Intravenous Infusion Of Prostacyclin Research Articles

Effect of delayed onset prostacyclin on markers of endothelial function and damage after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a neurological emergency. Delayed ischemic neurological deficit is one of the main causes of poor outcome after SAH and is probably caused, at least in part, by cerebral vasospasm. The pathophysiology of this is multifaceted, but endothelial damage and activation as well as glycocalyx damage have been implicated. Prostacyclin has been shown to protect damaged and activated endothelium and to facilitate glycocalyx repair. We investigated biomarkers of endothelial activation and damage in patients with SAH randomized to 5days prostacyclin infusion or placebo. Patients with aneurysmal SAH managed by coiling or surgery, and a World Federation of Neurological Surgeons score between 1 and 4, and Fisher grade 3 or 4, were treated with a continuous low-dose intravenous prostacyclin infusion or placebo initiated on day 5 and discontinued on day 10 after SAH. Blood samples were drawn from the patients before, during and after prostacyclin/placebo infusion. Soluble biomarkers of endothelial cell activation (sE-selectin, sVE-cadherin) and damage (sTM), glycocalyx damage (syndecan-1) and sympathoadrenal activation (adrenaline, noradrenaline), were measured by ELISA. Ninety patients were randomized. Prostacyclin infusion influenced neither biomarkers of sympathoadrenal activation, endothelial activation and damage nor biomarkers of endothelial glycocalyx breakdown. We did not find any effects on markers of sympathoadrenal activation, endothelial damage and activation, or glycocalyx degradation of delayed onset prostacyclin infusion compared to placebo. Further trials investigating early onset endothelial repair using prostacyclin are warranted.

Effectiveness and Safety of Inhaled Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Children

The introduction of prostanoid therapy has revolutionized the treatment of pulmonary arterial hypertension (PAH). However, continuous intravenous prostacyclin infusion poses significant risks and challenges, particularly in children. Inhaled treprostinil has been shown to be safe and efficacious in adults. This study describes the safety and efficacy of inhaled treprostinil in children with PAH. A retrospective analysis of 29 children treated with inhaled treprostinil for ≥6 weeks was performed. Effects of inhaled treprostinil on exercise capacity, functional class, and echocardiographic and hemodynamic data were evaluated. Adverse events were documented. Patients received 3 to 9 breaths (6 μg/breath) of inhaled treprostinil 4 times/day. All were receiving background PAH therapy; 12 had previously received parenteral prostanoid. Inhaled treprostinil was discontinued in 4 patients because of symptoms including cough and bronchospasm (n = 3) and progression of PAH (n = 1). Mild side effects including cough (n = 9) and sore throat (n = 6) did not require discontinuation of therapy. World Health Organization functional class improved in 19 and was unchanged in 10; exercise capacity significantly improved with the 6-minute walk distance, improving on follow-up from 455.7 ± 71.5 to 498 ± 70 m (p = 0.01) and peak oxygen consumption increasing from 25.5 ± 10.2 to 27.4 ± 10 (p = 0.04). In conclusion, inhaled treprostinil was associated with improvement in exercise capacity and World Health Organization functional class when added to background targeted PAH therapy in children and had an acceptable safety profile. Based on these early data, further study of inhaled treprostinil appears warranted in pediatric patients with PAH.

Segmental cerebral vasoconstriction: Successful treatment of secondary cerebral ischaemia with intravenous prostacyclin

We describe a 23-year-old male patient who presented with spontaneous intermittent and increasing attacks of severe, left-sided thunderclap headache combined with rapidly progressive muscle weakness and dysphasia, including gradual loss of consciousness. Subsequent CT, MRI and DSA showed progressive brain ischaemia and oedema within the left cerebral hemisphere with strict ipsilateral segmental arterial vasoconstriction. Despite extensive medical care, including steroids, the patient deteriorated rapidly. However, the clinical course changed dramatically within 15 h after the start of an intravenous infusion of prostacyclin at a dose of 0.9 ng/kg/min, with an almost complete recovery of consciousness and speech. In addition the pathophysiological alterations seen on magnetic resonance (imaging and digital) subtraction angiography including diffusion-weighted imaging and apparent diffusion coefficient maps shortly before prostacyclin treatment were clearly reduced when the patient was examined 3-4 days later and he continued to recover thereafter. Although not fully compatible, our case had several clinical characteristics and radiological findings reminiscent of those of the 'segmental reversible vasoconstriction syndrome', sometimes called the Call-Fleming syndrome.

New lines in therapy of Raynaud’s phenomenon

Current knowledge about the pathogenesis of Raynaud's phenomenon (RP) results in novel approaches for therapy. Vasospasm without endothelial damage is thought to be the main cause for primary RP. The pathogenesis of secondary forms of RP is supposed to be initiated primary by endothelial damage. The aim of the review is to present main groups of medications as well as non-pharmacological regimen, that are used for the treatment of RP. The necessity of immediate assessment and treatment in severe forms of the disease with digital ulcers is highlighted. The mild forms of primary RP can be controlled by non-pharmacologic approaches. If the effect is insufficient, medications of first choice are calcium channel blockers. In the severe forms of the disorder, intravenous infusion of prostacyclin as well as endothelin-1 receptor antagonists and specific inhibitors of phosphodiesterase-5 are the treatment of choice. Treatment in the future may include selective blockers of alpha-2c adrenergic receptors, inhibitors of protein tyrosine kinase and Rho-kinase, as well as calcitonin gene-related peptide.

Adenoassociated Virus–Mediated Prostacyclin Synthase Expression Prevents Pulmonary Arterial Hypertension in Rats

Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway of prostacyclin production. The therapeutic option of intravenous prostacyclin infusion in patients with pulmonary arterial hypertension is limited by the short half-life of the drug and life-threatening catheter-related complications. To develop a better delivery system for prostacyclin, we examined the feasibility of intramuscular injection of an adenoassociated virus (AAV) vector expressing PGIS for preventing monocrotaline-induced pulmonary arterial hypertension in rats. We developed an AAV serotype 1-based vector carrying a human PGIS gene (AAV-PGIS). AAV-PGIS or the control AAV vector expressing enhanced green fluorescent protein was injected into the anterior tibial muscles of 3-week-old male Wistar rats; this was followed by the monocrotaline administration at 7 weeks. Eight weeks after injecting the vector, the plasma levels of 6-keto-prostaglandin F(1alpha) increased in a vector dose-dependent manner. At this time point, the PGIS transduction (1x10(10) genome copies per body) significantly decreased mean pulmonary arterial pressure (33.9+/-2.4 versus 46.1+/-3.0 mm Hg; P<0.05), pulmonary vascular resistance (0.26+/-0.03 versus 0.41+/-0.03 mm Hg x mL(-1) x min(-1) x kg(-1); P<0.05), and medial thickness of the peripheral pulmonary artery (14.6+/-1.5% versus 23.5+/-0.5%; P<0.01) as compared with the controls. Furthermore, the PGIS-transduced rats demonstrated significantly improved survival rates as compared with the controls (100% versus 50%; P<0.05) at 8 weeks postmonocrotaline administration. An intramuscular injection of AAV-PGIS prevents monocrotaline-pulmonary arterial hypertension in rats and provides a new therapeutic alternative for preventing pulmonary arterial hypertension in humans.

Low-dose prostacyclin improves cortical perfusion following experimental brain injury in the rat.

It was recently shown that prostacyclin at a low dose reduces cortical cell death following brain trauma in the rat. Conceivably, prostacyclin with its vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing properties improved a compromised perfusion caused by post-traumatic vasoconstriction, microthrombosis and increased microvascular permeability. The objective of the present study was therefore to investigate the hemodynamic effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid percussion brain injury or a sham procedure, animals were treated with a continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1), or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or 48 h of treatment. Blood flow values in the injured cortex were transiently reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma from a corresponding value of about 1.6 mL x min(-1) in the sham group, with recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent increase in blood flow which reached statistical significance 48 h following trauma. Brain water content and PS increased in the injured cortex post trauma and the higher dose of prostacyclin increased these parameters further at 48 h compared to the vehicle group (p < 0.05). The latter effects of prostacyclin cannot be attributed to an increase in permeability, as prostacyclin did not influence PS or brain water content following sham trauma. In fact prostacyclin has been shown to have permeability-decreasing properties. We conclude that prostacyclin improves cortical perfusion following brain trauma. The simultaneous aggravation of brain edema can be explained by an increased surface area, perhaps in combination with increased capillary hydrostatic pressure.

Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial

ObjectivesThe purpose of this study was to assess the efficacy and safety of beraprost sodium, an orally active prostacyclin analogue, in New York Heart Association (NYHA) functional class II and III patients with pulmonary arterial hypertension (PAH). BackgroundPulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has been proven effective. However, this treatment is associated with serious complications arising from the complex delivery system. MethodsIn this double-blind, placebo-controlled study, 130 patients with PAH were randomized to the maximal tolerated dose of beraprost (median dose 80 μg four times a day) or to placebo for 12 weeks. The primary end point was the change in exercise capacity assessed by the 6-min walk test. Secondary end points included changes in Borg dyspnea index, cardiopulmonary hemodynamics and NYHA functional class. ResultsPatients treated with beraprost improved exercise capacity and symptoms. The difference between treatment groups in the mean change of 6-min walking distance at week 12 was 25.1 m (95% confidence interval [CI]: 1.8 to 48.3, p = 0.036). The difference in the mean change of Borg dyspnea index was −0.94 (95% CI: −1.63 to −0.24, p = 0.009). In the sub-group of patients with primary pulmonary hypertension, the difference in the mean change of 6-min walking distance was 46.1 m (95% CI: 3.0 to 89.3, p = 0.035). Cardiopulmonary hemodynamics and NYHA functional class had no statistically significant changes. Drug-related adverse events were common in the titration phase and decreased in the maintenance period. ConclusionsBeraprost improves exercise capacity and symptoms in NYHA functional class II and III patients with PAH and, in particular, in those with primary pulmonary hypertension.

Cellular pathophysiology and therapy of pulmonary hypertension

The identification of several mutations of the bone morphogenetic protein receptor 2 (BMPR2) gene, a member of the transforming growth factor β receptor family, gives hope for new insights into the pathophysiology of pulmonary hypertension. Genetic predisposition might dictate the responses of pulmonary artery fibroblasts, smooth muscle cells, and endothelial cells, as well as platelets and leukocytes, or their specific interactions with different extrinsic factors. These cells possess distinct subtypes and interact with each other. Pulmonary hypertension is associated with vasoconstriction, remodeling, and in situ thrombosis of the pulmonary arteries, but the initial events and their relationship to the genetic background are presently unknown. Current therapeutic approaches are based on our knowledge of the physiologic regulation of pulmonary artery tone, pathophysiologic changes, and our clinical experience with different treatment strategies. Beyond diuretics and anticoagulants, prostaglandins are generally accepted therapeutic agents for primary pulmonary hypertension and related diseases, whereas high-dose calcium-channel blockers are reserved for a small subset of patients, those who respond favorably to vasodilators in an acute test. Long-term intravenous prostacyclin infusion has become the most important specific therapy for primary pulmonary hypertension and associated diseases. However, this therapy is hampered by catheter complications and systemic side effects. Alternative application routes of prostacyclin or its stable analogs may avoid these problems. Inhaled application of the prostacyclin analog iloprost results in predominant pulmonary vasodilation with few systemic side effects and may possess clinical efficacy similar to that of intravenous prostacyclin. Inhaled nitric oxide is widely accepted as a screening agent for active responders to vasodilators and has a similar hemodynamic profile as inhaled iloprost, although the percentage of responders is considerably lower. However, there are unsolved toxicologic questions and practical difficulties concerning the safe long-term application of nitric oxide. Combining inhaled vasodilators with phosphodiesterase inhibitors may prolong the duration of the effects and improve the convenience of inhaled therapy for pulmonary hypertension. Therapeutic approaches in the future may aim at the transforming growth factor β pathway and at the identification of early stages of the disease to prevent further disease progression. (J Lab Clin Med 2001;138:367-77)

Catastrophic Antiphospholipid Syndrome

Catastrophic Antiphospholipid Syndrome

Diagnosis and management of primary pulmonary hypertension.

Pulmonary arterial hypertension in children can occur secondary to shunt lesion like ventricular septal defect, patent ductus arteriosus or it may be idiopathic, the so-called primary pulmonary hypertension (PPH). The progression of PPH is usually rapid in children as compared to adults and the mean survival is 2-3 years after the diagnosis is made. Histological changes in the form of medical muscular hypertrophy, intinal hyperplasia and later angiornatous, plexiform lesions occur in pulmonary vasculature. The pulmonary vasculature normally is a high flow, low resistance circuit and allows large blood flow without marked increase in pulmonary arterial pressure. However, with prolonged increased flow or any other vasoconstrictor stimulus, histological changes start occurring in the pulmonary bed resulting in increasing pressure in pulmonary artery. Right ventricular hypertension follows resulting in right ventricular hypertrophy and later dysfunction. Life threatening arrhythmias may result in sudden death in some of these patients. Clinical presentation is in the form of exertional dyspnoea with syncope at times. Over 50% of children with PPH are helped by vasodilators. They may be treated with calcium channel blockers (e.g. nifedipine, dose titrated to blood pressure) orally. Those not responding to oral vasodilators can be put on chronic inhaled nitric oxide or continuous intravenous prostacyclin infusion. Chronic anticoagulation therapy may also increase survival. In symptomatic cases, blade/balloon atrial septostomy may increase survival in patients of PPH with intact atrial sptum. For children not responding to medical therapy, lung transplantation may be the answer in near future.

A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension

OBJECTIVEWe sought to compare the acute hemodynamic effects of inhaled nitric oxide (NO) and aerosolized iloprost in primary pulmonary hypertension (PPH).BACKGROUNDInhalation of the stable prostacyclin analogue iloprost has recently been described as a novel therapeutic strategy for PPH and may offer an alternative to continuous intravenous infusion of prostacyclin or inhalation of NO.METHODSDuring right heart catheterization, 35 patients with PPH sequentially inhaled 40 ppm of NO and 14 to 17 μg of iloprost, and the effects on hemodynamics and blood gases were monitored.RESULTSBoth NO and iloprost caused significant increases in cardiac output, mixed-venous oxygen saturation and stroke volume as well as significant decreases in pulmonary artery pressure and pulmonary vascular resistance, whereas only inhaled iloprost significantly increased the arterial Po2(p = 0.01). Compared with inhaled NO, aerosolized iloprost was more effective in reducing pulmonary artery pressure (−8.3 ± 7.5 mm Hg vs. −4.3 ± 8.8 mm Hg; p = 0.0001) and the pulmonary vascular resistance (−447 ± 340 dynes·s·cm−5vs. −183 ± 305 dyne·s·cm−5; p < 0.0001). Furthermore, aerosolized iloprost caused a significantly greater increase of the cardiac output compared with NO (+0.7 ± 0.6 liter/min vs. +0.3 ± 0.4 liter/min; p = 0.0002) and had a more pronounced effect on the mixed-venous oxygen saturation (p = 0.003).CONCLUSIONSDuring acute drug testing, aerosolized iloprost was more potent than inhaled NO as a pulmonary vasodilator in PPH at the doses used in this study.

Management of acute nontraumatic upper limb ischemia.

A retrospective review of all patients presenting to a tertiary referral center with acute nontraumatic upper limb ischemia between January 1992 and June 1997 was undertaken to examine the role of intraarterial thrombolysis in the management of such cases. Twenty-one patients were identified in the radiology and vascular surgery departments' registers. Twenty (95%) underwent angiography, demonstrating subclavian artery occlusion in four, axillary in two, brachial in 13, and one at the digital level. Intraarterial thrombolysis was attempted in 12 patients. There were three technical failures, all requiring embolectomy. Six had complete lysis and resolution of their symptoms. One patient had partial lysis but experienced no further rest pain. Thrombolysis was unsuccessful in two cases with one subsequently requiring embolectomy and the other surgical bypass. Three patients had surgical intervention as their primary procedure with two favorable outcomes and one ending in above-elbow amputation. Five patients were treated conservatively with heparin, resulting in three partial and two full recoveries. One patient experienced complete resolution of symptoms with an intravenous prostacyclin infusion. Both electrocardiograms (ECG) and echocardiograms (ECHO) were of limited diagnostic aid, and long-term warfarin anticoagulation was prescribed to all patients. There was no recurrence of upper limb ischemia at a median follow up of 18 months. Intraarterial thrombolysis is an effective first line treatment for acute nontraumatic upper limb ischemia in selected cases.

Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: a case series.

Treatment of patients with secondary pulmonary hypertension has been unsatisfactory. To describe exercise capacity, functional class, and hemodynamic variables after long-term intravenous infusion of prostacyclin in patients with secondary pulmonary hypertension. Case series. Academic referral center. 33 patients with secondary, precapillary pulmonary hypertension (New York Heart Association class III or IV). Continuous intravenous prostacyclin administered by portable infusion pump on a compassionate-use basis. Functional class, treadmill time, and hemodynamic variables. Patients were followed for an average of 12.7 +/- 5.6 months. Exercise tolerance and New York Heart Association class improved in each patient. The duration of treadmill exercise increased from 186 seconds to 491 seconds, an increase of 305 seconds (95% CI, 194 to 417 seconds; P < 0.001). Mean pulmonary artery pressure decreased from 60 mm Hg to 46 mm Hg, a decrease of 14 mm Hg (CI, 9 to 19 mm Hg; P < 0.001). Cardiac output increased from 3.90 L/min to 6.30 L/min, an increase of 2.40 L/min (CI, 1.56 to 3.25 L/min; P < 0.001). The pulmonary vascular resistance decreased from 1143 dynes x s/cm5 to 575 dynes x s/cm5, a decrease of 567 dynes x s/cm5 (CI, 407 to 727 dynes x s/cm5; P < 0.001). Patients with collagen vascular disease, congenital heart disease, and portopulmonary hypertension were analyzed with other patients and separately. All groups had a statistically significant reduction in mean pulmonary artery pressure and a statistically significant increase in cardiac output. Intravenous prostacyclin may be effective in the treatment of patients with certain types of secondary pulmonary hypertension.

Effects of intravenous administration of prostacyclin on regional blood circulation in awake rats.

1. The effects of intravenous infusion of prostacyclin (PGI2, 0.1, 0.2, 0.3 and 1.0 microg kg(-1) min(-1) lasting 5 min) on regional blood flow and regional vascular resistance have been studied in awake rats using the radioactive microsphere method. 2. The control values of blood flow to the heart, kidney, small intestine, hind limb muscle, pericranial skin and brain as well as the corresponding vascular resistance were not modified by an i.v. infusion (0.1 ml min(-1)) of Tris-buffer (the vehicle of PGI2). 3. The i.v. infusion of PGI2 produced graded dose-dependent decreases of MAP (r=0.87, P<0.001; ED20=0.73 [0.13-2.55] microg kg(-1) min(-1)) as well as decreases of vascular resistance in the heart (r=0.83, P<0.001; ED30=0.17 [0.09-0.31] microg kg(-1) min(-1)), pericranial skin (r=0.88, P<0.001; ED30=0.28 [0.18-0.43] microg kg(-1) min(-1)) and small intestine (r=0.74, P<0.001; ED30=0.21 [0.11-0.39] microg kg(-1) min(-1)), which led to dose-related increases of blood flow to these territories. 4. On the contrary, PGI2 increased vascular resistance in skeletal muscle (r=0.73, P<0.001; ED30=0.20 [0.10-0.39] microg kg(-1) min(-1)) with corresponding reductions in blood flow. The low doses reduced renal blood flow but there were no significant changes during the high ones. Cerebral vessels did not dilate during any infusion of PGI2 and cerebral blood flow decreased as MAP fell (r=0.56, P<0.01). 5. We conclude that, in awake rats, the coronary vessels are extremely sensitive to the vasodilating effect of PGI2 and that the mesenteric vessels and those of the pericranial skin are very responsive too. Moreover, autoregulation is inefficient to maintain cerebral blood flow during infusion of PGI2.

The acute effects of prostacyclin on pulmonary hemodynamics in patients with pulmonary hypertension secondary to systemic sclerosis.

To determine whether patients with isolated pulmonary hypertension secondary to systemic sclerosis (SSc) have a pulmonary vasculature that is responsive to treatment with vasodilators. Seven SSc patients with pulmonary hypertension underwent right heart catheterization. Pulmonary pressures and cardiac output were measured before and during a systemic intravenous infusion of prostacyclin. Both pulmonary arterial mean pressure and pulmonary vascular resistance decreased significantly with prostacyclin infusion (median decrease 11% and 32%, respectively), with a concomitant increase in cardiac output (median increase 26%). No adverse hemodynamic effects were noted during the infusion. Vasospasm contributes to the pulmonary hypertension complicating SSc. This feature may be amenable to treatment with vasodilators.

Low-dose prostacyclin has potent capillary permeability-reducing effect in cat skeletal muscle in vivo.

The dose-response effects of intravenous infusion of prostacyclin on capillary permeability (the capillary filtration coefficient technique), hydrostatic capillary pressure, transcapillary filtration, and vascular tone were analyzed in vivo on cat skeletal muscle from a normal and an increased permeability level. Increased permeability was accomplished by intra-arterial infusion of tumor necrosis factor-alpha or histamine. Permeability effects of bradykinin were also analyzed. Prostacyclin decreased capillary permeability by 8% at a dose of 0.1 ng.kg-1.min-1 and at most by 30% below control attained at 2 ng.kg-1.min-1, also with no effect on vascular tone and hydrostatic capillary pressure. The permeability increase by tumor necrosis factor-alpha and histamine (by 54 and 73%) was more than counteracted by the simultaneous infusion of prostacyclin at 2 ng.kg-1.min-1. The vasodilator effect of tumor necrosis factor-alpha was also restituted. Indomethacin (prostacyclin inhibitor)-induced increase in capillary permeability (25%) was more than restituted by prostacyclin at 2 ng.kg-1.min-1. Surprisingly, bradykinin decreased capillary permeability. We conclude that endogenous prostacyclin may be a physiological regulator of capillary permeability and that low-dose prostacyclin infusion may have clinical relevance in states of increased permeability.

Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III

We evaluated the effects of antithrombin III (AT III) on the pulmonary vascular injury induced by injecting rats with lipopolysaccharide (LPS) to investigate the possible usefulness of AT III as a treatment for acute respiratory distress syndrome. The intravenous administration of AT III prevented the pulmonary accumulation of leukocytes (as evaluated by myeloperoxidase activity) and the increase in pulmonary vascular permeability to 125I-bovine serum albumin induced by LPS. The increase in pulmonary vascular permeability induced by LPS administration was unaffected by various anticoagulants but was inhibited by the leukocytopenia induced by nitrogen mustard or by the administration of a granulocyte elastase inhibitor, ONO-5046. AT III given alone, but not heparin plus AT III or Trp49-modified AT III, which lacks affinity for heparin, significantly increased the plasma concentration of 6-keto-prostaglandin F1alpha, suggesting that the interaction of AT III with heparin-like substances at the endothelial cell surface promotes the release of prostacyclin from endothelial cells in vivo. Trp49-modified AT III failed to prevent the LPS-induced accumulation of leukocytes and vascular injury. The pulmonary accumulation of leukocytes and vascular injury induced by LPS were not prevented by administering AT III to rats that were pretreated with indomethacin. The continuous intravenous infusion of prostacyclin prevented the LPS-induced pulmonary accumulation of leukocytes and vascular injury. Findings suggest that AT III depends on its ability to promote the release of prostacyclin, a potent inhibitor of leukocyte activation, from endothelial cells to prevent pulmonary vascular injury induced by LPS.

Intravenous infusion of prostacyclin to prevent platelet thrombus during microvascular anastomoses

Two cases are presented where the use of epoprostenol sodium (prostacyclin) was used intraoperatively to prevent platelet thrombus during arterial microvascular anastomoses. Both patients required a free muscle transfer at an unfavourable time following injury when platelet thrombus formation was a significant risk.

Effect of Prostacyclin on Microvascular Pressures in a Patient With Pulmonary Veno-Occlusive Disease

Continuous-infusion prostacyclin improves symptom scores and decreases mortality in patients with primary pulmonary hypertension, but use of prostacyclin in patients with pulmonary veno-occlusive disease may precipitate pulmonary edema. A patient with pulmonary veno-occlusive disease received a graduated intravenous infusion of prostacyclin and pulmonary capillary pressures were calculated during prostacyclin dose ranging. Calculated capillary pressure increased with low-dose prostacyclin (< or = 6 ng/kg/min) but decreased with higher doses. These data suggest that the post-capillary pulmonary venules in our patient had reversible vasomotor tone, but required a higher dose of prostacyclin to vasodilate than did the precapillary arterioles.

964-14 Beneficial Effects of Beraprost Sodium in Patients with Pulmonary Hypertension

Intravenous infusion of prostacyclin (PGI 2 ) is considered to be one of the most effective vasodilating remedy in patients with pulmonary hypertension (PH). To determine whether beraprost sodium (BPS), a oral PGI 2 derivative, clinically available in Japan, is also effective in PH. We selected 11 patients (3 males, 8 females, 42 ± 13 years old) with moderate to severe PH (NYHA III≈IV) dueto primary or inoperable thromboembolic PH. Hemodynamic measurements by means of cardiac catheterization were performed before and immediately after single dose of oral BPS (60–100 JLg). and restudied after 1 to 2 months of chronic administration (20–40 μg, t.i.d.). (1) Acute effects; There were significant decrease in mean pulmonary artery pressure (PAm) (70 ± 13→55 ± 12 mmHg, p &lt; 0.01) and total pulmonary resistance (TPR) (19.9 ± 10.6→ 16.8 ± 11.7 u, p &lt; 0.05). and increase in cardiac output (CO) (3.0 ± 1.1→3.5 ± 1.7 I/min, p &lt; 0.05) at the maximum effects. TPR decreased more than 20% in 5 of 11 patients. There were also slight but not significant decrease in mean systemic blood pressure (SAm)(81 ± 10to 73 ± 4 mmHg)taken as a whole, but obviously fell in 3 patients more than 30%. (2) Chronic effects; PAm (47.5 ± 7 mmHg) and TPR (14.1 ± 3.4 u) significantly decreased, and CO (3.5 ± 0.8I/min) significantly increased compared with baseline values. TPR decreased more than 20% in all but one patient. SAm (81 ± 8 mmHg) were not significantly reduced, and did not fall more than 20% in any patient. All patients are alive and in better conditions during 12.1 ± 6.1 months follow up with chronic adminis-tration. In conclusion, BPS could provide afavorable remedy in the treatment of patients with PH.