C5-blocking antibody reduces fluid requirements and improves responsiveness to fluid infusion in hemorrhagic shock managed with hypotensive resuscitation

2007 ◽  
Vol 102 (2) ◽  
pp. 673-680 ◽  
Author(s):  
Russell M. Peckham ◽  
Michael T. Handrigan ◽  
Timothy B. Bentley ◽  
Michael J Falabella ◽  
Andrew D. Chrovian ◽  
...  
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Fold Increase ◽  
Sprague Dawley ◽  
Blocking Antibody ◽  
Fluid Infusion ◽  
Hypotensive Resuscitation ◽  
Sprague Dawley Rats ◽  
Prolonged Hypotension

Hypotensive resuscitation strategies and inhibition of complement may both be of benefit in hemorrhagic shock. We asked if C5-blocking antibody (anti-C5) could diminish the amount of fluid required and improve responsiveness to resuscitation from hemorrhage. Awake, male Sprague-Dawley rats underwent controlled hemorrhage followed by prolonged (3 h) hypotensive resuscitation with lactated Ringer’s or Hextend, with or without anti-C5. Anti-C5 treatment led to an estimated 62.3 and 58.5% reduction in the volume of Hextend and lactated Ringer’s, respectively. In the subgroup of animals with a positive mean arterial pressure (MAP) response to fluid infusion following prolonged hypotension, anti-C5 treatment led to an estimated 4.7- and 4.1-fold increase in mean arterial pressure response per unit Hextend and lactated Ringer’s infused, respectively. We observed no significant postresuscitation metabolic differences between the anti-C5 groups and controls. Whether anti-C5 could serve as a volume-sparing adjunct that improves responsiveness to fluid administration in humans deserves further study.

Abstract P29: Impaired Systemic but Preserved Cerebral Microcirculation Following Hemorrhagic Shock and Fluid Resuscitation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Zhi Wan ◽  
Shijie Sun ◽  
Giuseppe Ristagno ◽  
Yongqin Li ◽  
Max H Weil ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Orthogonal Polarization ◽  
Cerebral Microcirculation ◽  
Sprague Dawley ◽  
Fluid Infusion ◽  
Descending Aorta ◽  
Shed Blood ◽  
Sprague Dawley Rats ◽  
Orthogonal Polarization Spectral

Background: Decreases in buccal microcirculation are associated with severity and outcomes of circulatory shock. However, there is evidence that cerebral function is unimpaired after even severe states of hemorrhagic shock. We therefore hypothesized that in severe states of hemorrhagic shock with profound decreases in buccal microcirculation, the cerebral microcirculation may be preserved. Method: Craniotomies were performed in 15 male Sprague-Dawley rats, weighing 450–550g, to expose the parietal cortex for visualization of microcirculation. Animals were then bled via a catheter advanced into the descending aorta. An estimated 35% or 25% of blood volume was bled over 60 minutes and measurements were compared with unbled control. Sixty minutes after onset of hypotension, bled animals received normal saline infused over 30 minutes in amounts equivalent to two times the volume of shed blood. Cerebral and buccal microcirculations were visualized with orthogonal polarization spectral imaging. Result: Reductions in mean arterial pressure (MAP) were partially reversed after fluid infusion (Figure 1 ). Buccal microcirculation was restored to baseline level after the 25% blood loss and partially restored after the 35% loss. The cerebral microcirculation, however, was unchanged during both hemorrhagic hypotension and following volume repletion. Conclusion: In contrast to the striking reduction in arterial pressure and systemic microcirculation, the cerebral microcirculatory blood flow was preserved during hemorrhagic shock of moderate and severe degrees. These findings confirm a dissociation between the macrocirculation and the cerebral microcirculation.

Arginine vasopressin-induced natriuresis in the anaesthetized rat: involvement of V1 and V2 receptors

1993 ◽  
Vol 136 (2) ◽  
pp. 283-288 ◽  
Author(s):  
C. P. Smith ◽  
R. J. Balment
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Arginine Vasopressin ◽  
Plasma Concentrations ◽  
Receptor Subtypes ◽  
Vasopressin Receptor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Anaesthetized Rat

ABSTRACT The present study was undertaken to determine the involvement of the two established vasopressin receptor subtypes (V1 and V2) in arginine vasopressin (AVP)-induced natriuresis and also to determine whether changes in mean arterial pressure (MAP) and/or the renally active hormones atrial natriuretic peptide (ANP), angiotensin II (AII) and aldosterone are a prerequisite for the expression of AVP-induced natriuresis. In Sprague–Dawley rats which were anaesthetized with Inactin (5-ethyl-5-(1′-methylpropyl)-2-thiobarbiturate) and infused with 0·077 mol NaCl/l, infusion of 63 fmol AVP/min was found to be natriuretic whereas an approximately equipotent dose of the specific V2 agonist [deamino-cis1, d-Arg8]-vasopressin (dDAVP) did not induce natriuresis. The specific V1 antagonist [β-mercapto-β,β-cyclopenta-methylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin when administered prior to infusion of 63 fmol AVP/min did not inhibit AVP-induced natriuresis. AVP-induced natriuresis was not accompanied by changes in MAP or in the plasma concentrations of the renally active hormones ANP, AII or aldosterone. These results suggest that neither the V1 nor the V2 receptor subtypes are involved in AVP-induced natriuresis. In addition, it was found that changes in MAP, plasma ANP, All or aldosterone concentrations were not a prerequisite for AVP-induced natriuresis. Journal of Endocrinology (1993) 136, 283–288

Area postrema: essential for support of arterial pressure after hemorrhage in rats

1990 ◽  
Vol 258 (6) ◽  
pp. R1472-R1478 ◽  
Author(s):  
K. M. Skoog ◽  
M. L. Blair ◽  
C. D. Sladek ◽  
W. M. Williams ◽  
M. L. Mangiapane
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Data Acquisition ◽  
Area Postrema ◽  
Plasma Renin ◽  
Base Line ◽  
Sprague Dawley ◽  
Time Period ◽  
Sprague Dawley Rats

Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP-lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP-lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP-lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage.

Abstract P616: Evidence That The Extracellular Domain Of Na + /K + Atpase Is The Receptor For Cyclic Gmp-Induced Natriuresis

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
John J Gildea ◽  
Nancy L Howell ◽  
Susanna R Keller ◽  
Robert M Carey
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Control Period ◽  
Extracellular Domain ◽  
Sprague Dawley ◽  
Binding Studies ◽  
Urine Sodium ◽  
Sprague Dawley Rats ◽  
Normal Rat ◽  
Change In Mean

Previous studies from our laboratory have shown that extracellular renal interstitial (RI) cyclic guanosine 3’5’-monophosphate (cGMP) increases urine sodium (Na + ) excretion (U Na V) at the renal proximal tubule (RPT) in rats via activation of Src family kinase. Extracellular cGMP engenders this response through an unknown receptor. We hypothesized that cGMP binds to the extracellular domain of Na + /K + -ATPase (NKA) on basolateral membranes of RPT cells inhibiting Na + transport. In the present study, we evaluated the effect of RI infusion of rostafuroxin (RF), a digitoxigenin derivative that specifically displaces oubain (OUA) binding from NKA, on U Na V in the presence of RI cGMP infusion. Volume expanded, uninephrectomized, 12-week-old female Sprague-Dawley rats received RI infusions of vehicle (D 5 W) (N=8), RI cGMP (18, 36, and 72 μg/kg/min; each dose for 30 min; N=10), or RI cGMP + RF (0.012 μg/kg/min; N=5) for 90 min following a 30 min control period with RI infusion of vehicle D 5 W. RI cGMP infusion induced a significant natriuresis from 0.39 ± 0.06 μmol/min to 1.03 ± 0.21 (P<0.05), 1.17 ± 0.19 (P<0.01), and 1.94 ± 0.16 (P<0.001) μmol/min at 18, 36, and 72 μg/kg/min cGMP, respectively. RI co-infusion of cGMP + RF abolished the cGMP-induced natriuresis at all doses (F=16.05, P<0.001). There was no change in mean arterial pressure during any infusion. To further demonstrate that cGMP binds to NKA, we performed a series of competitive binding studies in isolated RPTs from normal rat kidneys (N=4 for each) with bodipy-OUA (2 μM) + cGMP (10 μM) and 8-[Biotin]-AET-cGMP (2 μM) + OUA (10 μM). In the presence of cGMP, bodipy-OUA fluorescence intensity was reduced from 1422.1 ± 63 to 1072.5 ± 64 relative fluorescent units (RFU, P<0.01). In the presence of OUA, 8-[Biotin]-AET-cGMP staining was reduced from 1916.3 ± 144 to 1492.2 ± 84 RFU (P<0.05). Serving as control, biotinylated cAMP (N=2) did not demonstrate any fluorescence above background. Together, these data suggest that cGMP may compete with RF for binding on NKA and that the extracellular domain of NKA may serve as the receptor for cGMP-induced natriuresis.

Hemorrhagic shock induces G-CSF expression in bronchial epithelium

1997 ◽  
Vol 273 (5) ◽  
pp. L1058-L1064 ◽  
Author(s):  
Christian Hierholzer ◽  
Edward Kelly ◽  
Katsuhiko Tsukada ◽  
Eric Loeffert ◽  
Simon Watkins ◽  
...  
Keyword(s):  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Fold Increase ◽  
Bronchial Epithelium ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Inflammatory Processes ◽  
Csf Levels

Hemorrhagic shock (HS) initiates a series of inflammatory processes that includes the activation of polymorphonuclear granulocytic neutrophils (PMN). We tested the hypothesis that HS induces granulocyte colony-stimulating factor (G-CSF), a cytokine that augments PMN effector functions, in the lungs of rats. Sprague-Dawley rats were subjected to compensated or decompensated HS followed by resuscitation and death at 4 or 8 h. Animals subjected to HS demonstrated acute lung injury with PMN infiltration, edema, and hypoxia. Using semiquantitative reverse transcriptase-polymerase chain reaction, we detected a 1.9- to 7.1-fold increase in G-CSF mRNA levels in the lung of animals subjected to HS compared with sham controls. Levels of G-CSF mRNA increased with increased duration of the ischemic phase of resuscitated shock. In situ hybridization revealed that bronchoepithelial cells were the major cellular site of G-CSF mRNA. Thus production of G-CSF mRNA by bronchoepithelial cells is dramatically increased in a rat model of HS that also demonstrated lung injury. Increased local G-CSF levels may contribute to PMN recruitment and activation and resultant lung injury in HS.

Effects of arterial hypotension on microvascular oxygen exchange in contracting skeletal muscle

2006 ◽  
Vol 100 (3) ◽  
pp. 1019-1026 ◽  
Author(s):  
Brad J. Behnke ◽  
Danielle J. Padilla ◽  
Leonardo F. Ferreira ◽  
Michael D. Delp ◽  
Timothy I. Musch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Contractile Function ◽  
Muscle Blood Flow ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Exercise Onset ◽  
Muscle Contractile ◽  
Hypovolemic Hypotension

In healthy animals under normotensive conditions (N), contracting skeletal muscle perfusion is regulated to maintain microvascular O2 pressures (Pmv[Formula: see text]) at levels commensurate with O2 demands. Hypovolemic hypotension (H) impairs muscle contractile function; we tested whether this condition would alter the matching of O2 delivery (Q̇o2) to O2 utilization (V̇o2), as determined by Pmv[Formula: see text] at the onset ofmuscle contractions. Pmv[Formula: see text] in the spinotrapezius muscles of seven female Sprague-Dawley rats (280 ± 6 g) was measured every 2 s across the transition from rest to 1-Hz twitch contractions. Measurements were made under N (mean arterial pressure, 97 ± 4 mmHg) and H (induced by arterial section; mean arterial pressure, 58 ± 3 mmHg, P < 0.05) conditions; Pmv[Formula: see text] profiles were modeled using a multicomponent exponential fitted with independent time delays. Hypotension reduced muscle blood flow at rest (24 ± 8 vs. 6 ± 1 ml−1·min−1·100 g−1 for N and H, respectively; P < 0.05) and during contractions (74 ± 20 vs. 22 ± 4 ml−1·min−1·100 g−1 for N and H, respectively; P < 0.05). H significantly decreased resting Pmv[Formula: see text] and steady-state contracting Pmv[Formula: see text](19.4 ± 2.4 vs. 8.7 ± 1.6 Torr for N and H, respectively, P < 0.05). At the onset of contractions, H reduced the time delay (11.8 ± 1.7 vs. 5.9 ± 0.9 s for N andH, respectively, P < 0.05) before the fall in Pmv[Formula: see text] and accelerated therate of Pmv[Formula: see text] decrease (time constant, 12.6 ± 1.4 vs. 7.3 ± 0.9 s for N and H, respectively, P < 0.05). Muscle V̇o2 was reduced by 71% at rest and 64% with contractions in H vs. N, and O2 extraction during H averaged 78% at rest and 94% during contractions vs. 51 and 78% in N. These results demonstrate that H constrains the increase of skeletal muscle Q̇o2 relative to that of V̇o2 at the onset of contractions,leading to a decreased Pmv[Formula: see text]. According to Fick's law, this scenario will decrease blood-myocyte O2 flux, thereby slowing V̇o2 kinetics and exacerbating the O2 deficit generated at exercise onset.

scholarly journals Chronic renal artery insulin infusion increases mean arterial pressure in male Sprague-Dawley rats

2018 ◽  
Vol 314 (1) ◽  
pp. F81-F88 ◽  
Author(s):  
Debra L. Irsik ◽  
Jian-Kang Chen ◽  
Michael W. Brands
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Artery ◽  
Insulin Infusion ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Novel Approach ◽  
Sprague Dawley Rats

Hyperinsulinemia has been hypothesized to cause hypertension in obesity, type 2 diabetes, and metabolic syndrome through a renal mechanism. However, it has been challenging to isolate renal mechanisms in chronic experimental models due, in part, to technical difficulties. In this study, we tested the hypothesis that a renal mechanism underlies insulin hypertension. We developed a novel technique to permit continuous insulin infusion through the renal artery in conscious rats for 7 days. Mean arterial pressure increased by ~10 mmHg in rats that were infused intravenously (IV) with insulin and glucose. Renal artery doses were 20% of the intravenous doses and did not raise systemic insulin levels or cause differences in blood glucose. The increase in blood pressure was not different from the IV group. Mean arterial pressure did not change in vehicle-infused rats, and there were no differences in renal injury scoring due to the renal artery catheter. Glomerular filtration rate, plasma renin activity, and urinary sodium excretion did not differ between groups at baseline and did not change significantly with insulin infusion. Thus, by developing a novel approach for chronic, continuous renal artery insulin infusion, we provided new evidence that insulin causes hypertension in rats through actions initiated within the kidney.

Chronic Lability of Arterial Pressure in the Rat Does Not Evolve into Hypertension

1980 ◽  
Vol 59 (s6) ◽  
pp. 405s-407s ◽  
Author(s):  
W. T. Talman ◽  
D. R. Alonso ◽  
D. J. Reis
Keyword(s):  
Heart Rate ◽  
Standard Deviation ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Electrolytic Lesions ◽  
The Mean ◽  
Catecholamine Neurons

1. In rats, electrolytic lesions of the A2 group of catecholamine neurons result in lability of arterial pressure without hypertension. 2. To establish whether labile arterial pressure, when chronic, will lead to fixed hypertension, we placed lesions in the A2 area of adult male Sprague-Dawley rats and measured mean arterial pressure, heart rate and their variability (expressed as the standard deviation) 11 months later. Controls were age-matched, unoperated or sham-operated rats. 3. In rats with A2 lesions: (a) the mean arterial pressure was lower (103 ± 7.5 mmHg; n = 6; P&lt;0.05) than in sham-operated (123 ± 4.7 mmHg; n = 4) or unoperated (120 ± 3.1 mmHg; n = 9) controls; (b) the standard deviation of mean arterial pressure was higher (16 ± 1.8 mmHg; P&lt;0.001) than in sham-operated (5 ± 0.7 mmHg) or unoperated controls (7 ± 0.6 mmHg); (c) the mean and standard deviation of heart rate did not differ between groups. No histopathological changes were detected in the A2 group. 4. Chronic lability of arterial pressure does not evolve into sustained hypertension nor does it induce systemic lesions.

scholarly journals Animal model of the abdominal compartment syndrome as a single insult and as a second insult in rats

2003 ◽  
Vol 18 (spe) ◽  
pp. 29-36 ◽  
Author(s):  
João Baptista de Rezende-Neto ◽  
Alcino Lázaro da Silva ◽  
José Renan Cunha-Melo
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Compartment Syndrome ◽  
Abdominal Compartment Syndrome ◽  
Venous Pressure ◽  
Male Rats ◽  
Sprague Dawley ◽  
Mechanically Ventilated ◽  
Abdominal Compartment

The objective of this paper was to develop a clinically relevant abdominal compartment syndrome experimental model, as a single insult and as a second insult flowing hemorrhagic shock. In the single insult model, Sprague-Dawley male-rats are anesthetized, invasively monitored (central venous pressure and mean arterial pressure), and mechanically ventilated during intraperitoneal injection of air to provoke the abdominal compartment syndrome (25 mmHg) for 60 minutes. In the two insult model, Sprague-Dawley male-rats are anesthetized, invasively monitored (mean arterial pressure) and bled to a mean arterial pressure of 30 mmHg for 45 minutes. Fluid resuscitation is accomplished by infusing 0.9% sodium chloride solution (0.9% NaCl) 33.2 ml/kg plus 75% of shed blood volume. During this phase a laparotomy is performed. Two hours after the beginning of the hemorrhagic shock phase the animals are anesthetized, intubated (orotracheal), mechanically ventilated (mean arterial pressure), and the intra-abdominal pressure is increased to 25 mmHg for 60 minutes, as a second insult. A 0.9% NaCl solution is infused during this phase (45 ml/kg/h). Hemorrhagic shock and the abdominal compartment syndrome behave as clinically relevant additive insults.

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