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Biomedical subjects

R Rabinovici

Publications and source records attributed to R Rabinovici.

At least 55 records · Page 3Linked to original sources
PubMed1992

"Scoop and run" or stabilize hemorrhagic shock with normal saline or small-volume hypertonic saline?

The controversy over a policy of "scoop and run" or stabilizing hemorrhagic shock when evacuation time is short has not yet been settled. Small volumes of hypertonic saline have been suggested as effective therapy when the scoop-and-run policy is adopted. In the present study small-volume hypertonic saline treatment and normal saline treatment of "uncontrolled" hemorrhagic shock (UCHS) in rats were compared with no treatment, which best simulates the scoop-and-run policy. The rats were randomly assigned to three groups. Uncontrolled hemorrhagic shock was induced by 12% resection of the terminal portion of the rats' tails. In group I (n = 13) the animals were untreated. In group II (n = 6) UCHS was treated by administering 41.5 mL/kg 0.9% NaCl (NS). In group III (n = 6) UCHS was treated by administering 5 mL/kg 7.5% NaCl (HTS). Resection of the rats' tails in group I was followed by bleeding of 3.3 +/- 0.3 mL in 15 minutes with a fall in mean arterial pressure (MAP) from 100.9 +/- 7 to 63.5 +/- 5 mm Hg (p less than 0.001). The early bleeding and hemodynamic responses were similar in all three groups. Further blood loss in the first hour in group I was 0.5 +/- 0.2 mL, and MAP rose spontaneously to 73.2 +/- 6 mm Hg (p less than 0.05). The NS infusion in group II was followed by further bleeding of 4.1 +/- 0.9 mL (p less than 0.01) and a further fall in MAP to 53.8 +/- 7 mm Hg (p less than 0.01) after 60 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Platelet activating factor mediates interleukin-2-induced lung injury in the rat.

Interleukin-2 was recently shown to cause acute lung injury characterized by microvascular permeability defect, interstitial edema, and leukosequestration. Similar responses can also be produced by platelet activating factor (PAF). Thus, the present study aimed to examine whether PAF plays a key role in the development of IL-2-induced lung injury in the anesthetized rat. Intravenous infusion (60 min) of recombinant human IL-2 at 10(5)-10(6) U/rat (n = 7-9) dose-dependently elevated lung water content (27 +/- 1%, P less than 0.01), myeloperoxidase activity (+84 +/- 23%, P less than 0.05), and serum thromboxane B2 (990 +/- 70%, P less than 0.01), but failed to alter blood pressure, hematocrit, serum tumor necrosis factor-alpha, and circulating leukocytes and platelets. Pretreatment (-30 min) with a potent and specific PAF antagonist, BN 50739 (10 mg/kg, intraperitoneally, n = 6) prevented the pulmonary edema (P less than 0.05) and thromboxane B2 production (P less than 0.01), and attenuated the elevation of lung myeloperoxidase activity (+18 +/- 16%, P less than 0.05) induced by IL-2. These data suggest that PAF is involved in the pathophysiological processes leading to IL-2-induced lung injury, and point to the potential therapeutic capacity of PAF antagonists in preventing pulmonary edema during IL-2 therapy.

Animals↗
PubMed1992

Hemodynamic, hematologic and eicosanoid mediated mechanisms in 7.5 percent sodium chloride treatment of uncontrolled hemorrhagic shock.

Hypertonic saline solution (HTS) (7.5 percent sodium chloride [NaCl]) treatment (5 milliliters per kilogram) of rats subjected to uncontrolled hemorrhagic shock (n = 7) caused an initial partial recovery of blood pressure (+38 +/- 5 percent, p<0.05) and cardiac index (+48 +/- 6 percent, p<0.01) followed by increased bleeding (+53 +/- 5 percent versus rats treated with 0.9 percent NaCl, p<0.05), secondary shock (mean arterial pressure [MAP] 23 +/- 7 millimeters of mercury, p<0.01) and decreased survival (-54 +/- 15 minutes versus control, p<0.05). The increased blood loss resulted from: 1, increased vascular pressure and vasodilatation (total peripheral resistance index -27 +/- 5 percent, p<0.05), as initial bleeding occurred when MAP and cardiac index are increased compared with the control group (+88 +/- 10 percent, p<0.05 and +82 +/- 7 percent, p<0.01, respectively) and as the concomitant infusion of angiotensin II, a potent vasoconstrictor, delayed the HTS-induced bleeding (resumed at 60 minutes), and 2, a defect in platelet aggregation reflected by decreased adenosine diphosphate (ADP)-induced maximal aggregation (-79 percent versus rats treated with 0.9 percent NaCl, p<0.05) and increased EC50 of ADP (+159 percent, p<0.05). These hemodynamic and hematologic responses might be mediated at least in part by prostacyclin, a vasodilator and antiplatelet aggregator, as HTS-treated rats markedly elevated the 6-keto-PGF1 alpha per thromboxane B2 ratio (+140 +/- 12 percent, p<0.01) and pretreatment with indomethacin decreased blood loss and improved MAP and survival. These data point out potential untoward hemodynamic and hematologic consequences of HTS treatment in traumatic injury in which control of bleeding cannot be confirmed.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Biological responses to exchange transfusion with liposome-encapsulated hemoglobin.

The present study evaluates the biological responses to 10% blood volume infusion ("top-loading," n = 7) or 50% blood volume exchange transfusion (n = 8) with a new preparation of liposome-encapsulated hemoglobin (LEH) in the conscious rat. Top-loading did not affect systemic hemodynamic variables but induced transient thrombocytopenia (-36% +/- 7%; P less than 0.05) and elevation of plasma thromboxane B2 (12.4 +/- 3.8 pg/100 microliters vs. undetectable levels at the control; P less than 0.05). Rats exchanged with LEH maintained mean arterial pressure (MAP) during the 3 hr observation period, whereas control (0.9% NaCl or lactated Ringer's solution) animals developed hypotension (-23 +/- 5 mm Hg, P less than 0.05). The maintenance of MAP in the LEH group resulted from the opposing effects of LEH-induced increase in total peripheral resistance index (TPRI; +0.06 +/- 0.01 mm Hg/ml/min/kg; P less than 0.05), and decreased cardiac index, (Cl, -25 +/- 6 ml/min/kg, P less than 0.05). In contrast, the decline in MAP in the control groups could be attributed to the lower Cl (-65 +/- 8 ml/min/kg; P less than 0.05). All rats developed metabolic acidosis (base excess of -9.7 +/- 0.6 mmol/liter; P less than 0.05), which was transient in the LEH group but progressive in the control groups. These data support the possible use of LEH as a blood substitute when massive transfusions are needed.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Platelet-activating factor in cardiovascular stress situations.

Since the elucidation of its chemical structure two decades ago, platelet-activating factor (PAF) has emerged as an important mediator of various cardiovascular stress situations. Most notably, PAF was implicated as a key factor in the septic shock syndrome, based on the similarities between endotoxin and PAF biological effects, the elevation of circulating and tissue levels of PAF during endotoxemia, and the protective effect of PAF antagonists in the septic state. In addition, accumulating data suggest the involvement of PAF in the pathophysiological processes associated with ischemia, hemorrhage and trauma, where PAF exerts its effects directly on cells and blood elements or indirectly through interactions with other mediators such as cytokines and prostaglandins. Nevertheless, the relative contribution of PAF to the pathophysiological processes in endotoxemia is still unknown and should await further investigations. The primary aims of this chapter are: to delineate the effects of PAF on the cardiovascular system, to summarize the data which suggest the involvement of PAF in stress situations of the cardiovascular system, and to identify areas where future experimental efforts should be focused.

Animals↗
PubMed1991

Priming by platelet-activating factor of endotoxin-induced lung injury and cardiovascular shock.

Platelet-activating factor (PAF) is a glycerophospholipid known for its unusual potent vasoactive and proinflammatory activities. The present study examined whether PAF might serve as a priming factor in endotoxin-induced tumor necrosis factor-alpha (TNF alpha) synthesis, cardiovascular shock, and lung injury in anesthetized rats. Intravenous infusion of PAF (1 pmol/kg/min for 60 minutes, n = 5) alone or endotoxin (0.1 micrograms/kg i.v. bolus, n = 5) failed to alter blood pressure, serum TNF alpha and thromboxane B2, platelet and leukocyte count, and hematocrit, nor was lung histology, myeloperoxidase activity, and water content changed. In contrast, the combined administration of PAF and endotoxin markedly elevated serum TNF alpha (1,359 +/- 362 pg/ml, n = 5, p less than 0.01) and thromboxane B2 (43 +/- 5 pg/100 microliters, n = 8, p less than 0.01) along with hypotension, hemoconcentration, leukopenia, and thrombocytopenia. Most notably, the combined regimen caused neutrophil aggregation, adhesion, and accumulation into the lung parenchyma along with platelet-fibrin deposits in postcapillary venules, pulmonary edema, and increased lung myeloperoxidase activity. The role of PAF in this process was confirmed by 1) the prevention of the priming effect by pretreatment with the PAF antagonist BN 50739 (n = 5), and 2) the failure of lyso-PAF, the cardinal nonactive PAF-metabolite, to prime for endotoxin-induced production of TNF alpha (n = 4). These data suggest that PAF could serve as a key mediator in priming for endotoxin-induced tissue injury, especially the typical pulmonary pathophysiology of adult respiratory distress syndrome, a severe pathological outcome of septic shock, burns, and multiple organ injury.

Animals↗
PubMed1991

Perforated duodenal ulcer in the elderly.

In a 10-year retrospective review of 41 patients aged greater than or equal to 65 years and treated for perforated duodenal ulcer, an attempt was made to characterize the clinical and laboratory profile and evaluate treatment policy for this surgical emergency in the elderly. In 1/3 of the series no accurate history was obtainable. Peroperative findings were sometimes discordant with laboratory data. Vagotomy and drainage were performed in ten low-risk patients and simple closure with omentopexy in 26. Conservative treatment was employed in four patients, three of whom recovered while one later required closure. Gastroenterostomy was performed in one case. A patient with severe mesenteric thrombosis had no perforation-related surgery. Vagotomy and drainage were associated with significantly fewer complications and shorter hospital stay than simple closure, no mortality (vs. 8%) in closure) and only one recurrence during follow-up averaging 37 months. This small, non-randomized series does not permit conclusive recommendations, but the data advocate definitive surgery in properly selected cases and stress the importance of associated pathology for decisions on treatment.

Acute Disease↗
PubMed1991

Effect of injured vessel size on bleeding following hypertonic saline infusion in "uncontrolled" hemorrhagic shock in anesthetized rats.

Hypertonic saline (HTS) infusion in "uncontrolled" hemorrhagic shock (UCHS) leads to increased bleeding from injured vessels, fall in mean arterial pressure (MAP), and early mortality. The effect of injured vessel size on blood loss in response to HTS treatment was studied in Neurolidal Ketalar anesthetized Hebrew University strain rats. The animals were randomly assorted into 4 groups: In group I (n = 8) UCHS was induced by resection of 8% of the terminal portion of the rats' tail and the animals were untreated. In group II (n = 8) UCHS was induced as in group I and the animals were treated with 5 ml/kg NaCl 7.5% (HTS). In group III (n = 9) UCHS was induced by 50% resection of the animal's tail, and the animals were untreated. In group IV (n = 12) UCHS was induced as in group III and the animals were treated with 5 ml/kg HTS Resection of 8% of the animal's tail was followed by bleeding of 2.6 +/- 0.3 ml and fall in MAP from 107 +/- 7 to 80 +/- 10 torr (P less than .005) within 5 min. Resection of 50% of the animal's tail was followed by bleeding of 4.3 +/- 0.4 ml (P less than .01) and fall in MAP to 41 +/- 6 torr (P less than .001) after 5 min. Infusion of HTS in group II was followed by further blood loss of 4.9 +/- 07 ml within 4 hr while in untreated group I, blood loss was only 3.4 +/- 0.4 ml (P less than .05), MAP remained unchanged, and there was no mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Control of bleeding is essential for a successful treatment of hemorrhagic shock with 7.5 per cent sodium chloride solution.

Small volume hypertonic saline (HTS) solution resuscitation has been shown to restore hemodynamic derangements and to protect against mortality in "controlled" hemorrhagic shock (CHS), but it exacerbates the shock state in "uncontrolled" hemorrhagic shock (UCHS). To study the mechanisms associated with the divergent outcome of HTS treatment in CHS versus UCHS, HTS was administered to anesthetized rats (n = 7) subjected to 15 per cent resection of the tail followed by controlled or uncontrolled bleeding. HTS treatment of UCHS increased bleeding (13.3 +/- 1.6 milliliters, p less than 0.05), dropped mean arterial pressure (MAP) (-84.5 +/- 8.9 millimeters of mercury, p less than 0.001), central venous pressure (zero millimeters of mercury, p less than 0.001) and cardiac index (CI) (41 per cent of basal value, p less than 0.001) and increased acidosis (pH 7.23 +/- 0.12, p less than 0.05) and mortality (mean survival time 75 +/- 15 minutes versus 122 +/- 23 minutes of untreated rats, p less than 0.05). In contrast, when administered after application of a ligature proximal to the resection site (at 15 minutes), HTS completely reversed the changes in MAP, CI and total peripheral resistance index (TPRI), and improved mean survival time (172 +/- 7 minutes, p less than 0.05). These data support the assumption that HTS should be used in the treatment of hemorrhagic shock only after bleeding was controlled.

Acidosis↗
PubMed1990

Cecal volvulus.

A review of 561 cases of cecal volvulus that were published between 1959 and 1989 along with 7 new cases, was performed to characterize the clinical and laboratory profile and to evaluate the various surgical options in treating this life-threatening condition. The age and sex distribution of these patients have changed over the years and shifted toward older patients (mean, 53 years) and female predominance (female:male ratio, 1.4:1). The clinical presentation was usually of distal closed-loop small bowel obstruction. Forty-six percent of the plain abdominal radiographs were suspected for cecal volvulus, but only 17 percent were diagnostic. Barium enema had a high rate of accuracy (88 percent) and was associated with minimal complications. True volvulus was 6 times more common than bascule, and gangrenous cecum was found in 20 percent of cases. Detorsion alone and cecopexy had almost similar complications, mortality, and recurrence rates (15, 10, and 13 percent, respectively), whereas, resection, which was performed primarily for gangrenous cecum, had higher rates. However, the highest rates of complications (52 percent), mortality (22 percent), and recurrence (14 percent) were noticed after cecostomy. These data suggest that resection should be reserved for patients with necrotic cecum and that detorsion is sufficient for patients with viable cecum. Cecostomy should be abandoned.

Adolescent↗
PubMed1990

Pharmacologic profile of BN 50739, a new PAF antagonist in vitro and in vivo.

The effect of a new PAF antagonist BN 50739 was studied on PAF-induced [3H]-serotonin release from washed rabbit platelets in vitro and on PAF-induced hypotension in vivo. BN 50739 competitively inhibited PAF-induced [3H]-serotonin release from the platelets in a dose-dependent manner. In the presence of 4, 10 and 50 nM of BN 50739, the concentration of PAF inducing 50% maximal [3H]-serotonin release from the platelets (EC50) increased from 2.15 nM to 5.10, 45.10 and 900 nM, respectively. The IC50 of BN 50739 for PAF (10 nM) induced [3H]-serotonin release was 3.67 nM. Under the same experimental condition, the IC50s of BN 50726, BN 50730, BN 50741, WEB 2086, SRI 63-441 and BN 52021 were 5.40, 4.61, 6.88, 5.98, 40.90 nM and 14.90 microM, respectively. PAF-induced hypotension in conscious rats was also inhibited dose-dependently by i.p. pretreatment of BN 50739 (3 and 10 mg/kg). PAF-induced hypotension was diminished both in magnitude and duration in rats pretreated with BN 50739. These data taken together indicate that BN 50739 is a most potent PAF antagonist in vitro and in vivo.

Animals↗
PubMed1990

The danger of high compliance balloons for esophageal dilatation in achalasia.

High compliance balloons, commonly used for pneumatic dilatation of achalasia patients, theoretically subject the widened esophageal wall, proximal to the narrow zone, to increased pressure, and subsequently to a higher risk of perforation. The new type of inelastic cylindrically shaped balloons, such as the Gruntzig-type and Rigiflex Achalasia Dilator, seems to be safer, since it increases esophageal wall tension in the stenotic zone only. The purpose of this study was to present a pathophysiological consideration of this assumption, together with two cases which support it.

Adult↗
PubMed1990

Effect of gram-negative endotoxin on levels of serum corticosterone, TNF alpha, circulating blood cells, and the survival of rats.

The relationship between serum tumor necrosis factor (TNF alpha), circulating blood cells, plasma corticosterone (CS), and survival was studied in conscious rats injected intravenously with E. coli lipopolysaccharide (LPS, 0.0001-28.8 mg/kg). The TNF alpha response was dose-related, peaked at 90-120 min after LPS injection, and subsided 6 hr later. The CS response showed an earlier onset, prolonged (greater than 12 hr) duration, and a broader dose-response pattern. White blood cells (WBC) and platelet depletion peaked at 2-4 and 24-48 hr post-LPS, respectively; however, no changes in the cell count were observed at LPS doses which produced greater than 50% maximal increase in TNF alpha levels. Survival curves for each of the LPS doses were significantly different from the doses of LPS which elicited TNF alpha release. Systemic injection of human recombinant TNF alpha (h-rTNF alpha), which produced plasma levels of TNF alpha 10 x 10(7) U/ml, much higher than the maximal TNF alpha levels produced by LPS, 1-2 x 10(5) U/ml, failed to affect survival, plasma WBC, or hematocrit. Our data suggest that factors other than TNF alpha produced by high doses of LPS are essential in eliciting LPS-induced death.

Animals↗
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

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↗