scholarly journals Tirilazad mesylate (U-74006F) inhibits effects of endotoxin in dogs

1995 ◽  
Vol 268 (5) ◽  
pp. H1847-H1855 ◽  
Author(s):  
H. Zhang ◽  
H. Spapen ◽  
P. Manikis ◽  
P. Rogiers ◽  
G. Metz ◽  
...  
Keyword(s):  
Endotoxic Shock ◽  
Left Ventricular ◽  
Oxygen Extraction ◽  
Volume Index ◽  
Whole Body ◽  
Control Group ◽  
Stroke Work ◽  
Critical Oxygen ◽  
Group 3 ◽  
Group 2

The present study explored the effects of a potent antioxidant, the 21-aminosteroid U-74006F, on the systemic and regional hemodynamics and the oxygen extraction capabilities during endotoxic shock. Twenty-four anesthetized dogs were randomized into three groups. Group 1 (n = 8) served as control. Group 2 (n = 8) and group 3 (n = 8) received 2 mg/kg iv of Escherichia coli endotoxin, followed 30 min later by saline infusion. Group 3 was given U-74006F as an intravenous bolus of 80 micrograms/kg followed by an infusion of 10 micrograms.kg-1.min-1, and group 2 received an equivalent volume of vehicle. Tamponade was induced 30 min later to study the oxygen extraction capabilities of the animals. Compared with the endotoxin-alone group, the U-74006F-treated dogs maintained higher mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index and lower pulmonary vascular resistance. They also showed a higher fractional blood flow to mesenteric and renal beds. Endotoxin administration increased whole body critical oxygen delivery (DO2crit) from 7.7 +/- 2.4 to 12.0 +/- 1.9 ml.kg-1.min-1 (P < 0.05), but U-74006F decreased DO2crit to 7.8 +/- 2.0 ml.kg-1.min-1 (P < 0.05 vs. endotoxin alone). Endotoxin decreased critical oxygen extraction ratio (O2ERcrit) from 75.0 +/- 12.7 to 44.3 +/- 8.7% (P < 0.05), but U-74006F increased O2ERcrit to 64.1 +/- 11.2% (P < 0.05 vs. endotoxin alone). U-74006F also decreased endotoxin-induced elevation of mesenteric and renal DO2crit and markedly increased regional O2ERcrit. Systemic and regional blood lactate concentrations were lower in the U-74006F-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Diaspirin cross-linked hemoglobin improves oxygen extraction capabilities in endotoxic shock

2000 ◽  
Vol 89 (4) ◽  
pp. 1437-1444 ◽  
Author(s):  
Jacques Creteur ◽  
Haibo Zhang ◽  
Daniel De Backer ◽  
Qinghua Sun ◽  
Jean-Louis Vincent
Keyword(s):  
Blood Flow ◽  
Cardiac Index ◽  
Cardiac Tamponade ◽  
Regional Blood Flow ◽  
Endotoxic Shock ◽  
Oxygen Extraction ◽  
Whole Body ◽  
Control Group ◽  
Tissue Oxygen ◽  
Critical Oxygen

We studied the effects of diaspirin cross-linked hemoglobin (DCLHb), a cell-free hemoglobin derived from human erythrocytes, on blood flow distribution and tissue oxygen extraction capabilities in endotoxic shock. Eighteen pentobarbital sodium-anesthetized, mechanically ventilated dogs received 2 mg/kg of E. coli endotoxin, followed by saline resuscitation to restore cardiac filling pressures to baseline levels. The animals were randomly divided into three groups: six served as control, six received DCLHb at a dose of 500 mg/kg ( group 1) and six DCLHb at a dose of 1,000 mg/kg ( group 2). Cardiac tamponade was then induced by saline injection in the pericardial sac to progressively reduce cardiac index and thereby allow study of tissue oxygen extraction capabilities. DCLHb had a dose-dependent vasopressor effect but did not significantly alter cardiac index or regional blood flow. During cardiac tamponade, critical oxygen delivery was 12.8 ± 0.7 ml · kg−1 · min−1 in the control group, but 8.6 ± 0.9 and 8.2 ± 0.7 ml · kg−1 · min−1 in groups 1 and 2, respectively (both P < 0.05 vs. control group). The critical oxygen extraction ratio was 39.1 ± 3.1% in the control group but 58.7 ± 12.8% and 60.2 ± 9.0% in groups 1and 2, respectively. We conclude that DCLHb can improve whole body oxygen extraction capabilities during endotoxic shock in dogs.

Vasopressin vs. norepinephrine in endotoxic shock: systemic, renal, and splanchnic hemodynamic and oxygen transport effects

2003 ◽  
Vol 95 (2) ◽  
pp. 803-809 ◽  
Author(s):  
Jorge A. Guzman ◽  
Ariosto E. Rosado ◽  
James A. Kruse
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Endotoxic Shock ◽  
Venous Blood ◽  
Study Groups ◽  
Left Ventricular ◽  
Metabolic Effects ◽  
Venous Blood Flow ◽  
Stroke Work ◽  
Group 2

The effects of intravenous norepinephrine (NE, group 1) and vasopressin (AVP, group 2) infusions on systemic, splanchnic, and renal circulations were studied in anesthetized dogs under basal conditions and during endotoxic shock. Under basal conditions, AVP infusion induced a 12 ± 7% drop in left ventricular stroke work, a 45 ± 5% fall in portal venous blood flow, and a 31 ± 13% decrease in intestinal mucosal blood flow ( P < 0.05). AVP also decreased splanchnic oxygen delivery (Do2) and increased splanchnic and renal oxygen extraction significantly during basal conditions. Except for more pronounced brady-cardia among animals in group 2, the systemic and splanchnic changes were comparable between study groups during endotoxic shock. AVP infusion restored renal blood flow and Do2 in endotoxic shock compared with animals resuscitated with NE, which had persistently low renal blood flow and Do2. Our data demonstrate that, in contrast to NE, administration of AVP effectively restores renal blood flow and Do2 with comparable systemic and splanchnic hemodynamic and metabolic effects in endotoxin-induced circulatory shock.

Abstract 2488: Correlation Between The Severity Of Diastolic Dysfunction And Cardiac Torsion

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sung-Ji Park ◽  
Chinami Miyazaki ◽  
Charles J Bruce ◽  
Diego Bellavia ◽  
Fletcher A Miller ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Early Stage ◽  
Mitral Annulus ◽  
Left Ventricular ◽  
Control Group ◽  
Compensatory Mechanism ◽  
Diastolic Velocity ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Backgrounds: Left ventricular torsion (LVtor) is an integral part of systole and untwisting plays an important role in diastole. The aim of this study was to characterize LVtor and untwisting in different grades of diastolic dysfunction. Methods: We studied 135 patients with normal LV EF with various grades of diastolic dysfunction (40 group1:mild,42 group 2:moderate,and 22 group 3:severe dysfunction) and 31 controls with normal diastolic function. Apical and basal short axis rotations were measured by 2D STE. LVtor was defined as net difference between apical and basal rotation. Results: Age, gender, and EF were similar in 3 groups and control. Mitral annulus early diastolic velocity was reduced in all 3 groups (see table ). Peak LVtor was significantly greater in group 1 compared with control, group 2 and group 3. The time from peak LVtor to Mitral valve opening, and to peak early diastolic velocity were significantly delayed in group 1 compared to control (p=0.0030 and 0.0409, respectively). The twisting rate and untwisting rate were found to be highest in group 1. Conclusions: Systolic torsion and diastolic untwisting are significantly increased in patients with mild diastolic dysfunction. In patients with advanced diastolic dysfunction with increased filling pressure, torsion and untwisting are normalized. Hence, vigorous LV torsion appears to be a compensatory mechanism during an early stage of diastolic dysfunction to maintain normal filling in the setting of reduced longitudinal myocardial motion.

Effects of isoproterenol on myocardial relaxation rate: influence of the level of load

1993 ◽  
Vol 265 (5) ◽  
pp. H1645-H1653 ◽  
Author(s):  
N. Coudray ◽  
J. P. Beregi ◽  
Y. Lecarpentier ◽  
D. Chemla
Keyword(s):  
Relaxation Rate ◽  
Muscle Length ◽  
Dose Dependence ◽  
Left Ventricular ◽  
Control Group ◽  
Shortening Velocity ◽  
Myocardial Relaxation ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The present work was undertaken to test the hypothesis that the level of the load faced by the myocardium influences the effects of isoproterenol on relaxation rate. Responses to cumulative doses of isoproterenol (from 10(-10) to 10(-6) M) were studied in rat left ventricular papillary muscle stimulated 12 beats/min at 29 degrees C in 0.5 mM extracellular calcium and preloaded at initial muscle length corresponding to apex of length-active tension curve (Lmax; group 1, n = 20) or at 95% of Lmax (group 2, n = 9). A control group (group 3, n = 8) was studied every 15 min for 75 min. We measured maximum unloaded shortening velocity (Vmax), normalized positive and negative peak force derivatives (+dF and -dF, respectively) of the fully isometric twitch, and peak lengthening velocity of the isotonic twitch with preload only (Vlmax). In group 1, Vmax and +dF increased under 10(-10) and 10(-9) M isoproterenol, respectively, and -dF increased under 10(-9) M isoproterenol (115 +/- 13 vs. 96 +/- 12 mN.s-1.mm-2, P = 0.01). Conversely, Vlmax increased under 10(-7) M isoproterenol only (2.34 +/- 0.19 vs. 1.45 +/- 0.18 Lmax/s, P < 0.001). In group 2, both -dF and Vlmax increased under 10(-7) M isoproterenol only (P = 0.015 and 0.011, respectively). In group 3, -dF and Vlmax did not vary in time. Our results suggest a load-revealed (or length-revealed) difference in the dose dependence of the various biochemical processes involved in the effects of isoproterenol during myocardial relaxation.

scholarly journals Protective effects of N-acetyl-L-cysteine in endotoxemia

1994 ◽  
Vol 266 (5) ◽  
pp. H1746-H1754 ◽  
Author(s):  
H. Zhang ◽  
H. Spapen ◽  
D. N. Nguyen ◽  
M. Benlabed ◽  
W. A. Buurman ◽  
...  
Keyword(s):  
Cell Damage ◽  
Left Ventricular ◽  
Oxygen Extraction ◽  
Control Group ◽  
Stroke Work ◽  
Protective Effects ◽  
Oxygen Extraction Ratio ◽  
Endotoxin Challenge ◽  
Stroke Work Index ◽  
Ventricular Stroke Work Index

Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Normovolemic hemodilution improves oxygen extraction capabilities in endotoxic shock

2001 ◽  
Vol 91 (4) ◽  
pp. 1701-1707 ◽  
Author(s):  
Jacques Creteur ◽  
Qinghua Sun ◽  
Omar Abid ◽  
Daniel De Backer ◽  
Philippe Van Der Linden ◽  
...  
Keyword(s):  
Endotoxic Shock ◽  
Tissue Perfusion ◽  
Canine Model ◽  
Extraction Ratio ◽  
Oxygen Extraction ◽  
Whole Body ◽  
Oxygen Extraction Ratio ◽  
Mechanically Ventilated ◽  
Critical Oxygen ◽  
Normovolemic Hemodilution

We studied the effects of normovolemic hemodilution on tissue oxygen extraction capabilities in a canine model of endotoxic shock. Eighteen anesthetized and mechanically ventilated dogs underwent normovolemic hemodilution with 6% hydroxyethyl starch solution to reach hematocrit (Hct) levels around 40, 30, or 20% before the administration of 2 mg/kg of Escherichia coli endotoxin. Cardiac tamponade was then induced by repeated injections of normal saline into the pericardial sac to reduce cardiac output and study whole body oxygen extraction capabilities. Whole body critical oxygen delivery was lower in the Hct 20% and 30% groups (8.4 ± 0.4 and 10.4 ± 0.7 ml · kg−1 · min−1, respectively) than in the Hct 40% group (12.8 ± 0.8 ml · kg−1 · min−1) (both P < 0.005). The whole body critical oxygen extraction ratio was higher in the Hct 30% and 20% groups (49.1 ± 8.2 and 55.2 ± 4.6%, respectively) than in the Hct 40% group (37.1 ± 4.4 %) (both P < 0.05). Liver critical oxygen extraction ratio was also higher in the Hct 30% and 20% groups than in the Hct 40% group. The arterial lactate concentrations and the gradient between ileum mucosal Pco 2 and arterial Pco 2 were lower in the Hct 20% and 30% groups than in the Hct 40% group. We conclude that, during an acute reduction in blood flow during endotoxic shock in dogs, normovolemic hemodilution is associated with improved tissue perfusion and increased oxygen extraction capabilities.

scholarly journals Hypertrophy of unaffected cardiomyocytes correlates with severity of cardiomyopathy in female patients with Fabry disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Cristina Chimenti ◽  
Romina Verardo ◽  
Andrea Frustaci
Keyword(s):  
Fabry Disease ◽  
Wall Thickness ◽  
Left Ventricular ◽  
Female Patients ◽  
Maximal Wall Thickness ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.

scholarly journals Preservation of Contractile Reserve and Diastolic Function by Inhibiting the NLRP3 Inflammasome with OLT1177® (Dapansutrile) in a Mouse Model of Severe Ischemic Cardiomyopathy Due to Non-Reperfused Anterior Wall Myocardial Infarction

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3534
Author(s):  
Joseph Aliaga ◽  
Aldo Bonaventura ◽  
Eleonora Mezzaroma ◽  
Yogesh Dhakal ◽  
Adolfo Gabriele Mauro ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Function ◽  
Nlrp3 Inflammasome ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Control Group ◽  
Contractile Reserve ◽  
Standard Diet ◽  
Group 3 ◽  
Group 1

Interleukin-1β (IL-1β), a product of the NLRP3 inflammasome, modulates cardiac contractility and diastolic function. We proposed that OLT1177® (dapansutrile), a novel NLRP3 inhibitor, could preserve contractile reserve and diastolic function after myocardial infarction (MI). We used an experimental murine model of severe ischemic cardiomyopathy through the ligation of the left coronary artery without reperfusion, and after 7 days randomly assigned mice showing large anterior MI (>4 akinetic segments), increased left ventricular (LV) dimensions ([LVEDD] > 4.4 mm), and reduced function (LV ejection fraction <40%) to a diet that was enriched with OLT1177® admixed with the chow in the diet at 3.75 g/kg (Group 1 [n = 10]) or 7.5 g/kg (Group 2 [n = 9]), or a standard diet as the no-treatment control group (Group 3 [n = 10]) for 9 weeks. We measured the cardiac function and contractile reserve with an isoproterenol challenge, and the diastolic function with cardiac catheterization at 10 weeks following the MI surgery. When compared with the control (Group 3), the mice treated with OLT1177 (Group 1 and 2) showed significantly greater preservation of their contractile reserve (the percent increase in the left ventricular ejection fraction [LVEF] after the isoproterenol challenge was +33 ± 11% and +40 ± 6% vs. +9 ± 7% in the standard diet; p < 0.05 and p < 0.005 for Group 1 and 2, respectively) and of diastolic function measured as the lower left ventricular end-diastolic pressure (3.2 ± 0.5 mmHg or 4.5 ± 0.5 mmHg vs. 10.0 ± 1.6 mmHg; p < 0.005 and p < 0.009 respectively). No differences were noted between the resting LVEF of the MI groups. These effects were independent of the effects on the ventricular remodeling after MI. NLRP3 inflammasome inhibition with OLT1177® can preserve β-adrenergic responsiveness and prevent left ventricular diastolic dysfunction in a large non-reperfused anterior MI mouse model. OLT1177® could therefore be used to prevent the development of heart failure in patients with ischemic cardiomyopathy.

scholarly journals Heart in Acromegaly: The Echocardiographic Characteristics of Patients Diagnosed with Acromegaly in Various Stages of the Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Agata Popielarz-Grygalewicz ◽  
Jakub S. Gąsior ◽  
Aleksandra Konwicka ◽  
Paweł Grygalewicz ◽  
Maria Stelmachowska-Banaś ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Healthy Volunteers ◽  
Global Longitudinal Strain ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Volume Index ◽  
Control Group ◽  
Glucose Metabolism Disorders ◽  
Acromegalic Cardiomyopathy ◽  
The Right

To determine whether the echocardiographic presentation allows for diagnosis of acromegalic cardiomyopathy. 140 patients with acromegaly underwent echocardiography as part of routine diagnostics. The results were compared with the control group comprising of 52 age- and sex-matched healthy volunteers. Patients with acromegaly presented with higher BMI, prevalence of arterial hypertension, and glucose metabolism disorders (i.e., diabetes and/or prediabetes). In patients with acromegaly, the following findings were detected: increased left atrial volume index, increased interventricular septum thickness, increased posterior wall thickness, and increased left ventricular mass index, accompanied by reduced diastolic function measured by the following parameters: E’med., E/E’, and E/A. Additionally, they presented with abnormal right ventricular systolic pressure. All patients had normal systolic function measured by ejection fraction. However, the values of global longitudinal strain were slightly lower in patients than in the control group; the difference was statistically significant. There were no statistically significant differences in the size of the right and left ventricle, thickness of the right ventricular free wall, and indexed diameter of the ascending aorta between patients with acromegaly and healthy volunteers. None of 140 patients presented systolic dysfunction, which is the last phase of the so-called acromegalic cardiomyopathy. Some abnormal echocardiographic parameters found in acromegalic patients may be caused by concomitant diseases and not elevated levels of GH or IGF-1 alone. The potential role of demographic parameters like age, sex, and/or BMI requires further research.

Use of Continuous Blood Volume Monitoring to Detect Inadequately High Dry Weight

1996 ◽  
Vol 19 (7) ◽  
pp. 411-414 ◽  
Author(s):  
F. Lopot ◽  
P. Kotyk ◽  
J. Bláha ◽  
J. Forejt
Keyword(s):  
Blood Volume ◽  
Vena Cava ◽  
Extracellular Fluid ◽  
Dry Weight ◽  
Whole Body ◽  
The Status ◽  
Varying Length ◽  
Group 3 ◽  
Group 2 ◽  
Total Body

A continuous blood volume monitoring (CBVM) device (Inline Diagnostics, Riverdale, USA) was used to study response to prescribed ultrafiltration during haemodialysis (HD) in 66 stabilised HD patients. Fifty percent of patients showed the expected linear decrease in BV right from the beginning of HD (group 1), 32% exhibited no decrease at all (group 2), while eighteen percent formed the transient group 3 which showed a plateau of varying length after which a decrease occurred. The correct setting of dry weight was verified through evaluation of the ratio of extracellular fluid volume to total body water (VEC/TBW) in 26 patients by means of whole body multifrequency impedometry MFI (Xitron Tech., San Diego, USA) and through measurement of the Vena Cava Inferior diameter (VCID) pre and post HD (in 6 and 5 patients from groups 1 and 3 and from group 2, respectively). The mean VEC/TBW in groups 1 and 3 was 0.56 pre and 0.51 post HD as compared to 0.583 and 0.551 in group 2. VCID decreased on average by 14.1% in groups 1 and 3 but remained stable in group 2. Both findings thus confirmed inadequately high estimation of dry weight. Since CBVM is extremely easy to perform it can be used as a method of choice in detecting inadequately high prescribed dry weight. The status of the cardiovascular system must always be considered before final judgement is made.

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