Prostacyclin Therapy Research Articles

Intravenous prostacyclin in thrombotic thrombocytopenic purpura: case report and review of the literature

The use of prostacyclin infusion in thrombotic thrombocytopenic purpura is consistent with the hypothesis that patients may lack a plasma factor stimulating prostacyclin production. However, prostacyclin therapy, alone or in combination with aspirin, dipyridamole, steroid and plasmapheresis, failed in many cases. We here describe the case of a patient who responded dramatically to a combination of prostacyclin and plasma infusions, after conventional therapy had failed (plasmapheresis, fresh frozen plasma infusions). Prostacyclin was infused intravenously initially for 120 h from 4 to 9 ng kg min-1 and then continuously for 48 h at 9 ng kg min-1. Despite the scarcity of case reports in the literature, we conclude that the failure of prostacyclin in thrombotic thrombocytopenic purpura appears to be related to insufficient doses and/or duration of therapy.

Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction

Current limitations of recombinant tissue-type plasminogen activator (rt-PA) therapy for acute myocardial infarction include failure to achieve recanalization in 25% of patients, reocclusion and reperfusion injury. IIoprost, a stable analogue of prostacyclin (PGIZ), has been demonstrated to facilitate thrombolysis and reduce myocardial stunning in experimental models. To evaluate combined therapy, rt-PA (100 mg 3 h) and IIoprost (2 ng/kg per min for 48 h) were administered to 25 patients and then rt-PA alone (same dose) was given to an additional 25 patients with evolving myocardial infarction. At 90 min after drug administration, infarct-related vessel patency was observed in 11 (44%) of 25 who received rt-PA plus Iloprost compared with 15 (60%) of 25 who received rt-PA alone (p = 0.26). At 1 week, reocclusion had occurred in 3 (14%) of 21 patients who received combined therapy compared with 6 (26%) of 23 patients treated with rt-PA alone (p = 0.46).Ejection fraction increased significantly from baseline to 7 days for rt-PA alone whereas it decreased with combined therapy (rt-PA alone: 47.3 ± 11.5% at baseline to 50.4 ± 9.8% at 7 days; rt-PA plus Iloprost: 51.3 ± 10.1% at baseline to 49.0 ± 9.4% at 7 days; difference between groups p = 0.05). At 4 h after therapy, fibrinogen decreased 33% for rt-PA plus Iloprost compared with a 52% for rt-PA alone (p = 0.001). Fibrinogen degradation products increased 60% more for rt-PA alone than for rt-PA plus Iloprost. Thus, the combination of rt-PA plus Iloprost at the doses employed did not improve immediate or follow-up coronary artery patency or left ventricular functional recovery compared with that achieved with rt-PA alone.

Primary pulmonary hypertension

Primary pulmonary hypertension has become a very treatable disease given the recent advances in medical therapy. Any patient with unexplained right ventricular enlargement or pulmonary hypertension needs a thorough workup to determine the cause. Patients with primary pulmonary hypertension should be referred to a specialized Center of Excellence to evaluate potential therapies on a case-by-case basis. Warfarin anticoagulation is generally recommended in all patients. Some patients (approximately 20%) will have a dramatic response to high doses of calcium channel blockers; the remainder are generally helped by the use of continuous intravenous prostacyclin therapy. Lung transplantation remains the final treatment option for patients in whom medical therapy fails.

Modification of pulmonary hypertension secondary to congenital heart disease by prostacyclin therapy.

We have shown that PGI2 is a powerful but not selective pulmonary vasodilator, and we believe that there is a role for PGI2 in pulmonary vascular disease secondary to congenital heart disease, but much work remains to be done, including comparisons of PGI2 with other vasodilators. The role of PGI2 in altering the cellular and chemical events producing pulmonary vascular disease secondary to congenital heart disease, and any role in long-term treatment, is largely unexplored.

Review article : Prostacyclin therapy during cardiopulmonary bypass—is it beneficial?

Review article : Prostacyclin therapy during cardiopulmonary bypass—is it beneficial?

The effects of itnravenous ZK36-374, a stsable prostacyclin analogue, on normal volunteers

Prostacyclin (PGI 2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivatives with a similar action to PGI 2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. β-thromboglobulin, 6-keto-PGF 1α and TXB 2 were measuerd by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2μm AdP and 2μg collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2μm ADP and 0.5 μg collagen. βTG also fell significantly, as did the levels of 6-keto-PGF 1α and TXB 2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.

Effect of prostacyclin and prazosin in the treatment of congestive heart failure; with special reference to the sympathetic nervous system.

Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacyclin (PG I2) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22 +/- 11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0 +/- 7.9 to 15.0 +/- 6.6 mmHg (p less than 0.001), mean arterial pressure from 98.9 +/- 12.8 to 76.2 +/- 7.0 mmHg (p less than 0.001), systemic vascular resistance from 2,574 +/- 384 to 1,368 +/- 283 dynes X sec X cm-5 (p less than 0.001), pulmonary vascular resistance from 1,008 +/- 451 to 443 +/- 135 dynes X sec X cm-5 (p less than 0.001) and pulmonary arteriolar resistance from 330 +/- 111 to 189 +/- 73 dynes X sec X cm-5 (p less than 0.001). The cardiac index increased from 2.0 +/- 0.37 to 3.2 +/- 0.59 l/min/m2 (p less than 0.001), and the stroke index from 27.6 +/- 8.69 to 42.0 +/- 0.62 ml/m2 (p less than 0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of ischaemic stroke with prostacyclin.

Ten patients with ischaemic stroke were treated with prostacyclin (2.5-5.0 ng/kg/min i.v. in 6 h courses 4-10 times during 1-2.5 days). In all patients a dramatic regression of hemiplegia, or hemiparesis, or aphasia occurred in the first few hours of prostacyclin infusion. Four to eight weeks later 6 patients left the clinic without neurological deficit; 3 patients had minor residual hemiparesis in upper limbs. In one patient, the occlusion of the contralateral carotid artery led to his death. It is considered that an antagonism may exist between endogenous cerebral prostanoids and prostacyclin and may have been responsible for the beneficial effects of prostacyclin therapy.

Prostacyclin therapy in patients with congestive heart failure

The acute hemodynamic effects of intravenous prostacyclin (PGI 2), in doses of 22 ± 11 ng/kg per min were studied in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean (±standard deviation) pulmonary capillary wedge pressure decreased from 21.0 ± 7.9 to 15.0 ± 6.6 mm Hg (p < 0.001), mean arterial pressure from 98.9 ± 12.8 to 76.2 ± 7.0 mm Hg (p < 0.001), systemic vascular resistance from 2,574 ± 384 to > 1,368 ± 283 dynes s cm −5 (p < 0.001), pulmonary vascular resistance from 1,008 ± 451 to 443 ± 135 dynes s cm −5 (p < 0.001) and pulmonary arteriolar resistance from 330 ± 111 to 189 ± 73 dynes s cm −5 (p < 0.001). Heart rate increased from 78 ± 21 to 82 ± 24 beats/min (p = not significant [NS]), cardiac index from 2.0 ± 0.37 to 3.2 ± 0.59 liters/min per m 2 (p < 0.001) and stroke index from 27.6 ± 8.69 to 42.0 ± 0.62 cc/m 2 (p < 0.001). With prostacyclin, moreover, coldness of the limbs and face disappeared, and patients felt warmth and mild flushing of the face. After prostacyclin, plasma norepinephrine levels, renin activity and aldosterone concentrations rose from 824 ± 375 to 880 ± 468 pg/ml (NS), 0.68 ± 1.36 to 0.95 ± 1.21 ng/ml per h (NS), and 6.64 ± 2.50 to 6.38 ± 2.88 ng/dl (NS), respectively, while plasma epinephrine increased from 140 ± 80 to 250 ± 154 pg/ml (p < 0.025).

Prostacyclin therapy in patients with congestive heart failure

Prostacyclin therapy in patients with congestive heart failure

Prostacyclin therapy in peripheral arterial disease.

Abstract Thirty patients with advanced peripheral arterial disease of lower extremities were treated with a single or multiple courses of prostacyclin /2–10 ng/kg/min intraarterially or intravenously for about 72 hours/. The observation period ranged from 2 to 15 months. The sustained improvement, as evidenced by alleviation of rest pain and healing of ischemic ulcers, occurred in 40 per cent of patients. Severity of local symptoms and arteriographic localization of the lesions are of essential prognostic value for the efficacy of prostacyclin therapy, however, they do not comprise all of the factors which determine responsiveness to prostacyclin. Platelet activity as assessed by several in vitro and in vivo methods was suppressed during the therapy, and returned to normal shortly after termination of the infusions. These short-lasting anti-platelet as well as vasodilatory effects of prostacyclin are in contrast with persistance of the clinical improvement which occurred in a substantial number of patients.

SUCCESSFUL THERAPY OF ADVANCED ARTERIOSCLEROSIS OBLITERANS WITH PROSTACYCLIN

Five patients with advanced arteriosclerosis obliterans of the lower extremities, as evidenced by resting pain, ischæmic ulcers, and focal necrosis, received intra-arterial infusions of prostacyclin at doses of 5-10 ng/kg/min for 72 h. Within 2 days of termination of the infusion, pain at rest had disappeared in all patients. In three of the five, the necrosis had completely regressed and the ischæmic ulcers healed within 2 months. The other two patients showed considerable improvement. Prostacyclin therapy was not associated with changes in the radiographic appearance of the major blood-vessels. However, muscle blood-flow, as measured by xenon-133 clearance, was significantly in- creased both during prostacyclin infusion and for the 6 weeks of measurement after its termination.