Analysis of coagulation and fibrinolysis during intravenous infusion of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction

Coagulation and fibrinolysis were studied in patients with acute myocardial infarction during intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 90 min, n = 101), streptokinase (1,500,000 IU over 60 min, n = 61), or placebo (n = 40). In the rt-PA group, the plasma level of rt-PA antigen was 1.2 +/- 0.6 micrograms/ml (mean +/- SD) and the euglobulin fibrinolytic activity (EFA) was 910 +/- 735 IU t-PA/ml. In the streptokinase group, the EFA was equivalent to 430 +/- 435 IU t-PA/ml. At the end of the infusion, the plasma fibrinogen level measured with a coagulation rate assay was decreased to 57 +/- 33% of the preinfusion value in the rt-PA group, to 7 +/- 10% in the streptokinase group, and remained unchanged in the placebo group. Fibrinogen-fibrin degradation products increased to 0.75 +/- 0.54 mg/ml in the streptokinase group but to only 0.10 +/- 0.13 mg/ml in the rt-PA group. The plasma levels of alpha 2-antiplasmin, plasminogen, and factor V decreased to between 30% and 45% in the rt-PA group but significantly more in the streptokinase group (to between 15% and 25%). Thus rt-PA induced much less systemic fibrinolytic activation than streptokinase. In the patients who received rt-PA, a weak correlation (r = .21, n = 89, .1 greater than p greater than .05) was found between the extent of fibrinogen breakdown at 90 min and the plasma rt-PA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (activase) in acute myocardial infarction

A new, predominantly single chain preparation of recombinant tissue-type plasminogen activator was evaluated to determine coronary thrombolytic efficacy in 100 patients with acute myocardial infarction. At 3.6 +/- 1.2 hours (mean +/- SD) from symptom onset, patients received either intravenous tissue plasminogen activator (1.25 mg/kg body weight over 3 hours) or placebo on a 3:1 randomized, double-blind basis. Coronary angiography, performed 68 +/- 13 minutes after initiation of the study drug infusion, demonstrated patency of the infarct-related artery in 40 (57%) of 70 patients in the tissue plasminogen activator group compared with 3 (13%) of 23 patients in the placebo group (p less than 0.001). Patients in the placebo group were then eligible to receive intracoronary streptokinase. At 90 minutes the patency was observed in 49 (69%) of 71 tissue plasminogen activator patients compared with 5 (24%) of 21 placebo patients (p less than 0.001). At 120 minutes patency was observed in 59 (79%) of 75 patients of the tissue plasminogen activator group and in 10 (40%) of 25 in the intracoronary streptokinase/placebo group. A nadir value of less than 100 mg/dl fibrinogen occurred in 8 (11%) of 73 patients receiving tissue plasminogen activator versus 8 (40%) of 20 patients treated with intracoronary streptokinase (p = 0.002). Moderate or severe bleeding episodes occurred in 39% of patients treated with tissue plasminogen activator compared with 32% of patients who received placebo/intracoronary streptokinase (p = NS). Thus, this tissue plasminogen activator preparation achieves a high rate of recanalization and, at the doses employed, exhibits increased fibrinogen sparing compared with intracoronary streptokinase.     

Rate of fibrinogen breakdown related to coronary patency and bleeding complications in patients with thrombolysis in acute myocardial infarction--results from the PRIMI trial.

Four hundred and one patients with acute myocardial infarction of less than 4 h duration were randomized to receive intravenous thrombolytic treatment with either 80 mg of full length unglycosylated single-chain-urokinase plasminogen activator (INN saruplase) or 1.5 million IU of streptokinase delivered over a 60 min period. Angiographic patency rates were higher at 60 min in saruplase treated patients (71.8% vs 48%; P less than 0.001), but did not differ significantly at 90 min (71.2% vs 63.9%; P = 0.15). Fibrinogen levels dropped markedly in both groups, the decrease being delayed and less pronounced with saruplase. Total fibrin and fibrinogen degradation products and D-dimer values rose earlier and to higher peak values in streptokinase treated patients. In both groups marked plasminogen and alpha 2-antiplasmin consumption was observed. Lower fibrinogen levels, and in particular the faster rate of fibrinogen breakdown, were associated with higher patency rates at 90 min (P less than 0.05). Patients with bleeding complications had lower 'lowest points' and a more rapid decrease in fibrinogen (P less than 0.05). These findings were not related to the drug used. Increased heparin levels at 6 to 12 h were correlated to bleeding complications in streptokinase treated patients. It is concluded that the rate of fibrinogen breakdown during and following thrombolytic treatment for acute myocardial infarction is related to early vessel patency and bleeding complications.     

Comparison of intracoronary and intravenous methods of thrombolytic streptokinase therapy of patients with myocardial infarct

Intracoronary streptokinase (250.000 units over 60-90 min) was administered within 7.8 +/- 0.4 hrs after the onset of myocardial infarction symptoms to 85 patients, and intravenous streptokinase (500.000 units over 5-10 min) was given within 4.8 +/- 0.4 hrs to 46 myocardial infarction patients. Coronary angiography was conducted 1 to 3 hours after intravenous streptokinase administration. Coronary arterial reperfusion was achieved in 62% of patients in the former group, and in 66% in the latter one. Reperfusion was seen in 84% of patients in the first 3 hours after the onset of infarction, and in 60-66% at later dates. Hypofibrinogenemia did not become critical and persisted for one more day in cases of intravenous streptokinase infusions, as compared to the intracoronary route. Intravenous administration of 500.000 units streptokinase at the rate of 100.000-50.000 U/min is an effective and safe method for the treatment of myocardial infarction, and its prospective application in health practices appears quite promising.     

Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial

Forty-five patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were prospectively randomized, two for one, to treatment of acute coronary thrombosis with intravenous recombinant human tissue-type plasminogen activator (rt-PA) or placebo. Each of five additional consecutive patients was treated with a high dose of rt-PA for 2 hr. Twenty-five of 33 patients (75%) receiving 0.5 to 0.75 mg/kg of rt-PA over 30 to 120 min had angiographically proven recanalization within 90 min of initiation of therapy. Only one of 14 patients given placebo had spontaneous recanalization within 45 min (p less than .001). Thirteen placebo-treated patients were crossed over to the intracoronary rt-PA group. Nine (69%) exhibited subsequent recanalization within 45 min. Levels of circulating fibrinogen decreased after treatment with rt-PA by an average of only 8% of baseline values. None of the patients manifested a depletion of fibrinogen level to below 100 mg/dl. Six patients who were completely unresponsive to rt-PA were subsequently treated with intracoronary streptokinase and none responded. Thus, either intravenous or intracoronary rt-PA induced coronary thrombolysis without eliciting clinically significant fibrinogenolysis in patients with evolving myocardial infarction due to thrombotic coronary occlusion.     

Intracoronary versus intravenous streptokinase in acute myocardial infarction

To assess the relative efficacy of coronary thrombolysis using intracoronary versus intravenous streptokinase, 32 patients with acute myocardial infarction were randomly assigned to receive intracoronary (n = 17) and intravenous streptokinase (n = 15). All patients underwent selective coronary arteriography before and after administration of streptokinase by either route within 4 hours of the onset of symptoms. Intravenous streptokinase was given as 750,000 units over 30 minutes, while a mean dose of 180,000 units was required for thrombolysis in the group having intracoronary delivery. Recanalization occurred in 71.4% (10 of 14) of patients receiving streptokinase, by the intracoronary group in contrast to only 25% of patients (3 of 12) who received the drug intravenously (P less than 0.05). Spontaneous thrombolysis was seen in 17.6% and 20% of the patients in the groups having intracoronary and intravenous delivery, respectively. Bleeding complications were few in both groups. Thus, when baseline coronary arteriography is performed, recanalization with intracoronary streptokinase is more effective in the treatment of acute myocardial infarction than intravenous streptokinase.     

Coronary thrombolysis in dogs with intravenously administered human pro-urokinase

Coronary thrombolysis was induced by infusion of highly purified human pro-urokinase isolated from a transformed kidney cell line (ACHN) or by infusion of urokinase of urinary origin in anesthetized dogs with 1-hr-old clots in the left anterior descending coronary artery. The clots were induced with a copper coil and thrombolysis was detected by repeat coronary angiography. Intravenous infusion of pro-urokinase at a rate of 10 micrograms/kg/min for 30 min in two dogs did not induce thrombolysis, which was only obtained after 8 and 15 min of its subsequent intracoronary administration. Intravenous infusion of pro-urokinase at a rate of 20 micrograms/kg/min for 30 min in four dogs induced coronary thrombolysis within 23 +/- 2 min (mean +/- SEM). This was not associated with systemic fibrinolytic activation because the alpha 2-antiplasmin and fibrinogen levels did not decrease. Intravenous infusion of urokinase at a rate of 10 micrograms/kg/min for 30 min elicited thrombolysis in four of seven dogs within an average of 19 +/- 2 min. In the other three dogs thrombolysis was only obtained within 11 +/- 3 min of its subsequent intracoronary infusion. Administration of urokinase was associated with systemic fibrinolytic activation as evidenced by a decrease of alpha 2-antiplasmin to about 10% and of fibrinogen to 43 +/- 13% of the preinfusion value. It is concluded that intravenous infusion of pro-urokinase at a sufficiently high rate produces coronary thrombolysis without systemic fibrinolysis in dogs.     

Coronary thrombolysis with human single-chain, urokinase-type plasminogen activator (pro-urokinase) in patients with acute myocardial infarction

Single-chain, urokinase-type plasminogen activator (pro-urokinase), isolated from the conditioned medium of a human renal adenocarcinoma cell line, was administered to six patients with evolving myocardial infarction of less than 5 hours' duration and angiographically confirmed total occlusion of the infarct-related coronary artery. The agent was infused intravenously at a rate of 40 mg over 60 minutes immediately followed in three patients by intracoronary infusion of 20 mg over 30 minutes. In four of the six patients complete reperfusion was obtained during intravenous administration and in one patient after 20 minutes of intracoronary infusion. One patient did not respond. The infusion caused significant changes in the fibrinogen level and generation of fibrinogen breakdown products in only one patient. Single-chain, urokinase-type plasminogen activator can induce clot-selective coronary thrombolysis in patients with acute myocardial infarction.     

Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase

The recent establishment of a firm therapeutic role for reperfusion in acute myocardial infarction has stimulated interest in the development of more ideal thrombolytic agents. Anisoylated plasminogen streptokinase activator complex (APSAC) is a new plasminogen activator possessing properties that are promising for intravenous thrombolytic application in acute myocardial infarction. To assess the reperfusion potential of intravenous APSAC, a multi-center, angiographically controlled reperfusion trial was performed. An approved thrombolytic regimen of intracoronary streptokinase served as a control. Consenting patients with clinical and electrocardiographic signs of acute myocardial infarction were studied angiographically and 240 qualifying patients with documented coronary occlusion (flow grade 0 or 1) were randomized to treatment in less than 6 h of symptom onset (mean 3.4 h, range 0.4 to 6.0) with either intravenous APSAC (30 U in 2 to 4 min) or intracoronary streptokinase (160,000 U over 60 min). Both groups also received heparin for greater than or equal to 24 h. Reperfusion was evaluated angiographically over 90 min and success was defined as advancement of grade 0 or 1 to grade 2 or 3 flow. Rates of reperfusion for the two treatment regimens were 51% (59 of 115) at 90 min after intravenous APSAC and 60% (67 of 111) after 60 min of intracoronary streptokinase (p less than or equal to 0.18). Reperfusion at any time within the 90 min was observed in 55 and 64%, respectively (p less than or equal to 0.16). Time to reperfusion occurred at 43 +/- 23 min after intravenous and 31 +/- 17 min after intracoronary therapy. The success of intravenous therapy was dependent on the time to treatment: 60% of APSAC patients treated within 4 h exhibited reperfusion compared with 33% of those treated after 4 h (p less than or equal to 0.01). Reperfusion rates were also dependent on initial flow grade (p less than or equal to 0.0001): 48% (81 of 168) for grade 0 (APSAC = 43%, streptokinase = 54%), but 78% for grade 1 (APSAC = 78%, streptokinase = 77%). APSAC given as a rapid injection was generally well tolerated, although the median change in blood pressure at 2 to 4 min was greater after APSAC than after streptokinase (-10 versus -5 mm Hg). Mean plasma fibrogen levels fell more at 90 min after the sixfold higher dose of APSAC than after streptokinase (to 32 versus 64% of control). Reported bleeding events were more frequent after APSAC but occurred primarily at the site of catheter insertion and no event was intracranial.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prospective randomized trial of intravenous and intracoronary streptokinase in acute myocardial infarction

To evaluate the relative thrombolytic efficacy and complications of intracoronary vs high-dose, short-term intravenous streptokinase infusion in patients with acute myocardial infarction, we performed baseline coronary arteriography and then randomly allocated 51 patients with acute myocardial infarction to receive either intracoronary (n = 25) or intravenous (n = 26) streptokinase. Patients getting the drug by the intracoronary route received 240,000 IU of streptokinase into the infarct-related artery over 1 hr, whereas those getting the drug by the intravenous route received either 500,000 IU of streptokinase over 15 min (n = 10) or 1 million IU of streptokinase over 45 min (n = 16). Angiographically observed thrombolysis occurred in 76% (19/25) of the patients receiving intracoronary streptokinase, in 10% (1/10) of the patients receiving 500,000 IU of streptokinase intravenously, and in 44% (7/16) of the patients receiving 1 million IU of streptokinase intravenously. Among patients in whom thrombolysis was observed, mean elapsed time from onset of streptokinase infusion until lysis was 31 +/- 18 min in patients receiving intracoronary streptokinase and 38 +/- 20 min in those receiving intravenous streptokinase (p = NS). Among patients in whom intravenous streptokinase "failed," intracoronary streptokinase in combination with intracoronary guidewire manipulation recanalized only 7% (1/15). Fibrinogen levels within 6 hr after streptokinase were significantly lower in the patients receiving intravenous streptokinase (39 +/- 17 mg/dl) than the levels in those receiving intracoronary streptokinase (88 +/- 70 mg/dl) (p less than .05) but were similar 24 hr after streptokinase in the two groups. Bleeding requiring transfusion occurred in one patient in each group. Thus, in this prospective randomized trial of intracoronary vs intravenous streptokinase, hemorrhagic complications were few, although both regimens produced a systemic lytic state. Although the thrombolytic efficacy of intracoronary streptokinase was superior to that of high-dose, short-term intravenous streptokinase, the higher-dose intravenous regimen (1 million IU over 45 min) achieved thrombolysis in a significant minority (44%) of patients and might be useful therapy for patients not having access to emergency catheterization.     

Clinical pharmacology in patients with evolving myocardial infarction of tissue-type plasminogen activator produced by recombinant DNA technology

This study was performed to characterize selected pharmacologic properties and effects on the fibrinolytic system of tissue-type plasminogen activator synthesized by recombinant DNA technology (rt-PA) in 12 patients treated for coronary thrombosis. rt-PA was infused parenterally (by the intracoronary route in four patients and intravenously in eight) in doses of 8.3, 12.5, or 16.7 micrograms/kg/min for 30 to 60 min, yielding a total dosage of 20 to 40 mg/patient. The drug induced coronary thrombolysis in 10 of the 12 patients treated (83%), including six of the eight given rt-PA intravenously. No bleeding complications were encountered. Serial blood samples were obtained before, during, and after infusion of rt-PA and analyzed for t-PA antigen (i.e., immunoassayable rt-PA protein), functional fibrinolytic activity attributable to rt-PA, fibrinogen, plasminogen, alpha 2-antiplasmin, fibrinogen degradation products, prothrombin time, activated partial thromboplastin time, and protamine-corrected thrombin time. Pretreatment plasma t-PA antigen levels averaged 16.5 +/- 5(SD) ng/ml. Peak plasma values were generally proportional to dose, averaging 3330 +/- 1201 ng/ml. Approximately 90% of peak level was reached in 30 min, with a plateau at peak reached within 40 min. Functional t-PA activity increased monotonically in a comparable fashion. Curves for disappearance of both t-PA antigen and functional activity from plasma were monoexponential for at least two half-lives (r = .99 for both) and were concordant. The observed half-lives were similar, averaging 8.3 and 9.1 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

An angiographic study of intracoronary streptokinase versus intravenous tissue plasminogen activator after failed coronary thrombolysis with intravenous streptokinase

Objective The medical treatment of failed intravenous streptokinase in patients with acute transmural myocardial infarction using angiographic endpoints.Design Prospective open angiographic comparison of intracoronary streptokinase with intravenous tissue plasminogen activator. Setting: Single center study in a tertiary institution.Subjects Eighty-five patients with acute myocardial infarction within 4 hours after symptom onset. Treatment regimens: The subjects received 1.5 million U intravenous streptokinase. Coronary angiography within 48 hours (median 19 hours) showed infarct-related vessel patency in 65 patients (76%). In the catheterization laboratory the 20 patients (24%) with failed intravenous streptokinase received repeat thrombolysis immediately after angiography. The first 10 patients with failed intravenous streptokinase received intracoronary streptokinase at a dose of 4000 U/min in the occluded infarctrelated artery for a maximum of 1 hour. The subsequent 10 patients received high-dose front-loaded intravenous tissue plasminogen activator (100 mg in 1 hour).Results In none of the patients receiving repeat streptokinase was reperfusion obtained. In 6 of 10 (60%) of the patients receiving tissue plasminogen activator, reperfusion was seen within 60 minutes (p < 0.005 vs. intracoronary streptokinase). One patient (5%) died and two refused follow-up angiography. Seventeen (88%) patients underwent angiography 3 months later according to the protocol. Two patients showed a persistently reperfused infarct-related artery, three reoccluded, four spontaneously reperfused, and eight had a persistently occluded infarct-related artery. The left ventricular ejection fraction was slightly higher at 3 months, and there were no differences between the patients with open vessels (increase + 7.7 ± 5.8%) and those with persistently occluded vessels (increase +5.8 ± 6.8%)Conclusions Repeat thrombolysis after failed intravenous streptokinase can be achieved with front-loaded intravenous tissue plasminogen activator but not with intracoronary streptokinase. Although patient numbers are small and repeat thrombolysis was performed rather late, this study leads the way to affordable optimization of thrombolysis, which needs large-scale testing.     

Plasmin inhibitors in the prevention of systemic effects during thrombolytic therapy: specific role of the plasminogen-binding form of alpha 2-antiplasmin.

To delineate the role of plasmin inhibitors, especially the two molecular forms of alpha 2-antiplasmin (that is, the plasminogen-binding and the nonplasminogen-binding forms), in the control of systemic effects during thrombolytic therapy, the consumption of plasmin inhibitors and the degree of fibrinogen breakdown were studied in 35 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) or streptokinase. At a low degree of plasminogen activation (in six patients treated with rt-PA), plasminogen-binding alpha 2-antiplasmin was consumed first. At a higher degree of plasminogen activation (in 20 patients), plasminogen-binding alpha 2-antiplasmin became exhausted (less than 20%) and other plasmin inhibitors (that is, nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin) were consumed. After extensive plasminogen activation (in nine patients treated with streptokinase), plasminogen-binding alpha 2-antiplasmin consumption was complete and nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin were consumed to about 30% to 50% of the pretreatment level. No significant C1-inactivator consumption occurred, even at extreme degrees of plasminogen activation. Fibrinogen breakdown as a marker for systemic effects correlated strongly with consumption of plasminogen-binding alpha 2-antiplasmin. Fibrinogen breakdown did occur, but only when the amount of plasminogen-binding alpha 2-antiplasmin was decreased to less than 20% of the pretreatment level. The other plasmin inhibitors could not prevent fibrinogen breakdown. These results were confirmed by in vitro studies. It is concluded that plasminogen-binding alpha 2-antiplasmin is the most important inhibitor of plasmin in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombolytic therapy in acute myocardial infarction: Review of clinical trials

Intracoronary infusion of streptokinase is associated with recanalization rates of 60 to 90% immediately after the procedure. Mortality data in published trials are conflicting. In 125 registry patients who had paired contrast ventriculograms before streptokinase infusion and hospital discharge, improvement in ejection fraction correlated with incomplete coronary obstruction before angiography, the presence of collateral vessels to the infarct area and recanalization of complete obstruction. In assessing the risk/benefit ratio of intracoronary streptokinase infusion, the risks of angiography in the setting of acute myocardial infarction, reocclusion, bleeding and such secondary interventions as angioplasty or bypass surgery must be considered. Intravenous infusion of conventional doses of streptokinase was associated with improved survival in some trials in which therapy began within 12 hours after the onset of infarction. Immediate recanalization rates in patients who received large doses of intravenous streptokinase were lower than those associated with intracoronary streptokinase infusion. The risks and benefits of high-dose intravenous streptokinase administration must still be assessed.     

Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

More rapid thrombolysis with coronary venous retroinfusion of streptokinase compared with intravenous administration. An experimental study in canines

The efficacy of coronary venous retroinfusion vs intravenous administration of streptokinase was compared in 20 closed chest dogs with copper coil induced thrombosis of the left anterior descending coronary artery. Streptokinase was continuously infused for 60 min (100 IU kg-1 min-1) starting 60 min after coronary artery occlusion. Time to clot lysis was determined by coronary angiography performed at 5 min intervals. Complete lysis occurred in eight out of 10 dogs receiving intravenous streptokinase and in all 10 dogs in the coronary venous group. Time to thrombolysis was significantly shorter with coronary venous retroinfusion (23 +/- 8 min) than after systemic infusion (62 +/- 26 min; P less than 0.001). Recovery of ischaemic zone left ventricular systolic function, studied by two-dimensional echocardiography, was significantly better in the animals that received retrograde streptokinase than in the group that received intravenous streptokinase (17 +/- 12% vs -2 +/- 16%; P less than 0.05). Myocardial necrosis expressed as a percentage of the risk area was 8 +/- 12% after retroinfusion of streptokinase compared with 32 +/- 25% (P less than 0.005) after intravenous administration. In conclusion, coronary venous administration of streptokinase was more effective than intravenous therapy as determined by more rapid clot lysis which resulted in improved functional recovery of the ischaemic myocardium and a significant reduction in myocardial necrosis.     

Intrapleural instillation of streptokinase. Effects on systemic fibrinolysis

Ten consecutive patients aged 25 to 75 with postoperative empyema or hemothorax conventionally treated with drainage without sufficient effect were given intrapleural instillations of streptokinase (Kabikinase, 250,000 IE) for 4 hours). The effects on systemic fibrinolysis were studied. Venous blood samples for determination of fibrinolytic activity on fibrin plates, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrinogen, fibrin(ogen) degradation products (FDP) and thrombin time were taken before instillation, after instillation and then after 24 hours. Preinstillation values were compared to the values 4 and 24 hours after instillation with Student's paired t-test. There were no differences in fibrinolytic activity, alpha 2-macroglobulin and thrombin time. There was a slight increase in plasminogen, alpha 2-antiplasmin and fibrinogen, probably due to an acute phase reaction. Fibrin degradation products showed an increase with border line significance. These changes are not consistent with generalized fibrinolysis, and it is concluded that intrapleural instillations of streptokinase can be given safely in the early posttraumatic or postoperative period.     

Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

Background

Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared with intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route.

Methods

FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 μg as boli) and a standard intravenous infusion of 140 μg/kg/min were administered in a randomized fashion.

Results

Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-μg intracoronary bolus and 140-μg/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-μg bolus, resulted in mean FFR values that were significantly (P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-μg intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration.

Conclusions

This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 μg. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 μg/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR.     

Do different doses of intravenous streptokinase alter the frequency of coronary reperfusion in acute myocardial infarction?

This study assessed the relative efficacy of 3 doses of intravenous streptokinase in causing hypofibrinogenemia and coronary reperfusion in patients with acute myocardial infarction. Accordingly, 56 patients (50 men and 6 women, ages 58 +/- 10 years [mean +/- standard deviation]) with evolving acute myocardial infarction and chest pain less than or equal to 5 hours in duration were assigned to receive varying doses of streptokinase. Twenty were administered 500,000 units during 145 minutes, 18 were given 750,000 units during 30 minutes and 18 received 1.5 million units in 60 minutes of streptokinase. Serum creatine kinase was measured on admission and 6, 12, 18 and 24 hours after the initiation of streptokinase. The time intervals from onset of pain to peak creatine kinase and from streptokinase administration to peak creatine kinase were used to determine the occurrence of reperfusion. The plasma fibrinogen concentration was measured 30, 60, 90 and 120 minutes after the initiation of streptokinase. For the 3 groups, the time from onset of pain to peak creatine kinase was less than 17 hours and the time from streptokinase to peak creatine kinase was 6 or 12 hours in 15 (75%), 16 (89%) and 12 patients (67%), respectively (differences not significant). The plasma fibrinogen concentration decreased to 45 +/- 34 mg/dl, 19 +/- 14 mg/dl and 29 +/- 43 mg/dl, respectively, during the 2 hours after streptokinase was begun (p less than 0.05 for the first versus the second and third values).(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary thrombolysis after intracoronary and intravenous administration of streptokinase to myocardial infarct patients

Coronary thrombolysis by intracoronary and intravenous streptokinase (SK) is reported in myocardial infarction patients. Forty-two patients were examined within the first 6 hours of infarction: they were subjected to coronary-angiography on admission and 24 hours later, and their plasma fibrinogen levels were measured repeatedly for 2 days. SK administration was intracoronary in 24 patients and intravenous in 18. Rapid intravenous SK injection was not inferior to intracoronary administration in terms of efficiency. Although coronary reperfusion takes a somewhat longer time in cases of intravenous SK treatment, its technical simplicity and relative safety, as well as the fact that it can be started early suggest that it is a promising method of treatment for myocardial infarction.