Unloading
Dotaz
Zobrazit nápovědu
American journal of cardiology, ISSN 0002-9149 vol. 68, no. 14, November 1991
131D s. : tab., grafy ; 30 cm
- MeSH
- infarkt myokardu MeSH
- kardiovaskulární látky MeSH
- remodelace komor MeSH
- Publikační typ
- kongresy MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
- farmakoterapie
Impressively increasing availability of mechanical circulatory/cardiac support systems (MCSs) worldwide, together with the deepening of the knowledge of critical care medical practitioners, has inevitably led to the discussion about further improvements of intensive care associated to MCS. An appealing topic of the left ventricle (LV) overload related to VA ECMO support endangering myocardial recovery is being widely discussed within the scientific community. Unloading of LV leads to the reduction in LV end-diastolic pressure, reduction in pressure in the left atrium, and decrease in the LV thrombus formation risk. Consequently, better conditions for myocardial recovery, with comfortable filling pressures and a better oxygen delivery/demand ratio, are achieved. The combination of VA ECMO and Impella device, also called ECPELLA, seems to be a promising strategy that may bring the improvement of CS mortality rates. The series of presented trials and meta-analyses clearly showed the potential benefits of this strategy. However, the ongoing research has brought a series of new questions, such as whether Impella itself is the only appropriate unloading modality, or any other approach to unload LV would be beneficial in the same way. Benefits and potential risks of LV unloading and its timing are being discussed in this current review.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.
- MeSH
- atrofie patologie MeSH
- krysa rodu rattus MeSH
- myokard patologie MeSH
- pohlavní steroidní hormony MeSH
- srdce * MeSH
- srdeční komory patologie MeSH
- transplantace srdce * škodlivé účinky metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: The aim of this study was to quantify and understand the unloading effect of percutaneous balloon atrial septostomy (BAS) in acute cardiogenic shock (CS) treated with venoarterial (VA) extracorporeal membranous oxygenation (ECMO). BACKGROUND: In CS treated with VA ECMO, increased left ventricular (LV) afterload is observed that commonly interferes with myocardial recovery or even promotes further LV deterioration. Several techniques for LV unloading exist, but the optimal strategy and the actual extent of such procedures have not been fully disclosed. METHODS: In a porcine model (n = 11; weight 56 kg [53-58 kg]), CS was induced by coronary artery balloon occlusion (57 minutes [53-64 minutes]). Then, a step-up VA ECMO protocol (40-80 mL/kg/min) was run before and after percutaneous BAS was performed. LV pressure-volume loops and multiple hemoglobin saturation data were evaluated. The Wilcoxon rank sum test was used to assess individual variable differences. RESULTS: Immediately after BAS while on VA ECMO support, LV work decreased significantly: pressure-volume area, end-diastolic pressure, and stroke volume to ∼78% and end-systolic pressure to ∼86%, while superior vena cava and tissue oximetry did not change. During elevating VA ECMO support (40-80 mL/kg/min) with BAS vs without BAS, we observed 1) significantly less mechanical work increase (122% vs 172%); 2) no end-diastolic volume increase (100% vs 111%); and 3) a considerable increase in end-systolic pressure (134% vs 144%). CONCLUSIONS: In acute CS supported by VA ECMO, atrial septostomy is an effective LV unloading tool. LV pressure is a key component of LV work load, so whenever LV work reduction is a priority, arterial pressure should carefully be titrated low while maintaining organ perfusion.
- MeSH
- kardiogenní šok * diagnóza terapie MeSH
- lidé MeSH
- mimotělní membránová oxygenace * metody MeSH
- modely nemocí na zvířatech MeSH
- prasata MeSH
- vena cava superior MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The peripheral venoarterial extracorporeal life support (V-A ECLS) in cardiogenic shock (CS) may lead to LV overload. The transaortic suction device (Impella, ABIOMED Inc., Danvers, MA) was compared to the pulmonary artery (PA) drainage, for LV unloading efficacy during V-A ECLS in a porcine cardiogenic shock model. A dedicated CS model included 12 swine (21 ± 1.8-week-old and weighing 54.3 ± 4.6 kg) supported with V-A ECLS and randomized to Impella or PA-related LV drainage. LV unloading and end-organ perfusion were evaluated through the PA catheter and LV pressure/volume analysis. The LV end-diastolic volume sharply dropped with Impella (143.6 ± 67.4 vs 123 ± 75.7 mL) compared to a slight decrease in the PA cannula group (134.1 ± 39.9 vs 130.1 ± 34.7 mL), resulting in an overall stroke work and pressure-volume area reductions with both techniques. However, stroke work reduction was more significant in the Impella group (V-A ECLS 3998.8 ± 2027.6 vs V-A ECLS + Impella 1796.9 ± 1033.9 mm Hg × mL, P = 0.016), leading to a more consistent pressure-volume area reduction (Impella reduction 34.7% vs PA cannula reduction 9.7%) In terms of end organ perfusion, central and mixed O2 saturation improved with V-A ECLS, and subsequently, remaining unchanged with either Impella or PA cannula as unloading strategy (SVmO2: Impella 86.0 ± 5.8 vs 87.8 ± 5.8; PA cannula 82.5 ± 10.7 vs 82.5 ± 11.3 %). Transaortic suction and PA drainage provided effective LV unloading during V-A ECLS while maintaining adequate end-organ perfusion. Impella provides a greater LV unloading effect and reduces more effectively the total LV stroke work.
Cells use homology-dependent DNA repair to mend chromosome breaks and restore broken replication forks, thereby ensuring genome stability and cell survival. DNA break repair via homology-based mechanisms involves nuclease-dependent DNA end resection, which generates long tracts of single-stranded DNA required for checkpoint activation and loading of homologous recombination proteins Rad52/51/55/57. While recruitment of the homologous recombination machinery is well characterized, it is not known how its presence at repair loci is coordinated with downstream re-synthesis of resected DNA We show that Rad51 inhibits recruitment of proliferating cell nuclear antigen (PCNA), the platform for assembly of the DNA replication machinery, and that unloading of Rad51 by Srs2 helicase is required for efficient PCNA loading and restoration of resected DNA As a result, srs2Δ mutants are deficient in DNA repair correlating with extensive DNA processing, but this defect in srs2Δ mutants can be suppressed by inactivation of the resection nuclease Exo1. We propose a model in which during re-synthesis of resected DNA, the replication machinery must catch up with the preceding processing nucleases, in order to close the single-stranded gap and terminate further resection.
- MeSH
- biologické modely MeSH
- DNA metabolismus MeSH
- enzymy opravy DNA metabolismus MeSH
- homologní rekombinace * MeSH
- poškození DNA * MeSH
- proliferační antigen buněčného jádra metabolismus MeSH
- rekombinační oprava DNA * MeSH
- rekombinasy metabolismus MeSH
- Saccharomyces cerevisiae enzymologie genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Phosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced heart failure with reduced ejection fraction before heart transplant or left ventricular assist device implantation to decrease right ventricular (RV) afterload and mitigate the risk of right heart failure. Conflicting evidence exists regarding the impact of these drugs on RV contractility. The aim of this study was to explore the acute effects of PDE5i on ventricular-vascular coupling and load-independent RV contractility. METHODS: Twenty-two patients underwent right heart catheterization and gated equilibrium blood pool single photon emission computed tomography, before and after 20 mg intravenous sildenafil. Single photon emission computed tomography and right heart catheterization-derived data were used to calculate RV loading and contractility. RESULTS: PDE5i induced a decrease in the right atrial pressure (-43%), pulmonary artery (PA) mean pressure (-26%), and PA wedge pressure (PAWP; -23%), with favorable reductions in pulmonary vascular resistance (-41%) and PA elastance (-40%), and increased cardiac output (+13%) (all P < 0.01). The RV ejection fraction increased with sildenafil (+20%), with no change of RV contractility (P = 0.74), indicating that the improvement in the RV ejection fraction was related to enhanced RV-PA coupling (r = 0.59, P = 0.004) by a decrease in the ventricular load. RV diastolic compliance increased with sildenafil. The decrease in the PAWP correlated with RV end-diastolic volume decrease; no relationship was observed with the change in LV transmural pressure, suggesting decreased pericardial constraint. CONCLUSIONS: Acute PDE5i administration has profound RV afterload-reducing effects, improves the RVEF, decreases RV volumes, and decreases the PAWP, predominantly through relief of pericardial constraint, without effects on RV chamber contractility. These findings support further study of PDE5i in protection of RV function in advanced heart failure with reduced ejection fraction who are at risk of RV failure.
The main reason for the emergency implantation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is the restoration of adequate systemic perfusion, while protecting the failing heart and promoting myocardial recovery are equally important goals. Following initial haemodynamic stabilization and often the urgent revascularization of the culprit lesion, the clinical focus is then directed towards the most efficient strategy for cardioprotection. Frequent echocardiography measurements may help to estimate the degree of unwanted left ventricular (LV) overloading during VA-ECMO. Additionally, the estimation of high LV filling pressures by Doppler echocardiography or their (in-)direct measurement using a dedicated surgical left atrial pressure line and conventional pulmonary artery catheter in a wedge position or a pigtail catheter in the left ventricle can be performed. Mechanical overload of the left ventricle is the major adverse effect and an obvious mechanistic and prognostic challenge of contemporary ECMO care. Many efforts are under way to overcome this phenomenon by LV unloading, which was effectively achieved by the current combined approach using an axial decompression device, while novel technical developments and approaches are tested and urgently anticipated. The aim of this report is to introduce in depth pathophysiological background, current concepts, and future perspectives in LV unloading strategies.
- Publikační typ
- časopisecké články MeSH
The sliding clamp, PCNA, plays a central role in DNA replication and repair. In the moving replication fork, PCNA is present at the leading strand and at each of the Okazaki fragments that are formed on the lagging strand. PCNA enhances the processivity of the replicative polymerases and provides a landing platform for other proteins and enzymes. The loading of the clamp onto DNA is performed by the Replication Factor C (RFC) complex, whereas its unloading can be carried out by an RFC-like complex containing Elg1. Mutations in ELG1 lead to DNA damage sensitivity and genome instability. To characterize the role of Elg1 in maintaining genomic integrity, we used homology modeling to generate a number of site-specific mutations in ELG1 that exhibit different PCNA unloading capabilities. We show that the sensitivity to DNA damaging agents and hyper-recombination of these alleles correlate with their ability to unload PCNA from the chromatin. Our results indicate that retention of modified and unmodified PCNA on the chromatin causes genomic instability. We also show, using purified proteins, that the Elg1 complex inhibits DNA synthesis by unloading SUMOylated PCNA from the DNA. Additionally, we find that mutations in ELG1 suppress the sensitivity of rad5Δ mutants to DNA damage by allowing trans-lesion synthesis to take place. Taken together, the data indicate that the Elg1-RLC complex plays an important role in the maintenance of genomic stability by unloading PCNA from the chromatin.
- MeSH
- chromatin metabolismus MeSH
- DNA-helikasy genetika MeSH
- DNA biosyntéza MeSH
- methylmethansulfonát toxicita MeSH
- mutace MeSH
- nestabilita genomu * MeSH
- poškození DNA * MeSH
- proliferační antigen buněčného jádra metabolismus MeSH
- rekombinace genetická MeSH
- Saccharomyces cerevisiae - proteiny chemie genetika metabolismus MeSH
- strukturní homologie proteinů MeSH
- suprese genetická MeSH
- transportní proteiny chemie genetika metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
