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Biomedical subjects

R Rabinovici

Publications and source records attributed to R Rabinovici.

At least 19 recordsLinked to original sources
PubMed1995

Aspiration-induced lung injury: role of complement.

OBJECTIVES: To examine the role of complement in the development of acid aspiration-induced lung injury in the rat. It was postulated that inhibition or depletion of complement attenuates aspiration-induced lung injury. DESIGN: Controlled animal trial. SETTING: Animal Laboratory, Jefferson Medical College, Philadelphia, PA. SUBJECTS: Anesthetized rats. INTERVENTIONS: Aspiration was induced by the intratracheal administration of 0.2 mL of 0.1 N hydrochloric acid (n = 7) and lung injury was evaluated by determining water content, myeloperoxidase activity, protein concentration, and leukocyte count in bronchoalveolar lavage fluid. Muscle PO2 was directly measured using a thin-film chamber oxygen sensor and serum tumor necrosis factor-alpha was assayed by enzyme-linked immunosorbent assay. The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by cobra venom factor (n = 7) on lung injury was evaluated. MEASUREMENTS AND MAIN RESULTS: Acid aspiration induced pulmonary leukosequestration, edema, and a microvascular permeability defect, along with tissue hypoxia. Pretreatment with soluble complement receptor type 1 (complement inhibition) or cobra venom factor (complement depletion) significantly reduced lung edema (-61 +/- 7%; p < .05), eliminated protein accumulation in bronchoalveolar lavage fluid (p < .01), and improved (p < .05) tissue oxygenation. In contrast, there was no effect of soluble complement receptor type 1 or of cobra venom factor on leukosequestration. CONCLUSIONS: Acid aspiration induces lung injury through a complement-dependent mechanism that leads to microvascular permeability defects. Therefore, the possibility that complement inhibitors may have a salutary effect in humans with aspiration-induced lung injury should be investigated.

Animals↗
PubMed1995

Thoracic duct injury in penetrating neck trauma.

Thoracic duct laceration from penetrating neck trauma is a rare injury associated with significant morbidity. Seventy-one cases published in the English literature in the last 50 years, along with one new case, were reviewed in an attempt to characterize the clinical profile, treatment, and outcome.

Adult↗
PubMed1994

Lyophilized liposome encapsulated hemoglobin: evaluation of hemodynamic, biochemical, and hematologic responses.

OBJECTIVE: To characterize the hemodynamic, biochemical, and hematologic responses to the administration of the oxygen-carrying fluid lyophilized liposome-encapsulated hemoglobin in the conscious, normovolemic rat. DESIGN: Prospective, randomized trial. SETTING: Animal laboratory, Jefferson Medical College. SUBJECTS: Eighty-four male Sprague-Dawley rats. INTERVENTIONS: Catheters were introduced into the right atrium (through the jugular vein) and both femoral arteries of test animals, and a thermistor was placed in the ascending aorta through the left common carotid artery for infusion of lyophilized liposome-encapsulated hemoglobin, blood collection, and blood pressure (BP) and cardiac output determinations. MEASUREMENTS AND MAIN RESULTS: Lyophilized liposome-encapsulated hemoglobin (n = 8) infusion (1 mL/min iv) at 1 or 6 mL/kg (10% of estimated blood volume) had no detectable effect on BP, cardiac output, total peripheral resistance, and heart rate during the 5-hr observation period. The infusion also had no effect on hematocrit, leukocyte count, and serum tumor necrosis factor-alpha concentrations. Survival at 7 days was 100% (n = 20). Lyophilized liposome-encapsulated hemoglobin caused transient (2-hr) thrombocytopenia (-24 +/- 9% vs. a Ringer's lactate control group, p < .01), and marginally increased serum thromboxane B2 concentrations (14.6 +/- 6 pg/100 microL, p < .01). CONCLUSIONS: These data suggest that lyophilized liposome-encapsulated hemoglobin can be safely administered to conscious rats, supporting the development of this substance as a potential blood substitute.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Role of complement in endotoxin/platelet-activating factor-induced lung injury.

C receptor-1 is a protein involved in the regulation of C3 and C5-convertases. Recombinant human soluble C receptor-1 has recently been produced and shown to reduce infarct size in a rat model of myocardial ischemia/reperfusion injury. The present study aimed to investigate whether recombinant human soluble C receptor-1 exerts any protective effect on pulmonary injury produced in a rodent model of adult respiratory distress syndrome. In this model, Escherichia coli endotoxin (LPS, 0.1 microgram/kg) combined with platelet-activating factor (1 pmol/kg/min over 60 min, n = 10) caused microvascular lung injury characterized by elevation of myeloperoxidase activity, deposition of C3 and C5b-9 on the endothelium of pulmonary vessels, and pulmonary edema. Furthermore, bronchoalveolar lavage revealed increased neutrophil count and elevated protein concentration. These pulmonary responses were associated with elevated serum TNF-alpha. Pretreatment (10 min, i.v.) with recombinant human soluble C receptor-1 at 10 mg/kg (n = 13), but not at 1 mg/kg, prevented the LPS/platelet-activating factor-induced pulmonary edema (p less than 0.01) and changes in the bronchoalveolar lavage fluid cell count (p less than 0.01) and protein concentration (p less than 0.05), and attenuated the deposition of C3 and C5b-9 to lung vessels. There was no effect on lung myeloperoxidase activity and serum TNF-alpha. Also, C depletion by cobra venom factor (500 U/kg, i.v.) eliminated the pulmonary edema and elevated leukocyte count in bronchoalveolar lavage fluid, but had no effect on lung myeloperoxidase activity and serum TNF-alpha. These data suggest that C factors may play an important role in the pathophysiology of adult respiratory distress syndrome.

Animals↗
PubMed1992

Pharmacological profile of G619, a new platelet aggregation inhibitor.

G619, a 4-OH-isophthalic acid derivative, was studied for its capacity to inhibit platelet aggregation. G619 dose-dependently inhibited U46619, collagen, ADP, PAF, thrombin and epinephrine-induced platelet aggregation in vitro. The IC50 values for inhibition of U46619-induced human and rabbit platelet aggregation were 39 and 43 microM, respectively. G619, at 100 microM, inhibited high concentration collagen (10 micrograms/ml)-induced aggregation of rabbit platelets pretreated with indomethacin and increased the level of cAMP in washed rabbit platelets by 30% (p less than 0.01 vs basal). However, G619, did not inhibit fibrinogen binding to GPIIb/IIIa receptor, phosphodiesterase, U46619-induced contractile responses on canine saphenous vein or rabbit aorta, calcium-induced vasoconstriction and thrombin or PAF-induced elevation of [Ca++]i in platelets in vitro. In vivo, the U46619-induced maximal thrombocytopenia in rats was reduced from 40% (vehicle) to 22% and 18% by 10 and 30 mg/kg of G619 i.v., respectively. G619 (30 mg/kg) had no effect on the U46619-induced vasopressor response or sudden death in rats, and had no effect on TxB2 formation. Our results indicate that G619 is a broad-spectrum platelet aggregation inhibitor and may have its effect on a common mechanism for platelet aggregation besides an effect on the thromboxane A2 receptor.

Adenosine Diphosphate↗
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↗