Experimental data indicate that stimulation of the nitric oxide-soluble guanylate cyclase(sGC)-cGMP-PKG pathway can increase left ventricular (LV) capacitance via phosphorylation of the myofilamental protein titin. We aimed to test whether acute pharmacological sGC stimulation with BAY 41-8543 would increase LV capacitance via titin phosphorylation in healthy and deoxycorticosteroneacetate (DOCA)-induced hypertensive pigs. Nine healthy Landrace pigs and 7 pigs with DOCA-induced hypertension and LV concentric hypertrophy were acutely instrumented to measure LV end-diastolic pressure-volume relationships (EDPVRs) at baseline and during intravenous infusion of BAY 41-8543 (1 and 3 μg·kg −1 ·min −1 for 30 min, respectively). Separately, in seven healthy and six DOCA pigs, transmural LV biopsies were harvested from the beating heart to measure titin phosphorylation during BAY 41-8543 infusion. LV EDPVRs before and during BAY 41-8543 infusion were superimposable in both healthy and DOCA-treated pigs, whereas mean aortic pressure decreased by 20–30 mmHg in both groups. Myocardial titin phosphorylation was unchanged in healthy pigs, but total and site-specific (Pro-Glu-Val-Lys and N2-Bus domains) titin phosphorylation was increased in DOCA-treated pigs. Bicoronary nitroglycerin infusion in healthy pigs ( n = 5) induced a rightward shift of the LV EDPVR, demonstrating the responsiveness of the pathway in this model. Acute systemic sGC stimulation with the sGC stimulator BAY 41-8543 did not recruit an LV preload reserve in both healthy and hypertrophied LV porcine myocardium, although it increased titin phosphorylation in the latter group. Thus, increased titin phosphorylation is not indicative of increased in vivo LV capacitance. NEW & NOTEWORTHY We demonstrate that acute pharmacological stimulation of soluble guanylate cyclase does not increase left ventricular compliance in normal and hypertrophied porcine hearts. Effects of long-term soluble guanylate cyclase stimulation with oral compounds in disease conditions associated with lowered myocardial cGMP levels, i.e., heart failure with preserved ejection fraction, remain to be investigated.
Infective endocarditis, particularly after implanting valve prostheses, poses significant surgical challenges, often requiring complex interventions. We describe a case of a 37-year-old male with Staphylococcus aureus endocarditis, unsuccessfully treated with mechanical valve prostheses. Continued infection led to the destruction of the intervalvular fibrous body, necessitating a Commando procedure involving radical debridement and replacement of both aortic and mitral valves with complex patch reconstruction. Prosthesis selection remains contentious, considering recurrence risk and long-term prognosis. Our case underscores timely intervention and meticulous technique in managing such complex situations. It highlights successful strategies for treating infective endocarditis with destruction of aortomitral continuity, emphasizing the pivotal role of the Commando procedure.
Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia in humans and is associated with an increased risk of stroke, morbidity and death. Arterial hypertension (HT) is found in 60–80% of AF patients, is an independent predictor of new-onset AF and contributes to AF progression via unknown mechanisms. We previously established a large animal model of rapid atrial pacing (RAP) induced atrial fibrillation combined with DOCA (desoxycorticosterone acetate) induced HT showing that HT increases AF stability. In this study, we aimed to investigate how arterial hypertension affects the progression of atrial fibrillation. Methods: 17 landrace pigs were implanted with custom made, telemetrically controllable pacemakers to induce AF. DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (RAP + DOCA), the other 8 animals served as controls (RAP). Pacemakers were activated at a rate of 600/min two weeks prior to the final experiment which included transthoracic echocardiography, basic hemodynamic measurements, left and right atrial invasive electrophysiologic studies (measurement of atrial effective refractory periods – AERP – at S1 cycle lengths 400, 350, 300, 250 and 200ms), 3D electroanatomic mapping, high density epicardial multielectrode array mapping as well as histological analysis. Results: Both groups had comparable body weight (RAP + DOCA: 46.3 ± 6.1 kg; RAP: 44.9 ± 4.5; n.s.), cardiac output (4.6 ± 0.8 vs. 4.6 ± 1.2, n.s.), pulmonary arterial pressure (21.6 (16;27) vs. 24.5 (21;26), n.s.), left ventricular end diastolic pressure (13.1 ± 5.4 vs. 11.6 ± 4.8; n.s.) and left atrial pressure (7.6 ± 2.6 vs. 9.6 ± 4.6; n.s.). Animals in the RAP + DOCA group had significant arterial hypertension (109.9 (100,137) vs. 82.8 (79,96) mmHg, p < 0.05), concentric left ventricular hypertrophy (unchanged end-diastolic volume; end diastolic diameter of the intraventricular septum: 17(15,18) vs. 11.5(10,13) mm, p < 0.01), atrial dilatation (77.9 ± 23.4 vs. 119.1 ± 31.3 cm2, p < 0.01) and increased left (33.5 ± 8.4 vs. 24.9 ± 5.6 g, p < 0.05) and right (23.7 ± 2.9 vs. 19.4 ± 3.1 g, p < 0.05) atrial weights. AF duration after pacemaker activation was significantly higher in RAP + DOCA animals, while left and right atrial effective refractory periods at every measured S1 cycle length were unaltered. Epicardial multielectrode mapping showed increased conduction velocities on both atrial free walls (p < 0.05). Enhanced conduction velocity during closed chest 3D electroanatomic mapping of the whole atria in DOCA + RAP animals could be confirmed for the left, but not for the right atrium. Interestingly, this increased AF stability was not associated with increased AF complexity in both atria: mean AF cycle length, waves per cycle length, number of epicardial breakthroughs and mean conduction velocity during atrial fibrillation were unaltered. HT was associated with severe structural remodelling. Histologic evaluation showed biatrial cardiomyocyte hypertrophy (cross-section cardiomyocyte area: LA: 243.7 ± 41.8 vs. 174.4 ± 36.0 µm2, p < 0.01, RA: 271.6 (232,326) vs. 186.8(169,202) µm2, p < 0.01) as well as interstitial fibrosis (LA: 14.0 ± 2.2 vs. 8.5 ± 1.6 %, p < 0.001; RA: 14.4 ± 3.4 vs. 8.3 ± 1.5 %, p < 0.001). Conclusion: In this model of secondary hypertension, higher AF stability after two weeks of rapid atrial pacing was associated with both structural and electrical remodelling. Arterial hypertension triggers hypertrophic and profibrotic pathways which contribute to AF progression early in the disease. This underlines the importance of strict blood pressure control in patients with arterial hypertension to prevent progression of the disease.
Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs ( n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls ( n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model.
Objectives: The hyperbaric oxygen therapy (HBO) can be used to increase the oxygen content in the blood and is therefore a useful treatment in several diseases such as: ischemia, wound healing problems, gas gangrene or air embolism. Successful treatment of HBO in ischemic insult is still controversial. The aim of this study was to evaluate patients with neurological deficits after cardiac surgeries, which were consequently treated with HBO.
Four hours after surgery for aortic valve stenosis and tricuspid valve regurgitation, an unknown foreign body was present on the routine chest X-ray. We performed re-sternotomy in order to retrieve this foreign body. The foreign body was easy to move on fluoroscopy but we could not extract it. We concluded that the foreign body was in a subdiaphragmatic location. As a consequence, we performed gastroscopy. A white, frothy mass (similar to an undissolved effervescent tablet) within an ulcerated lesion was seen and partially extracted.
