Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs

Purpose  

To determine reciprocal and synergistic effects of acute intracranial hypertension and ARDS on neuronal and pulmonary damage and to define possible mechanisms.     

Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility

Objective

Prostacyclins have been suggested to exert positive inotropic effects which would render them particularly suitable for the treatment of right ventricular (RV) dysfunction due to acute pulmonary hypertension (PHT). Data on this subject are controversial, however, and vary with the experimental conditions. We studied the inotropic effects of epoprostenol at clinically recommended doses in an experimental model of acute PHT.

Design and setting

Prospective laboratory investigation in a university hospital laboratory.

Subjects

Six pigs (36?±?7?kg).

Interventions

Pigs were instrumented with biventricular conductance catheters, a pulmonary artery (PA) flow probe, and a high-fidelity pulmonary pressure catheter. Incremental doses of epoprostenol (10, 15, 20, 30, 40?ng?kg^–1?min^–1) were administered in undiseased animals and after induction of acute hypoxia-induced PHT.

Measurements and results

In acute PHT epoprostenol markedly reduced RV afterload (slopes of pressure-flow relationship in the PA from 7.0?±?0.6 to 4.2?±?0.7?mmHg?min?l^–1). This was associated with a paradoxical and dose-dependent decrease in RV contractility (slope of preload-recruitable stroke-work relationship from 3.0?±?0.4 to 1.6?±?0.2?mW?s?ml^–1; slope of endsystolic pressure-volume relationship from 1.5?±?0.3 to 0.7?±?0.3?mmHg?ml^–1). Left ventricular contractility was reduced only at the highest dose. In undiseased animals epoprostenol did not affect vascular tone and produced a mild biventricular decrease in contractility.

Conclusions

Epoprostenol has no positive inotropic effects in vivo. In contrast, epoprostenol-induced pulmonary vasodilation in animals with acute PHT was associated with a paradoxical decrease in RV contractility. This effect is probably caused indirectly by the close coupling of RV contractility to RV afterload. However, data from normal animals suggest that mechanisms unrelated to vasodilation are also involved in the observed negative inotropic response to epoprostenol.     

High rate of isolated right ventricular dysfunction in patients with non-significant CT pulmonary angiography

Background

Right ventricular (RV) dysfunction and pulmonary hypertension (PH) are commonly unrecognized in the emergency department (ED), but are associated with poor outcomes. Prior research has found a 30% prevalence of isolated RV dysfunction in ED patients after non-significant computed tomographic pulmonary angiography (CTPA). We aimed to prospectively define the prevalence of RV dysfunction and/or PH in short of breath ED patients, and assess outcomes.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review

Introduction  

Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care.     

Efficiency of prostacyclin in the treatment of protamine-mediated right ventricular failure and acute pulmonary hypertension

Protamine is used after cardiopulmonary bypass was stopped in order to reverse the anticoagulant effects of heparin administered during open-heart operations. Adverse hemodynamic responses to protamine are common, ranging from minor perturbations to cardiovascular collapse. The aim of the present study was to investigate whether a prostacyclin is effective in the treatment of protamine-mediated acute pulmonary hypertension and right ventricular failure in the perioperative period of isolated coronary artery bypass grafting (CABG) operations. In sixty-eight (1.78%) of 3800 patients who underwent isolated CABG, acute pulmonary hypertension and right ventricular failure developed during or following the protamine infusion. These 68 patients were included in the study and were randomized into two groups. Thirty-eight of the patients received prostaglandin I(2) (PGI(2)), norepinephrine and dopamine (PGI(2) group), whereas 30 patients received nitroglycerin, norepinephrine and dopamine (control group). Hemodynamic data were recorded before and after the above drug combinations. The mean value of left ventricle ejection fraction significantly increased (p < 0.05) and mean values of central venous pressure, pulmonary artery systolic and diastolic pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance significantly decreased (p < 0.05) in the PGI(2) group. The mean value of pulmonary capillary wedge pressure significantly decreased (p < 0.05) and the mean value of central venous pressure significantly increased (p < 0.05) in the control group. In conclusion, prostacyclin (PGI(2)) is effective in the treatment of protamine-mediated acute pulmonary hypertension and right ventricular failure in the perioperative period in isolated CABG operations. This finding may be an important contribution to the treatment of severe protamine complications during open-heart operations.     

Sildenafil attenuates pulmonary arterial pressure but does not improve oxygenation during ARDS

Objective  

Pulmonary hypertension is a characteristic feature of acute respiratory distress syndrome (ARDS) and contributes to mortality. Administration of sildenafil in ambulatory patients with pulmonary hypertension improves oxygenation and ameliorates pulmonary hypertension. Our aim was to determine whether sildenafil is beneficial for patients with ARDS.     

Cardiovascular magnetic resonance tagging of the right ventricular free wall for the assessment of long axis myocardial function in congenital heart disease

Background

Right ventricular ejection fraction (RV-EF) has traditionally been used to measure and compare RV function serially over time, but may be a relatively insensitive marker of change in RV myocardial contractile function. We developed a cardiovascular magnetic resonance (CMR) tagging-based technique with a view to rapid and reproducible measurement of RV long axis function and applied it in patients with congenital heart disease.

Methods

We studied 84 patients: 56 with repaired Tetralogy of Fallot (rTOF); 28 with atrial septal defect (ASD): 13 with and 15 without pulmonary hypertension (RV pressure > 40 mmHG by echocardiography). For comparison, 20 healthy controls were studied. CMR acquisitions included an anatomically defined four chamber cine followed by a cine gradient echo-planar sequence in the same plane with a labelling pre-pulse giving a tag line across the basal myocardium. RV tag displacement was measured with automated registration and tracking of the tag line together with standard measurement of RV-EF.

Results

Mean RV displacement was higher in the control (26 ± 3 mm) than in rTOF (16 ± 4 mm) and ASD with pulmonary hypertension (18 ± 3 mm) groups, but lower than in the ASD group without (30 ± 4 mm), P < 0.001. The technique was reproducible with inter-study bias ± 95% limits of agreement of 0.7 ± 2.7 mm. While RV-EF was lower in rTOF than in controls (49 ± 9% versus 57 ± 6%, P < 0.001), it did not differ between either ASD group and controls.

Conclusions

Measurements of RV long axis displacement by CMR tagging showed more differences between the groups studied than did RV-EF, and was reproducible, quick and easy to apply. Further work is needed to assess its potential use for the detection of longitudinal changes in RV myocardial function.     

Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension

OBJECTIVE: Arginine vasopressin is a promising systemic vasopressor in settings such as vasodilatory shock and cardiopulmonary resuscitation. The evidence that arginine vasopressin may also have a pulmonary vasodilatory effect makes it an attractive drug for the treatment of circulatory shock secondary to right ventricular failure and pulmonary hypertension. In the present study, we evaluated the effects of arginine vasopressin on right ventricular function and ventriculovascular coupling in the setting of moderate acute pulmonary hypertension and compared these effects with those of phenylephrine. DESIGN: Prospective laboratory investigation using an established model of acute pulmonary hypertension. SETTING: University hospital laboratory. SUBJECTS: Seven adult beagle dogs weighing 8-14 kg. INTERVENTIONS: After acute instrumentation to measure right ventricular pressure and volume with the conductance technique and pulmonary artery flow and pressure with high-fidelity transducers, the stable thromboxane analogue U46619 was infused continuously to obtain stable pulmonary hypertension. Phenylephrine and arginine vasopressin were administered consecutively in continuous infusions at doses titrated to achieve a 25% increase in aortic pressure. MEASUREMENTS AND MAIN RESULTS: Phenylephrine and arginine vasopressin both increased total pulmonary vascular resistance and arterial elastance without influencing characteristic impedance. Both drugs decreased cardiac output and stroke volume. Right ventricular hydraulic power output was reduced by arginine vasopressin but not by phenylephrine. Most importantly, arginine vasopressin caused a 31% decrease in right ventricular contractility measured as the slope of the preload recruitable stroke work relationship, whereas contractility was preserved during phenylephrine infusion. CONCLUSIONS: In the present model, arginine vasopressin causes pulmonary vascular constriction and exerts an important negative inotropic effect on the right ventricle. These findings suggest that one should be cautious in the use of arginine vasopressin when right ventricular function is compromised.     

Effects of different tidal volumes in pulmonary and extrapulmonary lung injury with or without intraabdominal hypertension

Purpose

We hypothesized that: (1) intraabdominal hypertension increases pulmonary inflammatory and fibrogenic responses in acute lung injury (ALI); (2) in the presence of intraabdominal hypertension, higher tidal volume reduces lung damage in extrapulmonary ALI, but not in pulmonary ALI.

Methods

Wistar rats were randomly allocated to receive Escherichia coli lipopolysaccharide intratracheally (pulmonary ALI) or intraperitoneally (extrapulmonary ALI). After 24?h, animals were randomized into subgroups without or with intraabdominal hypertension (15?mmHg) and ventilated with positive end expiratory pressure?=?5?cmH₂O and tidal volume of 6 or 10?ml/kg during 1?h. Lung and chest wall mechanics, arterial blood gases, lung and distal organ histology, and interleukin (IL)-1??, IL-6, caspase-3 and type III procollagen (PCIII) mRNA expressions in lung tissue were analyzed.

Results

With intraabdominal hypertension, (1) chest-wall static elastance increased, and PCIII, IL-1??, IL-6, and caspase-3 expressions were more pronounced than in animals with normal intraabdominal pressure in both ALI groups; (2) in extrapulmonary ALI, higher tidal volume was associated with decreased atelectasis, and lower IL-6 and caspase-3 expressions; (3) in pulmonary ALI, higher tidal volume led to higher IL-6 expression; and (4) in pulmonary ALI, liver, kidney, and villi cell apoptosis was increased, but not affected by tidal volume.

Conclusions

Intraabdominal hypertension increased inflammation and fibrogenesis in the lung independent of ALI etiology. In extrapulmonary ALI associated with intraabdominal hypertension, higher tidal volume improved lung morphometry with lower inflammation in lung tissue. Conversely, in pulmonary ALI associated with intraabdominal hypertension, higher tidal volume increased IL-6 expression.     

Unexpected death from a colloid cyst

Background

Colloid cysts are usually benign brain tumors, which rarely cause acute neurological deterioration with sudden death due to an acute increase of intracranial pressure. So far, the final pathophysiology and clinical signs of impending death are unclear in this context.

Aim

We present a case of an adolescent who presented with symptoms similar to gastroenteritis.

Results

He unexpectedly developed a generalized seizure, acute pulmonary edema and life-threatening cardiac dysrhythmia.

Conclusion

Subtle distinctions between symptoms due to intracranial hypertension, which typically cause headache and vomiting, and true gastroenteritis are discussed as well as the pathophysiology of neurogenic pulmonary edema and the origin of cerebral-triggered cardiac dysrhythmias.     

Diagnostic accuracy of cardiovascular magnetic resonance imaging of right ventricular morphology and function in the assessment of suspected pulmonary hypertension results from the ASPIRE registry

Background

Cardiovascular Magnetic Resonance (CMR) imaging is accurate and reproducible for the assessment of right ventricular (RV) morphology and function. However, the diagnostic accuracy of CMR derived RV measurements for the detection of pulmonary hypertension (PH) in the assessment of patients with suspected PH in the clinic setting is not well described.

Methods

We retrospectively studied 233 consecutive treatment naïve patients with suspected PH including 39 patients with no PH who underwent CMR and right heart catheterisation (RHC) within 48hours. The diagnostic accuracy of multiple CMR measurements for the detection of mPAP ≥ 25 mmHg was assessed using Fisher’s exact test and receiver operating characteristic (ROC) analysis.

Results

Ventricular mass index (VMI) was the CMR measurement with the strongest correlation with mPAP (r = 0.78) and the highest diagnostic accuracy for the detection of PH (area under the ROC curve of 0.91) compared to an ROC of 0.88 for echocardiography calculated mPAP. Late gadolinium enhancement, VMI ≥ 0.4, retrograde flow ≥ 0.3 L/min/m² and PA relative area change ≤ 15% predicted the presence of PH with a high degree of diagnostic certainty with a positive predictive value of 98%, 97%, 95% and 94% respectively. No single CMR parameter could confidently exclude the presence of PH.

Conclusion

CMR is a useful alternative to echocardiography in the evaluation of suspected PH. This study supports a role for the routine measurement of ventricular mass index, late gadolinium enhancement and the use of phase contrast imaging in addition to right heart functional indices in patients undergoing diagnostic CMR evaluation for suspected pulmonary hypertension.     

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.     

Pimobendan improves right ventricular myocardial contraction and attenuates pulmonary arterial hypertension in rats with monocrotaline-induced pulmonary arterial hypertension

Purpose

The present study aimed to evaluate the therapeutic effect of pimobendan treatment for pulmonary hypertension (PH) in rats administered monocrotaline (MCT).

Methods

Fifty-four 12-week-old male Sprague–Dawley rats were injected with monocrotaline or saline solution. Serial echocardiography and right ventricular systolic pressure (RVSP) measurement via a cardiac catheter were performed. After injection of MCT, rats received oral pimobendan (MCT/pimobendan group) or no treatment (MCT group) until undergoing echocardiography and cardiac catheter insertion.

Results

Right ventricular systolic pressure in the MCT/pimobendan group was lower than that in the MCT group at 6 weeks. Right ventricle free wall (RVFW) myocardial systolic velocity (Sm) in the MCT group showed a reduction compared with the saline group at 2 weeks. RVFW Sm in the MCT/pimobendan group was preserved as compared with the saline group at 2 weeks. RVFW Tei index in the MCT/pimobendan group showed a reduction compared with the saline group and the MCT group at 2 weeks. Echocardiography in the MCT/pimobendan group showed improvement compared with MCT rats.

Conclusions

Both a reduction in RVSP and improvement in myocardial contraction were demonstrated with administration of pimobendan in rats with PH induced by MCT. Echocardiography evaluation of systolic function seems to be useful for monitoring excess administration of pimobendan.     

Changes in overall ventricular myocardial architecture in the setting of a porcine animal model of right ventricular dilation

Background

Chronic pulmonary regurgitation often leads to myocardial dysfunction and heart failure. It is not fully known why secondary hypertrophy cannot fully protect against the increase in wall stress brought about by the increased end-diastolic volume in ventricular dilation. It has been assumed that mural architecture is not deranged in this situation, but we hypothesised that there might be a change in the pattern of orientation of the aggregations of cardiomyocytes, which would contribute to contractile impairment.

Methods

We created pulmonary valvular regurgitation by open chest, surgical suturing of its leaflets in seven piglets, performing sham operations in seven control animals. Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we demonstrated significantly increased right ventricular volumes in the test group. After sacrifice, diffusion tensor imaging of their hearts permitted measurement of the orientation of the cardiomyocytes.

Results

The helical angles in the right ventricle approached a more circumferential orientation in the setting of right ventricular RV dilation (p = 0.007), with an increased proportion of surface-parallel cardiomyocytes. In contrast, this proportion decreased in the left ventricle. Also in the left ventricle a higher proportion of E3 angles with a value around zero was found, and conversely a lower proportion of angles was found with a numerical higher value. In the dilated right ventricle the proportion of E3 angles around ?90° is increased, while the proportion around 90° is decreased.

Conclusion

Contrary to traditional views, there is a change in the orientation of both the left ventricular and right ventricular cardiomyocytes subsequent to right ventricular dilation. This will change their direction of contraction and hinder the achievement of normalisation of cardiomyocytic strain, affecting overall contractility. We suggest that the aetiology of the cardiac failure induced by right vetricular dilation may be partly explained by morphological changes in the myocardium itself.

     

Inhaled activated protein C protects mice from ventilator-induced lung injury

Introduction  

Activated Protein C (APC), an endogenous anticoagulant, improves tissue microperfusion and endothelial cell survival in systemic inflammatory states such as sepsis, but intravenous administration may cause severe bleeding. We have thus addressed the role of APC delivered locally by inhalation in preventing acute lung injury from alveolar overdistention and the subsequent ventilator-induced lung injury (VILI). We also assessed the effects of APC on the activation status of Extracellular- Regulated Kinase 1/2 (ERK) pathway, which has been shown to be involved in regulating pulmonary responses to mechanical stretch.     

Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease

Background

Cardiovascular magnetic resonance (CMR) provides non-invasive and more accurate assessment of right ventricular (RV) function in comparison to echocardiography. Recent study demonstrated that assessment of RV function by echocardiography was an independent predictor for mortality in patients with interstitial lung disease (ILD). The purpose of this study was to determine the prognostic significance of CMR derived RV ejection fraction (RVEF) in ILD patients.

Methods

We enrolled 76 patients with ILD and 24 controls in the current study. By using 1.5 T CMR scanner equipped with 32 channel cardiac coils, we performed steady-state free precession cine CMR to assess the RVEF. RV systolic dysfunction (RVSD) was defined as RVEF ≤45.0% calculated by long axis slices. Pulmonary hypertension (PH) was defined as mean pulmonary artery pressure (mPAP) of more than 25 mmHg at rest in the setting of pulmonary capillary wedge pressure ≤15 mmHg.

Results

The median RVEF was 59.2% in controls (n = 24), 53.8% in ILD patients without PH (n = 42) and 43.1% in ILD patients with PH (n = 13) (p < 0.001 by one-way ANOVA). During a mean follow-up of 386 days, 18 patients with RVSD had 11 severe events (3 deaths, 3 right heart failure, 3 exacerbation of dyspnea requiring oxygen, 2 pneumonia requiring hospitalization). In contrast, only 2 exacerbation of dyspnea requiring oxygen were observed in 58 patients without RVSD. Multivariate Cox regression analysis showed that RVEF independently predicted future events, after adjusting for age, sex and RVFAC by echocardiography (hazard ratio: 0.889, 95% confidence interval: 0.809 – 0.976, p = 0.014).

Conclusions

The current study demonstrated that RVSD in ILD patients can be clearly detected by cine CMR. Importantly, low prevalence of PH (17%) indicated that population included many mild ILD patients. CMR derived RVEF might be useful for the risk stratification and clinical management of ILD patients.     

The prognostic value of markers of right ventricular dysfunction in pulmonary embolism: a meta-analysis

Introduction  

In pulmonary embolism (PE) without hemodynamic compromise, the prognostic value of right ventricular (RV) dysfunction as measured by echocardiography, computed tomography (CT) or biological (natriuretic peptides) markers has only been assessed in small studies.     

Echocardiographic evaluation of left and right ventricular diastolic function in patients with chronic obstructive pulmonary disease.

The aim of this study was to investigate the effects of chronic obstructive pulmonary disease (COPD) on left ventricular and right ventricular diastolic and systolic functions. Forty-eight patients with severe COPD were studied. Patients were divided into 2 subgroups according to pulmonary artery pressures: 25 patients with pulmonary hypertension (group 1) and 23 patients with normal pulmonary artery pressure (group 2). As a control group, 59 normal subjects were studied (group 3). Patients in group 1 had higher tricuspid peak A velocity, lower tricuspid E velocity, longer isovolumetric relaxation time, higher mitral A wave, lower mitral E wave, and slower color propagation velocity than groups 2 and 3. There was no significant difference between left ventricular diastolic filling parameters between groups 2 and 3. Patients with COPD and pulmonary hypertension have left and right ventricular diastolic dysfunction. However, patients with COPD and normal pulmonary artery pressure have normal left and right ventricular diastolic function.     

Airway response to acute mechanical stress in a human bronchial model of stretch

Introduction  

Lung inflation may have deleterious effects on the alveoli during mechanical ventilation. However, the consequences of stretch during excessive lung inflation on basal tone and responsiveness of human bronchi are unknown. This study was undertaken to devise an experimental model of acute mechanical stretch in isolated human bronchi and to investigate its effect on airway tone and responsiveness.     

Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension

Introduction

The use of low-dose dobutamine to maintain hemodynamic stability in pulmonary hypertension may have a detrimental effect on gas exchange. The aim of this study was to investigate whether inhaled nitric oxide (INO), dobutamine and a combination of the two have beneficial effects in patients with end-stage airway lung disease and pulmonary hypertension.

Method

Hemodynamic evaluation was assessed 10 min after the administration of each drug and of their combination, in 28 candidates for lung transplantation.

Results

Administration of INO caused a reduction in mean pulmonary arterial pressure (MPAP), an increase in PaO₂ with a significant reduction in venous admixture effect (Q _s/Q _t).Dobutamine administration caused an increase in cardiac index and MPAP, with a decrease in PaO₂ as a result of a higher Q_s/Q_t. Administration of a combination of the two drugs caused an increase in the cardiac index without MPAP modification and an increase in PaO₂ and Q _s/Q _t.

Conclusion

Dobutamine and INO have complementary effects on pulmonary circulation. Their association may be beneficial in the treatment of patients with mild to moderate pulmonary hypertension.