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.
- Klíčová slova
- animal model, atrial septostomy, cardiogenic shock, left ventricular unloading, venoarterial extracorporeal membrane oxygenation,
- 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
INTRODUCTION: Inherited thrombophilias represent a concerning risk factor due to a proclivity to an aberrant clot formation. However, in patients with left ventricular assist device (LVAD), their impact on bleeding and thrombotic complications remains still poorly understood. The aim of the present study was to evaluate the effect of thrombophilic mutation directed anticoagulation therapy on adverse clinical outcomes in LVAD patients. MATERIALS AND METHODS: About 138 consecutive patients indicated for LVAD implant (HeartMate II, Abbott, Plymouth, USA) were prospectively screened for three major thrombophilic mutations: factor II (prothrombin), factor V Leiden, and homozygous methylenetetrahydrofolate reductase (MTHFR). Subsequently, discordant individualized anticoagulation targets of INR 2.5-3.0 in thrombophilia positive and INR 1.8-2.2 in negative patients were established; notably without anti-platelet agents given the center standard of care. RESULTS: Mean age was 50 ± 12.7 years, 83% male. Mean duration of support was 464.5 days (SD 482.9; SEM 41.1) and median of 310 days (IQR 162; 546). Full thrombophilia positive cohort analysis has not revealed any significant impact on event free survival. In contrast, detailed analysis of specific thrombophilias subsets has revealed Factor II prothrombin mutation as a significant predisposition for the pump thrombosis risk (SHR 10.48; p = 0.001) despite more aggressive prespecified anticoagulation target. Moreover, the incidence of bleeding events in prothrombin group was also significantly increased (SHR 6.0; p = 0.03). CONCLUSIONS: Our observations suggest that specific thrombophilias in LVAD patients may pose different intensity predisposition for thrombotic complications. Factor II (prothrombin) positive mutation was identified as significant risk factor associated with the pump thrombosis.
- Klíčová slova
- Thrombophilias, hemocompatibility, individualized anticoagulation, pump thrombosis, ventricular assist device,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- podpůrné srdeční systémy * škodlivé účinky MeSH
- prospektivní studie MeSH
- protrombin MeSH
- trombofilie * diagnóza genetika MeSH
- trombóza * genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- protrombin MeSH
Extracorporeal life support (ECLS) is a treatment modality that provides prolonged blood circulation, gas exchange and can partially support or fully substitute functions of heart and lungs in patients with severe but potentially reversible cardiopulmonary failure refractory to conventional therapy. Due to high-volume bypass, the extracorporeal flow is interacting with native cardiac output. The pathophysiology of circulation and ECLS support reveals significant effects on arterial pressure waveforms, cardiac hemodynamics, and myocardial perfusion. Moreover, it is still subject of research, whether increasing stroke work caused by the extracorporeal flow is accompanied by adequate myocardial oxygen supply. The left ventricular (LV) pressure-volume mechanics are reflecting perfusion and loading conditions and these changes are dependent on the degree of the extracorporeal blood flow. By increasing the afterload, artificial circulation puts higher demands on heart work with increasing myocardial oxygen consumption. Further, this can lead to LV distention, pulmonary edema, and progression of heart failure. Multiple methods of LV decompression (atrial septostomy, active venting, intra-aortic balloon pump, pulsatility of flow) have been suggested to relieve LV overload but the main risk factors still remain unclear. In this context, it has been recommended to keep the rate of circulatory support as low as possible. Also, utilization of detailed hemodynamic monitoring has been suggested in order to avoid possible harm from excessive extracorporeal flow.
Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is a technique used in patients with severe heart failure. The aim of this study was to evaluate its effects on left ventricular afterload and fluid accumulation in lungs with electrical impedance tomography (EIT). In eight swine, incremental increases of extracorporeal blood flow (EBF) were applied before and after the induction of ischemic heart failure. Hemodynamic parameters were continuously recorded and computational analysis of EIT was used to determine lung fluid accumulation. With an increase in EBF from 1 to 4 l/min in acute heart failure the associated increase of arterial pressure (raised by 44%) was accompanied with significant decrease of electrical impedance of lung regions. Increasing EBF in healthy circulation did not cause lung impedance changes. Our findings indicate that in severe heart failure EIT may reflect fluid accumulation in lungs due to increasing EBF.
- MeSH
- elektrická impedance MeSH
- hemodynamika MeSH
- koronární cirkulace fyziologie MeSH
- mimotělní membránová oxygenace škodlivé účinky metody MeSH
- modely nemocí na zvířatech MeSH
- plíce patofyziologie MeSH
- prasata MeSH
- respirační insuficience etiologie patologie MeSH
- srdeční selhání metabolismus patologie terapie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Hypoxic-ischemic encephalopathy (HIE) is a neonatal condition that occurs as a consequence of perinatal asphyxia, which is caused by a number of factors, commonly via compression of the umbilical cord, placental abruption, severe meconium aspiration, congenital cardiac or pulmonary anomalies and birth trauma. Experimental studies have confirmed that male rat pups show a higher resistance to HIE treatment. Moreover, the long-term consequences of hypoxia in male are more severe in comparison to female rat pups. These sex differences can be attributed to the pathophysiology of hypoxia-ischemia, whereby studies are beginning to establish such gender-specific distinctions. The current and sole treatment for HIE is hypothermia, in which a reduction in temperature prevents long-term effects, such as cerebral palsy or seizures. However, in most cases hypothermia is not a sufficient treatment as indicated by a high mortality rate. In the present review, we discuss the gender differences within the pathophysiology of hypoxia-ischemia and delve into the role of gender in the incidence, progression and severity of the disease. Furthermore, this may result in the development of potential novel treatment approaches for targeting and preventing the long-term consequences of HIE.
- MeSH
- apoptóza MeSH
- asfyxie novorozenců komplikace MeSH
- lidé MeSH
- mozek metabolismus MeSH
- mozková hypoxie a ischemie etiologie metabolismus terapie MeSH
- novorozenec MeSH
- oxidační stres MeSH
- pohlavní dimorfismus * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The growth in the experimental research of facilities to support extracorporeal circulation requires the further development of models of acute heart failure that can be well controlled and reproduced. Two types of acute heart failure were examined in domestic pigs (Sus scrofa domestica): a hypoxic model (n=5) with continuous perfusion of the left coronary artery by hypoxic deoxygenated blood and ischemic model (n=9) with proximal closure of the left coronary artery and controlled hypoperfusion behind the closure. The aim was a severe, stable heart pump failure defined by hemodynamic parameters changes: a) decrease in cardiac output by at least 50 %; b) decrease in mixed venous blood saturation to under 60 %; c) left ventricular ejection fraction below 25 %; and d) decrease in flow via the carotid arteries at least 50 %. Acute heart failure developed in the first group in one animal with no acute mortality and in the second group in 8 animals with no acute mortality. In the case of ischemic model the cardiac output fell from 6.70+/-0.89 l/min to 2.89+/-0.75 l/min. The saturation of the mixed venous blood decreased from 83+/-2 % to 58+/-8 %. The left ventricular ejection fraction decreased from 50+/-8 % to 19+/-2 %. The flow via the carotid arteries decreased from 337+/-78 ml/min to 136+/-59 ml/min (P
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a method used for the treatment most severe cases of decompensated heart failure. The purpose of this study was to evaluate the risk of the formation of microembolisms during VA-ECMO-based therapy. Heart failure was induced with simultaneous detection of microembolisms and the measurement of blood flow rate in the common carotid artery (CCA) without VA-ECMO (0 l/min) and at the VA-ECMO blood flow rate of 1, 2, 3 and 4 l/min. If embolisms for VA-ECMO 0 l/min and the individual regimes for VA-ECMO 1, 2, 3, 4 l/min are compared, a higher VA-ECMO flow rate is accompanied by a higher number of microembolisms. The final microembolism value at 16 min was for the VA-ECMO flow rate of 0 l/min 0.0 (0, 1), VA-ECMO l/min 7.5 (4, 19), VA-ECMO 2 l/min 12.5 (4, 26), VA-ECMO 3 l/min, 21.0 (18, 57) and VA-ECMO 4 l/min, 27.5 (21, 64). Such a comparison is statistically significant if VA-ECMO 0 vs. 4 l/min p<0.0001, 0 vs. 3 l/min p<0.01 and 1 vs. 4 l/min p<0.01 are compared. The results confirm that high VA-ECMO flow rates pose a risk with regards to the formation of a significantly higher number of microemboli in the blood circulation and that an increase in blood flow rates in the CCA corresponds to changes in the VA-ECMO flow rates.
- MeSH
- akutní nemoc MeSH
- arteria carotis communis diagnostické zobrazování patofyziologie MeSH
- embolie diagnostické zobrazování patofyziologie MeSH
- mikrocirkulace fyziologie MeSH
- mimotělní membránová oxygenace škodlivé účinky trendy MeSH
- modely nemocí na zvířatech * MeSH
- prasata MeSH
- rychlost toku krve fyziologie MeSH
- srdeční selhání diagnostické zobrazování patofyziologie terapie MeSH
- ultrasonografie dopplerovská metody trendy MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Infant rats, together with their mother, were exposed to the simulated altitude of 7,000 m for 8 hours per day since birth to the age of 17 days. Animals were studied the 25th day, 8 days after the last exposure to hypoxia. The experimental and control animals were sacrificed the 25th day by the transaortic perfusion with 4% buffered neutral formaldehyde under ether anaesthesia. Brains were processed for classical neurohistological analysis (Nissl staining), Fluoro-Jade B and Hoechst. Cortical area in the AP plane 3 mm posterior to bregma was subjected to quantification and "laminar analysis" of the neurones count. The findings were as follows: a) The cytoarchitectonics of the brain in animals exposed to hypoxia was not severely damaged. b) The thickness of neocortex is in the experimental animals lower than that in the controls. c) The "laminar analysis" of neocortex showed a relative increase of neuronal density in layers I., II., V. and VI. of the cortex. d) The electrical stimulation of sensorimotor cortex 8 days after the end of hypoxia brought about prolongation of evoked cortical after discharges. These results demonstrate that the intermittent hypobaric hypoxia has a profound effect on morphological maturation of the central nervous system in infant rats. Hypoxia influenced the excitation-- inhibition mechanisms of cortical neurones.
To achieve a better understanding of learning and declarative memory under mild transient stress, we investigated the effect of brief hypobaric hypoxia on spatial orientation in rats. Young male Wistar rats aged 30 days were exposed for 60 min to hypobaric hypoxia, simulating an altitude of 7,000 m (23,000 ft) either shortly prior to attempting or after mastering an allothetic navigation task in the Morris water maze with a submerged platform. The post-hypoxic group performed significantly better in the navigation task than the control animals (the mean difference in escape latencies was 11 seconds; P=0.0033, two-way ANOVA with repeated measures, group x session). The experimental group also achieved a remarkably higher search efficiency (calculated as a percentage of successful trials per session), especially during the first four days following hypoxic stress (P=0.0018). During the subsequent training, the post-hypoxic group performed better than the control animals, whilst the efficiency levels of both groups progressively converged. Spatial memory retention and recall of well-trained rats were not affected by the transient hypobaric hypoxia. These results indicate that brief hypobaric hypoxia enhances rats' spatial orientation. Our findings are consistent with several studies, which also suggested that mild transient stress improves learning.
- MeSH
- bludiště - učení * MeSH
- fyziologická adaptace MeSH
- hypoxie komplikace patofyziologie MeSH
- krysa rodu Rattus MeSH
- orientace * MeSH
- potkani Wistar MeSH
- psychomotorický výkon * MeSH
- vnímání prostoru * MeSH
- výšková nemoc komplikace patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Some antidepressant drugs, especially tricyclic ones--(TCA), have cardiovascular side effects. To compare the effects of antidepressant drugs, the electrocardiogram (ECG), vectorcardiogram (VCG), and body surface maps (BSM) were recorded in psychiatric patients without cardiovascular diseases treated by a) TCA amitriptyline or dosulepin (daily dose 50-200 mg, 22 patients), b) lithium (serum level 0.66 +/- 0.08 meq/l, 21 patients), c) selective serotonine reuptake inhibitor citalopram (daily doses 20-60 mg, 30 patients), and in 23 control patients. In the TCA-treated patients, the heart rate was increased, QT and RR intervals shortened (p < 0.01, antimuscarinic effect). This was not observed in lithium- and citalopram-treated patients. All antidepressants decreased the absolute maximum values of depolarization isointegral maps, lithium and TCA reduced the initial and citalopram the later phase of depolarization. Citalopram slightly diminished the amplitude of the R wave. The results confirm the antimuscarinic effects of TCA in therapeutic doses and specify the intraventricular effects of antidepressants.
- MeSH
- amitriptylin škodlivé účinky MeSH
- antagonisté muskarinových receptorů MeSH
- antidepresiva tricyklická škodlivé účinky MeSH
- antidepresiva škodlivé účinky MeSH
- citalopram škodlivé účinky MeSH
- dospělí MeSH
- dothiepin škodlivé účinky MeSH
- duševní poruchy farmakoterapie MeSH
- elektrofyziologie MeSH
- elektrokardiografie MeSH
- kardiovaskulární nemoci chemicky indukované patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lithium škodlivé účinky MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- srdce účinky léků patofyziologie MeSH
- srdeční frekvence účinky léků MeSH
- tachykardie chemicky indukované MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amitriptylin MeSH
- antagonisté muskarinových receptorů MeSH
- antidepresiva tricyklická MeSH
- antidepresiva MeSH
- citalopram MeSH
- dothiepin MeSH
- lithium MeSH
- selektivní inhibitory zpětného vychytávání serotoninu MeSH
