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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin D2 (PGD2) produced by platelets can inhibit aggregation via activation of platelet adenylate cyclase. PGD2 activation of platelet cyclase in platelet membrane fractions was studied in 20 consecutive patients hospitalized with acute deep-vein thrombosis and/or pulmonary embolism. In nine patients, PGD2-stimulated enzyme activity was decreased at all concentrations of PGD2 studied. This altered enzyme sensitivity was specific for PGD2 as basal enzyme activity, and prostaglandin E1, prostaglandin I2, and sodium fluoride stimulated adenylate cyclase was normal. The effect of PGD2 on platelet aggregation and 14C-serotonin release was also studied in one patient where a four-fold higher concentration of PGD2 was required to inhibit collagen-induced 14C-serotonin release. Binding studies using [3H]PGD2 as a radioligand indicated that this patient's platelets bound 10 fmole PGD2/10(8) platelets compared to 30 fmole/10(8) platelets in a normal control. Five patients had follow-up studies between 2 and 7 mo after their acute thrombotic event, and PGD2-stimulated adenylate cyclase activity returned towards normal in four. Since PGD2 is synthesized in platelets at concentrations sufficient to inhibit aggregation and activate adenylate cyclase, diminished platelet sensitivity to this prostaglandin could result in "hyperactivity" and contribute to the thrombosis observed in these patients.
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PMID:Diminished platelet adenylate cyclase activation by prostaglandin D2 in acute thrombosis. 38 Jun 88

We report the vascular surgical strategies and results in 13 patients with heparin-associated thrombocytopenia and describe useful in vitro techniques for the evaluation of anticoagulant therapy. Thirteen of 40 patients with heparin-associated thrombocytopenia had 18 cardiovascular procedures done to save life or limb. Greenfield filters were placed in eight patients to prevent pulmonary embolism. Eight patients had 10 arterial procedures, with alternative anticoagulation that used dextran or warfarin in five cases. In three cases iloprost, a derivative of prostacyclin and a potent platelet inhibitor, was infused intraoperatively and heparin was given. Both the use of alternative anticoagulants and platelet suppression by iloprost were clinically effective strategies. The concurrent measurement of plasma levels of beta-thromboglobulin and fibrinopeptide A in two patients confirmed that both approaches can successfully prevent activation of platelets and plasma coagulation during arterial surgery. One operative death occurred; all vascular reconstructions remained patent at 3 to 6 months. In two patients who received heparin alone for arterial surgery, both procedures resulted in thrombosis and limb loss. When major venous thromboembolism is complicated by heparin-associated thrombocytopenia, insertion of a Greenfield vena cava filter should be considered if there is significant risk of pulmonary embolism. When necessary, arterial surgery is feasible in patients with heparin-associated thrombocytopenia if alternative anticoagulation or adequate suppression of platelet reactivity can be achieved.
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PMID:Surgical management of heparin-associated thrombocytopenia. Strategies in the treatment of venous and arterial thromboembolism. 245 20

Drugs with pharmacological activity limited to the pulmonary circulation are not at present available. Serotonin antagonists, specific thromboxane A2 inhibitors and prostacyclin may offer new possibilities for the treatment of certain forms of pulmonary arterial hypertension (PAH), but their clinical efficacy remains to be evaluated. Vasodilators simultaneously influence the pulmonary and systemic vascular resistances, and their overall hemodynamic effects in patients with PAH are therefore unpredictable. Therapeutic trials with such drugs should be closely monitored to avoid serious adverse reactions. Oral administration of beta-adrenergic agents, such as salbutamol or terbutaline, is preferable to digoxin in the treatment of patients with right ventricular failure due to chronic obstructive bronchitis. Right ventricular failure following massive pulmonary embolism may be aggravated by reduced blood flow through the right coronary artery. Increase of aortic perfusion pressure (e.g. noradrenaline) should be considered as a therapeutic measure in patients with arterial hypotension.
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PMID:[Pharmacology of the pulmonary circulation]. 286 81

Reversible causes of pulmonary hypertension, such as mitral stenosis or pulmonary embolism, should be corrected causally. The therapy of pulmonary hypertension is difficult in those diseases where the causes or mechanisms are not understood or are unknown. In chronic obstructive lung disease, the primary objective is to improve airflow and alveolar ventilation (theophylline, beta-sympathicomimetics). Long-term oxygen (more than 18 hours a day) should be used in patients with paO2 below 55 mm Hg, since a reduction in pulmonary vascular resistance and a prolonged survival has been demonstrated. The role of vasodilator therapy (hydralazine, nitrates, diazoxide, captopril, calcium-blockers and others) in chronic obstructive lung disease remains uncertain. In primary pulmonary hypertension, a pulmonary vasodilator is recommended after demonstrating (for example with an infusion of prostaglandin I2), that the increased pulmonary vascular resistance is still reversible. The initiation of therapy should be performed cautiously under hemodynamic monitoring.
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PMID:Treatment of pulmonary hypertension. 287 21

Humoral factors released from platelets during pulmonary embolism may be the cause of several attendant cardiopulmonary abnormalities. This study examines the role of thromboxanes (Tx) after experimental embolism induced with 0.5 g/kg autologous clot in four groups of five dogs: (a) untreated embolized controls; (b) pretreatment with the Tx synthetase inhibitor, imidazole 25 mg/kg . h i.v., starting 30 min before embolization; (c) pretreatment with the cyclooxygenase inhibitor indomethacin, 5 mg/kg, 12 h per os and 1 mg/kg, 1 h i.v. before the experiment; (d) treatment with prostacyclin (PGI(2)) 100 etag/kg . min i.v. for 1 h, 1 h after embolization. Within 30 min, embolization led to increases of 6-keto-PGF(1alpha), the stable hydrolysis product of PGI(2), from 0.11+/-0.08 etag/ml (mean+/-SD) to 0.33+/-0.10 etag/ml (P < 0.005) and TxB(2), the stable product of TxA(2), from 0.10+/-0.04 etag/ml to 0.38+/-0.06 etag/ml (P < 0.001). Increases were observed in total dead space (V(D)/V(T)) from 0.46+/-0.03 to 0.61+/-0.08 (P < 0.025, physiologic shunting (Q(S)/Q(T)) from 16+/-4% to 38+/-9% (P < 0.01), pulmonary vascular resistance (PVR) from 2.27+/-0.59 mm Hg.min/liter to 9.21+/-1.90 mm Hg.min/liter (P < 0.005) and mean pulmonary arterial pressure from 14+/-6 mm Hg to 34+/-1 mm Hg (P < 0.001). Cardiac index (CI) fell from 139+/-11 ml/kg.min to 95+/-17 ml/kg.min in 4 h (P < 0.025). Imidazole pretreatment prevented a rise of TxB(2), but not 6-keto-PGF(1alpha); indomethacin blocked both. Both agents maintained V(D)/V(T) at base line and limited increases in Q(S)/Q(T) and PVR. CI was higher after imidazole pretreatment compared with controls (P < 0.025). Indomethacin led to intermediate levels of CI. PGI(2) lowered TxB(2) (P < 0.025), V(D)/V(T) (P < 0.025), Q(S)/Q(T) (P < 0.025) and PVR (P < 0.05) within 30 min. During PGI(2) infusion, CI was higher than controls. Concentrations of TxB(2) correlated with V(D)/V(T), r = 0.79 and Q(S)/Q(T), r = 0.69 (P < 0.001). Treatment of three dogs with the imidazole derivative ketoconazole, 10 mg/kg IV, 30 min after 0.75 g/kg autologous clot resulted in a lowering of physiologic dead space, but no other improvement of cardiopulmonary function. These results show that a number of cardiopulmonary abnormalities induced by pulmonary embolism are related directly or indirectly to platelet secretions and that V(D)/V(T) is closely allied to TxA(2) levels.
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PMID:Thromboxane mediation of cardiopulmonary effects of embolism. 628 1

The contributions of thromboxane A2 (TXA2) and prostacyclin (PGI2) to the effects of acute pulmonary embolism were evaluated in 18 open-chest rabbits. All rabbits received autologous whole-blood-clot embolus (.4 cc) by way of a catheter in the right ventricle. Pulmonary artery (PA) and left atrial (LA) pressures, and aortic flow (AOQ) were recorded. The stable metabolites of TXA2 (TXB2) and PGI2 (6-Keto PGF1) were assayed by radioimmunoassay at pre- and post-embolization periods (+5, +10, +20, +30, and +40 minutes). Significant elevations of pulmonary vascular resistance (PVR) (normalized), PA pressure, and reduction of AOQ were noted comparing pre-embolus to +5 minute time intervals. A negative correlation was reached between PGI2 and AOQ at +40 minutes (p less than .05). Five of the 13 rabbits died prematurely. At +5 minutes these 5 rabbits had higher PVR (p less than .001) and lower AOQ (p less than .01) than their living counterparts. At +10 minutes AOQ was still significantly lower (p less than .005) and TXB2 was higher (p less than .05) in the premature death group. We conclude that TXB2 is significantly but transiently elevated early following acute pulmonary embolism and may contribute to mortality. In contrast PGI2 does not appear to play an immediate role in the hemodynamic events following embolization but does rise to significant levels later in the course possibly in an attempt to compensate for reduced flow.
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PMID:The release of thromboxane A2 and prostacyclin following experimental acute pulmonary embolism. 634

Pulmonary emboli may impair myocardial performance, causing declines in cardiac index (CI) and right and left ventricular stroke work (LVSW) because of mechanical events. We postulate that embolism also leads to the generation of a humoral factor(s) that may reduce cardiac contractility. Eleven mongrel dogs were infused with 0.5 gm/kg clot. Decreases in CI and LVSW were observed 1 hour after embolization. The stable metabolites of prostacyclin and thromboxane (Tx) A2--6-keto-PGF1 alpha and TxB2, respectively--increased within 30 minutes (P less than 0.005, P les than 0.001) and then decreased. These changes did not correlate with the declines in CI or LVSW. Plasma from embolized animals used to bathe an isolated rat papillary muscle reduced developed tension (Tpd) (P less than 0.001) and decreased calcium ATPase (Ca++-ATPase) activity of a myofibril preparation (P less than 0.001) obtained from rat cardiac muscle. The correlation between the reduction of TPd and myofibril Ca++-ATPase activity was 0.72 (P less than 0.001). The decline in Ca++-ATPase was also related to the decreases in CI (r = 0.59, P less than 0.001) and LVSW (r = 0.57, P less than 0.001). Five animals pretreated with indomethacin prior to embolization had no decrease in LVSW as compared with controls (P less than 0.001). Postembolism plasma did not depress papillary muscle Tpd and did not lower Ca++-ATPase activity of myofibrils. Anesthesia itself did not alter cardiopulmonary function. These results suggest that pulmonary emboli cause the release of a negative inotropic agent(s) into plasma that affects energy availability in the heart and reduces contractility. The production of this agent(s) is inhibited by indomethacin pretreatment.
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PMID:Circulating negative inotropic agent(s) following pulmonary embolism. 646 Oct 81

Pulmonary hypertension (PH) may develop because of a spectrum of insults to the lungs; in some patients, there seems to be no cause. Noninvasive tests, such as standard chest radiography, electrocardiography, and transthoracic Doppler echocardiography, provide effective screening if PH is suspected. This synopsis focuses on these screening studies and the more common clinical problems, including primary cardiac abnormalities, obstructive sleep apnea, chronic pulmonary embolism, pulmonary parenchymal problems, connective tissue disorders, cirrhosis with portal hypertension, and use of appetite suppressants, that should be considered when PH exists. Treatment options for PH, including intravenous prostacyclin (epoprostenol), and investigational agents such as subcutaneous or oral prostacyclin analogues and oral endothelin receptor antagonists are described.
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PMID:Pulmonary hypertension: diagnostics and therapeutics. 1085 24

Primary pulmonary hypertension (PPH) is a condition characterized by sustained elevation of pulmonary artery pressure (PAP) without demonstrable cause. The most common symptom at presentation is dyspnea. Other complaints include fatigue, chest pain, syncope, leg edema, and palpitations. Right heart catheterization is diagnostic, showing a mean PAP >25 mmHg at rest and >30 mmHg during exercise, with a normal pulmonary capillary wedge pressure. In the National Institutes of Health-PPH registry, the median survival period was 2.8 years. Treatment is aimed at lowering PAP, increasing cardiac output, and decreasing in situ thrombosis. Vasodilators have been used with some success in the treatment of PPH. They include prostacyclin, calcium-channel blockers, nitric oxide and adenosine. Anticoagulation has also been advised for the prevention of deep vein thrombosis, pulmonary embolism, and in situ thromboses of the lungs. New drug treatments under investigation include L-arginine, plasma endothelin-I, and bosentan. Use of oxygen, digoxin, and diuretics for symptomatic relief have also been recommended. Patients with severe PPH refractory to medical management should be considered for surgery.
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PMID:Primary pulmonary hypertension. 1172 93

Pulmonary arterial hypertension is a severe disease that has been ignored for a long time. However, over the past 20 yrs chest physicians, cardiologists and thoracic surgeons have shown increasing interest in this disease because of the development of new therapies, that have improved both the outcome and quality of life of patients, including pulmonary transplantation and prostacyclin therapy. Chronic thromboembolic pulmonary arterial hypertension (CTEPH) can be cured surgically through a complex surgical procedure: the pulmonary thromboendarterectomy. Pulmonary thromboendarterectomy is performed under hypothermia and total circulatory arrest. Due to clinically evident acute-pulmonary embolism episodes being absent in > 50% of patients, the diagnosis of CTEPH can be difficult. Lung scintiscan showing segmental mismatched perfusion defects is the best diagnostic tool to detect CTEPH. Pulmonary angiography confirms the diagnosis and determines the feasibility of endarterectomy according to the location of the disease, proximal versus distal. The technique of angiography must be perfect with the whole arterial tree captured on the same picture for each lung. The lesions must start at the level of the pulmonary artery trunk, or at the level of the lobar arteries, in order to find a plan for the endarterectomy. When the haemodynamic gravity corresponds to the degree of obliteration, pulmonary thromboendarterectomy can be performed with minimal perioperative mortality, providing definitive, excellent functional results in almost all cases.
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PMID:Chronic thromboembolic pulmonary hypertension. 1508 67


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