Evaluation of left ventricular systolic function using cine MRI--application to hypertrophic cardiomyopathy

Cine MRI is a useful means to analyse the anatomical and functional changes of hypertrophic cardiomyopathy. The visual evaluation of hypertrophic regions and the motion patterns of their walls is in most cases possible on cine MR images. To complement a subjective method a certain quantitative analysis is necessary. Left ventricular regional systolic function can be quantitatively evaluated using cine MRI images printed on films. There is a good correlation between % thickness of LV wall and its thickness at end diastolic phase. The comparison of % thickness of normal subjects with that of hypertrophic cardiomyopathies shows a tendency of its value being less at the region of more severe hypertrophic change.     

Changes in left ventricular diastolic function 6 months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy

BACKGROUND: Nonsurgical septal reduction therapy (NSRT) decreases left ventricular outflow tract (LVOT) gradient and improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). NSRT effects on LV/left ventricular diastolic function are currently unknown. METHODS AND RESULTS: HOCM patients (n=29) had Doppler echocardiography at baseline and 6 months after NSRT to evaluate changes in LV volume, pre-A-wave pressure, early diastolic mitral annulus velocity (Ea) by tissue Doppler, and tau. At 6 months, a significant reduction in LVOT gradient (from 53.6+/-15 to 6+/-5 mm Hg; P<0.001) was accompanied by improvement in exercise duration (from 284+/-147 to 408+/-178 seconds; P=0.04) and New York Health Association class (from III to I; P<0.001). Pre-A pressure (18+/-6 to 14+/-5 mm Hg; P<0.01) and tau (62+/-8 to 51+/-8 ms; P<0.01) decreased, whereas Ea (5.8+/-1.8 to 8+/-1.8 cml/s; P<0.01) and LV end-diastolic volume (117+/-16 to 130+/-22 mL; P<0.01) increased. CONCLUSIONS: NSRT improves LV relaxation and compliance, which contributes to the symptomatic relief seen at 6 months.     

Effects of Ca(2+)-channel drugs on K(+)-induced respiration in skeletal muscles

The immunogenicity and pathogenicity of a strain of respiratory syncytial (RS) virus modified by sequential induction of three temperature-sensitive (ts) mutations have been evaluated by intranasal administration to 22 adult volunteers. This modified virus, a triple ts mutant designated ts1C, was derived from a double mutant ts1B evaluated in a previous trial. The original isolate (strain RSS-2) and all its derivatives were propagated throughout in human diploid cells in a specially assigned laboratory. The triple mutant ts1C is unable to multiply in MRC-5 cells at 37 degrees C and above. Following nasal administration of ts1C, immune responses were observed in volunteers with low pre-existing neutralizing antibody titres. The ability of mutant ts1C to induce upper respiratory tract disease in adults was greatly diminished in comparison with the non-ts wild-type virus, but not markedly more so than a previously tested double ts mutant (ts1B) which replicates at 37 degrees C. Mutant ts1C, however, may have greater potential as a live vaccine in view of its inherently greater genetic stability.     

The effect of the ingestion of ethanol on obstruction of the left ventricular outflow tract in hypertrophic cardiomyopathy

BACKGROUND: Ethanol causes vasodilation, which might have an adverse effect, due to increased obstruction of the left ventricular outflow tract, in patients with hypertrophic obstructive cardiomyopathy. We assessed the hemodynamic effects of the ingestion of ethanol, in an amount commonly consumed socially, in patients with hypertrophic cardiomyopathy. METHODS: We performed echocardiography in 36 patients before and several times after the ingestion of either 50 ml of 40 percent ethanol or an isocaloric placebo with the aroma of rum. Each patient received both ethanol and placebo, on different days. The patients, but not the physicians, were blinded to the content of the drink. We measured the sizes of the left atrium and left ventricle, the left-ventricular-wall thickness, blood pressure, heart rate, the degree of systolic anterior motion of the mitral valve, and the pressure gradient across the left ventricular outflow tract. RESULTS: The ingestion of ethanol regulated in a significant drop in the mean (+/- SD) systolic blood pressure (from 130.5 +/- 18.6 to 122.5 +/- 20.3 mm Hg, P<0.001), a significant increase in systolic anterior motion of the mitral valve (from a grade of 2.1 to a grade of 2.5, P<0.001), and a 63 percent increase in the mean gradient across the left ventricular outflow tract (from 38.1 +/- 26.5 to 62.2 +/- 42.4 mm Hg, P<0.001). These changes, which were not associated with symptoms, did not occur after the ingestion of placebo. CONCLUSION: The ingestion of a small amount of ethanol caused an increase in the gradient across the left ventricular outflow tract in patients with hypertrophic obstructive cardiomyopathy, which could have and adverse clinical effect.     

Effects of postural changes on left atrial function in patients with hypertrophic cardiomyopathy

BACKGROUND: We assessed left atrial function in normal subjects and in patients with hypertrophic cardiomyopathy (HCM) by using Doppler echocardiography at the supine position and after sudden standing. METHODS AND RESULTS: Twenty-seven patients with hypertrophic obstructive cardiomyopathy (HOCM), 17 patients with HCM, and 35 normal subjects were studied. From the transmitral Doppler flow velocities, peak early and late (E and A) waves, E/A ratio, and time velocity integrals (Ei and Ai) were calculated. Left atrial active contribution (LAAC) was assessed as the ratio Ei/(Ei + Ai). Furthermore, isovolumetric relaxation time (IVRT) was estimated by means of Doppler echocardiography. In the supine position, the E/A ratio was similar in the 3 groups. Conversely, LAAC was significantly higher in patients with HOCM (24.4 +/- 2.0) and in patients with HCM (23.3 +/- 3.3) compared with normal subjects (20.3 +/- 2.3, P <.001 and P <.05, respectively). After sudden standing, LAAC increased significantly in normal subjects by 11%, in patients with HOCM by 24%, and in patients with HCM by 13% (P <.001). Similarly, IVRT increased significantly in all study groups (P <. 001). By using stepwise forward multiple linear regression analysis, we found that LAAC was associated with age, IVRT, and body mass index in the supine position and with diastolic blood pressure and IVRT in the standing position. CONCLUSIONS: Left atrial contribution to left ventricular filling was increased after sudden changes of posture in normal subjects and in patients with HOCM or HCM.     

Creation of additional left ventricular tract in female patient with hypertrophic cardiomyopathy]

We report a case of Guillain-Barré syndrome and associated cytomegalovirus infection during pregnancy. A 15-year-old black adolescent had progressive ascending paralysis and vague sensory symptoms during week 10 of her first pregnancy. Diagnosis of Guillain-Barré syndrome was confirmed by electrophysiologic findings consistent with acute demyelinating polyradiculoneuropathy. A mild elevation of anti-GM1 antibodies was also detected. The patient improved with plasmapheresis treatment; however, fetal death occurred 10 weeks later. Cytomegalovirus placentitis was confirmed histologically. Acute demyelinating polyneuropathy during pregnancy warrants consideration of a concomitant, primary maternal and fetal cytomegalovirus infection.     

The effect of gender on left ventricular function immediately after the wingate test

The effect of gender on left ventricular systolic function and exercise haemodynamics in healthy young subjects was studied during 30-s all-out sudden strenuous dynamic exercise. A group of 22 men [19.3 (SD 1) years] 20 women [19.1 (SD 1) years] volunteered to participate in this study. Two-dimensional direct M-mode and Doppler echocardiograph studies were performed with the subject in the sitting position. The Doppler examination of flow was located with continuous-wave, interrogating ascending aorta measurements. The subjects completed the study without showing any electrocardiograph abnormalities. An interaction effect with stroke volume (P < 0.05) was characterized by a decrease in the men and an increase of stroke volume in the women. Cardiac output rose significantly (P < 0.05) up to 14.5 (SD 6) 1.min-1) for the men and 12.1 (SD 4) 1.min-1 for the women compared to the rest values [5.8 (SD 0.4) and 4.7 (SD 0.5) 1.min-1, respectively]. Flow velocity integral and acceleration time differed significantly between the two groups at rest (P < 0.05). During exercise these differences showed an interaction effect (P < 0.05). These results would indicate that normal men and women respond to sudden strenuous exercise by reducing their left ventricular systolic function, with a significantly greater decrease in women (P < 0.05). The gender differences in the haemodynamic responses during the present study, may, as suggested by others, be attributable to differences in energy metabolism. In addition, changes in Doppler parameters of aortic flow, haemodynamics and blood pressure responses during sudden strenuous exercise differed markedly from those seen before with endurance exercise.     

Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy

In this study, regional diastolic patterns and their relations with transmitral Doppler inflow were investigated in hypertrophic cardiomyopathy (HC) by pulsed Doppler tissue imaging (DTI). Doppler echocardiography and DTI of basal septum and lateral wall (apical 4-chamber view) were performed in 20 patients (15 men and 5 women) with HC and in 10 healthy subjects (7 men and 3 women). Diabetes, hypertension, coronary artery and valvular disease, mitral regurgitation, New York Heart Association functional classes III to IV, sinus tachycardia, atrial fibrillation, and inadequate echocardiograms were exclusion criteria. Peak velocity and time-velocity integral of early and late waves and their ratios, and deceleration and isovolumic relaxation times were determined by standard Doppler and by DTI at the septal and lateral wall levels. The 2 groups were comparable for age, heart rate, blood pressure, and ejection fraction. Transmitral peak velocity and time-velocity integral E/A ratios were reduced (both p <0.05) and deceleration and isovolumic relaxation times prolonged (both p <0.00001) in HC. Septal DTI showed lower peak velocity and time-velocity integral e/a ratios (p <0.00001 and p <0.001, respectively) and lengthened regional deceleration (p <0.01) and isovolumic (p <0.001) relaxation times. DTI of the lateral wall showed a prolongation of deceleration and isovolumic relaxation times (both p <0.01). By dividing HC according to transmitral E/A, 8 patients with E/A <1 had lower DTI septal e/a ratio (p <0.01) and prolonged septal deceleration and isovolumic relaxation times (both p <0.01) but no changes in DTI pattern of lateral wall than 12 patients with E/A > 1. In conclusion, DTI is useful and complementary to standard Doppler imaging to characterize diastolic properties in HC, reflecting a typical pattern of intramyocardial impaired relaxation at the level of hypertrophied septum and also providing information about the degree of this regional impairment. The lateral wall presents minor changes in diastolic times, which indicate how diastolic asynchrony is not confined to the hypertrophied segment in HC.     

Recovery of cardiac function by long-term left ventricular support in patients with end-stage cardiomyopathy

Effects of long-term left ventricular (LV) support on end-stage cardiomyopathy patients is unclear. We applied our LV assist system (LVAS) to six heart transplant candidates, aged 17 to 49, with dilated cardiomyopathy, including one dilated phase hypertrophied cardiomyopathy. LVAS was installed between the left atrium and the ascending aorta, and the pump was positioned parecorporeally. In all patients, their general condition improved, and their pump flows were kept at 4 to 5 L/min. Exercise was started after stabilization of their general condition under constant pump flow. Natural heart size and function were examined by echocardiography. In the beginning of assist, all patients showed impaired cardiac function and LV dilation. During LV assist, systolic function measured by ejection time improved in all patients. Left ventricular end-diastolic dimension (LVDd), showed a remarkable decrease in two patients, who were weaned from LVAS after 3 months of support. They are doing well more than 1 year and 3 years after removal; peak VO2 levels (ml/min/kg) were 30 at 1.2 years and 27 at 2.7 years after removal. In the other four patients, however, LVDd had no remarkable changes, and three could not be weaned from LVAS. The last was discontinued from LVAS after 5 months of support because of infection and died 2 months after removal. From this experience, long-term LVAS may provide the chance for recovery of the natural heart in patients with end-stage cardiomyopathy. The patients whose hearts showed remodeling were able to be weaned from LVAS, and their heart function maintained in good condition for several years.     

Familial hypertrophic cardiomyopathy. Cardiac ultrasonic abnormalities in genetically affected subjects without echocardiographic evidence of left ventricular hypertrophy

AIMS: It is not known whether the apparent normality of echocardiographic examination results, in subjects bearing a mutation for hypertrophic cardiomyopathy but without ultrasonic left ventricular hypertrophy, is due to incomplete phenotypic expression, or inaccurate echocardiographic criteria. The aim of this study was to search for echocardiographic abnormalities in these patients. METHODS AND RESULTS: Echocardiography was performed in 100 subjects from two families with a mutation in the beta-MHC (720) or My-BPC (714) genes. We compared genetically affected subjects with an apparently normal left ventricle (thickness < 13 mm) (20 patients), and nonaffected first-degree relatives (61 normal subjects). (1) Patients had a thicker left ventricular wall (9.7 +/- 1.4 vs 8.9 +/- 1.4 mm, P = 0.03), a greater indexed mass (107 +/- 18 vs 97 +/- 17 g. m-2, P = 0.03), a larger left atrium (27 +/- 9 vs 23 +/- 10 mm3, P = 0.09) and lower wall stress (78 +/- 11 vs 89 +/- 15 10(3) dynes. cm-2, P = 0.002); these differences were highly significant after adjustment for height, age and systolic blood pressure either for wall thickness (P = 0.000003), mass (P = 0.005) or atrial volume (P = 0.001), and the ventricular systolic dimension appeared smaller (P = 0.01); (2) results remained significant (P < 0.01) when a lower cut-off value (< or = 11 mm) or only adults (> or = 18 years) were considered; (3) a subanalysis of Family 714 (13 patients, 25 normals matched for sex, age and height) showed the same trends. CONCLUSION: In familial hypertrophic cardiomyopathy, genetically affected subjects with an apparently normal heart by echocardiography show slight ultrasonic structural and functional left ventricular modifications, suggesting that the phenotype of the disease is a continuous spectrum from normal structure to typical hypertrophy.     

Long-term effect of inducible silent ischaemia on left ventricular systolic function

A new method of thin section preparation of III-V semiconductors and multilayers for transmission electron microscopy (TEM) is presented that exhibits considerable advantages over conventional methods such as ion beam milling and jet thinning. GaAs thin films and multilayers of GaAs/In chi Ga1-chi As/GaAs are grown over an etch release layer of AlAs on GaAs substrates by molecular beam epitaxy (MBE). Planar TEM sections prepared by selective etching from these samples show improved ability to image film morphology and dislocation arrangements, and the resulting large thin electron transparent areas facilitate dislocation density measurements and detection of spatial variations. Avoidance of radiation effects and wedge shaping, both common to ion milled samples, allows this method to be used to prepare uniform thickness standards of single layer GaAs films for EDS analysis or lattice imaging.     

Variable distributions of Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors on embryonic rat dorsal horn neurons

1. By measuring the apparent reversal potential (aErev) of kainate- and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA)-evoked currents associated with changes in extracellular Ca2+ concentration ([Ca2+]e), we have been able to identify embryonic dorsal horn neurons grown in tissue culture that express Ca(2+)-permeable non-N-methyl-D-aspartic acid (NMDA) receptors. 2. The relative expression of Ca(2+)-permeable and Ca(2+)-impermeable non-NMDA receptors varies from cell to cell. This was evident from the range of a ErevS observed for kainate-evoked currents in a 0 mM [Na+]e, 10 mM [Ca2+]e bath. Under these conditions, aErev ranged from -96 to -21 mV, suggesting that the percentage of the non-NMDA receptors on each neuron that are Ca(2+)-permeable is variable. 3. To determine the extent to which the variability in aErev is due to variable receptor expression rather than experimental variability, we compared the effects of changes in [Ca2+]e on kainate-evoked currents and NMDA-evoked currents on the same cells. Assuming that all of the NMDA receptors on each neuron have a similar Ca2+ permeability, this approach provides an index of the sensitivity of our assay system. The reversal potential of NMDA-evoked currents in 10 mM [Ca2+]e ranged from -30 to -7 mV, whereas on the same population of neurons, the aErev of kainate-evoked currents ranged from -92 to -40 mV. 4. The rectification properties of the non-NMDA currents were generally linear or outwardly rectifying in normal bath solution. When the PCa/PCs ratio in 0 mM [Na+]e, 10 mM [Ca2+]e bath solution was assessed as a function of the rectification index in standard bath, a poor correlation was found between Ca2+ permeability and the rectification index. 5. The aErev of kainate-evoked currents was similar to that of cyclothiazide-enhanced AMPA-evoked currents observed on the same cells (-66.5 +/- 18.4 and -64.0 +/- 13.9 mV, mean +/- SD, respectively). This suggests that kainate is primarily activating the AMPA receptor and that the majority of non-NMDA receptors on embryonic dorsal horn neurons in culture are high-affinity AMPA receptors. 6. Immunocytochemical evidence suggests that the AMPA receptor subunits GluR1-4 are expressed to a variable degree from cell to cell in our cultures. We found evidence for low levels of expression of the kainate receptor subunits GluR5-7. The immunocytochemical observations support the physiological data indicating that much of the kainate-evoked current recorded in our experiments can be accounted for by kainate activation of AMPA receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Syncope and ventricular arrhythmias in hypertrophic cardiomyopathy are not related to the derangement of coronary microvascular function

Non-sustained ventricular tachycardia on Holter and syncope have been considered risk factors for sudden death in hypertrophic cardiomyopathy. AIMS: In these patients the coronary vasodilator reserve is impaired despite normal coronaries, so we evaluated the correlation between the severity of coronary vasodilator reserve impairment and the occurrence of syncope and non-sustained ventricular tachycardia. METHODS AND RESULTS: Eighty-four patients with hypertrophic cardiomyopathy (62 males, age 43 +/- 12 years) had a two-dimensional echocardiographic study and a 48-h Holter. Myocardial blood flow was measured by positron emission tomography, at baseline and after dipyridamole, and the coronary vasodilator reserve was computed as dipyridamole myocardial blood flow/baseline myocardial blood flow. In 27 patients, subendocardial and subepicardial myocardial blood flow was measured in the septum and the subendocardial/subepicardial ratio was computed. Twenty of 84 patients had at least one syncopal episode, and 26 had at least one run of non-sustained ventricular tachycardia on Holter. Baseline and dipyridamole myocardial blood flow, coronary vasodilator reserve, and baseline and dipyridamole subendocardial/subepicardial myocardial blood flow ratio were similar in patients with and without syncope and with and without non-sustained ventricular tachycardia on Holter. However, patients with non-sustained ventricular tachycardia had larger left ventricular end-diastolic (47 +/- 6 vs 44 +/- 5 mm, P < 0.05) and end-systolic diameters (30 +/- 6 vs 27 +/- 4 mm, P < 0.05). CONCLUSIONS: (1) Coronary vasodilation is not more severely impaired in patients with hypertrophic cardiomyopathy and syncope or non-sustained ventricular tachycardia. (2) The left ventricle is more dilated in hypertrophic cardiomyopathy with non-sustained ventricular tachycardia.     

Effects of transdermal nitroglycerin on left ventricular function after acute myocardial infarction

Progressive left ventricular dysfunction in acute myocardial infarction patients is associated with a poor prognosis. It has been shown that some therapeutic measures which have the potential for limiting the infarct size and preserving ventricular function, are also able to reduce the incidence of congestive heart and improve survival. The aim of this protocol was to assess the effects of transdermal nitroglycerin administered within 72 hours after the onset of acute myocardial infarction and for the following 6 months, on left ventricular function. A total of 98 consecutive acute myocardial infarction patients were randomly allocated, within 72 hours of onset of symptoms, to a double-blind 6-month-therapy with either 10 mg/24 hour transdermal nitroglycerin or placebo. Patients underwent two-dimensional echocardiography at entry, after 2 weeks, 3 months and 6 months. In the nitroglycerin group, end-diastolic volume increased during the follow-up (+6.7%, p < 0.05) while end-systolic volume remained nearly unchanged; ejection fraction and stroke volume increased progressively (+6.3%, p < 0.05, +14.2%, p < 0.05, respectively) and a important reduction of percent of dyssynergic segments was present (-19.2%, p < 0.005). In the placebo group end-diastolic volume and end-systolic volume slightly increased during the follow-up (+2% and +4.9% respectively); ejection fraction and stroke volume remained nearly unchanged during the study; percent of dyssynergic segments showed an important decrease after 2 weeks and 6 months (-21.3%, p < 0.005). A clinically relevant increase (> 20%) in ejection fraction was present more frequently in the nitroglycerin than in the placebo group (p < 0.001). In conclusion, the early (within 72 hours) and prolonged (6 months) administration of transdermal nitroglycerin in acute myocardial infarction improves ejection fraction and stroke volume but does not modify ventricular remodeling.     

Contrasting effects of carbachol, McN-A-343 and AHR-602 on Ca(2+)-mobilization and Ca(2+)-influx pathways in taenia caeci

1. We compared the binding profiles and contractile mechanisms of putative muscarinic M1 agonists McN-A-343 and AHR-602 with those of carbachol in smooth muscle of guinea-pig taenia caeci. 2. McN-A-343 and AHR-602, as well as carbachol, completely displaced the atropine-sensitive binding of [3H]-quinuclidinyl benzilate to muscarinic receptors present in the membrane preparation. The potency order for the affinity of these agents for muscarinic receptors was carbachol > McN-A-343 > AHR-602. 3. In the presence of 2.2 mM extracellular Ca2+, McN-A-343 and AHR-602 induced contraction corresponding to 79 and 85%, respectively, of the maximal contraction to 0.1 mM carbachol. Contractions induced by these agents were mediated via activation of the muscarinic receptor subtype that had a high affinity for 4-DAMP (M3 selective) but a low affinity for pirenzepine (M1 selective) and AF-DX 116 (M2 selective). These contractions were inhibited by an L-type Ca2+ channel blocker, verapamil. 4. In Ca(2+)-free solution containing 2 mM EGTA, carbachol elicited a transient contraction whereas no contraction was observed in response to McN-A-343 and AHR-602. Application of McN-A-343 or AHR-602 inhibited the carbachol-induced contraction in Ca(2+)-free solution, and this inhibition was surmounted by a higher concentration of carbachol. 5. The EC50 value for carbachol-induced contraction in the presence of extracellular Ca2+ was approximately 175 times lower than that in the absence of Ca2+. After treatment with propylbenzilylcholine mustard, carbachol induced contraction only in the presence of extracellular Ca2+. 6. The results suggest that in the taenia caeci there is a greater receptor reserve for muscarinic M3 receptor-mediated Ca2+ influx than for M3 mediated Ca2+ release. The compounds McN-A-343 and AHR-602 are agonists of the Ca2+ influx pathway, but do not appear to stimulate the Ca2+ release pathway.     

Transient normalization of systolic and diastolic function after support with a left ventricular assist device in a patient with dilated cardiomyopathy

A 19-year-old man who had fulminant heart failure caused by an idiopathic dilated cardiomyopathy was supported with a left ventricular assist device for 183 days as a bridge to heart transplantation. At the time of intended transplantation it was noted that the patient's heart had returned to normal size, had a normal ejection fraction, and was able to maintain normal pressures and flows. In view of the apparent recovery of cardiac properties, the left ventricular assist device was explanted and the transplantation was not performed. However, the heart dilated, ejection fraction worsened, and the patient died of heart failure exacerbated acutely by a systemic viral illness. Although such recovery of systolic function is uncommon, as use of the left ventricular assist devices becomes more widespread other physicians might encounter similar findings and, in this regard, they might find our experience useful as they contemplate their treatment options.     

Effects of partial left ventriculectomy on left ventricular performance in patients with nonischemic dilated cardiomyopathy

OBJECTIVES: This study sought to assess the effects of partial left ventriculectomy (PLV) on left ventricular (LV) performance in a series of consecutive patients with nonischemic dilated cardiomyopathy. BACKGROUND: Reduction of LV systolic function in patients with heart failure is associated with an increase of LV volume and alteration of its shape. Recently, PLV, a novel surgical procedure, was proposed as a treatment option to alter this process in patients with dilated cardiomyopathy. METHODS: We studied 19 patients with severely symptomatic nonischemic dilated cardiomyopathy, before and 13+/-3 days after surgery, and 12 controls. Single-plane left ventriculography with simultaneous measurements of femoral artery pressure was performed during right heart pacing. RESULTS: The LV end-diastolic and end-systolic volume indexes decreased after PLV (from 169 to 102 ml/m2, and from 127 to 60 ml/m2, respectively, p < 0.0001 for both). Despite a decrease in LV mass index (from 162 to 137 g/m2, p < 0.0001), there was a significant decrease in LV circumferential end-systolic and end-diastolic stresses (from 277 to 159 g/cm2, p < 0.0001 and from 79 to 39 g/cm2, p = 0.0014, respectively). Ejection fraction improved (from 24% to 41%, p < 0.0001); the stroke work index remained unchanged. CONCLUSIONS: The PLV improves LV performance by a dramatic reduction of ventricular end-systolic and end-diastolic stresses. Further studies are needed to assess whether this effect is sustained during long-term follow-up and to define the role of PLV in the treatment of patients with dilated cardiomyopathy.     

Characterization of Ca(2+) flows essential in ornithine decarboxylase induction by L-asparagine in rat hepatoma cells using Ca(2+) flow inhibitors

L-Asparagine stimulates bi-directional Ca(2+) flows and induces ornithine decarboxylase in Reuber H-35 hepatoma cells. Previously it has been shown that these effects are completely, but reversibly inhibited by lanthanum chloride. In this study we examined the role(s) of Ca(2+) flows using more specific Ca(2+) flow inhibitors. It was shown that ornithine decarboxylase induction was inhibited by CdCl(2) and verapamil at concentrations above 1 mu M and 100 mu M respectively, but was unaffected by as much as 300 mu M NiCl(2), 1 mM nifedipine, or 10 mu M omega-conotoxin. Enzyme induction was blocked by the Ca(2+)-ATPase pump antagonists vanadate and Compound 48/80 in a dose-dependent manner. These results, taken together with the observations that extracellular Ca(2+) is essential for enzyme induction but a substantial elevation of cytoplasmic [Ca(2+)] is not, suggest that Ca(2+) inflow independent of the receptor-activated Ca(2+) channels, and the Ca(2+)-ATPase mediated Ca(2+) out-flow, are both important factors in the action of L-asparagine.