Assessment of right ventricular function in healthy Great Danes and in Great Danes with dilated cardiomyopathy.

INTRODUCTION: Right ventricular (RV) dysfunction is a significant negative prognostic indicator in human dilated cardiomyopathy (DCM). Many RV indices are weight-dependent, and there is a lack of reference values for the right heart in giant breed dogs (over 50 kg), including Great Danes (GDs). This study aimed to compare indices of RV function in echocardiographically normal GDs, those with preclinical DCM (PC-DCM), and those with DCM and congestive heart failure (DCM-CHF). ANIMALS: A total of 116 client-owned adult GDs: 74 normal, 31 with PC-DCM, and 11 with DCM-CHF. METHODS: A retrospective, single-center cohort study assessed RV function using free-wall RV longitudinal strain (RVLS), strain rate, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and pulsed-wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (TDI S'). Relationships between DCM status and RV function indices were analyzed. RESULTS: RV function, measured by TAPSE (P=0.001), FAC (P<0.001), and TDI S' (P<0.001), decreased in dogs with PC-DCM and DCM-CHF compared to healthy dogs, with FAC being lower in DCM-CHF compared to PC-DCM (P=0.048). RVLS impairment was more significant in the DCM-CHF group than in the PC-DCM group (P=0.048). RVLS had the highest area under the curve (0.899) for differentiating between normal and DCM-CHF dogs. CONCLUSION: As DCM progresses, echocardiographic variables of RV function, including TAPSE, FAC, TDI S', RVLS, and strain rate, worsen, indicating impaired RV systolic function in GDs affected by DCM.

Long-term outcome and troponin I concentrations in Great Danes screened for dilated cardiomyopathy: an observational retrospective epidemiological study.

INTRODUCTION: Dilated cardiomyopathy (DCM) is common in Great Danes (GDs) but screening for this condition can be challenging. We hypothesised that cardiac troponin-I (cTnI) concentration is elevated in GDs with DCM and/or ventricular arrhythmias (VAs), and is associated with reduced survival time in GDs. ANIMALS: One hundred and twenty-four client-owned GDs assigned echocardiographically as normal (n = 53), equivocal (n = 37), preclinical DCM (n = 21), or clinical DCM (n = 13). MATERIALS AND METHODS: A retrospective epidemiological study. Echocardiographic diagnosis, VAs, and contemporaneous cTnI concentrations were recorded. Diagnostic accuracy and cTnI cut-offs were determined with receiver operating characteristic analyses. Effects of the cTnI concentration and disease status on survival and cause of death were explored. RESULTS: Median cTnI was greater in clinical DCM (0.6 ng/mL [25th-75th percentiles: 0.41-1.71 ng/mL]) and GDs with VAs (0.5 ng/mL [0.27-0.80 ng/mL], P<0.001). Elevated cTnI detected these dogs with good accuracy (area under the curve: 0.78-0.85; cut-offs 0.199-0.34 ng/mL). Thirty-eight GDs (30.6%) suffered a cardiac death (CD); GDs suffering CD (0.25 ng/mL [0.21-0.53 ng/mL]) and specifically sudden cardiac death (SCD) (0.51 ng/mL [0.23-0.72 ng/mL]) had higher cTnI than GDs dying of other causes (0.20 ng/mL [0.14-0.35 ng/mL]; P<0.001). Elevated cTnI (>0.199 ng/mL) was associated with shorter long-term survival (1.25 years) and increased risk of SCD. Great Danes with VAs had shorter survival times (0.97 years). CONCLUSIONS: A cardiac troponin-I concentration is a useful adjunctive screening tool. Elevated cTnI is a negative prognostic indicator.

Isolated by dry lands: integrative analyses unveil the existence of a new species and a previously unknown evolutionary lineage of Brazilian Lanceheads (Serpentes: Viperidae: Bothrops) from a Caatinga moist-forest enclave

Here we describe a new species of Lancehead (Bothrops jabrensis sp. nov.) based on three individuals sampled from a previously unknown population from Pico do Jabre, an isolated and small Caatinga moist-forest enclave (CMFE) located in northeastern Brazil. Although this new species has an external morphology resembling those found in representatives of the Bothrops jararaca (Wied-Neuwied, 1824) species group, B. jabrensis can be diagnosed by a combination of meristic and color characters. Molecular phylogenetic analysis indicates the new species represents a unique and highly divergent lineage within Bothrops revealing the existence of a previously unknown phylogenetic lineage that has been evolving as an independent unit for more than 8 million years. Additionally, the estimated divergence time of this lineage conflicts with some proposed scenarios of historical processes associated with the evolution of CMFEs. Finally, the uniqueness of this species indicates its relevance for the maintenance of the phylogenetic diversity of Lanceheads in South America. Like other CMFEs, Pico do Jabre is consistently threatened by poaching, illegal fires, deforestation for agricultural purposes, and illegal logging. The restricted distribution of B. jabrensis, in a small and disturbed CMFE, strongly suggests that this species is critically endangered and is likely approaching extinction as a natural population.

Assessment of left ventricular function in healthy Great Danes and in Great Danes with dilated cardiomyopathy using speckle tracking echocardiography.

OBJECTIVES: Assess global circumferential and radial systolic and diastolic myocardial function with speckle tracking echocardiography (STE) in healthy Great Danes (GD) and in GD diagnosed with dilated cardiomyopathy (DCM). ANIMALS: Eighty-nine GD were included in the study: 39 healthy (normal group [NORMg]) and 50 diagnosed with DCM (DCMg). METHODS: This was a retrospective study. Signalment and echocardiographic diagnosis were obtained from the medical records of GD assessed between 2008 and 2012. Speckle tracking echocardiography analysis of circumferential (C) and radial (R) strain (St) and strain rate (SR) in systole (S), early (E) and late (A) diastole was performed at the levels of the mitral valve (MV), papillary muscles (PM) and apex (Ap) of the left ventricle. Univariable and multivariable analysis was performed to identify differences between groups. RESULTS: Speckle tracking echocardiography variables increase from the MV towards the Ap of the left ventricle in both NORMg and DCMg dogs, some reaching statistical significance. Most of the variables (28/31) were lower in DCMg than in NORMg dogs: statistically significant variables included radial SR at the Ap in systole (p=0.029), radial strain at the PM (p=0.012), circumferential SR at the PM in systole (p=0.031), circumferential and radial SR at the MV in early diastole (p=0.019 and p=0.049, respectively). CONCLUSIONS: There are significant differences in STE variables between NORMg and DCMg Great Danes, although the overlap between the two groups may indicate that these variables are not sufficiently discriminatory. STE variables are not sufficiently sensitive to use in isolation as a screening method.

Beyond the grave: When is cell death critical for immunity to infection?

Immune cell death is often observed in response to infection. There are three potential beneficial outcomes after host cell death: (1) the removal of an intracellular niche for microbes, (2) direct microbicidal activity of released components and (3) the propagation of an inflammatory response. Recent findings suggest that three forms of non-apoptotic regulated cell death, pyroptosis, necroptosis and NETosis, can impact on immunity to bacterial infection. However, it is challenging to design experiments that unequivocally prove the advantageous effects of regulated cell death on immunity. Recent advances in the genetic manipulation of regulated cell death and danger-associated molecular patterns and 'alarmins', such as HMGB1 and the IL-1 family, may hold the key to delineating the consequences of cell death in immunity to infection.

A pedigree-based genetic appraisal of Boxer ARVC and the role of the Striatin mutation.

The objective of this paper was to investigate by pedigree-based genetic means the origins and inheritance of arrhythmogenic right ventricular cardiomyopathy (ARVC) in UK Boxers and assess the role of the proposed causal mutation in the gene, Striatin (STRN). All ARVC cases traced back to a small number of imported American dogs deriving from the group of Boxers studied by Harpster (1983) to define the disease, strongly suggesting that the disease is the same in the two countries. Dogs with and without the STRN mutation were found in both ARVC affected and normal Boxers showing that the mutation is not responsible for the disease. Evidence was found that the STRN mutation is, however, genetically linked with the gene responsible on the same chromosome. The linkage implies that the two genes can separate by meiotic recombination such that both ARVC-affected and ARVC-unaffected lines of dogs may carry either the STRN mutation or its wild-type allele. These have been found. Homozygotes for the STRN mutation tended to be severely affected at early ages, suggesting that there is an interaction between the known effects of the STRN mutation on the cardiomyocyte and ARVC.

Left atrial size, atrial function and left ventricular diastolic function in cats with hypertrophic cardiomyopathy.

OBJECTIVES: To describe left atrial size, left atrial volume, left atrial function and left ventricular diastolic function in healthy cats and those with hypertrophic cardiomyopathy without and with congestive heart failure. METHODS: A retrospective study of 61 client-owned, 21 healthy, 21 asymptomatic hypertrophic cardiomyopathy and 19 with hypertrophic cardiomyopathy and congestive heart failure cats. Data were retrieved from clinical records and echocardiography archives. Left atrial diameter and volumes were measured. Left atrial function was investigated using changes in diameter (fractional shortening) and volume (Simpson's method; left atrial ejection fraction). Conventional echocardiographic indices of left ventricular diastolic function were recorded. RESULTS: Left atrial diameter and left atrial volume measurements were significantly higher in hypertrophic cardiomyopathy with congestive heart failure cats compared with asymptomatic hypertrophic cardiomyopathy and healthy cats (P < 0·001). Left atrial passive, active and complete ejection fraction distinguished between hypertrophic cardiomyopathy with congestive heart failure and asymptomatic hypertrophic cardiomyopathy (P < 0·001). Hypertrophic cardiomyopathy with congestive heart failure cats had significantly lower mitral A wave velocity (P = 0·016) and atrial complete emptying based on diameter and volume measurements (P = 0·008 and P < 0·001, respectively) compared with asymptomatic hypertrophic cardiomyopathy cats. CLINICAL SIGNIFICANCE: Left atrial volume is obtainable by echocardiography in cats. Left atrial volume and atrial function may indicate chronicity and severity of diastolic dysfunction associated with hypertrophic cardiomyopathy and congestive heart failure. Left atrial function was reduced in cats with hypertrophic cardiomyopathy and congestive heart failure compared with healthy and asymptomatic hypertrophic cardiomyopathy groups.

Screening for dilated cardiomyopathy in Great Danes in the United Kingdom.

BACKGROUND: Great Danes (GD) are predisposed to dilated cardiomyopathy (DCM), but little is known about progression, clinical manifestations, or inheritance in dogs in the UK. For echocardiographic screening, breed-specific reference intervals (RI) are required. OBJECTIVES: To document the prevalence, clinical manifestations, and inheritance of DCM in UK GD. To establish RI for Doppler echocardiography (ECHO) in GD. ANIMALS: One hundred and seven client-owned GDs. METHODS: Echocardiographic screening study. Dogs were scored on ECHO and ECG variables and classified as normal (NORM), equivocal (EQUIV), or affected (AFX). Forty NORM dogs were used to determine RI for ECHO. Pedigrees from all dogs were examined for mode of inheritance. RESULTS: The prevalence of DCM in this population, based on score, was 35.6%. Significant differences in M mode left ventricular dimensions (MMLVD) were identified between male and female dogs (P < .011). RI for MMLVD and transformed MMLVD (allometric scaling) were lower than previously suggested. When dogs were reclassified using amended RI for MMLVD, prevalence increased to 47%. End-systolic volume index more reliably identified AFX dogs than other systolic function indices. Ventricular arrhythmias (VA) were commonly identified, with the highest prevalence in AFX dogs (54%). Pedigree analysis suggested an autosomal dominant mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: The prevalence of DCM in UK GD is higher than previously reported and autosomal dominant inheritance is likely. Sex or body weight-dependent RI should be used for ECHO in GD and current RI might underestimate ESVI in GD. VA might play an important role in GD with DCM.

Contractile, but not endothelial, dysfunction in early inflammatory arthritis: a possible role for matrix metalloproteinase-9.

BACKGROUND AND PURPOSE: Excess morbidity/mortality in rheumatoid arthritis (RA) is associated with increased incidence of cardiovascular disease. In this 'proof-of-concept' study, vascular function was characterized in the murine collagen-induced arthritis (mCIA) model, the benchmark choice for evaluation of the pathological processes and assessment of new therapies. EXPERIMENTAL APPROACH: Mice in the very early stages of arthritis development [and appropriate naïve (non-immunized) age-matched controls] were used in the study. Blood pressure was measured using tail cuff plethysmography. Vascular function in rings of isolated aorta was studied with isometric tension myography. Levels of NO metabolites (NO(x)), MMP-9 protein and IL-1ß in plasma and MMP-9 protein in aortic homogenates were quantified. KEY RESULTS: Impaired vascular contractile responses in arthritis were unaffected by ex vivo inhibition of NOS (endothelial/neuronal and inducible) or COX activities. Endothelium-dependent and -independent relaxation, plasma NO(x) and blood pressure were unaffected by arthritis. Plasma and aortic homogenate MMP-9 protein levels were increased significantly in arthritis. Incubation of aortic tissues from naïve control animals with exogenous MMP-9 impaired subsequent contractile responses, mirroring that observed in arthritis. A role for IL-1ß in perpetuating contractile dysfunction and increasing aortic MMP-9 was excluded. CONCLUSIONS AND IMPLICATIONS: These data identify for the first time a relationship between early arthritis and contractile dysfunction and a possible role for MMP-9 therein, in the absence of overt endothelial dysfunction or increased NO production. As such, MMP-9 may constitute a significant target for early intervention in RA patients with a view to decreasing risk of cardiovascular disease.

Retrospective evaluation of the use of amiodarone in dogs with arrhythmias (from 2003 to 2010).

OBJECTIVES: To evaluate the efficacy of amiodarone in dogs with refractory supraventricular and ventricular arrhythmias and to document the side effects in treated dogs. METHODS: Records of 28 dogs were retrospectively searched to document indication for amiodarone administration, heart rate, alkaline phosphatase, alanine aminotransferase, thyroxine (T4) and thyroid stimulating hormone values before and after starting treatment and during follow-up periods. RESULTS: Sixteen dogs with supraventricular and 12 dogs with ventricular arrhythmias were treated with amiodarone. Amiodarone treatment significantly reduced the heart rate (P<0.001) and resulted in improvement in the severity of the arrhythmia and clinical signs in 26 dogs. There were no significant differences in alkaline phosphatase (P=0.596), alanine aminotransferase (P=0.842), T4 (P=0.789) and thyroid stimulating hormone (P=0.064) before and after starting amiodarone. On maintenance therapy, median amiodarone blood levels were within the accepted reference range (0.5 to 2.0 mg/L) at 0.8 mg/L (range 0.2 to 11.6 mg/L), but the majority of the desethylamiodarone levels were below normal at 0.1 mg/L (range 0.1 to 0.9 mg/L), based on human reference intervals (0.5 to 2.0 mg/L). CLINICAL SIGNIFICANCE: Amiodarone may be an effective and safe alternative to treat supraventricular and ventricular arrhythmias in dogs, when common anti-arrhythmic drugs are not effective or contraindicated.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Comparison of stress induced by manual restraint and immobilisation in the estuarine crocodile, Crocodylus porosus.

This study compared the stress induced in captive estuarine crocodiles, Crocodylus porosus, by two different handling methods: manual restraint (noosing with ropes) and immobilization by electro-stunning. To stun, a short charge (approx. 6 s) at 110 V was delivered to the back of the necks of C. porosus using a custom-built device, which immobilized the animals for 5-10 min. Immobilized and restrained animals were measured and sexed, and the condition of the skin assessed. Blood samples were taken from some animals immediately after restraint or immobilization. Other animals were returned to their pens to recover for periods of 30 min, 1, 4, 12, 24 or 48 hours after which they were stunned and blood samples taken. Individual animals (mean body length 1.96 m, N=99) were bled only once. Haematocrit and haemoglobin concentrations were measured and plasma samples were analysed for corticosterone, glucose and lactate levels. Following restraint, there were significant increases in haematocrit, haemoglobin, glucose, lactate and corticosterone concentrations in C. porosus. For restrained animals, recovery to baseline levels occurred after approximately 8 hours. The stress response of stunned animals was significantly reduced compared to manually captured and restrained crocodiles. Both groups showed a significant increase in haematocrit, haemoglobin concentration and lactate levels, however the magnitude of change was significantly reduced, and recovery was faster in stunned animals. No increase in either glucose or corticosterone levels occurred with immobilisation. The results imply that immobilization by electro-stunning is much less stressful.

The influence of age on outcome after operation for the carpal tunnel syndrome. A prospective study.

Decompression of the carpal tunnel is a common surgical procedure. Although the incidence of the carpal tunnel syndrome increases with age, there is no clear information available on the outcome of surgery in relation to age. We studied prospectively 87 consecutive patients who underwent decompression, using a validated self-administered questionnaire, and found that improvement in symptoms and function decreased with increasing age. This was most marked in patients over the age of sixty years.

Sources of elevated serum androgens in postmenopausal women who develop breast cancer.

Postmenopausal women with elevated serum androgens are at an increased risk of breast cancer. High dehydroepiandrosterone sulfate concentrations in these women suggest increased adrenal secretion. Both the adrenals and ovaries could contribute to elevated concentrations of androstenedione (Delta4A). 11beta-Hydroxyandrostenedione (11betaOHA) is elevated, and the Delta4A:11betaOHA ratio is depressed when the adrenals are the primary source of elevated Delta4A in women. Conversely, Delta4A:11betaOHA is elevated when the ovaries are the primary source. We prospectively evaluated associations of serum 11betaOHA and Delta4A:11betaOHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of elevated Delta4A related to risk. Fifty-three postmenopausal women who were not taking estrogens when they donated blood and were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served as cases. Two controls, who were also postmenopausal and not taking estrogens, were matched to each case on age, date, and time of blood collection. Serum Delta4A concentration was significantly (trend P = 0.02) positively associated with breast cancer risk. Adjusted risk ratios for women in the lowest to highest tertiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9-6.5]. However, neither 11betaOHA concentration nor Delta4A:11betaOHA was related to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5-3.6) for 11betaOHA and 1.0, 1.2, and 1.2 (95% CI, 0.4-3.5) for Delta4A:11betaOHA. Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum Delta4A in postmenopausal women who develop breast cancer, but rather both may contribute.

Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA).

OBJECTIVE: To prospectively evaluate relationships of organochlorine pesticides and polychlorinated biphenyls (PCBs) with breast cancer, we conducted a case-control study nested in a cohort using the Columbia, Missouri Breast Cancer Serum Bank. METHODS: Women donated blood in 1977-87, and during up to 9.5 years follow-up, 105 donors who met the inclusion criteria for the current study were diagnosed with breast cancer. For each case, two controls matched on age and date of blood collection were selected. Five DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] analogs, 13 other organochlorine pesticides, and 27 PCBs were measured in serum. RESULTS: Women in the upper three quartiles of hexachlorobenzene were at twice the risk of breast cancer compared to those in the lowest quartile. However, there was no evidence for a dose-response relationship, and the association was limited to women whose blood was collected close to the time of diagnosis. Women with higher serum levels of other organochlorine pesticides and PCBs showed no increased risk of breast cancer overall, although positive associations were suggested for PCB-118 and PCB-138 when blood was collected close to the time of diagnosis. CONCLUSIONS: Results of this study do not support a role for organochlorine pesticides and PCBs in breast cancer etiology.

Comparison of clinical and digital assessment of nuclear optical density.

To compare the standardised Nidek EAS-1000 densitometric analysis of the lens with clinical assessment of the nucleus at an early stage of cataract development, 1,200 eyes of 1,204 participants of the VECAT study were assessed at the baseline using both subjective and objective lens grading. Standardisation of the automatic slit image analysis was achieved using a custom-designed EAS-1000 Software version 3.01c. Among 6 measurements of nuclear optical density, the mean pixel luminescence of integrated anterior nuclear density correlated best with clinical assessment (R = 0.662, p < 0.001). Variance components that interfere with the assessment are defined.

Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)

To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.

Future directions for resuscitation research. V. Ultra-advanced life support.

Standard external cardiopulmonary resuscitation (SECPR) frequently produces very low perfusion pressures, which are inadequate to achieve restoration of spontaneous circulation (ROSC) and intact survival, particularly when the heart is diseased. Ultra-advanced life support (UALS) techniques may allow support of vital organ systems until either the heart recovers or cardiac repair or replacement is performed. Closed-chest emergency cardiopulmonary bypass (CPB) provides control of blood flow, pressure, composition and temperature, but has so far been applied relatively late. This additional low-flow time may preclude conscious survival. An easy, quick method for vessel access and a small preprimed system that could be taken into the field are needed. Open-chest CPR (OCCPR) is physiologically superior to SECPR, but has also been initiated too late in prior studies. Its application in the field has recently proven feasible. Variations of OCCPR, which deserve clinical trials inside and outside hospitals, include 'minimally invasive direct cardiac massage' (MIDCM), using a pocket-size plunger-like device inserted via a small incision and 'direct mechanical ventricular actuation' (DMVA), using a machine that pneumatically drives a cup placed around the heart. Other novel UALS approaches for further research include the use of an aortic balloon catheter to improve coronary and cerebral blood flow during SECPR, aortic flush techniques and a double-balloon aortic catheter that could allow separate perfusion (and cooling) of the heart, brain and viscera for optimal resuscitation of each. Decision-making, initiation of UALS methods and diagnostic evaluations must be rapid to maximize the potential for ROSC and facilitate decision-making regarding long-term circulatory support versus withdrawal of life support for hopeless cases. Research and development of UALS techniques needs to be coordinated with cerebral resuscitation research.