Background
The major concern in patients who have suffered from cardiac arrest (CA) and undergone successful extracorporeal cardiopulmonary resuscitation (E‐CPR) is poor neurological outcomes. In ...this study, we aimed to introduce a rat model of selective brain perfusion (SBP) during E‐CPR to improve the neurological outcome after CA.
Methods
The rats underwent 7 min of untreated asphyxial CA and then were resuscitated with E‐CPR for 30 min. The right external jugular vein and right femoral artery were separately cannulated to the E‐CPR outflow and inflow. The right common carotid artery was cannulated from the proximal to the distal side for SBP. Subsequently, rats were removed from E‐CPR, wounds were closed, and 90 min of intensive care were provided. Neurological deficit scores were tested after 4 h of recovery when the rats were mechanical ventilation‐free. S100 calcium‐binding protein B (S100B) and glial fibrillary acidic protein (GFAP) were detected through immunohistochemistry (IHC) of brain tissue.
Results
The rats that received SBP while resuscitated by E‐CPR showed markedly better neurological performances after 4‐h recovery than those resuscitated by E‐CPR only. The IHC staining of GFAP and S100B in the hippocampus was low in the rats receiving SBP during E‐CPR, but only GFAP showed significant differences.
Conclusions
We successfully developed a novel and reproducible rat model of SBP while resuscitated by E‐CPR to ameliorate the neurological performances after CA. This achievement might have opportunities for studying how to improve the neurological outcome in the clinical condition.
Extracorporeal cardiopulmonary resuscitation with selective brain perfusion system in a rat model.
Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested to reduce the risk of cardiovascular events owing ...to their pleiotropic effects on the vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition of vascular smooth muscle cell proliferation. The major beneficial effect of statins in maintaining vascular homeostasis is the induction of nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) in endothelial cells. The mechanisms underlying the increased NO bioavailability and eNOS activation by statins have been well-established in various fields, including transcriptional and post-transcriptional regulation, kinase-dependent phosphorylation and protein-protein interactions. However, the mechanism by which statins affect the metabolism of L-arginine, a precursor of NO biosynthesis, has rarely been discussed. Autophagy, which is crucial for energy homeostasis, regulates endothelial functions, including NO production and angiogenesis, and is a potential therapeutic target for cardiovascular diseases. In this review, in addition to summarizing the molecular mechanisms underlying increased NO bioavailability and eNOS activation by statins, we also discuss the effects of statins on the metabolism of L-arginine.
Display omitted
•The regulatory mechanisms of statins in the regulation of eNOS expression and eNOS activity.•The role of L-arginine metabolism in the statins-elicited NO bioavailability.•The potential therapeutic effects of statins on the treatment of vascular diseases.
Triangular gold nanoplates (TAuNPs) were prepared by a one-step rapid growth method and then reduced and stabilized on two-dimensional nano mica nanoplatelets (NMPs). We also prepared TAuNP/NMP ...nanohybrids with a three-dimensional lightning-rod effect by oxidative etching. The surface of the delaminated NMPs (only 1 nm thick) is highly charged and can provide a large specific surface area; thus, it can be used as a substrate for the stable growth of gold nanoplates. In addition, by controlling relevant synthesis parameters, the edge length of the TAuNPs can be easily adjusted in the range of 30-90 nm. During reduction of the TAuNPs, the cationic surfactant cetyltrimethylammonium chloride was added as a protective agent to surround the TAuNPs; consequently, the surface was positively charged, which facilitates adsorption for detecting molecules with negative charges. When nanohybrids were used in surface-enhanced Raman spectroscopy (SERS) to detect adenine molecules, the limit of detection concentration was 10
−9
M. The Raman enhancement factor was 5.7 × 10
7
, and the relative standard deviation (RSD) was 9.8%. Finally, this method was applied to the biological detection of
Staphylococcus aureu
s, and the surface charge and hydrophilic properties of the material significantly improved the SERS signal of
S. aureus
. The limit of detection concentration was 10
2
CFU mL
−1
, and the RSD was 11.2%. The TAuNP/NMP nanohybrids can provide very rapid and sensitive SERS detection of biomolecules.
Triangular gold nanoplates (TAuNPs) were prepared by a one-step rapid growth method and then reduced and stabilized on two-dimensional nano mica nanoplatelets (NMPs).
Extracorporeal life support (ECLS) is a world-famous life-saving method. Until now, changes in arterial wave properties due to ECLS have remained unexamined. In this study, we determined the effects ...of ECLS on arterial wave properties and ventricular/arterial coupling in male Wistar rats with the measured aortic pressure alone. Ascending aortic pressure signals were measured before ECLS and at 30, 60, and 90 min after weaned off. The aortic pressure signal then calculated by fourth-order derivative to obtain an assumed triangular flow wave. The ratio of mean systolic pressure to mean diastolic pressure (P
/P
), a parameter for evaluating the matching condition between myocardial oxygen demand and supply, was significantly higher after ECLS. The magnitude of forward pressure (|P
|) augmented by ECLS prevailed over the backward pressure (|P
|), leading to a decline in wave reflection factor. P
/P
was positively linearly correlated with |P
| (P
/P
= 0.9177 + 0.0078 × |P
|, r = 0.8677; P < 0.0001). These findings suggest that |P
| was a predominant factor responsible for the mismatch between the myocardial oxygen demand and supply in rats after ECLS phase of experiment.
The cardiac pumping mechanics can be characterized by both the maximal systolic elastance (
E
max
) and theoretical maximum flow (
Q
max
), which are generated using an elastance–resistance model. ...The signals required to fit the elastance–resistance model are the simultaneously recorded left ventricular (LV) pressure and aortic flow (
Q
m
), followed by the isovolumic LV pressure. In this study, we evaluated a single-beat estimation technique for determining the
E
max
and
Q
max
by using the elastance–resistance model based solely on the measured LV pressure and cardiac output. The isovolumic LV pressure was estimated from the measured LV pressure by using a non-linear least-squares approximation technique. The measured
Q
m
was approximated by an unknown triangular flow (
Q
tri
), which was generated by using a fourth-order derivative of the LV pressure. The
Q
tri
scale was calibrated using the cardiac output. Values of
E
max
triQ
and
Q
max
triQ
obtained using
Q
tri
were compared with those of
E
max
mQ
and
Q
max
mQ
obtained from the measured
Q
m
. Healthy rats and rats with chronic kidney disease or diabetes mellitus were examined. We found that the LV
E
max
and
Q
max
can be approximately calculated using the assumed
Q
tri
, and they strongly correlated with the corresponding values derived from
Q
m
(
P
< 0.0001;
n
= 78):
E
max
triQ
= 51.9133 + 0.8992 ×
E
max
mQ
(
r
2
= 0.8257;
P
< 0.0001);
Q
max
triQ
= 2.4053 + 0.9767 ×
Q
max
mQ
(
r
2
= 0.7798;
P
< 0.0001). Our findings suggest that the proposed technique can be a useful tool for determining
E
max
and
Q
max
by using a single LV pressure pulse together with cardiac output.
Pigs have anatomical and physiological characteristics comparable to those in humans and, therefore, are a favorable model for immune function research. Interferons (IFNs) and inflammasomes have ...essential roles in the innate immune system. Here, we report that G10, a human-specific agonist of stimulator of interferon genes (STING), activates both type I IFN and the canonical NLRP3 inflammasome in a STING-dependent manner in porcine cells. Without a priming signal, G10 alone transcriptionally stimulated Sp1-dependent
expression, thus triggering activation of the nuclear factor-κB (NF-κB) signaling pathway and thereby priming inflammasome activation. G10 was also found to induce potassium efflux- and NLRP3/ASC/Caspase-1-dependent secretion of IL-1β and IL-18. Pharmacological and genetic inhibition of NLRP3 inflammasomes increased G10-induced type I IFN expression, thereby preventing virus infection, suggesting negative regulation of the NLRP3 inflammasome in the IFN response in the context of STING-mediated innate immune activation. Overall, our findings reveal a new mechanism through which G10 activates the NLRP3 inflammasome in porcine cells and provide new insights into STING-mediated innate immunity in pigs compared with humans.
Without affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes. In this ...study, we investigated whether low-dose atorvastatin exerts any beneficial effect on vascular dynamics in streptozotocin (STZ)-induced diabetes in male Wistar rats.
Diabetes was induced using a single tail-vein injection of STZ at 55 mg kg-1. The diabetic rats were treated daily with atorvastatin (10 mg kg-1 by oral gavage) for 6 weeks. They were also compared with untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. A thiobarbituric acid reactive substances measurement was used to estimate the malondialdehyde content.
The high plasma level of total cholesterol in the diabetic rats did not change in response to this low-dose treatment with atorvastatin. Atorvastatin resulted in a significant increase of 15.4% in wave transit time and a decrease of 33.5% in wave reflection factor, suggesting that atorvastatin may attenuate the diabetes-induced deterioration in systolic loads imposed on the heart. This was in parallel with its lowering of malondialdehyde content in plasma and aortic walls in diabetes. Atorvastatin therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the diminished ratio of left ventricular weight to body weight.
These findings indicate that low-dose atorvastatin might protect diabetic vasculature against diabetes-associated deterioration in aorta stiffness and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived malondialdehyde.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Extracorporeal life support (ECLS) systems are life-saving devices used for treating patients with severe cardiopulmonary failure. In this study, we implemented a rat model of ECLS without the ...administration of inotropes or vasopressors.
The rats underwent 5 min of untreated asphyxial cardiac arrest and were resuscitated by ECLS for 30 min. The right external jugular vein and right femoral artery were separately cannulated to the ECLS outflow and inflow, respectively. Thereafter, ECLS was terminated, wounds were closed, and mechanical ventilation was provided for another 90 min. Subsequently, blood gas and hemodynamic analyses were performed. The plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) were measured 120 min after reperfusion.
The metabolic rate of lactate in the group of asphyxial cardiac arrest rescued by ECLS was slow; therefore, the pH at 120 min after reperfusion was significantly lower in this group than that in the group of normal rats treated with ECLS. The hemodynamic data showed no between-group differences. The plasma levels of CRP, IL-6, IL-10, and TNF-α increased after ECLS treatment.
We successfully established a rodent ECLS model, which might be a useful approach for studying the pathophysiology induced by ECLS under clinical conditions.
In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the effects of ...acetyl-l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship.
Diabetes was induced by a single tail vein injection of 55 mg kg(-1) streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L(-1) in drinking water) or oxfenicine (150 mg kg(-1) by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max). Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance.
When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E max associated with the unaltered Q max. Acetyl-l-carnitine (but not oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl-l-carnitine or oxfenicine resulted in an increase in E max, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q max showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Q max corresponded to an increase in total vascular resistance when treated with oxfenicine.
Acetyl-l-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes-induced deterioration in myocardial intrinsic contractility associated with unaltered LV internal resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. ...Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.
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