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Skin Flap Physiology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Colin MacIver, Stergios Doumas
Recent studies have shown that this detrimental effect can be blocked in experimental porcine transverse rectus abdominis myocutaneous (TRAM) flaps by tezosentan, a endothelin receptor blocker. The authors suggest that tezosentan improves oxygenation and metabolism in the jeopardized contralateral flap tissue, probably as a result of a decrease in venous vascular resistance and fluid extravasation.49
Pharmacological therapy
Published in ILEANA PIÑA, SIDNEY GOLDSTEIN, MARK E DUNLAP, The Year in Heart Failure, 2005
KIRKWOOD ADAMS, HERBERT PATIERSON
Tezosentan, a dual endothelin receptor antagonist, has been previously shown to improve short-term haemodynamics in patients with stable chronic heart failure. In this trial, the effects of intravenous tezosentan were studied in a group of patients admitted for treatment of acute heart failure. One key issue remains, the proper dose of tezosentan for patients with acute heart failure. This study provides strong evidence that the doses studied to date are probably above the optimal ones. The doses in this study produced similar beneficial effects on haemodynamics. In addition, there was evidence of increased adverse events with the higher dosage, suggesting that further studies with the dose <50 mg/h should be conducted. Nevertheless, this therapy remains a potentially useful one for patients with acute, decompensated heart failure. Additional trials to better define the dose response and clinical effectiveness of tezosentan in this clinical setting are underway.
Newer approaches and novel drugs for inhalational therapy for pulmonary arterial hypertension
Published in Expert Opinion on Drug Delivery, 2020
Ali Keshavarz, Hossam Kadry, Ahmed Alobaida, Fakhrul Ahsan
Although all three currently approved ERAs demonstrated potent prolonged efficacy in PAH, the main limiting factors for the widespread application of ERA for treatment of PAH patients are life-threatening adverse effects associated with long-term therapy, including elevation of liver transaminase levels, decrease in hemoglobin levels [71]. The inhalation route of application has been suggested to minimize systemic side effects and to restrict the action of these substances to the lungs and maximize their deposition. Leuchte et al. demonstrated that aerosolization of selective ETA (BQ-123) and a dual selective ETA and ETB receptor blocker (Tezosentan) attenuated pulmonary vasoconstriction, improved arterial oxygenation, and decreased mPAP without significant systemic side-effect [78].
Pinealectomy and melatonin administration in rats: their effects on pulmonary edema induced by α-naphthylthiourea
Published in Drug and Chemical Toxicology, 2023
Mohammed Raed Abdullah Al Gburi, Eyup Altinoz, Hulya Elbe, Melike Ozgul Onal, Umit Yilmaz, Nesibe Yilmaz, Melike Karayakali, Mehmet Demir
In the ANTU model, when the amount of fluid in the interstitial lung space rises above its capacity, there will be drainage of lung interstitial fluid into the pleural space through the visceral pleura. After i.p. ANTU administration to rats, pulmonary edema and PE develop, which reach their maximum level within 4 h. The resulting edema either disappears completely within 24–48 h or the condition worsens, causing the death of the rat (Cunningham and Hurley 1972). In our study, over a 4-h period, severe acute lung injury occurred in all rats injected with 10 mg/kg dose i.p of ANTU. In this injury, PE formation, LW/BW and PE/BW ratios increase detected. In two different studies investigating the effects of dexmedetomidine (Hancı et al. 2012) and endothelin receptor antagonist Tezosentan on lung damage caused by ANTU in rats, the fluid accumulation and weight values in the lungs of the rats in the ANTU groups were found to be higher than in the control and treatment groups (Atalay et al. 2012). In studies investigating the curative effects of exogenous sulfur dioxide (Huang et al. 2009) and the counter-effect of methylprednisolone on lung injury in rats, an increase in LW/BW ratios was detected (You et al. 2014). In our study, the fluid accumulation and weight values in the lungs of rats in the ANTU and ANTU + PINX groups were significantly higher than the control groups and all MLT treatment groups. There were also significant decreases in fluid accumulation and weight values in the lungs of the rats in the MLT group injected with MLT compared to the ANTU group. In a study in which the same dose of MLT (10 mg/kg i.p.) was administered daily to mice, it was revealed that MLT significantly reduced body weight loss, mortality, lung infiltration with polymorphonuclear neutrophils, and edema formation (Genovese et al. 2005). In our study, the picture of the disease was worse in rats given ANTU and pinealectomy. However, it was determined that effusion, pulmonary edema, and inflammatory cell infiltration developed less in the groups which given MLT.