2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS).

A deterioration of renal function is one preoccupying complication of iodinated radiocontrast agents in clinical practice. These compounds have direct toxic effects on renal cells, which are only in part related to their physicochemical properties. The hyperosmolal monomeric ionic radiocontrast agents, like diatrizoate, have the highest toxicity, whereas renal cells are less affected by (nonionic) compounds with reduced osmolality. The toxic effects include cellular energy failure, a disruption of calcium homeostasis, a disturbance of tubular cell polarity and programmed cell death (apoptosis). The molecular mechanisms of the direct cytotoxicity are still unclear, although oxidative stress has been implicated. Radiocontrast cytotoxicity has been demonstrated in glomerular mesangial cells and in renal epithelial cells in vitro. In vivo, the direct cellular toxicity of radiocontrast agents is compounded with alterations in blood flow and/or viscosity, ultimately resulting in renal medullary hypoxia, which is a hallmark feature of the complex clinical syndrome of radiocontrast nephropathy.

The radiocontrast/hypertonicity-induced DNA fragmentation of MDCK cells is attenuated by taurine but not by NAC. Because both agents are antioxidants, the antioxidant property is not sufficient for the observed cytoprotective effect. Hence, the antiapoptotic effect of taurine has to be attributed to other, yet to be defined mechanisms. Our results suggest that pharmacological doses of taurine may be particularly protective against RCIN.

The DNA fragmentation of MDCK cells induced by diatrizoate is related to its hypertonicity in this in vitro model of radiocontrast cytotoxicity. Nuclear disintegration with subsequent cell death may contribute to the pathophysiology of radiocontrast-induced nephropathy, particularly in the hypertonic/hypoxic environment of the renal medulla. The present results underscore the importance of avoiding hyperosmolal urine states in patients at high risk of radiocontrast-induced nephropathy.

Background: Longitudinal strain (LS) is a sensitive marker of systolic function. Recent findings suggest that both myocardial contractility and loading conditions determine LS. The aim of this study was to investigate whether LS reflects the connection of cardiac contractility to afterload (termed ventriculoarterial coupling [VAC]) rather than mere contractility in rat models of hemodynamic overload-induced heart failure (HF). Methods: Pressure overload-induced HF was evoked by transverse aortic constriction (TAC; n = 14). Volume overload-induced HF was established by an aortocaval fistula (ACF; n = 12). Age-matched sham-operated animals served as controls for TAC (n = 14) and ACF (n = 12), respectively. Pressure-volume analysis was carried out to compute contractility (slope of end-systolic pressure-volume relationship [ESPVR]), afterload (arterial elastance [E a ]), and VAC (E a /ESPVR). Preload was evaluated by meridional end-diastolic wall stress. Speckle-tracking echocardiography was performed to assess LS. Results: The TAC group presented with maintained ESPVR, increased E a , and enhanced meridional enddiastolic wall stress. In contrast, the ACF group was characterized by reduced ESPVR, decreased E a , and enhanced meridional end-diastolic wall stress. VAC increased in both HF groups. Furthermore, LS was also impaired in both HF models (À5.9 6 0.6% vs À12.9 6 0.5%, TAC vs Sham t [P < .001], and À11.7 6 0.7% vs À13.5 6 0.4%, ACF vs Sham a [P = .048]). Statistical analysis revealed that strain parameters were determined predominantly by afterload in the TAC group and by contractility in the ACF group, while preload had a minor effect. In the entire study population, LS showed a correlation with VAC (R = 0.654, P < .001) but not with ESPVR (R = 0.058, P = .668). Conclusions: Under pathophysiologic conditions when both contractility and afterload become altered, LS reflects VAC rather than mere contractility.