Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate.

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed.

The effect of active immunization against aldosterone on the colonic potential response and sodium excretion in rabbits.

1. A group of rabbits was actively immunized against aldosterone and their subsequent response to infused aldosterone and to dietary sodium restriction was compared with that of a control group. 2. Colonic electrical potential difference (CP) was used as an index of relative mineralocorticoid activity in both groups of animals. 3. Infusion of aldosterone produced a rise in CP to a maximum of -50 to -70 mV at rates of infusion of 55-270 pmol min-1 kg-1. In contrast, the immune group showed no change until infusion dose rates of 2700 pmol min-1 kg-1 were used. 4. During dietary sodium restriction, CP increased in normal rabbits to a significantly greater degree than in immune animals although cumulative urinary sodium losses were the same in both groups. 5. The ability of the immune animals to remain in sodium balance despite physiological aldosterone blockade suggests that aldosterone is not an essential component of their sodium-conservation mechanisms.

Adrenergic influences on the electrical potential across the colonic mucosa of the rabbit.

1. An investigation was undertaken of the role of adrenergic influences on the transient change in colonic potential difference (p.d.) induced by handling in the rabbit. 2. P.d. was increased from 9-5 +/- 0-5 to 27-05 +/- 1-94 mV during a 2 hr period of handling and wrapping. Atropine and alpha-adrenergic block during this 2 hr period did not alter the magnitude of the response and the response in adrenalectomized animals was not significantly different from that of normal animals. 3. 'Total' adrenergic block and selective beta-adrenergic block abolished the change in p.d. with handling and infusion of an alpha-receptor agonist during the 2 hr period significantly reduced the response. 4. The changes in colonic p.d. with handling were greatly increased by the infusion of a beta-receptor agonist during the 2 hr test period. 5. The results indicate that the change in colonic p.d. with handling is a direct effect of the autonomic nervous system mediated via beta-receptors and that the changes were not related to the effects of circulating catecholamines or to changes in aldosterone production.

A comparison on natriuresis after oral and intravenous sodium loading in sodium-depleted rabbits: evidence for a gastrointestinal or portal monitor of sodium intake.

1. Rabbits in balance on a low sodium diet were given doses of sodium chloride either orally or intravenously. 2. Those receiving oral doses responded with a much greater natriuresis than those receiving intravenous ones. 3. This could be explained by the existence of a sodium input monitor somewhere in the gut or portal circulation.

A comparison of natriuresis after oral and intravenous sodium loading in sodium-depleted man: evidence for a gastrointestinal or portal monitor of sodium intake.

1. Dietary sodium reduction in man is followed by rapid conservation of sodium by the kidneys. The rapidity of this response suggests that the gastrointestinal tract is involved in early recognition of changes in sodium intake or in mediation of the compensatory response. 2. In order to test the hypothesis, 100 mmol of sodium was given to normal volunteers in balance on a low-sodium diet (5 mmol/24 h): the dose was given either orally or intravenously. 3. Those who received their sodium orally excreted it more rapidly than those who received it intravenously and the difference was most marked in the first 8 h after the dose. 4. This finding is consistent with the presence of an input receptor for sodium in the gastrointestinal tract.

[Comparative randomized study of the effectiveness of intravenous recombinant tissue-type plasminogen activator and intravenous streptokinase in patients with acute myocardial infarct. Report of the European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator]. / Vergleichende randomisierte Untersuchung zur Wirksamkeit von rekombinantem Gewebe-Plasminogen-Aktivator i.v. und Streptokinase i.v. bei Patienten mit akutem Herzinfarkt. Bericht der Europäischen Gemeinschafts-Studiengruppe für rekombinanten Gewebe-Plasminogen-Akivator.

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1,500,000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the difference ranges from +30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Randomised trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Report from the European Cooperative Study Group for Recombinant Tissue-type Plasminogen Activator.

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1 500 000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the differences ranges from +/- 30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Double-blind randomised trial of intravenous tissue-type plasminogen activator versus placebo in acute myocardial infarction.

In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.