Effects of ATP-sensitive potassium channel blockers on vascular hyporeactivity, mesenteric blood flow, and survival in lipopolysaccharide-induced septic shock model

2016 ◽  
Vol 94 (8) ◽  
pp. 858-867
Author(s):  
Mustafa Boz ◽  
Pergin Atilla ◽  
Alper B. Iskit ◽  
Mustafa Ilhan
Keyword(s):  
Blood Pressure ◽  
Septic Shock ◽  
Blood Flow ◽  
Channel Blocker ◽  
Therapeutic Effects ◽  
Channel Blockers ◽  
Shock Model ◽  
Mesenteric Blood Flow ◽  
Vascular Hyporeactivity ◽  
Selective Blocker

In this study, the possible therapeutic effects of various ATP-sensitive potassium channel (KATP) blockers (glibenclamide, repaglinide, 5-HD, HMR-1098) have been tested in experimental septic shock model. Rats were given lipopolysaccharide (1 mg·kg−1) to create experimental shock model and 4 h later, under 400 mg·kg−1 chloral hydrate anesthesia, parameters such as blood pressure, mesenteric blood flow, the response of mesenteric circulation to phenylephrine (vasoconstrictor stimulation), and organ and oxidative damage were analyzed. Also 75 mg·kg−1 lethal dose of lipopolysaccharide was given to mice and effects of KATP blockers on survival have been tested. Non-selective blocker glibenclamide with sulphonylurea structure and sarcolemmal KATP channel blocker HMR-1098, which have the similar chemical structure, have improved the pathological parameters such as decrease in mesenteric blood flow, vascular hyporeactivity, but could not prevent the decrease in blood pressure, and oxidative and organ damage that were observed in the shock model. Also, both blockers have decreased the mortality rate from 80% to 40%–50%. Similar (preventive) therapeutic effects were not observed with non-selective blocker repaglinide and mitochondrial KATP channel blocker 5-HD, which were non-sulphonylurea structure. As a result, only KATP channel blockers that have sulphonylurea structure can be a new therapeutic approach in septic shock.

Effects of nicotine on canine intestinal blood flow and oxygen consumption

1984 ◽  
Vol 246 (2) ◽  
pp. G195-G203
Author(s):  
R. H. Gallavan ◽  
Y. Tsuchiya ◽  
E. D. Jacobson
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Muscle Tension ◽  
Intestinal Blood Flow ◽  
Mesenteric Blood Flow ◽  
State Response ◽  
Arterial Blood ◽  
Intestinal Circulation

The purpose of this study was to determine the effects of nicotine on intestinal blood flow and oxygen consumption. The intravenous infusion of nicotine at doses corresponding to those experienced by smokers produced a transient increase in systemic arterial blood pressure and mesenteric blood flow. Subsequently a steady-state response developed that consisted of a reduction in mesenteric blood flow due to both a decrease in blood pressure and an increase in intestinal vascular resistance. This increase in resistance was probably due to increased levels of circulating catecholamines. The intra-arterial infusion of nicotine into the intestinal circulation at doses experienced by the average smoker had no effect on either intestinal blood flow or oxygen consumption. Similarly, under in vitro conditions nicotine had no direct effect on intestinal vascular smooth muscle tension. Thus, nicotine appears to reduce intestinal blood flow indirectly as a result of its systemic effects.

Effect of vasopressors on organ blood flow during endotoxin shock in pigs

1987 ◽  
Vol 252 (2) ◽  
pp. H291-H300 ◽  
Author(s):  
M. J. Breslow ◽  
C. F. Miller ◽  
S. D. Parker ◽  
A. T. Walman ◽  
R. J. Traystman
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Left Ventricle ◽  
Arterial Blood Pressure ◽  
Endotoxin Shock ◽  
Organ Blood Flow ◽  
Shock Model ◽  
Blood Pressure Elevation ◽  
Arterial Blood

A volume-resuscitated porcine endotoxin shock model was used to evaluate the effect on organ blood flow of increasing systemic arterial blood pressure with vasopressors. Administration of 0.05–0.2 mg/kg of Escherichia coli endotoxin (E) reduced mean arterial blood pressure (MAP) to 50 mmHg, decreased systemic vascular resistance to 50% of control, and did not change cardiac output or heart rate. Blood flow to brain, kidney, spleen, and skeletal muscle was reduced during endotoxin shock, but blood flow to left ventricle, small and large intestine, and stomach remained at pre-endotoxin levels throughout the study period. Four groups of animals were used to evaluate the effect of vasopressor therapy. A control group received E and no vasopressor, whereas the other three groups received either norepinephrine, dopamine, or phenylephrine. Vasopressors were administered starting 60 min after E exposure, and the dose of each was titrated to increase MAP to 75 mmHg. Despite the increase in MAP, brain blood flow did not increase in any group. Norepinephrine alone increased blood flow to the left ventricle. Kidney, splanchnic, and skeletal muscle blood flow did not change with vasopressor administration. The dose of norepinephrine required to increase MAP by 20–25 mmHg during E shock was 30 times the dose required for a similar increase in MAP in animals not receiving E. We conclude that hypotension in the fluid resuscitated porcine E shock model is primarily the result of peripheral vasodilatation, that the vascular response to vasoconstrictors in this model is markedly attenuated following E administration, that blood pressure elevation with norepinephrine, dopamine, and phenylephrine neither decreases blood flow to any organ nor increases blood flow to organs with reduced flow, and that norepinephrine, dopamine, and phenylephrine affect regional blood flow similarly in this model.

scholarly journals Effects of vasopressin and terlipressin in ovine septic shock on mesenteric blood flow and survival

Critical Care ◽  
2007 ◽  
Vol 11 (Suppl 4) ◽  
pp. P19 ◽  
Author(s):  
Sebastian Rehberg ◽  
Christian Ertmer ◽  
Matthias Lange ◽  
Andrea Morelli ◽  
Hugo Van Aken ◽  
...  
Keyword(s):  
Septic Shock ◽  
Blood Flow ◽  
Mesenteric Blood Flow

Role of the hypothalamic PVN in the reflex reduction in mesenteric blood flow elicited by hyperthermia

2008 ◽  
Vol 295 (6) ◽  
pp. R1874-R1881 ◽  
Author(s):  
Feng Chen ◽  
Melissa Dworak ◽  
Yuliang Wang ◽  
Joo Lee Cham ◽  
Emilio Badoer
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Body Temperature ◽  
Core Body Temperature ◽  
Separate Group ◽  
Control Group ◽  
Mesenteric Blood Flow ◽  
Significant Difference ◽  
Core Body

The hypothalamic paraventricular nucleus (PVN) is an important integrative center in the brain. In the present study, we investigated whether the PVN is a key region in the mesenteric vasoconstriction that normally accompanies an increase in core body temperature. Anesthetized rats were monitored for blood pressure, heart rate, mesenteric blood flow, and vascular conductance. In control rats, elevation of core body temperature to 41°C had no significant effect on blood pressure, increased heart rate, and reduced mesenteric blood flow by 21%. In a separate group of rats, muscimol was microinjected bilaterally (1 nmol/side) into the PVN. Compared with the control group, there was no significant difference in the blood pressure and heart rate responses elicited by the increase in core body temperature. In contrast to control animals, however, mesenteric blood flow did not fall in the muscimol-treated rats in response to the elevation in core body temperature. In a separate group, in which muscimol was microinjected into regions outside the PVN, elevating core body temperature elicited the normal reduction in mesenteric blood flow. The results suggest that the PVN may play a key role in the reflex decrease in mesenteric blood flow elicited by hyperthermia.

scholarly journals Central hemodynamic and splanchnic circulation in children with meningococcal septic shock

2017 ◽  
Vol 8 (1) ◽  
pp. 91-97
Author(s):  
M. A. Georgiyants ◽  
V. A. Korsunov ◽  
O. M. Olkhovska
Keyword(s):  
Blood Pressure ◽  
Septic Shock ◽  
Blood Flow ◽  
Cardiac Output ◽  
Ejection Fraction ◽  
Stroke Volume ◽  
Blood Flow Rate ◽  
Healthy Children ◽  
Group I ◽  
Meningococcal Septic Shock

Meningococcal infection is caused by the bacterium Neisseria meningitidis (also termed meningococcus). Invasive meningococcal disease remains a rare infectious disease not only with high mortality but also with important morbidity and remains as a leading cause of sepsis and septic shock. The pathogenic mechanisms of microcirculatory disorders in meningococcal septic shock have been subject to controversy. This article presents the results of a study of 11 paediatric patients’ (4 boys and 7 girls) with meningococcal septic shock (Group I) who were hospitalized at the Regional Children's Infectious Hospital from 2009 to 2011. The average age of the patients was 37.4 ± 8.4 mo. Septic shock was diagnosed according to International Pediatric Sepsis Consensus Conference: definitions of criteria for sepsis and organ dysfunction in paediatrics. Heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, average blood pressure, SpO2 were monitored. The cardiac output, ejection fraction, fraction shortening, stroke volume were measured by ultrasound in M-mode by Teichholz method. Blood circulation in the a. mesenterica, a. hepatica, a. lienalis, a. renal sinister, v. porta, v. lienalis, v. renal sinister was determined by impulse Doppler’s wave. Acid-base and electrolytes level in serum, nitric oxide (NO), endothelin I, creatinine, C-reactivity protein and lactate blood level were measured. The control group consisted of 21 healthy children (9 boys and 12 girls), aged 37.5 ± 5.4 mo. in average (Group II). We used t-criteria (Student’s) and correlation with R-criteria (Spearmen) for statistical analysis. The data showed a statistically significant lower fraction of ejection, fraction of shortening, stroke volume in Group I. Moreover, our data showed a statistically high level of mesenterial and portal blood flow rate and high pulse index in v. renal sinister compared to healthy children. The blood level of NO was increased in Group I as well as in Group II. Direct correlations were determined between the level of NO and mesenteric, hepatic arterial and venous blood flow rate. Statistically significant inverse correlations between the level of NO and pulse resistive index in splanchnic vessels were discovered as well as inverse correlations between the NO level and the indicator of the severity of condition on PRISM scale (r = –0.952). At the same time, we have found no correlation between splanchnic circulation value and cardiac output. Based on the results of this study, we consider that NO has organ protective effects in children with meningococcal sepsis. Future research should aim to introduce new strategies of intensive care for patients with meningococcal septic shock with early use of inotrope and NO-donor therapy in fluid restriction combination. 

Baroreceptors, α1-adrenergic receptors, and regulation of mesenteric blood flow

1999 ◽  
Vol 78 (1) ◽  
pp. 54-57
Author(s):  
Isam Abu-Amarah ◽  
William A Cupples
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Adrenergic Receptors ◽  
Separate Experiment ◽  
Adrenergic Blockade ◽  
Arterial Baroreflex ◽  
Mesenteric Blood Flow ◽  
Dynamic Regulation ◽  
Mesenteric Circulation ◽  
Flow Transfer

In the mesenteric circulation of the rat a myogenic autoregulatory system operates at 0.1-0.15 Hz. Negative admittance phase in the region above 0.2 Hz suggested operation of an arterial baroreflex. The present study was designed to test this interpretation and to identify the neurotransmitter involved. In rats anesthetized with isoflurane, blood pressure and mesenteric blood flow (transit time ultrasound) were measured with central mechanisms intact, after sinoaortic denervation, and after denervation of the mesenteric bed. Sinoaortic denervation abrogated the negative phase in the band from 0.3 to 0.6 Hz and increased admittance gain in this region. Subsequent mesenteric denervation had no further effect on the pressure-flow transfer function. In a separate experiment, α1-adrenergic blockade reduced, but did not remove, the negative admittance phase in the 0.2- to 0.5-Hz band without altering admittance gain. It is concluded that the baroreflex acting on the mesenteric circulation can be identified by admittance phase, but that admittance gain is uninformative. Part of the response is mediated by α1-adrenergic transmission.Key words: mesenteric, α1-adrenergic receptors, dynamic regulation.

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