Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension

1997 ◽  
Vol 83 (6) ◽  
pp. 1968-1975 ◽  
Author(s):  
Richard J. Brilli ◽  
Brian Krafte-Jacobs ◽  
Daniel J. Smith ◽  
Dominick Roselle ◽  
Daniel Passerini ◽  
...  

Brilli, Richard J., Brian Krafte-Jacobs, Daniel J. Smith, Dominick Roselle, Daniel Passerini, Amos Vromen, Lori Moore, Csaba Szabó, and Andrew L. Salzman. Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension. J. Appl. Physiol. 83(6): 1968–1975, 1997.—We examined the pulmonary and systemic hemodynamic effects of administering soluble nitric oxide (NO) donor compounds (NO/nucleophile adducts, i.e., NONOates) directly into the trachea of animals with experimentally induced pulmonary hypertension. Steady-state pulmonary hypertension was created by using the thromboxane agonist U-46619. Yorkshire pigs were randomly assigned to one of four groups: group 1, intratracheal saline (control; n = 8); group 2, intratracheal sodium nitroprusside ( n = 6); group 3, intratracheal ethylputreanine NONOate ( n = 6); and group 4, intratracheal 2-(dimethylamino)-ethylputreanine NONOate (DMAEP/NO; n = 6). Pulmonary and systemic hemodynamics were monitored after drug instillation. Group 4 had significant reductions in pulmonary vascular resistance index (PVRI) at all time points compared with steady state and compared with group 1 ( P < 0.05), whereas systemic vascular resistance index did not change. The mean change in mean pulmonary arterial pressure in group 4 was −33.1 ± 1.2% compared with +6.4 ± 1.3% in group 1( P < 0.001), and the mean change in mean arterial pressure was −9.3 ± 0.7% compared with a control value of −0.9 ± 0.5% ( P < 0.05). Groups 2 and 3 had significant decreases in both PVRI and systemic vascular resistance index compared with steady state and with group 1. In conclusion, intratracheal instillation of a polar-charged tertiary amine NONOate DMAEP/NO results in the selective reduction of PVRI. Intermittent intratracheal instillation of selective NONOates may be an alternative to continuously inhaled NO in the treatment of pulmonary hypertension.

2018 ◽  
Vol 9 (2) ◽  
pp. 102-107 ◽  
Author(s):  
Mélanie Gaubert ◽  
Noémie Resseguier ◽  
Franck Thuny ◽  
Franck Paganelli ◽  
Jennifer Cautela ◽  
...  

Objective: Impaired vascular tone plays an important role in cardiogenic shock. Doppler echocardiography provides a non-invasive estimation of systemic vascular resistance. The aim of the present study was to compare Doppler echocardiography with the transpulmonary thermodilution method for the assessment of systemic vascular resistance in patients with cardiogenic shock. Methods: This prospective monocentric comparison study was conducted in a single cardiology intensive care unit (Hopital Nord, Marseille, France). We assessed the systemic vascular resistance index by both echocardiography and transpulmonary thermodilution in 28 patients admitted for cardiogenic shock, on admission and after the introduction of an inotrope or vasopressor treatment. Results: A total of 35 paired echocardiographic and transpulmonary thermodilution estimations of the systemic vascular resistance index were compared. Echocardiography values ranged from 1309 to 3526 dynes.s.m2/cm5 and transpulmonary thermodilution values ranged from 1320 to 3901 dynes.s.m2/cm5. A statistically significant correlation was found between echocardiography and transpulmonary thermodilution ( r=0.86, 95% confidence interval (CI) 0.74, 0.93; P<0.0001). The intraclass correlation coefficient was 0.84 (95% CI 0.72, 0.92). The mean bias was −111.95 dynes.s.m2/cm5 (95% CI −230.06, 6.16). Limits of agreement were −785.86, 561.96. Conclusions: Doppler echocardiography constitutes an accurate non-invasive alternative to transpulmonary thermodilution to provide an estimation of systemic vascular resistance in patients with cardiogenic shock.


2021 ◽  
pp. 036354652110469
Author(s):  
Benjamin R. Saks ◽  
Vivian W. Ouyang ◽  
Elijah S. Domb ◽  
Andrew E. Jimenez ◽  
David R. Maldonado ◽  
...  

Background: Access to quality health care and treatment outcomes can be affected by patients’ socioeconomic status (SES). Purpose: To evaluate the effect of patient SES on patient-reported outcome measures (PROMs) after arthroscopic hip surgery. Study Design: Cohort study; Level of evidence, 3. Methods: Demographic, radiographic, and intraoperative data were prospectively collected and retrospectively reviewed on all patients who underwent hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and labral tear between February 2008 and September 2017 at one institution. Patients were divided into 4 cohorts based on the Social Deprivation Index (SDI) of their zip code. SDI is a composite measure that quantifies the level of disadvantage in certain geographical areas. Patients had a minimum 2-year follow-up for the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), International Hip Outcome Tool—12, and visual analog scale (VAS) for both pain and satisfaction. Rates of achieving the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were calculated for the mHHS, NAHS, and VAS pain score. Rates of secondary surgery were also recorded. Results: A total of 680 hips (616 patients) were included. The mean follow-up time for the entire cohort was 30.25 months. Division of the cohort into quartiles based on the SDI national averages yielded 254 hips (37.4%) in group 1, 184 (27.1%) in group 2, 148 (21.8%) in group 3, and 94 (13.8%) in group 4. Group 1 contained the most affluent patients. There were significantly more men in group 4 than in group 2, and the mean body mass index was greater in group 4 than in groups 1 and 2. There were no differences in preoperative radiographic measurements, intraoperative findings, or rates of concomitant procedures performed. All preoperative and postoperative PROMs were similar between the groups, as well as in the rates of achieving the MCID or PASS. No differences in the rate of secondary surgeries were reported. Conclusion: Regardless of SES, patients were able to achieve significant improvements in several PROMs after hip arthroscopy for FAIS and labral tear at the minimum 2-year follow-up. Additionally, patients from all SES groups achieved clinically meaningful improvement at similar rates.


1984 ◽  
Vol 57 (6) ◽  
pp. 1829-1833 ◽  
Author(s):  
L. J. McNabb ◽  
K. M. Baldwin

The hemodynamic and metabolic effects of exercise were measured in Crotalaria-induced pulmonary hypertension in rats. The Crotalaria group had increased preexercise heart rate, mean pulmonary arterial pressure (PAP), arteriovenous O2 content difference, right ventricular work index (RVWI), and total pulmonary vascular resistance index (TPVRI) and decreased mean systemic blood pressure (BP), arterial O2 content (CaO2), venous O2 content (CvO2), cardiac index (CI), stroke volume index (SVI), and left ventricular work index (LVWI). The Crotalaria group during exercise had increased PAP, RVWI, TPVRI, and total systemic vascular resistance index and decreased BP, O2 consumption, CaO2, CvO2, CI, SVI, LVWI, O2 pulse index, and exercise duration. It is hypothesized that abnormal right ventricular function was a primary factor in the reduced exercise tolerance of the Crotalaria group.


1994 ◽  
Vol 76 (6) ◽  
pp. 2785-2793 ◽  
Author(s):  
J. Meyer ◽  
F. Hinder ◽  
J. Stothert ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
...  

We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun] L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O2 consumption was unaffected by treatment.


2019 ◽  
Vol 08 (02) ◽  
pp. 113-118
Author(s):  
Hakan AK ◽  
Iskender Samet Daltaban ◽  
Sevilay Vural

Abstract Aim In this experimental study, we aimed to investigate possible healing effects of memantine hydrochloride, an N-methyl-d-aspartate (NMDA) antagonist, with clinical, biochemical, and histopathologic methods on acute peripheral nerve injury (PNI). Material and Method Forty-eight adult Wistar albino rats were divided into four groups (n = 12). The groups were arranged as sham-operated group (group 1), acute compression model group (group 2), trauma + low-dose memantine group (group 3), and trauma + high-dose memantine group (group 4). Memantine was administered intraperitoneally for 7 days. Subjects were sacrificed after the measurement of the sciatic nerve function index (SNFI) on the eighth day. Cyclooxygenase 2 (COX-2) and tumor necrosis factor-α (TNF-α) levels were measured in nerve tissues. Histopathologic evaluation was performed by electron microscopy. Results The mean sciatic function index (SFI) scores of groups 1 to 4 were +3.27 (standard deviation [SD] ±4.66),–18.2 (SD = ±11.7),–8.5 (SD = ±7.5), and–2.5 (SD = ±9), respectively. The mean COX-2 values were 0.98 ng/mL (SD = ±0.51), 1.89 ng/mL (SD = ±0.22), 1.39 ng/mL (SD = ±0.36), and 1.35 ng/mL (SD = ±0.59), respectively. TNF-α values were 0.09 pg/mL (SD = ±0.23), 1 pg/mL (SD = ±0.96), 0.46 pg/mL (SD = ±0.55), and 0.48 pg/mL (SD = ±0.78), respectively. Group 1 showed normal histologic findings. Group 2 showed marked edema particularly in large-diameter myelins. Myelin configurations were detected in large myelinated axons in group 3. The number of mast cells in endoneurium was high in group 4. Conclusion The efficacy of memantine in the acute phase of PNI appears to be significant according to the SNFI and biochemical tests. However, histologic findings suggest that high doses of memantine have a negative effect on PNI.


2005 ◽  
Vol 39 (5) ◽  
pp. 869-884 ◽  
Author(s):  
Audrey J Lee ◽  
Teresa B Chiao ◽  
Mildred P Tsang

OBJECTIVE: To evaluate the efficacy of sildenafil for treatment of pulmonary hypertension. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1977–March 2005), Cochrane Library, and International Pharmaceutical Abstracts (1977–March 2005) using the terms sildenafil and pulmonary hypertension. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. Studies including >5 patients with primarily adult populations were included in the review. DATA SYNTHESIS: The treatment of pulmonary hypertension is challenging. Sildenafil has recently been studied as monotherapy and in combination with other vasodilators in the management of pulmonary hypertension. Eight hemodynamic studies and 12 clinical trials were reviewed (1 retrospective, 3 double-blind, 8 open-label). Sildenafil reduced pulmonary arterial hypertension and pulmonary vascular resistance/peripheral vascular resistance index and tended to increase cardiac output/cardiac index compared with baseline. Sildenafil was comparable to nitric oxide and at least as effective as iloprost or epoprostenol in terms of its pulmonary vasoreactivity. Combination therapy with iloprost, nitric oxide, or epoprostenol resulted in enhanced and prolonged pulmonary vascular effects. Clinical trials suggest that sildenafil improves exercise tolerance and New York Heart Association functional class, but large, randomized controlled trials are needed to confirm these findings. Overall, sildenafil was well tolerated. CONCLUSIONS: Overall, sildenafil is a promising and well-tolerated agent for management of pulmonary hypertension. Further well-designed trials are warranted to establish its place in the treatment of pulmonary hypertension.


2003 ◽  
Vol 112 (6) ◽  
pp. 506-510 ◽  
Author(s):  
Marcus Haug ◽  
Michael Fritz ◽  
Olivia Dan ◽  
Robert R. Lorenz ◽  
Sophie Wimberley ◽  
...  

Using a rat model of laryngeal transplantation, we sought to define the relationships between acute laryngeal rejection grade (RG) and cyclosporin A (CSA) concentration and CSA dosage. Five recipient Lewis rat groups (N = 10 per group) were administered intramuscular CSA doses of 1.0 (group 1), 2.5 (group 2), 5.0 (group 3), 7.5 (group 4), and 10 mg/kg per day (group 5) for 14 days. Immediately before sacrifice, 5 mL of whole blood was obtained to assay CSA trough levels by high-performance liquid chromatography. The specimens were graded microscopically by blinded reviewers by day of RG, 0 to 14 days after transplantation, as described in earlier reports. Despite high intragroup variability in CSA levels, significantly different mean CSA concentrations were achieved among all CSA dosage groups: 1,2,3,4, and 5 (.0001 < p < .02). The mean laryngeal RGs did not test significantly different from each other with groups 3, 4, and 5 (RG, 2.3 ± 1.3 versus 1.9 ± 1.1 versus 1.7 ±0.3, respectively, .2 < p < .6). The RG for group 1 was significantly greater than those for groups 2 through 5 (p < .001), and the group 2 RG was greater (p < .02) than those for groups 3, 4, and 5. Polynomial fitting was used to determine the continuous relationship between each individual specimen's CSA concentration and the RG. Significant pathological allograft rejection correlated with CSA concentrations below 250 ng/mL.


2011 ◽  
Vol 21 (3) ◽  
pp. 292-298 ◽  
Author(s):  
Srinivas Laksmivenkateshiah ◽  
Anil K. Singhi ◽  
Balu Vaidyanathan ◽  
Edwin Francis ◽  
Sundaram R. Karimassery ◽  
...  

AbstractObjectivesTo examine the utility of decline in arterial partial pressure of oxygen after exercise as a marker of pulmonary vascular obstructive disease in patients with atrial septal defect and pulmonary hypertension.MethodsTreadmill exercise was performed in 18 patients with atrial septal defect and pulmonary hypertension. Arterial blood gas samples were obtained before and after peak exercise. A decline in the arterial pressure of oxygen of more than 10 millimetres of mercury after exercise was considered significant based on preliminary tests conducted on the controls. Cardiac catheterisation was performed in all patients and haemodynamic data sets were obtained on room air, oxygen, and a mixture of oxygen and nitric oxide (30–40 parts per million).ResultsThere were 10 patients who had more than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise and who had a basal pulmonary vascular resistance index of more than 7 Wood units per square metre. Out of eight patients who had less than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise, seven had a basal pulmonary vascular resistance index of less than 7 Wood units per square metre, p equals 0.0001. A decline in arterial partial pressure of oxygen of more than 10 millimetres of mercury predicted a basal pulmonary vascular resistance index of more than 7 Wood units per square metre with a specificity of 100% and a sensitivity of 90%.ConclusionsA decline in arterial partial pressure of oxygen following exercise appears to predict a high pulmonary vascular resistance index in patients with atrial septal defect and pulmonary hypertension. This test is a useful non-invasive marker of pulmonary vascular obstructive disease in this subset.


1976 ◽  
Vol 81 (3) ◽  
pp. 673-679 ◽  
Author(s):  
Hugo Scaglia ◽  
Martha Medina ◽  
Ada L. Pinto-Ferreira ◽  
Guadalupe Vazques ◽  
Carlos Gual ◽  
...  

ABSTRACT The plasma concentrations and episodic fluctuations of immunoreactive FSH and LH as well as the pituitary sensitivity to LH-RH stimulation were evaluated in post-menopausal women. The subjects were divided into 4 groups according to age. Group 1: 60–70 years old (n=11), group 2: 70–80 years old (n=22), group 3: 80–90 years old (n=31) and group 4: 90–100 years old (n=8). Standards used in gonadotrophin radioimmunoassays included the LER-907 preparation and a pooled post-menopausal serum. Since it was found that circulating gonadotrophins have an immunological pattern different from that shown by the pituitary preparation, the results were expressed in mIU/ml calculated accordingly to the immunological behaviour of pooled post-menopausal sera. The mean (± se) plasma levels of FSH (mIU/ml) were: group 1: 105.9 ± 9.5, group 2: 149.3 ± 10.5, group 3: 124.8 ± 7.1 and group 4: 149.4 ± 25.3. The mean (± se) plasma levels of LH (mIU/ml) were: group 1: 81.9 ± 12.5, group 2: 95.4 ± 9.9, group 3: 84.3 ± 7.7 and group 4: 113.5 ± 19.1. No statistically significant differences were observed among the 4 groups. One patient from each group was randomly selected in order to evaluate their LH and FSH episodic release as well as their pituitary responsiveness to exogenous stimulation. A pulsatile plasma pattern of gonadotrophin and a normal pituitary response to LH-RH injection were observed in the 4 patients studied. The results are interpreted as demonstrating that normal pituitary gonadotrophin function and pituitary reserve and responsiveness to exogenous stimulation are maintained in women of advanced age.


Author(s):  
Patrick E. Aba

AbstractBackgroundDiabetes is associated with both biochemical and haematological complications. Combination therapy has been advocated to mitigate some of these complications.AimThis study was designed to investigate the effects of glibenclamide andMethodsThirty male Wistar rats were assigned into five groups of six rats each. Groups 2–5 rats received intraperitoneally, 160 mg/kg of alloxan monohydrate while group 1 rats served as normal control. Groups 2–5 rats were respectively treated with 10 mL/kg distilled water (DW), 2 mg/kg glibenclamide, 200 mg/kg GL and 2 mg/kg glibenclamide and 200 mg/kg GL, while group 1 rats received 10 mL/kg DW. All treatments wereResultsCreatinine and BUN values of groups 3 and 4 rats were comparable to that of group 1 but were significantly (p<0.05) lower when compared with those of groups 2 and 5. There were significant (p<0.05) increases in the mean hepatic glycogen content, RBC, PCV, and Hb of group 4 rats when compared to those of group 2.ConclusionsIt was concluded that a combination of glibenclamide and


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