Effects of prostacyclin and indomethacin on experimental delayed cerebral vasospasm

1983 ◽  
Vol 59 (5) ◽  
pp. 829-834 ◽  
Author(s):  
Toyokazu Fukumori ◽  
Eiichi Tani ◽  
Yukio Maeda ◽  
Atsuhiko Sukenaga
Keyword(s):  
Basilar Artery ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Content Type ◽  
Mean Values ◽  
Delayed Cerebral Vasospasm ◽  
Arterial Blood ◽  
Canine Basilar Artery ◽  
Dose Dependent

✓ Isolated canine basilar artery contracted by prostaglandin E2, hemoglobin, or serum was relaxed in a dose-dependent manner by the addition of 10−8M to 10−6M prostacyclin (PGI2), and was scarcely relaxed by 10−9M PGI2. In other studies, intravenous administration of PGI2 (25 or 75 ng/kg/min), indomethacin (4 mg/kg), or indomethacin (4 mg/kg) plus PGI2 (25 ng/kg/min) failed to reverse angiographic delayed vasospasm produced in vivo in the canine basilar artery by an intracisternal injection of blood. In addition, no significant increase occurred in mean values of regional cerebral blood flow (rCBF) with any treatments, and mean rCBF difference in dogs treated by PGI2 infusion at 25 ng/kg/min was 2.5 ± 1.2 ml/100 gm/min and only significantly increased (p < 0.01). Mean arterial blood pressure was significantly reduced by PGI2 infusion at 25 (p < 0.05) or 75 ng/kg/min (p < 0.005).

Effects of ML-9 on experimental delayed cerebral vasospasm

1989 ◽  
Vol 71 (6) ◽  
pp. 916-922 ◽  
Author(s):  
Kiyokazu Kokubu ◽  
Eiichi Tani ◽  
Masaru Nakano ◽  
Nobutaka Minami ◽  
Hideki Shindo
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Canine Model ◽  
Neurological Deficits ◽  
Content Type ◽  
Delayed Cerebral Vasospasm ◽  
Arterial Blood ◽  
Complete Reversal ◽  
The Mean ◽  
Dose Dependent

✓ Experimental delayed cerebral vasospasm was produced in a two-hemorrhage canine model. The spastic basilar artery was exposed via the transclival route under a surgical microscope, and was dilated by the topical application of 1-(5-chloronaphthalenesulfonyl)-1H-hexa-hydro-1,4-diazepine(ML-9), a selective antagonist of myosin light chain kinase. Dilation was dose-dependent, with a median effective dose (± standard deviation) of 51.4 ± 6.9 µM. In addition, 50 µM of ML-9 was injected into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, including a complete reversal of angiographic delayed vasospasm in three of seven dogs; in contrast, 150 µM of ML-9 was infused at 1.52 ml/min into the vertebral artery for 30 minutes, producing little dilation of the spastic basilar artery. In another study, the intracisternal perfusion of 50 µM of ML-9 at 1.48 ml/min for 30 minutes in dogs with an ICP of less than 200 mm H2O produced no serious electroencephalographic abnormalities, and the mean arterial blood pressure and pulse rate remained normal; no neurological deficits or significant histological abnormalities ascribable to the intracisternal ML-9 were found.

scholarly journals Virulent Bacteriophages Can Target O104:H4 Enteroaggregative Escherichia coli in the Mouse Intestine

2012 ◽  
Vol 56 (12) ◽  
pp. 6235-6242 ◽  
Author(s):  
Damien Maura ◽  
Matthieu Galtier ◽  
Chantal Le Bouguénec ◽  
Laurent Debarbieux
Keyword(s):  
Escherichia Coli ◽  
Dependent Manner ◽  
Content Type ◽  
Intestinal Pathogens ◽  
Colonization Model ◽  
Mouse Intestine ◽  
Further Development ◽  
Dose Dependent

ABSTRACTIn vivobacteriophage targeting of enteroaggregativeEscherichia coli(EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. These decreases in ileal and fecal bacterial concentrations were only transient, since 55989Str concentrations returned to their original levels 3 days later. These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophagesin vivofor the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.

Diaphragmatic microcirculation during halothane and isoflurane exposure in pentobarbital-anesthetized rats

1992 ◽  
Vol 73 (4) ◽  
pp. 1614-1618 ◽  
Author(s):  
A. Leon ◽  
J. Boczkowski ◽  
B. Dureuil ◽  
E. Vicaut ◽  
M. Aubier ◽  
...  
Keyword(s):  
Capillary Density ◽  
Baseline Period ◽  
Functional Capillary Density ◽  
Dependent Manner ◽  
Minimal Alveolar Concentration ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Isoflurane Group ◽  
Dose Dependent

We investigated the effects of halothane and isoflurane on diaphragmatic microcirculation in pentobarbital-anesthetized rats by in vivo video microscopy. After a baseline period, rats were randomly allocated into three groups according to administration of 0.5, 0.75, and 1 minimal alveolar concentration (MAC) of either halothane (group Hal, n = 16), isoflurane (group Iso, n = 14), or no halogenated agent (group C, n = 20) in three succeeding steps of 15 min. Mean arterial blood pressure (MAP), arteriolar diameters, and functional capillary density were analyzed in the last 3 min of each step. MAP remained unchanged in group C but decreased in a dose-dependent manner in both halogenated receiving groups. MAP was significantly lower in rats breathing Hal compared with those breathing Iso. Arterioles were classified in second (A2, n = 39), third (A3, n = 24), and fourth (A4, n = 30) order according to their relative location in the network. No changes in A2 and A3 diameters were noted in either group. A4 diameters remained unchanged in groups C and Iso, whereas a significant reduction was found in group Hal at 0.75 and 1 MAC exposure (P < 0.05 compared with baseline and with groups C and Iso, respectively). During Iso exposure, functional capillary density was not significantly different when compared with baseline and group C, whereas in group Hal it decreased significantly at 0.5, 0.75, and 1 MAC, amounting to 61.1 +/- 9, 30.7 +/- 10.3, and 22.8 +/- 6.3%, respectively, of baseline (P < 0.01 vs. baseline and P < 0.05 vs. groups Iso and C for 0.75 and 1 MAC).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chlorpromazine on experimental delayed cerebral vasospasm

1984 ◽  
Vol 61 (5) ◽  
pp. 857-863 ◽  
Author(s):  
Masaru Nakano ◽  
Eiichi Tani ◽  
Toyokazu Fukumori ◽  
Masayuki Yokota
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Neurological Deficits ◽  
Moderate Increase ◽  
Calmodulin Antagonist ◽  
Content Type ◽  
Theta Waves ◽  
Delayed Cerebral Vasospasm ◽  
Arterial Blood ◽  
Complete Reversal

✓ Experimental delayed cerebral vasospasm was produced in the canine basilar artery by intracisternal injections of blood 2 days apart. The spastic basilar artery was exposed via the transclival route under a surgical microscope, and was dilated by topical application of chlorpromazine, a calmodulin antagonist. Dilatation was dose-dependent, with a median effective dose of 37 ± 16 µM. In addition, 100 µM chlorpromazine was inserted into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, inducing a complete reversal of angiographic delayed cerebral vasospasm in two of five animals. In other studies, the intracisternal perfusion of 100 µM chlorpromazine at 1.48 ml/min for 30 minutes with an ICP of less than 200 mm H2O induced no serious abnormalities in mean arterial blood pressure and pulse rate of normal animals. Electroencephalography during the intracisternal perfusion of chlorpromazine showed a slight to moderate increase in occurrence of theta waves. No neurological deficits or significant histological abnormalities ascribable to intracisternal chlorpromazine were found.

scholarly journals Evaluation of the in vivo Antihypertensive Effect and Antioxidant Activity of HL-7 and HL-10 Peptide in Mice

2021 ◽  
Author(s):  
Zahra Setayesh-Mehr ◽  
Leila Vafadar Ghasemi ◽  
Ahmad Asoodeh
Keyword(s):  
Blood Pressure ◽  
Scorpion Venom ◽  
Antihypertensive Activity ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Arterial Blood ◽  
Antihypertensive Properties ◽  
Dose Dependent ◽  
Hl 7

Abstract In this study, the in vivo antioxidant and antihypertensive properties of peptides HL-7 with the sequence of YLYELR and HL-10 with the sequence of AFPYYGHHLG were identified from scorpion venom of H. lepturus were evaluated. To study the in vivo effects of peptides, D-galactose-induced and DOCA salt-induced mice models were used. The results of the antioxidant assay for both peptides showed that the activity of serum and liver catalase (CAT), as well as superoxide dismutase (SOD) enzymes, was significantly decreased in the D-galactose-induced group (NC), while MDA levels were increased in serum and the liver tissue samples (p<0.01). Compared with the D-galactose-induced mice, the peptide treated mice group had a higher activity of antioxidant enzymes namely CAT and SOD, as well as a lower lipid peroxidation level. Also, the results of antihypertensive activity for both peptides showed that systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the mice treated with the HL-7 and HL-10 peptides were significantly reduced in a dose-dependent manner (p<0.01). The administration of the HL-7 peptide at doses of 5 mg/kg BW (LP1) and 15 mg/kg BW (HP1) significantly diminished the mean arterial blood pressure (MAP) by 31 mmHg and 40.47 mmHg, respectively. Accordingly, treatment of mice with the HL-10 peptide at doses of 5 mg/kg BW (LP2) and 15 mg/kg BW (HP2) considerably lowered the MAP by 18.3 mmHg and 21.93 mmHg, respectively. Our findings suggest that both the HL-7 and HL-10 peptides could be potentially utilized as antihypertensive and antioxidant components.

scholarly journals Impact ofEimeria tenellaCoinfection onCampylobacter jejuniColonization of the Chicken

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Sarah E. Macdonald ◽  
Pauline M. van Diemen ◽  
Henny Martineau ◽  
Mark P. Stevens ◽  
Fiona M. Tomley ◽  
...  
Keyword(s):  
Well Being ◽  
Dependent Manner ◽  
Secondary Effects ◽  
Negative Effects ◽  
Content Type ◽  
Serovar Typhimurium ◽  
The Impact ◽  
Dose Dependent ◽  
Detrimental Impact

ABSTRACTEimeria tenellacan cause the disease coccidiosis in chickens. The direct and often detrimental impact of this parasite on chicken health, welfare, and productivity is well recognized; however, less is known about the secondary effects that infection may have on other gut pathogens.Campylobacter jejuniis the leading cause of human bacterial foodborne disease in many countries and has been demonstrated to exert negative effects on poultry welfare and production in some broiler lines. Previous studies have shown that concurrentEimeriainfection can influence the colonization and replication of bacteria, such asClostridium perfringensandSalmonella entericaserovar Typhimurium. Through a series ofin vivocoinfection experiments, this study evaluated the impact thatE. tenellainfection had onC. jejunicolonization of chickens, including the influence of variations in parasite dose and sampling time after bacterial challenge. Coinfection withE. tenellaresulted in a significant increase inC. jejunicolonization in the cecum in a parasite dose-dependent manner but a significant decrease inC. jejunicolonization in the spleen and liver of chickens. The results were reproducible at 3 and 10 days after bacterial infection. This work highlights thatE. tenellanot only has a direct impact on the health and well-being of chickens but can have secondary effects on important zoonotic pathogens.

scholarly journals Resuscitation with Lipid Emulsion

2014 ◽  
Vol 120 (4) ◽  
pp. 915-925 ◽  
Author(s):  
Michael R. Fettiplace ◽  
Belinda S. Akpa ◽  
Richard Ripper ◽  
Brian Zider ◽  
Jason Lang ◽  
...  
Keyword(s):  
Lipid Emulsion ◽  
Laboratory Data ◽  
Dependent Manner ◽  
Cardiovascular Toxicity ◽  
Intravenous Lipid Emulsion ◽  
Relative Contribution ◽  
Arterial Blood ◽  
Drug Sequestration ◽  
Dose Dependent

Abstract Background: Recent publications have questioned the validity of the “lipid sink” theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms such as hemodilution. To address these issues, the authors tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, the authors modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration, and inotropy to this response with the use of an in silico model. Methods: Rats were surgically prepared to monitor cardiovascular metrics and deliver drugs. After catheterization and instrumentation, animals received a nonlethal dose of bupivacaine to produce transient cardiovascular toxicity, then were randomized to receive one of the four treatments: 30% intravenous lipid emulsion, 20% intravenous lipid emulsion, intravenous saline, or no treatment (n = 7 per condition; 28 total animals). Recovery responses were compared with the predictions of a pharmacokinetic–pharmacodynamic model parameterized using previously published laboratory data. Results: Rats treated with lipid emulsions recovered faster than did rats treated with saline or no treatment. Intravenous lipid emulsion of 30% elicited the fastest hemodynamic recovery followed in order by 20% intravenous lipid emulsion, saline, and no treatment. An increase in arterial blood pressure underlay the recovery in both lipid emulsion–treated groups. Heart rates remained depressed in all four groups throughout the observation period. Model predictions mirrored the experimental recovery, and the model that combined volume, sequestration, and inotropy predicted in vivo results most accurately. Conclusion: Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, which is driven by a cardiotonic response that complements the previously reported sequestration effect.

Characteristics of relaxation induced by calcitonin gene—related peptide in contracted rabbit basilar artery

1995 ◽  
Vol 82 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Bernhard Sutter ◽  
Satoshi Suzuki ◽  
Neal F. Kassell ◽  
Kevin S. Lee
Keyword(s):  
Basilar Artery ◽  
Contractile Response ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Vascular Response ◽  
Content Type ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent ◽  
Fine Print

✓ Increasing evidence suggests that disturbances in the modulatory influence of the vasoactive peptide, calcitonin gene—related peptide (CGRP), contribute to the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, only limited success has been achieved in trials attempting to ameliorate vasospasm by modifying CGRP function. To better understand the potential utility of targeting CGRP-mediated relaxation, it is important both to identify the interactions CGRP may have with other elements of the vasospastic response and to characterize the mechanisms through which CGRP elicits vasodilative effects. The present studies examined the effects of CGRP on vascular responsiveness using tension measurements of ring strips of rabbit basilar artery maintained in vitro. Pretreatment of vessels with CGRP (100 nM) inhibited vasoconstrictor responses to the potent protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDB). This particular contractile response was selected because PKC-mediated vasoconstriction is a critical component of the vasospastic response after SAH. In a posttreatment paradigm, CGRP was also found to reverse established constriction responses to PDB (2 nM) and histamine (3 µM) in a dose-dependent manner. When tested against the maximum effective dose of PDB (30 nM) in the posttreatment paradigm, CGRP (100 nM) did not elicit significant relaxation. However, after washing both of these drugs out of the test chamber, a persistent effect of CGRP was revealed: the decay of PDB-induced contraction was accelerated in vessels that had previously been treated with CGRP. These findings indicate that CGRP elicits both immediate and sustained influences on contractile responses mediated by PKC. Finally, two potential mechanisms for the vascular response to CGRP were examined. Adenosine triphosphate (ATP)—sensitive K+ channels do not appear to participate in CGRP-mediated dilation; inhibitors of these channels, glibenclamide and tolbutamide, did not block CGRP-induced relaxation. In contrast, a possible role for the nucleotide cyclic adenosine monophosphate (cAMP) in the vascular response to CGRP was indicated by the dose-dependent elevation of cAMP levels by CGRP. Together these studies indicate that CGRP can modulate the contractile response to PKC activation. These effects are associated with increases in the levels of cAMP, but occur independently of fluxes through ATP-sensitive K+ channels.

Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage

1998 ◽  
Vol 88 (3) ◽  
pp. 557-561 ◽  
Author(s):  
Ryszard M. Pluta ◽  
John K. B. Afshar ◽  
Robert J. Boock ◽  
Edward H. Oldfield
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Blood Clot ◽  
Saline Control ◽  
Control Group ◽  
Content Type ◽  
Delayed Cerebral Vasospasm ◽  
Arterial Blood ◽  
Fine Print

Hemoglobin released from hemolysed erythrocytes has been postulated to be responsible for delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). However, the evidence is indirect and the mechanisms of action are unclear. Cerebrovascular tone is regulated by a dynamic balance of relaxing and contracting factors. Loss of the endothelium-derived relaxing factor—nitric oxide in the presence of oxyhemoglobin and overproduction of endothelin-1 stimulated by oxyhemoglobin have been postulated as causes of delayed cerebral vasospasm after SAH. Object. The authors aimed to investigate this hypothesis using in vivo microdialysis to examine time-dependent changes in the perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin in a primate model of SAH. Methods. Nine cynomolgus monkeys underwent right-sided frontotemporal craniectomy and placement of a semipermeable microdialysis catheter adjacent to the right middle cerebral artery (MCA). Saline (control group, three animals) or an arterial blood clot (SAH group, six animals) was then placed around the MCA and the catheter. Arteriographically confirmed vasospasm had developed in all animals with SAH but in none of the control animals on Day 7. The dialysate was collected daily for 12 days. Levels of oxyhemoglobin, deoxyhemoglobin, and methemoglobin were measured by means of spectrophotometry. Perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin peaked on Day 2 in the control monkeys and could not be detected on Days 5 to 12. Perivascular concentrations of oxyhemoglobin and deoxyhemoglobin peaked on Day 7 in the SAH group, at which time the concentrations in the dialysate were 100-fold higher than in any sample obtained from the control animals. Methemoglobin levels increased only slightly, peaking between Days 7 and 12, at which time the concentration in the dialysate was 10-fold higher than in samples from the control animals. Conclusions. This study provides in vivo evidence that the concentrations of oxyhemoglobin and deoxyhemoglobin increase in the cerebral subarachnoid perivascular space during the development of delayed cerebral vasospasm. The results support the hypothesis that oxyhemoglobin is involved in the pathogenesis of delayed cerebral vasospasm after SAH and implicate deoxyhemoglobin as a possible vasospastic agent.

scholarly journals Virulence-Suppressing Effects of Linezolid on Methicillin-Resistant Staphylococcus aureus: Possible Contribution to Early Defervescence

2012 ◽  
Vol 56 (4) ◽  
pp. 1744-1748 ◽  
Author(s):  
Sadako Yoshizawa ◽  
Kazuhiro Tateda ◽  
Tomoo Saga ◽  
Yoshikazu Ishii ◽  
Keizo Yamaguchi
Keyword(s):  
Staphylococcus Aureus ◽  
Inflammatory Cytokines ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Positive Culture ◽  
Dependent Manner ◽  
Content Type ◽  
Anti Inflammatory ◽  
Dose Dependent

ABSTRACTIn the present study, immunomodulatory effects of linezolid (LZD) on methicillin-resistanceStaphylococcus aureus(MRSA) infections were evaluated. We have retrospectively reviewed treatment effects of LZD on 52 patients with severe MRSA infections. Sixty-four percent of the febrile patients demonstrated significant defervescence within 3 days, despite the presence of positive culture results. We speculated that this finding might be due to early anti-inflammatory effects of LZD, and to investigate this further we initiatedin vivoexperiments using mice MRSA pneumonia models. Mice were treated with either LZD or vancomycin (VCM) immediately after intranasal administration of MRSA. Bacterial numbers and levels of inflammatory cytokines in the lungs were determined. Although the bacterial burden in the lungs was not apparently different between the two groups, LZD but not VCM treatment significantly reduced induction of inflammatory cytokines in the lungs (P< 0.05). To evaluate whether this anti-inflammatory response was due to suppression of virulence factor expression, filter-sterilized supernatants of MRSA incubated in broth overnight with sub-MICs of LZD were subcutaneously administered to mice. To clarify whether LZD possesses direct host-modulating activity, cytokine responses to the supernatants were examined in mice pretreated with LZD. Interestingly, MRSA solutions prepared in the presence of sub-MICs of LZD revealed significant suppression of interleukin 6 (IL-6) in a dose-dependent manner (P< 0.05), but pretreatment of mice with LZD revealed no changes in cytokines. These findings suggest that sub-MICs of LZD might suppress virulence factors of MRSA, which may be associated with a reduction in endogenous pyrogens. These data may explain at least in part early defervescence observed in LZD-treated individuals.

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