Showing papers by "Warren M. Zapol published in 1997"

Inhaled Nitric Oxide and Persistent Pulmonary Hypertension of the Newborn

Abstract: Background Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension. Methods In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used. Results Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels. Conclusions Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

Pulmonary Vasoconstriction and Hypertension in Mice With Targeted Disruption of the Endothelial Nitric Oxide Synthase (NOS 3) Gene

Abstract: NO, synthesized in endothelial cells by endothelial NO synthase (NOS 3), is believed to be an important endogenous pulmonary vasodilator substance that contributes to the normal low pulmonary vascular resistance. To selectively investigate the role of NOS 3 in the pulmonary circulation, mice with targeted disruption of the NOS 3 gene were studied. Pulmonary hemodynamics were studied by measuring pulmonary artery pressure, left ventricular end-diastolic pressure, and lower thoracic aortic flow by using a novel open-chest technique. Transient partial occlusion of the inferior vena cava was used to assess the pulmonary artery pressure-flow relationship. Tension developed by isolated pulmonary artery segments after acetylcholine stimulation was measured in vitro. The histological appearance of NOS 3–deficient and wild-type murine lungs was compared. NOS 3–deficient mice (n=27), when compared with wild-type mice (n=32), had pulmonary hypertension (pulmonary artery pressure, 19.0±0.8 versus 16.4±0.6 mm...

Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo.

Abstract: The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS). Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; P 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P50 decreased (P 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD.

Treatment of a hemoglobinopathy

Abstract: Disclosed are methods for treating a patient identified as having a hemoglobinopathy that is characterized by a reduced affinity of hemoglobin for oxygen. The methods involve providing gaseous nitric oxide and/or carbon monoxide for (i) inhalation by the patient or (ii) ex vivo treatment of the patient's erythrocytes. Alternatively, a nitric-oxide-releasing compound can be administered to the patient.

Medical composition for treating patient accompanied by bronchoconstriction and apparatus for inhalation of the same

Abstract: PROBLEM TO BE SOLVED: To obtain a medical composition capable of relaxing bronchoconstriction, especially constriction of bronchial smooth muscle by constituting the composition of a mixed gas containing NO gas and O2 gas obtained by mixing a specific component therewith just before inhalation by a patient. SOLUTION: This medical composition comprising NO gas and a mixed gas containing O2 is obtained by mixing, for example, a gas containing compressed NO gas in N2 gas with O2 /N2 mixed gas just before inhalation to a patient. The composition is inhaled by mammals having pulmonary vascularity contraction, asthma, etc., under one or more conditions corresponding to (a) a state of including no smoke of tobacco, (b) a state of inhaling as a mixed gas of NO gas, O2 gas and N2 gas, (c) a state of the inhaling concentration of NO gas being 1ppm, preferably 80-180ppm, (d) a state of maintaining the concentration of NO2 concentration under the safety limit ( =3min, preferably >=6min.