Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early reperfusion of occluded coronary arteries offers great promise as a method for minimizing myocardial damage after acute myocardial infarction. Such reperfusion is usually attempted via administration of fibrinolytic agents. Urokinase may hold marginal advantages over streptokinase, especially in patients with high preexisting titers of antistreptokinase antibodies. These minor differences, however, pale in comparison to important advantages demonstrated by the newly developed agent, tissue plasminogen activator (t-PA). The advantages of t-PA derive primarily from its property of binding to, and being activated by, fibrin. Consequently the generated plasmin is also fibrin-bound, the bound plasmin is protected from circulating antiplasmin and therefore more efficiently utilized, and circulating fibrinogen is spared. Preliminary clinical experience indicates that the frequency of favorable response after intravenous administration of t-PA is considerably greater than after SK. A major determinant of clinical benefit after reperfusion is the brevity of ischemia. Selective intracoronary infusion of fibrinolytic agent produces faster lysis than does intravenous infusion, and rate of lysis may be further accelerated by transcatheter disruption of clot and intrathrombic injections of highly concentrated urokinase or t-PA. Even maximally accelerated lysis, however, cannot fully compensate for the inherent delay imposed by catheterization. For that reason, prompt intravenous infusion of fibrinolytic agents, presumably t-PA, seems preferable to the intracoronary route. In the effort to initiate fibrinolytic therapy at the earliest feasible time after infarction, administration by paramedics, or even home administration after training, is a program worthy of exploration.
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PMID:Streptokinase, urokinase, and tissue plasminogen activator: pharmacokinetics, relative advantages, and methods for maximizing rates and consistency of lysis. 310 38

Thrombolytic agents may be useful in the treatment of cerebral ischemia caused by arterial thrombosis or embolic occlusion. A trial of intravenous human tissue-type plasminogen activator (rt-PA) was carried out in seven male Sprague-Dawley rats subjected to embolic cerebral ischemia, with eight control animals. One-hour-old autogenous blood clot was injected into the internal carotid artery. A 30-minute infusion of 10 micrograms/kg/minute of rt-PA or saline followed. Areas of ischemia at two hours post-embolization were assessed by digital image processing of serial iodo-14C-antipyrine autoradiographic images. The volumes of "no-flow" (NF) and "low-flow" (LF) regions were calculated. One animal in each group suffered no detectable ischemia; the remainder had well-defined regions of middle and posterior cerebral artery ischemia. No animal sustained a hemorrhagic lesion. Treatment produced no noticeable effect on the patency of cervical vessels. Total NF and LF volumes were less for the treated group but did not reach statistical significance by t-test. In middle cerebral distribution sections, however, LF volume was significantly less (p less than 0.05) for treated animals (150 vs. 191 mm3), primarily due to a more significant decrease in LF volume in the anterior-middle cerebral overlap zone (47 vs. 90 mm3; p less than 0.025). Fibrinogen levels were not altered by drug treatment (p greater than 0.30).
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PMID:The effect of intravenous tissue-type plasminogen activator in a rat model of embolic cerebral ischemia. 311 Nov 8

The hemorheologic changes in three groups of patients suffering from acute and chronic cerebrovascular diseases were studied. Firstly, a horizontal study on 57 patients with definite stroke and on 49 patients with TIA was made. Plasma viscosity, whole blood filtration rate, fibrinogen concentration and hematocrit were evaluated as markers of the rheological property of blood. Blood samples were drawn within 6 h from the onset of vascular syndrome. The findings were compared with values obtained in 112 as controls. At the same time, washed red cell filtration rate, together with lactoferrin, betaglucuronidase and beta-thromboglobulin plasma level were assayed. In both groups the onset of the vascular storm was associated with a marked increase of plasma fibrinogen and of blood and plasma viscosity and a significant decrease of whole blood filterability. Lactoferrin, betaglucuronidase and beta-thromboglobulin levels were also significantly increased. Following this, a longitudinal study was performed on 27 patients with definite stroke and 32 patients with TIA. The clinical regression of acute stroke was associated with the progressive reduction of rheological abnormalities. Finally, 81 patients with clinical diagnosis of cerebrovascular disease due to previous stroke or repeated TIA were studied together. An increase of blood viscosity, of fibrinogen concentration and of hematocrit and a decrease of blood filtration rate together with higher levels of beta-thromboglobulin were registered. These results confirm the existence of an association between CVD and hemorheological alterations and suggest more in depth research directed towards identifying the significance of these alterations in the pathogenesis of tissue ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemorheological factors in the pathophysiology of acute and chronic cerebrovascular disease. 316 Apr 74

Atherogenic traits, living habits, signs of preclinical disease, and susceptibility all contribute to cardiovascular disease. High low-density lipoprotein is positively related to coronary heart disease, and high high-density lipoprotein is inversely related. Systolic or diastolic hypertension at any age in either sex contributes powerfully. The impact of diabetes is greater for women and varies with the number of accompanying risk factors. High-normal fibrinogen values further escalate risk of these atherogenic factors. An atherogenic life-style is typified by a diet excessive in fat, calories, and salt; sedentary habits; unrestrained weight gain; and cigarette smoking. Moderate alcohol use may be beneficial. Use of oral contraceptives beyond age 35 years and in conjunction with cigarette smoking predisposes one to thromboembolism. Type A behavior carries an increased risk, and men married to more highly educated women and to women in white-collar jobs are more vulnerable. Signs of preclinical ischemia include silent myocardial infarction, left ventricular hypertrophy on ECG, blocked intraventricular conduction, and repolarization abnormalities. Measures of innate susceptibility include a family history of early cardiovascular disease. Quantitative combination of risk factors provides optimal prediction, including persons with multiple marginal abnormalities. Preventive management should also be multifactorial and requires a commitment to behavior modification and alteration in life-style.
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PMID:New perspectives on cardiovascular risk factors. 330 Feb 33

Clinical pathology is a valuable adjunct to physical examination of cases of colic. The present review considers evaluation of cases of colic for three main purposes: (1) making a prognosis, (2) deciding whether to operate, and (3) making a diagnosis. Blood tests noted to be useful for prognostication were hematocrit, lactate and urea nitrogen concentrations, pH, anion gap, fibrin/fibrinogen degradation products, antithrombin III activity, prothrombin time, and thrombin time. Horses with a poor prognosis often have relative polycythemia, marked lactic acidosis, high anion gap, azotemia, and coagulation abnormalities evidenced by increased fibrin/fibrinogen degradation products, decreased antithrombin III activity, and prolonged prothrombin and thrombin times. The decision to operate is usually a clinical one, supported by relative polycythemia, hyperglycemia, and, possibly, abnormal peritoneal fluid analysis. Diagnosis of the primary problem (causing the colicky signs) is also often based largely on physical examination. However, peritoneal fluid analysis provides worthwhile data, especially in cases of peritonitis or intestinal ischemia and infarction.
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PMID:Use of clinical pathology in evaluation of horses with colic. 332 25

Obstruction of the superficial femoral vein is, most of the time, secondary to atheroma. It is possible to correct it with a reconstructive procedure such as a by-pass. The results of 55 femoro-popliteal by-passes show that the mean age of the patients is between 50 and 60 years, that they are male, and often inveterate smokers. It is Fontaine's 2nd degree ischemia which is observed most of the time. The greater saphenous vein was always satisfactorily used. Three years after the procedure, the results of this venous autograft were studied and we noticed only four obstructions of the graft. These results seem related to higher fibrinogen levels, a defective heart condition, an insufficient diameter of the arteries receiving the graft. Only one leg amputation was performed at the level of the knee.
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PMID:[Femoral-popliteal by-pass by an internal saphenous vein graft]. 340 66

Thrombolytic therapy has been shown to be effective in reopening totally occluded arteries in acute myocardial infarction. Coronary thrombus is also believed to play a role in the pathophysiology of unstable angina and non-Q wave infarction. However, few patients with these two acute coronary syndromes have been treated with intracoronary streptokinase. Therefore, 100,000 to 300,000 IU (mean 177,000 +/- 80,000 IU) of intracoronary streptokinase was infused into 36 consecutive catheterized patients who either presented with an acute episode of unstable angina or had had a recent non-Q wave infarction and in whom a less than 100% occluded ischemia-producing artery could be identified. Qualitative techniques utilizing vessel magnification and quantitative analysis with digital subtraction were performed on the ischemia-producing coronary lesion before and immediately after streptokinase therapy and 3 to 10 days later in 18 patients who were restudied at the time of transluminal coronary angioplasty. Before streptokinase treatment, 24 (67%) of 36 ischemia-producing arteries contained eccentric, irregular lesions. The percent diameter stenosis and percent area stenosis in all ischemia-producing arteries averaged 83.8 +/- 8.3% and 94.8 +/- 3.3%, respectively. After streptokinase treatment there were 23 arteries (64%) with eccentric irregular lesions. The percent diameter stenosis and percent area stenosis in all ischemia-producing arteries were similar to pre-streptokinase values (82.9 +/- 5.9% and 93.8 +/- 4.0%, respectively). At restudy, there were also no significant changes in any quantitative or qualitative variable. Five individual patients showed a significant reduction in percent stenosis after streptokinase. This improvement was independent of duration of symptoms, use of heparin before angiography, streptokinase dose or reduction of fibrinogen levels post-streptokinase. Two additional patients deteriorated clinically and developed total occlusion of the ischemia-producing artery within 12 hours of streptokinase infusion. These data suggest that intracoronary streptokinase may be of limited utility in either unstable angina or recent non-Q wave infarction with a less than 100% occluded ischemia-producing artery. In these syndromes, thrombus may be organized or short infusions may be given too late to be effective. In some cases, thrombus may even be absent. Whether longer infusion of streptokinase or other thrombolytic agents will be of benefit remains to be determined.
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PMID:Quantitative and qualitative effects of intracoronary streptokinase in unstable angina and non-Q wave infarction. 355 76

Predictable vascular responses to burn injury can occur where blood vessels are occluded in and just beneath the site of trauma. The loss of vascular patency is linked to the development of ischemia in the surrounding skin. Several mechanisms may be responsible for this occlusion, and their identification will provide a logical means for prevention or reversal of the occlusion. The role of fibrin deposition was investigated here using a rat burn model. If an intravascular fibrin clot is a primary cause of early occlusion, the depletion of circulating fibrinogen should prevent its deposition. Ancrod, a pit viper venom trypsin-like proteinase, when given systemically, converts fibrinogen into a soluble product which does not clot. In studies here, the host is depleted of fibrinogen by intravenous injections of ancrod for 3 days before standard burn trauma. Burn injury in defibrinogenized rats resulted in greatly reduced local vascular occlusion. These results support the idea that vascular occlusion caused by burn injury is dependent on the deposition of fibrin. It is conjectured that the vascular occlusion of burn injury can be reversed by preventing or breaking down intravascular fibrin clots.
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PMID:Ancrod prevents vascular occlusion in thermally injured rats. 357 90

This is a prospective analysis of patients undergoing 34 treatments for arterial thromboses and emboli with intra-arterial thrombolytic therapy. These included acute arterial thromboses, graft thromboses, arterial emboli and pulmonary emboli. Twenty-seven of 34 patients treated had evidence of lysis, 14 had complete lysis, 13 had partial lysis and seven had no lysis. Both patients with occlusions for longer than three weeks failed to respond to treatment. Thirty-two patients presented with ischemia of the extremity. Twenty-four of 32 patients had limb salvage with eight subsequently undergoing amputation. No patient who was treated for claudication or who had a patent popliteal artery distal to the acute thrombosis failed to respond. Extensive tibioperoneal occlusion generally responded poorly compared with femoropopliteal or more proximal thrombi. Complications are divided into direct (drug related) and indirect (technique related). Four of 34 patients had an extensive hemorrhagic event with two suffering intracranial bleeding who ultimately died. All of the patients with extensive hemorrhagic episodes had serum fibrinogen levels of less than 50 milligrams per cent. During infusion, extensive distal emboli occurred in three with two of these patients requiring thrombectomy; one instance resolved with infusion. Minor distal emboli occurred in three and all resolved with continued infusion. We believe that intra-arterial thrombolytic therapy is a valuable adjunct in the treatment of acute arterial occlusion. The local infusion of lytic agents appears to be more efficient than systemic therapy. The tip of the infusion catheter should be placed into the thrombus for optimal lysis, but not advanced too far. The fibrinogen level is a sensitive indicator of systemic lysis and should be maintained above 50 milligrams per cent. Systemic lysis is obtained even with low dose infusion when therapy exceeds six hours. Intra-arterial infusion of thrombolytic agents can be performed safely in the immediate postoperative period as well as intraoperatively if specific guidelines are followed. Patients with massive unilateral pulmonary embolism can be efficiently treated with intra-arterial lytic therapy.
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PMID:Intra-arterial thrombolytic therapy in peripheral vascular disease. 358 18

Sixty-two patients hospitalized for recent angiographically documented arterial occlusion in the legs (46 femoropopliteal arteries and 16 grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a No. 4F or No. 5F catheter. This therapy combined a continuous urokinase (UK) infusion of 1000 U/kg/hr and a lysyl plasminogen (LYS-PLG) infusion of 15 mukat every 30 minutes. Angiographically confirmed lysis was obtained in 77% of the cases. Five percent of the patients had major and 8% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK and LYS-PLG is as effective as streptokinase but produces lower systemic fibrinolysis. However, local fibrinolysis remains a potentially hazardous procedure (10% suffered major complications) and must only be applied to patients with severe ischemia and little or no possibility of surgical intervention.
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PMID:Local thrombolysis in peripheral arteries and bypass grafts. 365 85


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