[The antagonistic function of the heart muscle sustains the autoregulation according to Frank and Starling : Part I: Structure and function of heart muscle]. / Die antagonistische Funktion des Herzmuskels unterstützt die Autoregulation nach Frank-Starling : Teil I: Struktur und Funktion des Herzmuskels.

In the tradition of Harvey and according to Otto Frank the heart muscle structure is arranged in a strictly tangential fashion hence all contractile forces act in the direction of ventricular ejection. In contrast, morphology confirms that the heart consists of a 3-dimensional network of muscle fibers with up to two fifths of the chains of aggregated myocytes deviating from a tangential alignment at variable angles. Accordingly, the myocardial systolic forces contain, in addition to a constrictive also a (albeit smaller) radially acting component. Using needle force probes we have correspondingly measured an unloading type of force in a tangential direction and an auxotonic type in dilatative transversal direction of the ventricular walls to show that the myocardial body contracts actively in a 3-dimensional pattern. This antagonism supports the autoregulation of heart muscle function according to Frank and Starling, preserving ventricular shape, enhances late systolic fast dilation and attenuates systolic constriction of the ventricle wall. Auxotonic dilating forces are particularly sensitive to inotropic medication. Low dose beta-blocker is able to attenuate the antagonistic activity. All myocardial components act against four components of afterload, the hemodynamic, the myostructural, the stromatogenic and the hydraulic component. This complex interplay critically complicates clinical diagnostics. Clinical implications are far-reaching (see Part II, https://doi.org/10.1007/s00059-018-4735-x).

[Antagonistic function of the heart muscle : Part II: Clinical implications]. / Die antagonistische Funktion des Herzmuskels : Teil II: Klinische Auswirkungen.

In the hypertrophic heart the myostructural afterload in the form of endoepicardial networks is predominant, which enhances myocardial hypertrophy. The intrinsic antagonism is derailed. Likewise, the connective tissue scaffold, i.e. the stromatogenic afterload, is enriched in the response to the derailment of antagonism in a hypertrophic heart up to regional captivation of the heart musculature. Due to the selective susceptibility of the auxotonic, contracting oblique transmural myocardial network for low dose negative inotropic medication, this promises to attenuate progress in myocardial hypertrophy. Volume reduction surgery is most effective in reducing wall stress as long as the myocardium is not critically fettered by fibrosis. The use of external mechanical circulatory support is then effective if the heart is supported in its resting mode, which means around a middle width and at minimal amplitude of motion. The takotsubo cardiomyopathy might possibly reflect an isolated, extreme stimulation of the intrinsic antagonism as a response to hormonally induced sensitization of the myocardium to catecholamine. A particular significant conclusion with respect to the diseased heart is that clinical diagnostics need new impulses with a focus on the analysis of local motion patterns and on myocardial stiffness reflecting disease-dependent antagonistic intensity. This would become a relevant diagnostic marker if corresponding (noninvasive) measurement techniques would become available.

Cardiovascular magnetic resonance assessment of acute cardiovascular effects of voluntary apnoea in elite divers.

BACKGROUND: Prolonged breath holding results in hypoxemia and hypercapnia. Compensatory mechanisms help maintain adequate oxygen supply to hypoxia sensitive organs, but burden the cardiovascular system. The aim was to investigate human compensatory mechanisms and their effects on the cardiovascular system with regard to cardiac function and morphology, blood flow redistribution, serum biomarkers of the adrenergic system and myocardial injury markers following prolonged apnoea. METHODS: Seventeen elite apnoea divers performed maximal breath-hold during cardiovascular magnetic resonance imaging (CMR). Two breath-hold sessions were performed to assess (1) cardiac function, myocardial tissue properties and (2) blood flow. In between CMR sessions, a head MRI was performed for the assessment of signs of silent brain ischemia. Urine and blood samples were analysed prior to and up to 4 h after the first breath-hold. RESULTS: Mean breath-hold time was 297 ± 52 s. Left ventricular (LV) end-systolic, end-diastolic, and stroke volume increased significantly (p < 0.05). Peripheral oxygen saturation, LV ejection fraction, LV fractional shortening, and heart rate decreased significantly (p < 0.05). Blood distribution was diverted to cerebral regions with no significant changes in the descending aorta. Catecholamine levels, high-sensitivity cardiac troponin, and NT-pro-BNP levels increased significantly, but did not reach pathological levels. CONCLUSION: Compensatory effects of prolonged apnoea substantially burden the cardiovascular system. CMR tissue characterisation did not reveal acute myocardial injury, indicating that the resulting cardiovascular stress does not exceed compensatory physiological limits in healthy subjects. However, these compensatory mechanisms could overly tax those limits in subjects with pre-existing cardiac disease. For divers interested in competetive apnoea diving, a comprehensive medical exam with a special focus on the cardiovascular system may be warranted. TRIAL REGISTRATION: This prospective single-centre study was approved by the institutional ethics committee review board. It was retrospectively registered under ClinicalTrials.gov (Trial registration: NCT02280226 . Registered 29 October 2014).

[Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)]. / Vancouver-Klassifikation von Nierentumoren : Empfehlungen der Konsenskonferenz der Internationalen Gesellschaft für Uropathologie (ISUP) 2012.

The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.