We have previously shown that distal anterior wall ischemia/reperfusion induces gene expression changes in the proximal anterior myocardial area, involving genes responsible for cardiac remodeling. ...Here we investigated the molecular signals of the ischemia non-affected remote lateral and posterior regions and present gene expression profiles of the entire left ventricle by using our novel and straightforward method of 2D and 3D image reconstruction. Five or 24h after repetitive 10min ischemia/reperfusion without subsequent infarction, pig hearts were explanted and myocardial samples from 52 equally distributed locations of the left ventricle were collected. Expressional changes of seven genes of interest (HIF-1α; caspase-3, transcription factor GATA4; myocyte enhancer factor 2C /MEF2c/; hexokinase 2 /HK2/; clusterin /CLU/ and excision repair cross-complementation group 4 /ERCC4/) were measured by qPCR. 2D and 3D gene expression maps were constructed by projecting the fold changes on the NOGA anatomical mapping coordinates. Caspase-3, GATA4, HK2, CLU, and ERCC4 were up-regulated region-specifically in the ischemic zone at 5 h post ischemia/reperfusion injury. Overexpression of GATA4, clusterin and ERCC4 persisted after 24 h. HK2 showed strong up-regulation in the ischemic zone and down-regulation in remote areas at 5 h, and was severely reduced in all heart regions at 24 h. These results indicate a quick onset of regulation of apoptosis-related genes, which is partially reversed in the late phase of ischemia/reperfusion cardioprotection, and highlight variations between ischemic and unaffected myocardium over time. The NOGA 2D and 3D construction system is an attractive method to visualize expressional variations in the myocardium.
Endocardial mapping of the left ventricle (LV) using the NOGA® XP Cardiac Navigation System can identify chronically ischemic and viable myocardium in patients with coronary artery disease by ...generating electromechanical maps. These maps are very useful when targeting myocardial tissue for injection of stem cells. We present the case of a woman who developed a perforation at the site of an LV aneurysm during NOGA mapping prior to the transendocardial injection of stem cells, as part of a multicenter clinical trial. The presence of an LV aneurysm is currently not a contraindication (or caution) to the use the NOGA mapping catheter. As the field of stem cell therapy evolves and the use of this technique increases, operators must be aware that the presence of an LV aneurysm may increase the risk of perforation during a NOGA mapping procedure.
•In clinical trials, endocardial mapping using the NOGA® XP Cardiac Navigation System is used to identify ischemic and viable myocardium in patients with coronary artery disease to guide the injection of stem cells or gene products.•The presence of an LV aneurysm from a prior myocardial infarction may represent a site within the LV at greater risk for perforation with manipulation of the relatively stiff NOGA catheter.•Therefore, greater caution is warranted during NOGA mapping in patients with an LV aneurysm.
Many cardiac catheter interventions require accurate discrimination between healthy and infarcted myocardia. The gold standard for infarct imaging is late gadolinium–enhanced MRI (LGE-MRI), but ...during cardiac procedures electroanatomical or electromechanical mapping (EAM or EMM, respectively) is usually employed. We aimed to improve the ability of EMM to identify myocardial infarction by combining multiple EMM parameters in a statistical model. From a porcine infarction model, 3D electromechanical maps were 3D registered to LGE-MRI. A multivariable mixed-effects logistic regression model was fitted to predict the presence of infarct based on EMM parameters. Furthermore, we correlated feature-tracking strain parameters to EMM measures of local mechanical deformation. We registered 787 EMM points from 13 animals to the corresponding MRI locations. The mean registration error was 2.5 ± 1.16 mm. Our model showed a strong ability to predict the presence of infarction (
C
-statistic = 0.85). Strain parameters were only weakly correlated to EMM measures. The model is accurate in discriminating infarcted from healthy myocardium. Unipolar and bipolar voltages were the strongest predictors.
Cell therapy has the potential to improve symptoms and clinical outcomes in refractory angina (RFA). Further analyses are needed to evaluate factors influencing its therapeutic effectiveness.
...Assessment of electromechanical (EM) parameters of the left ventricle (LV) and investigation of correlation between EM parameters of the myocardium and response to CD133+ cell therapy.
Thirty patients with RFA (16 active and 14 placebo individuals) enrolled in the REGENT-VSEL trial underwent EM evaluation of the LV with intracardiac mapping system. The following parameters were analyzed: unipolar voltage (UV), bipolar voltage (BV), local linear shortening (LLS). Myocardial ischemia was evaluated with single-photon emission computed tomography (SPECT). The median value of each EM parameter was used for intra-group comparisons.
Global EM parameters (UV, BV, LLS) of LV in active and placebo groups were 11.28 mV, 3.58 mV, 11.12%, respectively; 13.00 mV, 3.81 mV, 11.32%, respectively. EM characteristics analyzed at global and segmental levels did not predict response to CD133+ cell therapy in patients with RFA (Global UV, BV and LLS at rest
= -0.06;
= 0.2;
= -0.1 and at stress:
= 0.07,
= 0.09,
= -0.1, respectively; Segmental UV, BV, LLS at rest
= -0.2,
= 0.03,
= -0.4 and at stress
= 0.02,
= 0.2,
= -0.2, respectively). Multiple linear regression of the treated segments showed that only pre-injection SPECT levels were significantly correlated with post-injection SPECT, either at rest or stress (
< 0.05).
Electromechanical characteristics of the left ventricle do not predict changes of myocardial perfusion by SPECT after cell therapy. Baseline SPECT results are only predictors of changes of myocardial ischemia observed at 4-month follow-up.
Do Not Erase Wynne, Jessica
2021, 2021-06-22
eBook
A photographic exploration of mathematicians' chalkboards "A mathematician, like a painter or poet, is a maker of patterns, " wrote the British mathematician G. H. Hardy. In Do Not Erase, ...photographer Jessica Wynne presents remarkable examples of this idea through images of mathematicians' chalkboards. While other fields have replaced chalkboards with whiteboards and digital presentations, mathematicians remain loyal to chalk for puzzling out their ideas and communicating their research. Wynne offers more than one hundred stunning photographs of these chalkboards, gathered from a diverse group of mathematicians around the world. The photographs are accompanied by essays from each mathematician, reflecting on their work and processes. Together, pictures and words provide an illuminating meditation on the unique relationships among mathematics, art, and creativity.The mathematicians featured in this collection comprise exciting new voices alongside established figures, including Sun-Yung Alice Chang, Alain Connes, Misha Gromov, Andre Neves, Kasso Okoudjou, Peter Shor, Christina Sormani, Terence Tao, Claire Voisin, and many others. The companion essays give insights into how the chalkboard serves as a special medium for mathematical expression. The volume also includes an introduction by the author, an afterword by New Yorker writer Alec Wilkinson, and biographical information for each contributor. Do Not Erase is a testament to the myriad ways that mathematicians use their chalkboards to reveal the conceptual and visual beauty of their discipline—shapes, figures, formulas, and conjectures created through imagination, argument, and speculation.
Based on the contemporaneous and recent (domestic and foreign) literature and spatial plans, this paper examines the relationship between touristic and spatial planning in Croatia and Yugoslavia in ...the 1960s. The relationship is determined using the analytical-interpretative method of the then socio-political system, tourism and spatial policy, social planning, administrative bodies, institutions specialised for planning, tourist traffic, produced spatial plans, the intensity of building accommodation capacity, etc. In the first period after the end of the war, tourism developed in an uncontrolled manner because it was not the subject of coordinated socio-economic and spatial plans. Due to a growing interest for the inflow of foreign currencies from foreign tourists, tourism gradually gained significance and was regularly given priority in development plans. The new approach to spatial planning was most visible in the developed methodology of spatial plan production and the hotel architecture and constructed hotel complexes. Since the Croatian coast had the longest Adriatic shoreline in the then Yugoslavia, the longest tradition of tourism, and was the flagship among the republics in tourism development projections and the spatial planning of tourism (because of the developed methodology of plan production), the largest number of touristic spatial plans during the socialist period were made for the Croatian Adriatic coast (on multiple levels), and the greatest investments were made in building hotel capacity there. Despite the initial idea of developing tourism and equal accommodation options for all, the new tourism planning model transformed away from this basic idea and gave priority to exponential economic growth. This new approach to tourism was most visible through the establishment of a new network of organisations and institutions for planning tourism and tourism planning in a broader spatial context rather than only on the level of individual investments. All factors regarding the implementation of social plans could not have been taken into account because all the administrative and reorganisation factors as well as the dramatic events of the socio-political and economic system as a whole that took place in the 1990s could not have been predicted. The proper methodological steps for continued and coordinated planning in the 1960s introduced significant changes into the system of touristic and spatial planning. After the implementation of the plans began, the complexities of planning (numerous unpredictable factors) that influenced their realisation became apparent. The practice of planning was further complicated because plans often acted in an abstract and contradictory manner in a political system that had a limited capacity for realising quality—and in some cases utopian—plans.
Aims We aimed to quantify the release of biomarkers of myocardial damage in relation to direct intramyocardial injections of genes and stem cells in patients with severe coronary artery disease. ...Methods and results We studied 71 patients with ‘no-option’ coronary artery disease. Patients had, via the percutaneous transluminal route, a total of 11 ± 1 (mean ± SD) intramyocardial injections of vascular endothelial growth factor genes (n = 56) or mesenchymal stromal cells (n = 15). Injections were guided to an ischaemic area by electromechanical mapping, using the NOGA™/Myostar™ catheter system. Plasma CKMB (upper normal laboratory limit = 5 µg/L) was 2 µg/L (2–3) at baseline; increased to 6 (5–9) after 8 h (P < 0.0001) and normalized to 4 (3–5) after 24 h. A total of eight patients (17%), receiving a volume of 0.3 mL per injection, had CKMB rises exceeding three times the upper limit, whereas no patient in the group receiving 0.2 mL had a more than two-fold CKMB increase. No patient developed new ECG changes. There were no clinically ventricular arrhythmias and no death. Conclusion NOGA mapping followed by direct intramyocardial injections of stem cells or genes lead to measurable release of cardiac biomarkers compared with NOGA mapping alone. The increase in biomarkers was related to the injected volume.
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