Cardiac arrest resuscitation: neurologic prognostication and brain death.

Purpose Of Review: Persistent coma after cardiac arrest is a source of great emotional and financial cost to grieving family members in particular and the healthcare system in general. Neurologic prognostication helps guide appropriate discussions between family members and healthcare providers. Recent advances in therapeutic care increase the challenges, both medical and financial, on local practitioners.

Asthma, allergy, and airway hyperresponsiveness are not linked to the beta(2)-adrenoceptor gene.

Study Objectives: To exclude genetic linkage between the beta(2)-adrenoceptor gene and asthma, allergy, and methacholine airway hyperresponsiveness.

Design: The current study used six distinct intragene markers within the beta(2)-adrenoceptor gene, and evaluated genetic linkage between the beta(2)-adrenoceptor and asthma, allergy, or methacholine airway hyperresponsiveness in eight multiplex families.

Patients: Forty-nine members of eight multiplex families with a high incidence of asthma.

Genetic linkage analysis of susceptibility to particle exposure in mice.

Particle-induced increases in respiratory morbidity and mortality have been observed worldwide in industrialized cities but the toxicologic mechanisms have not been elucidated. It is hypothesized that subpopulations including the elderly and individuals with cardiopulmonary disease are particularly at risk to the effects of exposure. Genetic background is another important host factor that may contribute to interindividual responsivity to particulate exposure.

Facile detection of mitochondrial DNA mutations in tumors and bodily fluids.

Examination of human bladder, head and neck, and lung primary tumors revealed a high frequency of mitochondrial DNA (mtDNA) mutations. The majority of these somatic mutations were homoplasmic in nature, indicating that the mutant mtDNA became dominant in tumor cells. The mutated mtDNA was readily detectable in paired bodily fluids from each type of cancer and was 19 to 220 times as abundant as mutated nuclear p53 DNA.

Effects of loaded breathing and hypoxia on diaphragm metabolism as measured by (31)P-NMR spectroscopy.

Diaphragm fatigue may contribute to respiratory failure. (31)P-nuclear magnetic resonance spectroscopy is a useful tool to assess energetic changes within the diaphragm during fatigue, as indicated by P(i) accumulation and phosphocreatine (PCr) depletion. We hypothesized that loaded breathing during hypoxia would lead to diaphragm fatigue and inadequate aerobic metabolism.

Effect of arrest time and cerebral perfusion pressure during cardiopulmonary resuscitation on cerebral blood flow, metabolism, adenosine triphosphate recovery, and pH in dogs.

Objectives: To test the hypothesis that greater cerebral perfusion pressure (CPP) is required to restore cerebral blood flow (CBF), oxygen metabolism, adenosine triphosphate (ATP), and intracellular pH (pHi) levels after variable periods of no-flow than to maintain them when cardiopulmonary resuscitation (CPR) is started immediately.

Design: Prospective, randomized, comparison of three arrest times and two perfusion pressures during CPR in 24 anesthetized dogs.

Setting: University cerebral resuscitation laboratory.

Effect of the no-flow interval and hypothermia on cerebral blood flow and metabolism during cardiopulmonary resuscitation in dogs.

Background And Purpose: We sought (1) to determine the effect of brief periods of no flow on the subsequent forebrain blood flow during cardiopulmonary resuscitation (CPR) and (2) to test the hypothesis that hypothermia prevents the impact of the no-flow duration on cerebral blood flow (CBF) during CPR.

Methods: No-flow intervals of 1.5, 3, and 6 minutes before CPR at brain temperatures of 28 degreesC and 38 degreesC were compared in 6 groups of anesthetized dogs.

Asthma and bronchial hyperresponsiveness linked to the XY long arm pseudoautosomal region.

We examined the long arm XY pseudoautosomal region for linkage to asthma, serum IgE, and bronchial hyperresponsiveness. In 57 Caucasian families multipoint nonparametric analyses provide evidence for linkage between DXYS154 and bronchial hyperresponsiveness (P = 0.000057) or asthma (P = 0.

Proton NMR spectroscopy of solvent-saturable resonances: a new approach to study pH effects in situ.

It is shown that the effect of pH changes can be measured in proton NMR spectra through the pH sensitivity of the signal intensities of metabolite protons exchanging with water. To observe this phenomenon, pulse sequences must be used that can sensitively observe these exchangeable protons under physiological conditions, which is achieved by avoiding magnetization transfer signal losses due to water saturation for solvent suppression purposes. These methods provide an order-of-magnitude enhancement of many signals between 5 and 10 ppm, containing both N-bound protons as well as aromatic C-H protons coupled to them, the intensity of which is influenced by exchange-relayed saturation.

Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging.

The ability to measure the effects of local alterations in blood flow, blood volume and oxygenation by nuclear magnetic resonance has stimulated a surge of activity in functional MRI of many organs, particularly in its application to cognitive neuroscience. However, the exact description of these effects in terms of the interrelations between the MRI signal changes and the basic physiological parameters has remained an elusive goal. We here present this fundamental theory for spin-echo signal changes in perfused tissue and validate it in vivo in the cat brain by using the physiological alteration of hypoxic hypoxia.

Determination of cerebral glucose transport and metabolic kinetics by dynamic MR spectroscopy.

A new in vivo nuclear magnetic resonance (NMR) spectroscopy method is introduced that dynamically measures cerebral utilization of magnetically labeled [1-13C]glucose from the change in total brain glucose signals on infusion. Kinetic equations are derived using a four-compartment model incorporating glucose transport and phosphorylation. Brain extract data show that the glucose 6-phosphate concentration is negligible relative to glucose, simplifying the kinetics to three compartments and allowing direct determination of the glucose-utilization half-life time [t1/2 = ln2/(k2 + k3)] from the time dependence of the NMR signal.

Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice.

Exposures to the common air pollutant ozone (O3) cause decrements in pulmonary function and induce airway inflammation that is characterized by infiltration of polymorphonuclear neutrophils (PMNs; refs 1-4). Because of the impact that O3 may have on public health, it is critical to identify susceptibility factors. Highly reproducible, significant inter-individual variations in human pulmonary function responses to O3 support the hypothesis that genetic background is an important determinant.

Interleukin 9: a candidate gene for asthma.

Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of atopy and bronchial hyperresponsiveness. Recent studies localized a major gene for asthma to chromosome 5q31-q33 in humans. Thus, this segment of the genome represents a candidate region for genes that determine susceptibility to bronchial hyperresponsiveness and atopy in animal models.

Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice.

We investigated the mode of inheritance of susceptibility to nitrogen dioxide (NO2)-induced lung injury in inbred mice. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) mice, as well as F1, F2, and backcross (BX) populations derived from them, were exposed to 15 parts per million NO2 for 3 h. Six hours after exposure, animals were lavaged, and differential cell counts and cell viability (cytotoxicity) were measured.

Visual activation in alpha-chloralose-anaesthetized cats does not cause lactate accumulation in the visual cortex as detected by [1H]NMR difference spectroscopy.

The hypothesis that neuronal activation results in lactate accumulation due to mismatch between glucose and oxygen consumption was tested in the cat model of visual activation by monitoring cerebral metabolism with localized 1H nuclear magnetic resonance spectroscopy (MRS). Adult cats were anaesthetized with alpha-chloralose, paralysed and mechanically ventilated. Visual evoked potentials measured over the occipital cortex showed maximal amplitude at 2 Hz stimulation, but the latencies of the early cortical potentials, N1 and P1, were independent of stimulation frequency.

In vivo diaphragm metabolism: comparison of paced and inspiratory resistive loaded breathing in piglets.

Objective: We hypothesized that spontaneous, loaded diaphragm contractions would lead to diaphragm fatigue, which would correlate with inadequate oxidative metabolism as measured by phosphorus-31 nuclear magnetic resonance spectroscopy.

Design: Prospective, randomized, crossover trial.

Setting: University hospital research laboratory.

Correlation of the average water diffusion constant with cerebral blood flow and ischemic damage after transient middle cerebral artery occlusion in cats.

Magnetic resonance water diffusion imaging can detect early ischemic changes in stroke. Using a middle cerebral artery occlusion model, we examined which range of values of the orientation-independent diffusion quantity Dav = 1/3Trace(D) = 1/3(Dxx + Dyy + Dzz) is an early noninvasive indicator of reduced cerebral perfusion and focal brain injury. Cats underwent either a 30-min occlusion followed by 3.

Effect of aminophylline on high-energy phosphate metabolism and fatigue in the diaphragm.

Background: Diaphragmatic fatigue causes respiratory failure, for which aminophylline has been used as therapy. Because the mechanism of action of aminophylline in reversing diaphragmatic fatigue is unclear, we used in vivo 31P magnetic resonance spectroscopy (MRS) to determine the relation between diaphragmatic activation, force output, and aerobic metabolism.

Methods: Bilateral phrenic stimulation was used to pace the diaphragm in pentobarbital-anesthetized piglets (6-10 weeks old; n = 44).

Correlation of rapid changes in the average water diffusion constant and the concentrations of lactate and ATP breakdown products during global ischemia in cat brain.

Rapid changes in the average water diffusion constant, Dav = 1/3[Dxx+Dyy+Dzz], and in the concentrations of lactate and purine nucleotides and nucleosides were measured upon global ischemia (cardiac arrest) in cat brain, at a combined time resolution of 36 s (n = 7). At this time resolution, the normalized time curves of 1 - Dav and the increase in ATP breakdown product did not coincide, with the changes in Dav being most rapid. The normalized curves of 1 - Dav and the lactate increase coincided for the first 2-2.

Poor hemodynamic and metabolic recovery after global incomplete cerebral ischemia associated with short-term diabetes in dogs.

We determined the effect of 4-5 weeks of diabetes on ATP recovery following global incomplete cerebral ischemia. 31P magnetic resonance spectra of ATP, intracellular pH (pHi), and CBF (radiolabeled microspheres) were measured in three groups of anesthetized dogs (n = 8/group): chronic hyperglycemic diabetes (pancreatectomy followed by blood glucose of > 10 mM for 4-5 weeks); acute hyperglycemia (blood glucose of > 10 mM) during ischemia and reperfusion in nondiabetic dogs; and normoglycemic controls. Twenty minutes of incomplete ischemia was produced by ventricular fluid infusion to keep cerebral perfusion pressure (CPP) at 10 mm Hg during spontaneous variations in MABP.

Acidemia and brain pH during prolonged cardiopulmonary resuscitation in dogs.

Background And Purpose: Cardiopulmonary resuscitation (CPR) generating low perfusion pressures and beginning immediately after cardiac arrest maintains cerebral ATP but not cerebral pH or arterial pH. We tested the hypothesis that preventing severe arterial acidemia prevents cerebral acidosis, whereas augmenting arterial acidemia augments cerebral acidosis.

Methods: In dogs anesthetized with pentobarbital and fentanyl, cerebral pH and ATP were measured with 31P MR spectroscopy and blood flow was measured with radiolabeled microspheres.

Diabetic chronic hyperglycemia and cerebral pH recovery following global ischemia in dogs.

Background And Purpose: We determined the effect of chronic hyperglycemia associated with diabetes on recovery of cerebral pH after global incomplete cerebral ischemia.

Methods: 31P magnetic resonance spectra and cerebral blood flow (radiolabeled microspheres) were measured in three groups of dogs: (1) chronic hyperglycemic diabetes (pancreatectomy followed by blood glucose > 10 mmol/L for 3 months; n = 8); (2) acute hyperglycemia during ischemia and reperfusion in nondiabetic dogs (n = 8); and (3) normoglycemic controls (n = 8). Incomplete ischemia was produced for 20 minutes by ventricular fluid infusion followed by 3 hours of reperfusion.

Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain.

Changes in the diffusion constant of water during reversible brain ischemia and cardiac arrest were monitored with a 10-s time resolution. Results (five cats, three rats) indicate that these changes are reversible and that the bulk of the changes are not caused by temperature or motion related to brain pulsations and blood flow. The rapid time course of the changes corresponds to the known time course for changes in energy state, signal transduction, and ionic homeostasis.