Lower Pulmonary Artery Pressure Research Articles

Periodic acceleration (pGz) CPR in a swine model of asphyxia induced cardiac arrest: Short-term hemodynamic comparisons

Asphyxia is one of the most common causes of pediatric cardiac arrest, and becoming a more frequently recognized cause in adults. Periodic acceleration (pGz) is a novel method of cardiopulmonary resuscitation (CPR). pGz is achieved by rapid motion of the supine body headward-footward that generates adequate perfusion and ventilation during cardiac arrest. In a swine ventricular fibrillation cardiac arrest model, pGz produced a higher return of spontaneous circulation (ROSC), superior neurological outcome, less echocardiography evidence of post resuscitation myocardial stunning, and decreased indices of tissue injury. In contrast to standard chest compression CPR, pGz does not produce rib fractures. We investigated the feasibility of pGz in severe asphyxia cardiac arrest and assessed whether beneficial effects seen in the VF model of cardiac arrest could be realized. Sixteen swine weight 4+/-1 kg were anesthetized, tracheally intubated, and instrumented to measure, hemodynamics and echocardiography. Asphyxia was induced by occlusion of the tracheal tube. After loss of aortic pulsations (median time 10 min) animals were observed for three additional minutes following which all were in cardiac arrest. The animals were then randomized to receive 10 min of pGz or standard chest compression ventilation performed with a commercial device (Thumper). A single dose of epinephrine (adrenaline) and sodium bicarbonate were given and defibrillation attempted if appropriate for a maximum of 10 min. Both groups received fractional inspired O2 concentration of 100% during CPR and after resuscitation. Four animals in each group (50%) had an initial ROSC, however only two of the four initial survivors remained alive 3h after ROSC. There were no significant differences in blood pressure, coronary perfusion pressure during CPR and after early ROSC between groups. pGz treated animals had significantly lower pulmonary artery pressure; 20+/-4 mmHg compared to Thumper 46+/-5 mmHg, 30 min after ROSC (p<0.01). Surviving animals in both groups had severe myocardial dysfunction at 30 min after ROSC. At necropsy, 25% of the Thumper treated animals had rib fractures, while none occurred in the pGz group. In a lethal model of asphyxia cardiac arrest, pGz is equivalent to standard CPR, with respect to acute outcomes and resuscitation survival rates but is associated with significantly lower pulmonary artery pressures and does not produce traumatic rib fractures.

Inheritance of pulmonary arterial pressure in Angus cattle and its correlation with growth1

Pulmonary arterial pressure (PAP) is an indicator of resistance to blood flow through the lungs and when measured at high altitude is a reliable predictor of susceptibility of an animal to brisket disease, a noninfectious cardiac pulmonary condition. (Co)-variance components for PAP, birth weight, and adjusted 205-d weaning weight were estimated from 2,305 spring-born, registered Angus cattle from a Colorado ranch at an elevation of 1,981 m. A single measure of PAP was collected after weaning on animals born from 1984 to 2003. The same licensed veterinarian measured every animal. Multitrait animal models with and without PAP maternal effects were fitted for a pedigree including 132 sires and 793 dams. The interaction of year x sex was a significant fixed effect (P <0.05) for PAP, but age of dam was not. Age at PAP testing was a significant (P <0.1) linear covariate for PAP, and scores increased 0.012 +/- 0.007 mmHg X d(-1) of age. Heritability of PAP direct was 0.34 +/- 0.05. Maternal heritability converged to a boundary at 0.0, and the model with maternal genetic effects for PAP was not significantly better than a model with only direct effects. Phenotypically, PAP was uncorrelated with birth or weaning weights. Genetically, PAP appeared to have positive, unfavorable relationships with direct effects for birth (0.49 +/- 0.12) and weaning weight (0.50 +/- 0.18). Positive correlations imply sires whose offspring exhibited resistance to brisket disease had lower weights and gains. A model that evaluated PAP in females and males as different traits had heritability estimates for each sex of 0.38 +/- 0.07 and 0.46 +/- 0.09, respectively, with a genetic correlation of 0.64 +/- 0.12 between the sexes and was not significantly better than the model assuming homogeneity by sex and a unit genetic correlation between sexes. The results suggest that PAP is moderately heritable in spring-born Angus cattle acclimatized and tested at high altitude, and selection for low PAP scores would be effective. Selection for growth at low altitude will produce cattle less suited to high altitude.

Dilatation and Stenting of the Fontan Pathway: Impact of the Stenosis Treatment on Chronic Ascites

Low pulmonary artery pressure (PAP) and unobstructed flow in the pulmonary arteries (PA) and the systemic veins are the most important factors for optimal long-term Fontan hemodynamics. We retrospectively analyzed the impact of transcatheter interventions for treatment of stenoses in the Fontan pathway to optimize the circulation, with special attention to chronic ascites. Sixty-three of a total of 112 patients underwent heart catheterization 4.6 (1.0-11.4) years after Fontan operation. The median age of the patients at the end of follow-up was 11 (3.1-45) years. Patients were divided into two groups, one with chronic ascites and one without. The impact of elevated PAP and of morphologic stenoses in the Fontan pathway for the development of chronic ascites was analyzed. Ascites was observed in 11 patients; 5 of them had stenosis in the Fontan pathway (P = 0.010). High PAP of 15 mmHg or more (n = 13) was correlated positively with the development of ascites (5 of 13, P = 0.040). Twenty interventions for removal of stenosis in the Fontan pathway were performed in 14 patients. We observed temporary relief of ascites in all and complete resolution of ascites after alleviation of the stenosis in 2 patients with PAP <12 mmHg. Transcatheter treatment of stenosis can effectively improve the hemodynamics in Fontan circulation, even in patients without measurable pressure gradient. In those with low PAP, it may lead to the disappearance of chronic ascites.

Effect of Altitude on the Heart and the Lungs

This review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally reside near sea level. We briefly review the acute physiological adjustments and early acclimatization that occur in the cardiovascular system and the lungs of healthy individuals. These ensure life-sustaining oxygen delivery to the tissues despite a reduction in the partial pressure of inspired oxygen between 20% and 60% at 2500 and 8000 m, respectively. One of the acute adjustments, hypoxic pulmonary vasoconstriction (HPV), may be disadvantageous in those with a vigorous response and lead to 2 potentially lethal illnesses, high-altitude pulmonary edema (HAPE) and subacute mountain sickness (SAMS), which we present in more detail. Finally, on the basis of knowledge about the acute physiological adjustments and acclimatization and, when available, a review of the literature, we discuss the high-altitude tolerance of patients with coronary artery disease, congestive heart failure, arrhythmias, systemic hypertension, and pulmonary hypertension. ### Circulation The major effects of acute hypoxia on the heart and lung are shown in Figure 1. Hypoxia directly affects the vascular tone of the pulmonary and systemic resistance vessels and increases ventilation and sympathetic activity via stimulation of the peripheral chemoreceptors.1 Interactions occur between the direct effects of hypoxia on blood vessels and the chemoreceptor-mediated responses in the systemic and pulmonary circulation. Figure 1. Effects of hypoxia on systemic and pulmonary circulation. Unraveling the underlying mechanisms of the hypoxic vasodilatation of systemic arterioles is an active area of research. Several mechanisms appear to regulate local oxygen delivery according to the needs of the tissues2,3; for instance, the release of ATP from red blood cells and the generation of NO by various ways appear to regulate local oxygen delivery according to the needs …

Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia

Background: Brain abscesses and ischaemic strokes complicate pulmonary arteriovenous malformations (PAVMs). At risk individuals are poorly recognised. Stroke/abscess risk factors have not been defined. Methods: A cohort study of 323...

Consecutive use of sildenafil and bosentan for the treatment of pulmonary arterial hypertension associated with collagen vascular disease: sildenafil as reliever and bosentan as controller

Sildenafil and bosentan were added recently to the treatment with great expectations, effectiveness for the acute exacerbation of pulmonary arterial hypertension (PAH) is not fully examined. Two cases of acutely exacerbated PAH associated with collagen vascular diseases were treated first with sildenafil for six months followed by bosentan for another six months and the characteristics of this treatment modality were examined. Sildenafil showed an immediate effect which started in as early as approximately 30 min and was maximized in 60-90 min after oral ingestion. Continuous use of sildenafil for six months lowered pulmonary arterial pressure, pulmonary vascular resistance and the levels of brain natriuretic peptides along with an increased distance in 6-minute-walk, and replacement of it to with bosentan kept these effects. We think it as a treatment choice to use sildenafil first as a reliever and replace it with a controller bosentan, considering the immediate effects of sildenafil.

Beneficial effects of recombinant human activated protein C in a ewe model of septic shock*

To investigate the effects of activated protein C (APC) in a clinically relevant animal model of septic shock. Prospective, randomized, controlled study. University medical center research laboratory. Eighteen female sheep (body weight, 27-35 kg). Animals were fasted, anesthetized, invasively monitored, and mechanically ventilated before receiving 0.5 g/kg body weight of feces intraperitoneally to induce sepsis. Fluid resuscitation with Ringer lactate was titrated to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive agents or antibiotics were used. Two hours after the induction of sepsis, animals were randomized to receive an infusion of APC (24 microg x kg(-1) x hr(-1), n = 9) or an equivalent volume of vehicle (n = 9) throughout the experimental period. The APC-treated animals had significantly higher arterial pressure, urine output, PaO2/FIO2 ratios, and thoracopulmonary compliance than the control animals. They had lower pulmonary arterial pressure and arterial lactate concentrations than the control animals. Plasma colloid oncotic pressure was better maintained in the APC-treated group than in the control group (p < .05). Prothrombin time and activated partial thromboplastin time were altered less, and plasma D-dimer concentrations were significantly lower in the APC-treated group than in the control group (p < .05). The blood protein C concentration and platelet count were maintained better in the APC-treated group than in the control group (p < .05). APC administration was associated with significantly longer survival (median, 27 hrs vs. 20 hrs; p < .05). At postmortem examination, the lung wet/dry ratio was significantly lower in the APC group than in the control group (6.3 +/- 0.7 vs. 7.1 +/- 1.2, p < .05). In this clinically relevant model of septic shock due to fecal peritonitis, administration of APC had beneficial effects on hemodynamic variables, gas exchange, lactic acidosis, and coagulation abnormalities. Higher colloid oncotic pressures and lower lung wet/dry ratios at autopsy suggest preserved endothelial integrity. APC administration resulted in prolonged survival.

Severe Pulmonary Hypertension in Pediatric Primary Sjögren Syndrome

A 9-year-old girl with a history of xerostomia and recurrent bilateral parotid gland enlargement presented with purpura of the lower limbs and exertional dyspnea. She had hyperglobulinemia, positive ANA, SSA, and SSB and an abnormal Shirmer test leading to a diagnosis of primary Sjögren syndrome. Cardiologic and imaging investigations revealed severe isolated pulmonary hypertension and ruled out pulmonary fibrosis. Prednisolone and cyclophosphamide, together with anticoagulant and vasodilatory drugs therapy, induced a significant improvement of exertional dyspnea and lowered pulmonary artery pressure. This case and reports from the literature suggest that immune mechanisms, not just vasospasm, can be factors in some pulmonary hypertension.

Comparison of two dose regimens of arginine vasopressin in advanced vasodilatory shock

To evaluate the effects of two arginine vasopressin (AVP) dose regimens (0.033 vs. 0.067 IU/min) on treatment efficacy, hemodynamic response, prevalence of adverse events, and changes in laboratory variables. Retrospective, controlled study. A total of 78 patients with vasodilatory shock (mean norepinephrine dosage, 1.07 microg.kg-1.min-1; 95% confidence interval, 0.82-1.56 microg.kg-1.min-1). Supplementary infusion of AVP at 0.033 (n = 39) and 0.067 IU/min (n = 39). Cardiocirculatory, laboratory, and clinical variables were evaluated and compared between groups before and at 0.5, 1, 4, 12, 24, 48, and 72 hrs after initiation of AVP. Treatment efficacy was assessed by the increase in mean arterial blood pressure and the extent of norepinephrine reduction during the first 24 hrs of AVP therapy. Standard tests and a mixed-effects model were used for statistical analysis. Although the relative increase in mean arterial pressure was comparable between groups (0.033 vs. 0.067 IU/min: 16.8 +/- 18.4 vs. 21.4 +/- 14.9 mm Hg, p = .24), norepinephrine could be reduced significantly more often in patients receiving 0.067 IU/min. AVP at 0.067 IU/min resulted in a higher mean arterial pressure (p < .001), lower central venous pressure (p = .001), lower mean pulmonary arterial pressure (p = .04), and lower norepinephrine requirements (p < .001) during the 72-hr observation period. Increases in liver enzymes occurred more often in patients treated with 0.033 IU/min (71.8% vs. 28.2%, p < .001). The prevalence of a decrease in cardiac index (69.2% vs. 53.8%, p = .24), decrease in platelet count (94.8% vs. 84.6%, p = .26), and increase in total bilirubin (48.7% vs. 71.8%, p = .06) was not significantly different between groups. Bilirubin levels (3.1 +/- 3.4 vs. 5.2 +/- 5.5 mg/dL, p = .04) and base deficit (-7.2 +/- 4.3 vs. -3.9 +/- 5.9 mmol/L, p = .005) were lower and arterial lactate concentrations higher (76 +/- 67 vs. 46 +/- 38 mg/dL, p < .001) in patients receiving 0.033 IU/min. AVP dosages of 0.067 IU/min seem to be more effective to reverse cardiovascular failure in vasodilatory shock requiring high norepinephrine dosages than 0.033 IU/min.

Phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension: a case report

BackgroundPortopulmonary hypertension (PPHTN) is a severe complication in liver cirrhosis. PDE5 inhibitors lower pulmonary arterial pressure (PAP) in PPHTN. However, their effect on portal hypertension has not yet been investigated.Case presentationA 55 year old male patient presented with PPHTN and alcoholic liver cirrhosis. 10 mg of Tadalafil, a PDE5 inhibitor with a long half-life, was administered orally under continuous monitoring of pulmonary and portal hemodynamics. For maintenance therapy the patient received Sildenafil 20 mg bid.Tadalafil lowered mean PAP from 45 to 39 mmHg within 60 minutes. Cardiac output (CO) increased from 6.8 to 7.9 l/min. Central venous pressure (CVP) remained stable at 3 mmHg. Systolic and diastolic blood pressure was lowered from 167/89 to 159/86 mmHg. Pulse rate increased from 75 to 87 per min. Wedged hepatic vein pressure (WHVP) decreased from 21 to 18 mm Hg, hepatovenous pressure gradient (HVPG) decreased from 10 to 7 mmHg. Hemodynamic monitoring after 6 months of Sildenafil therapy revealed a sustained lowering of mean PAP. HVPG remained constant at 10 mmHg. Cardiac and pulmonary performance had further improved.ConclusionThis case report shows for the first time, that phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension.

Preliminary experience with inhaled milrinone in cardiac surgery☆

Inhaled administration of milrinone reduces pulmonary artery pressure. Pulmonary hypertension (PH) and right heart failure are associated with difficult separation from cardiopulmonary bypass (CPB). Therefore, inhaled milrinone could facilitate separation from CPB. To determine the impact and timing of administration of inhaled milrinone. A retrospective analysis of our experience on high-risk patients receiving inhaled milrinone was conducted to evaluate the postoperative course after administration of the drug. Seventy-three patients received inhaled milrinone from June 2002 to February 2005. Mean age was 64+/-13 years, with a mean preoperative Parsonnet score of 27+/-14. Inhaled milrinone (5mg) was administered before (n=30) or after (n=40) CPB, three patients had off-pump procedures and were excluded. CPB time was 145+/-78 min with cross-clamping times of 91+/-56 min without any significant difference between groups. Fifty-four patients (74%) had difficult separation from CPB, 14 patients (19%) required an intra-aortic balloon pump and 10 patients (14%) needed emergency reinitiation of CPB for hemodynamic instability. Ten patients died in the perioperative period (13.7%). Patients receiving inhaled milrinone prior to CPB initiation had a lowering pulmonary artery pressure after CPB (p<.01) and had less emergency reinitiation of CPB after weaning (3% vs 23%, p=.02) as compared to those with administration after CPB. No detectable side effects were directly linked to the administration of the drug. In this high-risk cohort, use of inhaled milrinone was well tolerated. Administration before initiation of CPB could help weaning from CPB.

Unexplained Pulmonary Hypertension in Elderly Patients

Background:Idiopathic pulmonary arterial hypertension (IPAH) preferentially affects young women. However, a subset of patients with IPAH is elderly. Our objective was to compare elderly (age ≥ 65 years) vs younger persons with unexplained pulmonary hypertension (PH) and a presumptive diagnosis of IPAH.Methods:Clinical, echocardiographic, hemodynamic, and survival data were collected on consecutive patients with suspected IPAH after evaluation in a large tertiary center PH clinic.Results:Of 197 patients (mean age ± SD, 52 ± 16 years; 80% female), 48 patients (24%) were elderly. Elderly and younger patients had similar symptom severity, systolic pulmonary artery (PA) pressure (82.7 ± 20.3 mm Hg vs 86.9 ± 18.8 mm Hg, respectively; p = 0.21), and severity of right ventricular enlargement and dysfunction. Elderly patients had higher pulmonary capillary wedge pressure (PCWP) [15.3 ± 7.3 mm Hg vs 11.1 ± 5.3 mm Hg; p < 0.0001] and more frequently failed (56%) to meet hemodynamic criteria for IPAH (PH with PCWP < 15 mm Hg) than did younger patients (19%). Elderly patients also had higher systemic systolic (p < 0.0001) and pulse (p < 0.0001) pressures and more cardiovascular disease. Among those patients with normal PCWP, elderly patients had worse survival than young patients (p = 0.007). Among those patients with elevated PCWP, elderly patients had lower PA pressures (p = 0.04) and better survival (p = 0.02).Conclusions:Elderly patients with clinically suspected IPAH often fail to meet hemodynamic criteria for IPAH due to elevated PCWP. Studies to define the proper diagnostic strategy and the safety and efficacy of pulmonary vasodilators in elderly patients with unexplained PH are needed.

PDE-5 inhibitors lower portal and pulmonary pressure in portopulmonary hypertension: Fig. 1—

To the Editors: Several studies have proved that inhibitors of phosphodiesterase (PDE)5 are potent compounds for lowering pulmonary pressure in pulmonary arterial hypertension. With great interest we read the study conducted by Reichenberger et al. 1 about the effect of sildenafil on portopulmonary hypertension (PPHTN). This is a specific condition characterised by an elevated pulmonary arterial pressure (PAP), increased pulmonary vascular resistance and a normal wedge pressure in a setting of underlying portal hypertension. Effective medical therapy is of great importance, as a markedly increased pulmonary pressure has a very poor prognosis in cirrhotic patients and is a contraindication for liver transplantation. The results of the studies by Reichenberger et al. 1 and others 2, 3 show that in these patients, inhibitors of PDE5 also lower PAP. However, Reichenberger et al. 1 focused on the effect …

Clinical differences between idiopathic and scleroderma‐related pulmonary hypertension

Pulmonary arterial hypertension related to scleroderma (PAH-Scl) is associated with high morbidity and mortality as well as poorer response to therapy and worse outcomes compared with the idiopathic form of PAH (IPAH). Scleroderma is an autoimmune disease that can affect left and right heart function directly through inflammation and fibrosis and indirectly through systemic and pulmonary hypertension. This study tested the hypothesis that an increased prevalence of left heart disease might explain the higher mortality in patients with PAH-Scl compared with patients with IPAH. The study was designed as a retrospective cohort study comparing the baseline clinical data from 91 consecutive patients (41 with IPAH and 50 with PAH-Scl). Cox proportional hazards models were used to predict the effect of clinical covariates on patient survival. Patients with PAH-Scl had a lower mean pulmonary artery pressure (46.6 mm Hg versus 54.4 mm Hg in patients with IPAH; P = 0.002) despite similar levels of cardiac dysfunction (cardiac index 2.2 and 2.1 liters/minute/m(2), respectively; P = 0.19). Echocardiography revealed similar degrees of right ventricular dysfunction in the 2 groups, whereas a predominance of left heart dysfunction was observed in patients with PAH-Scl. One- and three-year survival estimates were 87.8% and 48.9%, respectively, in patients with PAH-Scl and 95.1% and 83.6%, respectively, in those with IPAH. Patients with PAH-Scl were 3.06 times more likely to die than were patients with IPAH, after controlling for the presence of pericardial effusion; there was no significant change in increased risk of death in PAH-Scl after controlling for left heart disease. The results confirm that there are significant clinical and survival differences between IPAH and PAH-Scl. The presence of left heart disease, although more common in PAH-Scl, was not predictive of the higher mortality in these patients.

U50,488H Depresses Pulmonary Pressure in Rats Subjected to Chronic Hypoxia

In this study, we determined the effect of U50,488H (a selective kappa-opioid receptor agonist) on pulmonary artery in rats and investigated its prevention and treatment effects on hypoxic pulmonary hypertension (HPH). Isolated pulmonary arterial rings were superfused and the tension of the vessel was measured. The model of HPH was developed and indexes for hemodynamics and right ventricular hypertrophy were measured. We found that U50,488H relaxed the pulmonary artery rings in a dose-dependent manner and the effect was abolished by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. Intravenous administration of U50,488H significantly lowered mean pulmonary artery pressure (mPAP) in normal rats and this effect was also abolished by nor-binaltorphimine. Hypoxia induced severe HPH in rats and intraperitoneal administration of U50,488H (every other day) during chronic hypoxia reduced mPAP and attenuated right ventricular hypertrophy compared with the control group. Moreover, acute intravenous administration of U50,488H after the rats subjected to chronic hypoxia for 4 weeks significantly lowered mPAP. Thus, U50,488H has significant vasorelaxant effect in rat pulmonary artery and has certain preventive and therapeutic application in HPH.

A randomized trial of automated versus conventional protocol-driven weaning from mechanical ventilation following coronary artery bypass surgery☆

The Siemens servo 300 A ventilator has an automode function that allows automated weaning of patients from mechanical ventilation. Spontaneous breathing triggers the ventilator. After two spontaneously triggered breaths, the ventilator automatically changes from mandatory mechanical ventilation to spontaneous ventilation. If spontaneous breathing or triggering does not occur, the Siemens servo 300 A ventilator changes from spontaneous ventilation back to mandatory mechanical ventilation. We compared the effects of automated versus conventional protocol-driven weaning on the time until extubation in patients undergoing coronary artery bypass graft (CABG) surgery. In addition, we studied the effects of the mode of weaning on hemodynamic and physiologic parameters. Twenty consecutive male patients without respiratory disease scheduled for CABG at the University Hospital of Regensburg were entered into the study. Patients were randomized to postoperative ventilation with the Siemens 300 A/automode ventilator (group A, n = 10) or with the Siemens 300 ventilator (group B, n = 10). All patients were weaned from ventilation according to a standardized protocol. On average, patients in group A were younger and had lower pulmonary artery pressure (PAP) and higher cardiac output compared to patients in group B. However, patients in group A had longer ischemic and bypass times compared to patients in group B. Postoperative use of analgesia and sedation were similar in both groups. Time from tracheal intubation until extubation was 2 h shorter in patients assigned to automode ventilation compared to patients assigned to conventional ventilation (mean time group A 7.9 h, group B 10.0 h; p = 0.069). Peak airway pressure was reduced by 2 cm H2O at the beginning of spontaneous ventilation in group A compared to group B. After extubation, cardiac index showed a greater increase in patients assigned to group A compared to those in group B. Automode ventilator weaning trended toward more rapid extubation than did conventional protocol-driven ventilation in conjunction with a standardized weaning protocol. Physiologic and hemodynamic factors were better in patients using automode ventilation compared to patients using conventional ventilation. Automode ventilation was well tolerated and did not induce significant adverse effects.

A nitric oxide processing defect of red blood cells created by hypoxia: Deficiency of S-nitrosohemoglobin in pulmonary hypertension

The mechanism by which hypoxia [low partial pressure of O(2) (pO(2))] elicits signaling to regulate pulmonary arterial pressure is incompletely understood. We considered the possibility that, in addition to its effects on smooth muscle, hypoxia may influence pulmonary vascular tone through an effect on RBCs. We report that exposure of native RBCs to sustained hypoxia is accompanied by a buildup of heme iron-nitrosyl (FeNO) species that are deficient in pO(2-)governed intramolecular transfer of NO to cysteine thiol, yielding a deficiency in the vasodilator S-nitrosohemoglobin (SNO-Hb). S-nitrosothiol (SNO)-deficient RBCs produce impaired vasodilator responses in vitro and exaggerated pulmonary vasoconstrictor responses in vivo and are defective in oxygenating the blood. RBCs from hypoxemic patients with elevated pulmonary arterial pressure (PAP) exhibit a similar FeNO/SNO imbalance and are thus deficient in pO(2)-coupled vasoregulation. Chemical restoration of SNO-Hb levels in both animals and patients restores the vasodilator activity of RBCs, and this activity is associated with improved oxygenation and lower PAPs.

Intermediate-term outcome following the fontan operation: a survival, functional and risk-factor analysis☆

To investigate survival and risk factors influencing intermediate outcome after the Fontan procedure. Retrospective analysis of 122 patients operated between April 1991 and September 2002. Poor outcome was defined as late death or poor functional status (intractable supraventricular arrhythmias/NYHA 3-4) necessitating revision surgery. 64(52%) patients had an intermediate bi-directional cavo-pulmonary shunt (BCPS). 91 (76%) patients had a lateral tunnel total cavo-pulmonary connection, 21(17%) patients had an atrio-pulmonary connection and 10 (8%)patients had a Kawashima connection. There were 6 (5%)early deaths. Over a median follow up of 54 months (1-133), 12 (10%)patients have had surgical revision for poor functional status. There were 7 (6%) late deaths, 5 of which occurred after revision surgery. Univariate analysis identified older age at operation (>4 years) (P=0.04), higher postoperative pulmonary artery pressure at 24h (P=0.012), arrhythmia postoperatively (P=0.03) or during follow-up (P=0.01) and the requirement for anticoagulation during follow-up (P=0.03) as significant predictors of poorer outcome. Patients who had an intermediate BCPS (P=0.002) or Norwood Stage 1 (P=0.05) had a better outcome. Multivariate analysis identified an intermediate Glenn shunt and lower postoperative pulmonary artery pressure as significant predictors of better outcome. Actuarial freedom from death or revision is 93% (+/-2), 88% (+/-3), 86% (+/-4) and 69% (+/-7) at 1, 5, 7 and 9 years respectively. Actuarial freedom from death or revision for the lateral tunnel group is 92% (+/-2), 89% (+/-3), 85% (+/-5) and 66% (+/-10) respectively. Atrio-pulmonary connection results in a higher incidence of arrhythmias and failure than the lateral tunnel Fontan. Even in patients with a lateral tunnel Fontan there is a continuing hazard phase in the intermediate term. Mid-term outcome appears to be favorably influenced by an intermediate BCPS.

A Novel Inhaled Organic Nitrate That Affects Pulmonary Vascular Tone in a Piglet Model of Hypoxia-Induced Pulmonary Hypertension

Persistent pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance after birth leading to right-to-left shunting and systemic arterial hypoxemia. Inhaled nitric oxide (NO) is effective in reducing the need for extracorporeal membrane oxygenation, but it has potential toxicities, especially in an oxygen-rich environment. A number of other NO-based molecules have been given by inhalation, but their structure-function relationships have not been established. Recent studies have raised the idea that toxic and beneficial properties can be separated. We synthesized a novel organic nitrate [ethyl nitrate (ENO2)], tested it in vitro, and administered it to hypoxic piglets. ENO2 lowered pulmonary artery pressure and raised the Po2 in arterial blood but did not alter systemic vascular resistance or methemoglobin levels. In addition, we tested the effect of ENO2 in the presence of the thiol glutathione, both in vivo and in vitro, and found its action to be enhanced. Although ENO2 is less potent than inhaled NO on a dose-equivalency basis, pretreatment of hypoxic animals with glutathione, which may be depleted in injured lungs, led to a markedly enhanced effect (largely mitigating the difference in potency). These results suggest that ENO2 may hold promise as a safe alternative to NO, particularly in hypoxemic conditions characterized by thiol depletion.

Transcatheter device closure of atrial septal defects in the elderly: Technical considerations and short-term outcomes

Background Device closure of an atrial septal defect (ASD) results in symptom-reduction, right heart remodelling and lower pulmonary artery pressures. However it is unclear if there is a chronological limit to these benefits and whether device closure is safe in elderly subjects. The aim of this study was, therefore, to assess the safety and efficacy of device closure in patients > 60 years. Methods Retrospective study of Amplatzer Septal Occluder™ device closures from a single institution (May 1999–August 2002). Results Fifty subjects aged > 60 years (range 60–85 years) had ASD device closure (27% of the total cohort). Defect size and shunt size were similar for both younger and older groups (2.2 : 1 in both groups, p = 0.9) as were procedural duration, fluoroscopy time and device size deployed. Baseline right ventricular (RV) systolic pressure ((younger vs. older) 39 vs. 49 mmHg, p < 0.001) and right ventricular size (45 vs. 51 mm, p < 0.001) were greater in the older group. Following closure RV systolic pressure (49 vs. 45 mmHg, p < 0.01) and RV size (51 vs. 44 mm, p = 0.01) decreased in the older group. Conclusion Device closure of an ASD can be performed safely in older patients. The right heart shows signs of remodelling even in elderly subjects.