Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Robustness of MR Elastography in the Healthy Brain: Repeatability, Reliability, and Effect of Different Reconstruction Methods.

BACKGROUND: Changes in brain stiffness can be an important biomarker for neurological disease. Magnetic resonance elastography (MRE) quantifies tissue stiffness, but the results vary between acquisition and reconstruction methods. PURPOSE: To measure MRE repeatability and estimate the effect of different reconstruction methods and varying data quality on estimated brain stiffness. STUDY TYPE: Prospective. SUBJECTS: Fifteen healthy subjects. FIELD STRENGTH/SEQUENCE: 3T MRI, gradient-echo elastography sequence with a 50 Hz vibration frequency. ASSESSMENT: Imaging was performed twice in each subject. Images were reconstructed using a curl-based and a finite-element-model (FEM)-based method. Stiffness was measured in the whole brain, in white matter, and in four cortical and four deep gray matter regions. Repeatability coefficients (RC), intraclass correlation coefficients (ICC), and coefficients of variation (CV) were calculated. MRE data quality was quantified by the ratio between shear waves and compressional waves. STATISTICAL TESTS: Median values with range are presented. Reconstruction methods were compared using paired Wilcoxon signed-rank tests, and Spearman's rank correlation was calculated between MRE data quality and stiffness. Holm-Bonferroni corrections were employed to adjust for multiple comparisons. RESULTS: In the whole brain, CV was 4.3% and 3.8% for the curl and the FEM reconstruction, respectively, with 4.0-12.8% for subregions. Whole-brain ICC was 0.60-0.74, ranging from 0.20 to 0.89 in different regions. RC for the whole brain was 0.14 kPa and 0.17 kPa for the curl and FEM methods, respectively. FEM reconstruction resulted in 39% higher stiffness than the curl reconstruction (P < 0.05). MRE data quality, defined as shear-compression wave ratio, was higher in peripheral regions than in central regions of the brain (P < 0.05). No significant correlations were observed between MRE data quality and stiffness estimates. DATA CONCLUSION: MRE of the human brain is a robust technique in terms of repeatability. Caution is warranted when comparing stiffness values obtained with different techniques. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Visual exploration of emotional body language: a behavioural and eye-tracking study.

Bodily postures are essential to correctly comprehend others' emotions and intentions. Nonetheless, very few studies focused on the pattern of eye movements implicated in the recognition of emotional body language (EBL), demonstrating significant differences in relation to different emotions. A yet unanswered question regards the presence of the "left-gaze bias" (i.e. the tendency to look first, to make more fixations and to spend more looking time on the left side of centrally presented stimuli) while scanning bodies. Hence, the present study aims at exploring both the presence of a left-gaze bias and the modulation of EBL visual exploration mechanisms, by investigating the fixation patterns (number of fixations and latency of the first fixation) of participants while judging the emotional intensity of static bodily postures (Angry, Happy and Neutral, without head). While results on the latency of first fixations demonstrate for the first time the presence of the left-gaze bias while scanning bodies, suggesting that it could be related to the stronger expressiveness of the left hand (from the observer's point of view), results on fixations' number only partially fulfil our hypothesis. Moreover, an opposite viewing pattern between Angry and Happy bodily postures is showed. In sum, the present results, by integrating the spatial and temporal dimension of gaze exploration patterns, shed new light on EBL visual exploration mechanisms.

Beholders' sensorimotor engagement enhances aesthetic rating of pictorial facial expressions of pain.

The present study addresses a novel issue by investigating whether beholders' sensorimotor engagement with the emotional content of works of art contributes to the formation of their objective aesthetic judgment of beauty. To this purpose, participants' sensorimotor engagement was modulated by asking them to overtly contract the Corrugator Supercilii facial muscles or to refrain from any voluntary facial movement while judging the aesthetic value of painful and neutral facial expressions in select examples of Renaissance and Baroque paintings. Results demonstrated a specific increase in the aesthetic rating of paintings showing painful facial expressions during the congruent activation of the Corrugator Supercilii muscles. Furthermore, participants' empathetic traits and expertise in art were found to correlate directly with the amplitude of the motor enactment effect on aesthetic judgments. For the first time, we show the role of bottom-up bodily driven sensorimotor processes in the objective aesthetic evaluation of works of art.

Randomized controlled trial of the effectiveness of three different oral moisturizers in palliative care patients.

Most patients in palliative care have problems with dry mouth caused by medication or as a direct result of their condition. Dry mouth may cause problems that affect the primary disease negatively and contribute to poorer quality of life in palliative patients. This randomized controlled trial compared the efficacy of three different oral moisturizers: 17% watery solution of glycerol; oxygenated glycerol triester (marketed as Aequasyal in Europe and as Aquoral in the USA); and a newly developed product, Salient. Of the three products, glycerol provided the best relief from xerostomia directly after application, but had no effect after 2 h. By contrast, the effects of Aequasyal and Salient were largely maintained over the same period. The findings for oral discomfort and pain and speech problems showed a similar pattern. Despite its poor effect after 2 h, patients preferred glycerol over Salient and Aequasyal, probably because of the unpleasant taste of Aequasyal and the consistency and mode of application of Salient. Within the limitations of this study, none of the three products tested was found to be clinically completely adequate. However, the glycerol solution was preferred by this group of patients, and its short-lived effect can be compensated for by frequent applications.

Effect of glycerol on reconstructed human oral mucosa.

The majority of severely ill patients experience dry mouth. For institutionalized patients, this condition is commonly treated using glycerol as a lubricant. However, because of its possibly desiccating effect, some countries do not advocate the use of glycerol. This study aimed to investigate dose-dependent effects of glycerol on homeostasis and tissue integrity of in vitro-reconstructed normal human buccal mucosa (RNHBM). Primary keratinocytes and fibroblasts were isolated and expanded from biopsies of mucosa from eight healthy volunteers. Ninety-six samples of RNHBM were prepared and exposed for 24 h to 17%, 42.5%, or 85% glycerol, or to distilled H2 O (control). Sections were stained with haematoxylin and eosin (H&E) to evaluate epithelial thickness or used for immunohistochemistry to measure expression of Ki67 (proliferation), cleaved caspase-3 (apoptosis), and E-cadherin (tissue-integrity). Positive cells and cell layers, as detected by immunohistochemistry, were counted. Epithelial thickness, proliferation, and apoptosis were significantly increased by exposure to 42.5% and 85% glycerol. No significant differences in apoptosis or proliferation were found between controls and RNHBM exposed to 17% glycerol. E-cadherin expression was not significantly affected by exposure to any of the concentrations of glycerol tested. This study shows that glycerol affects tissue homeostasis, but not tissue integrity, of RNHBM at glycerol concentrations above 42.5%.

End-of-life palliative oral care in Norwegian health institutions. An exploratory study.

OBJECTIVE: To explore circumstances surrounding procedures and knowledge regarding oral care for terminal patients in Norwegian healthcare institutions. METHODS: A questionnaire was distributed to randomly selected hospitals (n = 19) and nursing homes (n = 57) in central and rural parts of Norway. The questionnaire included three closed-ended and three open-ended questions about oral care for terminal patients. If procedures existed, the respondents were asked to enclose or describe them. RESULTS: The response rate was 84% for hospitals and 79% for nursing homes. Of the responding institutions, 25% had no oral care procedures, nor did 48% recognise their importance. Insufficient knowledge about oral care was reported by 39%. Twenty-one different procedures were identified, and a great number of oral care products used. The most common was glycerol, used by 36% of the institutions. Only 2% used a concentration below 30% - the limit above which the glycerol has a desiccating rather than a moistening effect. The most common patient complaint was dry mouth (49%), followed by plaque, food particles and fungus infections, each experienced by 19%. The most common problem for the personnel was lack of knowledge (43%) and patient cooperation (38%). CONCLUSIONS: Some terminal patients do not receive adequate palliative oral care in Norwegian healthcare institutions. Those that do are exposed to a great number of undocumented procedures and sometimes harmful products. There is a need for evidence-based procedures for oral care for terminally ill patients in health institutions, establishing interprofessional palliative healthcare teams and in particular improved training of the nursing staff.

PRODIACOR: a patient-centered treatment program for type 2 diabetes and associated cardiovascular risk factors in the city of Corrientes, Argentina: study design and baseline data.

OBJECTIVE: To implement a controlled clinical trial (PRODIACOR) in a primary care setting designed 1) to improve type 2 diabetes care and 2) to collect cost data in order to be able to measure cost-effectiveness of three system interventions (checkbook of indicated procedures, patient/provider feedback and complete coverage of medications and supplies) and physician and/or patient education to improve psychological, clinical, metabolic and therapeutic indicators. All three Argentinean health subsectors (public health, social security and the private, prepaid system) are participants in the study. Patients of participating physicians were randomly selected and assigned to one of four groups: control, provider education, patient education, and provider/patient education; the system interventions were provided to all four groups. BASELINE RESULTS: Mean BMI was 29.8 kg/m(2); most subjects had blood pressure, fasting glucose and total cholesterol above targets recommended by international standards. Only 1% had had microalbuminuria measured, 57% performed glucose self-monitoring, 37% had had an eye examination and 31% a foot examination in the preceding year. Ten percent, 26% and 73% of people with hyperglycemia, hypertension and dyslipidemia, respectively, were not on medications. Most patients treated with either insulin or oral antidiabetic agents were on monotherapy as were those treated for hypertension and dyslipidemia. WHO-5 questionnaire scores indicated that 13% of the subjects needed psychological intervention. CONCLUSIONS: Baseline data show multiple deficiencies in the process and outcomes of care that could be targeted and improved by PRODIACOR intervention.

PROPAT: a study to improve the quality and reduce the cost of diabetes care.

OBJECTIVE: In PROPAT we implemented an integrated approach to diabetes care designed to improve the quality and reduce the cost of care. STUDY DESIGN AND METHODS: PROPAT was a case-control study matching patients by age and gender (diabetes:control ratio 1:2) within IOMA, a public employment-based health maintenance organization (HMO) of the Province of Buenos Aires, Argentina. Costs were evaluated using prevalence data from an HMO perspective. We currently report clinical and biochemical data and costs from the first 297 patients enrolled who completed 1 year in PROPAT, and compare them with those derived from control patients. RESULTS: All recommended practices recorded as care provided at baseline increased significantly 1 year after implementing PROPAT, with a parallel significant improvement in several clinical and biochemical parameters, and markedly lower total annual per capita costs. CONCLUSIONS: These results demonstrate that the implementation of a comprehensive diabetes care program can simultaneously improve quality while reducing costs.

The rat orthologue to the inhibitory receptor gp49B is expressed by neutrophils and monocytes, but not by NK cells or mast cells.

Mouse gp49B is a member of the leukocyte immunoglobulin-like receptor family. It is constitutively expressed by mast cells and certain myeloid cells, and expression can be induced on natural killer (NK) cells and T cells. We have cloned several rat cDNA, 78% identical to mouse gp49B at the amino acid level, that represent the rat orthologue to mouse gp49B. A mouse monoclonal antibody (WEN29) against rat gp49B was generated. By flow cytometry and Northern blot analysis, gp49B was found to be expressed by neutrophils and monocytes, but not NK cells (primary or IL-2-activated), T cells (resting or concanavalin A-stimulated) or peritoneal mast cells. Following pervanadate treatment, the tyrosine phosphatase SHP-1 was co-immunoprecipitated with gp49B in the macrophage cell line R2. In glutathione S-transferase pull-down experiments, the cytoplasmic tail of rat gp49B associated with the SH2 domains of both SHP-1 and SHP-2, dependent on intact and phosphorylated immunoreceptor tyrosine-based inhibition motifs (ITIM). Compared to mouse, the cytoplasmic domain of rat gp49B contains a third ITIM-like sequence (YLYASV) that was phosphorylated by several Src family tyrosine kinases, enhanced the phosphorylation of other ITIM, and bound to the SH2 domains of SHP-2, suggesting a role in the recruitment of downstream phosphatases.

Rat NKp46 activates natural killer cell cytotoxicity and is associated with FcepsilonRIgamma and CD3zeta.

NKp46 has been identified in the human, rat, mouse, monkey, and cattle. We have generated a monoclonal antibody, WEN23, against rat NKp46. By flow cytometry, NKp46 is expressed by all natural killer (NK) cells but not by T cells, B cells, granulocytes, monocytes, dendritic cells, or macrophages. Thus, NKp46/WEN23 is the first NK cell-specific marker in the rat. In a redirected lysis assay, preincubation of the effector cells with WEN23 augmented lysis of the Fc receptor (FcR)+ murine tumor target cells, indicating that NKp46 is an activating NK cell receptor. Moreover, preincubation of the effector cells with WEN23 F(ab')2 fragments reduced killing of target cells, confirming the activating function of NKp46 and indicating that the mouse tumor target cells express a ligand for rat NKp46. Lysis of FcR- mouse and human tumor target cells was reduced after incubation of effector cells with WEN23, suggesting that rat NKp46 recognizes a ligand that is conserved between primates and rodents. By Western blot and immunoprecipitation using WEN23, NKp46 is expressed as a monomer of approximately 47 kDa in interleukin-2-activated NK cells. The immunoreceptor tyrosine-based activation motif bearing adaptor proteins CD3zeta and the gamma chain of FcRI for IgE (FcepsilonRIgamma) with NKp46 from lysates of NK cells, indicating that rat NKp46 activates NK cell cytotoxicity by similar pathways as CD16.

Changes in collagenase and collagen gene expression after induction of aortocaval fistula in rats.

Progressive ventricular dilatation commonly accompanies the transition to overt failure in chronically overloaded hearts; however, only recently have studies begun to elucidate underlying molecular alterations. In particular, the potential role of altered myocardial expression of the procollagenase gene in this process has not previously been examined. Biventricular hypertrophy and dilatation were produced in rats by creating an abdominal aortocaval fistula. The time courses of changes in expression of collagen I and III genes and of the procollagenase gene (matrix metalloproteinase-1, MMP-1) were assessed by Northern blot hybridization. Expression of all three genes increased promptly; however, collagenase gene expression peaked much earlier (8 h) than did expression of either of the collagen genes (7 days), and all returned to baseline levels by 45 days. These data corroborate earlier reports of increased collagen gene expression in this model, but more importantly, they provide the first evidence of concurrent activation of collagenase gene expression, suggesting that enhancement of collagen degradation may be a prerequisite for structural cardiac dilatation.

[Evaluation of the quality of care for diabetic patients in Latin America]. / Evaluación de la calidad de la asistencia al paciente diabético en América Latina.

OBJECTIVE: To make a preliminary diagnosis of the quality of care that individuals with diabetes mellitus (DM) received in participating centers of the QUALIDIAB network in Latin America and the Caribbean, and to assess the potential usefulness of this information as well as the importance of expanding the QUALIDIAB network. METHODS: A total of 13,513 patient records from the QUALIDIAB network were analyzed, from public and private health care entities and from the Social Security systems of Argentina, Brazil, Chile, Colombia, Paraguay, and Uruguay. The study utilized: 1) quality-of-care indicators based on international reference values, 2) patient information on clinical, biochemical, and therapeutic parameters and on the rate of use of diagnostic and therapeutic materials, 3) a computer database program, and 4) a software program for statistical analysis. RESULTS: Among the patients studied, about half of them had suffered from diabetes for 5 years or less; this was true both for persons with type 1 diabetes (DM1) and for those with type 2 diabetes (DM2). Of the persons with DM1, 24% of them had a blood glucose level of < 4.4 mmol/L; this was true for 15% of those with DM2. The proportion of persons with a blood glucose level of > 7.7 mmol/L was 41% among those with DM1 and 57% among those with DM2. The frequencies of association between DM2 and other cardiovascular risk factors were: overweight/obesity, 59%; hypertension, 60%; total cholesterol > 5.5 mmol/L, 53%; high-density lipoprotein cholesterol < 1 mmol/L, 32%; triglycerides > 1.7 mmol/L, 45%; and smoking, 13%. Of the people with DM1, 20% of them had a body mass index < 19 kg/m2, probably reflecting deficient metabolic control and inadequate insulin intake. The systematic checking of metabolic control, other cardiovascular risk factors, and chronic DM complications was inadequate in from 3% to 75% of the cases, depending on the specific aspect considered. According to various patient-therapy-education indicators, only some one-quarter to one-half of the studied patients could play an active, effective role in DM control and treatment. Of the persons with DM1, 50% of them were treated with a mixed dose of insulin (NPH + regular insulin), administered in two daily injections in 43% of the cases. Among the patients, 5% of them received one daily insulin injection, and 9% of them received three daily insulin injections. Of the people with DM2, 13% of them treated it only with diet and 14% just with insulin. Among the patients receiving drug treatment, the oral hypoglycemics most used in monotherapy were sulfonylureas (33%), biguanides (9%), and a combination of these two (14%). Fewer than half of the people with diabetes received drug therapy for the associated cardiovascular risk factors. The frequency of patients' macroangiopathic and microangiopathic complications increased with the duration of their disease. Comparing patients who had had diabetes for 5 years or less with those who had had the illness for more than 20 years, the frequency of renal insufficiency and of amputations was around 7 times as great in the latter group; for peripheral neuropathy, it was 2 times as great, and for stroke 1.6 times as great. CONCLUSIONS: These results show the need to improve the quality of care for diabetic patients in Latin America and the Caribbean, and that QUALIDIAB could help do this. Expanding the QUALIDIAB network will help to more accurately diagnose the quality of that care in the Americas, and it will facilitate interventions aimed at optimizing the care. This, in turn, will improve the quality of life of persons who suffer from diabetes as well as diminish the socioeconomic costs of the disease.

UL-FS 49 (zatebradine) does not affect arterial baroreflex in conscious normal or aortic-constricted rats.

Heart-rate reduction is an important element of patient management during cardiac bypass surgery and in therapeutic measures for combating ischemia and relieving pain in patients with angina. UL-FS 49 is a novel bradycardic agent that purportedly acts solely on the sinoatrial node without potentially deleterious effects on arterial pressure and cardiac inotropism. However, little is known about influences of this agent on neuronal tissue and cardiovascular reflexes. Moreover, left ventricular hypertrophy, which often accompanies cardiovascular disease, is known to attenuate the arterial baroreflex and could have effects interactive with those of UL-FS 49. In this study, the effects of UL-FS 49 on the arterial baroreflex were tested in normal rats (N), rats with left ventricular hypertrophy 14 days after abdominal aortic constriction (AC), and sham-operated controls (SH). Arterial baroreflex sensitivity (BRS) was estimated as the slope of the relation between mean arterial pressure (independent variable) and the RR interval (dependent variable). At the time of study, the AC group had significantly greater mean arterial pressure than either SH or N (159 +/- 2, 122 +/- 3, and 124 +/- 3 mm Hg, respectively; mean +/- SEM, p < 0.01) and significantly greater left ventricular mass to body mass ratio than did SH (3.73 +/- 0.11, 2.33 +/- 0.11 mg/g; p < 0.01). As expected, BRS was significantly depressed in AC, compared with either SH or N (0.52 +/- 0.16, 1.48 +/- 0.12, 1.69 +/- 0.25 ms/mm Hg, respectively; p < 0.01). Despite its potent dose-dependent bradycardic effects in all three groups, UL-FS 49 did not affect BRS significantly in any group. These results show that the arterial baroreflex is largely unaffected by UL-FS 49 in both normal rats and rats with systemic hypertension and left ventricular hypertrophy.

Gated magnetic resonance imaging of normal and hypertrophied murine hearts.

Transgenic murine models are being used increasingly to explore the molecular basis of heart disease. Until recently, there were no means for noninvasive assessment of changes in mass and function of the murine heart because of its very small size and high heart rate. Transthoracic echocardiography has now been utilized to obtain noninvasive estimates of murine left ventricular (LV) wall thicknesses, internal dimension, and mass. However, this approach is based on one-dimensional (M-mode) measurements of the LV at its midwall that take no account of variations in LV chamber and wall dimensions along other minor axes and at other anatomic levels. Thus asymmetries in LV geometry, which can affect LV mass estimates, may be undetected. In this study, gated (diastolic) magnetic resonance imaging (MRI) was utilized to obtain two-dimensional images of the LV at four anatomic levels in intact, anesthetized mice. In 17 normal CD-1 mice (body mass, 18-47 g; gravimetric LV mass, 51-135 mg), LV mass estimates produced from the MRI data correlated well (r = 0.87) with LV mass determined gravimetrically. In addition, this approach identified changes in LV mass and wall thickness-to-chamber diameter ratio in a group of seven aortic-constricted mice (body mass, 32-39 g; gravimetric LV mass, 119-198 mg) with compensated and decompensated LV hypertrophy. These findings suggest that utility of MRI for serial, noninvasive assessment of experimentally induced alterations in mass and geometry of the murine heart.

Prolonged ejection duration helps to maintain pump performance of the renal-hypertensive-diabetic rat heart: correlations between isolated papillary muscle function and ventricular performance in situ.

OBJECTIVE: The purpose of this study was to examine the degree to which mechanical alterations in left ventricular papillary muscles of renal hypertensive-diabetic rat hearts correlate with functional measurements made on the same hearts in situ. METHODS: Female Wistar rats weighing 170-200 g were made hypertensive by placing a 0.24 mm clip on the left renal artery, and made diabetic 1 week later by a single intravenous injection of streptozotocin (60 mg/kg). Approximately 3-5 months later hemodynamic measurements including left ventricular pressure and dP/dtmax, arterial pressure and aortic flow were made on control and hypertensive-diabetic hearts in situ and correlated with mechanical measurements in left ventricular papillary muscles isolated from the same hearts. Body and tissue weights and biochemical and histological measurements were made at the time of sacrifice. RESULTS: Hypertensive-diabetic rats which survived to the time of study had decreased body weights, increased left ventricular weights and increased right ventricular weight to body weight and lung weight to body weight ratios. Those rats which died before the scheduled in-situ measurements had significantly more severe hypertension, greater left ventricular hypertrophy, increased right ventricular and lung weights, and more interstitial fibrosis than either surviving hypertensive-diabetics or controls. Rates of isometric tension development (normalized) and relaxation as well as shortening and relaxation velocities were significantly depressed in papillary muscles from hypertensive-diabetic rat hearts despite unchanged developed tension and peak shortening. Time to peak tension and time to peak shortening were markedly prolonged. Mean aortic flow was maintained in the hypertensive-diabetic group despite significant depression of left ventricular dP/dtmax (normalized), peak aortic flow, peak aortic flow acceleration and heart rate. There was also significant depression of left ventricular-dP/dtmax. Ejection duration was markedly prolonged and correlated with both time to peak shortening in vitro and with stroke volume in vivo. CONCLUSIONS: Surviving hypertensive-diabetic rats were not in overt congestive heart failure; nevertheless, their hearts showed abnormal contractile performance which was qualitatively and quantitatively similar to that of left ventricular papillary muscles obtained from them. Depression of peak aortic flow, peak aortic flow acceleration and heart rate in the hypertensive-diabetic group was offset by increased ejection duration, resulting in normal mean aortic flow. The close correlation of ejection duration with time to peak shortening of the isolated papillary muscles suggests that it is a manifestation of an intrinsic change in the myocardium. To the extent that this prolongation is already maximized, further decreases in contractile speed would be expected eventually to cause depressed pump function and congestive heart failure. The possibility that this sequence of events occurred in the dying animals needs to be examined by evaluating in-vitro and in-vivo myocardial function at various stages of this disease model.

Effects of hypertrophy and heart failure on [Na+]i in pressure-overloaded guinea pig heart.

Intracellular free sodium levels ([Na+]i) were assessed with 23Na nuclear magnetic resonance (NMR) spectroscopy in isolated, Langendorff-perfused normal, compensated hypertrophied, and hypertrophied failing guinea pig hearts under several conditions. Baseline [Na+]i measured with a shift reagent was significantly greater than normal in the compensated hypertrophied hearts (12.8 +/- 1.2 mmol/L v 6.4 +/- 0.7 mmol/L, means +/- SEM, P < .01), but not in the hypertrophied failing hearts (8.7 +/- 1.9 mmol/L, P = N.S.). Moreover, the highest levels of [Na+]i were seen just 3 to 4 weeks after aortic constriction. [Na+]i was inversely related to both time after aortic constriction (R = -0.71, P < .03) and to the degree of left ventricular hypertrophy (R = -0.79, P < .01), suggesting that the hypertrophied failing heart is capable of maintaining relatively normal [Na+]i. In addition, triple quantum filtered NMR measurements were made to assess changes in [Na+]i subsequent to altered perfusion or loading conditions. In hypertrophied failing hearts, but not normal hearts, low coronary perfusion pressure (60 cm H2O) was associated with relatively higher [Na+]i (ANOVA, P < .05), suggesting greater sensitivity of hypertrophied failing hearts to hypoperfusion. On the other hand, when all hearts were perfused at 90 cm H2O and intraventricular balloon volume was increased from 100 microL to 300 microL, [Na+]i increased significantly only in the normal guinea pig hearts (12.3 +/- 1.8%, P < .01). These findings suggest complex changes in the expression or modulation of proteins involved in Na+ regulation. Interpretation regarding the physiological significance of these changes depends on the specific mechanism(s) proposed. Previous work in this and other models of hypertrophy suggest that changes in the number or activity of both Na(+)-K(+)-ATPase and Na(+)-Ca2+ exchange proteins are involved.

Echocardiographic assessment of left ventricular mass and systolic function in mice.

The increasing use of transgenic mouse models for investigating the mechanisms of cardiac growth and function has made it important to develop noninvasive methods for assessing murine cardiac anatomy, size, and function. At present, murine cardiac mass can be determined only at necropsy. Left ventricular (LV) function can be assessed by use of various catheterization techniques, but these approaches are usually terminal procedures and provide no information about chamber anatomy and dimensions. Although transthoracic echocardiography has been used to study the LVs of rats and larger animals, the considerably smaller LV masses and somewhat faster heart rates of mice pose significant challenges to obtaining good-quality echocardiograms. In this study we tested the hypothesis that transthoracic echocardiography can image the murine LV as well as provide assessments of LV mass and function. Our results in a series of 33 mice, including normal, transgenic, and aortic-banded subgroups, demonstrate the capability of transthoracic two-dimensionally directed M-mode echocardiography in mice to (1) obtain good-quality images, (2) produce estimates of LV mass having good correlations with directly determined LV mass in normal mice, (3) detect LV hypertrophy noninvasively in different experimental models, and (4) identify impaired LV systolic function. Thus, echocardiography appears to be a promising approach for noninvasively assessing LV mass and function in mice.