Atrial signal variations and pacemaker malsensing during exercise: a study in the time and frequency domain.

To give some explanation for atrial malsensing in dual chamber pacing that occurs only during exercise, atrial electrograms from 33 patients were telemetrically recorded and analyzed in both the time and frequency domains. During exercise, an overall decrease from 6.4 +/- 1.9 to 5.6 +/- 1.9 mV (-11%) in the atrial signal amplitude was noted. Despite considerable variability among patients, marked changes occurred in 15 patients whose signals diminished by 11 to 49%. Slew rates showed a similar decrease from 1.35 +/- 0.45 to 1.18 +/- 0.45 V/s (-10.8%), with individual changes of as much as -51%. Signal attenuation in the time domain correlated well with frequency data, exhibiting a highly significant reduction of signal energy between 25 and 105 Hz. However, spectral distribution changed from rest to exercise, with a relative increase of signal energy in the range between 5 and 25 Hz and a decrease at higher frequencies. Individual changes differed widely when low (15 to 65 Hz) and high (65 to 115 Hz) frequencies were compared, but in a group of 11 patients signal attenuation in the high frequency band was more pronounced (-45%) than in the low frequency band (-23%). The clinical impact of the change in frequency distribution during ergometry was visualized by computer simulation of two different (low and high bandpass) filters. Although in individual patients, both characteristics may be favorable with respect to atrial sensing, it was observed in 11 patients that high pass filtering attenuates signal amplitudes by 10 to 24% in excess of the variation without filtering.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing.

OBJECTIVES: The study investigates the correlation between left ventricular function and QRS duration obtained by alternate right ventricular pacing sites. BACKGROUND: 1. Right ventricular apical pacing is associated with alterations of left ventricular contraction sequence. 2. A stimulation producing narrow QRS complexes is supposed to provide for better left ventricular contraction patterns. METHODS: Fourteen patients with third degree AV block received one ventricular pacing lead in apical position. The alternate lead was attached to that site on the septum that produced the smallest QRS complex as measured from the earliest to the last deflection in any of the orthogonal Frank leads (xyz). During atrial synchronous ventricular pacing, the AV delay was optimized individually and for each stimulation site using mitral valve doppler or impedance cardiography. By radionuclide ventriculography, the phase distribution histogram of left ventricular contraction was evaluated as area under the curve (AuC); systolic function was determined as ejection fraction (EF) and as absolute ejected counts (EC) in random order. The difference (delta) in QRS duration between apical and septal stimulation (deltaxyz) was correlated with the difference in phase distribution (deltaAuC) and ejection parameters (deltaEF, deltaEC). RESULTS: QRS duration was shorter with septal than with apical pacing in 9 out of 14 patients (64%); it was longer in 4 (29%), and no difference was seen in 1 patient. There was a significant positive correlation between the change in QRS duration (deltaxvz) and phase distribution (deltaAuC: r = 0.66393, p = 0.010) and a significant negative correlation to systolic function (deltaEF: r = 0.70931, p = 0.004; deltaEC: r = 0.74368, p = 0.002). CONCLUSIONS: In atrial synchronous right ventricular pacing, if the AV delay is adapted individually, decreased QRS duration obtained by alternate pacing sites is significantly correlated with homogenization of left ventricular contraction and with increased systolic function in acute tests.

Optimised function for determining time to peak creatine kinase and creatine kinase-MB as non-invasive reperfusion indicators after thrombolytic therapy in acute myocardial infarction.

STUDY OBJECTIVE: The aim of the study was to investigate the use of an optimised function to approximate and interpolate the time course of serum creatine kinase and creatine kinase-MB values after thrombolytic therapy in acute myocardial infarction. DESIGN: A three parameter interpolating function was developed which approximates the time course of serum enzyme levels. In the proposed function, time to peak creatine kinase and maximum of creatine kinase determined from raw data were used as starting parameters of the non-linear interpolation routine, thus providing ideal starting conditions for the iteration. The efficacy of the function was compared with that of three other functions cited in published reports (log-normal distribution function, modified gamma density function, three compartment function). SUBJECTS: Serum enzyme data from 20 patients with acute myocardial infarction were used in the comparisons. The patients have all been treated with anisoylated plasminogen streptokinase activator complex. RESULTS: In comparison with the other models, deviations of the experimental model function from the raw data were minimal. The fit remained stable for time intervals between blood samples of up to 6 h. CONCLUSIONS - Due to its numerical stability, the function outlined in this study is suitable for large clinical reperfusion trials. In the case of uncomplicated infarctions without thrombolytic therapy, the area under the creatine kinase activity curve could be directly calculated in terms of maximum activity and time to peak.

Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale.

OBJECTIVE: The diagnosis of a patent foramen ovale (PFO) as a cause of stroke is of increasing interest especially in young (<45 years) patients. METHODS: We studied potential right-to-left shunting using transesophageal echocardiography (TEE) and bilateral transcranial Doppler sonography (TCD) of the middle cerebral artery (MCA) simultaneously in 44 patients. All patients were younger than age 45 years and suffered from an acute ischemic stroke or transient ischemic attack. Other possible etiologies were excluded. Echo contrast medium was injected in an alternating mode via antecubital or femoral veins. Tests were performed with and without the Valsalva maneuver. The criteria for a PFO were that the contrast pass from the right to the left atrium (TEE) and early detection (<10 seconds) of more than 10 micro air bubbles in at least one MCA by TCD. RESULTS: A PFO was diagnosed in 22 patients (50%). The detection rate with TEE/TCD was 11.4%/4.5% via antecubital injection, 18%/13.6% via antecubital injection plus the Valsalva maneuver, 38.6%/36% via femoral injection alone, and 50%/50% via femoral injection plus the Valsalva maneuver. The difference between femoral and antecubital injections was significant with and without the Valsalva maneuver (p < 0.01, chi2 test). There were no differences between TEE and TCD after femoral injection with the Valsalva maneuver. The brain transit time was 4.6 +/- 2.1 seconds for femoral injection and 6.3 +/- 4.1 seconds for antecubital injection. CONCLUSIONS: The sensitivity in detecting a PFO was markedly increased by femoral injection. This may be caused by different inflow patterns to the right atrium: inferior vena caval flow is directed to the right atrial septum, whereas superior vena caval flow is directed to the tricuspid valve. Thus, femoral injection may help to improve the detection of PFO and may explain the differences between TEE and TCD findings in previous studies.

The significance of high levels of lipoprotein (a) compared with established risk factors in premature coronary artery disease: differences between men and women.

It was shown in a series of studies that increased lipoprotein (a) concentration is a strong and independent risk factor for coronary artery disease. The goal of this study was to determine the significance of elevated lipoprotein (a) levels for the existence and the early manifestation of coronary artery disease by systematically recording cardiovascular risk factors in diagnostic coronary angiographies in a larger group of patients, whereby particular attention was paid to sex-specific differences. In 1011 consecutive patients who underwent coronary angiography (731 men, 280 women, mean age 59 +/- 10 years), fasting blood samples were taken immediately before the angiographies to determine the levels of cholesterol, low density lipoprotein-, high density lipoprotein-cholesterol, triglycerides and lipoprotein (a). In addition, further risk factors were qualitatively recorded. The data evaluation was carried out using the SPSSx software package univariately and multivariately with stepwise discriminant analysis. In 231 patients (144 men, 87 women) either no or only discrete coronary findings appeared, while in 780 cases (587 men, 193 women) coronary artery disease with stenoses > 50% were found. Women with coronary artery disease were significantly older than men and demonstrated higher lipoprotein levels. Women as well as men with coronary artery disease differed from healthy controls by having higher levels of lipoprotein (a) and other lipoproteins, lipoprotein (a) having the smallest error probability (P < 0.0005). The early manifestation of coronary artery disease (below the 18th age percentile) in men (< 50 years) was connected with significantly higher levels of cholesterol, triglycerides and lipoprotein (a), which emphasized their atherogenic significance in the general view. The most striking finding was that in young women (< 53 years), compared to older women with coronary artery disease--corresponding to the age-determined prevalence--significantly lower concentrations of cholesterol, triglycerides and lipoprotein (a) were found. Possible explanations include later manifestation of coronary artery disease, a steeper increase of the lipids with age, particularly of lipoprotein (a), but also a different valence of the risk factors in women.

Effects of fenofibrate on angiographically examined coronary atherosclerosis and left ventricular function in hypercholesterolemic patients.

Within the framework of a prospective lipid-lowering intervention study 44 patients were treated over a period of 3 years with a lipid-lowering diet and 200-400 mg fenofibrate daily. The intervention led to statistically significant decreases in total cholesterol (Chol), low density lipoprotein cholesterol (LDL-Chol) and triglycerides levels, and to a significant increase in high density lipoprotein cholesterol (HDL-Chol) levels. Despite intervention, in 8 patients the HDL-Chol levels decreased by up to 20 mg/dl, where these were mainly patients with high initial values. Likewise, the triglycerides of 4 patients whose initial levels were relatively low increased (up to 49 mg/dl) and the LDL-Chol levels of 8 patients whose initial levels were also low increased (up to 49 mg/dl). Only minor success was achieved through the 6-week diet, but this was still slightly significant for Chol and LDL-Chol levels. A total of 21 patients underwent repeat angiography within 3 years for clinical reasons. For the evaluation of the angiographic progress a total of 98 minor and moderate stenoses was measured using digital image processing and automatic contour finding. The change in the angiographic parameters 'percent diameter reduction' (%DR) and 'percent plaque area' (%PA) correlated with on-treatment LDL-Chol levels (%DR change with LDL-Chol: r = 0.67, P = 0.0005; %DR change with Chol: r = 0.61, P = 0.002; %PA change with LDL-Chol: r = 0.40, P = 0.037; %PA change with Chol: r = 0.38, P = 0.044), while for HDL-Chol and triglycerides no influence on the angiographic progress could be demonstrated. On the basis of the reproducibility of the measuring methods the patients were classified in the categories 'regression', 'unchanged' and 'progression'. The patients classified as 'regression' (parameter: %DR change) showed an LDL-Chol mean value of 162 +/- 9 mg/dl, whereas those classified as 'unchanged' or 'progression' showed values of 189 +/- 25 mg/dl and 199 +/- 21 mg/dl, respectively (P = 0.014). A negative correlation appeared between the angiographic progress parameters and the initial degree of stenosis. The left ventricular ejection fraction in the second angiography showed relationships to lipoprotein levels and angiographic progress parameters.

Long-term follow-up of a randomized study of primary stenting versus angioplasty in acute myocardial infarction.

PURPOSE: Primary stenting leads to better short-term outcomes than does balloon angioplasty among patients with acute myocardial infarction, but there are no data available on long-term follow-up. SUBJECTS AND METHODS: We designed a randomized study with long-term follow-up to compare primary angioplasty with angioplasty accompanied by implantation of a silicon carbide-coated stent in patients within 24 hours after the onset of acute myocardial infarction. All 88 patients had lesions that were suitable for coronary stenting. RESULTS: There were 44 patients in each of the randomization groups. During long-term follow-up (mean +/- SD: 710+/-282 days), primary stenting was associated with a reduction in the combined endpoint of death, reinfarction, or target vessel revascularization (10 [23%] versus 19 [43%], P = 0.03); death (4 [9%] versus 8 [18%], P = 0.18); reinfarction (1 [2%] versus 4 [9%], P = 0.18); and target lesion revascularization (7 [16%] versus 15 [34%], P = 0.04). Rehospitalization due to ischemic events (unstable angina or reinfarction) was also less frequent in the stent group (6 [14%] versus 10 [23%], P = 0.20). CONCLUSION: Primary stenting in acute myocardial infarction is significantly superior to angioplasty alone in both short-term and long-term follow-up.

Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.

UNLABELLED: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h. METHODS: To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION: Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.

Cineradiography for determination of normal and abnormal function in mechanical heart valves.

To determine the diagnostic value of cineradiography of mechanical heart valves, 112 cinefluoroscopic studies were performed in 76 patients with 95 valve prostheses (caged ball or disk valves, tilting disk and bileaflet valves). A patient group (n = 45) presenting with clinical or echocardiographic findings suggestive of valve-related complications was compared with a control group (n = 31) without such symptoms. Disk-opening angles (mean +/- SD) for Medtronic Hall aortic valves were found to be significantly smaller (62.8 +/- 11.1 degrees) in patients than in control subjects (73.9 +/- 1.6 degrees; p < 0.05). Tissue ingrowth or thrombus formation, or both, demonstrated in 3 patients on subsequent reoperation, are considered as the main cause of incomplete or asymmetric disk opening. Opening and closing times did not differ significantly between patients and control subjects. Besides abnormal valve motion, structural defects such as strut fracture or leaflet escape could be rapidly detected by cineradiography if x-ray projections according to the particular valve design were used. Together with quantitative Doppler echocardiographic and clinical data, this method can help to give specific answers if the question is to either confirm or exclude imminent or acute valve malfunction. Thus, modern cineradiography is a highly valuable noninvasive diagnostic tool for both rapid management of emergency cases and routine follow-up of patients with mechanical heart valves.

Atrial defibrillation: can modifications in current implantable cardioverter-defibrillators achieve this?

Atrial fibrillation (AF), the most common arrhythmia resulting in hospital admission, is a major health problem. The limited efficacy of antiarrhythmic drugs to control this rhythm disorder and their potential proarrhythmic risk led to the development of new techniques to ameliorate the treatment of AF. Transvenous atrial defibrillation using endocardial electrodes has been shown to be effective at low energy levels. An implantable atrial defibrillator could be a potentially valuable treatment option for patients with paroxysmal AF that is medically refractory. Research is currently under way to investigate several critical issues concerning this new therapeutic concept: long-term efficacy, safety, patient's tolerance, and an acceptable cost/benefit ratio. It is well known that AF often complicates the use of the implantable cardioverter-defibrillator (ICD) for ventricular tachyarrhythmias. Therefore, it would seem desirable to implement the capability for atrial defibrillation into current ICD systems. It has been shown that atrial defibrillation, using endocardial lead configurations specifically designed for ventricular defibrillation, is feasible at energies well within the capabilities of current ICD technology. Further research is needed to evaluate if some enhancement of the lead configuration in combination with possible advanced technology could reduce the atrial defibrillation threshold to a well tolerated level as a prerequisite for automated atrial defibrillation, in ICD recipients with concomitant paroxysmal AF.

Treatment of unstable angina pectoris (European experience).

Unstable angina pectoris is used to describe accelerated angina, new onset of angina, or prolonged angina. The natural history of the angina varies according to clinical presentation. The 1-year mortality rate ranges from 2% to nearly 40%. Specific therapy includes nitrates, beta-adrenergic blockers, and/or calcium antagonists as well as antithrombotic therapy in the form of aspirin. Patients with severe angina at rest and ST- and T-wave changes should be admitted to a coronary care unit where full-dose heparin is administered. Coronary angiography should be performed in individuals who fail to respond to the conventional therapy in order to evaluate other therapeutic options, including percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery. In some cases, especially in patients with intracoronary thrombus, thrombolytic therapy may be beneficial.

Comparison of mortality from acute myocardial infarction in patients receiving anistreplase with those not receiving thrombolysis.

Within 1 year, 434 patients were admitted to 14 hospitals with suspected acute myocardial infarction (AMI) < or = 4 hours after the onset of symptoms. Group A consisted of 171 patients (39%) treated with thrombolysis, and group B consisted of 263 patients (61%) with contraindications. Patients in group A more likely had a "definite AMI" (92%; group A1) than patients in group B (67%; group B1). Group B1 had 277 contraindications (1.6/per patient) with increased risk for life-threatening bleeding being the most frequently recorded at admission. The in-hospital mortality in group A1 was 7% (11 of 158) and in group B1, 27% (47 of 177) (p < 0.0001). Age and type of therapy (thrombolysis or no thrombolysis) were identified as independent predictors of increased mortality (p < 0.0001 and < 0.05, respectively). Thus, although most patients with an AMI are excluded from thrombolytic therapy because of contraindications, our data suggest that their in-hospital mortality is unexpectedly high. Further evaluation of this group of patients is warranted to define the impact of contraindications as an independent factor of mortality.

Circannual variation of malignant ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators and either coronary artery disease or idiopathic dilated cardiomyopathy.

We studied the possible relation between the frequency of ventricular tachyarrhythmic events and thermal stress in patients with an implantable cardioverter-defibrillator (ICD) living in a locally limited area under homogeneous climatic conditions. The frequency of tachyarrhythmic events was correlated with the thermal stress level according to the "Klima Michel Model," a complete thermophysiologic model that calculates "felt-temperature" values on the basis of the outdoor temperature and further meteorologic data. During a mean follow-up time of 40 +/- 17 months (range 4 to 72), 761 ventricular tachyarrhythmic events occurred in 50 of 138 consecutive ICD recipients. Analysis of the monthly felt-temperature levels and the mean circannual variation of the registered ventricular arrhythmias suggested that very cold and very hot conditions may be associated with an increased frequency of ventricular tachyarrhythmias. This finding was confirmed by calculation of the sum of tachyarrhythmias on all 2,039 days of the follow-up period divided into 5-degree-step felt-temperature classes. Thus, thermal stress may be 1 factor triggering the occurrence of ventricular tachyarrhythmias in patients with cardiac disease and suppressed cardiac function. Part of the increase in cardiac mortality under above-average hot and cold atmospheric conditions may be attributed to ventricular arrhythmic events.

Antitachycardia pacing in patients with implantable cardioverter-defibrillators: inverse circadian variation of therapy success and acceleration.

We analyzed spontaneous ventricular tachycardias treated by antitachycardia pacing during long-term follow-up in 138 recipients of an implantable cardioverter-defibrillator. An inverse circadian variation of the antitachycardia pacing termination and acceleration rates with the worst antitachycardia pacing success during the time period with the highest episode frequency (morning hours) was demonstrated.

Assessment of heart rate variability by using different commercially available systems.

The results of heart rate variability analysis of the same Holter tape by using 4 different commercially available systems are statistically incomparable. This might have important implications when projecting and evaluating clinical trials.

Progression and regression of minor coronary arterial narrowings by quantitative angiography after fenofibrate therapy.

To study the effects of fenofibrate, a lipid-lowering medication, on patients with coronary artery disease, 191 minor coronary narrowings in 42 patients with coronary artery disease were analyzed by quantitative coronary angiography using computer-assisted contour detection. Computed parameters were percent diameter reduction and percent plaque area. A prospectively formed intervention group of 21 patients treated with special diet and fenofibrate (200 to 400 mg/day) was checked every 6 weeks with regard to risk factors. After a mean interval of 21 months, coronary angiography was repeated, using the same x-ray system and nearly identical projections. The intervention group was angiographically compared at follow-up with an untreated comparison group, also comprising 21 patients. Both groups had high initial serum cholesterol (mean 311 mg/dl) and low-density lipoprotein (LDL) cholesterol levels (mean 235 mg/dl). Only among the treated patients did lipid levels change significantly: cholesterol, -19%; LDL cholesterol, -20%; high-density lipoprotein cholesterol, +19%; and triglycerides, -30%. At angiographic follow-up, the changes in percent diameter reduction and percent plaque area correlated positively with the mean serum and LDL cholesterol levels of the intervention group. Significant differences were found in the change in percent plaque area between both groups. The intervention subgroup with angiographic regressions (11 patients) had significantly lower serum and LDL cholesterol levels than the intervention subgroup with angiographic progressions (10 patients). These results indicate the beneficial effect of fenofibrate on minor coronary narrowings. Because of its high reproducibility in measuring minor narrowings, quantitative coronary angiography proved to be a suitable method for angiographic follow-up.

Comparative rest and exercise hemodynamics of 23-mm stentless versus 23-mm stented aortic bioprostheses.

BACKGROUND: The hemodynamic superiority of stentless valves at rest has been generally accepted, but there is a lack of studies on exercise hemodynamics. METHODS: We assessed aortic valve hemodynamics at rest and during exercise in 10 patients with a 23-mm stentless aortic bioprosthesis (Medtronic Freestyle; Medtronic Europe SA/NV, St. Stevens Woluwe, Belgium), in 10 patients with a 23-mm stented aortic bioprosthesis (Carpentier-Edwards, SAV, model 2650; Baxter Edwards AG, Horw, Switzerland), and in 10 healthy volunteers (control group) by means of Doppler echocardiography. RESULTS: Gradients at rest and gradients on comparable maximum exercise levels were significantly lower in patients with stentless valves compared to those with stented valves (rest: 6 +/- 2/11 +/- 4 mm Hg [mean/peak] versus 12 +/- 3/21 +/- 10 mm Hg; exercise: 9 +/- 3/18 +/- 6 mm Hg [mean/peak] versus 22 +/- 8/40 +/- 11 mm Hg). Patients with stentless valves revealed, in comparison to healthy young men, significantly higher gradients, but the small gradient difference of 3/7 mm Hg (mean/peak) at rest remained nearly unchanged throughout the exercise protocol (4/8 mm Hg [mean/peak] at 25 W, 4/9 mm Hg at 50 W and 4/9 mm Hg at 75 W). In contrast, the gradient difference between patients with stented and stentless valves increased significantly from one exercise level to the next (6/12 mm Hg [mean/peak] at rest, 8/14 mm Hg at 25 W, 12/17 mm Hg at 50 W, and 15/25 mm Hg at 75 W). CONCLUSIONS: A stentless aortic bioprosthesis seems to be an appropriate aortic valve substitute, especially in patients who perform regular physical exercise.

Fibrinolytic effects of pro-urokinase combined with low-dose urokinase compared to high-dose urokinase in patients with acute myocardial infarction.

20 patients (6 females, 14 males) aged between 47 and and 75 years (mean: 62.6 yrs.) with acute myocardial infarction (onset of symptoms within 6 hours) were treated intravenously with either 200,000 U urokinase (UK) and 4.5 million U pro-urokinase (pro-UK) within 60 min (group I, N = 10), or 2.5 million U UK within 5 min (group II, N = 10). Blood samples for haemostatic and fibrinolytic function tests were taken prior to and repeatedly during the 24 hours following treatment. Peak fibrinolytic activity measured by fibrin plates was equivalent in both regimens. Average decreases, with lowest levels within 60 to 120 min following thrombolytic therapy, were observed of 27% and 70% for plasminogen, of 71% and 91% for alpha-2-antiplasmin, and of 20% and 74% for fibrinogen in group I and II, respectively. The reptilase time reached maximum values of 1.5- and 4.5-fold within 60 to 180 min. Peak levels of D-dimers and thrombin-antithrombin III complexes in group II were 2.6 and 3.2 times those of group I. After 24 hours, in contrast to group I, all these parameters still remained significantly different from pretreatment values in group II. These data indicate that, contrary to high-dose UK, pro-UK in combination with low-dose UK causes minor systemic fibrinolytic effects and is, therefore, assumed to be largely clot-specific, although the fibrinolytic potential is equivalent for both regimens.

Factors affecting the restenosis rate after percutaneous transluminal coronary angioplasty.

In an open study follow-up angiographies were performed independently from the clinical course on altogether 131 consecutive patients (99 men, 32 women) six months after percutaneous transluminal coronary angioplasty (PTCA). During this period patients received at least 320 mg of aspirin daily. Possible factors affecting the restenosis rate included age, sex, diabetes mellitus, arterial hypertension, abnormal lipid metabolism, smoking, dosage of aspirin administered, degree of stenosis shown by affected vessels before dilatation, number of vascular segments dilated and platelet reactivity. Restenosis was defined as a renewed narrowing of the dilated segment by 50% or more, with an increase in stenosis by at least 20%. In the present study the following restenosis rates were found six month after a primarily successful PTCA: 30% for the entire sample (39 out of 131 patients); 25% in patients with normal platelet function, 50% in those with mildly abnormal platelet function, and 60% in those with frankly abnormal platelet function; 24% in non-diabetic patients and 45% in diabetics. Analysis of the findings showed that abnormal platelet function and the presence of diabetes mellitus were the most important factors in the subsequent development of restenosis after angioplasty. The same also applied in a more restricted manner to the degree of stenosis present before angioplasty.

Neutrophil adhesion and activation during systemic thrombolysis in acute myocardial infarction.

In a pilot study, alterations of polymorphonuclear neutrophil function during systemic thrombolysis in acute myocardial infarction have been investigated in humans. The following parameters of neutrophil function were measured before and at 15 and 45 minutes after initiation of systemic thrombolysis with a recombinant tissue-type plasminogen activator in 20 patients with acute myocardial infarction: (1) neutrophil adhesion and (2) neutrophil activation. During systemic thrombolysis a significant decrease was observed in neutrophil adhesion (5.5+/-6.4 to 3.2+/-3.3; p<0.05), in phagocyting neutrophil activation (39+/-18 to 25+/-14%; p<0.05), and in resting neutrophil activation (9+/-7 to 3+/-4%; p<0.05). Successful reperfusion coincided with a significantly higher reduction of phagocyting neutrophil activation (40+/-14 to 20+/-12% vs. 39+/-24 to 26+/-19% in unsuccessful reperfusion; p<0.05), and of neutrophil adhesion (6.2+/-5.7 to 2.7+/-3.0 vs. 4.1+/-3.8 to 3.5+/-4.0 in unsuccessful reperfusion; p<0.05) during thrombolysis. Systemic thrombolysis in acute myocardial infarction is accompanied by a reduction in neutrophil adhesion and activation dependent on thrombolytic success.