Age-related differences in warning symbol comprehension and training effectiveness: effects of familiarity, complexity, and comprehensibility.

Age-related changes in selective attention, inhibitory efficiency, and the ability to form new associations suggest that older adults may have greater difficulty with more complex and less comprehensible symbols. We examined comprehension of symbols varying in terms of ratings of familiarity, complexity, and comprehensibility, by younger (aged 18-35) and older (aged 55-70) adults. It was found that older adults have greater difficulty than younger adults in comprehending warning symbols and that accident scenario training improves comprehension. Regression analyses indicated that familiarity and comprehensibility were important in determining performance on the pre-training comprehension test by both younger and older adults. However, training eliminated the effects of stimulus characteristics for younger adults, while older adults' comprehension continued to be significantly influenced by comprehensibility. We suggest that symbol design incorporates cues to knowledge to facilitate the linkage between new knowledge (i.e. the warning symbol) and relevant knowledge in long-term memory. Statement of Relevance: Symbol characteristics play an important role in age-related differences in warning symbol comprehension. To optimise comprehension by older adults, symbols should have a clear relationship with areal-world referent. Alternatively, symbol design could incorporate cues to knowledge to facilitate the linkage between new knowledge and relevant knowledge in long-term memory.

Changing drivers' attitudes towards mobile phone use through participative simulation testing and feedback.

OBJECTIVE: To assess the effectiveness of a simulation-based participative and feedback approach to change drivers' attitudes towards mobile phone use while driving. METHODS: 30 experienced drivers were tested. Five scenarios were developed to test drivers' performance with and without a secondary mobile phone task on a medium-fidelity fixed base driving simulator. The treatment group received feedback in the form of video playback of their driving performance, while the control group did not receive any feedback. Attitudes towards mobile phone use were assessed by a questionnaire before, immediately after, and again one month following the experiment to determine the duration of feedback effects. RESULTS: All 30 drivers reported willingness to engage in driving and talking on a mobile phone in some situations. The results of the simulated driving test showed that a secondary mobile phone task significantly degraded driving performance. The treatment group showed significant attitude change towards mobile phone use while driving; the control group had no attitude change. At the one month follow-up, a continued benefit of feedback was reflected in driver attitudes in the treatment group. CONCLUSIONS: Participative driving using simulation is a useful tool to demonstrate driving performance degradation in dual task conditions. It was found that feedback in the form of simulation playback is effective in changing drivers' attitudes towards mobile phone use and that attitude change is maintained over a follow-up period of one month.

Dissociation between driving performance and drivers' subjective estimates of performance and workload in dual-task conditions.

INTRODUCTION: The current study measured how concurrent driving and in-vehicle activities of different levels of engagement varied in terms of performance and subjective estimates of demand and performance. METHOD: In this test track study, 41 younger and older drivers completed a series of cognitive tasks while driving an instrumented vehicle. One task involved an engaging guessing game where drivers tried to guess the identity of an object. The other task involved a simple mental arithmetic task. RESULTS: We observed some dissociation between drivers' performance and their subjective reports. For instance, drivers tended to estimate their performance as better for the more engaging guessing task than the arithmetic task, though their performance was actually worse. At the same time, subjective estimates of workload across the two tasks did not vary in the dual-task condition even though they did in the single-task baseline conditions, suggesting that drivers failed to account for the added demands in dual-task situations. CONCLUSIONS: We discuss the implications of these findings for driver safety. IMPACT ON INDUSTRY: Crashes due to distraction can carry tremendous costs for employers, in terms of injury, disability, and loss of potentially productive work years, whether these crashes occur on or off the job.

The distraction effects of phone use during a crucial driving maneuver.

Forty-two licensed drivers were tested in an experiment that required them to respond to an in-vehicle phone at the same time that they were faced with making a crucial stopping decision. Using test track facilities, we also examined the influence of driver gender and driver age on these dual-task response capacities. Each driver was given task practice and then performed a first block of 24 trials, where one trial represented one circuit of the test track. Half of the trials were control conditions in which neither the stop-light was activated nor was the in-vehicle phone triggered. Four trials required only stop-light response and a further four, phone response only. The remaining four trials required the driver to complete each task simultaneously. The order of presentation of specific trials was randomized and the whole sequence was repeated in a second block giving 48 trials per driver. In-vehicle phone response also contained an embedded memory task that was evaluated at the end of each trial circuit. Results confirmed our previous observation that in the dual-task condition there was a slower response to the light change. To compensate for this slowed response, drivers subsequently brake more intensely. Most importantly, we recorded a critical 15% increase in non-response to the stop-light in the presence of the phone distraction task which equates with increased stop-light violations on the open road. These response patterns varied by driver age and driver gender. In particular, age had a large effect on task components that required speed of response to multiple, simultaneous demands. Since driving represents a highly complex and interactive environment, it is not possible to specify a simplistic relationship between these distraction effects and outcome crash patterns. However, we can conclude that such in-vehicle technologies erode performance safety margin and distract drivers from their critical primary task of vehicle control. As such it can be anticipated that a causal relation exists to collision events. This is a crucial concern for all in-vehicle device designers and for the many safety researchers and professionals seeking to reduce the adverse impacts of vehicle collisions.

The concept of abnormal hemispheric organization in addiction research.

In addition to the established areas of endogenous psychoses, the concept of abnormal hemispheric organization in the field of psychiatry is also generating ever greater interest in the area of research into addiction. On the basis of the demonstrably higher rate of developmental risk factors (pre-, peri-, postnatal), in particular the marker left-handedness (LH) has been interpreted as an indication of induced hemispheric 'malcontrol' in endogenous psychoses. In various studies, elevated rates of LH have also been shown in alcoholics. Alcoholism could be related to biological factors associated with anomalous cerebral dominance. In a joint study carried out by the Anton Proksch Institut in Vienna (Austria), and the University of Erlangen-Nuremberg (Germany) involving a total of 250 alcohol-dependent inpatients, the hypothesis of deviant laterality in the presence of an elevated frequency of developmental risk factors has been confirmed exclusively in male alcoholics. A comparison of subtypes has also revealed that Type IV in the Lesch typology, and Type II in the Cloninger classification, are more vulnerable subtypes. These results clearly show that there are differences to be found within the overall group of alcoholics, and underscore the need for subtyping and gender-specific studies.

Ribozymes as tools for therapeutic target validation in arthritis.

In this paper we describe a method for validating therapeutic gene targets in arthritic disease. Ribozymes are catalytic oligonucleotides capable of highly sequence-specific cleavage of RNA. We designed ribozymes that cleave the mRNA encoding stromelysin, a matrix metalloproteinase implicated in cartilage catabolism. Ribozymes were initially screened in cultured fibroblasts to identify sites in the mRNA that were accessible for binding and cleavage. Accessible sites for ribozyme binding were found in various regions of the mRNA, including the 5' untranslated region, the coding region, and the 3' untranslated region. Several ribozymes that mediated sequence-specific and dose-dependent inhibition of stromelysin expression were characterized. Site selection in cell culture was predictive of in vivo bioactivity. An assay for measuring cartilage catabolism in rabbit articular cartilage explants was developed. Ribozymes inhibited IL-1-stimulated stromelysin mRNA expression in articular cartilage explants, yet failed to inhibit proteoglycan degradation. This indicated that up-regulation of stromelysin was not essential for IL-1-induced cartilage catabolism. Broad applications of this approach in therapeutic target validation are discussed.

The representation of sublexical orthographic-phonologic correspondences: evidence from phonological dyslexia.

Although there is considerable evidence that grapheme and body units are involved in assembling phonology from print, there is little evidence supporting the involvement of syllabic representations. We provide evidence on this point from a phonological dyslexic patient (ML) who, as a result of brain damage, is relatively unable to read nonwords. ML was found to be able to perform tasks assumed to reflect processes involved in assembled phonology (i.e. segmentation, orthographic-phonologic conversion, and blending) when the units involved were syllables, but demonstrated considerable difficulty when they were onset, body, or phoneme units. Additionally, both ML and matched controls were much better able to find words in an anagrams task (Treiman & Chafetz, 1987) when they resulted from the combination of segments corresponding to syllables than when they did not. It is suggested that the relationship between print and sound is represented at multiple levels (including the syllable) (Shallice, Warrington, & McCarthy, 1983) and that ML's nonword reading impairment is the result of disruption of representations below the level of the syllable.

Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes.

BACKGROUND: Alterations in K+ channel expression and gating are thought to be the major cause of action potential remodeling in heart failure (HF). We previously reported the existence of a late Na+ current (INaL) in cardiomyocytes of dogs with chronic HF, which suggested the importance of the Na+ channel in this remodeling process. The present study examined whether this INaL exists in cardiomyocytes isolated from normal and failing human hearts. METHODS AND RESULTS: A whole-cell patch-clamp technique was used to measure ion currents in cardiomyocytes isolated from the left ventricle of explanted hearts from 10 patients with end-stage HF and from 3 normal hearts. We found INaL was activated at a membrane potential of -60 mV with maximum density (0.34+/-0.05 pA/pF) at -30 mV in cardiomyocytes of both normal and failing hearts. The steady-state availability was sigmoidal, with an averaged midpoint potential of -94+/-2 mV and a slope factor of 6.9+/-0.1 mV. The current was reversibly blocked by the Na+ channel blockers tetrodotoxin (IC50=1.5 micromol/L) and saxitoxin (IC50=98 nmol/L) in a dose-dependent manner. Both inactivation and reactivation of INaL had an ultraslow time course (tau approximately 0.6 seconds) and were independent of voltage. The amplitude of INaL was independent of the peak transient Na+ current. CONCLUSIONS: Cardiomyocytes isolated from normal and explanted failing human hearts express INaL characterized by an ultraslow voltage-independent inactivation and reactivation.

Abnormal mitochondrial function in myocardium of dogs with chronic heart failure.

Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria that include hyperplasia, reduced organelle size and compromised structural integrity. In the present study, we examined mitochondrial respiration in myocardium of 10 normal dogs and 10 dogs with chronic HF (LV ejection fraction 24+/-2%) produced by intracoronary micro-embolizations. Mitochondrial respiratory rates were determined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Basal respiratory rate (VO), respiratory rate after addition of substrates, glutamate and malate (VSUB) and state 3 respiratory rate (VADP, after addition of ADP), were measured in tissue samples from the subendocardial and subepicardial LV free wall, interventricular septum and right-ventricular free wall. No differences were observed in basal respiratory rates between normal and HF tissue, while VSUB was significantly lower in HF compared to normal. VADP was 50-60% lower in HF compared to normal tissue (P<0.001). The results indicate abnormal mitochondrial respiratory activity in myocardium of dogs with chronic HF. These findings support the concept of low myocardial energy production in HF that can contribute to the global cardiac dysfunction.

Relationship between action potential, contraction-relaxation pattern, and intracellular Ca2+ transient in cardiomyocytes of dogs with chronic heart failure.

Abnormalities of contractile function have been identified in cardiomyocytes isolated from failed human hearts and from hearts of animals with experimentally induced heart failure (HF). The mechanism(s) responsible for these functional abnormalities are not fully understood. In the present study, we examined the relationship between action potential duration, pattern of contraction and relaxation, and associated intracellular Ca2+ transients in single cardiomyocytes isolated from the left ventricle (LV) of dogs (n = 7) with HF produced by multiple sequential intracoronary microembolizations. Comparisons were made with LV cardiomyocytes isolated from normal dogs. Action potentials were measured in isolated LV cardiomyocytes by perforated patch clamp, Ca2+ transients by fluo 3 probe fluorescence, and cardiomyocyte contraction and relaxation by edge movement detector. HF cardiomyocytes exhibited an abnormal pattern of contraction and relaxation characterized by an attenuated initial twitch (spike) followed by a sustained contracture ('dome') of 1 to 8 s in duration and subsequent delayed relaxation. This pattern was more prominent at low stimulation rates (58% at 0.2 Hz, n = 211, 21% at 0.5 Hz, n = 185). Measurements of Ca2+ transients in HF cardiomyocytes at 0.2 Hz manifested a similar spike and dome configuration. The dome phase of both the contraction/relaxation pattern and Ca2+ transients seen in HF cardiomyocytes coincided with a sustained plateau of the action potential. Shortening of the action potential duration by administration of saxitoxin (100 nM) or lidocaine (30 microM) reduced the duration of the dome phase of both the contraction/relaxation profile as well as that of the Ca2+ transient profile. An increase of stimulation rate up to 1 Hz caused shortening of the action potential and disappearance of the spike-dome profile in the majority of HF cardiomyocytes. In HF cardiomyocytes, the action potential and Ca2+ transient duration were not significantly different from those measured in normal cells. However, the contraction-relaxation cycle was significantly longer in HF cells (314 +/- 67 ms, n = 21, vs. 221 +/- 38 ms, n = 46, mean +/- SD), indicating impaired excitation-contraction uncoupling in HF cardiomyocytes. The results show that, in cardiomyocytes isolated from dogs with HF, contractile abnormalities and abnormalities of intracellular Ca2+ transients at low stimulation rates are characterized by a spike-dome configuration. This abnormal pattern appears to result from prolongation of the action potential.

Effects of ACE inhibition on cardiomyocyte apoptosis in dogs with heart failure.

Cardiomyocyte apoptosis or programmed cell death has been shown to occur in end-stage explanted failed human hearts and in dogs with chronic heart failure (HF). We tested the hypothesis that early long-term monotherapy with an angiotensin-converting enzyme (ACE) inhibitor attenuates cardiomyocyte apoptosis in dogs with moderate HF. Left ventricular (LV) dysfunction (ejection fraction 30-40%) was produced in dogs by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 mo of therapy with enalapril (Ena, 10 mg twice daily, n = 7) or to no therapy at all (control, n = 7). After 3 mo of therapy, dogs were euthanized and the hearts removed. Presence of nuclear DNA fragmentation (nDNAf), a marker of apoptosis, was assessed in frozen LV sections using the immunohistochemical deoxynucleotidal transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method. Sections were also stained with ventricular anti-myosin antibody to identify cells of cardiocyte origin. From each dog, 80 fields (x40) were selected at random, 40 from LV regions bordering old infarcts and 40 from LV regions remote from any infarcts, for quantifying the number of cardiomyocyte nDNAf events per 1,000 cardiomyocytes. The average number of cardiomyocyte nDNAf events per 1,000 cardiomyocytes was significantly lower in Ena-treated dogs compared with controls (0.81 +/- 0.13 vs. 2.65 +/- 0.81, P < 0.029). This difference was due to a significantly lower incidence of cardiomyocyte nDNAf events in LV regions bordering scarred tissue (infarcts) in Ena-treated dogs compared with controls. We conclude that early long-term Ena therapy attenuates cardiomyocyte apoptosis in dogs with moderate HF. Attenuation of cardiomyocyte apoptosis may be one mechanism by which ACE inhibitors preserve global LV function in HF.

Evidence for the use of assembled phonology in accessing the meaning of printed words.

The role of assembled phonology in visual word recognition was investigated using a task in which participants judged whether 2 words (e.g., PILLOW-BEAD) were semantically related. Of primary interest was whether it would be more difficult to respond "no" to "false homophones" (e.g., BEAD) of words (BED) that are semantically related to target words than to orthographic controls (BEND). (BEAD is a false homophone of BED because-EAD can be pronounced /epsilon d/.) In Experiment 1, there was an interference effect in the response time data, but not in the error data. These results were replicated in a 2nd experiment in which a parafoveal preview was provided for the 2nd word of the pair. A 3rd experiment ruled out explanations of the false homophone effect in terms of inconsistency in spelling-to-sound mappings or inadequate spelling knowledge. It is argued that assembled phonological representations activate meaning in visual word recognition.

The clinical implications (or lack thereof) of vegetations detected by echocardiography in patients not thought to have endocarditis.

BACKGROUND: The clinical impact of echocardiographic demonstration of a vegetation (Veg) in patients in whom infective endocarditis (IE) is not suspected has not previously been analyzed. HYPOTHESIS: In this study, an echocardiographic database was interrogated to test whether discovery of a vegetation by echocardiography should result in treatment for endocarditis if IE is not suspected. METHODS: In all, 2,750 serial transthoracic echocardiograms (TTE) were reviewed to generate a list of reports containing the word Veg or thickening (Thk). A chart review of cases identified the impact the report had on patient management. To analyze reader bias due to echocardiographic requests, stating "rule out Veg or IE" as the reason for the study, an additional 1,000 serial TTE requests were segregated into two groups with and without this term. The incidence of the terms Veg or Thk in TTE reports of these groups was tabulated. RESULTS: Of 2,750 reports, 20 contained the word Veg. Blood cultures were drawn in 16 of 20, with 7 of 16 being positive. Therapy for IE was initiated in 5 of 7 patients with positive cultures. Of 1,000 requests reviewed in the second phase, 24% of those with rule out Veg as the indication for TTE (n = 29) had Veg and 7% had Thk, while in 971 cases with other indications for TTE 0.2% had Veg and 9.3% had Thk. CONCLUSIONS: Clinicians disregard TTE demonstration of Veg if clinical suspicion for IE is low. It is not clear whether the initial echo request biases the interpretation.

Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide.

Airway instillation of bacterial lipopolysaccharide (LPS) into rat lungs induces neutrophil accumulation, which is known to be intercellular adhesion molecule-1 (ICAM-1)-dependent. In the present study, ICAM-1 messenger RNA (mRNA) of whole lung was found to increase by 20-fold in this inflammatory model. This increase was reduced by 81% after treatment of animals with anti-tumor necrosis factor-alpha (TNF-alpha) antibody and by 37% after treatment with anti-interleukin-1 (IL-1) antibody. The same interventions reduced whole-lung ICAM-1 protein by 85% and 25%, respectively. The studies were extended to assess the locale in lung of ICAM-I upregulation. Lung vascular ICAM-1 content, which was assessed by vascular fixation of [125I]anti-ICAM-1, rose 4-fold after airway instillation of LPS. This rise was also TNF-alpha-dependent. Under the same experimental conditions, fixation of [125I]anti-ICAM-1 to airway surfaces increased 11-fold in a TNF-alpha-dependent manner. In situ hybridization and immunohistochemical analyses of lung tissue revealed ICAM-1 upregulation in the bronchiolar epithelium and in peribronchiolar smooth muscle. Soluble ICAM-1 could also be detected in bronchoalveolar lavage fluids (BALFs) of animals after intratracheal instillation of LPS. Retrieved alveolar macrophages showed a small, significant, and transient increase in surface expression of ICAM-1. These data indicate, at the very least, a dual compartmentalized (vascular and airway) upregulation of ICAM-1 after airway instillation of LPS. This upregulation requires TNF-alpha and IL-1. The functional significance of upregulated airway ICAM-1 remains to be determined.

Reverse remodeling in heart failure with intensification of vasodilator therapy.

BACKGROUND: Heart failure therapy with beta-receptor blockade has been shown to effect a partial reversal of left ventricular (LV) remodeling in heart failure. HYPOTHESIS: We tested the hypothesis that, in the absence of beta blockade, uptitration of angiotensin-converting enzyme (ACE) inhibitor and nitrate therapy over conventional dosages would improve symptoms as well as LV function in patients with severe heart failure. METHODS: For patients with nonischemic or ischemic cardiomyopathy, intensive high-dose angiotensin-converting enzyme inhibitor and nitrate therapy was uptitrated. Echocardiograms were obtained semiannually and evaluated in a blinded fashion. Of 99 patients in the study, aged 55 +/- 13 years, with heart failure for 5.2 +/- 3.1 years, 74 were men, 69 were Caucasian, and 34 had ischemic cardiomyopathy. The final dosage of enalapril was 40 +/- 23 mg/day of isosorbide dinitrate it was 153 +/- 127 mg/day. RESULTS: Initial New York Heart Association classification improved from 2.8 +/- 0.9 to 1.7 +/- 0.9 (p < 0.001) in 2.7 years of follow-up. Of the 99 patients, 72 further improved their ejection fraction. For the whole group, ejection fraction increased from 21 +/- 9% to 30 +/- 13% in 6 months (p < 0.001), with a reduction in LV end-diastolic size from 6.6 +/- 0.9 to 6.3 +/- 1.0 cm (p = 0.002), a decrease in the severity of mitral regurgitation from mild/moderate to only mild. Resting heart rate declined with no change over time in systemic systolic blood pressure. Final ejection fraction for nonischemic patients (n = 65) was 36 +/- 16% versus 23 +/- 9% for the ischemic population. CONCLUSIONS: Uptitration of high-dose ACE inhibitor and nitrate therapy to higher doses is well tolerated in severe heart failure, further improves both clinical status and LV systolic function, and is more effective in nonischemic than in ischemic cardiomyopathy.

Abnormalities of cardiocytes in regions bordering fibrous scars of dogs with heart failure.

Progressive deterioration of left ventricular function is a characteristic feature of the heart failure state and is often speculated to result from ongoing loss of viable myocytes. We previously showed that in dogs with chronic heart failure, cardiocyte death through apoptosis occurs in the border region of fibrous scars (old infarcts). In the present study we examined the structural integrity of cardiocytes in regions bordering fibrous scars using transmission electron microscopy. Morphometric studies were performed using left ventricular tissue obtained from ten dogs with chronic heart failure produced by intracoronary microembolizations. Mitochondrial number increased significantly with proximity to the scar, while mitochondrial size decreased leading to a gradual decrease in mitochondrial volume fraction. Severe injury to mitochondria was present in only 5% of organelles in myocytes far from the scar but increased markedly to 28-41% in myocytes adjacent to or incorporated within the scar. Similarly, severe myofibrillar abnormalities were present in only 3% of myocytes that were far from the scar but increased significantly to 12-73% in myocytes adjacent to or incorporated within the scar. These results indicate that in dogs with chronic heart failure, constituent myocytes of left ventricular regions bordering fibrous scars manifest heterogeneity in the extent of degeneration. The extent of degeneration is greatest in myocytes closest to the scar and least in myocytes far from the scar. We postulate that this wavefront of myocyte degeneration is a dynamic process that may lead to progressive expansion of the scar through loss of viable myocytes and ultimately may contribute, in part, to the progressive left ventricular dysfunction that characterizes the heart failure state.

Response of symptomatic myocardial ischemia in ischemic cardiomyopathy to intensive vasodilator therapy.

To determine the cardiovascular protective effects of angiotensin-converting enzyme inhibitors, we examined the response to intensive vasodilator therapy in patients with ischemic cardiomyopathy and ongoing angina pectoris. We found that for patients with ischemic cardiomyopathy and ongoing active angina, intensive vasodilator therapy with angiotensin-converting enzyme inhibition and nitrates improved not only heart failure-related symptoms, but also resulted in a significant improvement in symptomatic ischemia and ischemia-related morbid events.

Coronary artery aneurysm: a review.

Coronary artery aneurysm is defined as coronary dilatation which exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. This is an uncommon disease which has been diagnosed with increasing frequency since the advent of coronary angiography. The incidence varies from 1.5% to 5% with male dominance and a predilection for the right coronary artery. Atherosclerosis accounts for 50% of coronary aneurysms in adults. Reported complications include thrombosis and distal embolization, rupture and vasospasm. The natural history and prognosis remains obscure. Controversies persist regarding the use of surgical or medical management. The authors recommend surgery based on the severity of associated coronary stenosis rather than the mere presence of aneurysm. Medical therapy is indicated for the majority of patients and consists of antiplatelet and anticoagulant medication.

SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with heart failure.

The purpose of this study was to examine the activity and expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue specimens were obtained from six normal (NL) control dogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity was measured in isolated SR membrane fractions prepared from LV and RV myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs increased with increasing Ca2+ concentration and reached a plateau at 3 microM Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant differences in Ca(2+)-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+ uptake and ultimately to Ca2+ overload and global LV dysfunction.

Acute reversibility of pulmonary hypertension predicts neither long-term hemodynamic response nor outcome in patients awaiting heart transplantation.

For transplant wait-list patients with end-stage congestive heart failure, reversibility of pulmonary hypertension tested with acute administration of vasodilators is a prerequisite to listing for transplantation. We have shown that the magnitude of the initial pulmonary vasodilatory response to nitroprusside predicts neither the extent of the long-term hemodynamic response nor the subsequent need for transplantation versus clinical improvement and removal from transplant consideration.