6). Tc-sestamibi (55.5 MBq) in KH was perfused for 40 min and washed out for 40 min. The kinetic changes of Tc-sestamibi within myocardial tissue was monitored during the uptake and washout phases. Cardiac haemodynamic parameters, creatine kinase and lactate dehydrogenase leakage in coronary effluent, and myocardial infarct size were measured to assess myocardial injuries in rabbit hearts. RESULTS: In the early phases of uptake, there were no significantly different uptake rates of Tc-sestamibi between AD (before 20 min), IPC (before 15 min) and I/R myocardium (all P>0.05). Uptake rates of Tc-sestamibi in myocardium of the three groups all tended to increase, with the uptake time increasing. In the late phases of uptake, AD and IPC were significantly higher than I/R (all P<0.05). In the washout phases, the retention fractions of Tc-sestamibi in myocardium of the three groups all showed a descending tendency with washout time increasing. The retention fractions in AD and IPC were all higher than I/R (all P<0.05). There were no statistical differences in uptake rates and retention fractions of Tc-sestamibi between AD and IPC (all P>0.05). Cardiac haemodynamic parameters, creatine kinase and lactate dehydrogenase leakage, and myocardial infarct size demonstrated there is lighter injury in AD and IPC myocardium than in I/R (all P<0.05). The retention of Tc-sestamibi and myocardial infarction weight were significantly negatively correlated (r=-0.8384, P<0.001). CONCLUSION: Adenosine preconditioning has similar myocardial protective effects on ischaemia/reperfusion myocardium as does ischaemic preconditioning. Tc-sestamibi may be a sensitive and reliable measure for evaluating the importance and mechanism of ischaemic preconditioning and adenosine preconditioning.     

Evaluating the protective role of ischaemic preconditioning in rat hearts using a stationary small-animal SPECT imager and 99mTc-glucarate

OBJECTIVE: To examine the protective role of ischaemic preconditioning (IPC) in rat hearts using Tc-glucarate (GLA) and a stationary SPECT imager, FastSPECT. METHODS: Twenty-four rats with 30 min myocardial ischaemia and 150 min reperfusion (IR) were studied as follows. The IPC group (n=6) underwent IPC (five cycles of 4 min ligation of the left coronary artery and reflow) before IR. The control group (n=7) was treated by IR without IPC. The SPT group (n=6) was subjected to IPC and an adenosine antagonist, 8-(p-sulfophenyl)-theophylline (SPT). The vehicle group (n=5) received IPC and SPT carrier vehicle. GLA was delivered intravenously 30 min post-reperfusion, and 2-h dynamic cardiac images were acquired by FastSPECT. RESULTS: GLA showed 'hot-spot' accumulation in the ischaemic area-at-risk (IAR) and exhibited lower retention (% 5 min peak) in the IPC and vehicle groups (33.8+/-2.6 vs. 35.7+/-9.2, P>0.05) than in the control and SPT groups (63.1+/-5.3 vs. 54.8+/-4.8, P>0.05). The infarct size (% IAR) was larger in the control and SPT groups (48.2+/-6.3 vs. 41.7+/-6.3, P>0.05) than that in the IPC and vehicle groups (21.0+/-1.9 vs. 19.1+/-4.6, P>0.05). In terms of the ex-vivo IAR-to-normal radioactivity ratio, there was a statistical difference between the control and IPC groups (7.4+/-0.9 vs. 3.0+/-0.4), as well as the SPT and vehicle groups (7.4+/-1.0 vs. 3.4+/-0.5). CONCLUSION: IPC offers cardioprotection and relates to the activation of adenosine receptors in rat hearts. FastSPECT GLA imaging is not only useful in detecting early ischaemia-reperfusion injury, but also valuable in evaluating cardioprotection.     

A kinetic study on secretion and elimination of endogenous thyrotropin in the thyrotropin-releasing hormone test

Serum thyrotropin (TSH) concentrations in normal young men were measured by a high-sensitivity immunoradiometric assay before and after intravenous administration of 500 micrograms of TSH-releasing hormone (TRH). A kinetic model was applied to evaluate the secretion rate both before (V0) and after (V0 + V* at maximum rate) the administration of TRH, the elimination constant (K), the latent time (L) between TRH administration and start of the stimulated secretion, and the total amount of TSH (T) released in response to TRH. V0, V* and T varied widely from individual to individual, but correlated well with TSH before TRH administration (r = 0.93, 0.80 and 0.87, respectively). A few minutes (1.89 +/- 1.30 min) after the administration of TRH, the secretion of TSH (0.025 +/- 0.016 microU/min ml) was stimulated, and the total release over about 1 h was 12.5 +/- 5.6 microU/ml. Serum TSH was maximum at 31.5 +/- 5.7 min. The half-time of disappearance of TSH was 42 +/- 9 min. These data confirm that the stimulated secretion continues for more than 30 min, and that the pituitary releases 43.2 +/- 22.9 mU of TSH (assuming the distribution volume of TSH is 5.8% of body weight) in response to TRH, an amount which correlates closely (r = 0.91) with TSH before TRH administration.     

Assessment of mucociliary clearance in patients with tracheobronchoplasty using radioaerosol

To assess mucociliary clearance in patients with tracheobronchoplasty, radioaerosol inhalation scanning was performed in 14 patients. The unilateral total lung clearance curve was fitted into two compartmental curves, fast and slow, by least-squares techniques in order to assess mucociliary clearance of the bronchial tree quantitatively. Half-time (T 1/2) of the curve resulting from the subtraction of the slow compartment curve from the fast compartment curve was calculated. The mucociliary clearance of the bronchial tree post so-called lobectomy (N = 5) was intact (T 1/2; 13.1 +/- 7.3 min). On the other hand, the mucociliary clearance of the bronchial tree postreconstruction (N = 14) was prolonged (T 1/2; 28.3 +/- 10.6 min), compared with that of the control bronchial tree (N = 15, T 1/2; 11.9 +/- 3.9 min) (p less than 0.01). However, the mucociliary clearance of the bronchial tree postreconstruction showed improvement with the passage of time, and the original clearance was regained 5 to 12 mo after the operation. Radioaerosol inhalation studies revealed both the degree of impairment and the recovery time of mucociliary clearance in patients post-tracheobronchoplasty.