Adequate function of the microcirculation is vital to any tissue. To maintain an optimal function, microvascular networks must be able to adapt structurally to changes in the physical environment. ...Here we present a mathematical network model based on vessel wall mechanics. We assume based on experimental observations that longstanding change in transmural pressure elicits a change in the vascular wall-to-lumen ratio for maintaining circumferential wall stress at a certain level. In addition, experimental observations show that chronic change in fluid shear stress at the vascular wall elicits a persistent change in luminal diameter. On this basis we hypothesize that wall influencing substances released from the endothelium in response to shear stress have a certain optimal level in the vascular wall. Deviation from this level will cause vascular remodeling, i.e. a structural change in luminal diameter, until equilibrium is restored. The model explains several of the key features observed experimentally in the microcirculation in normotension and hypertension. Most importantly, it suggests a scenario where overall network structure and network hemodynamics depend on adaptation to local hemodynamic stimuli in the individual vessel. Simulated results show emanating microvascular networks with properties similar to those observed in vivo. The model points to an altered endothelial function as a key factor in the development of vascular changes characteristic of hypertension.
The purpose of the present study was to investigate the conducted Ca(2+) response to local electrical stimulation in isolated rat interlobular arteries. Interlobular arteries were isolated from young ...Sprague-Dawley rats, loaded with fura 2, and attached to pipettes in a chamber on an inverted microscope. Local electrical pulse stimulation (200 ms, 100 V) was administered by means of an NaCl-filled microelectrode (0.7-1 M(Omega)) juxtaposed to one end of the vessel. Intracellular Ca(2+) concentration (Ca(2+)(i)) was measured with an image system at a site approximately 500 microm from the location of the electrode. The expression of mRNA for pore-forming units Ca(V)3.1 and Ca(V)3.2 of voltage-sensitive T-type channels was investigated by using RT-PCR. Current stimulation elicited a conducted Ca(2+)(i) response. A positive electrode (relative to ground) increased Ca(2+)(i) to 145 +/- 7% of baseline, whereas the response was absent when the electrode was negative. This response was not dependent on perivascular nerves, because the conducted response was unaffected by TTX (1 microM). The conducted Ca(2+)(i) response was abolished by an ambient Ca(2+) free solution and blunted by nifedipine (1 microM). Rat interlobular arteries exhibited conducted Ca(2+)(i) response to current stimulation. This response was dependent on Ca(2+) entry. L-type Ca(2+) channels may play a role in this process.
We discuss the first Danish case in which a left ventricular assist device (HeartMate 2) could be explanted after 13 months of support due to cardiac recovery in a young patient who presented with ...severe dilated cardiomyopathy during pregnancy. Aggressive medical treatment with angiotensin converting enzyme inhibitor, beta blocker and aldosterone antagonist was used, and the patient remained stable without circulatory support several months after device removal.
BackgroundCardiomyopathy caused by aggregation and deposition of transthyretin amyloid fibrils in the heart (ATTR-CM) is divided into a hereditary (ATTRv) and a wild-type (ATTRwt) forms. While ...ATTR-CM has been considered a rare disease, recent studies suggest that it is severely underdiagnosed and an important cause of heart failure in elderly patients. Familial occurrence is implicit in ATTRv, but it is not expected in ATTRwt.Case summaryWe report a case series of two unrelated families each with two brothers diagnosed with ATTRwt. Genetic testing did not reveal mutations in the transthyretin gene. Family screening with electrocardiogram, echocardiography, and genetic testing did not raise any suspicion of ATTR in first-line family members.DiscussionFamilial occurrence of a rare, non-hereditary disease is statistically unlikely. Two siblings in two different families diagnosed with ATTRwt highlight that the aetiology of ATTRwt is poorly understood, and that genetic factors distinct from mutations in the transthyretin gene, as well as environmental factors, might contribute to the pathogenesis. Identifying such factors might reveal new therapeutic targets. To investigate this further, clinicians need to be aware of the possibility of familial occurrence of ATTRwt.
BACKGROUND—The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICD) in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) did not demonstrate an ...overall effect on all-cause mortality with ICD implantation. However, the pre-specified subgroup analysis suggested a possible age-dependent association between the ICD and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with non-ischemic systolic heart failure warrants further investigation.
METHODS—All 1116 patients from the DANISH study were included in this pre-specified subgroup analysis. We assessed the relationship between the ICD and mortality by age, and an optimal age cut-off was estimated non-parametrically using selection impact curves. Modes of death were divided into sudden cardiac death (SCD) and non-sudden death and compared between patients younger and older than this age cut-off, respectively, with the use of Chi2-analysis.
RESULTS—Median age of the study population was 63 years (range 21 - 84 years). There was a linearly decreasing relationship between the ICD and mortality with age, HR 1.03 (95% CI 1.003 - 1.06), p=0.03. An optimal age cut-off for ICD implantation was present at ≤70 years. There was an association between reduced all-cause mortality and the ICD in patients ≤70 years, HR 0.70 (0.51 - 0.96), p=0.03, but not in patients >70 years, HR 1.05 (0.68 - 1.62), p=0.84. For patients ≤70 years, SCD rate was 1.8 (1.3 - 2.5) and non-sudden death rate was 2.7 (2.1 - 3.5) events/100 patient years, whereas for patients older than 70 years SCD rate was 1.6 (0.8 - 3.2) and non-sudden death rate was 5.4 (3.7 - 7.8) events/100 patient years. This difference in modes of death between the two age groups was statistically significant (p=0.01).
CONCLUSIONS—In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cut-off for ICD implantation at ≤70 years yielded the highest survival for the population as a whole.
Purpose. Transthyretin is produced in the retina and approximately one quarter of patients with variant transthyretin amyloidosis (ATTRv) develop ocular involvement. Glaucoma is the most important ...ocular manifestation, leading to rapid loss of vision. The usefulness of glaucoma as a red flag for cardiac amyloidosis is unknown. Materials and Methods. On a national scale, we investigated the association between glaucoma and development of amyloidosis, compared to an age- and sex-matched population from the general population. Results. The study population included 365,496 subjects (1:1 ratio). Adjusted Cox-models showed no significant association between glaucoma and future diagnosis of amyloidosis (hazard ratio: 1.16 0.80-1.70, p = .44). Conclusion. We conclude that while ocular involvement is a possible early manifestation of ATTRv, nationwide data suggest that glaucoma is probably not useful as a red flag for cardiac amyloidosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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