Pulmonary hypertension associated with heart failure with preserved ejection fraction: acute hemodynamic effects of inhaled iloprost.

Iloprost, an inhaled synthetic prostacyclin analogue, improves hemodynamic and clinical status with minimal systemic adversity in patients with pulmonary arterial hypertension. Our single-site, prospective case series aimed to determine the effects of iloprost in subjects with group 2 pulmonary hypertension and heart failure with preserved ejection fraction. Patients referred to Boston Medical Center for initial evaluation of suspected pulmonary hypertension received a test dose of 2.5 µg inhaled iloprost, followed by two subsequent doses of 5 µg. Hemodynamic measurements were recorded for each inhalation after 15, 30, 60, and 90 minutes. Results were analyzed via paired t test and signed-rank test. Eight subjects fulfilled criteria and elected to enter the study. There was a reduction of pulmonary arterial pressure (by an average of 7.0 mmHg [P = 0.005] and 4.7 mmHg [P = 0.021] with the first and second 5-µg inhalations, respectively) and pulmonary vascular resistance (by an average of 161.9 dyn·s/cm(5) [P = 0.019] and 95.0 dyn·s/cm(5) [P = 0.014] with the first and second 5-µg inhalations, respectively). There were trends for increased cardiac output and decreased oxygen saturation. There were no changes in other vital or hemodynamic parameters, including pulmonary capillary wedge pressure. All patients completed each cycle of iloprost administration without preestablished termination criteria. In patients with pulmonary hypertension and heart failure with preserved ejection fraction, inhaled iloprost resulted in acute reduction of pulmonary arterial pressure and pulmonary vascular resistance. Further evaluation of iloprost in this subset of patients is warranted.

Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease.

Adiponectin (APN) is an adipocyte-derived factor that exists at high concentrations in serum and has anti-inflammatory and systemic vascular-protective properties. In this study, we investigated the role of APN in pulmonary vascular homeostasis. We found that APN localizes to the luminal side of blood vessels in lung and acts in vitro to block TNF-alpha-induced E-selectin upregulation in pulmonary artery endothelial cells. Targeted deletion of the APN gene in mice leads to a vascular phenotype in lung characterized by E-selectin upregulation and age-dependent increases in perivascular inflammatory cell infiltration and pulmonary arterial pressures. Taken together, these findings demonstrate an important role for APN in lung vascular homeostasis and suggest that APN-deficient states may contribute to the pathogenesis of inflammatory pulmonary vascular disease and to the development of pulmonary hypertension.

Etiology of decreased gastric nitric oxide in the critically ill.

BACKGROUND: Nitric oxide (NO) is present in the gas phase of the normal human stomach at a high concentration (1-10 ppm). The majority of this NO is produced from the reduction of dietary nitrate to nitrite and finally NO. Generation of this nonenzymatically produced gastric NO occurs only in an acidic environment. We examined NO concentrations in critically ill subjects and the mechanism for the observed perturbations. METHODS: Seven critically ill, intubated intensive care unit (ICU) patients (mean APACHE II score 16) and seven control patients were studied. Gastric NO concentrations were measured with a Sievers NO analyzer (GE, Boulder, CO). Nitrate and nitrite concentrations were determined by a modified Griess assay. Bacterial counts were determined by optical density at 600 nm. RESULTS: Gastric NO concentration was significantly lower in the critically ill group (102.7 ppb) compared with the control group (953.2 ppb), although this difference was abolished by treating the control group with omeprazole (54 ppb). Gastric nitrate and nitrite concentrations were similar in the control and ICU groups, suggesting that substrate deficiency was not a cause of the low intragastric NO. Gastric pH was significantly lower in the control subjects (3.0) compared with the ICU patients (6.3) and the control subjects after receiving omeprazole (6.5). ICU patients had a trend toward higher gastric bacterial load. CONCLUSION: In critically ill patients, markedly decreased NO concentrations are found in the gas of the stomach owing to a failure of gastric acidification.