Myokardinfarkt mit erhaltener Ejektionsfraktion – Beeinträchtigte Funktion des kardiorenalen Baroreflexes

1 Summary 1.1 Background and aims The number of patients with heart failure and renal insufficiency rises with older age. As a result, the burden on healthcare systems increases immensely, especially con-sidering the shifting global aging structures. The cardio-renal baroreflex plays an im-portant role in the regulation of the fluid balance and the development of hyperten-sion. The afferent nerve fibers from the cardio-renal baroreflex run along the vagus nerve, with which it regulates renal sympathetic nerve activity (RSNA). The task of the RSNA is the sodium and volume homeostasis in the human body. It has already been shown in previous studies that the regulation of RSNA by the cardio-renal reflex is reduced in experimental myocardial infarctions with reduced ejection fraction. In comparison, the present project investigated how a myocardial infarction with pre-served ejection fraction affects the cardiac afferents and the cardio-renal reflex. 1.2 Methods In an experiment, a myocardial infarction was induced in rats by tying off a coronary artery. After two weeks, a fluorescent dye was injected into the pericardium to cause retrograde migration of the dye. This allows the differentiation between cardiac neu-rons and other neurons. After another week, neurons were obtained from the nodose ganglion and a cell culture was set up. With the help of a laser, neurons with cardiac afferents were distinguished from other neurons. The ion channels of the neurons were stimulated by current injections using the patch-clamp technique and then the action potentials were measured. A comparison was made between tonic and phasic activity of the neurons. In addition, the renal sympathetic nerve activity was deter-mined in order to assess the influence on the cardio-renal baroreflex. Furthermore, the cardiac output was measured by echocardiography and the hearts and kidneys were histologically tested for fibrosis and inflammation markers. 1.3 Results For the experiments, 192 neurons from the nodose ganglion of the rats were exam-ined. The results showed that the neurons fired more (tonic) after a heart attack compared to the control group (infarction vs. control: 23.7 ± 2.86 vs. 15.5 ± 1.86 APs/600ms; mean ± SEM, t-test, p<0.05) (78.6% vs. 48.5%; Z-test, p<0.05). The control of the cardio-renal baroreflex passed to the RSNA and the overall RSNA was slightly increased. Increased synthesis of collagen I fibers was observed in the renal interstitium. 1.4 Conclusions The experiments showed that a myocardial infarction with a preserved ejection frac-tion (HFpEF) influenced the afferent path of the cardio-renal baroreflex through vari-ous steps. As a result, the regulation of the RSNA is disturbed and there are indica-tions of kidney fibrosis. It is important to understand the neurophysiological mecha-nisms responsible for the development of heart failure with preserved ejection frac-tion. This is the only way to develop suitable therapies that improve the prognosis. Currently there is no established prognostically relevant therapy and the number of the patients with HFpEF is increasing.