Wyniki wyszukiwania

Sortuj według:

Ogranicz wyniki do:

Selective inhibition of guanylate cyclase prevents impairment of hypoxic pulmonary vasoconstriction in endotoxemic mice

100%

Spohr F., Busch C. J., Teschendorf P., Weimann J.

Journal of Physiology and Pharmacology

2009

tom 60

nr 2

107-112

Nitric oxide (NO) may cause sepsis-induced impairment of hypoxic pulmonary vasoconstriction (HPV). Although NO exerts many of its actions by activating soluble guanylate cyclase (sGC), there are several cGC-independent mechanisms that may lead to NO-induced vasodilation during endotoxemia. We investigated the role of sGC for the regulation of HPV during lipopolysaccharide (LPS) induced endotoxemia using 1H-(1,2,4)oxadiazole(4,3-)quinoxaline-1-one (ODQ), a specific inhibitor of sGC, in isolated, perfused, and ventilated mouse lungs. Without ODQ, lungs from LPS-challenged mice constricted significantly less in response to hypoxia as compared to lungs from mice not treated with LPS (26 ± 27% vs. 134 ± 37%, respectively, p < 0.05). 20 mg/kg ODQ, but not 2 mg/kg or 10 mg/kg, restored the blunted HPV response in LPS-challenged mice as compared to mice not challenged with LPS (80±14 % vs. 98±21 %). ODQ had no effect on baseline perfusion pressures under normoxic conditions. Analysis of pulmonary vascular P-Q relationships suggested that the restoration of pulmonary vascular response to hypoxia by ODQ is associated with a restoration of pulmonary vascular properties during normoxia. Our data show in a murine model that specific inhibition of sGC may be a new approach to restore HPV during endotoxemia.

Worsening of long-term myocardial function after successful pharmacological pretreatment with cyclosporine

63%

Laudi S., Weimann J., Haschke M., Trump S., Schmitz V., Christians U., Kaisers U., Steudel W.

Journal of Physiology and Pharmacology

2007

tom 58

nr 1

Pretreatment with cyclosporine (CsA) decreases infarct size 24h after myocardial ischemia/reperfusion (I/R). The goal of this study was to determine effects of CsA pretreatment on long-term cardiac function after I/R-injury. Rats were randomly assigned to group1: vehicle-only, group2: CsA-5mg/kg/day, and group3: CsA-12.5mg/kg/day given orally for three days prior to I/R-injury (30 min of left anterior descending coronary artery occlusion). Post-I/R survival and cardiac function were evaluated 14 days after I/R-injury by echocardiography and invasive hemodynamic measurements. Rats with I/R-injury showed increased left ventricular pressure (LVEDP) compared to rats without I/R-injury (p<0.005). Although CsA initially decreased infarct size, no differences of LVEDP were seen 14 days after I/R-injury (vehicle: 21.2±8.9 mmHg, CsA-5mg/kg/day: 21.5±0.7 mmHg, CsA-12.5mg/kg/day: 20.5±9.4 mmHg). Ejection fraction and fractional shortening were decreased compared to baseline, but showed no differences between groups. On day 14, a dose-dependent increase in left ventricular end diastolic diameter was seen (p<0.001). CsA pretreatment was associated with a dose-dependent decrease in post-I/R-survival (vehicle: 56%, CsA-5mg/kg/day: 32%, CsA-12.5mg/kg/day: 16%; p=0.017). CsA pretreatment did not improve long-term cardiac function despite decreased infarct size 24h after I/R-injury, but increased post-I/R mortality significantly. Poor cardiac function after CsA pretreatment might be caused by left ventricular dilation.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Weimann J.

1 Busch C. J.

1 Christians U.

1 Haschke M.

1 Kaisers U.

1 Laudi S.

1 Schmitz V.

1 Spohr F.

1 Steudel W.

1 Teschendorf P.

1 Trump S.

1 2009

1 2007

Wyniki wyszukiwania

Selective inhibition of guanylate cyclase prevents impairment of hypoxic pulmonary vasoconstriction in endotoxemic mice

Worsening of long-term myocardial function after successful pharmacological pretreatment with cyclosporine