Biomedical subjects

M Schwaiger

Publications and source records attributed to M Schwaiger.

At least 73 records · Page 4Linked to original sources

PubMed2001

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

Adult↗

PubMed2001

Myocardial blood flow and flow reserve after coronary reimplantation in patients after arterial switch and ross operation.

BACKGROUND: Coronary reimplantation is used in therapy for congenital heart disease, such as in the arterial switch (ASO) and Ross operations. The adequacy of myocardial perfusion may remain a matter of concern. The aim of the present study was to stratify the effect of coronary reimplantation on myocardial perfusion and to highlight the clinical relevance of any attenuation in myocardial perfusion. METHODS AND RESULTS: A total of 21 children with transposition of the great arteries at a mean interval of 11.2+/-2.9 years after ASO and 9 adolescents at a mean interval of 4.2+/-2.1 years after the Ross procedure were investigated. All patients were asymptomatic and had a normal exercise capacity. On stress echocardiography, 2 of the ASO patients had dyskinetic areas within the left ventricular myocardium, and 5 had adenosine-induced perfusion defects on positron emission tomography. No coronary obstruction was detected on coronary angiography in any patient, but a common finding was right coronary dominance and a small caliber of the distal part of the left anterior descending artery. Coronary flow reserve (CFR) was significantly reduced in all patients after ASO when compared with 10 normal healthy volunteers (age, 25.6+/-5.3 years). CFR was normal in the 9 patients who had the Ross operation (age, 19.2+/-7.6 years); exercise-induced perfusion defects were not detected in the Ross patients. CONCLUSIONS: Children after ASO are asymptomatic, without clinical signs of coronary dysfunction. In contrast to patients who had the Ross operation, stress-induced perfusion defects and an attenuated CFR were documented. The prognostic implications of these findings and the clinical consequences are unclear; nevertheless, close clinical follow-up of ASO patients is mandatory.

Adolescent↗

PubMed2001

Myocardial efficiency and sympathetic reinnervation after orthotopic heart transplantation: a noninvasive study with positron emission tomography.

BACKGROUND: The lack of cardiac catecholamine uptake and storage caused by sympathetic denervation may influence performance of the transplanted heart. Reinnervation, occurring late after transplantation, may partially resolve these effects. In this study, oxidative metabolism and its relation to cardiac work were compared in allografts and normal and failing hearts, and the effects of sympathetic reinnervation were evaluated. METHODS AND RESULTS: Twenty-seven nonrejecting, symptom-free transplant recipients, 11 healthy control subjects, and 10 patients with severe dilated cardiomyopathy underwent PET with (11)C acetate for assessment of oxidative metabolism by the clearance constant k(mono) and radionuclide angiography or MRI for measurement of ventricular function, geometry, and work. Efficiency was estimated noninvasively by a work-metabolic index [WMI=(stroke volumexheart ratexsystolic pressure)/k(mono)]. In 14 of 27 transplants, presence of regional reinnervation was identified with PET and the catecholamine analogue (11)C hydroxyephedrine (extent, 24+/-14% of left ventricle). The WMI was comparable in normal subjects and reinnervated and denervated transplants (6.2+/-2.3 versus 4.9+/-2.0 versus 4.9+/-1.2. 10(6) mm Hg. mL; P=NS) and significantly lower in cardiomyopathy patients (3.0+/-1.3. 10(6) mm Hg. mL; P<0.001). For normal subjects and transplant recipients, the WMI was significantly correlated with afterload (peripheral vascular resistance; r=-0.65, P<0.01), preload (end-diastolic volume; r=0.78, P<0.01), and stroke volume (r=0.81, P<0.01) but not with hydroxyephedrine retention (transplants only; r=0.09, P=NS). CONCLUSIONS: After transplantation, cardiac efficiency is improved compared with failing hearts and comparable to normal hearts. Differences between denervated and reinnervated allografts were not surveyed. Additionally, the dependency on loading conditions and contractility was preserved, suggesting that normal regulatory interactions for efficiency are intact and that sympathetic tone does not play a role under resting conditions.

Aged↗

PubMed2001

Highly specific tumor binding of a 213Bi-labeled monoclonal antibody against mutant E-cadherin suggests its usefulness for locoregional alpha-radioimmunotherapy of diffuse-type gastric cancer.

A monoclonal antibody (E-cadherin delta 9-1) directed against a characteristic E-cadherin mutation (in-frame deletion of exon 9), found in diffuse-type gastric cancer but not in any normal tissue, was conjugated with the high linear energy transfer alpha-emitter 213Bi and tested for its binding specificity in s.c. and i.p. nude mice tumor models. After intratumoral application in s.c. tumors expressing mutant E-cadherin, the 213Bi-labeled antibody was specifically retained at the injection site as shown by autoradiography. After injection into the peritoneal cavity, uptake in small i.p. tumor nodules expressing mutant E-cadherin was 17-fold higher than in tumor nodules expressing wild-type E-cadherin (62% injected dose/g versus 3.7% injected dose/g). 78% of the total activity in the ascites fluid was bound to free tumor cells expressing mutant E-cadherin, whereas in control cells, binding was only 18%. The selective binding of the 213Bi-labeled, mutation-specific monoclonal antibody E-cadherin delta 9-1 suggests that it will be successful for alpha-radioimmunotherapy of disseminated tumors after locoregional application.

Animals↗

PubMed2001

Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography.

The alpha(v)beta3 integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the 18F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-D-Phe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[18F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized alpha(v)beta3, alpha(v)beta5, and alpha(IIb)beta3 as well as in vivo studies using alpha(v)beta3-positive and -negative murine and xenotransplanted human tumors demonstrated receptor-specific binding of the radiolabeled glycopeptide yielding high tumor:background ratios (e.g., 120 min postinjection: tumor:blood, 27.5; tumor:muscle, 10.2). First imaging results using a small animal positron emission tomograph suggest that this compound is suitable for noninvasive determination of the alpha(v)beta3 integrin status and therapy monitoring.

Animals↗

PubMed2001

Similarity of ventricular function in patients alive 5 years after randomization to surgery or angioplasty in the BARI trial.

BACKGROUND: Left ventricular ejection fraction (LVEF) is a recognized determinant of survival in patients with coronary artery disease. In major trials comparing surgical and percutaneous revascularization approaches, the long-term effect of the coronary revascularization strategy on LVEF has not been reported. METHODS AND RESULTS: In the NHLBI-sponsored Bypass and Angioplasty Revascularization Investigation (BARI) randomized trial comparing angioplasty and bypass surgery as initial treatment strategies, 1220 (75%) of the 1617 surviving randomized patients had their EF measured by radionuclide ventriculography 5 years after study entry. For the total study group, the 5-year EF in the CABG group (n=623) was 55.8+/-12.3, compared with 55.7+/-12.7 in PTCA group (n=597, P:=0.82). There was no significant difference in measured EF between the CABG group and the PTCA group within multiple subgroups determined by the presence or absence of diabetes, 3-vessel disease, complete revascularization, or prior myocardial infarction. In a multiple linear regression model developed to predict 5-year EF, treatment assignment to PTCA or CABG was not significant (P:=0.95). If an EF of 0 was imputed for patients who were dead and missing EF data, however, there was a higher EF in the CABG group (P:=0.0018) among diabetic patients only. CONCLUSIONS: In the BARI randomized trial, initial treatment assignment to angioplasty was not associated with any difference in long-term ventricular function compared with initial treatment assignment to surgery. These results apply, however, only to patients who were alive at 5 years.

Angioplasty↗

PubMed2001

Usefulness of intracoronary brachytherapy for in-stent restenosis with a 188Re liquid-filled balloon.

The objective of this randomized pilot trial with 21 patients was to evaluate the effectiveness of a rhenium-188 liquid-filled balloon system to prevent recurrent restenosis after percutaneous transluminal coronary angioplasty for in-stent restenosis. A significant benefit from brachytherapy was seen at 6-month repeat angiography, as well as during the clinical follow-up of 12 months.

Aged↗

PubMed2001

Activation of frontal premotor areas during suprathreshold transcranial magnetic stimulation of the left primary sensorimotor cortex: a glucose metabolic PET study.

We employed cerebral (18)Fluoro-deoxyglucose positron emission tomography ([(18)F]FDG-PET) to visualize neuronal activation of the frontal motor and premotor cortex during suprathreshold repetitive transcranial magnetic stimulation (rTMS) applied to the left primary sensorimotor hand area (SM1(HAND)). Twelve right-handed normal subjects underwent two [(18)F]FDG-PET measurements at baseline without rTMS and during suprathreshold 2 Hz rTMS of the left SM1(HAND). In the rTMS condition, 1,800 magnetic stimuli at an intensity of 140% of motor-resting threshold were delivered immediately after intravenous injection of [(18)F]FDG. Relative differences in the normalized regional cerebral metabolic rate for glucose (rCMRglc) between the rTMS condition and baseline were determined using a voxel-by-voxel Student's t-test and a volume-of-interest analysis. Data analysis was a priori restricted to primary motor and premotor areas in the frontal cortex, namely the SM1, the supplementary motor area (SMA), the lateral premotor cortex (PMC), and the caudal anterior cingulate cortex (ACC) of either hemisphere. In addition to a relative increase in normalized rCMRglc in the stimulated SM1(HAND), suprathreshold rTMS was associated with well-localized increases in normalized rCMRglc in the caudal SMA and ACC on the medial wall of the frontal cortex and in the right precentral gyrus in the lateral PMC rostrally to the SM1. These data demonstrate that a selective activation of the SM1(HAND) is paralleled by an activation of a distinct set of remote premotor areas, suggesting a functional interaction between the primary motor and premotor cortex in humans.

Adult↗

PubMed2001

Right lateralized motor cortex activation during volitional blinking.

Using H2 15O positron emission tomography in 6 healthy volunteers, we found that self-initiated and externally cued blinking activated the right primary motor cortex and supplementary motor area (SMA). The left dorsolateral prefrontal cortex (DLPFC) and the rostral SMA showed greater activation during the self-initiated task compared to the externally cued task. This study confirms the hypothesis of right hemispheric lateralization of volitional blinking derived from observations in stroke patients. Furthermore, it underscores the role of DLPFC and rostral SMA in self-initiated movements, which has been found in similar experiments with hand movements.

Aged↗

PubMed2001

Cortical correlates of gesture processing: clues to the cerebral mechanisms underlying apraxia during the imitation of meaningless gestures.

The clinical test of imitation of meaningless gestures is highly sensitive in revealing limb apraxia after dominant left brain damage. To relate lesion locations in apraxic patients to functional brain activation and to reveal the neuronal network subserving gesture representation, repeated H2(15O)-PET measurements were made in seven healthy subjects during a gesture discrimination task. Observing paired images of either meaningless hand or meaningless finger gestures, subjects had to indicate whether they were identical or different. As a control condition subjects simply had to indicate whether two portrayed persons were identical or not. Brain activity during the discrimination of hand gestures was strongly lateralized to the left hemisphere, a prominent peak activation being localized within the inferior parietal cortex (BA40). The discrimination of finger gestures induced a more symmetrical activation and rCBF peaks in the right intraparietal sulcus and in medial visual association areas (BA18/19). Two additional foci of prominent rCBF increase were found. One focus was located at the left lateral occipitotemporal junction (BA 19/37) and was related to both tasks; the other in the pre-SMA was particularly related to hand gestures. The pattern of task-dependent activation corresponds closely to the predictions made from the clinical findings, and underlines the left brain dominance for meaningless hand gestures and the critical involvement of the parietal cortex. The lateral visual association areas appear to support first stages of gesture representation, and the parietal cortex is part of the dorsal action stream. Finger gestures may require in addition precise visual analysis and spatial attention enabled by occipital and right intraparietal activity. Pre-SMA activity during the perception of hand gestures may reflect engagement of a network that is intimately related to gesture execution.

Adult↗

PubMed2001

Continuous transcranial magnetic stimulation during positron emission tomography: a suitable tool for imaging regional excitability of the human cortex.

In six healthy volunteers, H(2)(15)O positron emission tomography (PET) was employed to evaluate rate-dependent functional activation of the left primary sensorimotor hand area (SM1(HAND)) during subthreshold repetitive transcranial magnetic stimulation (rTMS). Using an eight-shaped coil, continuous trains of rTMS were delivered during nine 50-s H(2)(15)O PET scans. Nine different stimulation frequencies were used, ranging from 1 to 5 Hz. Stimulus intensity was set at 10% below active motor threshold. During three additional PET scans, an ineffective rTMS was applied via another eight-shaped coil, which was held 10 cm above the vertex. Statistical parametric mapping was employed to assess relative differences in normalized regional cerebral blood flow (rCBF) across conditions. Compared with ineffective rTMS, subthreshold rTMS increased normalized rCBF in the stimulated SM1(HAND). Moreover, the increase in rCBF in the left SM1(HAND) showed a linear positive relationship with the rate of rTMS, indicating a rate-dependent functional activation of the stimulated SM1(HAND). These data demonstrate that, by varying the variables of rTMS across scans, continuous rTMS during H(2)(15)O PET provides a noninvasive tool to study the regional excitability profile of a distinct cortical area.

Adult↗

PubMed2001

[Monitoring of response to neoadjuvant therapy by positron emission tomography (PET)].

Neoadjuvant therapy is frequently hampered by the lack of reliable non-invasive techniques for prediction and assessment of response. Positron emission tomography using the glucose analogue 18F-fluorodeoxyglucose (FDG-PET) provides a unique means of non-invasive assessment of tumor metabolism. Several recent studies have indicated that a reduction of tumor metabolic activity after neoadjuvant therapy is closely correlated with the degree of histopathological tumor regression. The reduction of metabolic activity may also allow one to predict subsequent response early during the course of therapy. Therefore FDG-PET may permit individualized therapy management. However, there is a requirement for larger-scale trials to assess this technique.

Female↗

PubMed2001

A prototype high-resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals.

To fully utilize positron emission tomography (PET) as a non-invasive tool for tissue characterization, dedicated instrumentation is being developed which is specially suited for imaging mice and rats. Semiconductor detectors, such as avalanche photodiodes (APDs), may offer an alternative to photomultiplier tubes for the readout of scintillation crystals. Since the scintillation characteristics of lutetium oxyorthosilicate (LSO) are well matched to APDs, the combination of LSO and APDs seems favourable, and the goal of this study was to build a positron tomograph with LSO-APD modules to prove the feasibility of such an approach. A prototype PET scanner based on APD readout of small, individual LSO crystals was developed for tracer studies in mice and rats. The tomograph consists of two sectors (86 mm distance), each comprising three LSO-APD modules, which can be rotated for the acquisition of complete projections. In each module, small LSO crystals (3.7 x 3.7 x 12 mm3) are individually coupled to one channel within matrices containing 2x8 square APDs (2.6 x 2.6 mm2 sensitive area per channel). The list-mode data are reconstructed with a penalized weighted least squares algorithm which includes the spatially dependent line spread function of the tomograph. Basic performance parameters were measured with phantoms and first experiments with rats and mice were conducted to introduce this methodology for biomedical imaging. The reconstructed field of view covers 68 mm, which is 80% of the total detector diameter. Image resolution was shown to be 2.4 mm within the whole reconstructed field of view. Using a lower energy threshold of 450 keV, the system sensitivity was 350 Hz/MBq for a line source in air in the centre of the field of view. In a water-filled cylinder of 4.6 cm diameter, the scatter fraction at the centre of the field of view was 16% (450 keV threshold). The count rate was linear up to 700 coincidence counts per second. In vivo studies of anaesthetized rats and mice showed the feasibility of in vivo imaging using this PET scanner. The first LSO-APD prototype tomograph has been successfully introduced for in vivo animal imaging. APD arrays in combination with LSO crystals offer new design possibilities for positron tomographs with finely granulated detector channels.

Animals↗

PubMed2001

Global and regional functional measurements with gated FDG PET in comparison with left ventriculography.

The purpose of this study was to validate the measurement of global and regional left ventricular cardiac function with ECG-gated fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) by comparison with the corresponding indices from X-ray left ventriculography (LVG). Twenty-six patients (23 men, 3 women, mean age 60.4 years) underwent LVG and ECG-gated (eight frames/cycle) FDG-PET within an interval of 10.2+/-6.8 days. A volumetric sampling approach was used to obtain both global (EF: ejection fraction) and regional [%WT: relative regional count increase from end-diastolic (ED) to end-systolic (ES) phase] functional parameters. The gated PET parameters were compared with the corresponding findings of LVG in seven myocardial segments. EF(gated PET) and EF(LVG) did not differ significantly (30%+/-10% vs 32%+/-10%, P=NS). The two EF values correlated significantly, showing no significant systematic measurement bias [EF(gated PET) = 2.61+0.86 x EF(LVG), R=0.84, P<0.0001]. Inter- and intra-observer reproducibility for EF were R=0.95, P<0.0001 and R=0.92, P<0.0001, respectively. Regional function was evaluated with LVG in 144 myocardial segments comprising 35 normokinetic, 70 hypokinetic and 39 a/dyskinetic segments. Visual analysis of LVG and gated PET correlated significantly (P<0.001), with an overall concordance ratio of 58% (83/144, kappa=0.35). Gated PET overestimated the regional function in 27% (39/144) and underestimated it in 15% (22/144). %WT showed significant differences between each pair of groups (a/dyskinesis, 13.2%+/-9.3%; hypokinesis, 17.1%+/-8.8%; normokinesis, 21.8%+/-10.9%). Inter- and intra-observer reproducibility was significant for %WT (R=0.77, P<0.0001 and R=0.79, P<0.0001, respectively). In conclusion, gated FDG PET permits assessment of global left ventricular cardiac function. In addition, assessment of regional function is feasible using the visual or the quantitative parameters.

Aged↗

PubMed2001

[The role of magnetic resonance imaging in the diagnosis of coronary disease].

As the number of diagnostic coronary angiographies without subsequent revascularization procedures is continuously rising, the need for non-invasive diagnostic procedures with a high diagnostic accuracy is well appreciated. Because of the technical advances in magnetic resonance imaging (MRI) over the last few years, major improvements have been made in the functional assessment of wall motion, myocardial perfusion and coronary flow measurements, as well as the visualization of the anatomy of the coronary arteries by MRI. Besides these classical parameters of ischemia and anatomical pathology, for the first time MRI might offer the possibility to not only non-invasively assess the lumen of the coronary arteries, but also to visualize the vessel wall. Thus, early manifestations of coronary artery disease may be detectable for the identification of patients with preclinical disease as candidates for aggressive risk modification. In this review the current status as well as future perspectives of MRI are discussed.

Angioplasty, Balloon, Coronary↗

PubMed2001

How heterogeneous is the cardiac autonomic innervation?

The rich autonomic innervation of the heart plays an important role in modifying cardiovascular function. Recently developed in vivo scintigraphic imaging techniques allow for visualization of the autonomic innervation of the heart. Studies using the modalities have shown heterogeneity of sympathetic innervation in various kinds of pathological conditions as well as normal human heart. The inferioposterior region shows typically less sympathetic innervation than the anterior region. In addition, neuropathic processes appear to commence in inferior-apical regions extending towards the base of the heart. Arrhythmogeneity has been related to the heterogeneous innervation of the heart and heterogeneous uptake of radiolabeled catecholamine analogues, such as I-123 metaiodobenzylguanidine, can be found in patients with arrhythmia. In dilated cardiomyopathy, reduced uptake indicates a poor prognosis which allows risk stratification for patients with heart failure. Heterogeneity of the reinnervation process following heart transplantation has also been investigated. Evidence was found of reinnervation primarily in the basal anterioseptal region and to a lesser degree in the inferioposterior and apical regions. Tracer approaches are uniquely suited to identify regionally altered innervation and provide tools for linking information on cardiac autonomic innervation with other clinical aspects.

Arrhythmias, Cardiac↗

PubMed2001

Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies.

The aim of this study was to identify the functional cerebral network involved in the central processing of itch and to detect analogies and differences to previously identified cerebral activation patterns triggered by painful noxious stimuli. Repeated positron emission tomography regional cerebral blood flow (rCBF) measurements using O15-labeled water were performed in six healthy right-handed male subjects (mean age 32 +/- 2 years). Each subject underwent 12 sequential rCBF measurements. In all subjects a standardized skin prick test was performed on the right forearm 2 min before each rCBF measurement. For activation, histamine was applied in nine tests in logarithmically increasing concentrations from 0.03 to 8%. Three tests were performed with isotonic saline solution serving as a control condition. Itch intensity and unpleasantness were registered with a visual analogue scale during each test. Subtraction analysis between activation and control conditions as well as correlation analysis with covariates were performed. Itch induced a significant activation in the predominantly contralateral somatosensory cortex and in the ipsilateral and contralateral motor areas (supplementary motor area (SMA), premotor cortex, primary motor cortex). Additional significant activations were found in the prefrontal cortex and the cingulate gyrus, but not in subcortical structures nor in the secondary somatosensory cortex. In correlation analyses, several cortical areas showed a graded increase in rCBF with the logarithm of the histamine concentration (bilateral sensorimotor areas and cingulate cortex; contralateral insula, superior temporal cortex and prefrontal cortex) and with itch unpleasantness (contralateral sensorimotor cortex, prefrontal cortex and posterior insula; ipsilateral SMA). Induction of itch results in the activation of a distributed cerebral network. Itch and pain seem to share common pathways (a medial and a lateral processing pathway and a strong projection to the motor system). In contrast to pain activation studies, no subcortical (i.e. thalamic) activations were detected and correlation analyses suggest differences in subjective processing of the two sensations.

Adult↗

PubMed2001

Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes.

Although previously it was believed that apoptosis could not occur in the terminally differentiated tissue, such as adult heart muscle cells, recent studies in endomyocardial biopsies from patients with dilated cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histologic evidence of apoptosis. Whereas neurohormonal activation during heart failure leads to compensatory hemodynamic alterations, coupled with ventricular dilatation, it induces transcription factors and myocyte hypertrophy. Persistent growth stimulation in terminally differentiated cells may lead paradoxically to apoptotic cell death. The apoptosis in cardiomyopathic hearts is associated with cytochrome c release from mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3. Although the caspases are duly processed, the fragmentation of the nuclear proteins (including DNA) is completed less frequently, and only a variable degree of fragmentation of cytoplasmic proteins (including contractile proteins) is observed. It is hypothesized that release of cytochrome c from mitochondria should interfere with energy production and lead to functional impairment and variable loss of contractile proteins in a living heart muscle cell should contribute to systolic dysfunction. Because a nuclear blueprint is retained, however, the dysfunctional cell may continue to exist and in favorable conditions, such as with LVAD support, the apoptotic process may subside. Potential feasibility of reversal of heart failure should renew efforts to develop more targeted pharmaceutical intervention within the apoptotic cascade and allow newer paradigm for the management of heart failure.

Animals↗