Einfluss von Dapagliflozin auf die pulmonale Hypertonie induziert durch pulmonal-venösen Rückstau
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Beschreibung
Left sided congestive heart failure (HF) is the most common type of HF and pulmonary hypertension (PH) due to left heart disease (PH-LHD). It represents the most prevalent form of PH. Venous congestion from the left atrium leads to an increase in pressure in the pulmonary vessels. This retrograde back pressure causes pathological changes, particularly in the small pulmonary vessels. In fact, PH has a significant impact on mortality. Therefore, research for successful therapy is highly relevant. However, there is no approved drug available for patients with group 2 PH.
In recent years, several SGLT-2 inhibitors have shown promise as a novel treatment option for HF but the effect on PH-LHD remains unexplored. For this aim, we utilized our recently developed rat PH-LHD model of pulmonary vein banding (PVB). In this model, the unilateral stenosis of the left pulmonary vein results in retrograde backflow into the lungs similar to patients with PH-LHD. In contrast to these patients, however, the left ventricular function remains unaffected rat PH-LHD model. This enables an investigation of the impact of the SGLT-2 inhibitor dapagliflozin on vascular remodeling independent of the effects on LV function. Wistar-Kyoto rats underwent either PVB or SHAM surgery. After 20 days post surgery, the animals were treated orally with either placebo or dapagliflozin for 4 weeks. A therapeutic effect was demonstrated using a variety of methods, including scoring, echocardiographic phenotyping, invasive haemodynamics and histological evaluations. Treatment with dapagliflozin led to a significant increase in water and food intake, while the progression of body weight was similar to placebo treated animals. Compared to placebo treated rats, dapagliflozin led to a significant reduction in vascular remodeling and mast cell density after PVB. As mast cells, are known to substantially influence pro-inflammatory processes, such a reduction signifies high clinical relevance. Furthermore, there was a notable reduction in right ventricular pressure during dobutamin induced sympathetic stimulation and right ventricular hypertrophy after PVB compared to placebo treated animals.
These data demonstrate that dapagliflozin has a positive effect on pulmonary vasculature in a model of PH-LHD.
Autor*in
Leonhard Anton Blumrich
Themen in »Einfluss von Dapagliflozin auf die pulmonale Hypertonie induziert durch pulmonal-venösen Rückstau«
Pulmonale Hypertonie (PH) PH bei Linksherzerkrankung (PH-LHD) Pulmonalvenenbanding (PVB-Modell) Dapagliflozin Vaskuläres Remodeling Rechtsventrikuläre Belastung / Hypertrophie