Cardiac dysfunction after acute endotoxin administration in conscious sheep

1991 ◽  
Vol 260 (5) ◽  
pp. H1474-H1481 ◽  
Author(s):  
K. Sugi ◽  
J. Newald ◽  
L. D. Traber ◽  
J. P. Maguire ◽  
D. N. Herndon ◽  
...  
Keyword(s):  
Sham Group ◽  
Systolic Pressure ◽  
Simultaneous Increase ◽  
Maximum Pressure ◽  
Ovine Model ◽  
Myocardial Depression ◽  
Dimension Analysis ◽  
Pressure Development ◽  
Pulmonary Arterial ◽  
Conscious Sheep

We evaluated cardiac function in an unanesthetized ovine model of hyperdynamic endotoxemia. The animals were instrumented for crystallographic dimension analysis of the left ventricle (LV) and measurement of LV, aortic, atrial, central venous, and pulmonary arterial pressures, and cardiac output. Seven sheep received 1.5 micrograms/kg of Escherichia coli endotoxin [lipopolysaccharide (LPS) LPS-P group] and were compared to a sham group. The sham group demonstrated no significant change in any of the variables. In the LPS-P group, the cardiac index increased (5.7 +/- 0.4 to 7.9 +/- 0.6 l.min-1.m-2) between 8 and 12 h after LPS. Concomitantly, the maximum elastance of LV end-systolic pressure-volume relations significantly decreased (2.88 +/- 0.27 mmHg/ml) compared with baseline (3.89 +/- 0.50 mmHg/ml). Other indexes of the LV contractility (maximum pressure development and ejection fraction) were also reduced. There was a simultaneous increase in the LV end-systolic and diastolic volumes. These findings confirm the hypothesis that there is a myocardial depression during LPS in the ovine model.

Thromboxane synthase inhibition and cardiopulmonary function during endotoxemia in sheep

1991 ◽  
Vol 71 (4) ◽  
pp. 1376-1381 ◽  
Author(s):  
K. Fujioka ◽  
K. Sugi ◽  
T. Isago ◽  
J. T. Flynn ◽  
L. D. Traber ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Systolic Pressure ◽  
Lymph Flow ◽  
Thromboxane Synthase ◽  
Thromboxane Synthase Inhibitor ◽  
Dimension Analysis ◽  
Pulmonary Arterial ◽  
Synthase Inhibitor ◽  
Lung Lymph ◽  
Lung Lymph Flow

We studied the cardiopulmonary response to endotoxin (lipopolysaccharide, LPS) in sheep with and without the administration of a thromboxane synthase inhibitor, OKY-046. The animals were instrumented for crystalographic dimension analysis of the left ventricle (LV) and for measurement of LV, aortic, left atrial, and pulmonary arterial pressures and cardiac index, as well as lung lymph flow. They received 1.0 micrograms/kg of Escherichia coli LPS with (n = 8) and without (n = 8) OKY-046 (10 mg/kg bolus, then 10 micrograms.kg-1.min-1). OKY-046 prevented the increase of pulmonary arterial pressure and the decrease of cardiac index that occurred during the early phase of endotoxemia. Between 8 and 12 h after LPS, cardiac index increased from 6.8 +/- 0.7 to 8.9 +/- 0.51.min-1.m-2. Concomitantly, the end-systolic pressure-diameter relationship (ESPDR, sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7. Other indexes of the LV contractility (+dP/dtmax) were also reduced. OKY-046 prevented the decreases of ESPDR and +dP/dtmax. OKY-046 also attenuated the increased lung lymph flow changes seen with LPS.

scholarly journals FRI0152 PULMONARY HYPERTENSION IN NEWLY DIAGNOSED SPANISH PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: DATA FROM THE RELES COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 660.2-660
Author(s):  
J. Álvarez Troncoso ◽  
Á. Robles Marhuenda ◽  
F. Mitjavila Villero ◽  
F. J. García Hernández ◽  
A. Marín Ballvé ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Pulmonary Hypertension ◽  
Lupus Erythematosus ◽  
Multivariable Analysis ◽  
Systolic Pressure ◽  
High Morbidity ◽  
Inception Cohort ◽  
Systemic Lupus ◽  
Factors Associated ◽  
Pulmonary Arterial

Background:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiorgan involvement. Pulmonary hypertension (PH) is an uncommon manifestation with high morbidity and mortality whose characteristics, prevalence and evolution in SLE are not completely defined.Objectives:Using data of patients from the inception cohort Registro Español de Lupus Eritematoso Sistémico (RELES), we aimed to to identify the factors associated with pulmonary hypertension (PH) in systemic lupus erythematosus (SLE).Methods:Prospective observational study on a multicenter Spanish inception cohort. Patients with SLE, diagnosed by the American College of Rheumatology (ACR) criteria, since January 2009, who had at least one transthoracic echocardiogram (TTE) performed were selected. Demographic data, diagnostic criteria, follow-ups, treatments and SLEDAI were analyzed.Results:Of 289 patients diagnosed with SLE with TTE performed, 15 (5.2%) patients were identified to have PH. Mean age was 56,9±7,7 years, of which 93,3% (14) were women and 80% (12) Caucasian. The ACR score at diagnosis was 4.66. Mean SLEDAI was 15. Only 5 patients had dyspnea at the time of diagnosis. Mean pulmonary arterial systolic pressure was 49.2±5.6 mmHg. Among the PH, 4 patients had pericarditis (26.6%), 3 (20%) valvulopathies (1 antiphospholipid syndrome), 1 patient pulmonary embolism and 1 shrinking lung. Multivariable analysis indicated that pericarditis (odds ratio (OR)=2.53), and valvulopathies (OR 8.96) were independently associated with the development of PH in SLE. Having PH was associated with older age at diagnosis (p<0.001), more dyspnea (p<0.001), higher ESR (p=0.007), more serositis (p<0.001), higher SLEDAI (p=0.011), higher SLICC (p <0.001), higher number of admissions (p=0.006) and higher mortality (p=0.003).Conclusion:PH in SLE is a serious comorbidity with high mortality. In the RELES cohort it was associated with increased disease activity, pericarditis and valvulopathies. Performing TTE in patients with SLE may favor early diagnosis and treatment.References:[1]Kim JS, Kim D, Joo YB, et al. Factors associated with development and mortality of pulmonary hypertension in systemic lupus erythematosus patients.Lupus. 2018;27(11):1769–1777.[2]Bazan IS, Mensah KA, Rudkovskaia AA, et al. Pulmonary arterial hypertension in the setting of scleroderma is different than in the setting of lupus: A review.Respir Med. 2018;134:42–46.Disclosure of Interests:Jorge Álvarez Troncoso: None declared, Ángel Robles Marhuenda: None declared, Francesca Mitjavila Villero: None declared, Francisco José García Hernández: None declared, Adela Marín Ballvé: None declared, Antoni Castro Consultant of: Actelion pharmaceuticals, GSK, MSD., Gonzalo Salvador Cervelló: None declared, Eva Fonseca: None declared, Isabel Perales Fraile: None declared, Guillermo Ruiz-Irastorza: None declared

Beta3-adrenergic stimulation restores endothelial mitochondrial dynamics and prevents pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Oliver ◽  
S.F Rocha ◽  
M Spaczynska ◽  
D.V Lalama ◽  
M Gomez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Therapeutic Strategy ◽  
Mitochondrial Dynamics ◽  
Systolic Pressure ◽  
Funding Source ◽  
Pulmonary Arterial

Abstract Background Endothelial dysfunction is one of the most important hallmarks of pulmonary arterial hypertension (PAH). This leads to anomalous production of vasoactive mediators that are responsible for a higher vascular tone and a subsequent increase in pulmonary artery pressure (PAP), and to an increased vascular permeability that favors perivascular inflammation and remodeling, thus worsening the disease. Therefore, preservation of the endothelial barrier could become a relevant therapeutic strategy. Purpose In previous studies, others and we have suggested the pharmacological activation of the β3-adrenergic receptor (AR) as a potential therapeutic strategy for pulmonary hypertension (PH) due to left heart disease. However, its potential use in other forms of PH remain unclear. The aim of the present study was to elucidate whether the β3-AR agonist mirabegron could preserve pulmonary endothelium function and be a potential new therapy in PAH. Methods For this purpose, we have evaluated the effect of mirabegron (2 and 10 mg/kg·day) in different animal models, including the monocrotaline and the hypoxia-induced PAH models in rats and mice, respectively. Additionally, we have used a transgenic mouse model with endothelial overexpression of human β3-AR in a knockout background, and performed in vitro experiments with human pulmonary artery endothelial cells (HPAECs) for mechanistic experiments. Results Our results show a dose dependent effect of mirabegron in reducing mean PAP and Right Ventricular Systolic Pressure in both mice and rats. In addition, the use of transgenic mice has allowed us to determine that pulmonary endothelial cells are key mediators of the beneficial role of β3-AR pathway in ameliorating PAH. Mechanistically, we have shown in vitro that activation of β3-AR with mirabegron protects HPAECs from hypoxia-induced ROS production and mitochondrial fragmentation by restoring mitochondrial fission/fusion dynamics. Conclusions This protective effect of mirabegron would lead to endothelium integrity and preserved pulmonary endothelial function, which are necessary for a correct vasodilation, avoiding increased permeability and remodeling. Altogether, the current study demonstrates a beneficial effect of the β3-AR agonist mirabegron that could open new therapeutic avenues in PAH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Programa de Atracciόn de Talento, Comunidad de Madrid

Serotonin transporter is not required for the development of severe pulmonary hypertension in the Sugen hypoxia rat model

2015 ◽  
Vol 309 (10) ◽  
pp. L1164-L1173 ◽  
Author(s):  
Michiel Alexander de Raaf ◽  
Yvet Kroeze ◽  
Anthonieke Middelman ◽  
Frances S. de Man ◽  
Helma de Jong ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Serotonin Transporter ◽  
Rat Model ◽  
Systolic Pressure ◽  
Serum Levels ◽  
Normal Function ◽  
Ventricular Systolic Pressure ◽  
Serotonin System ◽  
Pulmonary Arterial

Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild-type (WT) and knockout (KO) rats were exposed to the SuHx protocol. SERT KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs. 55 mmHg, intima thickness 38 vs. 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angioobliterative pulmonary hypertension in rats exposed to SuHx.

Hormonal changes in normal and polycythemic high-altitude natives

1995 ◽  
Vol 79 (3) ◽  
pp. 795-800 ◽  
Author(s):  
A. M. Antezana ◽  
J. P. Richalet ◽  
I. Noriega ◽  
M. Galarza ◽  
G. Antezana
Keyword(s):  
High Altitude ◽  
Systolic Pressure ◽  
Plasma Aldosterone ◽  
Control Group ◽  
Protective Mechanism ◽  
Hormonal Changes ◽  
Plasma Aldosterone Concentration ◽  
Pulmonary Arterial ◽  
Exercise Induced ◽  
Acute And Chronic Exposure

Acute and chronic exposure to high-altitude (HA) hypoxia inhibits the renin-angiotensin-aldosterone system and may modify the release of atrial natriuretic peptide (ANP) in sea-level (SL) natives. In HA natives, the release of these hormones could be influenced by changes in blood volume or pulmonary arterial pressure. Twenty-four men residing in La Paz, Bolivia, at 3,600 m were separated into two groups: one normocythemic (HAN; with hematocrit < 57%; n = 13) and the other polycythemic (HAP; with hematocrit > 57%; n = 11). A control group of 9 SL residents was studied in normoxia (SLN) as well as after 4 days spent at 4,350 m (SLH). The groups were tested for plasma active renin (PAR), plasma aldosterone concentration, ANP, and potassium and norepineprine concentrations at rest and after a maximal exercise. Pulmonary arterial systolic pressure was assessed by a Doppler technique. It was observed that PAR and plasma aldosterone concentration at rest and after exercise were lower in the SLH than in the SLN group. PAR and norepineprine concentration were higher among highlanders than in the SLN group. Renin response to exercise was normal among the HAN group and slightly decreased among the HAP group, and an exercise-induced increase in aldosterone was attenuated in both HA groups. Aldosterone response to renin was maintained among the SLH group but was attenuated in the HA groups, possibly owing to a protective mechanism against salt and water retention. Resting and exercise ANP was lower in the HA groups than in the SLN group.

Abstract 532: New Agonist of A2a Receptor Reduces Ventricular and Vascular Dysfunction in Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Allan K Alencar ◽  
Sharlene L Pereira ◽  
Arthur E Kummerle ◽  
Sharon S Langraf ◽  
Celso Caruso-Neves ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Systolic Pressure ◽  
Pulmonary Tissue ◽  
A2a Receptor ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance with subsequent remodeling and right ventricular hypertrophy. Vascular reactivity and ventricular function were investigated in rats with monocrotaline-induced PAH and treated with a new N-acylhydrazone derivative named as LASSBio-1359. METHODS: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Male Wistar rats received a single i.p. injection of monocrotaline (MCT) (60 mg/kg) for PAH induction and were randomly divided in groups which were treated with: saline, vehicle and LASSBio-1359 (50 mg/kg p.o.). After 14 days of treatment, some parameters were evaluated: pulmonary acceleration time (PAT); right ventricular systolic pressure (RVSP); vascular reactivity to acetylcholine; expression of iNOS in pulmonary tissue; wall thickness of pulmonary artery (PAWT). Results: PAT (ms) was increased from 26.2 ± 2.8 to 41.3 ± 3.9 in PAH group treated with vehicle (n=8, p<0.05) and was reduced to 24.2 ± 1.7 when PAH group was treated with LASSBio-1359. RVSP (mmHg) increased from 26.0 ± 2.0 to 55.2 ± 2.3 in PAH group (p<0.05) but was similar to control after treatment with LASSBio-1359 (31.8 ± 2.3 mm Hg). Ratio of right ventricle and body weight (mg/g) was 0.66 ± 0.02, 1.63 ± 0.16 and 0.87 ± 0.10 for control, vehicle- and LASSBio-1359-treated PAH groups, respectively. PAH promoted ventricular dysfunction which was reduced by LASSBio-1359. The pulmonary artery maximum relaxation (%) was 57.3 ± 5.5, 43.6 ± 1.2 and 61.4 ± 8.4 for control, vehicle and LASSBio-1359-treated groups indicating that PAH promoted endothelium injury which was recovered by LASSBio-1359. iNOS expression in pulmonary tissue was increased from 0.48 ± 1.31 to 0.98 ± 3.14 in PAH group and reduced to 0.53 ± 1.83 in rats treated with LASSBio-1359. The PAWT (%) were increased from 74.1 ± 1.3 to 90.2 ± 2.7 in PAH group (p<0.05) but was 74.4 ± 1.3 when treated with LASSBio-1359. This compound showed an in vitro vasodilatory activity mediated by activation of adenosinergic A2A receptor. Conclusion: LASSBio-1359 reduced ventricular and vascular dysfunction in monocrotaline-induced PAH in rats indicating a possible new alternative to treat PAH.

Direct measurement of flow from the posterior lymph hearts of hydrated and dehydrated toads (Bufo marinus).

1997 ◽  
Vol 200 (11) ◽  
pp. 1695-1702 ◽  
Author(s):  
J M Jones ◽  
A K Gamperl ◽  
A P Farrell ◽  
D P Toews
Keyword(s):  
Heart Rate ◽  
Stroke Volume ◽  
Systolic Pressure ◽  
Lymph Flow ◽  
Bufo Marinus ◽  
Experimental Chamber ◽  
Doppler Flow ◽  
Simultaneous Measurements ◽  
Pressure Development ◽  
Lymph Heart

Flow from the posterior lymph hearts of Bufo marinus was measured using Doppler flow probes. These probes were placed on the posterior vertebral vein and recorded flow as lymph was ejected from the heart. In resting, hydrated toads, mean lymph flow from one of the paired posterior lymph hearts was 25.9 +/- 4.9 ml kg-1 h-1, stroke volume was 8.9 +/- 1.4 microL kg-1 and lymph heart rate was 47.5 +/- 3.7 beats min-1. We estimate that, together, the paired posterior lymph hearts are capable of generating flows that are approximately one-sixtieth of the resting cardiac output. Mean peak systolic pressure developed by the posterior lymph hearts was 1.62 +/- 0.08 kPa. Simultaneous measurements of lymph heart pressure development and flow revealed that the outflow pore of the heart opened at a pressure of 0.71 +/- 0.04 kPa, approximately 113 +/- 5 ms into systole. When toads were moderately disturbed, stroke volume increased by as much as fourfold with little change in lymph heart rate (&lt; 5 beats min-1). When toads were dehydrated, lymph flow decreased by 70% at 12h and by 80% and 24h. Since there was only a modest non-significant decrease in lymph heart rate (30%), this reduction in flow was attributed to decreases in stroke volume (approximately 80%). Lymph heart flow and stroke volume returned to control values 30 min after adding water back into the experimental chamber. Stroke volume was clearly more important in regulating lymph flow than lymph heart rate under these conditions in Bufo marinus.

Effects of Crocin on CCL2/CCR2 Inflammatory Pathway in Monocrotaline-Induced Pulmonary Arterial Hypertension Rats

2021 ◽  
pp. 1-19
Author(s):  
Yanling Sheng ◽  
Xiaowei Gong ◽  
Jing Zhao ◽  
Yan Liu ◽  
Yadong Yuan
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Stress Responses ◽  
Systolic Pressure ◽  
Pathological Feature ◽  
Arterial Remodeling ◽  
Inflammatory Pathway ◽  
Ventricular Systolic Pressure ◽  
Rat Models ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary disease, in which pulmonary arterial remodeling is regarded as the prominent pathological feature. So far, the mechanism of PAH is still unclear, so its treatment remains a challenge. However, inflammation plays an important part in the occurrence and progression of PAH. It is well known that crocin has anti-inflammatory properties, so we investigated whether crocin could be a potential drug for the treatment of PAH rat models. Rats injected subcutaneously with monocrotaline (MCT) were treated with crocin via a gastric tube daily for four weeks. The results showed that crocin treatment significantly reduced the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) in the PAH rat models. Moreover, crocin treatment reduced the proliferation of pulmonary arteriole smooth muscle cells (PASMCs). In addition, crocin treatment not only relieved inflammatory cell infiltration and collagen fiber hyperplasia in the lung and right ventricle, but also decreased the expression of the CCL2/CCR2 inflammatory pathway in the lung of PAH rat models. Furthermore, crocin treatment reduced the inflammatory cytokines and oxidative stress responses. In summary, crocin may play a protective role in MCT-induced PAH rats by alleviating inflammatory response, improving pulmonary arterial remodeling, and preventing PAH. Therefore, crocin as a new treatment for PAH may be quite worthy of consideration.

Rhythm effects on contractility of the beating isovolumic left ventricle

1960 ◽  
Vol 199 (6) ◽  
pp. 1115-1120 ◽  
Author(s):  
B. Lendrum ◽  
H. Feinberg ◽  
E. Boyd ◽  
L. N. Katz
Keyword(s):  
Heart Rate ◽  
Left Ventricle ◽  
Systolic Pressure ◽  
Ventricular Volume ◽  
Contractile Force ◽  
Postextrasystolic Potentiation ◽  
Pressure Development ◽  
Induced Changes ◽  
Electrical Alternans

Variation in contractile force of the isovolumic contracting left ventricle of the dog was studied in open-chested in situ hearts. The electrocardiogram and intraventricular pressures were recorded at various heart volumes. Spontaneous changes in heart rate and rhythm occurred at all volumes. Isovolumic systolic pressure development (contractile force) varied with rate and rhythm. Contractile force increased with heart rate (treppe) regardless of pacemaker origin. When a premature beat was followed by a compensatory pause, the premature beat showed a decrease and the next beat an increase in contractile force (postextrasystolic potentiation). The magnitude of the changes varied directly with the prematurity of the beat. Mechanical alternans was observed with electrical alternans, despite the absence of significant volume change. Rate-induced changes, postextrasystolic potentiation and mechanical alternans were additive when they occurred simultaneously. For practical purposes, ventricular volume (filling), hence muscle fiber length, remained constant during these rate and rhythm change, therefore could not affect the strength of contraction. Contractile force changes directly attributable to rate and rhythm changes do, therefore, occur in the intact mammalian heart.

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