Intraventricular placement of a spring expander does not attenuate cardiac atrophy of the healthy heart induced by unloading via heterotopic heart transplantation.

An important complication of the prolonged left ventricle assist device support in patients with heart failure is unloading-induced cardiac atrophy which proved resistant to various treatments. Heterotopic heart transplantation (HTx) is the usual experimental model to study this process. We showed previously that implantation of the newly designed intraventricular spring expander can attenuate the atrophy when examined after HTx in the failing heart (derived from animals with established heart failure). The present study aimed to examine if enhanced isovolumic loading achieved by implantation of the expander would attenuate cardiac post-HTx atrophy also in the healthy heart. Cardiac atrophy was assessed as the ratio of the transplanted-to-native heart weight (HW) and its degree was determined on days 7, 14, 21 and 28 after HTx. The transplantation resulted in 32±3, 46±2, 48±3 and 46±3 % HW loss when measured at the four time points; implantation of the expander had no significant effect on these decreases. We conclude that enhanced isovolumic loading achieved by intraventricular implantation of the expander does not attenuate the development of cardiac atrophy after HTx in the healthy heart. This indicates that such an approach does not represent a useful therapeutic measure to attenuate the development of unloading-induced cardiac atrophy.

Mobilization of peripheral blood progenitor cells (PBPC) through a combination of chemotherapy and G-CSF in breast cancer patients and a possibility of unprocessed whole blood collection.

To support multicyclic, dose-intensive chemotherapy in breast cancer, we assessed the effects of reinfusing hematopoietic progenitors either as a leukapheresis product or as mobilized unprocessed whole blood. In this clinical study, 16 consecutive female breast cancer patients were given six cycles of chemotherapy regimen EC (epirubicin (150 mg/m2) and cyclophosphamide (1250 mg/m2) on day 1). In the first cycle, 24 h after chemotherapy, mobilization of the peripheral blood progenitor cells (PBPC) was started with growth factor G-CSF (Neupogen; Amgen-Roche) at a dose of 5 microg/kg/day for 13 days. In all other cycles G-CSF had been given at the same dose from day 7. On days 11, 12 and 13 the leukaphereses were performed and their products cryopreserved. On day 14 whole blood was collected. The median peak incidence of CFU-GM (granulocyte-macrophage colony-forming unit) in peripheral blood was approximately 50 times the baseline level. The leukapheresed PBPC were divided into portions and reinfused after the fourth, fifth and sixth chemotherapy courses. The support with mobilized whole blood was given after the second and third cycles. The effects of the support of whole blood vs leukapheresed PBPC on hematopoietic recovery were compared. The best yields of leukaphereses were achieved on day 13 after initiation of the chemotherapy. The mean number of CD34+ cells was 4.93 x 10(6)/kg (s.d. 2.7; range 0.36-10.54 x 10(6)/kg) the amount of CFU-GM was 2.18 x 10(5)/kg (s.d. 1.3; range 0.07-4.2 x 10(5)/kg). The yields of CFU-GM in 450 ml whole blood collected on day 14 reached 0.51 x 10(5)/kg (s.d. 0.28; range 0.05-1.5 x 10(5)/kg) and of CD34+ cells were 1.3 x 10(6)/kg (s.d. 0.8, range 0.18-2.58 x 10(6)/kg). PBPC yields in 450 ml of unprocessed whole blood were in some cases not sufficient for good hematopoietic recovery after the EC cycles. Grade 4 leukopenias and thrombocytopenias were two times higher in cycles with whole blood support than in cycles with cryopreserved PBPC support. An increase of PBPC harvest can be simply achieved by collecting larger amounts of unprocessed blood, as used by some authors.

Elevation of extracellular adenosine induces radioprotective effects in mice.

The radioprotective effectiveness of the elevation of extracellular adenosine induced in mice by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, a soluble adenosine pro-drug, was evaluated. Based on survival studies, endogenous hemopoietic spleen colony formation, and the postirradiation behavior of bone marrow granulocyte-macrophage colony-forming cells (GM-CFC), it was demonstrated that the combined administration of dipyridamole and AMP protects mice when given either 15 or 60 min before irradiation. It could be deduced that the radioprotective action is induced by at least two independent mechanisms: (1) protection by hypoxia as a result of the effect of the treatment on the cardiovascular system, and (2) and enhanced regeneration of the hemopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hemopoietic stem cells. Both of these protective mechanisms, which are able to increase the regeneration of hemopoiesis, seemed to be effective in enhancing the survival of mice given single radiation exposures, with a dose reduction factor for the LD50/30 of 1.11. The protective efficiency of the mechanisms enhancing the postirradiation recovery of hemopoiesis was also evident in experiments evaluating the survival of mice subjected to fractionated irradiation and a repeated administration of the protective agents.

The use of isoprenaline in experimental hyperthermia.

The paper presents the results of experiments in which the perfusion of Walker carcinoma 256 in rats was influenced by s.c. application of isoprenaline under conditions of 45 degrees C hyperthermia. Cumulation of heat energy in the tumor was selectively increased and higher speed of temperature rising was achieved. The changes in blood supply in tumor tissue and skin were quantitatively documented by a method of 86Rb uptake.

Radioprotective and hemodynamic effects of WR-2721 and cystamine in rats: time course studies.

In experiments on rats radioprotective dose of WR-2721 (200 mg/kg) and cystamine (50 mg/kg) exhibited significant protective effects against radiation death during the first hour after their i. m. administration. Gamma rays were delivered with the dose rate of 0.35-0.31 Gy/min in gradually increased doses for the calculation of LD values and relative efficacy of the whole body irradiation. WR-2721 afforded protection with the highest dose reduction factor (DRF) of 1.51, while the best DRF value after cystamine was 1.36. No protection was found when the interval between injection of both protectors and the beginning of irradiation was longer than 60 min. WR-2721 as well as cystamine induced in pentobarbital anesthetized rats significant depression of cardiac output, hypotension and bradycardia immediately after their i. m. injections. The signs of depression of the hemodynamics persisted throughout the 4-hour observation period. Our results indicate that the hemodynamic effects of WR-2721 and of cystamine are not important for their radioprotective actions in rats.

Radioprotective effect of inosine and its enhancement by magnesium and global hypoxia.

The slight radioprotective action of inosine, when injected intraperitoneally to mice shortly before gamma-irradiation, can be enhanced by the administration of magnesium aspartate. This effect can be explained by the additivity of the vasodilatory actions of both agents. Inosine increases the radioprotective effectiveness of hypobaric hypoxia (10% O2), probably due to the additivity of the hypoxic effects in radiosensitive tissues. Acute hypoxic toxicity, however, is decreased by inosine administration. The cumulation of radioprotective effects of inosine and of its antihypoxic action in vitally important organs can have a favourable influence in hypoxic radiotherapy.

Computer controlled multisensor thermocouple apparatus for invasive measurement of temperature.

The computer controlled apparatus for invasive measurement of temperature profile of biological systems based on original miniature multithermocouple probe is described in this article. The main properties of measuring system were verified by using the original testing device.

The multithermocouple for the use in radiothermotherapy.

The original multithermocouple probe developed for the use in radiothermotherapy is described in this article. On the basis of experimental measurements and theoretical assumptions the properties of the probe are exactly defined and the mathematical model of the probe is given and identified.

Technical note: Parasitic thermovoltage in the multithermocouple probe, its explanation and elimination.

The parasitic thermovoltage can influence the temperature measurement during hyperthermia using the miniature multithermocouple probes with a common wire. It was noticed that, when a thermocouple junction is placed in a sharp thermal gradient, a parasitic thermovoltage is added to the voltage of all remaining thermocouples situated in the direction to the tip of the probe. This article gives the theoretical explanation, experimental verification, and practical elimination of this phenomenon.

[Use of thermoelectric properties of materials with shape memory in medicine]. / Moznosti vyuzití termoelektrických vlastností materiálu s tvarovou pametí v medicíne.

Article deals with some possibilities of the combination of the shape memory and another physical properties of nitinol (Ti-Ni alloy) for application in the medicine. The thermoelectric properties of originally developed miniature thermocouple probe with the shape memory are described in details. The shape memory effect of the thermocouple is based on the use of the combination of the metals nitinol and constantan.

Enhancement of hypoxia radioprotection and decrease of hypoxia toxicity caused by adenosine monophosphate.

It was shown in experiments on mice that the radioprotective effects of adenosine monophosphate (AMP) or of a combination of Mg aspartate and AMP join with those induced by hypobaric hypoxia. The hypotensive effects of these drugs lead probably to hypoxia in radiosensitive tissues which acts additively with hypoxia elicited by way of respiration. Furthermore, Mg aspartate and AMP decrease the toxicity of high degrees of hypobaric hypoxia. These effects can be explained by the ability of adenosine liberated from AMP and of magnesium to increase brain and heart blood perfusion and/or to mitigate excessive sympathetic activity. The pharmacological effects of AMP and Mg aspartate are thus not only radioprotective but also energy preserving and protecting vitally important organs against hypoxia toxicity. These effects may be of favourable importance in hypoxic radiotherapy.

Contribution to some radiobiological aspects of the investigation of radiosensitizers of hypoxic cells. Part IV: Radiosensitizing effect of metronidazole evaluated on the level of postirradiation changes of bone marrow cellularity in rats protected by induced hypoxia of lower body half.

Radiosensitizing effect of metronidazole (Entizol, Polfa, Poland) was tested on an experimental model of ischaemized bone marrow. The changes of bone marrow cellularity were recorded after whole body irradiation of rats protected with abdomen compression during irradiation. With an increasing dose of irradiation proportional and significant decrease of nuclear elements in bone marrow occurred the third day after irradiation. Metronidazole administered to unprotected rats (without compression) did not show any effect. The abdomen compression led to a pronounced radioprotection but metronidazole administration reduced this effect significantly. Ischaemization of the lower half of rat body produced on the level of bone marrow cellularity the protection corresponding to DRF (dose reduction factor) = 1.96 the third day after irradiation. DRF value decreased to 1.52 by metronidazole application which corresponds to ER (enhancement ratio) = 1.29.

Effect of palmitoyl-DL-carnitine on the 3H-dihydroergotoxine intestinal absorption in rat.

Using the methods of rat intestine perfusion in situ and kinetics examination in vivo, absorption of 3H-dihydroergotoxine (3HDHE) from the gastrointestinal tract into systemic blood was investigated. The aim of the study was to increase absorption of the ergot alkaloid with palmitoyl-DL-carnitine (5 mg/rat). Low absorption of 3HDHE was demonstrated in contrast to fast and almost complete absorption of the model drug theophylline (5 mg kg-1). In the experiment this was evidenced by in situ continuous measurement of the administered activity (125 micrograms kg-1) into a reservoir. At the end of the experiment (120 min) the plasma activity reached 0.034 +/- 0.014%, retention in the intestine achieved more than 60%, uptake in the brain 0.044 +/- 0.015%, cumulative excretion in bile 1.50 +/- 0.31% of administered activity. Palmitoyl-DL-carnitine did not influenced the percentage of activity in the plasma and did not affect bile excretion, retention in the intestine and uptake in the brain. In the vivo experiment oral administration of 3HDHE into the stomach (222 micrograms kg-1) increased activity in plasma (0.069 +/- 0.020% within 24 h), cumulative excretion in urine was 6.1 +/- 3.6%, retention of the drug in the stomach and intestine 46 +/- 12%, activity of the brain 0.11 +/- 0.02%, in the kidney 0.39 +/- 0.17%, and in the liver 0.80 +/- 0.30%. After palmitoyl-DL-carnitine administration the activity of plasma reached 0.084 +/- 0.022% (NS), retention in gastrointestinal tract 39 +/- 9% (NS), activity in the liver 0.71 +/- 0.17% (NS), and activity in the kidney 0.42 +/- 0.13% (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of high energy electron irradiation on blood-brain barrier permeability to haloperidol and stobadin in rats.

The heads of rats were irradiated by 4 MeV electrons in doses 90, 180, and 360 Gy. The observed times of deaths ranged 120-600, 60-420, and 150-370 min after 90, 180, and 360 Gy, respectively. A dose dependent decrease of the brain uptake index of haloperidol was observed 1 and 3 h post radiation. On the other hand an increased brain uptake index was found for stobadin after head irradiation with doses of 180 and 360 Gy. Regional cerebral blood flow, blood pressure, and heart rate were not significantly altered in the period following irradiation with 180 Gy. The observed changes in blood-brain barrier (BBB) permeability seem to be the result of the damaged function of morphological structures forming the BBB rather than altered regional blood flow.

Characterization of the SAR-distribution of the Sigma-60 applicator for regional hyperthermia using a Schottky diode sheet.

INTRODUCTION: Characterization of the performance of an hyperthermia applicator by phantom experiments is an essential aspect of quality assurance in hyperthermia. The objective of this study was to quantitatively characterize the energy distribution of the Sigma-60 applicator of the BSD2000 phased array system operated within the normal frequency range of 70-120 MHz. Additionally, the accuracy of the flexible Schottky diode sheet to measure E-field distributions was assessed. MATERIAL AND METHODS: The flexible Schottky diode sheet (SDS) consists of 64 diodes mounted on a flexible 125 microm thick polyester foil. The diodes are connected through high resistive wires to the electronic readout system. With the SDS E-field distributions were measured with a resolution of 2.5 x 2.5 cm in a cylindrical phantom, diameter of 26 cm and filled with saline water (2 g/l). The phantom was positioned symmetrically in the Sigma-60 applicator. RF-power was applied to the 4-channel applicator with increasing steps from 25W to a total output of 400 W. RESULTS: The complete system to measure the E-field distribution worked fine and reliably within the Sigma-60 applicator. The E-field distributions measured showed that the longitudinal length of the E-field distribution is more or less constant, e.g. 21-19 cm, over the frequency range of 70-120 MHz, respectively. As expected, the radial E-field distributions show a better focusing towards the centre of the phantom for higher frequencies, e.g. from 15.3-8.7 cm diameter for 70-120 MHz, respectively. The focusing target could be moved accurately from the left to the right side of the phantom. Further it was found that the sensitivity variation of nine diodes located at the centre of the phantom was very small, e.g. < 3% over the whole frequency range. CONCLUSION: The SAR distributions of the Sigma-60 applicator are in good agreement with theoretically expected values. The flexible Schottky diode sheet proves to be an excellent tool to make accurate, quantitative measurements of E-field distributions at low (25 W) and medium (400 W) power levels. An important feature of the SDS is that it enables one to significantly improve quantitative quality assurance procedures and to start quantitative comparisons of the performance of the different deep hyperthermia systems used by the various hyperthermia groups.

Accuracy of electrical field measurement using the flexible Schottky diode sheet at 433 MHz.

In this study, the accuracy of Schottky diode sensors mounted as a two-dimensional array on a flexible 125 micro m thick polyester foil has been studied. The diodes are placed at a distance of 2.5 x 2.5 cm, resulting in a measuring area of 20 x 20 cm. The diodes are placed across the gap between both arms (3 x 5 mm) of a dipole, total length 12 mm. High resistance (1 M Omega/m) carbon transmission lines printed on the sheet are used to connect each electrical (E) field sensor to the read-out electronics and a data-acquisition system. It is demonstrated that the flexible Schottky diode sheet can quantitatively measure E-field distributions at 433 MHz with an overall accuracy of approximately 6% (1 SD). The largest contribution to the inaccuracy is related to the phantom heterogeneity. The absolute sensitivity of this electrical field sensor is 0.71 V/m per V/m of the applied external electromagnetic field. The DC-voltage signal of the diodes shows a more or less square root relation to the RF-power applied to the applicator over a 15-fold range. An important feature of the system is that it provides the ability to perform on-line monitoring of the E-field, i.e. the SAR distribution of 433 MHz applicators. Further, it enables the introduction of fast and easy quality control protocols for superficial hyperthermia applicators.

[The pathophysiologic basis for the incorporation of 99mTc-pyrophosphate into myocardial infarct]. / Príspevek k patofyziologické podstate inkorporace 99mTc-pyrofosfátu do srdecního infarktu.

The investigation studied the relation of 99mTc-pyrophosphate incorporation (99mTc-PYP) into experimental, 48-hours old myocardial infarction in dogs to tissue vascular supply and to the extent of necrotic tissue. The experimental myocardial infarction was induced in five animals during an operation by the ligation RIVA. The myocardial blood supply was measured in tissue samples, taken from transverse sections of the infarction by means of 86Rb captation. The extent of myocytolysis was measured by depletion of tissue creatine kinase (CK). In the subendocardial layer of the infarction it became obvious that 99mTc-PYP incorporation was proportional to the decrease of tissue blood supply. No relation between the extent of necrosis and the incorporation of the radioactive chemical was demonstrated. The accumulation of 99mTc-PYP requires the necrosis to be present, but its extent apparently does not influence the intensity of incorporation. In the subepicardial infarction layer there was neither a relation of the radioactive chemical cumulation to the blood flow, nor to the extent of the necrosis proved.