Modified natural and synthetically reconstituted surfactant therapies for acute lung injury caused by endotoxin in rats

Tashiro, Katsumi; Nishizuka, Kazuo; Matsumoto, Yutaka; Ohta, Keisuke; Suzuki, Yasutaka; Kobayashi, Tsutomu

doi:10.1034/j.1399-6576.1999.430807.x

Cited by 6 publications

(7 citation statements)

References 36 publications

(53 reference statements)

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“…Tashiro and colleagues [45] demonstrated in rat model of sepsisinduced adult respiratory distress syndrome (ARDS) that an artificial surfactant reconstituted with SP-B and SP-C was as effective as porcine modified natural surfactant in restoring oxygenation and normalising pressure-volume curves. Similarly, Walther et al [35] demonstrated that beractant spiked with supplemental SP-B and SP-C was superior to unmodified beractant in restoring oxygenation and normalised pressure-volume relationships in another rat surfactant wash-out model.…”

Section: Animal Studiesmentioning

confidence: 99%

Calfactant

Willson

2001

Expert Opinion on Pharmacotherapy

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Surfactant administration has proven remarkably effective in the prevention and treatment of infantile respiratory distress syndrome (IRDS) and may also be beneficial in other forms of acute lung injury. Several surfactant products are available commercially along with others in various phases of development and clinical trials. While all of these products share an ability to lower surface tension in vitro, there are substantial compositional differences that appear to affect their in vivo efficacy. At present, the 'modified natural' surfactants containing the hydrophobic surfactant proteins SP-B and SP-C appear most effective. Calfactant may have a particular advantage because of its relatively high content of SP-B and its lack of contamination with non-surfactant lipids and proteins.

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Section: Animal Studiesmentioning

confidence: 99%

Calfactant

Willson

2001

Expert Opinion on Pharmacotherapy

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“…Moreover, Tashiro and colleagues employed peak inspiratory pressures of 2.5 kPa and a PEEP of 0.75 kPa in the rat, without any evidence of pulmonary tissue damage [14]. 646 C. Hofstetter et al…”

Section: Discussionmentioning

confidence: 99%

“…In the rat, endobronchial or intrapulmonary administration of therapeutical agents has regularly been performed either by inhalation of aerosols during spontaneous breathing or by direct instillation of liquid preparations, respectively [11][12][13][14][15]. However, intratracheal instillation is not a physiological route of delivery and results from those investigations may not be transferable to the general clinical situation.…”

mentioning

confidence: 99%

Aerosol Delivery During Mechanical Ventilation to the Rat

Hofstetter

Flonder

Thein³

et al. 2004

Experimental Lung Research

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The authors have adjusted a jet nebulizer to a mechanical ventilator (Servo Ventilator, Siemens) to deliver an aerosol to rats. They aimed to clarify whether a modified jet nebulizer generating particles with a mass median aerodynamic diameter of 2 microm would be effective and safe in intubated ventilated rats. Fluorescent microspheres (diameter: 1.0 microm) were aerosolized to verify qualitatively and quantitatively intrapulmonary deposition. Particle deposition fraction was 3.8% (1.3%) of the delivered dose (median [interquartile range]). There was no evidence for any adverse event as assessed from heart rate, mean arterial pressure, PaO2 and PaCO2 before, during, and after nebulization. No pulmonary tissue trauma was detected histologically.

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“…Several different agents can be classified among this group including bronchospasmolytics [67][68][69], trypsin inhibitors [70,71], vasodilating agents [72][73][74] and surfactant substitutes [75][76][77][78].…”

Section: Paas That Enhance Efficiency Of Lung Ventilation and Gas Excmentioning

confidence: 99%

“…Infasurf ® (calfactant) Intratracheal Suspension is a sterile, non-pyrogenic lung surfactant intended for intratracheal instillation. It is an extract of natural surfactant from calf lungs, which includes phospholipids, neutral lipids, and hydrophobic surfactant-associated proteins B and C. Other examples of artificial surfactant are presented in [75][76][77][78]. …”

Section: Paas That Enhance Efficiency Of Lung Ventilation and Gas Excmentioning

confidence: 99%

Remediation of Cellular Hypoxic Damage by Pharmacological Agents

Minko¹,

Wang²,

Pozharov³

2005

CPD

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Many known pathological conditions lead to decreases in oxygen supply to various cells. When secondary cellular hypoxia becomes severe, it causes additional cellular damage, aggravating the primary disorder and leading to cell death. Therefore, remediation of secondary hypoxic damage should significantly increase the efficacy of the treatment of primary disease and prevent extensive cellular damage. Analysis of the literature and our experimental data show that the main mechanisms of secondary hypoxic cellular damage include lactate acidosis (lactic acidosis), the boost in free radical processes and the activation of apoptosis and necrosis. These factors result in damage to cellular membranes which in turn further limits oxygen supply leading to augmented hypoxic cellular damage. Therefore, to effectively break this vicious cycle of cellular hypoxia, antihypoxic therapy should simultaneously: (1) mitigate existing cellular hypoxic damage; (2) increase cellular ability to utilize available oxygen; (3) amplify the power of cellular antioxidant defense and (4) prevent hypoxic activation of apoptosis and necrosis. It is clear that such complex task cannot be fulfilled by a single pharmacological agent. Therefore, a complex multi component antihypoxic drug delivery system should be designed to address all the four desiderata indicated above. This review will examine existing pharmaceutical antihypoxic preparations and evaluate the new methods for the pharmacological remediation of cellular hypoxic damage and propose future directions for the design of the needed drug delivery systems.

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Modified natural and synthetically reconstituted surfactant therapies for acute lung injury caused by endotoxin in rats

Cited by 6 publications

References 36 publications

Calfactant

Calfactant

Aerosol Delivery During Mechanical Ventilation to the Rat

Remediation of Cellular Hypoxic Damage by Pharmacological Agents

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