Left Ventricular-arterial Coupling In Septic Cardiomyopathy

Objective:(1). To investigate the left ventricular arterial coupling in clinical studies of septic cardiomyopathy and reasonable way to treatment of septic cardiomyopathy;(2). To study the left ventricular arterial coupling and cardiac injury by adjusting the different tissue perfusion pressure in established endotoxin shock model of septic cardiomyopathy;(3). The focus is on ECMO treatment of septic cardiomyopathy by the role of ventricular arterial coupling.Methods:(1). A review in December2012-2014in January46patients with sepsis-induced cardiomyopathy (SIC) in department of Critical Care Medicine were recorded at different time points before and after SIC. Parameters including stroke volume index (SVI), cardiac index (CI), Global end-diastolic volume index (GEDI), central venous pressure (CVP), heart rate (HR), mean arterial pressure (MAP), lactate (Lac), central venous oxygen saturation (ScvO2), central venous and arterial carbon dioxide partial pressure difference (Pcv-aCO2) and norepinephrine (NE), analysis of cardiac elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees), stroke work (SW), total mechanical work (PVA), cardiac work efficiency (SW/PVA), comparison parameters between various time points and parameters correlation analysis. In non-survial group and survival group analysis the ventricular-arterial coupling.(2). The second part of the study is animal endotoxin shock models. hybrid dogs were divided into four groups:control group, group C (n=6):using the same surgical procedure and saline injections at the same point in time with an equal volume of experimental drugs. According to norepinephrine dose, maintain perfusion pressure at different levels in another three groups, A group-based MAP group(n=6), B group-based MAP decreased by10%(n=6) and D-based MAP decreased by15%group (n=6), hemodynamic monitoring point at a different time, transesophageal echocardiography to measure left ventricular end-diastolic volume EDV and left ventricular end-systolic volume ESV, evaluation of ventricular-arterial coupling and liver, kidney function and blood lactate levels, myocardial histopathological examination in end of the experiment.(3). After the establishment of the canine model of endotoxin shock with SIC, ECMO support is implemented by adjusting the flow including the low flow (0.1-1L), the moderate flow(1.1-2L) and high flow (2.1-3L)and recording hemodynamic parameters: heart rate HR, stroke volume SV, continuous cardiac output CCO, femoral artery systolic blood pressure SBP, cardiac Stroke volumeSW, total mechanical workPVA, work efficiencySW/PVA, and arterial elastance Ea, heart elastance Ees, left ventricular arterial coupling Ea/Ees, ejection fraction EF, left ventricular end-systolic volume ESV, left ventricular end-diastolic volume EDV, pulmonary artery wedge pressure PAOP and mixed venous oxygen saturation SvO2, lactate Lac, analyzes changes in SW and efficiency SW/PVA and evaluates left ventricular arterial coupling and its influence on cardiac function and tissue perfusion.The result:(1). Survival groups1. Ea/Ees affects external stroke work, work efficiency, stroke volume and is related to tissue perfusion.2. Before SIC24h and after SIC12h, the SVRI in a positive correlation with Ea; After SIC24h, there is an increase in arterial compliance;3. If12h Ees decreases by10.3%, MAP85mmHg is better than95mmHg;4. During SIC Ea, Ea/Ees increases, Ees decreases, Ea is related to SVRI;5.After SIC6h, Ees decreases to the lowest; after the SIC12h, Ees starts increasing;6. After SIC24h, Ea and Ea/Ees significantly reduces, after48hours Ees significantly increases; Death Group:After SIC30h, Ea sustains reducing, Ees is lower, and Ea/Ees is not improved;(2). Shock occurs with myocardial depression at LPS1h and8h after intravenous injection of endotoxin, cardiac function is presented with a "double-Valley phenomenon"; After resuscitation within endotoxin shock, hemodynamic characteristics is in line with the high CCO and low resistance, poor tissue perfusion, organ dysfunction; White blood cell count firstly increases and then decreases during endotoxin shock; AT "First Valley" myocardium is sensitive to dobutamine,2.5ug/kg.min can lower Ea/Ees, improve heart function, with dobu dose increases, Ea/Ees lower; Dobu at different doses, A, B, D each group Ea/Ees is no significant difference; At"second valley" dobu increase Ea/Ees with the dose increased and deterioration of heart function. There is not significant difference about Ea/Ees between the A, B groups; By maintaining MAP within different target, SVR is lower in D group than that in group A group (P<0.05), SVR was no difference between A and B groups (P>0.05); Within one hour after LPS injectied in endotoxin shock with SIC, Ea is lower and restores after resuscitation. Ea increases in A group than in group D; After LPS8h, Ea increases in B group compared with group D, in other time point, Ea is not significantly different;1hour after LPS injection A, B, D three groups Ees is significantly lower, in the LPS3-7h A group B Ees significantly is higher than that in group D, Ees higher in A group than in group B. But when at LPS8h, Ees is lower in A and B group than that in group D; After one hour injection of endotoxin shock with SIC, Ea/Ees increases significantly, after two hours the Ea/Ees significantly decreases; During3-7h in A, B, D groups Ea/Ees was lower than group C. In group A Ea/Ees is lowest but systolic function is strongest; After8h A, B group Ea/Ees increases significantly, SIC occurs again, while not in group D; At3-7h, A group SW highest, in group A and B SW is no significant difference, In8h A, B group SW decreases significantly while the D group SW dose not significantly decreases; Cardiac work efficiency is highest in A group of animals after LPS injection in LPS3-7h. In group A and B LPS8h animals cardiac work efficiency decreases, and work efficiency dose not decrease in group D; After endotoxin shock cardiac enzymes significantly increase, damage over time gradually increases; After LPS4h cardiac enzymes are significantly lower in group D than in group A; Among three groups, after LPS injection4,6hour, lactate dose not significantly increase, no significant difference between the groups, but8hours later group A, B lactate is significantly higher compared with group D; cardiac pathology general observation indicates cardiac papillary muscle bleeding and edema in group B, D than that in group C, A group papillary muscle with more bleeding and edema; Compared with the control group, in sepsis induced cardiomyopathy, myocardial fibers edema, group-based MAP and MAP decreased by10%of myocardial fibers were arranged apparently disorder, and even breakage, by contrast, group D myocardial fibers arranged in neat.(3).1. Cardiac suppression occored at one hour and8th hour after injection of endotoxin, at9th hour with the support of the peripheral VA-ECMO;2.ECMO flow0.1L to0.6L with elevated SBP (P<0.01), SW increased, while the0.7L SV and SBP decreased significantly, SW decreased. Later, no significant changes with the SBP, SW changed with SV changes, when2L SW significantly lower (P=0.039); Flow from the2.1L to2.2L when SBP decreased, SV decreased significantly (P=0.013), SW decreased significantly (P<0.01); later in2.3L, with SV increased, SW increased;3. Flow increased by a0.1L to0.4L, PVA reduced, SW/PVA increased (P<0.001); PVA increase in SBP increased when flow0.5L, SW/PVA reduced. Flow increased from1.1L to1.4L SBP did not decrease significantly, after that, PVA decreased more significantly, SW/PVA increased; Flow2.2L, ESV reduced, SW/PVA increased slightly, PVA has not increased in the flow2.5L, SW continually increase, SW/PVA increased, reaching74%(P=0.0021);4. When the flow was increased from0.1L to1L, SV no significant decline, while the SBP rise, Ea increased (P<0.01), while Ees increased and then decreased, flow increased from1.1L to2.0L, SBP no significant decline, SV decline, Ea increased (P=0.0101); flow increased from1.1L to1.4L when the ESV decreased, Ees increased, Ea/Ees falled, when the flow2.2L SV decreased significantly Ea increased (P<0.01), when flow2.3L, SV increased, Ea began to decline, ESV decreased, Ees increased, Ea/Ees1.45. Later SV increased, Ea decreased until3.0L; when in2.5L Ees increased (P<0.01), Ea/Ees decreased to0.69;5. Correlation analysis showed that SBP and ESV had positive correlation, r2=0.2790, P=0.0027; SBP and Ea/Ees positive correlation, r2=0.4687, P<0.0001;6. ECMO flow0.1L to0.4L, EF increased (P<0.001), after that SBP increased, ESV increased, EF decreased; ESV decreased in the medium and high flow, EF increased; When flow2.5L, with the Ea/Ees lower, EF increased to69%, there was fluild responsiveness;7.ECMO flow0.1L3.0L lactate levels decreased significantly (P=0.0347).8. After flowECMO/CCO between1.66-1.97(the best ECMO flow), ESV<SV, ventricular-arterial coupling was achieved in the best condition, by reducing ECMO flow increases cardiac work to achieve the reasonable match of the heart and EMCO function. Conclusion:1.(1). The genesis and development of SIC has close ties with left ventricular arterial coupling, heart and arterial elastance affect SIC happening and fate. The former is the foundation, latter is the precipitating factor;(2) Basic goals of treatment of septic cardiomyopathy is to keep ventricular-arterial couple. The short-term aim is to reduce arterial elastance, long-term strategy is to improve cardiac elastance;(3). Ea early falls when the SIC recovery, consistent with ventricular-arterial coupling improvement, Ees recovery delay;(4) Before and after SIC a low peripheral vascular resistance within36h can reduce arterial elastance Ea;(5) Ventricular artery coupling affects cardiac external work, work efficiency and stroke volume and associates with tissue perfusion.2.(1).That sepsis induced cardiomyopathy has different response to dobutamine suggesting a different pathogenesis of myocardial depression;(2). Sepsis induced cardiomyopathy occurs with ventricular-arterial coupling mismatched;(3). According optimal ventricular-arterial coupling, maintaining a low tissue perfusion pressure may retain cardiac work reserve and reduce the incidence of sepsis-induced cardiomyopathy;(4). Optimal ventricular arterial coupling helps reduce the incidence of septic induced cardiomyopathy.3.(1). The flow adjustment of EMCO can improve left ventricular arterial coupling and heart function;(2).While implementing VA-EMCO, the flow adjustment should be based on ventricular-arterial coupling, the best match can be achieved between the ECMO and heart function.