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At least 379 records · Page 21Linked to original sources
PubMed1992

Ventricular fibrillation does not depress postfibrillatory contractility in blood-perfused dog hearts.

We studied whether ventricular fibrillation depresses ventricular contractility in a blood-perfused heart. In 12 excised, cross-circulated dog hearts, we measured left ventricular pressure and myocardial oxygen consumption at a middle left ventricular volume as control and induced ventricular fibrillation electrically. Six hearts were subjected to 20 minutes of ventricular fibrillation (group A), and the other six hearts were subjected to 40 minutes of ventricular fibrillation (group B). Then we defibrillated the heart with direct current shock and measured left ventricular pressure, left ventricular volume, and myocardial oxygen consumption immediately, 10 minutes, 20 minutes, and 30 minutes after the defibrillation. Coronary perfusion pressure was maintained normal (around 100 mm Hg) by the arterial pressure of the support dog throughout each experiment. Ventricular contractility was quantified by the maximum value for the instantaneous pressure/volume ratio (Emax). Pooled data of both groups A and B showed that Emax immediately after defibrillation increased to 116% +/- 28% (p less than 0.05) of control level and Emax 10 minutes after defibrillation decreased to 84% +/- 17% (p less than 0.05) of control level. Then Emax recovered to the control level: 95% +/- 18% (p greater than 0.05) of control level at 20 minutes and 100% +/- 20% (p greater than 0.05) of control level at 30 minutes after defibrillation. Emax of group A was not different from that of group B at comparable measurement times after defibrillation. Changes in myocardial oxygen consumption per beat were in proportion to the changes in Emax. We conclude that ventricular fibrillation per se for 20 to 40 minutes does not depress postfibrillatory contractility when coronary blood perfusion is maintained normal in the dog left ventricle.

Animals↗
PubMed2005

Detrimental effects after dobutamine infusion on rat left ventricular function: mechanical work and energetics.

We have previously reported that continuous infusion of dobutamine into the coronary artery induces positive inotropic effects but induces no detrimental effects in cross-circulated, excised normal rat hearts and even in Ca2+ overload-induced contractile failing rat hearts. However, we hypothesized that some detrimental effects on left ventricular (LV) function are induced after continuous dobutamine infusion and the following clearance of blood dobutamine, as is the case after beta-adrenergic receptor stimulation. To test this hypothesis, we investigated LV mechanical work and energetics in the same type of preparations that underwent continuous dobutamine infusion and clearance of blood dobutamine. We found that both mean end-systolic pressure and systolic pressure-volume area (PVA; a measure of total mechanical energy per beat) at midrange LV volume were significantly (P < 0.01) decreased. The mean myocardial oxygen consumption per beat intercept, which is composed of for the total Ca2+ handling in excitation-contraction coupling and basal metabolism, of the and PVA linear relation was also significantly (P < 0.05) decreased (n=8). The mean slope of the linear relation was unchanged in such hearts. Post-dobutamine basal metabolism was unchanged (n = 5 of the 8 hearts). The moderate proteolysis of a cytoskeleton protein, alpha-fodrin was identified (n = 7 of the 8 hearts with the decreased intercept), after clearance of blood dobutamine. In agreement with our hypothesis, the detrimental effect of the post-beta-adrenergic receptor stimulation was induced by a moderate concentration of dobutamine; we found systolic dysfunction due to the impairment of Ca2+ handling in excitation-contraction coupling in the rat LV and proteolysis of a cytoskeleton protein, alpha-fodrin.

Adrenergic beta-Agonists↗
PubMed1987

[A personal point of view to EC-IC bypass surgery in completed stroke after the co-operative study].

The role of EC-IC bypass surgery has become a very controversial issue recently. EC-IC anastomosis was performed in 132 patients of stroke in our institute. Thirty six of them which could be followed up completely had a completed stroke and ten of these showed a significant clinical improvement by the next day of surgery. We studied the angiograms, CT scans and dynamic CT studies of all 36 patients to determine the common factors responsible for a significant clinical improvement in these ten patients. It was found that patients with occlusion of middle cerebral arteries and with good collateral circulation fared better than those with other lesions and good cross circulation. Site of low density on CT revealed patient with watershed low density did well. Characteristic of low density area was found to be a significant factors. If the low density area was homogeneous and well defined in an arterial territory, it was invariably associated with no improvement after surgery. Patients showing an improvement had scattered or irregular low density areas. Dynamic CT studies were not found to be significant.

Brain↗
PubMed1977

Changes in renal cyclic nucleotide content as a possible trigger to the initiation of compensatory renal hypertrophy in rats.

1. Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and cyclic guanosine 3', 5'-monophosphate (cyclic GMP) have been estimated in the kidneys of rats.2. Ten minutes after unilateral nephrectomy there was a threefold increase of cyclic GMP in the remaining kidney, which was accompanied by a moderate fall of cyclic AMP.3. The changes in cyclic nucleotides in the remaining kidney after unilateral nephrectomy were of short duration.4. When an anephric rat was cross-circulated with a normal litter-mate, there was an increase of cyclic GMP concentration in the kidneys of the latter, which reached its maximum 10 min after the establishment of the cross circulation.5. In experiments where one kidney of a litter-mate was transplanted to the neck of another rat, unilateral nephrectomy was not followed by changes of the level of cyclic nucleotides in either the transplanted or the remaining kidney. Bilateral nephrectomy, however, resulted in a marked increase of cyclic GMP in the transplanted kidney.6. The clamping of the blood vessels to one kidney for periods up to 10 min had the same effect as unilateral nephrectomy on the concentration of cyclic GMP in the remaining kidney. When the clamp was removed and the circulation restored, the concentrations of cyclic nucleotides returned to preoperative levels in both kidneys.

Animals↗
PubMedDate not supplied

Effects of lidocaine on pulmonary circulation during hyperoxia and hypoxia in the dog.

BACKGROUND AND OBJECTIVES: High concentrations of lidocaine have been found to cause pulmonary vasoconstriction and low concentrations (0.5-0.9 microgram/mL) to cause reversal of nitrous oxide-induced depression of hypoxic pulmonary vasoconstriction. This study was undertaken to examine the effects of high concentrations of lidocaine on pulmonary circulation during hyperoxic and hypoxic ventilation. METHODS: With use of cross-circulation consisting of ventilation and constant-flow perfusion of the left lower lobe (LLL) independently of all other lobes of the dog lung under nitrous oxide and halothane anesthesia, lidocaine was infused into the inflow system, so that plasma lidocaine concentrations in the inflow blood were maintained at either 5, 10, 20, 40, 70, or 140 micrograms/mL during ventilation with 50% oxygen or 3% oxygen. Mean arterial and venous pressures in the LLL (PAPLLL and PVPLLL), airway pressure of the LLL, and blood gas in LLL inflow and outflow were measured. RESULTS: High plasma concentration of lidocaine (140 micrograms/mL) in the LLL inflow produced a significant increase in PAPLLL during hyperoxia, while PAPLLL did not change significantly at the 5-70-micrograms/mL lidocaine concentration. In LLL outflow blood, PO2 increased significantly following a 140 micrograms/mL lidocaine infusion during hyperoxia, while in LLL inflow blood, PO2 did not change. The airway pressure of LLL also did not change. During hypoxia, hypoxic pulmonary vasoconstriction did not occur, and lower plasma concentrations of lidocaine (40-70 micrograms/mL) significantly constricted the lobar vessels. In addition, lidocaine at the 140-micrograms/mL concentration constricted the upstream vessels (presumably the lobar arteries) more strongly than the lobar veins during hypoxia. CONCLUSIONS: Extremely high concentrations (140 micrograms/mL) but not low concentrations (5-70 micrograms/mL) of lidocaine produced pulmonary vasoconstriction and reduced shunt. Lower concentrations of lidocaine constricted the hypoxic lobar vessels.

Anesthetics, Local↗
PubMed1979

Accurate volume determination in the isolated ejecting canine left ventricle by two-dimensional echocardiography.

Two-dimensional echocardiography can provide serial cross-sectional images of the left ventricular cavity. We examined whether such serial images from steady-state ejecting hearts would allow three-dimensional reconstruction and accurate volume estimation without major geometric assumptions. Cross-circulated, paced dog hearts were suspended in a blood-filled tank. Serial cross-sectional images were taken at 3-mm intervals along the vertical axis. Left ventricular cavity and muscle areas of each image were planimetered with a light-pen system and summated for volume: total volume = sigma (areas x 3 mm). Direct left ventricular volume was measured through the cardiac cycle with a volumetric chamber connected to a balloon in the ejecting left ventricle. In six hearts, 67 separate direct volume measurements (range 9.5--54.7 ml) from various points in the cardiac cycle were compared with the simultaneous echo volume measurements. By least squares linear regression, echo volume = 1.01 (direct volume) - 0.44 ml; r = 0.972, SEE = 2.93 ml. Provided accurate cross-sectional localization is available, these studies suggest that extremely accurate steady-state left ventricular volume can be determined noninvasively in the ejecting heart from multiple cross-sectional images.

Animals↗
PubMedDate not supplied

[Progressive decrease of the causes that maintain ventricular fibrillation after experimental coronary occlusion].

Progressive diminution of the causes that maintain ventricular fibrillation after coronary occlusion. Extracorporeal circulation was performed on a group of normal dogs in which a ligature was placed on the left anterior descending coronary artery, immediately beneath the bifurcation of the left coronary artery. The incidence of ventricular fibrillation was of 15 dogs out of 20 (table 1). In a control group without extracorporeal circulation ventricular fibrillation appeared in 24 dogs out of 30 (table 2). These results demonstrate that extracorporeal circulation performed with the idea of improving coronary circulation does not prevent ventricular fibrillation in coronary occlusion. In those dogs with the cross circulation, attempts to defibrillate the ventricles with an electric a.c. defibrillator (three electrical shocks applied directly on the myocardium every 4 or 5 minutes) were uniformly unsuccessful until a period ranging from 12 to 80 minutes elapsed after the onset of ventricular fibrillation. After these periods all fibrillating dogs were defibrillated and recovered either normal or idioventricular rhythm. It is assumed that a "fibrillator substance" liberated by the injury in the initial state of infarction is washed out of the myocardium, or a zone of increased excitability and conduction disturbance is progressively eliminated so that the chances of originating circus movements are diminished.

Animals↗
PubMed1997

Recombinant leptin exchanges between parabiosed mice but does not reach equilibrium.

Parabiosis experiments suggest that ob/ob mice are deficient in a circulating "lipostatic" signal but respond to such a signal when it is delivered in the cross circulation from their parabiotic partner. Identification of leptin as the mutation in ob/ob mice leads to the assumption that leptin is the lipostatic signal. The objective of these experiments was to determine the circulating half-life of leptin and to demonstrate whether it exchanged between parabiosed mice. Measurement of disappearance of recombinant leptin from serum in SWRJ mice indicated a circulating half-life of approximately 36 min. Single ob/ob mice or one member of a parabiosed pair of ob/ob mice received 50 micrograms recombinant murine leptin in two intraperitoneal injections a day for 10 days, starting 40 days after parabiosis surgery. Control mice and pairs received equivalent injections of vehicle. In single mice, leptin significantly reduced food intake, body weight, serum insulin, and pancreatic and liver weight. Leptin treatment of one member of a parabiosed pair of ob/ob mice reduced serum insulin, gut content (an index of food intake), and body fat in both partners. The injected parabiont lost more fat than its partner, and body temperature was increased only in the injected mouse, indicating that leptin did not reach equilibrium in the two animals. This was confirmed by Western blot analysis of serum leptin measured 2 h after injection. Therefore, although leptin can exchange between parabionts, its half-life is inadequate to allow equilibrium when a large concentration gradient exists between partners.

Animals↗
PubMed1999

Acute effect of tumor necrosis factor-alpha is minimal on mechanics but significant on energetics in blood-perfused canine left ventricles.

OBJECTIVES: We hypothesized that tumor necrosis factor-alpha (TNF-alpha) acutely alters left ventricular mechanoenergetics in blood-perfused hearts. To test this hypothesis, we examined the relation between left ventricular mechanics and energetics, both before and after infusion of TNF-alpha. DESIGN: Prospective, experimental study. SETTING: Research laboratory. SUBJECTS: Nine isolated, blood-perfused canine hearts. INTERVENTIONS: Recombinant human TNF-alpha (90 microg/min) was infused into the coronary circulation of the isolated hearts for 20 mins. MEASUREMENTS AND MAIN RESULTS: In the isolated, cross-circulated, blood-perfused canine left ventricles, left ventricular contractility was assessed through measurement of end-systolic elastance (Ees). Energetics were examined in terms of the end-systolic pressure-volume area-myocardial oxygen consumption (MVo2) relation. TNF-alpha concentration in coronary venous blood was >1000 ng/mL throughout the experiments. Nevertheless, infusion of TNF-alpha barely affected contractility acutely, i.e., there was a minimal decrease during the infusion (8.1+/-2.8% at 10 mins, p < .01) and a minimal increase after the infusion (11.2+/-2.5% at 10 mins, p< .01). Neither did the TNF-alpha infusion affect the slope of the end-systolic pressure-volume area-MVo2 relation. This finding indicated that the chemomechanical conversion efficiency remained unchanged. However, TNF-alpha infusion significantly increased the oxygen cost of contractility by 40% (1.25+/-0.13 vs. 1.75+/-0.24 mL oxygen.mL/mm Hg/beat, p< .05), indicating that MVo2 for the excitation-contraction coupling increased. CONCLUSIONS: TNF-alpha minimally alters left ventricular mechanics, but significantly changes energetics. The latter effect may result from changes in intracellular calcium handling.

Animals↗
PubMed1981

In situ estradiol and progestin (R5020) localization in the vascularly separated and isolated hypothalamus of the rhesus monkey.

A neurosurgical procedure has been developed for vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. Utilizing this preparation, the left and right halves of the hypothalamus were perfused simultaneously, but separately, with a dextran-blood solution. Radiolabeled steroids were directly perfused in the dextran-blood into either the left or right half of the hypothalamus. Studies with radiolabeled gonadal steroids indicate that the majority of the carotid circulation is confined to the hypothalamus-thalamus area in this brain preparation and the cross-circulation of labelled steroids between the left and right sides of the hypothalamus is less than 10%. The usefulness of the preparation is illustrated by an autoradiographic study of the in situ hypothalamic distribution of (3H)estradiol in ovariectomized rhesus monkeys and of the synthetic progestin(3H)R5020 in estrogen-primed, ovariectomized rhesus monkeys. The direct perfusion of the (3H) steroids into the hypothalamus greatly increases the sensitivity of such compared to systemic administration of the (3H) steroids. The perfusion of one-half of the hypothalamus with )3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H)steroid plus radioinert steroids permits in 1 animal, acting as its own control, the examination of a saturable distribution of a gonadal steroid in the rhesus monkey hypothalamus.

Animals↗
PubMed1995

Carbamazepine and its metabolites in human perfused placenta and in maternal and cord blood.

Placental transfer and metabolism of carbamazepine (CBZ) was studied in a dual recirculating placental cotyledon perfusion system and was also evaluated in 16 pairs of maternal venous and cord blood samples. Among the parameters studied as possible indicators of a successful perfusion, volume changes in perfusate divided the perfusions into two groups, whereas no significant differences between perfusions were noted in blood gas analysis or in antipyrine transfer. CBZ added into the maternal circulation crosses the placenta in the beginning quicker than antipyrine which is in agreement with the different lipid solubilities of these compounds. Because the transfer rates of antipyrine and CBZ were about the same, the mechanism of transfer of CBZ is probably similar to that of antipyrine (passive diffusion). No metabolites of CBZ could be detected in the perfusate by high-performance liquid chromatography (HPLC) or gas chromatography/mass spectrometry. With the improved HPLC methodology for CBZ metabolites, six metabolites were detected in clinical samples, including 10-hydroxy-10,11-dihydro-CBZ (10-OH-CBZ), which has been described earlier in only 1 uremic patient. Relative levels of metabolites showed significant individual differences. CBZ crosses perfused placenta rapidly, but this does not contribute to CBZ metabolites detected in maternal and fetal circulation.

Antipyrine↗
PubMed1992

Mechanisms by which cancer chemotherapeutic drugs induce emesis.

Because the area postrema seems essential for chemotherapy-induced vomiting, both circulating and/or neurally mediated stimuli in this area could trigger the emetic response. In our laboratories results of cross-circulation and direct intracerebroventricular infusion experiments in dogs do not support a role for circulating substances. The large increases in serum vasopressin induced by cisplatin were not blocked by inhibitors of the angiotensin-converting enzyme. In the ferret inhibition of serotonin synthesis with p-chloro-phenylalanine, administration of selective antagonists of 5-hydroxy-tryptamine3 (5-HT3) receptors, or visceral deafferentation inhibited the emetic response evoked by cisplatin or high-dose cyclophosphamide. The results suggest that serotonin plays an important role and that peripheral neural mechanisms are involved in the emetic response. The strong antiemetic efficacy of selective 5-HT3 antagonists also has been confirmed in humans. In cancer patients high-dose cisplatin increased the plasma and urinary levels of 5-hydroxy-indoleacetic acid (5-HIAA), but did not affect platelet and free plasma serotonin. The changes in 5-HIAA levels paralleled the onset and development of vomiting. No evidence of serotonin depletion has been obtained after high-dose cisplatin. Dacarbazine, another strongly emetogenic agent, increased urinary 5-HIAA; however, only small increases in 5-HIAA were produced with low-dose cisplatin or cyclophosphamide-containing regimens. Thus, emetogenicity appears to be directly related to the ability of the cytotoxic agent to release serotonin. In humans, antiemetics such as ondansetron, metoclopramide, and dexamethasone did not effect high-dose cisplatin-induced increases in serotonin metabolism. Therefore, these antiemetics seem not to affect the amount of serotonin released. The mechanism by which chemotherapeutic drugs induce serotonin release is unknown; however, release may occur by direct cytotoxicity on the gastrointestinal mucosa, including the enterochromaffin cells. Delayed emesis appears to be mediated by 5-HT3-independent mechanisms. It is proposed that emesis that develops despite high-dose ondansetron (residual emesis) should be considered delayed emesis. Residual and delayed episodes of emesis have similar time courses, are characterized by very mild emetic episodes and poor response to 5-HT3 antagonists, and are not associated with increases in serotonin metabolism.

Animals↗
PubMed1972

Polygraphic sleep study in craniopagus twins (where is the sleep transmitter?).

By means of polygraphic recordings complete independence of the sequence of sleeping and waking and of the two sleep states (REM and NREM) could be demonstrated in twins extensively conjoined at the skulls. Functionally important connections in the circulation of the two babies were found during subsequent preoperative investigations. These observations are at variance with the hypothesis of an extraneuronal humoral sleep-inducing factor based on crossed-circulation experiments in animals; moreover they raise a new question about the transportation of the sleepregulating biogenic amines.

Biogenic Amines↗
PubMed1991

The role of hematogenous and intrinsic precursor cells in lymphocyte production in murine bone marrow and thymus.

It is well recognized that the bone marrow contains cells that can repopulate a depleted thymus as well as cells that can be induced to express phenotypic markers characteristic of T cells. It is not known, however, to what extent thymocytopoiesis in the normal thymus relies on immigrant, bone marrow-derived cells, nor whether some T cell precursors have entered the bone marrow from the circulation. We used the parabiotic system to test whether thymocytopoiesis relies on progenitors intrinsic to the thymus or on cells that enter the organ from the circulation. In the same system, we have also investigated whether Thy-1- bone marrow lymphocytes that respond to phytohemagglutinin (PHA) by proliferation and Thy-1 expression are produced by myelogenous or hematogenous progenitors. Syngeneic CBA/HT6 and CBA/CaJ mice were joined in parabiotic union at 4-6 weeks of age. Cross circulation between the two partners was verified by the equilibration of Evans' blue dye injected into one partner and by the equilibration of PHA-responsive T cells in the spleen of the parabionts. Chromosome spreads were prepared from the PHA-stimulated T cell-depleted bone marrow and from spontaneously proliferating thymocytes as well as from thymocytes stimulated by PHA or Concanavalin A (Con A). The exchange of spleen colony-forming units (CFU-S) in the femoral marrow was assessed by karyotyping individual spleen colonies. Regardless of the length of parabiotic union, ranging from 4 to 20 weeks, Thy-1-, PHA-responsive bond marrow lymphocytes remained predominantly of the host type with only 3% being derived from the opposite partner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Successful intra-arterial fibrinolysis of the anterior choroidal artery in the acute stage of internal carotid artery occlusion: case report.

A 27-year-old man was admitted to our institution with the sudden development of right hemiparesis and dysarthria beginning an hour after the onset of symptoms on August 9, 1992. The patient was found on admission to have right hemiparesis (2/5), hemihypesthesia, hemianopia, dysarthria; he had transient atrial fibrillation. No abnormalities were detected on computed tomography (CT) scans, and cerebral blood flow studies undertaken following conventional CT scans revealed no low flow regions in the left cerebral hemisphere. But cerebral angiography disclosed an occlusion of the left internal carotid artery with well-developed cross-circulation via the anterior communicating artery and embolus lodged at the level of the anterior choroidal artery. Superselective fibrinolysis using Tracker-18 and 420,000 units of urokinase resulting in complete recanalization of the left anterior choroidal artery without distal migration of the embolus. Immediately after the procedure, his neurologic disturbance underwent complete resolution. In summary, fibrinolysis could be performed but limited to anterior choroidal artery in a case with an occlusion of the internal carotid artery with well-developed cross-flow via the anterior communicating artery; the patient's neurologic condition may deteriorate suddenly if fibrinolysis is incomplete and the embolus migrates to the internal carotid artery.

Acute Disease↗
PubMed1952

The pathogenesis of experimental dysentery intoxication; production of the lesions by cerebral circulation of the toxin.

All analysis of the mechanisms involved in the pathogenesis of the visceral lesions produced by Shiga toxin in the dog has indicated that the structural changes are produced by a vascular mechanism which is under control of the sympathetic nervous system. Paralysis of the latter at the myoneural junction or in the ganglia by means of drugs served to prevent the tissue changes as well as the hyperglycemia and hemoconcentration characteristic of the sympathomimetic response. The observations indicated that the toxin acted via a mechanism located in the central nervous system. Further studies of the action of Shiga toxin by means of cerebral cross-circulation are reported here. In these the cerebral blood flow of one dog derived from the circulation of the trunk and limbs of another. Injection of the toxin into the femoral vein of this latter dog resulted in the appearance of visceral lesions, hemoconcentration, and hyperglycemia in the former whose brain only received blood containing the toxin. The resulting visceral changes were identical with those observed in the intact unanesthetized dog which had received the toxin directly. The observations indicate that, in dogs, Shiga toxin produces its characteristic visceral lesions via the central nervous system. Possible mechanisms are discussed.

Animals↗
PubMed2002

Systemic site of action for pressor effect of angiotensin II injected into the fourth cerebral ventricle of rats?

Angiotensin II (ANG II) causes a systemic pressor effect when injected into the cerebral ventricles. In the rat fourth ventricle, the effective doses for the ANG II pressor effect are over 100 times larger than in the systemic circulation. Considering the discrepancy of doses, the possibility that ANG II may reach the systemic circulation and promote pressor effects, following injection into the fourth ventricle, was investigated. The effects on blood pressure of different vasoactive peptides that produce pressor responses when injected into the central nervous system were compared. Dose-response curves were obtained for intravenous or fourth cerebroventricular injections of ANG II, lysyl-vasopressin (LVP), bradykinin (BK), or endothelin-1 (ET-1). The ED50 ratios for intracerebroventricular/intraveneous injections were 110 for ANG II, 109 for LVP, 0.01 for BK, and approximately 0.4 for ET-1. In cross-circulation preparations, pressor responses occurred in the donor rat following injection into the fourth cerebral ventricle of the recipient animal, showing that effective doses of ANG II, administered to the fourth cerebral, reach the systemic circulation. The same results were obtained for the microinjection of 4 nmol of LVP into the fourth cerebral ventricle of recipient animals. High-performance reverse-phase liquid chromatography analyses of arterial blood showed that approximately 1% of the [125I]ANG II injected into the fourth cerebral ventricle may be recovered from the systemic circulation a few seconds after the microinjection. The systemic administration of the ANG II receptor antagonist losartan blocked the response to ANG II injected into the fourth ventricle whereas antagonist administration in the same ventricle did not. Angiotensin injections into the lateral ventricle produced pressor responses that were reduced by antagonist administration to the same ventricle but not by systemic administration of the antagonist. The data suggest that the pressor effect resulting from ANG II or LVP injections into the fourth cerebral ventricle may be due to the action of this peptide in the systemic circulation. On the other hand, the pressor effect due to ANG II microinjection into the lateral ventricle apparently results from the direct stimulation of central periventricular structures.

Angiotensin II↗
PubMed1998

Transport of brain-derived neurotrophic factor across the blood-brain barrier.

Brain-derived neurotrophic factor (BDNF) is a potential therapeutic agent for degenerative disorders of the central nervous system. In this report, we investigated the ability of BDNF to cross the blood-brain barrier (BBB). BDNF was stable in blood up to 60 min after i.v. injection, with evidence for aggregation, and had an early, rapid influx into brain. By 10 min, most of the BDNF sequestered by the cerebral cortex was associated with the parenchyma rather than with the endothelial cells, demonstrating complete passage across the BBB. A small dose of unlabeled BDNF enhanced the entry of 125I-BDNF from blood to brain after an i.v. bolus injection, whereas larger doses had no effect. In contrast, a large dose of unlabeled BDNF inhibited the influx of 125I-BDNF during in situ brain perfusion. After intracerebroventricular injection, the efflux of BDNF from brain to blood occurred at a rate similar to that for reabsorption of cerebrospinal fluid, and no evidence for self-inhibition was found. Therefore, we conclude that intact BDNF in the peripheral circulation crosses the BBB by a high-capacity, saturable transport system.

Animals↗