Reduction In PVR Research Articles

Pulmonary Artery Denervation Significantly Increases 6-Minute Walk Distance for Patients with Pulmonary Hypertension Associated with Left-Side Heart Failure: A Prospective, Randomized, and Sham-Controlled PADN-5 Study

Background: Heart failure (HF) is associated with sympathetic overactivation. Combined pre-capillary and post-capillary pulmonary hypertension (CpcPH) bears the same pathology as pulmonary arterial hypertension (PAH). Benefits of targeted-PAH medications for CpcPH patients are unknown. Pulmonary artery denervation (PADN), which showed benefit for both PAH and PH patients in a previous consecutive registry study, has not been studied in CpcPH patients using a randomized design. We therefore sought to assess the benefits of PADN for CpcPH patients. Methods: Of 865 patients with HF who were stable for ≥ 3 months and were admitted due to recent worsening of symptoms were enrolled, 387 patients after at least 3 days of treatment had a systolic pulmonary arterial pressure (PAP) ≥ 45 mmHg measured by echocardiography. Among them, 98 CpcPH patients (mean PAP≥25 mmHg, pulmonary capillary wedge pressure >15 mmHg, and pulmonary vascular resistance [PVR] > 3·0 Wood units) were randomly assigned to receive sildenafil plus anti-HF medication and sham PADN or PADN plus anti-HF medication without sildenafil. The primary endpoint was an increase in the 6-minute walk distance (6MWD) at the 6-month followup. PVR and clinical worsening were secondary endpoints. Pulmonary embolism was a safety endpoint. Findings: At the 6-month follow-up, the mean increases in the 6MWD were 83 m in the PADN group and 15 m in the sildenafil group ((least square mean difference 66 m, 95% confidence interval= 38·2-98·8; p<0·001). A 1-SD decrease in the 6MWD was strongly correlated with clinical worsening (corresponding hazard ratio [95% confidence interval] =3·02[ 1·05-8·74]; p=0·04). PADN treatment was associated with significant reduction (29·8%) in PVR and lower rate (16·7%) of clinical worsening, compared with 3·4% (hazard ratio [95% confidence interval] =4·73 [2·05-10·89]; p<0·001) and 40% (hazard ratio [95% confidence interval] =3·33 [1·29-8·59]; p=0·014) in the sildenafil group. At the end of the study, there were 7 all-cause deaths (5 in the sildenafil and 2 in the PADN group) and 2 embolisms (1 in each group). Interpretation: PADN is associated with significant improvements in hemodynamic parameters, cardiac function, and clinical outcomes, when compared with those after 6-month sildenafil treatment. Further studies are warranted to confirm the reduction of CpcPH-related events by PADN. Clinical Trial Number: Registration at clinicaltrials.com; identifier: NCT02220335 Funding Statement: National Science Foundation of China (NSFC 91639303 and NSFC 81770441). Declaration of Interests: CSL is the inventor of PADN patent, but not the owner. The remaining authors have nothing to disclosure. Ethics Approval Statement: The PADN-5 trial is a 4-center, randomized, and sham-controlled clinical trial, which was approved by the ethics committee at each participating center. All patients provided written informed consent. Sponsors had no access to the trial data and no role in the design, conduct, or reporting of the results. Clinical events were adjudicated by an independent committee.

Combined prostatic urethral lift and remodeling of the prostate and bladder neck: a modified transurethral approach in the treatment of symptomatic lower urinary tract obstruction.

The aim of the study was to evaluate the feasibility and safety of combining prostatic urethral lift (PUL) and a limited resection of the prostatic middle lobe or bladder neck incision in the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Twenty-eight patients were treated at two tertiary centers and followed prospectively. Patient evaluations included patient characteristics, relief of LUTS symptoms, erectile and ejaculatory function, continence, operative time and adverse events. Patients were followed for a mean of 10.9months. Patient characteristics were as follows: age 66years (46-85), prostate volume 39.6cc (22-66), preoperative IPSS/AUASI 20 (6-35)/QoL 3.9 (1-6)/peak flow 10.5mL/s (4.0-19)/post-void residual volume (PVR) 123mL (0-500). Mean operating time was 31min (9-55). Postoperative complications were minor except for the surgical retreatment of one patient for blood clot retention (Clavien 3b). One patient required catheterization due to urinary retention. Reduction of symptoms (IPSS -59.6%), increase in QoL (+49.0%), increase in flow (+111.5%), and reduction of PVR (-66.8%) were significant. Antegrade ejaculation was always maintained. Our data suggest that a combination of PUL and transurethral surgical techniques is feasible, safe, and effective. This approach may be offered to patients with moderate size prostates including those with unfavorable anatomic conditions for PUL. This procedure is still 'minimally invasive' and preserves sexual function. In addition, it may add to a higher functional efficacy compared to PUL alone. DRKS00008970.

Prostatic artery embolization versus transurethral resection of the prostate in the treatment of benign prostatic hyperplasia: protocol for a non-inferiority clinical trial.

BackgroundBenign prostatic hyperplasia (BPH) is a prevalent disease associated with lower urinary tract symptoms (LUTS). The standard of care for moderate-to-severe LUTS unresponsive to pharmacological treatment is the transurethral resection of the prostate (TURP). However, this intervention is not exempt from complications. Prostatic artery embolization (PAE) has been described as a new, effective and safe procedure for the treatment of LUTS secondary to BPH. To date, only one clinical trial has been published on the use of PAE for LUTS, but the study was methodologically flawed in terms of safety monitoring. Therefore, well-designed clinical studies are required to compare the efficacy and safety of both techniques in the treatment of LUTS secondary to BPH.Methods and designThis was a prospective, randomized, non-inferiority clinical trial comparing efficacy and safety of PAE and TURP in the treatment of BPH-related LUTS. A total of 60 patients diagnosed with BPH with obstructive moderate or severe LUTS refractory to medical therapy and candidates for TURP were randomized to either PAE or TURP. The presence and severity of LUTS were assessed using the validated Spanish version of the International Prostate Symptom Score (IPSS). Primary end points included improvement in maximum urinary flow rate (Qmax) as measured at baseline and 1 year after the intervention. Improvement in IPSS as measured at baseline and after the intervention, reduction in prostate volume, no deterioration or improvement of sexual function (International Index of Erectile Function [IIEF]), reduction in PSA and PVR, satisfaction of the patient with the operation and adverse events occurring during the study were secondary outcome measures.DiscussionThe aim of this clinical study was to investigate whether PAE is a valid therapeutic option for LUTS that is not inferior to TURP in terms of efficacy and safety. This study also helped to define the profile of candidates for PAE and analyzed the benefits and complications associated with this new technique.

Changing the strategy of balloon pulmonary angioplasty resulted in a reduced complication rate in patients with chronic thromboembolic pulmonary hypertension. A single-centre European experience.

To assess the safety and efficacy of a refined balloon pulmonary angioplasty (BPA) strategy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). There were 157 BPA sessions performed in 56 CTEPH patients (47 non-operable, nine after pulmonary endarterectomy; aged 58.6 ± 17.9 years; 28 females) with severely impaired pulmonary haemodynamics (mean pulmonary artery pressure [mPAP]: 51.3 ± 12.2 mm Hg, pulmonary vascular resistance [PVR]: 10.1 ± 3.9 Wood Units). The first 50 sessions aimed to recanalise chronic occlusions and prevent reocclusion with aggressive anticoagulation. The next 107 sessions aimed to relieve "web" and "ring" lesions using reduced tip load guidewires and less intensive anticoagulation. There was significant reduction in haemoptysis (22% vs. 7%, p = 0.01), vessel injury (30% vs. 13%, p = 0.01), and reperfusion pulmonary injuries (22% vs. 4%, p = 0.01) after changing the BPA strategy. Mortality at 14 days was also reduced (6% vs. 0%; p = 0.05). The cumulative survival rate was 94.6% at 24 months after the first BPA, which was more favourable than medically treated historic controls. In the 31 patients with > 3 BPA sessions, there was significant reduction of PVR (10.3 ± 3.7 vs. 5.9 ± 2.8 Wood Units; p = 0.01), mPAP (50.7 ± 10.8 vs. 35.6 ± 9.3 mm Hg; p = 0.01) and improvement in World Health Organisation functional class (3.19 ± 0.48 vs. 1.97 ± 0.80; p < 0.001). Balloon pulmonary angioplasty improves haemodynamics and outcome but requires refined strategy to limit early complication rate.

Beta-3 adrenergic agonists reduce pulmonary vascular resistance and improve right ventricular performance in a porcine model of chronic pulmonary hypertension.

Beta-3 adrenergic receptor (β3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of β3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of β3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of β3AR mRNA and the vasodilator response of β3AR agonists in pulmonary arteries. Single intravenous administration of the β3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different β3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of −2.0 Wood units/m2 for BRL37344 vs. +1.5 for vehicle, p = 0.04; and −1.8 Wood units/m2 for mirabegron vs. +1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in β3AR agonists-treated pigs. β3AR was expressed in human pulmonary arteries and β3AR agonists produced vasodilatation. β3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH.

Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH.

The aim of this systematic review is to determine the comparative effectiveness and safety of phosphodiesterase 5 inhibitors (PDE5-Is) and α-blockers used alone or combined for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). An electronic search of PubMed, Cochrane Library and Embase up to January 2014 was performed to identify randomized controlled trials comparing the efficacy and safety of PDE5-Is and α-blockers for treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, which assessed IPSS score, maximum flow rate, postvoided residual urine, quality of life and Erectile Function (IIEF) score as outcomes. Data were analyzed by fixed or random effect models using Cochrane Collaboration review manager software. A total of 12 studies were included. Our novel data demonstrated that there was a trend that α-blockers were more efficacious than PDE5-Is on decreasing IPSS score and increasing maximum flow rate. α-blockers were significantly more effective than PDE5-Is on reduction of postvoided residual urine with a mean difference of 3.67 (95% CI 1.56 to 5.77, P = 0.0006) and PDE5-Is showed greater effect than α-blockers on increasing IIEF score with a mean difference of 9.82 (95% CI 3.80 to 15.85, P = 0.001). In conclusion, our novel data demonstrated that PDE5-Is plus ABs ranked the highest on the improvement of LUTS/BPH. PDE5-Is monotherapy was also effective in this kind of disorder except less reduction of PVR than ABs. In addition, both combined- or mono-therapy were safe.

(757) - Hemodynamic Correlates and Prognostic Implication of Vasodilator Response in Reactive Pulmonary Hypertension Due To Left Heart Disease (PHLHD)

To study the hemodynamic correlates and prognostic implication of response to sodium nitroprusside (SNP) infusion. We included 64 consecutive patients with confirmed reactive PHLHD on catheterisation who were hospitalized for management of advanced heart failure (HF). SNP infusion was titrated to achieve a PVR reduction of >20%. SNP was stopped if mean blood pressure 20% with an unchanged/increased stroke volume. Endpoint was a composite of death, transplantation or ventricular assist device (VAD) as bridge to transplantation. Of the 64 patients [TABLE], 34 patients responded to SNP. Percentage change in PVR (r=-0.390) and pulmonary capacitance (r=-0.527) correlated with baseline PVR/systemic vascular resistance (SVR) ratio (both p<0.01). SNP infusion improved pulmonary hemodynamics [TABLE], lowered PVR/SVR ratio and resulted in greater increase in pulmonary capacitance (41% (27-52) vs 16% (9-27), p<0.01) in responders compared to non-responders. PVR/SVR ratio was independently associated with SNP response on multivariate analysis (p<0.01). Response to SNP was associated with lower composite endpoints - 8/34 vs 16/28 endpoints in responders and non-responders respectively [FIGURE] (p<0.01 on Log-rank test) over a median follow-up of 230 (71-421) days. Baseline PVR/SVR ratio is associated with response to SNP. Patients with reactive PHLHD responsive to SNP have a more favourable prognosis.TableResponders (n=34)Non-responders (n=28)pAge (years)50 (5)50 (3)0.946Males (n, %)28 (82)18 (68)0.185Severe MR (n, %)12 (36)14 (50)0.252LVEF (%)18 (3)26 (7)0.026LVESVi (ml/m2)55.9 (5.6)71.5 (20)0.090TAPSE (mm)12.7 (1.1)13.1 (1.7)0.618Peak VO2 (ml/kg/min)10.5 (1.1)10.2 (1.1)0.827stroke volume (ml)43.3 (4.2)48.6 (6.5)0.152stroke volume post-SNP51.7 (4.6)53.7 (6.5)0.598PVR (dyne.s/cm5)382 (53)498 (164)0.141PVR post-SNP232 (34)437 (161)0.007SVR (dyne.s/cm5)1842 (181)1631 (202)0.119SVR post-SNP1288 (75)1239 (155)0.548PVR/SVR ratio0.21 (0.02)0.28 (0.05)0.002PVR/SVR post-SNP0.18 (0.02)0.32 (0.07)<0.001 Open table in a new tab

Dorsal onlay buccal mucosal graft urethroplasty in female urethral stricture disease: a single-center experience

The aim of this report is to present our initial, short-term experience with dorsal onlay buccal mucosal graft urethroplasty (DBMGU) in women with urethral stricture. Between May 2011 and April 2013, eight women with moderate to severe bothersome lower urinary tract symptoms due to mid- or distal urethral stricture underwent DBMGU. All women were evaluated preoperatively with the American Urological Association (AUA) symptom score, uroflowmetry with post-void residual volume (PVR) estimation, urodynamic study, calibration with 14 F catheter, and voiding cystourethrography. Postoperatively, the women were followed at regular intervals with AUA symptom score, uroflowmetry, and PVR estimation. Increase in AUA symptom score, maximum flow rate (Q(max)) < 12 ml/s, and failure to calibrate with 18 F catheter were considered as recurrence of the disease. The mean age of the patients was 40.6 years. The mean follow-up period was 14.8 months. All women voided successfully after catheter removal. One patient was lost to follow-up after 3 months. There was significant improvement in AUA symptom score and Q(max) and reduction in PVR (p < 0.0001) at 3, 6, and 9 months. Two women had recurrence of stricture at 12 months, while another had recurrence at 18 months which was treated by urethral dilatation followed by a self-dilatation protocol. The limitations of the study include the small number of cases with short follow-up. DBMGU is a simple and safe method of urethroplasty in women with unsatisfactory results. Large size studies with long-term follow-up are desirable to document the success rates.

Diagnosis and treatment of pulmonary hypertension in infancy

Normal pulmonary vascular development in infancy requires maintenance of low pulmonary vascular resistance after birth, and is necessary for normal lung function and growth. The developing lung is subject to multiple genetic, pathological and/or environmental influences that can adversely affect lung adaptation, development, and growth, leading to pulmonary hypertension. New classifications of pulmonary hypertension are beginning to account for these diverse phenotypes, and or pulmonary hypertension in infants due to PPHN, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). The most effective pharmacotherapeutic strategies for infants with PPHN are directed at selective reduction of PVR, and take advantage of a rapidly advancing understanding of the altered signaling pathways in the remodeled vasculature.

Usefulness of Medical Therapy for Pulmonary Hypertension and Delayed Atrial Septal Defect Closure

A subset of adult patients with an open atrial septal defect (ASD) have pulmonary arterial hypertension (PAH). We sought to identify predictors of response to PAH-specific medical therapy in this group. Invasive hemodynamic and clinical parameters from 12 patients with an open ASD and PAH (pulmonary vascular resistance [PVR], 8.8 ± 1.2 Wood units; mean pulmonary artery pressure, 55 ± 6 mm Hg; Qp:Qs ratio, 1.1 ± 0.1; and 6-minute walk test distance of 1,046 ± 116 feet) were analyzed. Responders (n = 5) underwent successful ASD closure at 1.3 ± 0.3 years after initiation of medical therapy and were characterized by >30% reduction in PVR (7.2 ± 1.5 to 4.6 ± 0.9 Wood units) versus <20% in nonresponders (n = 7; 9.9 ± 1.7 to 8.2 ± 1.5 Wood units, p <0.03), increased 6-minute walk test distance (1,087 ± 174 vs 1,405 ± 109 feet, p = 0.05), and higher Qp:Qs ratio after therapy (1.9 ± 0.2 vs 1.1 ± 0.2, p <0.02). Body mass index was a significant clinical predictor of response (23.3 ± 1.9 vs 30.0 ± 2.1 kg/m(2), p <0.05) and the change in arterial saturation with exercise correlated inversely with change in PVR (r = -0.739, p <0.01). In conclusion, medical therapy led to a significant improvement in hemodynamic and clinical parameters in a subset of patients with an open ASD and PAH, who were able to safely undergo delayed ASD closure.

The Human Immunodeficiency Virus Type 1 Nef and Vpu Proteins Downregulate the Natural Killer Cell-Activating Ligand PVR

The human immunodeficiency virus type 1 (HIV-1) evades the immune responses of natural killer (NK) cells through mechanisms that have been partially deciphered. Here we show that in HIV-1-infected T lymphocytes, the early viral Nef protein downmodulates PVR (CD155, Necl-5), a ligand for the activating receptor DNAM-1 (CD226) expressed by all NK cells, CD8(+) T cells, and other cell types. This novel Nef activity is conserved by Nef proteins of laboratory HIV-1 strains (NL4-3, SF2) and of a patient-derived virus, but it is not maintained by HIV-2. Nef uses the same motifs to downregulate PVR and HLA-I molecules, likely by the same mechanisms. Indeed, as previously demonstrated for HLA-I, Nef reduces the total amounts of cell-associated PVR. Optimal downregulation of cell surface PVR by Nef also requires the presence of the late viral factor Vpu. In line with PVR reduction, the NK cell-mediated lysis of T cells infected by a wild-type but not Nef-deficient virus is virtually abrogated upon blocking of both DNAM-1 and another activating receptor, NKG2D, previously shown to mediate killing of HIV-infected cells. Together, these data demonstrate that the PVR downmodulation by Nef and Vpu is a strategy evolved by HIV-1 to prevent NK cell-mediated lysis of infected cells. The PVR downregulation reported here has the potential to affect the immune responses of other DNAM-1-positive cells besides NK cells and to alter multiple PVR-mediated cellular processes, such as adhesion and migration, and may thus greatly influence HIV-1 pathogenesis.

Phosphodiesterase 5 inhibition with sildenafil reverses exercise oscillatory breathing in chronic heart failure: a long‐term cardiopulmonary exercise testing placebo‐controlled study

Exercise oscillatory breathing (EOB) is a ventilatory abnormality that occurs in ∼20% of heart failure (HF) patients and carries a very unfavourable prognosis. Pulmonary vasoconstriction has been suggested to be involved in this disorder. We hypothesized that modulation of pulmonary vascular hypertone by oversignalling of the nitric oxide pathway with phosphodiesterase 5 (PDE5) inhibition might be beneficial. Accordingly, we performed a 1-year pilot trial with sildenafil in patients with HF and EOB. Among 122 HF cases, 32 presented with EOB during cardiopulmonary exercise testing (CPX) and were randomized to receive placebo (n = 16) or sildenafil (n = 16) at the dose of 50 mg three times a day, in addition to their current antifailure treatment. CPX-derived variables and pulmonary haemodynamics were assessed at 6 and 12 months. Sildenafil reversed EOB in 87% of patients at 6 months and 93% at 1 year, respectively (P < 0.01). This effect was accompanied by an improvement in functional performance (peak VO(2); from 9.6 to 12.4 and 13.2 mL/min/kg; P < 0.01) and exercise ventilation efficiency (ventilation to CO(2) production slope; from 41.1 to 32.7 and 31.5; P < 0.01). Chronic treatment with PDE5 inhibition significantly decreased pulmonary capillary wedge pressure (from 21 to 14 and 14 mmHg), mean pulmonary artery pressure (PAP; from 34.8 to 23 and 24 mmHg), and pulmonary vascular resistance (PVR; from 360 to 270 and 266 dyne/s/cm(5)) compared with placebo (P < 0.01 for each comparison). On exploratory analysis, there was a correlation between PAP and PVR and the decrease in EOB in the treatment group. Placebo did not alter any of the aforementioned variables. PDE5 inhibition in HF patients with EOB offers the dual advantage of improving functional capacity and modulating the EOB pattern. PAP and PVR reduction seem to underlie the correction of the breathing disorder. Whether reversal of this unfavourable prognostic signal can affect survival remains unconfirmed at the moment.

NORMAL BLOOD PRESSURE IN OBESITY IS ASSOCIATED WITH REDUCED PERIPHERAL VASCULAR RESISTANCE: 8B.05

Objective: The link between obesity and elevated blood pressure is firmly established. However, not all obese individuals are hypertensive, suggesting that adaptive mechanisms are present in at least some obese individuals which allow them to maintain normal levels of blood pressure (BP). The aim of the current study was to examine the mechanisms underlying different levels of BP in obese individuals. Design and Method: Data from 2511 individuals (1262 males) were available from The Enigma Study for the current analyses. All individuals were aged between 18–40 years, and were free of cardiovascular disease and medication. Detailed demographic, biochemical and haemodynamic data, including BP, cardiac output (CO) and peripheral resistance (PVR) were obtained in all individuals. They were then stratified according to BMI (normal weight, overweight and obese) using WHO criteria, and seated brachial BP (optimal, normal, high-normal and hypertensive) using JNC 6 criteria. For the current analyses, comparisons were made between 3 groups: normal-weight normotensives (controls, optimal and normal BP, n = 1360), obese normotensives (optimal and normal BP, n = 61) and obese hypertensives (n = 79). Results: Compared with controls, obese individuals were older, had an increased family history of hypertension and an adverse biochemical profile (P < 0.01 for all). In addition, heart rate, CO and stroke volume were all significantly elevated in obese individuals (P < 0.001 for all). However, the elevation in CO was more marked in obese individuals who were hypertensive (P < 0.05 versus obese normotensives). In contrast, PVR was significantly lower in obese individuals with normal BP (P < 0.05 versus controls and obese hypertensives). Conclusions: These data suggest that a reduction in peripheral resistance is an important mechanism by which some obese individuals maintain normal blood pressure despite having a significantly elevated cardiac output. Although the factors underlying the reduction in PVR in these individuals remain to be elucidated, they are likely to provide an intriguing insight into the pathophysiology of obesity-related hypertension.

Resuscitation From Hemorrhagic Shock Comparing Standard Hemoglobin-Based Oxygen Carrier (HBOC)-201 Versus 7.5% Hypertonic HBOC-201

Hemoglobin-based oxygen carrier (HBOC) resuscitation has been associated with increased systemic and pulmonary vascular resistances (SVR, PVR), which may result in reduced blood flow and severe pulmonary hypertension. The physiologic and immunologic properties of 7.5% hypertonic saline solution (HTS), such as reduction of SVR and PVR, as well as inhibition of neutrophil and endothelial activation may be beneficial in reducing some of these undesirable effects of HBOCs. The aim of this study was to evaluate the hemodynamic effects of the HBOC and HBOC-201 suspended in 7.5% hypertonic saline solution (HT-HBOC) when compared with standard HBOC resuscitation. Thirty-two domestic crossbred pigs (50-60 kg) were hemorrhaged to a mean arterial pressure (MAP) of 35 mm Hg +/- 5 mm Hg for 45 minutes and resuscitated to a baseline mean arterial pressure using the following groups: (1) sham, no hemorrhage; (2) shed blood + lactated Ringer's solution; (3) standard HBOC-201; (4) hypertonic saline 7.5%; (5) hypertonic 7.5% HBOC-201. After resuscitation, observation was continued for 4 hours. Hemodynamic variables, oxygen consumption, and arterial blood gases were monitored continuously. Data were analyzed using analysis of variance. SVR (p = 0.001), PVR (p = 0.001), and MPAP (p = 0.01) were significantly reduced in the HT-HBOC group compared with the standard HBOC group. In this model of hemorrhagic shock, hypertonic HBOC-201- resuscitated pigs had significantly reduced SVR and PVR, as well as mean pulmonary artery pressure (MPAP) and increased cardiac output. HT-HBOC may be beneficial in reducing the undesirable effects of standard HBOC-201. The mechanisms of these beneficial effects need to be investigated.

Abstract 2305: Pulmonary Vascular Reactivity And Prognosis In Patients With Chronic Thromboembolic Pulmonary Hypertension

Hemodynamic responder status defined as an acute decrease of mean pulmonary arterial pressure (mPAP)&gt;10mmHg and below 40mmHg is associated with improved outcome in patients (pts) with pulmonary arterial hypertension (PAH). Pulmonary vascular reactivity to nitric oxide (NO) is controversial in chronic thromboembolic pulmonary hypertension (CTEPH). We speculated that the magnitude of the acute decrease in mean pulmonary artery pressure (mPAP) after exposure to NO might reflect the degree of small vessel disease in CTEPH and thus, affect long-term outcome. Methods: Right heart catheterization was performed in 62 (55  ± 15 years, 32 female) pts with major-vessel CTEPH, at baseline and during inhalation of 40ppm NO. Within 25±15 days patients underwent pulmonary endarterectomy (PEA). Pts were followed for 11.3±26 months. Predictors of survival were analyzed by Cox regression analysis, and survival was described by Kaplan-Meier curves. Results: Significant reductions in mean pulmonary arterial pressure (mPAP; p&lt;0.001), pulmonary vascular resistance (PVR; p&lt;0.001) and an increase in mixed venous oxygen saturation following NO inhalation were demonstrated (p&lt;0.001) by a paired t-test. Stepwise multivariate analysis revealed the relative change of PVR after NO inhalation as a predictor of survival. Patients whose PVR during NO inhalation declined below 789.8 dynes.s.cm-5 had significantly better outcome than patients with above median PVR. There was a strong negative correlation between the relative change of PVR under NO and recurrent pulmonary hypertension after PEA (p=0.02). Conclusions: Patients with operable CTEPH demonstrated acute pulmonary vascular reactivity, mostly not corresponding to a complete responder status, but accounting for a wide range of decreases of mPAP [change of mPAP (%) (−10.9±14)] and PVR [change of PVR (%) (−17 ±15)]. Reduction of PVR under 800 dynes.s.cm-5 after inhalation of NO was associated with better outcome. Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with CTEPH undergoing PEA.

354: Effects of bosentan on both pulmonary vascular remodeling and cardiac function and remodeling in pulmonary hypertension

18/23 patients (78.3%). iNO was administered to 7 patients with PAH, and was associated with a significant reduction in MPAP (-8 mmHg, CI -2 to -13 mmHg, p 0.02), and PVR (-2.4 Wood units, CI -0.6 to -4.2 Wood units, p 0.02). Eleven patients with PAH were subsequently treated with sildenafil, median 150 (75-225) mg/day. Pulmonary haemodynamics were measured during treatment in 8/11 patients. Despite statistically significant reductions in both systolic and diastolic pulmonary arterial pressures, the reduction in MPAP during treatment was not significant. PVR showed a consistent fall of mean -4.6 Wood units (CI -1.9, -7.2 Wood units, p 0.01). Cardiac output and cardiac index also increased during treatment with sildenafil (p 0.03, respectively). There were no consistent changes in the 6 min walk test. Conclusions: Patients with severe pulmonary sarcoidosis have a high prevalence of PAH. Treatment with sildenafil was associated with a significant reduction in PVR in these patients.

Combination Therapy With Oral Sildenafil and Beraprost for Pulmonary Arterial Hypertension Associated With CREST Syndrome

Pulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in long-term combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome. Traces of the acute hemodynamic effects of beraprost (20 microg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours. After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 microg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome.

NITRIC OXIDE EFFECT ON PULMONARY HYPERTENSION BEFORE AND AFTER HEART TRANSPLANTATION

Introduction. The leading causes of postoperative mortality in heart transplantation is right-sided heart failure. This is primarily caused by preexisting elevated pulmonary artery pressures (PAP) and resistance (PVR) in the recipient. Inhaled nitric oxide (NO), an endothelium-derived relaxation factor can significantly reduce pulmonary vascular resistance. It has little effect on the systemic circulation due to its rapid metabolism in the pulmonary vasculature. Therefore NO may improve early survival in heart transplant recipients, and facilitate separation from CPB. Methods: Eleven consecutive patients scheduled for heart transplantation with elevated pulmonary artery pressures were evaluated (PAP systolic >or=to 45 mmHG, and / or PVR >or=to 4 Wood units) Prior to induction of anaesthesia a right ventricular ejection fraction catheter (RVEF) was inserted through the previously placed internal jugular vein catheter. A baseline set of hemodynamic numbers were taken before and after induction anaesthesia. After sternotomy and aortic cannulation, all vasodilators were discontinued and NO was administered at 0, 20, 40, and 80 ppm concentration and hemodynamics were again measured. After the donor heart transplantation, separation from cardiopulmonary bypass (CPB) was attempted using isoprenaline infusion to keep the heart rate [approximate]100. If separation from CPB was unsuccessful as evidenced by right heart dysfunction or elevated pulmonary artery pressures then the patient was placed back on CPB and NO was delivered in the lowest effective concentration and separation from CPB was attempted again. If separation from CPB was successful NO was continued in the postoperative period and weaned over 12-48 hours. Results: All patients were weaned from CPB. Of the eleven patients enrolled six required NO for separation from bypass. One patient died 72 hours postoperatively of right ventricular failure. All other patients survived. They were weaned from NO within 48 hours and discharged from hospital. The five patients not requiring NO for separation from bypass had significant reduction in PAP and PVR with induction of anaesthesia with little further improvement with NO pre and post bypass. (Table 1)Table 1: Hemodynamic Data For Patients Requiring No For Separation From CPBConclusion: Inhaled NO is an effective adjunct for separation for CPB in selected patients with elevated PA pressures after heart transplantation. Preoperative elevation of PA pressures often resolves with induction of anaesthesia. More patients are required to evaluate whether this will translate into decreased early postoperative mortality from right ventricular failure. Lower doses of NO should be evaluated to see whether they will be as effective.

Vasoactive drugs in pulmonary hypertension and right heart failure

The successful management of right ventricular dysfunction is a complex process and relies for its success on the identification, diagnosis and treatment of the underlying pathophysiological process. Pulmonary hypertension remains an area of significant clinical concern and active research. New pharmacological and mechanical treatment modalities are focusing on the successful reduction of PVR (without systemic hypotension) with subsequent preservation of right ventricular function.

Adenosine as a vasodilator in primary pulmonary hypertension.

The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension.