Early referrals save lives in advanced heart failure.

ABSTRACT: Heart failure (HF) is a chronic, progressive medical condition that can quickly cause deterioration of the patient's medical and functional status. Delay of HF diagnosis and improper treatment can lead to catastrophic patient outcomes. This case report describes a 62-year-old with HF with reduced ejection fraction secondary to nonischemic cardiomyopathy, s/p cardiac resynchronization therapy defibrillator in 2020. He presented to the emergency department for worsening shortness of breath and chest pain for 3 days and subsequently had cardiac arrest. The patient eventually underwent a successful implantation of left ventricular assist device as a bridge to transplant. Timely referral yields a better patient outcome. This case study illustrates a clinical pathway that can be used by primary care providers when considering referral of a patient with advanced HF (AHF) to an AHF center for management and possible advanced therapies.

Influence of lipids with hydroxyl-containing head groups on Fe2+ (Cu2+)/H2O2-mediated transformation of phospholipids in model membranes.

Under condition of ROS formation in lipid membranes, free radical reactions can proceed in both hydrophobic (peroxidation of lipids, POL) and polar (free radical fragmentation) parts of the bilayer. Free-radical fragmentation is typical for the lipids containing a hydroxyl group in ß-position with respect to an ester or amide bond. The present study has been undertaken to investigate free-radical transformations of phospholipids in model membranes containing lipids able to undergo fragmentation in their polar part. Liposomes from egg yolk lecithin containing saturated or monounsaturated glycero- and sphingolipids were subjected to the action of an HO* - generating system - Fe(2+)(Cu(2+))/H2O2/Asc, and the POL products were investigated. In parallel with this, the effects of monoacylglycerols and scavengers of reactive species on Fe(2+)(Cu(2+))/H2O2/Asc - mediated free-radical fragmentation of phosphatidylglycerols were studied. Hydroxyl-containing sphingolipids and glycerolipids, which undergo free-radical fragmentation under such conditions, manifested antioxidant properties in the model membranes. In the absence of HO groups in the lipid structure, the effect was either pro-oxidant or neutral. Monoacylglycerols slowed down the rate of both peroxidation in the hydrophobic part and free-radical fragmentation in the hydrophilic part of phospholipid membrane. Scavengers of reactive species inhibited the fragmentation of phosphatidylglycerol substantially. Thus, the ability of hydroxyl-containing lipids to undergo free-radical fragmentation in polar part apparently makes a substantial contribution to the mechanism of their protector action.

Fragmentation of mitochondrial cardiolipin by copper ions in the Atp7b-/- mouse model of Wilson's disease.

Cellular copper overload as found in Wilson's disease may disturb mitochondrial function and integrity. Atp7b(-/-) mice accumulate copper in the liver and serve as an animal model for this inherited disease. The molecular mechanism of copper toxicity in hepatocytes is poorly understood. Total mitochondrial lipids from liver of wild-type mice were subjected to oxidative stress by the Cu(2+)/H(2)O(2)/ascorbate system. Phosphatidic acid (PA) and phosphatidylhydroxyacetone (PHA) were detected as cardiolipin fragmentation products by thin-layer chromatography combined with MALDI-TOF mass spectrometry in oxidized samples, but not in unperturbed ones. The formation of PA and PHA in copper-treated model membrane correlated well with the decrease of cardiolipin. Mitochondrial lipids from Atp7b(-/-) mice of different age were analyzed for the presence of PA. While 32-weeks old wild-type (control) and Atp7b(-/-) mice did not show any PA, there was a steady increase in the amount of this lipid in Atp7b(-/-) mice in contrast to control with increasing age. Hepatocytes from elder Atp7b(-/-)mice contained morphologically changed mitochondria unlike cells from wild-type animals of the same age. We concluded that free-radical fragmentation of cardiolipin with the formation of PA is a likely mechanism that damages mitochondria under conditions of oxidative stress due to copper overload. Our findings are relevant for better understanding of molecular mechanisms for liver damage found in Wilson's disease.

Under-triage as a significant factor affecting transfer time between the emergency department and the intensive care unit.

INTRODUCTION: The purpose of the study was to identify factors that affect transfer times between the emergency department and the intensive care unit (ICU) in a community hospital. Patients who are transferred from the emergency department to the ICU are usually in critical condition and in need of prompt treatment by qualified personnel. As a result of delayed transfers, a patient may experience complications, such as increased mortality rates and longer hospital stays. METHODS: A quantitative descriptive correlational design was used in this study. Data were collected from the charts of 75 patients who were transferred from the emergency department to the ICU of a 142-bed community hospital in the eastern United States. "Delayed patients" were identified as those who were transferred after more than 4 hours. RESULTS: Forty-four patients (58.7%) spent more than 4 hours in the emergency department. Nineteen out of 25 patients (76%) with an Emergency Severity Index designation of 3 were identified as delayed. Delayed status and an Emergency Severity Index designation of 3 showed a significant correlation (r = -.339, P = .004). Eleven patients (64.7%) diagnosed with sepsis were delayed, compared with 6 who were not delayed. A total of 70.4% of female patients were delayed, compared with 52.1% of male patients. DISCUSSION: This study provides a more comprehensive view of the factors involved in delayed patient transfer and provides data needed for effective interventions to be developed. The results suggest significant problems with the under-triage of critically ill patients, specifically patients with sepsis. Future research should include a larger group of subjects and a multifactorial analysis.

Free radical fragmentation of cardiolipin by cytochrome c.

The effect of cytochrome c (cyt c) on degradation of cardiolipin in its polar part was investigated in cardiolipin/phosphatidylcholine (CL/PC) liposomes incubated with cyt c/H(2)O(2)/and (or) ascorbate by high-performance thin layer chromatography and MALDI-TOF mass spectrometry. It has been shown that phosphatidic acid (PA) and phosphatidylhydroxyacetone (PHA) were formed in the system under conditions where hydrogen peroxide favours a release of heme iron from cyt c. The formation of PA and PHA occurs via an OH-induced fragmentation taking place in the polar moiety of cardiolipin. Formation of fragmentation products correlated with the loss of CL in CL/PC liposomes incubated with cyt c/H(2)O(2)/ascorbate or with Cu(2+)/H(2)O(2)/ascorbate.

Formation of phosphatidic acid in stressed mitochondria.

Mitochondria are an important intracellular source of ROS as well as a sensitive target for oxidative damage under certain pathological conditions such as iron or copper overload. Mitochondrial membranes are rich in the tetraacyl phospholipid cardiolipin. Its integrity is important for efficient oxidative phosphorylation. Mouse liver mitochondria were subjected to oxidative stress by the Cu(2+)(Fe(2+))/H(2)O(2)/ascorbate system. Phosphatidic acid was detected in oxidized mitochondria, but not in unperturbed mitochondria. The Cu(2+)/H(2)O(2)/and (or not) ascorbate system caused the formation of phosphatidic acid and phosphatidylhydroxyacetone in cardiolipin liposomes. These products proceed via an HO*-radical induced fragmentation taking place in the polar moiety of cardiolipin. Mass spectrometry analysis of phosphatidic acid newly formed in mitochondria revealed that it has been derived from fragmentation of cardiolipin. Thus, free-radical fragmentation of cardiolipin in its polar part with the formation of phosphatidic acid is a likely mechanism that damages mitochondria under conditions of oxidative stress.

Iron-mediated free-radical formation of signaling lipids in a model system.

It has been shown using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and its combination with thin-layer chromatography (TLC) that the action of the ascorbate/Fe(2+)/H(2)O(2) oxidizing system on cardiolipin and galactocerebroside results in the formation of phosphatidic acid (PA) and ceramide (Cer), respectively. These data, when combined with results obtained on radiolysis of similar substances, allowed the conclusion that the formation of PA and Cer occurs via an OH-induced fragmentation taking place in polar moiety of the starting substrates.

Free-radical fragmentation of galactocerebrosides: a MALDI-TOF mass spectrometry study.

Analysis of final products of radiation-induced transformations of galactocerebrosides (GalCer) in aqueous dispersions has been performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and its combination of thin-layer chromatography (TLC). Ceramides were found to be the main products of GalCer gamma-radiolysis. From experimental results obtained in this study, as well as from the data available in the literature, an inference is made that the formation of ceramides occurs owing to fragmentation of radicals with an unpaired electron of the C2 atom of the carbohydrate moiety, formed from the starting compounds.

Radiation-induced free-radical transformation of phospholipids: MALDI-TOF MS study.

Under the action of free-radical reaction initiators on membrane phospholipids, complex processes are taking place in both hydrophobic and hydrophilic parts of the phospholipids. Realization of these processes results in a mixture consisting of the initial lipids and their peroxidation and fragmentation products. Identification of compounds in such mixtures requires analytical methods of high sensitivity, reproducibility and accuracy to be applied. These properties are characteristic of the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. In the studies of radiation-induced free-radical transformations of phosphatidylglycerol, the MALDI-TOF MS in combination with thin layer chromatography (TLC) has been shown to be able to detect and identify products of free-radical transformations taking place in both hydrophilic and hydrophobic parts of the phospholipid. Thus, the MALDI-TOF MS can serve as a suitable analytical tool to investigate free-radical transformations of lipids.

Novel (3,5-di-tert-butyl-2-hydroxy-phenylcarbamoyl)-alkanoic acids as potent antioxidants.

A series of novel phenolic antioxidants of amphiphilic structure has been synthesized. Investigations into the influence of aliphatic spacer length and nature of a hydrophilic anchor on the antioxidant activity allowed elucidating certain structure requirements for the membrane-addressed antioxidant designing.

Formation of phosphatidic acid, ceramide, and diglyceride on radiolysis of lipids: identification by MALDI-TOF mass spectrometry.

By use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, phosphatidic acid was found to be the main product of gamma radiolysis of cardiolipin, phosphatidylinositol, and phosphatidylglycerol. It has been shown that gamma irradiation of such glycolipids as cerebroside and galactosyl diglyceride leads to formation of ceramide and diglyceride, respectively. These findings, combined with those obtained earlier, allowed an assumption to be made that, owing to radiation-induced free radical fragmentation of lipids in their polar moiety, formation of signaling molecules can occur.

Synthesis and properties of 11-(3,5-di-tert-butyl-2-hydroxyphenylcarbamoyl)undecanoic acid, a new amphiphilic antioxidant.

Based on the membrane addressing concept, designing and synthesis of 11-(3,5-di-tert-butyl-2-hydroxyphenylcarbamoyl)undecanoic acid have been carried out. Antioxidant properties of the prepared compound were investigated in comparison with its non-amphiphilic analogues.