[Estrogens and cardiovascular diseases in the postmenopause].
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Cardiovascular Diseases↗
Biomedical subjects
W Rafflenbeul
Publications and source records attributed to W Rafflenbeul.
Concept of an antiatherosclerotic efficacy of calcium entry blockers. INTACT Investigators.
Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.
Animals↗
Anatomical progression of coronary artery disease in humans as seen by prospective, repeated, quantitated coronary angiography. Relation to clinical events and risk factors. The INTACT Study Group.
BACKGROUND: At present, there is extensive knowledge on the clinical course of coronary artery disease (CAD), whereas data on the underlying anatomical changes and their relation to clinical events are still limited. METHODS AND RESULTS: We investigated progression and regression of CAD prospectively over 3 years in 230 patients (average age, 53.2 years) with mild to moderate disease by applying quantitated, repeated coronary angiography. Minimal stenotic diameters, segment diameters, and percent stenosis were analyzed by the computer-assisted Coronary Angiography Analysis System (CAAS). Progression was defined either as an increase in percent stenosis of preexisting stenoses by greater than or equal to 20% including occlusions or as formation of new stenoses greater than or equal to 20% and new occlusions in previously angiographically "normal" segments. At first angiography, we found 838 stenoses greater than or equal to 20% (average degree, 39.3%) and 135 occlusions in the four major coronary branches (4.23 lesions per patient). At second angiography, 82 (9.8%) of the preexisting stenoses had progressed, 15 of them up to occlusion (1.8%; preocclusion degree averaging 46.6%; 29.7-65.6%). In addition, there were 144 newly formed stenoses (average degree, 39.2%) and 10 new occlusions. Hence, 25 (2.6%) of all stenoses had become occluded. Altogether, 129 patients (56.1%) showed progression: 68 (29.6%) with new lesions only, 27 (11.7%) with preexisting lesions, and 34 (14.8%) with both types. Regression (decrease in degree of stenoses greater than or equal to 20%) was present in 29 stenoses (3.6%) and 28 patients (12%). The incidence of new myocardial infarctions was low, with three originating from occluding preexisting stenoses and one from new stenoses; hence, only four (16%) of the 25 new occlusions led to myocardial infarctions. Risk factor analysis showed that cigarette smoking correlated significantly with the formation of new lesions (p = 0.001), whereas total cholesterol correlated with the further progression of preexisting stenoses (p = 0.017) but not with the incidence of new lesions. CONCLUSIONS: In patients with mild to moderate CAD, the angiographic progression is slow (in this study 18.7% of patients and 7% of stenoses per year) but exceeds regression (4.1% of patients and 1.2% of stenoses per year). Progression is predominantly seen in the formation of new coronary stenoses and less in growth of preexisting ones. Most of the stenoses were of a low degree (less than 50%), clinically not manifest including those going into occlusion and leading to myocardial infarction. Progression was influenced by risk factors, especially cigarette smoking (formation of new lesions) and high cholesterol levels (progression of preexisting stenoses).
Constriction, Pathologic↗
[Pharmacologic prevention of cardiovascular diseases with calcium antagonists].
The major impact of calcium-antagonists in prevention strategies of cardiovascular disease evolves from their modulation of signal transduction and metabolic processes controlled by calcium-ions as "second messenger" in cells participating in the early development of vascular atherosclerotic lesions, namely endothelial cells, vascular smooth muscle cells, monocytes/macrophages, T-lymphocytes and platelets. In accordance with experimental data suppression of angiographically early coronary lesions was documented in four independent clinical studies using quantitative analysis of repeated coronary angiography: Nifedipine and Nicardipine reduce angiographically "new" (minimal) lesions to 30-70%, in some cases already after 1 year of treatment. This anti-atherosclerotic effect is independent of known risk factors and indicates a new strategy in "primary" prevention of atherosclerotic vascular disease. In pre-infarction-syndromes calcium-antagonists demonstrate a tendency in attenuating anginal symptoms and progression into definitive infarction. Analysis of studies in acute infarction showed a neutral effect of calcium-antagonists with unchanged infarct-size, regional and global ventricular function or early mortality. In post-infarction patients only strict selection criteria (up to 60% of patients) as well as delayed onset of therapy (> 7 days after infarction) reduce the number of re-infarction and mortality. Subgroup analysis indicate that calcium antagonists with mild afterload reduction and minimal negative inotropic impact might be preferable. The suppression of "early" lesions should be regarded as the predominant benefit for future strategies in prevention of cardiovascular disease with calcium-antagonists.
Animals↗
Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy.
BACKGROUND: It has been suggested that thrombolysis in a feedback reaction may generate pro-coagulant activities. METHODS AND RESULTS: Fifty-five patients were treated with urokinase-preactivated prourokinase (n = 35) or tissue-type plasminogen activator (n = 20) for acute myocardial infarction and underwent coronary angiography at 90 minutes and at 24-36 hours into thrombolysis, and fibrinogen (Ratnoff-Menzie), D-dimer (ELISA) and thrombin-antithrombin III complex levels (ELISA) were measured. Primary patency was achieved in 39 patients (70.9%), 13 of whom (33.3%) suffered early reocclusion. Nonsignificant decreases in fibrinogen levels were observed while D-dimer levels increased +3,008 +/- 4,047 micrograms/l (p less than 0.01), differences not being significant in respect to the thrombolytic agents or to the clinical course. In contrast, while thrombin-antithrombin III complex levels decreased -4.4 +/- 13.0 micrograms/l in patients with persistent patency, they increased +7.5 +/- 13.6 micrograms/l in case of nonsuccessful thrombolysis (p less than 0.02) and +11.9 +/- 23.8 micrograms/l in case of early reocclusion (p less than 0.001). For patients with thrombin-antithrombin III complex levels greater than 6 ng/l 120 minutes into thrombolysis, the unfavorable clinical course was predicted with 96.2% sensitivity and 93.1% specificity. CONCLUSION: Generation of thrombin, occurring during thrombolysis, is a major determinant for the success of therapy and thrombin-antithrombin III levels may serve as predictors for the short-term prognosis.
Antithrombin III↗
Myocardial infarction. Secondary prevention with nifedipine.
The rationale for the use of nifedipine in patients with acute myocardial infarction (MI) is based on the various cardiovascular actions of the compound: reduction of myocardial oxygen consumption by attenuation of cardiac and vascular smooth muscle tension; augmentation of oxygen and substrate supply after increased coronary blood flow with dilatation of epicardial coronary arteries (particularly in coronary obstructions) and dilatation of coronary resistance and collateral vessels; myocardial 'protection', i.e. reduction of myocardial damage via a complex intracellular mechanism, the primary outcome of which is the maintenance of an energy level sufficient to preserve the ionic homeostasis of the myocyte. The effect of nifedipine on reinfarction and mortality rates was evaluated in 6 well designed studies involving 8670 patients with evolving or established acute MI. Compared with placebo, short term therapy (for up to 6 months) with nifedipine 30 to 120 mg/day initiated, in some patients, as early as 3 hours after the onset of symptoms did not reduce either reinfarction rate or mortality. In one study (SPRINT I) [Israeli Sprint Study Group 1988], where a regimen of nifedipine 30 mg/day was only started 7 to 21 days after infarction, the exceptionally low mortality rate (5.7%) over 10 months in the placebo group precluded the demonstration of a beneficial effect of nifedipine. These results collectively suggest that nifedipine does not prevent the 'secondary' coronary events of plaque rupture and thrombus formation associated with MI and sudden cardiac death. However, the suppression of early lesions by nifedipine (as demonstrated in the INTACT study [Lichtlen et al. 1990]) might reduce 'primary' progression and improve the long term survival after MI.
Female↗
[Problems of therapeutic trials in cardiology].
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Angioplasty, Balloon, Coronary↗
Retardation of angiographic progression of coronary artery disease by nifedipine. Results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). INTACT Group Investigators.
425 patients showing mild coronary artery disease (CAD) on arteriography were enrolled in a multicentre trial and randomised to treatment with nifedipine (80 mg/day) or placebo. The two groups were well matched for age, sex, and risk factors. 348 patients (82%) underwent repeat arteriography 3 years later; 282 (134 nifedipine, 148 placebo) had received treatment throughout, but treatment had been stopped in 39 nifedipine-treated and 27 placebo-treated patients after average periods of 354 and 467 days. Computer-assisted measurements of arteriograms from all restudied patients (175 placebo, 173 nifedipine) showed no significant differences in the number or severity of lesions on initial arteriograms, or in the progression or regression of existing lesions over 3 years. In contrast, the number of new lesions per patient was significantly lower in the nifedipine group than in the placebo group (0.59 vs 0.82 lesions per patient, a 28% reduction). Thus in patients with mild CAD nifedipine substantially suppresses disease progression as shown by the appearance of new lesions detectable by quantitative coronary arteriography.
Administration, Oral↗
Reproducible uniform coronary vasomotor tone with nitrocompounds: prerequisite of quantitative coronary angiographic trials.
In quantitative analysis of repeated coronary angiograms, a variable vasomotor tone of the epicardial coronary arteries may influence the accuracy of the results. Therefore, we evaluated the extent and reproducibility of coronary artery dilation with nitrocompounds. In 32 patients with coronary artery disease, the vasodilatory response of angiographically normal coronary segments to different nitrocompounds was analyzed with the computer-assisted contour detection system CAAS. Twenty patients received 5 mg or 10 mg of isosorbide dinitrate sublingually. After 10 to 15 min, a maximal diameter increase was measured with an average of 16 +/- 11% (5 mg: P less than 0.01) and 28 +/- 13% (10 mg: P less than 0.001) from control. Another 12 patients received 0.025 mg per kg body weight of SIN-1, the active metabolite of molsidomine, as an intravenous infusion over 5 min. A comparable maximal dilation (29 +/- 5%; P less than 0.001) occurred after 10 to 15 min and could not be enhanced further with 0.8 mg nitroglycerin administered sublingually (28 +/- 7%; n.s.). One hour after square root of Sin-1, coronary dilation was still 24 +/- 8% (P less than 0.001 compared with control), and 0.8 mg of nitroglycerin sublingually reestablished the previous maximal dilation of 28 +/- 8%. We conclude that high doses of nitrocompounds induce a reproducible maximal coronary dilation that eliminates a substantial source of error in quantitative analysis of repeated coronary angiograms. At present, sublingual administrations of either 10 mg isosorbide dinitrate once or 0.8 mg nitroglycerin repeatedly seem to represent the easiest practicable modes to achieve maximal coronary vasodilation for an adequate period.
Angiography↗
Coronary vasomotor tone in large epicardial coronary arteries with special emphasis on beta-adrenergic vasomotion, effects of beta-blockade.
Changes in coronary vasomotor tone of large epicardial coronary arteries today can be assessed quite accurately by exact measurements of coronary diameters applying computer assisted systems. The effect of various vasodilators (nitrates, calcium antagonists, EDRF-dependent compounds) was tested in this way. It appears that normal coronary artery segments reach a maximum of dilator reserve with an increase of luminal diameter of approximately 30-40%; different patterns of kinetics were, however, encountered. beta-Blocking agents, both non-selective (propranolol) and selective (atenolol), were found to lead to a gradual vasoconstriction, i.e., a decrease in diameter by approximately 20-25% over 20 min, an effect which is overcome by nitrates. New beta-blocking compounds with vasodilator properties, such as celiprolol, show no constriction. The vasoconstrictor effect of propranolol and atenolol may not only be due to the decrease of flow following the drop in myocardial oxygen consumption, but could also reflect an unopposed alpha-adrenergic tone. The clinical aspects of this observation are discussed.
Adrenergic beta-Antagonists↗
Elimination of variable vasomotor tone in studies with repeated quantitative coronary angiography.
In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone may have a significant influence on the coronary artery diameters, thereby increasing the variability in the measurements. To obtain objective data on these measurement variabilities, two protocols were designed to assess the influences of ionic and nonionic radiographic contrast media on the mean diameters of angiographically normal coronary arteries. The vessel sizes were determined with the CAAS using automated edge detection techniques. In 21 patients (study no. I), coronary angiograms were taken in identical angiographic projections before (control), and immediately following several (at average 7) subsequent diagnostic dye injections administered over a period of about 7 min. The ionic contrast agent diatrizoate 76% induced a coronary dilation of 19 +/- 7% (mean +/- s.d., p less than 0.001; n = 10); the nonionic agent iopromide 370 increased the coronary artery diameters by only 6 +/- 4% (p less than 0.01; n = 11). In another 11 patients (study no. II) coronary angiograms were obtained using the nonionic contrast medium iopamidol 300 at 5, 8, 10 and 11 min after the control acquisition; this protocol was repeated in the same patients with diatrizoate 76%. With iopamidol, coronary diameter changes were not significant at any time; with diatrizoate, however, coronary dilation was measured at 10 min (2 +/- 2%; p less than 0.01) and at 11 min (10 +/- 3%; p less than 0.001). In a third study it was tested, whether standardization of coronary vasomotor tone (e.g. in coronary angiographic follow-up studies) is possible by the induction of a reproducible maximum coronary dilation with nitrocompounds. In 12 patients, the mean diameters of angiographically normal coronary segments were analyzed before and at various times after i.v. administration (over 4 min) of 0.025 mg SIN-1/kg bodyweight. Coronary dilation was maximal at 10 or 15 min after the onset of the SIN-1-infusion (29 +/- 5%; p less than 0.001). 0.8 mg nitroglycerin given s.l. at 15 min did not further dilate the coronary arteries (28 +/- 7%). One hour after SIN-1, coronary dilation still amounted to an average of 24 +/- 8% (p less than 0.001) and became 'maximal' again, when 0.8 mg nitroglycerin was again administered sublingually (28 +/- 8%; p less than 0.001). In conclusion, short-term variability of coronary vasomotor tone induced by ionic radiographic contrast media can be eliminated by the use of nonionic contrast agents and observation of injection intervals of at least 2 min. In quantitative coronary angiographic follow-up studies, as well as during acute interventions (e.g., PTCA), identical baseline vasomotor tone can be achieved by induction of the maximal coronary dilation using nitrocompounds.
Adult↗
Vasodilatory effects of nisoldipine on coronary arteries--correlation with plasma levels.
Vasomotion of angiographically normal and stenotic epicardial coronary arteries was analyzed up to 15 minutes after the onset of an intravenous infusion (4 minutes) of 0.5 mg (13 patients, group A) or 1 mg nisoldipine (13 patients, group B). After both doses the maximal increase of the mean diameters of normal coronary segments was achieved not before the 15th minute, averaging 11 +/- 6% in group A (p less than 0.001) and 18 +/- 9% in group B (p less than 0.001). Eleven of 15 and 8 of 9 coronary stenoses in groups A and B dilated to 5-80% and 15-70%, respectively. The nisoldipine concentration reached maximal levels at the end of the infusion (fourth minute) with an average of 8 +/- 4 ng/ml and 17 +/- 7 ng/ml in groups A and B, respectively. A significant correlation between nisoldipine plasma levels and dilation of normal coronary segments was obtained only with the individual maxima of these parameters and only in group A (p less than 0.01). The hysteresis of the coronary dilation in relation to the drug plasma levels may be due to the high receptor affinity of nisoldipine. In either group nisoldipine provoked a persistent increase in coronary sinus oxygen saturation (p less than 0.01) and a substantial and prolonged drop in systolic and diastolic aortic pressure (p less than 0.001). Both doses of nisoldipine induced a rise in heart rate (p less than 0.01) and a slight drop in the rate-pressure product (p less than 0.05).
Adult↗
Features of the angiographic evaluation of the INTACT study. International Nifedipine Trial on Antiatherosclerotic Therapy.
INTACT (International Nifedipine Trial on Antiatherosclerotic Therapy) is a prospective, placebo-controlled, randomized, double-blind, multicenter trial analyzing the influence of 80 mg nifedipine/day on the angiographic progression of early stage coronary atherosclerosis. Coronary angiograms were taken in identical projections before and after a treatment period of 3 years. Quantitative analysis of the angiograms was performed with the computer-assisted contour detection system CAAS. For definition purposes, the coronary artery system was subdivided into 25 different segments, including all anatomic variants. Measurement parameters of segments were mean and minimal diameter, and of stenoses minimal diameter, percentage diameter reduction (at least 20%), length, and plaque area. The variable extent of the changes of these parameters in the different projections analyzed per patient in the two study angiograms was considered by separate computation of the maximal, mean, and minimal changes over these projections; the comparison of the parameter changes between the two treatment groups was performed separately according to these three modes. For all parameters, this comparison was performed on the basis of the individual 25 segments, as well as after aggregation of individual segments to arteries (RCA, LAD, and LCX), to groups of large and small segments, and to the entire coronary artery system. Assessment of changes of the coronary (patho)morphology by quantitative analysis of coronary angiograms is associated with a number of methodical limitations, which may lead to a certain variability of the results. However, due to the double-blind feature of INTACT, this variability should be comparable in the two groups of this study, allowing for a conclusive comparison.
Angiography↗
Retardation of coronary artery disease in humans by the calcium-channel blocker nifedipine: results of the INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy).
Experimental studies have demonstrated a 30-50% reduction in the development of atheromatous lesions of the aorta in rabbits fed a diet rich in cholesterol when they were treated with nifedipine. Based on these favorable results, we designed a multicenter, placebo (PL)-controlled, randomized, double-blind study, to test the effect of 80 mg nifedipine (NIF) per day versus placebo on the progression of mild coronary artery disease (CAD) (further development of existing stenoses, especially formation of new stenoses and occlusions) over a duration of 3 years. Progression of CAD was assessed by coronary angiograms performed at entrance and at completion of the study, using a computer-assisted analysis system (CAAS) to quantitate various stenosis parameters (percent degree of stenosis and minimal stenosis diameter). Of the 425 patients enrolled, 348 (82%) underwent a second angiogram; 66 of them, however, terminated treatment prematurely after an average of 359 (placebo) and 467 days (nifedipine). A total of 282 patients (148 on placebo, 134 on nifedipine) completed the trial with full-length treatment. There were no differences between the two groups in the progression of the existing stenoses. Patients on nifedipine, however, demonstrated significantly fewer new lesions (stenoses greater than 20% or occlusions) than those on placebo: In the 282 patients undergoing the full-length treatment, there were 73 patients on placebo (49%) with 118 new lesions (0.8/patient) and 54 patients on nifedipine (40%) with 78 new lesions (0.58/patient), a difference of -27% (p = 0.031 by Cochran's linear trend test). The difference was greatest in the left anterior descending branch, with 28 patients on placebo developing 33 new lesions (0.22/patient), versus 16 patients on nifedipine with 18 new lesions (0.13/patient) (-40%; p = 0.045); and in the left circumflex branch, where 34 patients on placebo exhibited 39 new lesions (0.26/patient) versus 23 patients on nifedipine with 22 new lesions (0.16/patient) (-38%, p = 0.033). No differences were observed in the right coronary artery, the vessel with the highest number of existing and new lesions [PL] versus 0.27 [NIF] new lesions/patient) (-7.6%, p = 0.381). Hence, INTACT confirmed the previous experimental studies and demonstrates a significant reduction in newly formed coronary lesions in patients on nifedipine when compared with those on placebo, especially in the presence of early coronary artery disease.
Adult↗
Role of thrombolysis and thrombin in patients with acute coronary occlusion during percutaneous transluminal coronary angioplasty.
In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.
Angioplasty, Balloon, Coronary↗
Coronary dilation with nitrocompounds and calcium antagonists.
The vasodilatory effects of nitrocompounds and calcium antagonists on epicardial coronary arteries represent substantial antianginal mechanisms in the presence of coronary vasospasm or eccentric coronary stenoses. With high doses of nitrocompounds, angiographically normal coronary segments can be dilated by an average of approx. 30%, some coronary stenoses even by up to 100%, usually without severe reduction of blood pressure. With calcium antagonists, a similar extent of dilation of normal coronary arteries and eccentric stenoses can be obtained. Our own group demonstrated an average dilation of normal coronary arteries of about 20% after intravenous administration of dihydropyridine calcium antagonists; however, the average systolic blood pressure dropped below 100 mmHg after these compounds. Hence, although in isolated human coronary arteries high concentrations of calcium antagonists were shown to induce a considerably greater vasodilation than nitrocompounds, the early drop in blood pressure prohibits a higher dosage of calcium antagonists in vivo. In the presence of coronary artery disease, particularly when associated with coronary vasospasm, a combination of the two groups of compounds might be recommendable, since an addition of the effects of coronary vasomotor tone is likely. Furthermore, the antianginal effects of a reduction of preload and afterload are complementary.
Angina Pectoris↗
[Incidence of residual thrombi following successful thrombolytic therapy in acute myocardial infarct and their significance for the rate of early re-occlusion. A report of a multicenter dose-finding study for thrombolytic therapy with urokinase preactivated natural prourokinase (TCL 598)].
Thrombolysis with urokinase preactivated prourokinase was performed in 74 patients. At control angiography, 90 min into thrombolysis, in 39 (52.7%) patients the infarct-related coronary artery was found patent. However, 26 out of the 39 patients (66.7%) with a patent infarct artery demonstrated angiographic signs of residual coronary thrombi. With an estimated average of 75 +/- 25% in both, patients with and without residual thrombus, the severity of the residual stenosis after thrombolysis was found to be independent from the presence of angiographic signs of residual coronary artery thrombosis. In patients with residual coronary thrombi, however, a trend towards poorer coronary perfusion was observed (50% vs 77% of the patients with prompt antegrade [TIMI grade III] perfusion [p less than 0.2]. Control angiography performed 24 to 36h after thrombolysis revealed reocclusion of the infarct artery in 26.3% of the patients with residual coronary thrombi, while none of the infarct vessels without angiographic signs of residual thrombosis had reoccluded (p less than 0.05). At follow-up angiography 17 to 23 days after thrombolysis this difference in the incidence of reocclusions had further increased to 43.8% of patients with vs 12.5% of patients without residual coronary thrombus (p less than 0.01). Thus, after thrombolysis, residual thrombotic material remaining in the infarct related vessel seems to be a major risk factor, indicating early reocclusion of the infarct artery.
Angioplasty, Balloon, Coronary↗
Coronary vasodilation with dihydropyridines--a pharmacokinetic study.
In 26 patients with coronary artery disease, the mean diameters of angiographically 'normal' epicardial coronary arteries were assessed with the aid of a computer-assisted contour detection system (CAAS) before and up to 15 min after onset of a 4-min intravenous-infusion of 2 mg nifedipine (13 patients, group I) or 1 mg nisoldipine (13 patients, group II). Maximal coronary dilation amounted to 20 +/- 9% (4th min) in group I and to 18 +/- 9% (15th min) in group II. In addition, in group II changes of the minimal diameters of 9 coronary obstructions were measured; the maximum increase averaged 28 +/- 15% (7th min). In order to compare the pharmacokinetic properties of these compounds the dilation of the 'normal' coronary segments was correlated with the respective drug plasma levels; maximal plasma concentrations averaged 62 +/- 21 ng ml-1 (7th min) in group I and 17 +/- 7 ng ml-1 (4th min) in group II respectively. A positive, linear correlation between coronary dilation and plasma levels was only found with nifedipine (P less than 0.05); with nisoldipine, however, coronary dilation developed in form of a hysteresis curve, when plotted against plasma levels, probably due to the high receptor affinity of this substance. The prolonged efficacy of nisoldipine could be favourable in oral long-term treatment of patients with coronary artery disease.
Adult↗