Impaired Ventricular Performance Research Articles

Mitral Transcatheter Edge-to-Edge Repair and Clinical Value of Novel Echocardiographic Biomarkers: A Hypothesis-Generating Study.

Longitudinal data on reverse cardiac remodeling and outcomes after transcatheter edge-to-edge repair (TEER) are limited. A total of 78 patients with severe mitral regurgitation (MR) were included retrospectively. All patients had echocardiography at baseline and again six months after TEER. They were monitored for a primary composite endpoint, consisting of heart failure hospitalization and cardiovascular death, over 13 months. Significant decreases in the left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and the left atrial reservoir were observed after TEER. Additionally, there was a decrease in the pulmonary artery systolic pressure and an increase in the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. A post-TEER TAPSE/PASP ratio of <0.47 (HR: 4.76, p-value = 0.039), and a post-TEER left atrial reservoir of <9.0% (HR: 2.77, p-value = 0.047) were associated with the primary endpoint. Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricle and pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up. The prognostic significance of LA strain and the TAPSE/PASP ratio should be validated in subsequent large-scale prospective studies.

Comparison of methods for delivering cardiac resynchronization therapy: electrical treatment targets and mechanisms of action

ABSTRACT Introduction Cardiac resynchronization therapy (CRT) has been developed as a treatment for patients with conduction system dysfunction and impairment of ventricular performance. The aim is to restore more physiological cardiac activation and thereby improve cardiac function, symptoms, and outcomes. Areas covered In this review, we discuss potential electrical treatment targets for patients with heart failure and how these electrical treatment targets may determine the optimal pacing approach for delivering CRT. Expert Opinion The most well-established method for delivering CRT is biventricular pacing (BVP). BVP improves symptoms and reduces mortality in patients with left bundle branch block (LBBB). However, patients continue to suffer from heart failure symptoms and decompensations despite receiving BVP. There may be scope to deliver more effective CRT since BVP does not restore physiological ventricular activation. Furthermore, the results with BVP in patients with non-LBBB conduction system disease have been generally disappointing. Alternative pacing approaches to BVP are now available, including conduction system pacing and left ventricular endocardial pacing. These newer pacing approaches offer exciting potential to not only offer an alternative to coronary sinus lead implantation in the case of implant failure but to potentially deliver more effective treatment in LBBB and maybe even extend the indications for CRT beyond LBBB.

Ventricular function and biomarkers in relation to repair and pulmonary valve replacement for tetralogy of Fallot

ObjectiveCardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for...

Regional right ventricular longitudinal systolic strain for detection of severely impaired right ventricular performance in pulmonary hypertension.

Right ventricular (RV) function is identified as a key determinant of the outcome in patients with pulmonary hypertension (PH). Several studies have assessed the role of peak global longitudinal RV strain in PH patients; however, less emphasis was given to the RV regional longitudinal strain. The aim of this study was to evaluate the regional RV systolic strain in PH patients and investigate the relationship of these parameters with the severity of PH. RV regional longitudinal peak systolic strain (LPSS) and strain rate (LPSSR) were measured using speckle tracking echocardiography on 100 patients with PH who underwent right heart catheterization, and 29 control subjects. Severe PH was identified by a decreased cardiac index (CI) (<2.0L/min/m2 ). LPSS and LPSSR of the RV free wall were significantly lower in PH patients than control subjects, especially when comparing the basal and mid regions (P<.001). When comparing severe PH and nonsevere PH, basal and mid LPSS and LPSSR were significantly lower (P<.001). RV free wall mid LPSSR correlated with CI (r=-.703, P<.001). In the multiple logistic regression analysis, mid LPSSR was identified as an independent predictor of severe PH (odds ratio 1.82; 95% confidential interval 1.39-2.40; P<.001). In the receiver operating characteristics curve analysis, a cutoff value of mid LPSSR of -0.92s-1 predicted severe PH, with a sensitivity and specificity of 75.0% and 93.7%, respectively (AUC=0.889, P<.001). RV free wall mid longitudinal peak systolic strain rate may be useful for the detection of severely impaired RV performance in PH.

Role of the Ghanaian Clinical Pharmacist in Providing Evidence-based Pharmacotherapy for Heart Failure Patients: The Way Forward

<i>Background</i>: Heart failure is extensively characterized as a disorder arising from a complex interaction between impaired ventricular performance and neurohormonal activation. In order to achieve optimal therapeutic outcomes, all heart failure patients must be managed by a multidisciplinary team of healthcare providers, using evidence-based Pharmacotherapy. <i>Purpose</i>: The aim of this article is to assess the clinical role of the Ghanaian Pharmacists in optimizing Pharmacotherapy for heart failure patients based on internationally established clinical roles of Pharmacists. <i>Methods</i>: A literature search was conducted via google scholar using the “search engine” terms: Pharmacist, Clinical Role, Heart failure to look for all studies published in English. The search revealed a total of 98 studies. Only the studies that discussed the role of the clinical Pharmacists specific to heart failure or generally for patients with cardiovascular diseases were included; All other studies were excluded. A Total of 54 studies were used for data analysis. Clinical Pharmacists who are somehow involved in the management of heart failure patients were interviewed to ascertain their roles as members of a multidisciplinary team and their responses documented. <i>Conclusions</i>: A Multidisciplinary team approach including a Clinical Pharmacists with expertise in cardiovascular therapeutics, is required in the management of heart failure patients in order to improve therapeutic outcomes. The current clinical role of the Ghanaian Pharmacist in the management of heart failure patients is substandard.

Impaired Right Ventricular Performance Is Associated with Adverse Outcome after Hypoxic Ischemic Encephalopathy.

Rationale: Asphyxiated neonates with hypoxic ischemic encephalopathy (HIE) are at risk of myocardial dysfunction; however, echocardiography studies are limited and little is known about the relationship between hemodynamics and brain injury.Objectives: To analyze the association between severity of myocardial dysfunction and adverse outcome as defined by the composite of death and/or abnormal magnetic resonance imaging.Methods: Neonates with HIE undergoing therapeutic hypothermia were enrolled. Participants underwent echocardiography at 24 hours, 72 hours (before rewarming), and 96 hours (after rewarming). Cerebral hemodynamics were monitored by near-infrared spectroscopy and middle cerebral artery Doppler.Measurements and Main Results: Fifty-three patients with a mean gestation and birthweight of 38.8 ± 2.0 weeks and 3.33 ± 0.6 kg, respectively, were recruited. Thirteen patients (25%) had mild encephalopathy, 27 (50%) had moderate encephalopathy, and 13 (25%) had severe encephalopathy. Eighteen patients (34%) had an adverse outcome. Severity of cardiovascular illness (P < 0.001) and severity of neurologic insult (P = 0.02) were higher in neonates with adverse outcome. Right ventricle (RV) systolic performance at 24 hours was substantially lower than published normative data in all groups. At 24 hours, lower tricuspid annular plane systolic excursion (P = 0.004) and RV fractional area change (P < 0.001), but not pulmonary hypertension, were independently associated with adverse outcome on logistic regression. High brain regional oxygen saturation (P = 0.007) and low middle cerebral artery resistive index (P = 0.04) were associated with RV dysfunction on post hoc analysis.Conclusions: RV dysfunction is associated with the risk of adverse outcome in asphyxiated patients with HIE undergoing hypothermia. Echocardiography may be a valuable diagnostic and prognostic tool in this vulnerable population.

Right Ventricular Systolic Performance Determined by 2D Speckle-Tracking Echocardiography and Acute Kidney Injury After Cardiac Surgery

An association between central venous pressure and acute kidney injury (AKI) has been observed following cardiac surgery, but it is unknown whether this reflects intravascular volume status or impaired right ventricular (RV) myocardial performance. This study was performed to test the hypothesis that decreased RV peak longitudinal strain (PLSS), as measured by 2-dimensional speckle-tracking echocardiography, is associated with AKI following cardiac surgery. Retrospective observational cohort study. Cardiovascular intensive care unit in a 576-bed referral hospital. Adult patients having undergone cardiac surgery in whom a transthoracic echocardiogram (TTE) was performed within 48hours after chest closure. This was a retrospective study. Urine output and serum creatinine values were recorded at baseline and for 48hours after surgery. Statistical analysis was performed to identify differences in baseline demographic and echo-derived values between patients with and without postoperative AKI criteria. One hundred ninety-nine subjects had postprocessing of TTE performed. AKI was observed in 87% of patients (173 of 199). Age, body mass index, and preoperative serum creatinine were higher in the AKI group. The mean PLSS was -17.2% ± 4.3% versus -17.1% ± 3.7% in patients with AKI versus those without (p = 0.95). The calculated RV systolic pressure was elevated in the AKI group compared to the non-AKI group (38.9 ± 9.9 v 34.6 ± 7.9 mmHg, p = 0.02). In this cohort of cardiac surgery patients, speckle-tracking analysis of RV myocardial performance was feasible. Elevated RV systolic pressure associated with AKI, while speckle tracking-derived echocardiography measurements did not.

NYHA Functional Class and ASE Diagnosis Effects on Echo Variables and Cardiac Time Intervals with an Acoustic Array Approach

Introduction Clinical HF is most commonly described by TTE analysis of LVEF and criteria for diastolic impairment elaborated by the American Society of Echocardiography (ASE) standard of 2016. However, a binary classification of HFrEF vs. HFpEF can oversimplify the complexity of impaired ventricular performance. CTIs are sensitive, integrated markers of cardiac hemodynamics, and have previously been demonstrated to contain prognostic information equivalent to the echo parameters in various populations. HEMOTAG is the first device to derive hemodynamics wirelessly via any smartphone using cardiac vibrations and an ECG signal transduced via multiple anterior chest wall electrodes. The purpose of this study was to assess the extent to which CTIs from echo and HEMOTAG are related to NYHA functional class and ASE diastolic impairment criteria. Methods Within a 4 months period 136 consecutive patients undergoing TTE were recruited at an outpatient office. CTIs by HEMOTAG and Echo along with TTE report and cardiologist report were recorded. Of those (136), 60 patients had HF with recognized NYHA Class as determined by treating cardiologist and echo data for ASE criteria of diastolic dysfunction. Data were analyzed using MATLAB 2014a. Results Table 1 shows number of patients in three diastolic function groups plus a HFrEF group vs. NYHA Class. Fisher's exact test for independence between row and column factors produced p = 0.015, indicating that the number of patients in each heart failure group varied by NYHA Class. 2-way ANOVAs for each echo variable (TRmaxPG, E/e’, E, e’, E/A, LAVI) indicated that echo variables were sensitive to ASE criteria but not NYHA Class, while CTIs of AO (QRS to Aortic opening) and STR (AO/ET= QRS to Aortic opening /Aortic opening to Aortic closing) were sensitive to the interaction of NYHA Class and diagnosis. The results indicate that CTIs offer a unique perspective on the relationship between heart failure signs and symptoms and diagnosis. Conclusions Analysis of echo criteria for diastolic dysfunction indicated that echo variables varied by diagnosis but not NYHA Class. That is, the distribution of each echo variable for patients with no symptoms was not different from patients with severe symptoms. However, CTIs of AO and STR from Echo and HEMOTAG successfully demonstrated relationship between HF signs and symptoms and ASE diagnosis. Thus, CTIs may be a valuable tool to discriminate NYHA class better than echo measures of diastolic dysfunction. Larger studies are needed to further validate these findings.

GW28-e0058 Cardiac Mechanics in Children post Percutaneous Transcatheter Closure of Perimembranous Ventricular Septal Defect: Right and Left Ventricular Performance assessed by echocardiography

Percutaneous transcatheter closure of perimembranous ventricular septal defect (pmVSD) with occluder has been most widely used in China. Complications were most focused on aortic insufficiency, complete heart block, and etc. However, whether impaired ventricular performance occurs in pediatric

Decreased biventricular longitudinal strain shortly after congenital heart defect surgery.

Impaired ventricular performance in patients who underwent surgery for congenital heart defect (CHD) may ultimately result in clinical heart failure. It is therefore important to regularly evaluate the left ventricular (LV) and right ventricular (RV) performance. We evaluated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) before and after surgical correction of a CHD. Patients with CHD undergoing biventricular corrective surgery were included in this retrospective study. In addition, a group of healthy controls was included. The performance of LV, RV and interventricular septum (IVS) was assessed using mitral inflow velocities, TDI peak systolic (S'), peak early (E') and peak late (A') diastolic velocity. LV and RV global longitudinal strain (GLS) were assessed using STE. Measurements were performed preoperatively and at discharge. A total of 204 patients and 78 controls were included. All TDI measurements were significantly decreased after surgery. Nonetheless, LV S' and A' were still within normal limits. LV and RV GLS were significantly reduced after surgery and significantly lower compared to controls. A longer aortic cross-clamp time and cardiopulmonary bypass (CPB) time were associated with significantly lower TDI and strain parameters in the RV and IVS, but not in the LV. TDI and STE results generally imply a significantly lower ventricular performance in patients with CHD postoperatively. Furthermore, a negative correlation was observed between aortic cross-clamping and CPB time and several RV performance parameters. As this association was not observed in the LV, this could implicate less vulnerability of the LV to cardiopulmonary bypass.

INTERDEPENDENCE OF RIGHT VENTRICULAR SYSTOLIC FUNCTION AND LEFT VENTRICULAR FILLING AND ITS ASSOCIATION WITH OUTCOME FOR PATIENTS WITH PULMONARY HYPERTENSION

Although impaired right ventricular (RV) performance has been associated with adverse outcomes for pulmonary hypertension (PH) patients, the relationship between bi-ventricular interdependence and outcomes is not fully understood. We studied 96 PH patients. RV systolic function was assessed by RV

Interdependence of right ventricular systolic function and left ventricular filling and its association with outcome for patients with pulmonary hypertension.

Although impaired right ventricular (RV) performance has been associated with adverse outcomes for pulmonary hypertension (PH) patients, the relationship between bi-ventricular interdependence and outcomes is not yet fully understood. We studied 96 PH patients. RV systolic function was assessed by means of RV free-wall longitudinal speckle-tracking strain (RV-free), and left ventricular (LV) filling as early diastolic transmitral flow velocity (TMF-E). RV-free≤19% and TMF-E<60cm/s were adopted as pre-defined cut-offs for RV systolic dysfunction and LV under-filling, respectively, associated with worse outcomes. Long-term outcome was tracked over 2.2years. RV-free correlated significantly with TMF-E (r=0.57, p<0.001).TMF-E and RV-free were significantly lower in patients with than in those without cardiac events. RV systolic dysfunction and LV under-filling was observed in 35 patients. These features were associated with worse long-term survival compared to other sub-groups (log-rank p=0.012). A sequential Cox model based on clinical variables including world health organization functional class IV and brain natriuretic peptide >150pg/dl (χ(2)=1.2) was improved by the addition of RV-free (χ(2)=5.5, p=0.04) as well as of TMF-E (χ(2)=11.5, p=0.01). In conclusions, RV systolic function was shown to correlate significantly with LV filling in PH patients. In addition, not only assessment of RV systolic function, but also of a combined bi-ventricular parameter comprising RV systolic function and LV filling may well have clinical implications for more successful management of PH patients.

A Decision Support System for the Treatment of Patients with Ventricular Assist Device Support

Heart failure (HF) is affecting millions of people every year and it is characterized by impaired ventricular performance, exercise intolerance and shortened life expectancy. Despite significant advancements in drug therapy, mortality of the disease remains excessively high, as heart transplant remains the gold standard treatment for end-stage HF when no contraindications subsist. Traditionally, implanted Ventricular Assist Devices (VADs) have been employed in order to provide circulatory support to patients who cannot survive the waiting time to transplantation, reducing the workload imposed on the heart. In many cases that process could recover its contractility performance. The SensorART platform focuses on the management and remote treatment of patients suffering from HF. It provides an interoperable, extendable and VAD-independent solution, which incorporates various hardware and software components in a holistic approach, in order to improve the quality of the patients' treatment and the workflow of the specialists. This paper focuses on the description and analysis of Specialist's Decision Support System (SDSS), an innovative component of the SensorART platform. The SDSS is a Web-based tool that assists specialists on designing the therapy plan for their patients before and after VAD implantation, analyzing patients' data, extracting new knowledge, and making informative decisions. SDSS offers support to medical and VAD experts through the different phases of VAD therapy, incorporating several tools covering all related fields; Statistics, Association Rules, Monitoring, Treatment, Weaning, Speed and Suction Detection. SDSS and its modules have been tested in a number of patients and the results are encouraging.

Ventricular Performance After Surgery for a Congenital Heart Defect as Assessed Using Advanced Echocardiography: From Doppler Flow to 3D Echocardiography and Speckle-Tracking Strain Imaging

A varying degree of impairment of ventricular performance is observed over the long-term after surgery for a congenital heart defect (CHD). Impaired ventricular performance has been shown to be of prognostic value for increased risk of cardiovascular events in adult CHD patients. This emphasizes the importance of delineating the timing and cause of this postoperative impairment. Impairment of ventricular performance could develop over time as a consequence of residua, sequelae and complications of the CHD or surgical procedure. Yet, impaired ventricular performance has also been observed immediately after surgery and can persist and/or worsen over time. This postoperative impairment of ventricular performance is the focus of this review. This article provides an overview of echocardiographic techniques currently used to assess ventricular performance. Furthermore, we review current literature describing ventricular performance, as assessed using echocardiography, after correction of a CHD. In general, a decrease in ventricular performance is observed directly after surgery for CHD’s. Subsequent follow-up of ventricular performance is characterized by a varying degree of postoperative recovery. A consistent observation is the persistent impairment of right-ventricular performance after repair in several different subgroups of CHD patients ranging from ventricular septal defect repair to surgery for Tetralogy of Fallot.

A simple method to predict impaired right ventricular performance and disease severity in chronic pulmonary hypertension using strain rate imaging

The evaluation of right ventricular (RV) function is clinically important in pulmonary hypertension (PH) because of prognostic implications. Conventional echocardiography has been used to predict adverse outcomes in chronic PH, but there were certain limitations arising from the complexity of RV anatomy. We used strain rate imaging (SRI) to evaluate RV function in PH patients. Study population consisted of 50 patients (mean age 46 ± 13 years; 39 females) with chronic PH who underwent echocardiography including SRI within 24h of right heart catheterization. Mean value of peak systolic longitudinal strain obtained from basal and mid RV free wall were calculated. Reduced RV systolic contraction (fractional area change <32%) and cardiac index (CI) <2.0 L/min/m(2) were defined as impaired RV performance. Pulmonary vascular resistance (PVR) averaged 1195 ± 522 dyn · s · cm(-5). RV strain correlated closely with pulmonary artery systolic pressure (r = 0.53; p < 0.001) and PVR (r = 0.68; p < 0.001). RV strain best correlated with CI (r = -0.70; p < 0.001) among the invasive variables. After adjusting for various parameters that could influence the CI, this correlation remained robust (r = -0.63, p < 0.001). In a multivariate model, RV strain (odds ratio 1.65; 95% confidential interval 1.06-2.57; p = 0.028) was independently associated with impairment of RV performance. A cutoff value of -15.5% discriminated cases of impaired RV performance from those of preserved RV performance with a sensitivity of 100%, specificity of 84% and accuracy of 92%. RV strain correlates well with hemodynamic variables indicative of disease severity and help identify the cases of impaired RV performance in PH patients.

Heart Failure in Children

Why is heart failure in children important? If we just consider the number of individuals affected, adult heart failure is clearly a more compelling public health problem. However, the relatively small numbers belie the overall economic and social impact of pediatric heart failure. When a child is admitted to the hospital for heart failure, the costs are considerably higher for children than adults because of the frequent need for surgical or catheter-based intervention. The demands of medical care can fray the family structure and adversely affect parental economic productivity. When a child dies of heart failure, the economic impact is magnified enormously because of the number of potentially productive years lost per death. For these and other reasons, heart failure in children is a serious public health concern. In addition, growing numbers of children with heart failure are reaching adulthood because of the successful application of medical and surgical heart failure therapies and the improved outcomes of congenital heart surgery. A greater understanding of the pathophysiology of heart failure in childhood may help inform therapeutic strategies once these children become adults. Furthermore, given the recent explosion of research in the impact of cardiac development and cardiogenetics on pediatric cardiovascular disease, it is not outside the realm of possibility for a pediatric discovery to be made that will also benefit adults with heart failure. We may not yet be able to agree on a definition of heart failure, but the cardinal symptoms, dyspnea, anasarca (“dropsy”), and cachexia, were well recognized in antiquity.1 These symptoms were not specific for cardiac pathology, and it was not until the 17th century, when William Harvey definitively identified the heart as an organ that pumped blood rather than generating heat, that the heart could begin to be understood as a source of dyspnea, edema, and …

Heart failure: pathophysiology, risk assessment, community management and anaesthesia

Heart failure is a complex clinical syndrome caused by impaired ventricular performance. It is the final common pathway for a variety of cardiovascular disease processes, leading to potentially disabling symptoms and shortened life expectancy. Heart failure is common; currently, 1% of the population aged 50–59 yr, and 10% of those over 80 yr, have heart failure. Heart failure is the only major cardiovascular condition that is increasing in prevalence, because of an ageing population and improved survival from other cardiovascular diseases. Therefore, increasing numbers of patients with established heart failure will present for surgery. A diagnosis of heart failure has serious implications. If the underlying cause cannot be rectified, heart failure alone has a 50% 4 yr-mortality, and 50% of patients with severe heart failure (those who are symptomatic and require frequent medical attention) will die within 1 yr of diagnosis. Decompensated heart failure is a major clinical predictor of perioperative risk. If heart failure is present at the time of major vascular surgery, the risk of cardiac death is 12 times higher than in patients without heart failure. This article will describe the pathophysiology, diagnosis and anaesthetic implications of heart failure in the setting of non-cardiac surgery.

Local Activation or Implantation of Cardiac Progenitor Cells Rescues Scarred Infarcted Myocardium Improving Cardiac Function

Ischemic heart disease is characterized chronically by a healed infarct, foci of myocardial scarring, cavitary dilation, and impaired ventricular performance. These alterations can only be reversed by replacement of scarred tissue with functionally competent myocardium. We tested whether cardiac progenitor cells (CPCs) implanted in proximity of healed infarcts or resident CPCs stimulated locally by hepatocyte growth factor and insulin-like growth factor-1 invade the scarred myocardium and generate myocytes and coronary vessels improving the hemodynamics of the infarcted heart. Hepatocyte growth factor is a powerful chemoattractant of CPCs, and insulin-like growth factor-1 promotes their proliferation and survival. Injection of CPCs or growth factors led to the replacement of approximately 42% of the scar with newly formed myocardium, attenuated ventricular dilation and prevented the chronic decline in function of the infarcted heart. Cardiac repair was mediated by the ability of CPCs to synthesize matrix metalloproteinases that degraded collagen proteins, forming tunnels within the fibrotic tissue during their migration across the scarred myocardium. New myocytes had a 2n karyotype and possessed 2 sex chromosomes, excluding cell fusion. Clinically, CPCs represent an ideal candidate cell for cardiac repair in patients with chronic heart failure. CPCs may be isolated from myocardial biopsies and, following their expansion in vitro, administered back to the same patients avoiding the adverse effects associated with the use of nonautologous cells. Alternatively, growth factors may be delivered locally to stimulate resident CPCs and promote myocardial regeneration. These forms of treatments could be repeated over time to reduce progressively tissue scarring and expand the working myocardium.

Acute vasodilator effects of Rho-kinase inhibitors in neonatal rats with pulmonary hypertension unresponsive to nitric oxide

Pulmonary hypertension (PHT) in neonates is often refractory to the current best therapy, inhaled nitric oxide (NO). The utility of a new class of pulmonary vasodilators, Rho-kinase (ROCK) inhibitors, has not been examined in neonatal animals. Our objective was to examine the activity and expression of RhoA/ROCK in normal and injured pulmonary arteries and to determine the short-term pulmonary hemodynamic (assessed by pulse wave Doppler) effects of ROCK inhibitors (15 mg/kg ip Y-27632 or 30 mg/kg ip fasudil) in two neonatal rat models of chronic PHT with pulmonary vascular remodeling (chronic hypoxia, 0.13 Fi(O(2)), or 1 mg.kg(-1).day(-1) ip chronic bleomycin for 14 days from birth). Activity of the RhoA/ROCK pathway and ROCK expression were increased in hypoxia- and bleomycin-induced PHT. In both models, severe PHT [characterized by raised pulmonary vascular resistance (PVR) and impaired right ventricular (RV) performance] did not respond acutely to inhaled NO (20 ppm for 15 min) or to a single bolus of a NO donor, 3-morpholinosydnonimine hydrochloride (SIN-1; 2 mug/kg ip). In contrast, a single intraperitoneal bolus of either ROCK inhibitor (Y-27632 or fasudil) completely normalized PVR but had no acute effect on RV performance. ROCK-mediated vasoconstriction appears to play a key role in chronic PHT in our two neonatal rat models. Inhibitors of ROCK have potential as a testable therapy in neonates with PHT that is refractory to NO.

Role of platelet activating factor in pathogenesis of acute respiratory distress syndrome

Role of platelet activating factor in pathogenesis of acute respiratory distress syndrome