Effects of nitric oxide synthase inhibitor on hemodynamic change and O2 delivery in septic dogs

1995 ◽  
Vol 268 (5) ◽  
pp. H2017-H2023 ◽  
Author(s):  
C. Mitaka ◽  
Y. Hirata ◽  
K. Ichikawa ◽  
T. Uchida ◽  
K. Yokoyama ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Septic Shock ◽  
Cardiac Index ◽  
Systemic Vascular Resistance ◽  
Oxygen Delivery ◽  
Resistance Index ◽  
No Synthase ◽  
Systemic Vascular Resistance Index ◽  
Induced Hypotension ◽  
Synthase Inhibitor

To elucidate the role of nitric oxide (NO) in septic shock, we measured hemodynamic and pulmonary gas changes in anesthetized dogs after intravenous administration of bacterial lipopolysaccharide (LPS) with or without NO synthase inhibitor, NG-nitro-L-arginine (L-NNA). Infusion of LPS (250 ng.kg-1.min-1) for 2 h decreased mean arterial pressure over 1-4 h. Although L-NNA (10 mg/kg) blocked LPS-induced hypotension, it decreased cardiac index, oxygen delivery index, arterial pH, and arterial PO2 and increased systemic vascular resistance index in the presence or absence of LPS. Administration of NG-nitro-D-arginine (D-NNA, 10 mg/kg) alone caused fewer hemodynamic effects (increased systemic vascular resistance index and decreased cardiac index) than L-NNA alone. Our study provides evidence that L-NNA prevents endotoxin-induced hypotension but decreases cardiac output and oxygen delivery, effects that may, in part, be due to a nonspecific NO synthase-independent event. Thus clinical use of NO synthase inhibitors for the treatment of septic shock should be cautiously considered.

Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition

1994 ◽  
Vol 76 (6) ◽  
pp. 2785-2793 ◽  
Author(s):  
J. Meyer ◽  
F. Hinder ◽  
J. Stothert ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Index ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Resistance Index ◽  
No Synthase ◽  
Organ Blood Flow ◽  
Systemic Vascular Resistance Index ◽  
Blood Flows ◽  
Regional Blood Flows

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.

scholarly journals Maintaining oxygen delivery is crucial to prevent intestinal ischemia in critical ill patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254352
Author(s):  
Jochen J. Schoettler ◽  
Thomas Kirschning ◽  
Michael Hagmann ◽  
Bianka Hahn ◽  
Anna-Meagan Fairley ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Oxygen Saturation ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Oxygen Delivery ◽  
Intestinal Ischemia ◽  
Arterial Oxygen Saturation ◽  
Resistance Index ◽  
Arterial Oxygen ◽  
Systemic Vascular Resistance Index

Background Intestinal ischemia is a common complication with obscure pathophysiology in critically ill patients. Since insufficient delivery of oxygen is discussed, we investigated the influence of oxygen delivery, hemoglobin, arterial oxygen saturation, cardiac index and the systemic vascular resistance index on the development of intestinal ischemia. Furthermore, we evaluated the predictive power of elevated lactate levels for the diagnosis of intestinal ischemia. Methods In a retrospective case-control study data (mean oxygen delivery, minimum oxygen delivery, systemic vascular resistance index) of critical ill patients from 02/2009–07/2017 were analyzed using a proportional hazard model. General model fit and linearity were tested by likelihood ratio tests. The components of oxygen delivery (hemoglobin, arterial oxygen saturation and cardiac index) were individually tested in models. Results 59 out of 874 patients developed intestinal ischemia. A mean oxygen delivery less than 250ml/min/m2 (LRT vs. null model: p = 0.018; LRT for non-linearity: p = 0.012) as well as a minimum oxygen delivery less than 400ml/min/m2 (LRT vs null model: p = 0.016; LRT for linearity: p = 0.019) were associated with increased risk of the development of intestinal ischemia. We found no significant influence of hemoglobin, arterial oxygen saturation, cardiac index or systemic vascular resistance index. Receiver operating characteristics analysis for elevated lactate levels, pH, CO2 and central venous saturation was poor with an area under the receiver operating characteristic of 0.5324, 0.52, 0.6017 and 0.6786. Conclusion There was a significant correlation for mean and minimum oxygen delivery with the incidence of intestinal ischemia for values below 250ml/min/m2 respectively 400ml/min/m2. Neither hemoglobin, arterial oxygen saturation, cardiac index, systemic vascular resistance index nor elevated lactate levels could be identified as individual risk factors.

Pathogenetic mechanisms of venous congestion after the Fontan procedure

2001 ◽  
Vol 11 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Reiner Buchhorn ◽  
Dietmar Bartmus ◽  
Wolfgang Buhre ◽  
Joachim Bürsch
Keyword(s):  
Cardiac Index ◽  
Capillary Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Postoperative Period ◽  
Venous Pressure ◽  
Resistance Index ◽  
Venous Congestion ◽  
Systemic Vascular Resistance Index ◽  
Central Venous

Background: The hemodynamic status after a Fontan type procedure for definitive palliation of functionally univentricular hearts is dominated by a high central venous pressure, which seems to be one of several factors responsible for venous congestion appearing as a frequent complication in the early and late postoperative course. The purpose of our study was to find other hemodynamic parameters correlating with the presence of venous congestion and effusions in these patients. Methods: We compared the hemodynamic data of 18 patients who had an uneventful long-term course after a Fontan type procedure with the respective data of 10 patients who developed symptoms of venous congestion in the immediate postoperative period. Based on a theoretical model, we developed an algorithm to calculate mean hydrostatic capillary pressure from mean arterial pressure, systemic vascular resistance index and central venous pressure. Results: Pulmonary vascular resistance index (2.1 ± 1.0 mmHg L-1 min m2), mean left atrial pressure (9.7 ± 4.0 mmHg) and cardiac index (3.6 ± 0.6 1/min/m2) are mainly normal in patients with venous congestion in the immediate postoperative period, but mean hydrostatic capillary pressure is significantly higher compared to patients without venous congestion (24.3 ± 3.1 vs 18.3 ± 4.0 mmHg). Lower mean hydrostatic capillary pressures in these patients are due to a highly significant increase of systemic vascular resistance index (18.6 ± 4.2 versus 33.6 ± 6.6 mmHg L-1 min m2) and a concomitant decrease of cardiac index to 2.4 ± 0.3 1/min/m2. Conclusions: The increase of mean hydrostatic capillary pressure, caused by high central venous pressures but also by relatively low systemic vascular resistance indexes, seems to be the hemodynamic key parameter responsible for venous congestion and effusions in patients after a Fontan type procedure in the immediate postoperative period.

scholarly journals Hemodynamic Differences Between Women and Men with Elevated Blood Pressure in China

2021 ◽  
Author(s):  
Cesar Caraballo ◽  
Shiwani Mahajan ◽  
Jianlei Gu ◽  
Yuan Lu ◽  
Erica S Spatz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Cardiac Index ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Systemic Vascular Resistance ◽  
Resistance Index ◽  
Elevated Blood Pressure ◽  
Systemic Vascular Resistance Index ◽  
Elevated Blood

Background: Whether there are sex differences in hemodynamic profiles among people with elevated blood pressure is not well understood and could guide personalization of treatment. Methods and results: We described the clinical and hemodynamic characteristics of adults with elevated blood pressure in China using impedance cardiography. We included 45,082 individuals with elevated blood pressure (defined as systolic blood pressure of ≥130 mmHg or a diastolic blood pressure of ≥80 mmHg), of which 35.2% were women. Overall, women had a higher mean systolic blood pressure than men (139.0 [±15.7] mmHg vs 136.8 [±13.8] mmHg, P<0.001), but a lower mean diastolic blood pressure (82.6 [±9.0] mmHg vs 85.6 [±8.9] mmHg, P<0.001). After adjusting for age, region, and body mass index, women <50 years old had lower systemic vascular resistance index (beta-coefficient [β] -31.68; 95% CI: -51.18, -12.19) and higher cardiac index (β 0.07; 95% CI: 0.04, 0.09) than men of their same age group, whereas among those ≥50 years old women had higher systemic vascular resistance index (β 120.43; 95% CI: 102.36, 138.51) but lower cardiac index (β -0.15; 95% CI: -0.16, -0.13). Results were consistent with a propensity score matching sensitivity analysis, although the magnitude of the SVRI difference was lower and non-significant. However, there was substantial overlap between women and men in the distribution plots of these variables, with overlapping areas ranging from 78% to 88%. Conclusions: Our findings indicate that there are sex differences in hypertension phenotype, but that sex alone is insufficient to infer an individual's profile.

Effects of TNF-alpha on hemodynamic changes and circulating endothelium-derived vasoactive factors in dogs

1994 ◽  
Vol 267 (4) ◽  
pp. H1530-H1536 ◽  
Author(s):  
C. Mitaka ◽  
Y. Hirata ◽  
K. Ichikawa ◽  
K. Yokoyama ◽  
T. Emori ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Resistance Index ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Induced Hypotension ◽  
Vasoactive Factors ◽  
Anesthetized Dogs ◽  
Factor Alpha ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor

To elucidate the relation of tumor necrosis factor-alpha (TNF-alpha)-induced hemodynamic change to endothelium-derived vasoactive factors, we simultaneously measured hemodynamic parameters and circulating endothelin (ET)-1, ET-3, nitrite/nitrate (NOx), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in anesthetized dogs following administration of TNF-alpha with or without NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and indomethacin, a cyclooxygenase inhibitor. Natural human TNF-alpha (10 micrograms/kg, n = 5) with or without L-NNA (1 mg/kg, n = 5) or indomethacin (2 mg/kg, n = 5) was administered intravenously as a bolus, while administration of vehicle served as control (n = 5). After administration of TNF-alpha, mean arterial pressure and cardiac index significantly decreased, whereas systemic (SVRI) and pulmonary (PVRI) vascular resistance index increased. Plasma levels of ET-1, ET-3, NOx, and 6-keto-PGF1 alpha significantly (P < 0.01) increased at 1 h. L-NNA or indomethacin blocked TNF-alpha-induced hypotension and remarkably increased SVRI but did not affect decreased cardiac index. Our data suggest that endogenous ET-1 may partly contribute to TNF-alpha-induced increases in SVRI and PVRI, against which ET-3, NO, and prostacyclin may function as compensatory vasodilators.

scholarly journals Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Matthias Rau ◽  
Kirsten Thiele ◽  
Niels-Ulrik Korbinian Hartmann ◽  
Alexander Schuh ◽  
Ertunc Altiok ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Resistance Index ◽  
Stroke Volume Index ◽  
Left Ventricular ◽  
Volume Index ◽  
Hemodynamic Parameters ◽  
Mitral Inflow ◽  
Ventricular Filling Pressure

Abstract Background In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters and cardiac function. Thus, this study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index, cardiac index, and stroke volume index, as well as echocardiographic measures of cardiac function. Methods In this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Hemodynamic and echocardiographic parameters were assessed after 1 day, 3 days and 3 months of treatment. Results Baseline characteristics were not different in the empagliflozin (n = 22) and placebo (n = 20) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 h; day 1: 48.4 ± 34.7 g/24 h; p < 0.001) as well as urinary volume (1740 ± 601 mL/24 h to 2112 ± 837 mL/24 h; p = 0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of systemic vascular resistance index, nor on cardiac index, stroke volume index or pulse rate at any time point. In addition, echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejections fraction and strain analysis. However, empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/eʹ) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p = 0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/s; day 1: 0.73 ± 0.2 m/sec; p = 0.003). Conclusions Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months, but leads to rapid and sustained significant improvement of diastolic function. Trial registration EudraCT Number: 2016-000172-19; date of registration: 2017-02-20 (clinicaltrialregister.eu)

Functional difference between SP and NKA: relaxation of gastric muscle by SP is mediated by VIP and NO

1993 ◽  
Vol 264 (4) ◽  
pp. G678-G685
Author(s):  
J. G. Jin ◽  
S. Misra ◽  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
No Synthase ◽  
No Production ◽  
Neurokinin A ◽  
Functional Difference ◽  
Receptor Agonists ◽  
Gastric Muscle ◽  
Guinea Pig Stomach ◽  
Synthase Inhibitor

The mechanism of action of endogenous tachykinins [substance P (SP) and neurokinin A and B (NKA and NKB)] and of receptor-specific tachykinin analogues (SP methyl ester (SPME), [beta-Ala8]NKA-(4-10), and senktide) was examined in circular muscle of guinea pig stomach. Cross-desensitization studies confirmed that SPME and SP interacted with NK-1 receptors, [beta-Ala8]NKA-(4-10) and NKA with NK-2 receptors, and senktide and NKB with NK-3 receptors. NK-1 and NK-3-receptor agonists induced relaxation and stimulated vasoactive intestinal peptide (VIP) release and nitric oxide (NO) production: tetrodotoxin abolished VIP release, NO production, and relaxation, converting the response to NK-1-receptor agonists to contraction; the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) abolished NO production, partly inhibited VIP release (56-64%, P < 0.01), and abolished relaxation; the VIP antagonist VIP-(10-28) partly inhibited NO production (73-74%, P < 0.001) and relaxation (56-58%, P < 0.01); and atropine augmented relaxation by 28-35% (P < 0.01). The pattern of inhibition implied that: 1) relaxation was mediated by VIP and NO; 2) VIP release was partly dependent on NO production, since it was strongly inhibited by L-NNA; and 3) NO was largely produced by the action of VIP on muscle cells, since it was strongly inhibited by VIP-(10-28). NK-2-receptor agonists elicited only contraction that was not affected by tetrodotoxin; these agonists also inhibited VIP release, NO production, and relaxation induced by NK-1- and NK-3-receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study 

2020 ◽  
Author(s):  
Matthias Rau ◽  
Kirsten Thiele ◽  
Niels-Ulrik Korbinian Hartmann ◽  
Alexander Schuh ◽  
Ertunc Altiok ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Resistance Index ◽  
Stroke Volume Index ◽  
Left Ventricular ◽  
Volume Index ◽  
Hemodynamic Parameters ◽  
Mitral Inflow ◽  
Ventricular Filling Pressure

Abstract Background: In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters and cardiac function. Thus, this study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index, cardiac index, and stroke volume index, as well as echocardiographic measures of cardiac function.Methods: In this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Hemodynamic and echocardiographic parameters were assessed after 1 day, 3 days and 3 months of treatment. Results: Baseline characteristics were not different in the empagliflozin (n=22) and placebo (n=20) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 hrs; day 1: 48.4 ± 34.7 g/24 hrs; p<0.001) as well as urinary volume (1740 ± 601 mL/24 hrs to 2112 ± 837 mL/24 hrs; p=0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of systemic vascular resistance index, nor on cardiac index, stroke volume index or pulse rate at any time point. In addition, echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejections fraction and strain analysis. However, empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/e’) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p=0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/sec; day 1: 0.73 ± 0.2 m/sec; p=0.003). Conclusions: Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months, but leads to rapid and sustained significant improvement of diastolic function.

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