To investigate the association of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and coronary endothelial function.In 289 patients with coronary artery disease we assessed coronary endothelium-dependent and -independent vascular responses to intracoronary infusion of acetylcholine, adenosine, and nitroglycerin, respectively, and determined plasma ADMA and l-arginine concentrations by HPLC. After 6 months of treatment with either cerivastatin, nifedipine, cerivastatin+nifedipine, or placebo, coronary vascular function testing as well as ADMA and l-arginine determinations were repeated. We observed no correlation of plasma ADMA or l-arginine concentration and coronary response to acetylcholine, adenosine or nitroglycerin baseline, and no correlation of changes of ADMA or l-arginine plasma concentration with changes in coronary function (all r and rho<0.3, all p>0.05).At physiological plasma concentrations ADMA appears to have only little impact on coronary endothelial function.

Today it is generally accepted that diet has to be implemented into the strategies for primary and secondary prevention of cardiovascular disease, in particular coronary artery disease. Possible cardioprotective mechanisms of a prudent nutrition include beneficial effects on lipid profile, oxidative stress, thromboembolic events and suppression of arrhythmias as well as sudden death. Common to all diets recommended by professional organisations, like the American Heart Association or the European Society of Cardiology, the replacement of saturated fatty acids and trans fatty acids with polyunsaturated fatty acids is regarded as a key feature.

Angiographic follow-up studies on the evolution of coronary artery disease are of increasing relevance. It has still to be evaluated which coronary segments are predominantly involved in the process of atherosclerosis and, thus, should be preferably included in the analysis. Therefore, the correlation of progression and regression of coronary disease with the diameter and location (proximal, mid or distal) of coronary segments was investigated from the data of the INTACT-study, in which 25 different coronary segments were defined including anatomic variants of rather distal segments. In 348 patients with coronary artery disease, standardized coronary angiograms were repeated within 3 years and were quantitatively analyzed (CAAS). In 1063 coronary stenoses (% diameter stenosis > 20%) compared from both angiograms, progression and regression were not influenced by diameter nor location of arterial segments. In the follow-up angiograms, the number of new lesions (stenoses and occlusions) per coronary segment differed with regard to segment diameter (> 3 mm: 64/1125 (6%); 2-3 mm: 139/1967 (7%); < 2 mm: 44/1756 (2%); p < 0.001) and location of segments (proximal: 86/1285 (7%); mid: 84/1193 (7%); distal: 77/2370 (3%); p < 0.001). Out of 77 distal new lesions, only 25 (32%) were found in segments < 2 mm in diameter. Since the absolute number of new lesions was high in distal coronary segments, but low in segments with diameters < 2 mm, angiographic follow-up studies should analyze coronary segments at any location, but may neglect segments with diameters smaller than 2 mm.

Animal experiments demonstrated a significant suppressive effect of various calcium channel blockers on the formation of atherosclerotic lesions. Therefore, a prospective, placebo-controlled, randomized, double blind multicenter study was performed to investigate the inhibitory influence of the calcium channel blocker nifedipine (80 mg/day) on the progression of coronary artery disease in man. Study endpoints were changes of coronary morphology documented by coronary angiography with particular respect to the formation of new coronary stenoses. In 348 out of 425 patients included in the study, coronary angiograms were repeated after three years. The angiograms were standardized by induction of a maximal coronary vasodilation with high doses of nitrates and by using absolutely identical angiographic projections. Quantitative analysis of coronary cineangiograms was performed with the computer-assisted contour detection system CAAS. Parameters were mean and minimal diameter of all segments and minimal stenosis diameter, percent diameter stenosis, length and plaque area of all stenoses. Continuous intake of study medication was registered in 282 patients, 134 on nifedipine and 148 patients on placebo. In these patients, a total of 3808 coronary segments with 893 stenoses (greater than or equal to 20% diameter reduction in at least one angiographic projection) were compared on the baseline and follow-up cineangiograms. The changes in all angiographic parameters analyzed averaged over all patients by considering all angiographic projections analyzed, indicated significant progression of the disease (p less than 0.006). The average changes in all parameters were even about three times more profound, when in the individual patients only the respective projections indicating the maximal changes were considered for the calculation (p less than 0.001). However, with neither of these two analysis modes, the differences in progression between the treatment groups were statistically significant. In the follow-up angiograms, a total of 196 new coronary lesions (185 stenoses, 11 occlusions) were found at previously normal arterial sites. In patients on nifedipine, an average of only 0.58 new lesions per patient were detected versus 0.80 lesions per patient on placebo (-27%; p = 0.031). INTACT is the first prospective angiographic trial on the progression of coronary artery disease using computer-assisted quantitative coronary angiography in such a high number of patients. All parameters analyzed indicated significant progression of coronary artery sclerosis. Nifedipine had no influence on the progression of preexisting coronary stenoses, but inhibited significantly the formation of new angiographically recognizable lesions. Further prospective coronary angiographic trials with calcium channel blockers using a comparably exact method are needed to confirm the results of this study.

Kalzium ist das häufigste Kation im menschlichen Körper. Seine Bewegungen durch die Membran erregbarer Zellen und seine Akkumulation innerhalb der Zelle sind von fundamentaler Bedeutung für die spezifische Aktivität von Geweben. Allgemein ist die Konzentration von Kalzium im Zytosol nur ein geringer Anteil der Kalziumkonzentration im Plasma und weitgehend unabhängig von den normalen Schwankungen im Plasma-Kalzium [12]. Daher liegt eine wesentliche Voraussetzung für die intrazelluläre Kalziumhomöostase in einem sehr präzisen Modulationsmechanismus der Eintritts- und Austrittsrate von Kalzium im Zusammenwirken mit der Funktion des sarkoplasmatischen Retikulums und der Mitochondrien. Eine Steigerung des intrazellulären Kalziums auf abnormal hohe Spiegel kann Zellschäden oder Zelltod verursachen. Zellmembranen weisen eine niedrige Permeabilität für Kalzium auf, das in die Zellen im wesentlichen durch spezifische Kalziumkanäle eintritt.

Calcium is the most common cation in the human body. Its movements through the membrane of excitable cells and its accumulation within the cell are of fundamental importance for the specific activity of tissues. Generally, the concentration of calcium in the cytosol is only a small fraction of the calcium concentration in the plasma, and it is largely independent of the normal variations in plasma calcium [12]. Therefore, a prerequisite for intracellular calcium homeostasis is a very precise modulation mechanism of the entry and efflux rate of calcium together with functioning sarcoplasmic reticulum and mitochondria. Increasing intracellular calcium to abnormally high levels may cause cell injury or cell death. Cell membranes exhibit a low permeability to calcium which enters cells predominantly through specific calcium channels.

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.

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<0.001) and 18±9% in group B (p<0.001). Eleven of 15 and 8 of 9 coronary stenoses in groups A and B dilated to 5–80% and 15–70%, respectively.

In the spectrum of acute ischemic syndromes, unstable angina pectoris is characterized by specific features in the patients history, including recent occurrence of angina at rest, or brought on by minimal exertion, as well as the deterioration of a chronic stable angina into more severe, prolonged or more frequent anginal attacks (crescendo angina). Typical electrocardiographic criteria include reversible ST-segment deviations and/or variable T-wave inversions. Cardiac enzymes are usually not elevated.

The natural history of coronary artery stenosis has to be studied by comparison of coronary angiograms of the same patient taken at different times. Unfortunately, although thousands of coronary angiograms are performed each year, only a limited number of repeated studies is available, particularly in patients who are medically treated over an interval of more than one year.

The effect of optimal medical therapy on coronary arterial anatomy was evaluated in 25 patients with unstable angina pectoris. Coronary arterial diameter and the extent of stenosis were exactly quantified in two successive coronary angiograms performed in each patient at approximately a 1 year interval (range 4 to 31 months, average 12.4 months). The measuring device was a vernier caliper with an accuracy of 0.05 mm. After 1 year of medical treatment 69 stenoses of the three major coronary branches showed no significant change: The average degree of area obstruction of 27 stenoses of the right coronary artery was 79 and 84 percent in the initial and second studies, respectively; that of 26 stenoses of the left anterior descending artery 78 and 77 percent, respectively, and that of 16 stenoses of the left circumflex artery 73 and 83 percent, respectively. In 11 patients, 14 stenoses showed a distinct progression of more than 20 percent area obstruction. All six stenoses showing more than 90 percent obstruction in the first angiogram progressed to complete obstruction within 1 year. In five other patients area obstruction in five stenoses regressed by more than 20 percent. The anatomy of vessel segments distal to obstructions remained unchanged within 1 year. It is concluded from these quantitative measurements that the distribution and severity of coronary lesions are similar in patients with stable and unstable angina pectoris. Coronary anatomy showed no significant change after 1 year of medical treatment. The rate of progression was substantially lower than previously reported in patients with stable angina pectoris.