Long-term prognosis after out-of-hospital cardiac arrest and primary percutaneous coronary intervention.

AIMS: To study the long-term survival after out-of-hospital cardiac arrest and successful cardiopulmonary resuscitation (CPR) in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). MATERIAL AND METHODS: In-hospital and 2-year survival of 40 patients treated with primary PCI after out-of-hospital cardiac arrest and STEMI was compared with that of a reference group of 325 STEMI patients, without cardiac arrest, also treated with primary PCI in the same period. RESULTS: In the group with out-of-hospital cardiac arrest, both in-hospital and 2-year mortality was 27.5%. In the reference group, in-hospital and 2-year mortality was 4.9 and 7.1%, respectively. After discharge from hospital there was no significant difference in mortality between the groups. CONCLUSION: Long-term prognosis is good in selected patients after successful out-of-hospital CPR and STEMI treated with primary PCI.

[Long-term follow-up of 100 patients with acute myocardial infarction treated with angioplasty]. / Langtidsresultater etter primaer angioplastikk hos 100 pasienter med akutt hjerteinfarkt.

BACKGROUND: There is little information available on long-term follow up of patients treated with primary angioplasty for acute myocardial infarction. MATERIAL AND METHODS: 100 consecutive patients with acute ST-elevation myocardial infarction and symptoms of less than six hours' duration were treated with primary angioplasty. Clinical examination was performed in 97 patients and exercise stress test in 74 patients 11-37 months (mean 20 months) later. Patients were observed for survival up to 48 months. RESULTS: 24 patients had been rehospitalized, 16 because of chest pain. 77 patients were treated with beta blocker, 83 with statins, and 95 with antithrombotic medication. 84 patients were in NYHA (New York's Heart Association's classification's) class I at follow-up examination. Three patients died. 11 patients had a serious event, reinfarction (n = 3) or need for revascularization (n = 8) during the first 13 months. Total cumulative mortality rates after one and three years were 3% (95% CI 1-8) and 11% (95% CI 6-19). INTERPRETATION: The good initial results in primary angioplasty are maintained in long-term follow-up. This is in accordance with reports from centres abroad.

Low molecular weight heparin prevents activation of coagulation in a hypobaric environment.

It is commonly thought that people are at increased risk of venous thrombosis during air flights, but the magnitude of the risk is unknown. Suggested risk factors are hypobaric hypoxia, stasis, and dehydration. In a previous experimental study, we found immediate activation of coagulation as determined by the levels of prothrombin fragments 1 + 2 (F(1 + 2)) and thrombin-antithrombin complex (TAT) after rapid exposure to a hypobaric and hypoxic environment (76 kPa). The aim of the present study was to examine the ability of low molecular weight heparin (LMWH) to prevent such activation. Twelve healthy male volunteers were given 40 mg enoxaparin as a single subcutaneous injection 1 h prior to exposure from 96.3 to 76 kPa. We found no activation of coagulation as judged by F(1 + 2) or TAT. Anti-activated factor X activity levels and release of tissue factor pathway inhibitor was normal. We conclude that high prophylactic doses of a LMWH most probably prevent activation of coagulation in a hypobaric environment.

[Angiographic results of primary angioplasty in acute myocardial infarction]. / Angiografiske resultater av primaer angioplastikk ved akutt hjerteinfarkt.

BACKGROUND: Percutaneous angioplasty is an alternative to thrombolysis to reestablish coronary blood flow in patients with transmural myocardial infarction. At present, this treatment option is not widely accepted in Norway. MATERIAL AND METHODS: From 1996 to 1998, one hundred consecutive patients were treated with angioplasty for acute transmural infarction. The angiography showed one-vessel disease in 55%, two-vessel in 25%, and multivessel in 20%. The infarct related artery was the LAD in 44%, the CX in 14%, the RCA in 41%, and bypass graft in one. 92% had TIMI 0 or 1 flow. Stent was placed in 73%, GPIIb/IIIa was used in 11% and temporary pacemaker placed in 5%. RESULTS: Successful angioplasty was performed in 95%, 3% was not done, and 2% failed. Peripheral stenoses were treated in 15% and stenoses in other arteries in 10%. Complications and events within 24 hours related to the angioplasty were seen in 9%. CONCLUSION: Primary angioplasty for acute myocardial infarction can be done with high primary success, good short-term results and few complications.

[Hundred patients with acute myocardial infarction treated with primary angioplasty]. / Ett hundre pasienter behandlet med primaer angioplastikk ved akutt hjerteinfarkt.

BACKGROUND: Much attention has lately been focused on primary angioplasty in the treatment of acute myocardial infarction. This report describe our results in 100 patients. MATERIAL AND METHODS: 100 consecutive patients with acute ST elevation myocardial infarction and a history of less than six hours were treated with primary angioplasty. The mean time from start of symptoms until establishment of reperfusion of the infarct related artery was 224 minutes; "the door-to-balloon" time was 69 minutes. RESULTS: Angioplasty was successful in 95% of all patients. Mean ejection fraction measured before discharge in 71 patients was 56%. Hospital and 30-days' mortality was 1%. New revascularization was needed in 6%. Average observation period in the coronary care unit was 1.8 days; no patient needed treatment for ventricular arrhythmias after angioplasty. The first 24 hours 24% had symptomatic congestive heart failure, reduced to 11% at hospital discharge on day 6. Acute rehospitalization within the first 30 days was necessary in 7%, but only in 2% for chest pain. INTERPRETATION: Our results are comparable to those of other high volume centres and show well preserved ventricular function and low hospital and 30-days' morbidity and mortality.

Left ventricular function and infarct size 20 months after primary angioplasty for acute myocardial infarction.

OBJECTIVE: To study changes in left ventricular function and infarct size during long-term follow-up after acute myocardial infarction treated with primary angioplasty. DESIGN: From 1996 to 1998, 100 consecutive patients were treated with primary angioplasty for acute ST-elevation myocardial infarction. Angioplasty was successful in 95% of the patients. Global left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography before discharge, after 6 weeks and after a mean follow-up time of 20 months. Infarct size was assessed by technetium 99m-tetrofosmin myocardial perfusion tomography (SPECT) at rest, performed at the same time intervals. RESULTS: Mean LVEF was 56% at discharge, 55% after 6 weeks and 57% after 20 months of follow-up. No significant improvement in LVEF was observed. Only 8% of the patients at follow-up had LVEF lower than 40%. After 1 week, a mean perfusion defect of 19% was measured by SPECT. After 6 weeks and 20 months of follow-up, the mean perfusion defects were reduced to 14% (p < 0.001) and 15%, respectively. CONCLUSION: Left ventricular function was well preserved with a mean LVEF of 57% 20 months after primary angioplasty for acute myocardial infarction. No significant change in LVEF was observed from 1 week after angioplasty to follow-up. Infarct sizes as assessed by SPECT imaging with tetrofosmin were reduced from 1 to 6 weeks, but did not change further during long-term follow-up. The reduction in the perfusion defects over time was probably due to gradual relief of stunning.

Reduced autonomic activity during stepwise exposure to high altitude.

Several studies have shown increased sympathetic activity during acute exposure to hypobaric hypoxia. In a recent field study we found reduced plasma catecholamines during the first days after a stepwise ascent to high altitude. In the present study 14 subjects were exposed to a simulated ascent in a hypobaric chamber to test the hypothesis of a temporary reduction in autonomic activity. The altitude was increased stepwise to 4500 m over 3 days. Heart rate variability (HRV) was assessed continuously in seven subjects. Baroreceptor reflex sensitivity (BRS) was determined in eight subjects with the 'Transfer Function' method at baseline, at 4500 m and after returning to baseline. Resting plasma catecholamines and cardiovascular- and plasma catecholamine- responses to cold pressor- (CPT) and mental stress-test (MST) were assessed daily in all and 12 subjects, respectively. Data are mean +/- SEM. Compared with baseline at 4500 m there were lower total power (TP) (35 457 +/- 26 302 vs. 15 001 +/- 11 176 ms2), low frequency (LF) power (3112 +/- 809 vs. 1741 +/- 604 ms2), high frequency (HF) power (1466 +/- 520 vs. 459 +/- 189 ms2) and HF normalized units (46 +/- 0.007 vs. 44 +/- 0.006%), P < or = 0.001. Baroreceptor reflex sensitivity decreased (15.6 +/- 2.1 vs. 9.5 +/- 2.6 ms mmHg(-1), P = 0.015). Resting noradrenaline (NA) decreased (522 +/- 98 vs. 357 +/- 60 pmol L(-1), P = 0.027). The increase in systolic blood pressure (SBP) and NA during mental stress was less pronounced (21 +/- 4 vs. 10 +/- 2% and 25 +/- 9 vs. -2 +/- 8%, respectively, P < 0.05). The increase in SBP during cold pressor test decreased (16 +/- 3 vs. 1 +/- 6%, P = 0.03). Diastolic blood pressure, HR and adrenaline displayed similar tendencies. We conclude that a transient reduction in parasympathetic and sympathetic activity was demonstrated during stepwise exposure to high altitude.

Association between acute hypobaric hypoxia and activation of coagulation in human beings.

The risk of venous thrombosis is thought to be increased by flying. In a study of 20 healthy male volunteers who were suddenly exposed to a hypobaric environment similar to that encountered within aeroplane cabins, markers of activated coagulation transiently Increased by two-fold to eight-fold. We suggest that hypobaric hypoxia, with sedentariness and dehydration, may cause this increased risk of venous thrombosis.

Dose-dependent release of endogenous tissue factor pathway inhibitor by different low molecular weight heparins.

Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous and subcutaneous injections of heparins, and may thus contribute to the antithrombotic effect of heparins. A previous study suggested different abilities of various low molecular weight heparins (LMWH) to release endogenous TFPI, but the dose-response relationship was not determined. In the present study, the dose-response relationship for escalating doses of two LMWHs, dalteparin and enoxaparin, on the release of endogenous TFPI was investigated. Six healthy male participants were given 50, 100 and 200 U/kg dalteparin and 0.5, 1.0 and 2.0 mg/kg enoxaparin as a single subcutaneous injection. The study was a randomized, cross-over design with a 1-week wash-out period between each injection. Peak free TFPI antigen and TFPI activity were detected after only 1 h, whereas anti-activated factor X (anti-FXa) and anti-activated factor II (anti-FIIa) activities were detected after 2-6 h. Putative therapeutic equivalent doses of dalteparin and enoxaparin gave similar release of endogenous TFPI, but dissimilar effects on anti-FXa and anti-FIIa activities.

A new sensitive chromogenic substrate assay of tissue factor pathway inhibitor type 1.

The present assay is a modification of our previously published two-stage chromogenic substrate assay of tissue factor pathway inhibitor type-1 (TFPI) activity [1]. In the first stage, the reaction mixture was made with factor VIIa (FVIIa) molecules in excess of tissue factor (TF) binding sites and contained diluted plasma, recombinant FVIIa (10 nM), recombinant TF (1/400 vol/vol), bovine factor Xa (1,1 nM), I-2882(R) (100 microg/ml), and CaCl(2) (10 mM). The fibrin polymerisation inhibitor I-2882(R) was added to the reaction mixture to prevent formation of cross-linked fibrin. In the second stage, residual TF/FVIIa catalytic activity was measured by the addition of a substrate mixture that contained bovine factor X and a chromogenic substrate (S-2222(R)). Standard curves were constructed using serial dilutions (0-1%) of pooled normal plasma. The dose-response relationship for serial dilutions of plasma was linear. The intra-assay coefficient of variations (CVs) for pre- and postheparin plasma samples (i.e., normal and high TFPI levels) were 1.7% and 9.9%, respectively; the inter-assay CVs were 10.0% and 19. 7%, respectively. The effect of variation in antithrombin activity on the assay was approximately 5%. The present assay correlated fairly well with our previously published assay (r=0.82, n=100) and with a commercial TFPI activity assay (Actichrome(R) TFPI Activity Assay, American Diagnostica, Greenwich, CT, USA; r=0.90, n=100), as well as with an antigen assay for TFPI total antigen (Imubind(R), American Diagnostica; r=0,96, n=100). Altman and Bland plots revealed that our previous assay underestimated TFPI activity at high TFPI levels (i.e., postheparin TFPI samples) compared with the other methods.

Physiological function of tissue factor pathway inhibitor and interaction with heparins.

Tissue factor pathway inhibitor (TFPI) is now recognized as a major physiological anticoagulant. Its main role is to modulate factor VIIa/tissue factor catalytic activity. Another important role is to potentiate the effect of heparins. TFPI is released from the vascular endothelium after injection of either unfractionated heparin (UFH) or low-molecular-weight heparins (LMWHs), which may then provide high concentrations of TFPI at sites of tissue damage and ongoing thrombosis. In dilute prothrombin-time-based assays, released TFPI contributes approximately one-third to the anticoagulant effect of heparin, the remaining being accounted for by antithrombin. Released TFPI, but not plasma TFPI, contains the basic carboxy-terminal tail which is important for the anticoagulant effect. UFH and LMWH exert differential effects on intravascular TFPI. UFH, but not LMWH, given in therapeutic doses, is associated with a progressive depletion of TFPI, which is associated with a strong rebound activation of coagulation after cessation of treatment. Such depletion may explain the apparent superior efficacy of LMWH observed in clinical trials.

Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin, but not with two low molecular weight heparins.

Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous (i.v.) and subcutaneous (s.c.) injections of heparins, and may thus contribute to the antithrombotic effect of heparins. We have recently shown that total TFPI activity, plasma free TFPI antigen, and heparin releasable TFPI were partially depleted during repeated and continuous i.v. infusion of unfractionated heparin (UFH), but not during s.c. treatment with a low molecular weight heparin (LMWH). The difference may be attributed to a different mode of action or the different mode of administration. In the present randomized cross-over study, s.c. administration of therapeutic doses of UFH was compared with s.c. administration of two LMWHs. 12 healthy male volunteers were treated for 3 d with UFH, 250 U/kg twice daily, dalteparin, 200 U/kg once daily, and enoxaparin, 1.5 mg/kg once daily. Six participants were also treated with UFH, 300 U/kg once daily. On day 5 a single dose of either drug was given. Peak levels of total TFPI activity and free TFPI antigen were detected 1 h after injection, whereas maximal prolongation of activated partial thromboplastin time (APTT) and peak levels of anti-factor Xa activity and anti-factor IIa activity were detected after 4 h. On UFH administered twice daily, free TFPI antigen decreased by 44% from baseline level before the first injection on day 1 to pre-injection level on day 5. On UFH administered once daily, basal free TFPI antigen decreased by 50%, 56% and 27% on day 2, 3 and 5 respectively, compared with day 1. Minimal depletion of TFPI was detected during treatment with LMWHs. The study demonstrates the different modes of action of LMWHs and UFH and may help to explain the superior antithrombotic efficacy of LMWHs.

[Angioplasty in heart arrest]. / Angioplastikk ved hjertestans.

Early onset of cardiopulmonary resuscitation (CPR) and defibrillation are the most important factors for improving outcome after cardiac arrest. Many patients do not receive thrombolytic therapy after prolonged CPR, as there is a fear of serious bleeding complications. Ten patients with cardiac arrest and acute myocardial infarction were treated with primary angioplasty after prolonged CPR. Angioplasty was successful in nine of the patients, and left ventricular function was well preserved after six weeks. Primary angioplasty is highly effective and safe in establishing reperfusion in selected patients with acute myocardial infarction and cardiac arrest.

Serum phospholipids are the main environmental determinants of activated factor VII in the most common FVII genotype. European Union Concerted Action "Clotart".

BACKGROUND AND OBJECTIVE: Numerous studies have emphasized the role of triglyceride-rich lipoproteins and of Factor VII (FVII) polymorphisms in determining levels of FVII activity. DESIGN AND METHODS: This study was undertaken to evaluate the role of other lipid fractions and the interaction between lipids and FVII in subjects with recognised genotypes. Volunteer subjects (n=459) from 5 European countries were studied. Blood samples were drawn irrespective of the time of day or fasting status. Levels of FVII activity (FVIIc), activated FVII (FVIIa) and FVII antigen (FVIIAg) were evaluated with reference to a number of lipid parameters (HDL-, LDL- and total cholesterol, triglycerides, phospholipids, lipoprotein(a), and apoliproptein A1). The two most common FVII polymorphisms were analyzed in combination (353R/Q and 5'F7; alleles M1/M2 and A1/A2, respectively). RESULTS: Homozygotes for the A1 and M1 alleles (M11/A11) had significantly higher FVII levels. At multiple regression analysis the strongest predictor of FVIIa and FVIIc was the concentration of phospholipids. This interaction was confined to the A11M11 genotype subjects. INTERPRETATION AND CONCLUSIONS: These data indicate that lipids contribute mainly to FVIIa levels through their phospholipid content, and that the degree of this contribution is strictly dependent on FVII genotypes.

Hepatocyte growth factor in serum after injection of unfractionated and low molecular weight heparin in healthy individuals.

Soluble heparin displaces the cytokine hepatocyte growth factor (HGF) from heparan sulphate proteoglycans on the cell surface and in the extracellular matrix into the circulation. We examined serum HGF elevation after heparin injections, and whether there is a difference between unfractionated heparin (UH) and low molecular weight heparin (LMWH) in their ability to increase serum HGF. 20 healthy individuals were randomized to a single injection of intravenous or subcutaneous UH or LMWH. There was a significant increase in HGF from pretreatment values. This HGF was bioactive. When these preparations were compared on the basis of their serum concentrations (anti-factor Xa activity or molar concentrations), the increase in HGF was greater in individuals receiving UH than LMWH. When UH or LMWH were administered over a 5 d period, the increase in HGF, as well as the difference between treatments to induce HGF, remained stable throughout the treatment. In five patients treated with continuous intravenous heparin infusion HGF was increased throughout the treatment period of 5-7 d. In summary, the rise in bioactive HGF after heparin treatment was stable during continued treatment. UH was more potent in inducing HGF increase than LMWH, both after a single injection and after several days of treatment.

Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF)-induced blood coagulation, which is increased several-fold in post-heparin plasma and thought to contribute significantly to the antithrombotic action of heparin. In the present study we investigated whether subcutaneous (s.c.) administration of a low molecular weight heparin (LMWH), enoxaparin, had a different effect on intravascular pools of TFPI compared with continuous i.v. infusion of unfractionated heparin (UFH). 18 healthy male volunteers were randomly assigned to continuous i.v. infusion with UFH (initially 450 U/kg/24 h, n = 6) or to s.c. treatment with LMWH once daily (enoxaparin, 1.5 mg/kg, n = 12) for 72 h. A bolus injection of 5000 IU UFH i.v. caused an 8-13-fold increase in plasma-free TFPI antigen (TFPI Ag), followed by a progressive decrease (81 +/- 4%, P<0.001) during the 72 h infusion with UFH. 4 h after discontinuation of the infusion, basal free TFPI Ag and heparin-releasable TFPI were significantly decreased compared with the concentrations before the infusion (30 +/- 9%, and 27 +/- 7%, respectively). In contrast, LMWH treatment did not reduce either basal or heparin-releasable TFPI Ag. The changes in plasma TFPI Ag by UFH and LMWH were statistically different between groups both in pre- (P<0.001) and post-heparin (P<0.0001) plasma. The differential effect of UFH and LMWH on intravascular pools of TFPI may contribute to the understanding of the apparent superior efficacy of LMWHs in the treatment of both arterial and venous thrombosis.

[Angioplasty in acute myocardial infarction]. / Angioplastikk ved akutt hjerteinfarkt.

20 patients with acute myocardial infarction and a medical history of less than six hours were treated with immediate percutaneous transluminal coronary angioplasty. The median time from start of symptoms until establishment of reperfusion of the infarct related artery was 190 minutes, and the time from admission to insertion of the balloon was 52 minutes. Angioplasty was successful in all patients, with no serious complications. All patients experienced pain relief immediately after angioplasty. No patients died or had further infarctions. None needed hospitalization during the first three months of follow up. Eight patients had an exercise test between five and seven days after angioplasty and the other 12 at their six-week check up; there were no signs of ischemia or anginal pain. Measurement of global ejection fraction one week and six weeks after treatment showed median normal values and no significant changes (58% versus 57%). Myocardial perfusion imaging was carried out in eight patients both before hospital discharge and six weeks later. Normalization and improvement was seen in six patients using this method, whereas the perfusion was found unaltered in two patients. Hibernation or stunning, or both are suggested as possible explanations for this. We found the method highly effective and safe in selected patients.