Thoracic epidural anesthesia impairs the hemodynamic response to acute pulmonary hypertension by deteriorating right ventricular-pulmonary arterial coupling

OBJECTIVE: Thoracic epidural anesthesia is increasingly used in critically ill patients. This analgesic technique was shown to decrease left ventricular contractility, but effects on right ventricular function have not been reported. A deterioration of right ventricular performance may be clinically relevant for patients with acute pulmonary hypertension, in which right ventricular function is an important determinant of outcome. In the present study, we tested the hypothesis that thoracic epidural anesthesia decreases right ventricular contractility and limits its capacity to tolerate pulmonary hypertension. DESIGN: Prospective, placebo-controlled study using an established model of acute pulmonary hypertension. SETTING: University hospital laboratory. SUBJECTS: A total of 14 pigs (mean weight, 35 +/- 2 kg). INTERVENTIONS: After instrumentation with an epidural catheter, biventricular conductance catheters, a pulmonary flow probe, and a high-fidelity pulmonary pressure catheter, seven pigs received thoracic epidural anesthesia and seven pigs served as control. Hemodynamic measurements were performed in baseline conditions and after induction of pulmonary hypertension via hypoxic pulmonary vasoconstriction (Fio2 of 0.15). MEASUREMENTS AND MAIN RESULTS: Ventricular contractility was assessed using load- and heart rate-independent variables. Right ventricular afterload was characterized with instantaneous pressure-flow measurements. In baseline conditions, thoracic epidural anesthesia decreased left but not right ventricular contractility. In untreated animals, pulmonary hypertension was associated with an increase in right ventricular contractility and cardiac output. Pretreatment with thoracic epidural anesthesia completely abolished the positive inotropic response to acute pulmonary hypertension. As a result, ventriculo-vascular coupling between the right ventricle and pulmonary-arterial system deteriorated, and cardiac output was significantly lower in animals with thoracic epidural anesthesia than in untreated controls during hypoxia-induced pulmonary hypertension. CONCLUSIONS: Thoracic epidural anesthesia inhibits the native positive inotropic response of the right ventricle to increased afterload and deteriorates the hemodynamic effects of acute pulmonary hypertension.     

The right ventricle: interaction with the pulmonary circulation

The primary role of the right ventricle (RV) is to deliver all the blood it receives per beat into the pulmonary circulation without causing right atrial pressure to rise. To the extent that it also does not impede left ventricular (LV) filling, cardiac output responsiveness to increased metabolic demand is optimized. Since cardiac output is a function of metabolic demand of the body, during stress and exercise states the flow to the RV can vary widely. Also, instantaneous venous return varies widely for a constant cardiac output as ventilatory efforts alter the dynamic pressure gradient for venous return. Normally, blood flow varies with minimal changes in pulmonary arterial pressure. Similarly, RV filling normally occurs with minimal increases in right atrial pressure. When pulmonary vascular reserve is compromised RV ejection may also be compromised, increasing right atrial pressure and limiting maximal cardiac output. Acute increases in RV outflow resistance, as may occur with acute pulmonary embolism, will cause acute RV dilation and, by ventricular interdependence, markedly decreased LV diastolic compliance, rapidly spiraling to acute cardiogenic shock and death. Treatments include reversing the causes of pulmonary hypertension and sustaining mean arterial pressure higher than pulmonary artery pressure to maximal RV coronary blood flow. Chronic pulmonary hypertension induces progressive RV hypertrophy to match RV contractility to the increased pulmonary arterial elastance. Once fully developed, RV hypertrophy is associated with a sustained increase in right atrial pressure, impaired LV filling, and decreased exercise tolerance. Treatment focuses on pharmacologic therapies to selectively reduce pulmonary vasomotor tone and diuretics to minimize excessive RV dilation. Owning to the irreversible nature of most forms of pulmonary hypertension, when the pulmonary arterial elastance greatly exceeds the adaptive increase in RV systolic elastance, due to RV dilation, progressive pulmonary vascular obliteration, or both, end stage cor pulmonale ensues. If associated with cardiogenic shock, it can effectively be treated only by artificial ventricular support or lung transplantation. Knowing how the RV adapts to these stresses, its sign posts, and treatment options will greatly improve the bedside clinician’s ability to diagnose and treat RV dysfunction.     

Treatment of low cardiac output complicating acute pulmonary hypertension in normovolemic goats

In eight anesthetized ventilated goats, the hemodynamic effect of isoproterenol (ISU), dopamine (DOP), norepinephrine (NE), nitroglycerin (NTG), and Ringer's lactate (RL) infusion was evaluated after inducing acute pulmonary hypertension (PHN) to decrease cardiac output. Therapy with ISU significantly (p less than .05) increased cardiac output, but also increased transmural right ventricular end-diastolic pressure (RVEDPTM) and heart rate (HR) and decreased stroke volume (SV) and right ventricular ejection fraction (RVEF). NE increased cardiac output, mean arterial pressure (MAP), systemic vascular resistance (SVR), and RVEF. DOP decreased pulmonary vascular resistance (PVR) and increased cardiac output, MAP, and RVEF, but also significantly increased HR. NTG increased cardiac output and RVEF while decreasing SVR and PVR. Intravascular volume expansion by RL infusion increased cardiac output, SV, and RVEDPTM and decreased HR and PVR. The results of this study indicate that volume loading may be the treatment of choice to restore cardiac output in the face of acute PHN. NE and NTG may be effective as an adjunct therapy. Although ISU and DOP increase cardiac output, the concomitant elevation in HR is undesirable.     

Effects of levosimendan on acute pulmonary embolism-induced right ventricular failure

OBJECTIVE: Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Fourteen anesthetized piglets. INTERVENTIONS: Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 microg/kg was administered in 10 mins followed by 0.2 microg/kg/min or same volumes of isotonic saline. MEASUREMENTS AND MAIN RESULTS: Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 +/- 0.17 to 5.58 +/- 0.37 mm Hg/mL, decreased Ees from 1.75 +/- 0.12 to 1.29 +/- 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 +/- 0.20 to 0.24 +/- 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload. CONCLUSIONS: A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.     

血管加压素对心肺转流术后血管麻痹综合征患者血流动力学的影响

目的评价血管加压素对心肺转流术(CPB)后血管麻痹综合征患者血流动力学的影响。方法选取CPB下心脏手术后发生血管麻痹综合征患者14例,分为去甲肾上腺素(NE)组(NE组)和血管加压素(AVP)组(AVP组)。NE组患者输注NE维持平均动脉血压>65 mmHg,当NE输注速率>0.4μg/(kg.min)则加用AVP 0.01～0.04 U/min;AVP组患者输注AVP0.01～0.04 U/min,必要时使用NE维持患者平均动脉血压>65 mmHg。于血管麻痹综合征诊断时(T1,基础值)、注药后24 h(T2)、48 h(T3)、72 h(T4)分别记录两组患者心率(HR)、平均动脉压(MAP)、平均肺动脉压(MPAP)、心排血量(CO)、肺毛细血管楔压(PCWP)、中心静脉压(CVP)及尿量,计算体循环血管阻力(SVR)及肺循环血管阻力(PVR)。并记录儿茶酚胺药物使用量及不良反应。结果两组患者年龄、体重、性别构成比,术前EF、术前治疗用药情况、CPB时间、主动脉阻断时间比较差异无统计学意义(P>0.05)。两组患者血压维持稳定。与NE组比较,AVP组SVR T2时增加;HR T2～3时显著降低(P<0.05);NE需要量T2～4明显降低(P<0.05);尿量明显增加(P<0.05)。结论 AVP可以改善CPB术后血管麻痹综合征患者的血流动力学。     

Ventricular interaction: from bench to bedside

Decreased right ventricle (RV) output results in decreased left ventricle end-diastolic volume (LVEDV) and output by series interaction. Direct ventricular interaction may also have a major effect on LV function. Thus, decreased LVEDV caused by reduced RV output may be further reduced by a leftward septal shift and pericardial constraint. This has been shown to be true in acute and chronic pulmonary hypertension and is now also apparent in severe congestive heart failure. The use of intracavitary LV end-diastolic pressure (LVEDP) to assess LVEDV is inappropriate if pressure surrounding the LV is increased: the surrounding pressure should be subtracted from LVEDP to calculate the effective distending (transmural) pressure which governs preload. If the surrounding pressure increases more than LVEDP, transmural LVEDP and LVEDV will decrease despite the increased LVEDP. Thus, the use of filling pressure to reflect changes in LVEDV has led to erroneous conclusions regarding changes in myocardial compliance and contractility. It is now clear that volume loading may reduce LVEDV and stroke work in pulmonary embolism, chronic lung disease and severe congestive heart failure despite increased LVEDP. The decreased stroke work is a result of reduced LV preload, not decreased contractility as would be suggested if filling pressure is used to reflect preload.     

Heterogeneity of the vasoconstrictor effect of vasopressin in septic shock

OBJECTIVE: To determine whether pressor doses of vasopressin impair organ blood flow in endotoxic shock. DESIGN: Graded doses of vasopressin or phenylephrine, starting at the clinically recommended doses for pressure support in septic shock, were intravenously infused during endotoxic shock. SETTING: University hospital surgical research laboratory. SUBJECTS: Twelve random-bred female Yorkshire pigs. INTERVENTIONS: We measured mean arterial pressure, cardiac output, heart rate, pulmonary artery occlusion pressure, and carotid, mesenteric, renal, and iliac blood flows. MEASUREMENTS AND MAIN RESULTS: Low doses of vasopressin (typically used in the clinical management of septic shock) raised arterial pressure by increasing systemic vascular resistance without a significant preferential effect in the circulations measured. However, moderately greater doses of vasopressin had a very heterogeneous vasoconstrictor action; although there was no significant vasoconstriction in the carotid and iliac circulations, mesenteric and renal blood flows decreased markedly. Furthermore, at pressor doses vasopressin improved cerebral perfusion. CONCLUSIONS: The vasoconstrictor action of exogenous low-dose vasopressin in endotoxic shock does not impair blood flow to any of the vascular beds examined. However, moderately higher doses of vasopressin may induce ischemia in the mesenteric and renal circulations. The data indicate that the safe dose range for exogenous vasopressin in septic shock is narrow and support the current practice of fixed low-dose administration, generally 0.04 units/min and in no case exceeding 0.1 units/min.     

Effect of incremental positive end-expiratory pressure ventilation on right ventricular function in anesthetized pigs: A thermodilution study

The effects of positive end-expiratory pressure (PEEP) ventilation on right ventricular preload, after-load, and contractility under physiologic circumstances are controversial. We studied hemodynamics and right ventricular volumes (thermodilution) in 12 anesthetized pigs in which PEEP was increased by steps of 5 cm H₂O at 15 minute intervals (0 to 20 cm H₂O). At 20 cm H²O PEEP, cardiac output decreased by 2.0 ± 0.7 (mean ± SD) L/min, and mean arterial blood pressure by 50 ± 14 mm Hg. Heart rate increased by 39 ± 24 b/min. At 20 cm H₂O PEEP, right ventricular stroke volume fell by 25 ± 7 mL, end-diastolic volume by 50 ± 21 mL, end-systolic volume by 25 ± 17 mL, and ejection fraction by 17% ±0 10% (all p <.005). For mean values during PEEP, end-diastolic volume linearly and inversely related to central venous pressure. Stroke volume, ejection fraction, and end-systolic volume linearly and positively related to end-diastolic volume; relations did not differ from those without PEEP. Transmural mean pulmonary artery pressure linearly and positively related to cardiac output. Transmural systolic pulmonary artery pressure and central venous pressure linearly and positively related to endsystolic and end-diastolic volumes, respectively. We conclude that, during incremental PEEP ventilation up to 20 cm H₂O in anesthetized pigs with an intact baroreceptor reflex, a rise in intrathoracic pressure induces a linear fall in right ventricular preload and stroke volume at an unaltered pump function. Right ventricular ejection fraction and afterload diminish as a normal response to decreased preload. There are no effects on pulmonary vascular resistance, and right ventricular compliance and contractility, in spite of coronary hypotension and tachycardia.     

Right ventricular dysfunction in patients with septic shock

Using a rapid computerized thermodilution method, we examined the evolution of right ventricular performance in 23 patients with septic shock. Nine survived the episode of septic shock. The other 14 patients died of refractory circulatory shock. Significant right ventricular systolic dysfunction, defined as decreased ejection fraction (-39%) and right ventricular dilation (+38%) was observed in all patients with septic shock. However, in the survivors, increased right ventricular preload may prevent hemodynamic evidence of right ventricular pump failure by utilizing the Frank-Starling mechanism to maintain stroke volume. Conversely, in the nonsurvivors, right ventricular dysfunction was more prononced two days after the onset of septic shock, leading to a fall in stroke. In the last patients, a decrease in contractility appears to be the major factor accounting for decreased right ventricular performance, as evidenced by the marked increase in end-systolic volume (+27%) without significant change in pulmonary artery pressure, during the later stage of septic shock. The observed right ventricular pump failure then appears associated with an alteration in diastolic mechanical properties of this ventricle, as suggested by a leftward displacement of the individual pressure-volume curves.     

Management strategies for patients with pulmonary hypertension in the intensive care unit

OBJECTIVE: Pulmonary hypertension may be encountered in the intensive care unit in patients with critical illnesses such as acute respiratory distress syndrome, left ventricular dysfunction, and pulmonary embolism, as well as after cardiothoracic surgery. Pulmonary hypertension also may be encountered in patients with preexisting pulmonary vascular, lung, liver, or cardiac diseases. The intensive care unit management of patients can prove extremely challenging, particularly when they become hemodynamically unstable. The objective of this review is to discuss the pathogenesis and physiology of pulmonary hypertension and the utility of various diagnostic tools, and to provide recommendations regarding the use of vasopressors and pulmonary vasodilators in intensive care. DATA SOURCES AND EXTRACTION: We undertook a comprehensive review of the literature regarding the management of pulmonary hypertension in the setting of critical illness. We performed a MEDLINE search of articles published from January 1970 to March 2007. Medical subject headings and keywords searched and cross-referenced with each other were: pulmonary hypertension, vasopressor agents, therapeutics, critical illness, intensive care, right ventricular failure, mitral stenosis, prostacyclin, nitric oxide, sildenafil, dopamine, dobutamine, phenylephrine, isoproterenol, and vasopressin. Both human and animal studies related to pulmonary hypertension were reviewed. CONCLUSIONS: Pulmonary hypertension presents a particular challenge in critically ill patients, because typical therapies such as volume resuscitation and mechanical ventilation may worsen hemodynamics in patients with pulmonary hypertension and right ventricular failure. Patients with decompensated pulmonary hypertension, including those with pulmonary hypertension associated with cardiothoracic surgery, require therapy for right ventricular failure. Very few human studies have addressed the use of vasopressors and pulmonary vasodilators in these patients, but the use of dobutamine, milrinone, inhaled nitric oxide, and intravenous prostacyclin have the greatest support in the literature. Treatment of pulmonary hypertension resulting from critical illness or chronic lung diseases should address the primary cause of hemodynamic deterioration, and pulmonary vasodilators usually are not necessary.     

Right ventricular performance in patients with acute respiratory failure

To examine the right ventricular response to acute respiratory failure, serial studies of biventricular performance were analysed in 34 such patients, specifically detailing the role of associated underlying disease. During the initial study, the 34 patients with acute respiratory failure had a higher right ventricular end-diastolic volume than the control group (+21%), associated with a decrease in right ventricular ejection fraction, abnormalities which tended to return to normal values in the 15 survivors. In the 9 patients who died of refractory hypoxemia with severe pulmonary hypertension, the right ventricular dilation allowed to maintain stroke volume. In contrast, in 8 patients who died of septic shock, biventricular function was progressively altered (right and left ventricular ejection fraction= -37% and -35%). In 4 patients who died of cardiogenic shock (viral myocarditis), the cardiac function was the lowest (right and left ventricular ejection fraction= -59% and -60%). Only patients with acute respiratory failure associated with septic shock or viral myocarditis are unable to maintain their stroke volume.     

Arginine vasopressin in 316 patients with advanced vasodilatory shock

OBJECTIVE: To assess the effects of arginine vasopressin (AVP) on hemodynamic, clinical, and laboratory variables and to determine its adverse side effects in advanced vasodilatory shock. DESIGN: Retrospective study. PATIENTS: A total of 316 patients. INTERVENTIONS: AVP infusion (4 units/hr). MEASUREMENTS AND MAIN RESULTS: Cardiocirculatory, laboratory, and clinical variables were evaluated before, 0.5, 1, 4, 12, 24, 48, and 72 hrs after administration of AVP. AVP increased mean arterial pressure, systemic vascular resistance, and stroke volume index. Heart rate, central venous pressure, mean pulmonary arterial pressure, norepinephrine, milrinone, and epinephrine requirements decreased. There was no difference in the hemodynamic response between patients with septic shock, postcardiotomy shock, or systemic inflammatory response syndrome. Cardiac index decreased in 41.1% of patients during AVP treatment. In patients with hyperdynamic circulation before AVP, cardiac index decreased, whereas it remained uncharged or tended to increase in patients with normodynamic or hypodynamic circulation. During the course of AVP treatment, liver enzymes (28.5% of patients) and total bilirubin concentrations (69.3% of patients) increased, whereas platelet count decreased (73.4% of patients). Simultaneous hemofiltration significantly contributed to the decrease in platelet count (p < .001) and increase in bilirubin (p < .001). Whereas patients with an increase in bilirubin were more likely to die, a decrease in cardiac index or platelet count and an increase in liver enzymes did not affect mortality. Systemic inflammatory response syndrome as admission diagnosis, a high degree of multiple organ dysfunction, and norepinephrine requirements of >0.5 microg x kg x min before AVP treatment were independent risk factors for death from advanced vasodilatory shock treated with AVP. If norepinephrine dosages exceeded 0.6 microg x kg x min before AVP treatment, a substantial increase in mortality occurred. CONCLUSIONS: Supplementary AVP infusion improved cardiocirculatory function in advanced vasodilatory shock, but an increase in liver enzymes and bilirubin, and a decrease in platelet count occurred during AVP therapy, particularly during simultaneous hemofiltration. Initiation of AVP infusion before norepinephrine requirements exceeding 0.6 microg x kg x min may improve outcome.     

Metaraminol and dobutamine for the treatment of hypotension associated with epidural block

In 14 patients undergoing major abdominal surgery, epidural analgesia was performed and cardiovascular changes were examined by insertion of Swan-Ganz catheters. To counteract the hypotensive episodes associated with epidural block, Dobutamine (1-3 micrograms/kg body wt min-1) and Metaraminol (0.5-1.5 micrograms/kg body wt min-1) in various doses were infused and the effects of these vasoactive agents were examined. Epidural analgesia decreased arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure and central venous pressure associated with marked decrease in cardiac index, stroke volume index, left ventricular and right ventricular stroke work without changes in systematic vascular resistance, pulmonary vascular resistance or heart rate. The infusion of Metaraminol caused a marked increase in arterial pressure, pulmonary arterial pressure, wedge pressure and central venous pressure. Calculated variables of stroke volume, systemic vascular resistance, left and right stroke work and cardiac work increased significantly. The infusion of Dobutamine caused a marked increase in arterial and pulmonary arterial pressure, wedge pressure, central venous pressure and cardiac index associated with those calculated changes of left and right stroke work and cardiac work, which were increased markedly. On the other hand, heart rate, stroke volume and pulmonary vascular resistance did not show any remarkable changes. Our study indicates that the fall in arterial blood pressure associated with epidural block may be due to marked decrease in cardiac output, and the infusion of Dobutamine is one of the desirable methods to counteract the hypotensive episode.     

Vasopressin and ischaemic heart disease: more than coronary vasoconstriction?

During advanced vasodilatory shock, arginine vasopressin (AVP) is increasingly used to restore blood pressure and thus to reduce catecholamine requirements. The AVP-related rise in mean arterial pressure is due to systemic vasoconstriction, which, depending on the infusion rate, may also reduce coronary blood flow despite an increased coronary perfusion pressure. In a murine model of myocardial ischaemia, Indrambarya and colleagues now report that a 3-day infusion of AVP decreased the left ventricular ejection fraction, ultimately resulting in increased mortality, and thus compared unfavourably with a standard treatment using dobutamine. The AVP-related impairment myocardial dysfunction did not result from the increased left ventricular afterload but from a direct effect on cardiac contractility. Consequently, the authors conclude that the use of AVP should be cautioned in patients with underlying cardiac disease.     

犬肺动脉高压模型连续热稀释法的应用

背景：以往小动物肺动脉高压模型有创测压方法一般根据生物信号采集系统的压力波形图引导,采用右心导管法进行压力测定;由于设备技术和动物体积的限制无法应用肺动脉导管测定心输出量及肺血管阻力。目的：在脱氢野百合碱诱导建立犬肺动脉高压模型中利用Swan-Ganz七腔漂浮导管和Vigilance系统根据连续热稀释法测定心输出量、肺血管阻力,肺动脉压力,探讨连续心排量法在肺动脉高压动物模型中的应用价值。方法：10只比格犬随机分成2组：实验组用脱氢野百合碱右心房注射的方法建立肺动脉高压的动物模型,对照组右心房注射二甲基酰胺做对照;在用药前,用药后8周使用漂浮导管和Vigilance系统分别测定两组犬右心房收缩压、右心室收缩压、肺动脉收缩压、平均肺动脉压力、肺毛细血管楔压及心输出量。结果与结论：实验组用药后肺血管阻力显著上升（P=0．00）,实验组用药后心输出量显著减少（P〈0．05）。使用连续热稀释法测定肺血管阻力和心输出量较传统的间断热稀释法更准确稳定。利用漂浮导管和Vigilance系统根据连续热稀释法原理在脱氢野百合碱诱导的犬肺动脉高压模型中进行肺血管阻力和心输出量测定,该方法具有准确稳定、可重复操作和对实验模型创伤小的优点。     

Levosimendan improves right ventriculovascular coupling in a porcine model of right ventricular dysfunction

OBJECTIVE: Experimental data suggest that levosimendan has pulmonary vasodilatory properties which, in combination with its positive inotropic effects, would render it particularly attractive for the treatment of right ventricular dysfunction. To test this hypothesis, we developed an experimental model of right ventricular failure and analyzed the effects of levosimendan on ventriculovascular coupling between the right ventricle and pulmonary artery (PA). DESIGN: Prospective, randomized, placebo-controlled animal study. SETTING: University hospital laboratory. SUBJECTS: Fourteen pigs (mean weight 36 +/- 1 kg). INTERVENTIONS: Pigs were instrumented with biventricular conductance catheters, a PA and right coronary artery flow probe, and a high-fidelity pulmonary pressure catheter. Right ventricular dysfunction was induced by repetitive episodes of ischemia/reperfusion in the presence of temporary PA constriction. Pigs were randomly assigned to receive levosimendan (120 mg/kg/hr [corrected] for 10 mins followed by continuous infusion of 60 mg/kg/hr [corrected] for 45 mins) or the placebo (control). MEASUREMENTS AND MAIN RESULTS: Induction of right ventricular dysfunction resulted in a 42% decrease in contractility (reduction in slope of preload recruitable stroke work [Mw] from 2.5 +/- 0.4 to 1.8 +/- 0.5 mW x sec x mL(-1); p = .02) and a 60% increase in right ventricular afterload (effective pulmonary arterial elastance [PA-Ea] from 0.6 +/- 0.1 to 1.0 +/- 0.3 mm Hg x mL(-1); p < .01). Right ventriculovascular coupling, as assessed by the quotient of right ventricular end-systolic elastance (E(max)) over PA-Ea, decreased from 1.23 +/- 0.38 to 0.64 +/- 0.21 (p = .03). Treatment with levosimendan improved right ventricular contractility (Mw from 1.9 +/- 0.4 to 2.9 +/- 0.5 mW x sec x mL(-1); p < .01), lowered right ventricular afterload (PA-Ea from 1.1 +/- 0.3 to 0.8 +/- 0.3 mm Hg x mL(-1); p = .02), and restored right ventriculovascular coupling to normal values (E(max)/PA-Ea = 1.54 +/- 0.51). Levosimendan also significantly increased coronary blood flow and left ventricular contractility (Mw from 7.2 +/- 3.3 to 9.5 +/- 2.9 mW x sec x mL(-1); p = .01) but did not affect biventricular diastolic function. CONCLUSIONS: In an experimental model of acute right ventricular dysfunction, levosimendan improved global hemodynamics and optimized right ventriculovascular coupling via a moderate increase in right ventricular contractility and a mild reduction of right ventricular afterload.     

感染性休克患者右心室功能不全的研究

目的：观察感染性休克患者右心室功能的变化,为防治感染性休克患者的右心室功能不全进一步提供理论依据。方法：选择急救中心1997年10月至2000年10月3月年收治的感染性休克患者36例,运用REF－1^TM右心功能监测仪和HP监护仪,结合超声心动图观察右心室射血分类（RVEF）、右心室室壁应力（RVWS）、充盈早期最大流速（E）与晚期最大流速（A）之比（E／A）充盈早期最大流速减速时间（Dte)、平均肺动脉压（mPA)、肺血管阻力指数（PVRI）、中心静脉压（CVP）、右心室舒张末容积指数（）RVEDVI）、心排指数（CI）、肺动脉嵌压（PAWP）。右心室每搏作功指数（RVSWI）和右心室作功指数（RCWI）的变化。结果：休克早期患者即出现轻度右心室功能不全,表现为RCWI、RVSWI、RVEF、E／A、Dte的下降及RVWS的增加;随着休克病情的恶化,RCWI、RVSWI、RVEF、E／AD Dte的进一步下降及RVWS的进一步增加;而休克纠正后,RVEF和RVWS基本恢复正常,RCWI、RVSWI、E／A、Dte及RVWS均未见明显改善。结论：“感染性休克患者早期右心室功能减退,晚期出现右心衰竭;随着休克的纠正,右心室功能一定程度的改善,但未完全恢复正常。     

Effects of levosimendan versus dobutamine on pressure load-induced right ventricular failure

OBJECTIVE: A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Fifteen anesthetized dogs. INTERVENTIONS: Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 microg/kg/min or levosimendan 12 microg/kg for 10 mins followed by 0.1 and 0.2 microg/kg/min. MEASUREMENTS AND MAIN RESULTS: We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 +/- 0.07 to 3.01 +/- 0.28 mm Hg/mL, decreased Ees from 1.17 +/- 0.09 to 0.58 +/- 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 +/- 0.09 to 0.22 +/- 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state. CONCLUSIONS: A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects.     

Hemodynamic effects of different lung-protective ventilation strategies in closed-chest pigs with normal lungs

OBJECTIVE: The benefits of lung-protective ventilation strategies used for acute respiratory distress syndrome in subjects with normal lungs are uncertain. The purpose of this study was to investigate the hemodynamic effects of conventional lung-protective ventilation (CLPV) and high-frequency oscillatory ventilation (HFOV) in a normal lung animal model. DESIGN: Prospective laboratory investigation. SETTING: Animal laboratory in a university medical center. SUBJECTS: Seven landrace pigs (mean weight 41 kg). INTERVENTIONS: Pigs were ventilated at random conventionally with positive end-expiratory pressure 2-3 cm H2O and tidal volume 10-12 mL/kg (control), with CLPV (positive end-expiratory pressure 10 cm H2O, tidal volume 6 mL/kg), or with HFOV. Hemodynamics were analyzed after insertion of biventricular conductance catheters and a pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: The protective strategies led to higher mean airway pressures and severe hypercapnia with acidosis, which was only significant with CLPV. Compared with control, oxygenation was worse with CLPV and HFOV. With HFOV and CLPV, mean arterial pressure, cardiac output, and stroke volume decreased significantly; pulmonary arterial elastance increased. The slope of the end-diastolic pressure volume relationship for the left and right ventricle remained unchanged (preserved ventricular function), whereas the intercept increased with both protective strategies (augmented intrathoracic pressure); left and right end-diastolic volumes decreased significantly. CONCLUSIONS: In the absence of a fluid resuscitation strategy, CLPV and HFOV caused decreased mean arterial pressure, cardiac output, and stroke volume and worsened oxygenation in this normal lung animal model. This resulted primarily from a biventricular decrease in preload.     

Hemodynamic effects of continuous norepinephrine infusion in dogs with and without hyperkinetic endotoxic shock

We compared, at constant preload maintained by polygeline (gelatin) infusion, the hemodynamic effects of continuous infusion of norepinephrine (0.5, 1, and 1.5 micrograms/kg X min) in anesthetized dogs with and without hyperdynamic endotoxic shock. In both groups, norepinephrine infusion increased systolic, diastolic and mean aortic BP, cardiac index, stroke index, index of myocardial contractility, and mean pulmonary artery pressure. No significant change in right atrial pressure, left ventricular end-diastolic pressure, heart rate, systemic vascular resistance, or pulmonary vascular resistance was observed. Oxygen consumption index and oxygen extraction ratio remained unchanged. Increases in systolic aortic BP were dose-related, whereas maximal effects on other variables were obtained at 0.5 to 1 microgram/kg X min. The rise in aortic pressure resulted from an increased cardiac index but not from an increased systemic vascular resistance. Stroke index increased as contractility improved. The slight alpha-adrenergic effect of continuous, low-dose norepinephrine infusion did not impede the beneficial effects of the marked beta-adrenergic stimulation on cardiac function. The combination of these two effects improved hemodynamic disturbances of hyperdynamic endotoxic canine shock.