Biomedical subjects

R J Hariri

Publications and source records attributed to R J Hariri.

29 records · Page 2Linked to original sources

PubMed1992

Differential effects of cyclo-oxygenase and thromboxane synthetase inhibition on ventilation-perfusion relationships in acid aspiration-induced acute lung injury.

Cyclo-oxygenase metabolites are important regulators of pulmonary vascular and airway tone and may act to regulate ventilation-perfusion (VA/Q) relationships. Hypoxemia that follows aspiration of gastric acid is associated with increased venous admixture, and plasma levels of thromboxane (TX) B2 and 6-keto-PGF2 alpha are increased after experimental acid-induced acute lung injury. The present study was designed to determine the effects of cyclo-oxygenase metabolites on VA/Q relationships in canine acid aspiration. Eighteen anesthetized dogs received 0.2 mL/kg 0.1 N HCl intratracheally; six were pretreated with ibuprofen (IBU), a cyclo-oxygenase inhibitor, 12.5 mg/kg IV, and six other dogs received OKY-046 (OKY), a TX synthetase inhibitor, 0.5 mg/kg IV. The remaining six animals (ACID) served as controls. Continuous distributions of ventilation and perfusion were evaluated with the multiple inert gas elimination technique. Within 30 minutes, acid injury resulted in significant (p < 0.05) decreases in PaO2 from baseline values by 44.7 +/- 5.4 and 47.6 +/- 4.8 mm Hg in the ACID and OKY groups, respectively. Although decreased, the change in PaO2 of 21.0 +/- 4.8 mm Hg in IBU animals was significantly (p < 0.05) attenuated in comparison with the other groups. Ibuprofen increased pulmonary vascular resistance, attenuated perfusion to shunt and low VA/Q areas, and reduced ventilation to unperfused areas for the first 2 hours after acid injury (all p < 0.05), whereas OKY exacerbated hypoxemia and VA/Q inequality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Fluid percussion barotrauma chamber: a new in vitro model for traumatic brain injury.

Advances in the understanding of the pathophysiology of traumatic brain injury have implicated a number of cellular events as fundamental to the evolution of neurologic dysfunction in this process. Following the primary biomechanical insult, a highly complex series of biochemical changes occur, some of which are reversible. The development of fluid percussion injury as an in vivo model for traumatic brain injury has greatly improved our ability to study this disease. However, a comparable in vitro model of biomechanical injury which would enable investigators to study the response to injury in isolated cell types has not been described. We have developed a model of transient barotrauma in cell culture to examine the effects of this form of injury on cell metabolism. This model employs the same fluid percussion device commonly used in in vivo brain injury studies. The effect of this injury was evaluated in monolayers of human glial cells. Cell viability by trypan blue exclusion and the production of leukotrienes following increasing barotrauma was investigated. This model provided a reproducible method of subjecting cells in culture to forces similar to those currently used in animal experimental head injury.

Barotrauma↗

PubMed1990

Leukotriene production by human glia.

Elevated intracranial pressure and acute cerebrovascular changes following head injury remain the principle challenge in the management of traumatic brain injury. Recent work has demonstrated that leukotrienes can induce increases in blood brain barrier permeability and alter cerebrovascular dynamics. We investigated whether human astroglia in culture: 1. generate specific leukotrienes; 2. how they metabolize leukotrienes, and; 3. if astroglia generate leukotrienes in response to barotraumatic injury. Human astroglial cultures established from normal human brain obtained at surgery were exposed to either ionophore, exogenous 3H-LTC4, or barotraumatic injury. Supernatants were assayed for specific leukotrienes by one of three methods: HPLC, radioimmunoassay, or enzyme-immunoassay. Glial cells exposed to exogenous LTC4 metabolized nearly all of the LTC4 to LTD4 and LTE4 within 20 minutes. Glial cells stimulated with ionophore produced mostly LTC4 at five minutes after stimulation and LTD4 and LTE4 at fifteen minutes after stimulation. Glial cells subject to barotraumatic injury produced LTC4 in concentrations of 40-200 pg/ml 15 minutes after injury. These results demonstrate that human astroglial cells are capable of rapidly generating and degrading LTC4 and this capability of glial cells may play an important role in the pathophysiology of cerebrovascular changes following head injury.

Calcimycin↗

PubMed1989

Human glial cell production of lipoxygenase-generated eicosanoids: a potential role in the pathophysiology of vascular changes following traumatic brain injury.

Acute cerebrovascular changes which occur following traumatic brain injury represent a highly complex, multifactorial pathophysiologic process which is poorly understood. It is now recognized that, under normal conditions, the brain is a source of a variety of arachidonic acid metabolites which are synthesized by both cyclooxygenase and lipoxygenase. The specific cellular source of these highly vasoactive substances remains controversial. Recent work has demonstrated that lipoxygenase products were detected by immunosensitive assay in whole brain samples from a gerbil concussive injury model, yet the production of leukotrienes could not be accounted for by cerebral vessels and their contents alone. It has been theorized that the probable source for these metabolites is the cortical neuron. We sought to elucidate whether cultured human glial cells, obtained from specimens removed at the time of surgery, are a significant source of lipoxygenase products as measured by high performance liquid chromatography (HPLC). We observed that these cells consistently produced 5, 12, and 15-HETE class eicosanoids despite failure to produce significant cyclooxygenase products. These preliminary findings are of considerable interest because these lipoxygenase products are known to be highly vasoactive as well as potent mediators of increased vascular permeability. Since it is known that mechanical perturbation of cell membranes stimulates the release of arachidonic acid from membrane phospholipids, it is conceivable that the production of these eicosanoids following traumatic brain injury could account for local cerebrovascular changes including both vasospasm and interstitial edema formation.

Brain Injuries↗

PubMed1988

Aging and arteriosclerosis. Cell cycle kinetics of young and old arterial smooth muscle cells.

Intimal cell proliferation is a "hallmark" of atherosclerosis. Myointimal hyperplasia in arteries has been shown to be dependent on age after vascular endothelial denudation and injury associated with vascular transplantation. Because myointimal thickening is greater in aged rats than in younger rats, and aortic segments from old rats transplanted into young syngeneic recipients have a greater myointimal proliferative response to injury than its host environment, the authors examined the cell cycle distributions of old and young rat arterial smooth muscle cells (SMCs) by flow-cytometric analysis. They observed that there is an apparent age-dependent variation in the cell cycle distribution. Moreover, old SMCs have a greater percentage of their population in the S phase and not G2/M, compared with young SMCs; and there is a decrease in the percentage of old cells in the G0/G1 phase as compared with young SMCs. These differences may reflect the cellular changes observed during myointimal hyperplasia following vascular injury. It is concluded that our data support the hypothesis that the proliferation of SMCs is dependent, in part, on those processes related to aging as well as to the phenotypic state of the cell.

Aging↗

PubMed1986

Shock and tissue injury induced by recombinant human cachectin.

Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. Recombinant human cachectin was infused into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.

Animals↗

PubMed1986

Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury.

Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals. Thus, 20-26-mo-old Fischer 344 rats developed greater and more persistent intimal proliferative lesions than did 2-5-mo-old rats after aortic endothelial denudation. 3 d after deendothelialization, intimal thickness was increased two-fold in both old and young animals. However, 14 d after endothelial injury, intimal thickness had increased nearly five times in old animals, but had regressed to normal in young animals. Intimal thickness of young aortic grafts transplanted into young recipients did not differ significantly from adjacent host aorta or autotransplanted aortic segments 6 wk after surgery. In contrast, intimal thickness of old grafts transplanted into young recipients was eight times greater than adjacent young host aorta 6 wk after surgery. The density of cell nuclei in the intima of old grafts was also much greater than that in young grafts. Thus, in two experimental models of vascular injury, old rats have consistently had greater myointimal hyperplasia than young rats. The increased proliferative response of aortic smooth muscle cells after vascular injury of old animals may contribute to the increased prevalence of vascular disease with age.

Aging↗

PubMed1986

Effect of naloxone on cerebral perfusion and cardiac performance during experimental cerebral ischemia.

Transient global cerebral ischemia (TGI) was induced in awake rats using the "four-vessel" occlusion model of Pulsinelli and Brierley. Blood pressure, arterial blood gases, cerebral blood flow, and cardiac output were measured during the acute (up to 2 hours) and chronic (2 to 72 hours) postischemic time periods. Coincident with the onset of TGI, cardiac output and caudate blood flow were depressed. The former returned to baseline within 30 minutes after the conclusion of TGI, and the latter progressed to hyperemia at 12 hours (81.8 +/- 4.9 vs 68.6 +/- 3.9 ml/min/100 gm tissue (mean +/- standard error of the mean] and oligemia at 72 hours (45.5 +/- 4.8 ml/min/100 gm tissue) post-TGI in the untreated control rats. Arterial blood gases and blood pressure were unchanged. Naloxone (1mg/kg) given at the time of TGI or as late as 60 minutes post-TGI and every 2 hours thereafter for 24 hours or bilateral cervical vagotomy prevented the depression in cardiac output and blocked the hyperemic-oligemic cerebral blood flow pattern that was predictive of stroke in this rat model. Changes in cardiac output after TGI in this model appear to be mediated by parasympathetic pathways to the heart from the brain stem. Opiate receptor blockade probably blocks endogenous opioid peptide stimulation of these brain-stem circulatory centers, which results in inhibition of parasympathetic activity and improvement in cardiac output. The usefulness of naloxone in the treatment of experimental stroke may be a function of its ability to improve cerebral perfusion in pressure-passive cerebrovascular territories. Variations in cardiac output during experimental stroke may explain the dissimilar responses to naloxone treatment reported by other investigators of experimental stroke.

Animals↗

PubMed1985

Dual-ended, multifunction tools for microsurgery.

A new concept in microsurgical instrumentation is herein described and the rationale for its design presented in the context of surgical efficiency. This new concept employs bipolarity or dual-endedness as a means to enable the microsurgeon to have access to various instruments without the need to exchange tools. The elimination of instrument exchange has increased the speed with which a microsurgeon can perform a variety of procedures as well as decrease fatigue associated with continuous visual reaccommodation between the microscope and surrounding operating room. Following considerable modification through several prototypical stages and long periods of laboratory testing, these instruments boast ideal balance in the hands of the surgeon, and the capacity for modification by the user, allowing a variety of instrument combinations. Hence, personal preference can dictate the ultimate tool configuration, thereby allowing customization of the instruments to the procedure as well as the surgeon, by virtue of an interlocking mechanism between instrument components. The resulting economy of movement and reduced instrument handling engendered by the use of these instruments reduces operating time and often eliminates the need for a highly trained surgical assistant. These instruments can be fitted with a removable extension allowing unipolar use or extended instrument length. Simplicity of design makes these instruments conducive to standard cleaning and sterilization procedures.

Humans↗

PubMed1985

Incomplete recovery of muscle cell function following partial but not complete ischemia.

A simultaneous comparison of the effect of partial and total ischemia on skeletal muscle was made in dogs. The totally ischemic muscle had larger changes in adenosine triphosphate (ATP), creatine phosphate (CP), and cellular transmembrane potential difference (PD) during the 3-hour ischemic period than the partially ischemic muscle. Following recovery, all measured parameters in the totally ischemic muscle returned to normal, but paradoxically the PD in the partially ischemic muscle remained depressed despite the return to normal levels of ATP and CP. Contrary to the results in partially and totally ischemic brain tissue there was no evidence for higher levels of lactic acid in the partially ischemic muscle that could explain the persistent alteration in muscle cell function.

Adenosine Triphosphate↗

PubMed1983

Effect of low dose gamma-butyrolactone therapy on forebrain neuronal ischemia in the unrestrained, awake rat.

Low dose gamma-butyrolactone (GBL) therapy alters the natural history of experimental forebrain ischemia in the awake rat. After 30 minutes of four-vessel ischemia, repeated hydrogen cerebral blood flow determinations in awake rats over 72 hours revealed that low dose GBL therapy prevented the development of regional cerebral hyperemia and later the prolonged cerebral hypoperfusion that was experienced by the nontreated controls. Moreover, the low dose GBL-treated group had significantly less neuronal tissue loss than that in comparable brain regions of the nontreated controls. Before the stroke studies, GBL dose-response experiments performed on normal rats indicated that high dose GBL therapy produced seizures, systemic hypertension, metabolic acidosis, hyperthermia, and death.

4-Butyrolactone↗