Showing papers by "Warren M. Zapol published in 2005"
TL;DR: It is suggested that the overall increase in oxygen, mediated by the formation of passive continental margins along the Atlantic Ocean during the opening phase of the current Wilson cycle, was a critical factor in the evolution, radiation, and subsequent increase in average size of placental mammals.
Abstract: On the basis of a carbon isotopic record of both marine carbonates and organic matter from the Triassic-Jurassic boundary to the present, we modeled oxygen concentrations over the past 205 million years. Our analysis indicates that atmospheric oxygen approximately doubled over this period, with relatively rapid increases in the early Jurassic and the Eocene. We suggest that the overall increase in oxygen, mediated by the formation of passive continental margins along the Atlantic Ocean during the opening phase of the current Wilson cycle, was a critical factor in the evolution, radiation, and subsequent increase in average size of placental mammals.
288 citations
TL;DR: In this paper, Sildenafil (50 mg) and inhaled NO (80 ppm) were administered to patients with congestive heart failure and pulmonary hypertension to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor.
198 citations
TL;DR: It is indicated that LTs play a central role in the lung injury and impaired oxygenation induced by HVT ventilation, and administration of MK886, a 5LO-activity inhibitor, or MK571, a selective cysteinyl-LT(1) receptor antagonist, largely prevented ventilator-induced lung injury.
Abstract: Rationale: Mechanical ventilation with high VT (HVT) progressively leads to lung injury and decreased efficiency of gas exchange. Hypoxic pulmonary vasoconstriction (HPV) directs blood flow to well-ventilated lung regions, preserving systemic oxygenation during pulmonary injury. Recent experimental studies have revealed an important role for leukotriene (LT) biosynthesis by 5-lipoxygenase (5LO) in the impairment of HPV by endotoxin. Objectives: To investigate whether or not impairment of HPV contributes to the hypoxemia associated with HVT and to evaluate the role of LTs in ventilator-induced lung injury. Methods: We studied wild-type and 5LO-deficient mice ventilated for up to 10 hours with low VT (LVT) or HVT. Results: In wild-type mice, HVT, but not LVT, increased pulmonary vascular permeability and edema formation, impaired systemic oxygenation, and reduced survival. HPV, as reflected by the increase in left pulmonary vascular resistance induced by left mainstem bronchus occlusion, was markedly impair...
53 citations
TL;DR: Intravenous dipyridamole augments and prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with severe PH and, when administered in combination with NO inhalation, can identify PH reversibility in potential cardiac transplant recipients in whom a pulmonary vasODilator response to inhalation of NO alone is not observed.
Abstract: Background Irreversible, severe pulmonary hypertension (PH) can produce right heart failure and early mortality after cardiac transplantation. We hypothesized that dipyridamole, an inhibitor of Type 5 phosphodiesterase, would augment the ability of inhaled nitric oxide (NO) to identify reversibility of PH. Methods In 9 patients with congestive heart failure (CHF) and severe PH who were breathing 100% oxygen during right heart catheterization, we administered inhaled NO (80 ppm) alone and in combination with intravenous dipyridamole (0.2-mg/kg bolus, with an infusion of 0.0375 mg/kg/min). Results Compared with breathing oxygen alone, NO inhalation decreased pulmonary artery pressure and pulmonary vascular resistance (PVR) (by 10 ± 4% and 26 ± 12% [mean ± SEM], respectively; both p p p 5 in 3 of 7 patients who had a PVR of >200 dyne·s/cm 5 when breathing oxygen alone, whereas the combination of NO and dipyridamole decreased PVR to 5 in 2 additional patients. Conclusions Intravenous dipyridamole augments and prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with severe PH and, when administered in combination with NO inhalation, can identify PH reversibility in potential cardiac transplant recipients in whom a pulmonary vasodilator response to inhalation of NO alone is not observed.
18 citations
Patent•
04 Feb 2005
TL;DR: In this article, the authors disclosed methods for enhancing the therapeutic or prophylactic effectiveness of an inhaled therapeutic gas by injecting it to a mammal with a compound that sensitizes soluble guanylate cyclase.
Abstract: Methods for enhancing the therapeutic or prophylactic effectiveness of an inhaled therapeutic gas are disclosed. The methods include administering to a mammal by inhalation a therapeutically effective amount of gaseous nitric oxide or carbon monoxide, and administering to the mammal a composition containing a compound that sensitizes soluble guanylate cyclase.
8 citations
TL;DR: The hypotheses that direct stimulation of sGC by BAY 41-2272 would produce pulmonary vasodilation and augment the pulmonary responses to inhaled NO or CO were tested.
Abstract: Background Inhaled nitric oxide (NO) is a potent and selective pulmonary vasodilator. NO induces cGMP synthesis by activating soluble guanylate cyclase (sGC) in ventilated lung regions. Carbon monoxide (CO) has also been proposed to modulate smooth muscle tone via activation of sGC. We tested the hypotheses that direct stimulation of sGC by BAY 41-2272 would produce pulmonary vasodilation and augment the pulmonary responses to inhaled NO or CO.
1 citations
Patent•
04 Feb 2005
TL;DR: Procede d'amelioration de l'efficacite therapeutique ou prophylactique d'un gaz therapeutiques inhale as discussed by the authors, is consistent for administrer a un mammifere par inhalation, and a composition contenant un compose rendant sensible a guanylate cyclase soluble.
Abstract: Procede d'amelioration de l'efficacite therapeutique ou prophylactique d'un gaz therapeutique inhale. Les procedes consistent a administrer a un mammifere par inhalation une quantite therapeutiquement efficace d'un oxyde nitrique gazeux ou d'un monoxyde de carbone, et a administrer au mammifere une composition contenant un compose rendant sensible a la guanylate cyclase soluble.