Effects of norepinephrine and 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 norepinephrine and dobutamine on RV-PA coupling in this model of RV failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twenty-two anesthetized dogs. INTERVENTIONS: Animals underwent transient (90-min) PA constriction to induce persistent RV failure. They were randomly assigned to control, norepinephrine, or dobutamine group. Norepinephrine was administered at 0.1 and 0.5 microg x kg x min or dobutamine at 5 and 10 microg x kg x min. MEASUREMENTS AND MAIN RESULTS: We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We also 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. The transient PA constriction persistently increased PA resistance and elastance, increased Ea from 0.8+/-0.1 to 2.7+/-0.3 mmHg/mL, decreased Ees from 1.1+/-0.1 to 0.5+/-0.1 mm Hg/mL, and decreased Ees/Ea from 1.2+/-0.1 to 0.2+/-0.1. Norepinephrine restored arterial pressure, increased RV contractility, and increased but did not normalize RV-PA coupling and cardiac output. Dobutamine restored arterial pressure, markedly increased RV contractility, and normalized RV-PA coupling and cardiac output. Compared with norepinephrine, dobutamine decreased PA resistance and elastance and increased RV contractility and RV-PA coupling. CONCLUSIONS: A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Dobutamine restores RV-PA coupling and cardiac output better than norepinephrine because of its more pronounced inotropic effect.     

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.     

Effect of levosimendan on right ventricular systolic and diastolic functions in patients with ischaemic heart failure

OBJECTIVES: Levosimendan is a novel positive inotropic calcium sensitiser agent used in acute left heart failure. In this study, the effect of levosimendan on the right ventricular systolic and diastolic functions was evaluated by tissue Doppler comparing them with dobutamine in patients with ischaemic heart failure. METHODS: Patients having an acute decompensated heart failure with ischaemic cardiomyopathy and left ventricular ejection fraction <40% were included in the study. Before and 24-h after treatment, peak systolic (Sa), peak early (Ea), peak late (Aa) diastolic annular velocities and Ea/Aa ratio from tricuspid lateral annulus by tissue Doppler and systolic pulmonary artery pressure (SPAP) were measured. RESULTS: Sa, Ea and the Ea/Aa ratio were significantly increased in the levosimendan group whereas SPAP was significantly reduced. In the dobutamine group, no significant differences were observed in the Sa, Ea, Aa and Ea/Aa ratio in spite of a significant reduction in SPAP. Decrease in SPAP was greater in the levosimendan group (p=0.002). CONCLUSION: Levosimendan improves right ventricular systolic and diastolic functions.     

Effects of positive end-expiratory pressure on right ventricular function in COPD patients during acute ventilatory failure

Objective To examine the effects of external positive end-expiratory pressure (PEEP) on right ventricular function in chronic obstructive pulmonary disease (COPD) patients with intrinsic PEEP (PEEPi).Design Prospective study.Setting General intensive care unit in a university teaching hospital.Patients Seven mechanically ventilated flow-limited COPD patients (PEEPi=9.7±1.3 cmH₂O, mean±SD) with acute respiratory failure.Intervention Hemodynamic and respiratory mechanic data were collected at four different levels of PEEP (0-5-10-15 cmH₂O).Measurements and results Hemodynamic parameters were obtained by a Swan-Ganz catheter with a fast response thermistor. Cardiac index (CI) and end-expiratory lung volume (EELV) reductions started simultaneously when the applied PEEP was approximately 90% of PEEPi measured on 0 cmH₂O (ZEEP). Changes in transmural intrathoracic pressure (PEEPi,cw) started only at a PEEP value much higher (120%) than PEEPi. The reduction in CI was related to a decrease in the right enddiastolic ventricular volume index (RVEDVI) (r=0.61;p<0.001). No correlation between CI and transmural right atrial pressure was observed. The RVEDVI was inversely correlated with PEEP-induced changes in EELV (r=–55;p<0.001), but no with PEEPi,cw (r=–0.08; NS). The relationship between RVEDVI and right ventricular stroke work index, considered an index of contractility, was significant in three patients, i.e., PEEP did not change contractility. In the other patients, an increase in contractility seemed to occur.Conclusions In COPD patients an external PEEP exceeding 90% of PEEPi causes lung hyperinflation and reduces the CI due to a preload effect. The reduction in RVEDVI seems related to changes in EELV, rather than to changes in transmural pressures, suggesting a lung/heart volume interaction in the cardiac fossa. Thus, in COPD patients, application of an external PEEP level lower than PEEPi may affect right ventricular function.This study was supported in part by a grant from the Consiglio Nazionale delle Ricerche, Italy     

左西孟旦联合多巴酚丁胺对老年急性心力衰竭患者心功能及炎症相关指标的影响

目的 探讨左西孟旦联合多巴酚丁胺对老年急性心力衰竭患者心功能及炎症相关指标的影响.方法 选取2019年1月至2020年1月在该院接受治疗的老年急性心力衰竭患者165例,分为联合组(83例)和单药组(82例).单药组给予多巴酚丁胺治疗,联合组给予左西孟旦联合多巴酚丁治疗,比较两组临床疗效、血清氨基末端B型利钠肽前体(NT-proBNP)、C反应蛋白(CRP)、降钙素原(PCT)、中性粒细胞与淋巴细胞比值(NLR)等.结果 治疗后,联合组总有效率高于单药组,差异有统计学意义(P<0.05);联合组血清NT-proBNP、CRP、PCT、NLR低于单药组,左室射血分数(LVEF)、短轴缩短率(FS)、6 min步行距离均高于单药组,左室舒张末内径(LVIDd)、呼吸频率均低于单药组,差异均有统计学意义(P<0.05).结论 左西孟旦联合多巴酚丁胺治疗老年急性心力衰竭患者疗效显著,可有效改善患者心功能及炎症状态.     

Effects on right ventricular function of a change from dopamine to dobutamine in critically ill patients

In 15 critically ill patients requiring adrenergic support, right ventricular ejection fraction (RVEF) and right ventricular (RV) volumes were measured by the thermodilution technique receiving 5 micrograms/kg.min of dopamine and after replacement by the same dose of dobutamine. Shift from dopamine to dobutamine resulted in significant increases in stroke index from 28.1 +/- 3.6 to 31.0 +/- 3.8 ml/m2 (p less than .01) and significant decreases in pulmonary artery balloon-occluded pressure from 15.1 +/- 1.0 to 13.9 +/- 1.2 mm Hg (p less than .05) and right atrial pressure (RAP) from 14.0 +/- 1.3 to 12.2 +/- 1.1 mm Hg (p less than .05). RVEF increased slightly but significantly from 21.5 +/- 2.7% to 23.7 +/- 2.9% (p less than .01) so that RV end-diastolic volume (RVEDVI) was unchanged (140 +/- 12 vs. 141 +/- 12 ml, nonsignificant). RVEDVI/RAP ratio increased from 11.3 +/- 1.0 to 12.9 +/- 1.1 ml/mm Hg (p = .037). These results support the view that dobutamine has more favorable effects on RV function than dopamine in critically ill patients in the absence of profound hypotension and also indicates that higher filling pressures under dopamine administration can be related to changes in ventricular pressure/volume relationship.     

Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: a pilot study

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is frequently associated with increased pulmonary vascular resistance and thus with systolic load of the right ventricle. We hypothesized that levosimendan, a new calcium sensitizer with potential pulmonary vasodilator properties, improves hemodynamics by unloading the right ventricle in patients with ARDS. DESIGN: Prospective, randomized, placebo-controlled, pilot study. SETTING: Twenty-two-bed multidisciplinary intensive care unit of a university hospital. PATIENTS: Thirty-five patients with ARDS in association with septic shock. INTERVENTIONS: Patients were randomly allocated to receive a 24-hr infusion of either levosimendan 0.2 microg/kg/min (n = 18) or placebo (n = 17). Data from right heart catheterization, cardiac magnetic resonance, arterial and mixed venous oxygen tensions and saturations, and carbon dioxide tensions were obtained before and 24 hrs after drug infusion. MEASUREMENTS AND MAIN RESULTS: At a mean arterial pressure between 70 and 80 mm Hg (sustained with norepinephrine infusion), levosimendan increased cardiac index (from 3.8 +/- 1.1 to 4.2 +/- 1.0 L/min/m) and decreased mean pulmonary artery pressure (from 29 +/- 3 to 25 +/- 3 mm Hg) and pulmonary vascular resistance index (from 290 +/- 77 to 213 +/- 50 dynes/s/cm(5)/m(2); each p < .05). Levosimendan also decreased right ventricular end-systolic volume and increased right ventricular ejection fraction (p < .05). In addition, levosimendan increased mixed venous oxygen saturation (from 63 +/- 8 to 70 +/- 8%; p < .01). CONCLUSIONS: This study provides evidence that levosimendan improves right ventricular performance through pulmonary vasodilator effects in septic patients with ARDS. A large multiple-center trial is needed to investigate whether levosimendan is able to improve the overall prognosis of patients with sepsis and ARDS.     

Post-resuscitation right ventricular dysfunction: delineation and treatment with dobutamine

Newly qualified doctors are ill equipped to deal with pre-hospital trauma emergencies. There is a public perception that medical education provides both experience and knowledge in this field. In Birmingham, United Kingdom (UK), committed doctors and nurses trained in pre-hospital care have evolved a specific course designed to equip the medical undergraduate to deal with pre-hospital trauma scenario. The pre-hospital trauma course for medical students has run annually from 1993 to 2000. The course caters for 200 students with a faculty of 30 instructors. Successful completion of the course which is rigorously assessed grants a certificate awarded by the Faculty of Pre-hospital Care at the Royal College of Surgeons of Edinburgh. Most importantly it equips the undergraduate with essential theoretical knowledge and practical skills to handle a pre-hospital trauma emergency.     

Effects of piroximone on the right ventricular function in severe heart failure patients

Objectives

To assess the effects of piroximone, a phosphodiesterase inhibitor, on right ventricular function in patients with heart failure.

Design

Randomized study: patients were randomly assigned to the piroximone infusion rate of 5 or 10 μg/kg/min.

Setting

Cardiologic intensive care unit.

Patients

12 consecutive patients with severe heart failure.

Interventions

Right heart catheterization was performed using a Swan-Ganz ejection fraction thermodilution catheter.

Measurements and results

Measurements of right ventricular ejection fraction (RVEF), end-diastolic and end-systolic right ventricular volumes were obtained using the thermodilution principle. To determine contractility indexes, the relationships between end-systolic pulmonary arterial pressure (ESPAP) over right ventricular end-systolic volume (RVESV) and ESPAP over RVEF were calculated during the infusion of prostacyclin at incremental infusion rates of 2, 4, 6 and 8 ng/kg/min. The slope of the relation between ESPAP over RVESV shifted during piroximone therapy from 7.635±1.632 to 1.975±0.432 (p<0.01) and from 6.092±1.99 to 1.028±0.853 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively. The slope of the relation between ESPAP over RVEF decreased from ?0.414±0.296 to ?0.821±0.257 (p<0.01) and from ?0.127±0.048 to ?0.533±0.135 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively.

Conclusions

This study suggests a positive action of piroximone on right ventricular contractility at these 2 dosages. This approach using this type of catheter allowed us to determine right ventricular inotropic indexes.     

Right ventricular hemangioma causing right ventricular inflow obstruction and right heart failure.

We report a patient who presented with symptoms of right heart failure. Transesophageal echocardiography revealed a right ventricular mass, causing right ventricular inflow obstruction. Coronary angiography revealed a characteristic tumor blush. After successful surgical resection, histologic findings were consistent with a right ventricular hemangioma.     

左西孟旦与多巴酚丁胺治疗脓毒症心肌病疗效对比

目的 比较应用左西孟旦和多巴酚丁胺治疗脓毒症心肌病患者的临床效果.方法 回顾性分析福建省立医院2018年1月至2020年12月收治的66例脓毒症心肌病患者,按照治疗方法的不同分为多巴酚丁胺组(n=32)和左西孟旦组(n=34),分别在常规治疗的基础上应用多巴酚丁胺和左西孟旦.分析治疗前后2组患者的N末端B型利尿钠肽原(N-terminal pro-brain natriuretic peptide,NT-proBNP)、肌钙蛋白I、乳酸水平、氧合指数、住院时间、住院死亡率、去甲肾上腺素总剂量以及不良反应情况.结果 治疗前,两组患者的NT-proBNP、肌钙蛋白I、乳酸、氧合指数差异无统计学意义(P>0.05);治疗后,两组患者的NT-proBNP、乳酸、肌钙蛋白I水平比治疗前降低,氧合指数比治疗前升高(均P<0.05).治疗后,左西孟旦组患者的NT-proBNP、肌钙蛋白I、乳酸水平、住院时间和去甲肾上腺素总剂量比多巴酚丁胺组低,氧合指数比多巴酚丁胺组高(均P<0.05);与多巴酚丁胺组相比,左西孟旦组心律失常发生率下降,差异有统计学意义(P<0.05).两组死亡率差异无统计学意义(P>0.05).结论 左西孟旦与多巴酚丁胺相比,能更好地改善脓毒症心肌病患者的心功能,稳定血流动力学,减少住院时间,但无法降低住院死亡率.     

Evolving targeted therapies for right ventricular failure

Introduction: Although right and left ventricular embryological origins, morphology and cardiodynamics differ, the notion of selectively targeted right ventricular therapies remains controversial.

Areas covered: This review focuses on both the currently evolving pharmacologic agents targeting right ventricular failure (metabolic modulators, phosphodiesterase type V inhibitors) and future therapeutic approaches including epigenetic modulation by miRNAs, chromatin binding complexes, long non-coding RNAs, genomic editing, adoptive gene transfer and gene therapy, cell regeneration via cell transplantation and cell reprogramming and cardiac tissue engineering.

Expert opinion: Strategies for adult right ventricular regeneration will require a more holistic approach than strategies for adult left ventricular failure. Instances of right ventricular failure requiring global reconstitution of right ventricular myocardium, attractive approaches include: i) myocardial patches seeded with cardiac fibroblasts reprogrammed into cardiomyocytes in vivo by small molecules, miRNAs or other epigenetic modifiers; and ii) administration of miRNAs, lncRNAs or small molecules by non-viral vector delivery systems targeted to fibroblasts (e.g., episomes) to stimulate in vivo reprogramming of fibroblasts into cardiomyocytes. For selected heritable genetic myocardial diseases, genomic editing affords exciting opportunities for allele-specific silencing by site-specific directed silencing, mutagenesis or gene excision. Genomic editing by adoptive gene transfer affords similarly exciting opportunities for restoration of myocardial gene expression.     

Assessment of right ventricular function by right ventricular systolic time intervals in acute respiratory failure

OBJECTIVE: Whether right ventricular systolic time intervals accurately reflect right ventricular function in patients with acute respiratory failure was determined by assessing the correlation between right ventricular systolic time intervals and the right ventricular end-systolic pressure-volume relationship. DESIGN: A prospective study. SETTING: A surgical intensive care unit in a university hospital. PATIENTS: Twenty patients with acute respiratory failure. MEASUREMENTS AND MAIN RESULTS: Right ventricular systolic time intervals were determined by the simultaneous graphic display of the electrocardiogram, the phonocardiogram, and the pulmonary artery pressure curve and were expressed as a ratio of the pre-ejection period/right ventricular ejection time. The total electromechanical systole was measured from the onset of the electrocardiographic wave complex to the pulmonic component of the second heart sound. Right ventricular ejection time was measured from the rapid upstroke of the pulmonary artery pressure curve to the dicrotic notch. Right ventricular ejection fraction, from which right ventricular end-systolic volume was derived, was measured by the thermodilution technique. Pulmonary artery dicrotic notch pressure was used as an estimate of right ventricular end-systolic pressure. Data were collected at the baseline and after one or two alterations in preload, to define the right ventricular end-systolic pressure-volume relationship line. There was an inverse correlation between the pre-ejection period/right ventricular ejection time ratio and the slope of the right ventricular end-systolic pressure-volume relationship line (r2 = .67; p < .0001). When patients were divided into two groups, based on the pre-ejection period/right ventricular ejection time ratio, the slope of the right ventricular end-systolic pressure-volume relationship line was lower in the group with a high pre-ejection period/right ventricular ejection time ratio (p < .0001). No difference in other hemodynamic data, between the two groups, was noted. CONCLUSIONS: These data suggest that right ventricular systolic time intervals reflect right ventricular performance accurately in patients with acute respiratory failure.     

Left ventricular systolic function affects right atrial pressure as prognosticator in patients with heart failure

The International Journal of Cardiovascular Imaging - The effect of the left ventricular ejection fraction (LVEF) on the prognostic impact of the right atrial pressure (RAP) in patients with heart...     

Comparison between dobutamine and levosimendan for management of postresuscitation myocardial dysfunction

OBJECTIVE: To investigate the effects of levosimendan, a nonadrenergic inotropic calcium sensitizer, in comparison with adrenergic dobutamine for the management of postresuscitation myocardial dysfunction following resuscitation from prolonged cardiac arrest. DESIGN: Randomized prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Male Yorkshire-cross domestic pigs INTERVENTIONS: Ventricular fibrillation was induced in male domestic pigs weighing between 35 and 40 kg. Cardiopulmonary resuscitation, including precordial compression and mechanical ventilation, was started after 7 mins of untreated cardiac arrest. Electrical defibrillation was attempted after 5 mins of cardiopulmonary resuscitation. Each animal was successfully resuscitated without pharmacologic intervention. Resuscitated animals were randomized to treatment with levosimendan, dobutamine, or saline placebo. The inotropic agents or an equivalent volume of placebo diluents was administered 10 mins after restoration of spontaneous circulation. Levosimendan was administered in a loading dose of 20 microg.kg over 10 mins followed by a 220-min infusion of 0.4 microg.kg.min. Dobutamine was infused into the right atrium in an amount of 5 microg.kg.min. Treatment was continued for a total of 230 mins. MEASUREMENTS AND MAIN RESULTS: Levosimendan and dobutamine produced comparable increases in cardiac output. However, levosimendan produced significantly greater left ventricular ejection fraction and fractional area changes compared with dobutamine and saline placebo. CONCLUSIONS: Levosimendan has the potential of improving postresuscitation myocardial function. It is likely to serve as an alternative to dobutamine as an inotropic agent for management of postresuscitation myocardial dysfunction.     

Influence of constant sustained positive airway pressure on right ventricular performance

Objective The detrimental effect of positive airway pressure on right ventricular (RV) performance is controversial and the aim of this study was to determine the effects of constant positive airway pressure without ventilatory fluctuation on RV performance with the aid of a pulmonary arterial catheter equipped with a rapid response thermistor for measuring RV ejection fraction (RVEF) and RV end-diastolic volume index (RVEDVI).Design A prospective, clinical study.Setting The central operating theatre of a university hospital.Patients Nine patients who had major surgery and required right heart catheterization for normal clinical management.Measurements and results Cold indicator was injected into the RV 4 or 5 times for each airway pressure (0, 10 or 20 cmH₂O) which was maintained manually stable for 15 s, and 9 paired data were analyzed by repeated-measures analysis of variance. They are separated into two groups; RVEF at zero airway pressure greater (A group) or less (B group) than 0.4. In A group (7 patients), increasing airway pressures (0 vs 10 vs 20 cmH₂O) did not affect RVEF (0.55±0.05 vs 0.54±0.06 vs 0.56±0.04), RVEDVI (69±36 vs 73±29 vs 58±20 ml·m^–2), or stroke volume index (SVI: 38±18 vs 40±17 vs 33±13 ml·beat^–1 ·m^–2); however, in B (2 patients), RVEF (0.35 and 0.38 vs 0.31 and 0.28 vs 0.19 and 0.17) and SVI (35 and 28 vs 32 and 27 vs 27 and 23) decreased, while RVEDVI increased (99 and 73 vs 103 and 97 vs 146 and 132).Conclusions In most patients, the changes in RVEF, SVI, and RVEDVI did not occur under constant positive airway pressure, therefore the changes reported in mechanically ventilated patients may not attributable to the extent of positive airway pressure but rather to abrupt increases in airway pressure. There appears, however, to be patients whose RV function is so disturbed that they cannot cope with increased afterloads.