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Biomedical subjects

G Feuerstein

Publications and source records attributed to G Feuerstein.

At least 127 records · Page 7Linked to original sources
PubMed1990

Liposome-encapsulated hemoglobin: an oxygen-carrying fluid.

From the original concept of encapsulating hemoglobin in an inert shell, LEH has evolved into a fluid proven to carry oxygen, capable of surviving for reasonable periods in the circulation, and amenable to large-scale production. The formula for the outer shell evolved from synthetic, nonlipid materials, to egg-lecithin-based lipid mixtures, to distearoyl-phosphatidylcholine-based blends. The fabrication technology started with the production of milliliter quantities and methods detrimental to the hemoglobin and developed into high-pressure extrusion systems producing multi-liter quantities without damaging the hemoglobin. The development of methods for analysis and quality control of LEH has been difficult: even techniques for measuring basic characteristics of size and methemoglobin are still being standardized. In vivo studies have established that LEH has a circulation half-life of 16-20 hr and can carry oxygen sufficient to sustain life, but safety has yet to be proven. In each of the general areas mentioned above, there are opportunities for further improvement and characterization. The source of the hemoglobin and the coencapsulation of hemoglobin modifiers needs to be reassessed now that human hemoglobin has been cloned and functional hemoglobin can be produced by using fermentation techniques. The development of routine methods for quality control and assurance must accompany the production of large quantities of LEH for preclinical studies. Whether or not the LEH can and should be manufactured as a lyophilized product must be assessed. Animal studies must done to prove safety as well as efficacy in a variety of clinical models, including hemorrhagic and septic shock as well as various levels of isovolemic exchange. One approach toward the improvement of the LEH is to alter the liposome surface to increase its biocompatibility. The evolution of biocompatible liposome surfaces has included carbohydrate moieties, as carbohydrates are expressed on the majority of biological membrane surfaces including the red cell. It has been demonstrated that inclusion of carbohydrate components such as gangliosides into the liposomal bilayer results in increased circulation times. As a result, these ganglioside-containing liposomes may exhibit a reduced impact on the RES system. Goins et al. have examined methods of introducing the ganglioside GM1 into LEH preparations. The long-term preservation of LEH is essential for its use by paramedics both in civilian and military trauma settings.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist.

BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its capacity to block PAF, endotoxin and recombinant human tumor necrosis factor-alpha (rTNF)-mediated effects. In vitro, BN 50739 blocked PAF-induced platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), respectively. In the conscious rat, pretreatment (30 min) with BN 50739 (n = 5-13) dose-dependently attenuated PAF-induced hypotension (-5 +/- 5 vs. - 43 +/- 2 mm Hg, P less than .01) and shortened the recovery time of mean arterial pressure (22 +/- 13 vs. 325 +/- 46 sec, P less than .01). BN 50739 (10 mg/kg i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 +/- 1 vs. 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs. 60%, P less than .05). Only partial protection was conveyed by BN 50739 against the hypotensive response to endotoxin (115 +/- 3 vs. 91 +/- 4 mm Hg, P less than .03). Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of plasma thromboxane B2 (21.2 +/- 0.8 vs. 46.7 +/- 11.8 pg/100 microliters, P less than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs. 26,430 +/- 3541 U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Platelet-activating factor. A putative mediator in central nervous system injury?

Platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a potent lipid autacoid produced by many cell types. Platelet-activating factor is produced by cerebellar granule cells in culture and has been extracted from brain tissue. Multiple platelet-activating factor receptors have been demonstrated in brain tissue. Activation of platelet-activating factor receptors in transformed neuronal cell lines involved increases in intracellular calcium. Platelet-activating factor has potent actions on cerebral vessels and cerebral metabolism when administered in vivo, but may not have direct effects on brain microvessels. Excessive platelet-activating factor production in pathological states of the nervous system such as neurotrauma and stroke has been shown in only a few models (e.g., spinal cord ischemia and reperfusion or focal repercussion brain injury). In multiple studies using highly specific and potent platelet-activating factor antagonists, reversal or prevention of key consequences of brain injury such as hypoperfusion following ischemia, reperfusion and edema, inflammatory cell accumulation, neurologic/motor deficits, and neuronal salvage were demonstrated. This review provides and analyzes evidence in support of the role that platelet-activating factor might have in modulation of brain function and pathophysiological processes in brain ischemia and trauma.

Animals↗
PubMed1990

Improved biological properties of synthetic distearoyl phosphatidyl choline-based liposome in the conscious rat.

We have previously produced and tested a liposome preparation based on hydrogenated soy lecithin (HSL-L) for the purpose of designing blood replacement in the form of liposome encapsulated hemoglobin (LEH). While these liposomes had acceptable physicochemical properties which addressed many of the desirable characteristics of "artificial blood," they produced hypotension, hemoconcentration, and thrombocytopenia when administered to rats. The following studies present improved synthetic distearoyl phosphatidylcholine-based liposomes (sDSPC-L) which were compared to the HSL-L for their biological effects in the conscious normovolemic rat (n = 6 - 11). HSL-L induced hypotension (-25 +/- 3 mmHg, P less than 0.01), tachycardia (+88 +/- 11 beats/min, P less than 0.01), decrease in cardiac index (-33 +/- 4%, P less than 0.01), and elevation of the total peripheral resistance index (+0.450 +/- 0.003 mmHg/ml/min/kg, P less than 0.01). The hematologic responses to HSL-L were: leukocytosis (+6,070 +/- 1,064/microliters, P less than 0.01), hemoconcentration (+4.0 +/- 0.1%, P less than 0.01), 0.01), and thrombocytopenia (-160 +/- 18 X 10(3)/microliters, P less than 0.01). Plasma thromboxane B2 (TXB2) was elevated to 30.4 +/- 5.6 pg/100 microliters (P less than 0.01). In contrast, the only effects induced by sDSPC-L were slight tachycardia (+37 +/- 9 beats/min, P less than 0.05) and a marginal increase in plasma TXB2 to 9.7 +/- 3.3 pg/100 microliters (P less than 0.05). All effects, except for those related to cardiac output and peripheral resistance, were transient. These data underscore the importance of pure synthetic DSPC in improving the biological effects of liposomes and suggest sDSPC-L as a promising vehicle for encapsulating hemoglobin.

Animals↗
PubMed1990

Protective effect of BN 50739, a new platelet-activating factor antagonist, in endotoxin-treated rabbits.

Platelet-activating factor (PAF) has been demonstrated in the circulation and organs of animals exposed to gram negative endotoxins, whereas PAF antagonists have been shown to exhibit some efficacy in modifying the course of endotoxemia. In this study we evaluated BN 50739, a novel specific PAF antagonist, for its capacity to block PAF or lipopolysaccharide endotoxin (LPS)-mediated effects in rabbits. Pretreatment with BN 50739 (3 and 10 mg/kg i.p.) inhibited PAF (500 pmol/kg i.v.)-induced thrombocytopenia, leukopenia and plasma thromboxane B2 elevation in a dose-dependent manner. The inhibitory effect lasted 3.5 to 4.5 hr. BN 50739 (10 mg/kg) prevented the early phase of LPS (50 micrograms/kg i.v.)-induced thrombocytopenia and thromboxane B2 elevation, and reduced the 24-hr mortality rate from 75 to 22% (P less than .05). Post-treatment with BN 50739 increased the 10-hr survival rate from 33 to 87% (P less than .05); however, it had no effect on the 24-hr mortality. BN 50739 did not affect LPS-induced leukopenia or the elevation in plasma tumor necrosis factor. Our data support possible therapeutic efficacy of PAF antagonists in septic shock despite their inability to prevent the generation of tumor necrosis factor.

Animals↗
PubMed1990

Biological responses to liposome-encapsulated hemoglobin (LEH) are improved by a PAF antagonist.

Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying blood substitute. Previous studies in our laboratory with hydrogenated soy lecithin-based LEH indicated that while this solution maintained some physicochemical and oxygen-carrying properties of red blood cells, it evoked several transient (30-120 min) untoward biological responses, such as hypertension, tachycardia, thrombocytopenia, hemoconcentration, and elevation of plasma thromboxane B2 (TXB2). Such biochemical, hematological, and hemodynamic derangements are also produced by platelet-activating factor (PAF). The purpose of this study was to test the biological responses to administration of a newly produced synthetic distearoyl phosphatidylcholine-based LEH (s-DSPC-LEH) in the normal conscious rat (n = 6-11) and to examine the role of PAF in these processes. Systemic (IV) administration of S-DSPC-LEH caused transient hypotension (-23 +/- 8 mmHg, P less than 0.05), bradycardia (-24 +/- 11 bpm, P less than 0.05) followed by tachycardia (+62 +/- 21 bpm, P less than 0.05), decreased cardiac index (217 +/- 21 ml/min/kg, P less than 0.01), increased peripheral resistance (0.570 +/- 0.003 mmHg/ml/min/kg, P less than 0.01), transient leukocytosis (+6,870 +/- 1,801/microliters, P less than 0.05), hemoconcentration (+5.2 +/- 0.4%, P less than 0.01), thrombocytopenia (-160 +/- 18 X 10(3)/microliters, P less than 0.01), and increase in plasma TXB2 (45.0 +/- 1.9 pg/100 microliters, P less than 0.01). Separate infusion of the liposome vehicle or free hemoglobin, the two components of s-DSPC-LEH, did not evoke any consistent responses. Administration of the PAF antagonist BN 50739 (10 mg/kg, i.p.) 30 min prior to LEH prevented the hemodynamic changes and hemoconcentration induced by s-DSPC-LEH. These data suggest that hemoglobin/phospholipid interactions might account for the transient side effects of s-DSPC-LEH, possibly through interactions with blood elements and the resultant production of PAF and TXA2. Furthermore, PAF antagonists incorporated into or co-administered with LEH might enhance its biological applications.

Animals↗
PubMed1989

Receptor binding of fluorinated histidine analogs of thyrotropin-releasing hormone in various regions of the rat brain.

Binding properties of [4(5)-fluoro-imidazole-His2]-TRH (4(5)-F-TRH), [2-trifluoromethyl-imidazole-His2]-TRH (2-CF3-TRH) and [4(5)-trifluoromethyl-imidazole-His2]-TRH (4(5)-CF3-TRH), three novel TRH analogs, have been evaluated in rat pituitary, hypothalamus, brainstem and cortex tissue. 4(5)-F-TRH, previously shown to elicit arterial pressor responses and prolactin release similar to those of TRH, binds to TRH receptors with low, micromolar affinity (Ki = 7.5-13.5 microM). 2-CF3-TRH, an analog of less cardiovascular but increased prolactin-releasing activity, shows Ki values of 3.3-4.9 microM. 4(5)-CF3-TRH, which shows comparable biological activity to 2-CF3-TRH, demonstrates a binding affinity which is virtually nonspecific (Ki = 0.39-1.01 mM). It is therefore concluded that the biological effects of these analogs are mediated either through low affinity TRH binding sites not recognized by [3H][3Me-His2]-TRH or through mechanisms not involving TRH receptors as such.

Animals↗
PubMed1989

The influence of cold or isolation stress on neuroinvasiveness and virulence of an attenuated variant of West Nile virus.

The effect of cold or isolation stress on neuroinvasiveness and virulence was investigated in mice inoculated with an attenuated WNV (WN-25) strain. The WN-25 variant differed from the parent strain by its inability to kill mice after I.P. injection though it was able to immunize even after injection with low doses of virus. Exposure of inoculated mice for 5 minutes a day to cold water (1 +/- 0.5 degrees C) for 8 days resulted in 60% mortality, while in nonstressed infected mice no death was observed. Cold or isolation stress increased the virus level in the brain to 8.9 and 7.4 log 10 PFU as compared to no virus in the infected control. Moreover, it was found that virus level in the spleen of stressed mice reached 3.4 and 3.7 log 10 PFU respectively, while in non-stressed mice no virus was detected. The virus which was isolated from the brain of moribund stressed mice was extremely virulent: I.P. inoculation of as little as 10 PFU caused death to normal non-stressed mice. We suggest that cold or isolation stress conditions in mice inoculated with an attenuated strain induce a selection process. The virus which was isolated from the brain of stressed mice changes its virulence and kills like wild type WNV.

Animals↗
PubMed1989

Voltage-sensitive calcium flux into bovine chromaffin cells occurs through dihydropyridine-sensitive and dihydropyridine- and omega-conotoxin-insensitive pathways.

The fluorescent Ca2+ indicator FURA-2 was used to characterize the depolarization-related intracellular Ca2+ signalling process in bovine adrenal chromaffin cells. Depolarization with high K+ (10-65 mM) gave rise to a very rapid increase in intracellular free Ca2+ concentration, which subsequently decayed slowly towards a "plateau". The size of this initial increase varied sigmoidally with the calculated membrane potential, the relationship being described well by a Boltzmann distribution function for a transition between two states (transition potential, -23 mV). A dihydropyridine calcium channel agonist [(+)202-791, 1 microM] raised intracellular free Ca2+ concentration further in the presence of 30 mM K+, and it enhanced the initial intracellular Ca2+ response to depolarization. Voltage-sensitive calcium channels in chromaffin cells are believed to include the L-type. Several dihydropyridine calcium channel antagonists [(-)202-791, nifedipine, nitrendipine; 1-5 microM], known to be active on L-type channels, caused only modest inhibition of K+ -induced increase in intracellular free Ca2+ concentration: c. 50% (at 30 mM K+) and 25% (at 40-70 mM K+). In addition, omega-conotoxin GVIA (1-10 microM), a blocker of neuronal N- and L-type calcium channels, reduced the initial increase in intracellular free Ca2+ concentration only slightly at 55 mM K+. Further, the dihydropyridine-insensitive component of the intracellular Ca2+ signal was also insensitive to omega-conotoxin, which was otherwise quite active in a central nervous rat in vivo preparation Gd3+ (40 microM), a potent calcium antagonist in the chromaffin cell, blocked the intracellular Ca2+ response to depolarization. When added at different times after K+ stimulation, however, Gd3+ reduced intracellular free Ca2+ concentration to control levels along a slow time course of several minutes. Similar results were obtained when EGTA was added to reduce extracellular Ca2+ concentration to sub-nanomolar levels, in the presence of high K+. We conclude that bovine chromaffin cells are equipped with at least two different classes of voltage-dependent calcium channels, only one of which is likely to be the L-type channel. We also propose that depolarization, in addition to stimulating Ca2+ influx, may also lead to enhancement of Ca2+ release from an intracellular store.

Adrenal Medulla↗
PubMed1989

Circulatory effects of PAF-acether in newborn piglets.

Platelet-activating factor (PAF-acether) is a lipid mediator that can exhibit potent vasoconstrictor influence in the pulmonary vessels. Therefore, the release of PAF-acether during inflammatory conditions in newborns might cause deleterious increases in pulmonary vascular tone. Thirty-four anesthetized open-chest newborn piglets were given 0.01-1 nmol PAF-acether iv. In separate experiments, animals were untreated or treated with either indomethacin (a cyclooxygenase inhibitor), SQ 29548 (a thromboxane receptor blocker), or LY 171883 (a leukotriene receptor blocker). The primary hemodynamic change was a 67 to 1,537% increase in the pulmonary vascular resistance index (PVRI) (P less than 0.01): mean pulmonary artery pressure (PAP) rose significantly at all doses tested, whereas only the largest dose consistently decreased cardiac index. Treatment with indomethacin or SQ 29548 prevented the decrease in cardiac index and attenuated the PAF-acether-induced rises in PAP and PVRI. Vehicle and LY 171883 had no effect. The inhibitory influence of indomethacin and SQ 29548 suggests that an important component of PAF-acether's pulmonary vasoconstrictor action is mediated (at least in the newborn piglet) by cyclooxygenase products, most likely thromboxane.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effects of PAF and BN 52021 on cardiac function and regional blood flow in conscious rats.

The effect of intravenous injections (0.1-3 nmol/kg) of platelet-activating factor (PAF) on blood pressure, heart rate, cardiac output, and blood flow (hindquarter, renal, mesenteric) were studied in conscious rats. PAF decreased blood pressure and total peripheral resistance (TPR) but increased heart rate; cardiac output was reduced by the highest dose. Low doses of PAF increased blood flow and decreased vascular resistance in all vascular beds, whereas high doses reduced mesenteric blood flow in part by increasing mesenteric vascular resistance. The hypotensive and cardiac effects of PAF were blocked by intravenous infusions of the selective PAF-receptor antagonists, 15 mg/kg BN 52021 and 1 mg/kg SDZ 63-441. BN 52021 also attenuated the hindquarter and renal responses to PAF, but the mesenteric responses remained relatively unchanged. The results indicate that PAF is a potent vasodilator of mesenteric greater than hindquarter = renal vessels at low doses and a cardiac depressant at high doses. A therapeutic role for the PAF antagonists BN 52021 and SDZ 63-441 is suggested in endotoxemia, anaphylaxis, and other disease states in which increased release of PAF contributes to key hemodynamic derangements.

Animals↗
PubMed1989

Validation of laser-Doppler flowmetry in measurement of spinal cord blood flow.

Laser-Doppler flowmetry (LDF) is a non-invasive method for continuous on-line monitoring of microvascular blood flow. LDF has previously been validated with established methods in various tissues, yet its validity and resolution in the central nervous system (CNS) remain unclear. We compared LDF with the microsphere method (MS) using two independent laser probes placed on the dorsal lumbar spinal cord (L5 laminectomy) of anesthetized rabbits (n = 9). After base-line flow measurements, spinal cord blood flow (SCBF) was increased (up to 50%) with phenylephrine (10-80 micrograms.kg-1.min-1 iv) and decreased (up to 50%) with chlorisondamine (10 mg/kg iv) or other stimuli. The percentage changes of lumbar SCBF and vascular resistance (VR) from the base line obtained by LDF and MS excellently agreed (rBF = 0.86, rVR = 0.94, P less than 0.0001). LDF estimated also the absolute SCBF values parallel to MS (r = 0.77, P less than 0.001). In conclusion, the validity of LDF in estimating the SCBF and dynamic changes of BF and VR is confirmed. Therefore, LDF may prove useful for monitoring CNS microcirculation in normal or pathophysiological states.

Animals↗
PubMed1989

L-649,923: an antagonist of cardiac and vascular leukotriene D4 receptors.

The capacity of L-649,923--sodium (beta S, gamma R*)-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propylthio)-ga mma- hydroxy-beta-methylbenzene butanoate--to block vascular receptors of leukotriene D4 (LTD4) was examined in the conscious rat. Hindquarter (HQ), renal, and mesenteric blood flow and vascular resistance were evaluated in the conscious rat chronically equipped with miniaturized Doppler probes for organ blood flow measurement by directional pulsed Doppler technique. In addition, cardiac output was measured by thermodilution technique in conscious rats equipped with minithermistors in the ascending aorta. Systemic hemodynamic variables, mean arterial pressure, and heart rate were monitored through femoral catheters. LTD4 (1 or 10 micrograms/kg) produced a marked dose dependent increase in the mesenteric vascular resistance associated with a marked decrease in blood flow whereas no consistent effects were demonstrated in the renal circulation. LTD4, at 1 microgram/kg, increased the HQ blood flow whereas the higher dose of LTD4 produced a biphasic response: an early increase followed by a decrease in blood flow. Infusion of LTD4, 3 micrograms/kg per min over 10 min decreased cardiac output and increased total peripheral resistance. L-649,923 (10 or 30 mg/kg, i.v.) effectively blocked the LTD4-induced mesenteric constriction and the second phase of HQ vasoconstriction but did not modify the LTD4 induced HQ vasodilation. L-649,923 also effectively attenuated the cardiac effects of LTD4 infusion. These studies suggest that L-649,923 could preserve cardiac and vascular functions in pathologic states mediated by cysteinyl leukotrienes, such as traumatic or endotoxin shock.

Animals↗
PubMed1989

Acute and chronic effects of eicosapentaenoic acid (EPA) on the cardiovascular system.

Several studies have shown that the development of high blood pressure in spontaneously hypertensive rats (SHR) can be attenuated by feeding them modified fat diets. In the present study, eight weeks after treatment with eicosapentaenoic acid (EPA; 100 mg/kg/day s.c.) SHR had lower systolic blood pressure (BP); (tail-cuff plethysmography) compared to saline-injected SHR: 180.0 +/- 2 vs. 204.0 +/- 1 mmHg, respectively, (p less than 0.001). There was no significant difference in the BP of EPA and saline-treated WKY (Wistar-Kyoto) rats. Heart rate (HR) decreased with age in both the SHR and WKY rats and no significant effect of EPA was observed in WKY rats; the decrease in heart rate in the SHR group was significantly diminished. EPA did not significantly alter growth rate of SHR and WKY rats. However, aged-matched WKY rats weighed more than the SHR. The pressor responses to norepinephrine in doses of 0.3 and 3.0 microgram/kg, i.v., as well as plasma NE, DOPA and MHPG, were also not significantly affected by EPA-supplementation in both SHR and WKY rats. Data from the present study support the view that EPA might be an effective treatment of hypertension that develops via mechanisms unrelated to sympathetic activity or vascular reactivity to adrenergic neurotransmitters.

Animals↗
PubMed1989

Mechanisms of central hemodynamic and sympathetic regulation by mu opioid receptors: effects of dermorphin in the conscious rat.

The effects of i.c.v. administered dermorphin, a highly selective mu-opioid agonist, on cardiac function and renal, mesenteric and hindquarter blood flow were studied in conscious rats. Core temperature, blood gases, arterial plasma levels of norepinephrine, epinephrine, dopamine, 3,4-dihydroxyphenylalanine and dihydroxyphenylacetic acid (DOPAC) also were examined. Cardiac output was measured using a thermodilution technique and regional blood flows using directional pulsed Doppler velocimetry. Dermorphin, at doses of 0.1-100 nmol/kg, increased blood pressure and hindquarter blood flow, renal and mesenteric resistance, and core temperature. Higher doses (1-5 mumol/kg) caused respiratory depression, acidosis, and shock despite profound sympatho-adrenomedullary stimulation. Circulating levels of catecholamines were significantly increased at the dermorphin doses of 0.1-100 nmol/kg. At the 100 nmol/kg dose, plasma levels of epinephrine, norepinephrine, the dopamine metabolite dihydroxyphenylacetic acid and the catecholamine precursor 3,4-dihydroxyphenylalanine were increased by 2-15-fold. The data indicate that mu opioid receptor stimulation exerts potent effects on cardiorespiratory functions, activates the sympathoadrenomedullary system and produces a pattern of blood flow changes consistent with the stress-induced "defense" response (skeletal muscle vasodilation and splanchnic vasoconstriction). Excessive mu opioid receptor stimulation leads to shock due to respiratory and hemodynamic collapse.

Analgesics, Opioid↗
PubMed1989

Characterization of hemodynamic, hematologic, and biochemical responses to administration of liposome-encapsulated hemoglobin in the conscious, freely moving rat.

To improve the outcome of trauma victims and of patients undergoing high-blood-loss surgical procedures and to avoid the many serious complications of blood transfusion, there is a need for an oxygen-carrying blood substitute. Synthetic erythrocytes composed of liposome-encapsulated hemoglobin (LEH) represent one of the significant research efforts in this direction. The purpose of the present study was to examine some of the cardiovascular, hematologic, and biochemical effects of a recently developed LEH preparation in the conscious rat (n = 7). LEH increased mean arterial pressure (MAP) by +18.7 +/- 4.7 mm Hg (P less than 0.01) and heart rate (HR) by +117 +/- 18 beats/min (P less than 0.05). Platelet count dropped to 40% of basal value (P less than 0.01), while plasma thromboxane B2 (TXB2) increased by +25.1 +/- 5.4 pg/100 microliters (P less than 0.001). There was no effect on plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Hemoglobin and hematocrit levels were elevated as well as the white blood cell count [( WBC] lymphocytosis). The platelet and TXB2 responses to LEH showed negative correlation (R = -0.56, P less than 0.01). The injection of the liposome vehicle (LIP) decreased MAP by -16.5 +/- 5.1 mm Hg (P less than 0.01) and platelets, but increased HR, WBC, and TXB2. All observed effects exerted by LEH and LIP were transient, and basal levels obtained 120 min after LEH injection. These data suggest that while LEH maintains some physicochemical properties of red blood cells, its biological properties at the present time indicate potential cardiovascular and hematological liabilities. Furthermore, it seems that the phospholipid bilayer alone or in combination with free Hb might be responsible for the biological effects of LEH.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Leukotriene D4 and hypoxia: differential effects on the pulmonary and systemic circulations in newborn piglets.

Hypoxia-induced release of cysteinyl leukotriene from pulmonary macrophages has been considered an important mechanism mediating hypoxic pulmonary vasoconstriction in the immature circulation. However, studies leading to this conclusion blocked hypoxic pulmonary vasoconstriction by relatively nonspecific LT antagonists. We have evaluated this hypothesis further by separate measurement of the hemodynamic effects of leukotriene D4 (LTD4) and hypoxia before and after administration of the highly specific leukotriene D4/E4 antagonist LY 171883 (LY). Anesthetized, open-chest newborn piglets were exposed to LTD4 0.1-3 micrograms/kg IV, or to hypoxia (12% 02 + 88% N2, for 3 min) prior and subsequent to LY 30 mg/kg IV (n = 7) or saline vehicle (n = 5). LTD4 administration before LY caused a 37% - 446% increase in pulmonary vascular resistance index (PVRI) (p less than 0.05). With LTD4 mean pulmonary artery pressure (PAP) rose 14% - 69% (p less than 0.05), left ventricular end-diastolic pressure (LVEDP) rose 18% - 160% (p less than 0.05) and systemic vascular resistance index (SVRI) increased 88% - 100% (p less than 0.05). Cardiac index (CI) and left ventricular shortening fraction (LVSF) fell only at peak LTD4 dose (92 +/- 7 to 49 +/- 8 ml/kg/min, 12 +/- 1 to 6 +/- 1%, both p less than 0.05). Hypoxia produced a 69% rise in PAP and a 122% increase in PVRI, both p less than 0.01. LY abolished LTD4-induced changes in PVRI, PAP, LVEDP, CI, SVRI, and LVSF, but had no effect on the hypoxic rise in PAP and PVRI. Thus, doses of LY which completely inhibited the substantial circulatory actions of LTD4 failed to alter hypoxic pulmonary vasoconstriction. The results suggest that acute hypoxic pulmonary vasoconstriction in newborn piglets is not attenuated by selective LTD4/E4 receptor antagonism.

Acetophenones↗