Category Archives: Lung injury

Canadian Neighbor Pharmacy: Use of Calcium Channel Blockers in Hypoxic Lung Disease

vasodilatorsThe rationale for considering the combined use of vasodilators and low-flow oxygen in patients with COPD and hypoxemia is based on five hypotheses. The extent to which these hypotheses are correct will likely determine the long-term usefulness of vasodilators in these patients.

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Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 1)

lipopolysaccharide-induced injury (part 1)

In the past decade leukotrienes (LTs), formed by 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP), have been implicated as mediators of ischemic damage and lipopolysaccharide- (LPS) induced shock . Recently it was shown that perfusion of isolated rabbit heart with polymorphonuclear leukocytes (PMNL) induces synthesis of sul-phidopeptide LTs (sLTs), and subsequent damage of coronary circulation and myocardium . BAY X1005, a quino-line inhibitor of sLT synthesis, was shown to have a significant cardioprotective effect in this system. Continue reading

Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 8)

 lipopolysaccharide-induced injury (part 8)

Thus, we believe that evidence presented by Rossoni et al on the phenomenon of transcellular synthesis of sLT from PMNL-derived LTA4 by the vascular coronary bed in perfused rabbit heart is of a more generalized nature and is strictly applicable to our lung system. The inhibitory action of BAY X1005 in our experiments proves that the pneumotoxic action of LPS is mediated by sLT, but, most important, it provides new experimental support for the hypothesis that pulmonary tissue can produce significant amounts of sLTs from blood-derived LTA4 via transcellular conversion, which further propagate the effects of LT released from blood cells or other sources . Continue reading

Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 7)

Although our conclusion on the importance of LT in development of LPS-induced lung injury is based only on indirect evidence, ie, inhibition of sLT synthesis, it is strongly supported by the following. First, during sepsis LT concentration in lungs is always increased . Second, administration of exogenous sLT (LTC4, LTD4, LTE4) produces in lungs a shock-like state consisting of constriction of bronchi and lung parenchyma, stimulation of vascular smooth muscle and increase in pulmonary artery pressure with subsequent reductions in regional blood flow and promotion of vascular leakage of fluid into the lungs . Continue reading

Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 6)

induced injury (part 6)

DISCUSSION
Intravenous injection of E coli LPS into experimental animals induces septic shock that, mostly fatal, is manifested by systemic hypotension and pulmonary hypertension associated with respiratory failure, vascular injury and disseminated intravascular coagulation . The main clinical complication of shock is acute lung injury (acute respiratory distress syndrome), which is characterized by pulmonary arterial hypertension, obturation of pulmonary blood vessels, increased shunt fraction, formation of atelectasis, arterial hypoxemia and a drop in cardiac output . Continue reading

Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 5)

In Krebs-perfused lungs, endotoxin (E Coli LPS, serotype 0127:B8) injected directly into the perfusion system at a concentration of 5 |ig/mL did not affect PAP (n=8).

However, in lungs perfused with homologous blood, LPS induced a marked increase in PAP within 7 to 10 mins after administration. PAP reached a maximal, more than fourfold, increase usually between 60 and 80 mins. Such an increase was accompanied by symptoms of pulmonary edema. BAY X1005 10 |ig/mL, administered into the perfusion circuit 20 mins before LPS, lowered the rise in PAP induced by LPS by 72±2.1% (n=15), as measured 70 mins after LPS administration (Figure 2). Continue reading

Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 4)

 lipopolysaccharide-induced injury (part 4)

The time from death to the setting of perfusion flow was approximately 20 mins. BAY X1005 (3 to 10 |jM) and LPS (5 |ig/mL) were injected directly into the lung reperfusion circuit. BAY X1005 was administered 20 mins before LPS. Experimental protocols were approved by the appropriate institutional ethical review committee of Jagiellonian University, Krakow, Poland.
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Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 3)

ipopolysaccharide-induced injury (part 3)

Perfusion flow was set at 23 mL/min, providing a perfusion pressure of 9.8±3 mmHg (mean ± SD; n=25). PAP was monitored continuously with an Isotec pressure transducer (Healthdyne Cardiovascular Inc, Marietta, Georgia, USA). Because a constant flow perfusion pump was used, changes in PAP are interchangeable with changes in pulmonary vascular resistance. All results of pulmonary vascular resistance in this study are expressed as changes in PAP. Lung effluent was withdrawn via the left atrial cannula. During the initial period (25 to 30 mins) of lung perfusion (stabilization of baseline PAP and elimination of circulating blood elements) it was discarded. Continue reading

Pulmonary protection by leukotriene synthesis inhibitor BAY X1005 against lipopolysaccharide-induced injury (part 2)

General acceptance of sLTs as major mediators of LPS-induced shock, strengthened by the likelihood that their transcellular synthesis occurs in the pulmonary vascular bed, prompted us to explore whether BAY X1005, a new, potent, selective LT synthesis inhibitor that binds to FLAP and demonstrates systemic anti-inflammatory and antiallergic properties (10,11), can protect blood-perfused lungs against LPS-induced increase in pulmonary arterial perfusion pressure (PAP) and reduce pneumotoxicity of LPS.

ANIMALS AND METHODS
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