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1.
Cardiovasc Res ; 116(1): 158-170, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30873524

RESUMO

AIMS: Heart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism. METHODS AND RESULTS: In an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P < 0.05). While sublingual microcirculation was significantly compromised in CPR and E-CPR, CO delivery demonstrated a significant improvement in microvascular function (microvascular flow index: Sham 2.9 ± 0.1; CPR 2.2 ± 0.1; E-CPR 1.8 ± 0.1; CO-E-CPR 2.7 ± 0.1; P < 0.01). Histological and serological myocardial damage markers were significantly reduced (hsTroponin-T Sham 0.01 ± 0.001; CPR 1.9 ± 0.2; E-CPR 3.5 ± 1.2; CO-E-CPR 0.5 ± 0.2 ng/mL; P < 0.05). DAMP signalling was decreased ipse facto leading to influence of cardioprotective heat shock and cyclooxygenase response. CONCLUSIONS: CO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs.


Assuntos
Monóxido de Carbono/farmacologia , Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Parada Cardíaca/terapia , Hemodinâmica/efeitos dos fármacos , Mucosa Bucal/irrigação sanguínea , Miócitos Cardíacos/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Alarminas/metabolismo , Animais , Modelos Animais de Doenças , Parada Cardíaca/sangue , Parada Cardíaca/patologia , Parada Cardíaca/fisiopatologia , Microcirculação/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Recuperação de Função Fisiológica , Transdução de Sinais , Sus scrofa , Fatores de Tempo
2.
Am J Emerg Med ; 36(10): 1738-1744, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29395757

RESUMO

AIM: Standardized modeling of cardiac arrest and cardiopulmonary resuscitation (CPR) is crucial to evaluate new treatment options. Experimental porcine models are ideal, closely mimicking human-like physiology. However, anteroposterior chest diameter differs significantly, being larger in pigs and thus poses a challenge to achieve adequate perfusion pressures and consequently hemodynamics during CPR, which are commonly achieved during human resuscitation. The aim was to prove that standardized resuscitation is feasible and renders adequate hemodynamics and perfusion in pigs, using a specifically designed resuscitation board for a pneumatic chest compression device. METHODS AND RESULTS: A "porcine-fit" resuscitation board was designed for our experiments to optimally use a pneumatic compression device (LUCAS® II, Physio-Control Inc.), which is widely employed in emergency medicine and ideal in an experimental setting due to its high standardization. Asphyxial cardiac arrest was induced in 10 German hybrid landrace pigs and cardiopulmonary resuscitation was performed according to ERC/AHA 2015 guidelines with mechanical chest compressions. Hemodynamics were measured in the carotid and pulmonary artery. Furthermore, arterial blood gas was drawn to assess oxygenation and tissue perfusion. The custom-designed resuscitation board in combination with the LUCAS® device demonstrated highly sufficient performance regarding hemodynamics during CPR (mean arterial blood pressure, MAP 46 ±â€¯1 mmHg and mean pulmonary artery pressure, mPAP of 36 ±â€¯1 mmHg over the course of CPR). MAP returned to baseline values at 2 h after ROSC (80 ±â€¯4 mmHg), requiring moderate doses of vasopressors. Furthermore, stroke volume and contractility were analyzed using pulse contour analysis (106 ±â€¯3 ml and 1097 ±â€¯22 mmHg/s during CPR). Blood gas analysis revealed CPR-typical changes, normalizing in the due course. Thermodilution parameters did not show persistent intravascular volume shift. CONCLUSION: Standardized cardiopulmonary resuscitation is feasible in a porcine model, achieving adequate hemodynamics and consecutive tissue perfusion of consistent quality.


Assuntos
Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Animais , Pressão Arterial , Gasometria , Reanimação Cardiopulmonar/instrumentação , Modelos Animais de Doenças , Hemodinâmica/fisiologia , Humanos , Suínos
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