[Acute hypertension following dexamethasone. A critical incident during anesthesia]. / Hypertensive Krise nach Dexamethason. Ein schwerer Anästhesiezwischenfall.

Prior to anesthesia a 65-year-old patient received 8 mg dexamethasone to prevent postoperative nausea and vomiting (PONV). Instantly she reported tingling and burning followed by intense pain in the genital region spreading to the whole body. Shortly later she complained about shortness of breath and pre-cordial pain. Acute hypertension could only be lowered by NTG, beta-blockade and induction of anesthesia. The ECG showed ST-segment depressions and troponin-T was elevated (0.3 ng/ml). Coronary angiography revealed no significant stenosis and an abdominal CT scan showed no evidence of a pheochromocytoma. Urine metabolites of catecholamines were negative. Thus, the most likely diagnosis was stimulation of endogenous catecholamines by painful stress after dexamethasone injection with the consequence of myocardial ischemia. As a result we now routinely inject dexamethasone after anesthesia induction as prophylaxis for PONV.

[Lyme carditis and symptomatic sinus node dysfunction]. / Symptomatische Sinusknotendysfunktion bei Lyme-Karditis.

Lyme carditis is typically associated with AV nodal conduction abnormalities. We describe the case of a 66 year old female patient, who experienced a series of syncopal attacks after several tick bites two weeks earlier. ECG monitoring revealed recurrent sinus arrest with a maximum pause duration of 8 seconds. After institution of antibiotic therapy for Lyme carditis, sinus node dysfunction resolved rapidly and the patient had no further syncopes. Pacemaker implantation was not necessary. We therefore have to assume that in this patient Lyme carditis was the cause of symptomatic sinus node dysfunction.

Lipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns.

BACKGROUND: Few published data in particular from the United States indicate that the implementation of guidelines for prevention of coronary heart disease (CHD) is far from optimal. The objective of our study was to identify the type and prevalence of lipid-lowering medications in a German outpatient CHD population and to examine the impact of applied treatment regimens on serum lipid levels. METHODS: Retrospective analysis of the washout phase of 2,856 CHD patients requiring lipid-lowering medication. Data are derived from a multicenter, randomized, open-label, parallel group clinical trial comparing the safety and efficacy of atorvastatin versus simvastatin in 591 centers in Germany. Medical history, physical examination, and serum lipid levels were obtained at the beginning of the washout phase (Week -6) and at the end of the washout phase (Week -1, i.e., 5 weeks after the discontinuation of all prior lipid-lowering medications). The data at Week -6 represented the lipid levels under real life conditions. The difference from the data at Week -1 reflected the therapeutic effects achieved by the previous lipid-lowering treatment. RESULTS: The mean low-density lipoprotein cholesterol (LDL-C) level at Week -6 was 173.4 +/- 42.5 mg/dl. Only 176 (6.2%) of 2,856 CHD patients were found to meet the target LDL-C level of <115 mg/dl at Week -6, only 76 (2.7%) patients had LDL-C levels <100 mg/dl, and 363 (12.7%) patients had LDL-C levels <130 mg/dl. After discontinuation of all prior lipid-lowering medications, mean LDL-C increased to 187.2 +/- 44.0 mg. This means that only a marginal 7.4% reduction in LDL-C level was achieved under real life treatment conditions. This limited LDL-C reduction was due mainly to the low prevalence of lipid-lowering treatment (65.5% of patients did not receive any medication at all) and inadequate dosing. With respect to the effect on LDL-C and total cholesterol, statins alone were superior to fibrates. CONCLUSION: The study shows that there is a wide gap between treatment guidelines and real life treatment patterns in Germany. Awareness of the risks of high cholesterol levels has to be increased among both patients and physicians. Available treatment guidelines should be better implemented.

[Guidelines for lowering lipids are too infrequently observed. Results of a retrospective study of coronary heart disease patients]. / Leitlinien zur Lipidsenkung zu wenig beachtet. Ergebnisse einer retrospektiven Analyse an KHK-Patienten.

UNLABELLED: The aim of this retrospective analysis was to investigate adherence to treatment guidelines in the secondary prevention of coronary heart disease. 3720 CHD patients treated in 591 doctor's offices throughout Germany were investigated. End points were serum lipid levels at week-6, i.e. screening investigation, and 5 weeks after discontinuation of the lipid-lowering medication (week-1). 3383 of the 3720 (90.9%) patients had LDL-C levels > = 115 mg/dl, and 3563 (95.8%) > = 100 mg/dl. At week-6 mean LDL-C was 167.7 +/- 43.5 and mean total cholesterol was 258.8 +/- 47.8 mg/dl. 5 weeks after discontinuation of lipid-lowering treatment, mean LDL-C increased by 5.6%, and mean total cholesterol by 3.7% in comparison with baseline at week-6. 2346 (69.3%) of the patients with LDL-C > = 115 at week-6 did not receive any prior lipid-lowering medication. Also, patients receiving lipid-lowering medication demonstrated an insufficient lipid decrease (only 14.4% of all treated patients had LDL-C levels < 115 mg/dl, and only 6.8% had levels < 100 mg/dl. CONCLUSION: So far, lipid-lowering guidelines for the secondary prevention of CHD are not being adequately implemented. Appropriate action to remedy this situation (e.g. establishment of Disease Management Programs) is needed. The aggressive use of lipid-lowering drugs is a must if the goals of the treatment guidelines are to be met, and morbidity and mortality of CHD lowered.

Safety of low-density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial).

Reduction in plasma lipids has been recognized as one of the primary cardiovascular risk reduction strategies in the secondary prevention of coronary heart disease (CHD). The primary end points of TARGET TANGIBLE were the safety (adverse events and laboratory measurements) and efficacy (responder rates) of therapy with atorvastatin versus simvastatin with the aim of achieving low-density lipoprotein (LDL) cholesterol lowering to < or =100 mg/dl (2.6 mmol/L). A total of 3,748 CHD patients with LDL cholesterol levels > or =130 mg/dl (3.4 mmol/L) entered a run-in diet phase of 6 weeks without any lipid-lowering drug therapy. At the end of the diet phase, 2,856 patients met the lipid criteria and were randomized to active treatment for 14 weeks. Patients received 10 to 40 mg of either drug in an optional titration design at 2:1 randomization for atorvastatin versus simvastatin. Adverse event rates were statistically equivalent (p<0.01) for simvastatin (35.7%) and for atorvastatin patients (36.3%). Both drugs were well tolerated; <5% of patients in both groups were withdrawn due to adverse events. In all, 37 atorvastatin patients (2%) and 27 simvastatin patients (3%) had serious adverse events. Drug-related side effects (elevations in creatine kinase, liver enzymes) occurred in both groups at similar rates with 10 atorvastatin patients (0.5%) and 5 simvastatin patients (0.5%) presenting confirmed transaminase elevations >3 x the upper limit of the normal range. Significantly fewer patients in the atorvastatin group (n = 724) required titration to 40 mg compared with the simvastatin group (n = 514) (38% vs. 54%, respectively; p<0.001). Atorvastatin resulted in a significantly greater number of patients reaching the LDL cholesterol goal than those treated with simvastatin, with 67% of atorvastatin patients and 53% of simvastatin patients reaching the target LDL cholesterol level of < or =100 mg/dl (2.6 mmol/L) (p<0.001). Both atorvastatin and simvastatin are safe for use by patients in the secondary prevention of CHD, with patients in both drug groups having similar adverse event rates. Despite the use of concomitant medications there was no drug-induced rhabdomyolysis with either atorvastatin or simvastatin.

Enhancement of platelet inhibition of ticlopidine plus aspirin vs aspirin alone given prior to elective PTCA.

BACKGROUND: In many patients today, elective percutaneous transluminal coronary angioplasty is followed by implantation of coronary stents to achieve optimal results. The current medical strategy to prevent early reocclusion is the inhibition of platelet aggregation by administration of ticlopidine, in addition to aspirin, immediately after the procedure. In order to inhibit platelet aggregation as early as possible, many centres begin to treat patients with additional ticlopidine the day before elective coronary intervention. The aim of this study was to determine the effect of this strategy on platelet aggregation before angioplasty. METHOD: Fifty-two consecutive patients admitted to hospital for elective balloon angioplasty were prospectively randomized to receive either standard oral aspirin 100 mg per day or standard therapy plus 250 mg ticlopidine at the time of admission and the morning before angioplasty. Adenosine diphosphate-, collagen- and epinephrine-induced platelet aggregation was measured immediately before the procedure by an investigator who was blinded concerning the arm of therapy. RESULTS: The two groups of patients were comparable in terms of age, sex, body mass index, anginal state, time interval between application of study drug and coronary intervention. Patients on aspirin and ticlopidine had a mean maximal platelet aggregation of 36 +/- 12% with adenosine diphosphate as agonist. For the control group, 54 +/- 12% was measured (P < 0.001). Myocardial infarction or emergency coronary bypass grafting did not occur in either group. Local haemorrhagic complications at the arterial access site occurred in five (aspirin) and six (aspirin and ticlopidine) patients (P = ns) none of them requiring blood transfusion. CONCLUSION: The additional application of ticlopidine to chronic aspirin therapy the day before elective coronary balloon angioplasty leads to a significantly higher inhibition of platelet aggregation at the time of the intervention. It seems to be safe compared to the standard procedure.

[3D echocardiography. Mathematical principles and technical realization]. / 3D-Echokardiographie. Mathematische Grundlagen und technische Realisierung.

The ultimate goal of any imaging technique for the investigation of the anatomy of the beating heart is a 3D-display of the cardiac morphology throughout a complete heart cycle. The reason for this interest is quite clear: 3D-imaging has the potential for a better understanding of the individual morphology under normal and pathological conditions and especially, if complex therapeutic decisions have to been made. In the clinical practice, the echocardiographer attempts to obtain a spatial information by a mental reassembling of the 2D echocardiographic images, that are obtained from different imaging planes. This procedure, however, is very subjective and, thus, highly susceptible for errors. Therefore, the 3D-echocardiography has been developed to replace this mental process by an "objective" and reproducible computerized reconstruction. Prerequisite for such a 3D-surface reconstruction is a cubic, isotropic digital data set with cubic data volumes, so called "Voxels" (Figure 1). The term "isotropic" means, that the resolution is identical in all directions, and that the data density within the cube is homogeneous. Those cubes are the mathematical basis for any 3D-reconstruction. At the first step on the way to 3D-images, the data cubes have to be filled with 2D echo information. So far, three principal modalities of image acquisition are available for the clinical routine: parallel scanning from the esophagus (Figure 2), rotational scanning (transesophageal--Figure 3a--or transthoracic--Figure 3b). In all cases, the imaging planes are incremented by an external stepper motor using a dedicated computer logic for gated image acquisition. At the present time, despite geometrical shortcomings, the TEE omniplane probe with rotational scanning is the most widely used system. It can be applied for standard investigations as well as for "3D"-data acquisition after only minor modifications. The process of 3D-reconstruction is a sequence of repeated steps of image processing. The first step is the elimination of a problem, that is common to all image reconstruction techniques from tomographic information: the imaging planes are recorded at different time points, and mostly under varying conditions. Although several gating techniques are implemented into the image acquisition, some variability is unavoidable, simply because neither the heart nor the surroundings can be frozen during image acquisition.(ABSTRACT TRUNCATED AT 400 WORDS)

[Possibilities and limitations of color duplex guided compression therapy of puncture-induced blood vessel lesions in the groin]. / Möglichkeiten und Grenzen der farbduplex-gesteuerten Kompressionstherapie von punktionsbedingten Gefässläsionen in der Leiste.

AIM: Colour Doppler imaging (CDI) is a useful tool for non-invasive diagnosis and treatment of postcatheterisation lesions of the femoral artery. The aim of the present study was to evaluate success and limitations of the method in unselected patients. MATERIAL AND METHODS: A total of 29 patients, including 24 patients with pseudoaneurysms and 5 patients with arteriovenous fistulas, were treated by CDI-guided compression therapy. RESULTS: 17 of 24 (71%) pseudoaneurysms, but only 1 of 5 (20%) arteriovenous fistulas were successfully occluded. Successful treatment of pseudoaneurysms was limited by continuous anticoagulation and local pain during compression. However, arteriovenous fistulas, except one, could not be occluded due to high flow velocities in the shunt. CONCLUSION: CDI-guided compression therapy is the treatment of choice for postcatheterisation pseudoaneurysms, while arteriovenous fistulas should be repaired surgically. If possible, anticoagulation therapy should be discontinued and analgesic drugs should be prescribed.

Optimum angiographic visualization of coronary segments using computer-aided 3D-reconstruction from biplane views.

Using a biplane multidirectional isocentric X-ray system, a computer-aided simulation procedure was developed to calculate the 3D structure of the coronary arteries. The algorithm uses the geometry of the biplane X-ray system and the alignments of corresponding points of the coronary arteries in two X-ray images acquired under different viewing angles. The identification of the corresponding points is greatly simplified by the calculation and display of the intersection lines of the confocal plane with the image intensifier entrances on the computer monitor. To minimize the total number of necessary corresponding points we used Bézier curves to match the courses of the coronary segments between neighboring corresponding points. The projection of the calculated 3D structure was found to be in very good agreement with the 2D course of the coronary arteries in the angiograms. The 3D structure can be viewed on the computer screen under any desired simulated projection angle within the geometrical limitation of the X-ray gantries. The user can select views on the computer monitor with orthogonal projection angles and minimal overlapping problems caused by under- and overlying structures. The method was applied in 10 cases of elective angioplasty. Previously taken diagnostic angiograms were used to reconstruct the arterial structure and to select favorable views for the forthcoming intervention.

Dynamic three-dimensional echocardiographic imaging of congenital heart defects in infants and children by computer-controlled tomographic parallel slicing using a single integrated ultrasound instrument.

Three-dimensional cardiac reconstruction generated from transesophageal interrogation can be performed using an integrated unit that captures, processes, and postprocesses tomographic parallel slices of the heart. This probe was used for infants and young children in the transthoracic position to evaluate the feasibility of producing three-dimensional cardiac images with capability for real-time dynamic display. Twenty-two infants and children (range 1 day-3.5 years) underwent image acquisition using a 16 mm 5 MHz 64 element probe placed over the precordium. Two infants were also imaged from the subcostal position. Data was obtained and stored over a single cardiac cycle after acceptable cardiac and respiratory gating intervals were met. The transducer was advanced in 0.5-1 mm increments over the cardiac structures using identical acquisition criteria. The images were reconstructed from the stored digital cubic format and could be oriented in any desired plane. In 9 of the 22 infants the images obtained were of optimal quality. The images obtained displayed normal cardiac structures emphasizing depth relationships as well as visualization of planes not generally demonstrated by two-dimensional imaging. Several lesions were also depicted in a unique fashion using this technique. Though the method employed was limited by movement artifact and reconstruction time, the quality of the three-dimensional display was excellent and enhanced by real-time demonstration. The transthoracic approach was successful in capturing sufficient data to create three-dimensional images, which may have further application in more accurate diagnosis of complex cardiac abnormalities and generation of planes of view which could duplicate surgical visualization of a lesion. Further assessment of the technique in infants with congenital heart disease is warranted.

[Incidence, predisposing factors, acute complications and prognostic significance of intracoronary thrombus formation during PTCA]. / Inzidenz, prädisponierende Faktoren, Akutkomplikationen und prognostische Bedeutung intrakoronarer Thrombenbildung während der PTCA.

UNLABELLED: Besides coronary artery dissection, intracoronary thrombus formation is known to be an important mechanism for acute coronary occlusion in the course of percutaneous transluminal coronary angioplasty (PTCA). Therefore, we analyzed 210 consecutive patients (217 dilated stenoses) to define the incidence and potential predisposing clinical and morphological factors of intracoronary thrombus formation. Intracoronary thrombus formation was angiographically detectable in 11% of the cases, a dissection in 21%. Acute PTCA-related coronary occlusion (incidence = 5.5%) was significantly associated with intracoronary thrombus formation (p < 0.001) but less so with dissection (p = 0.074). Acute redilatation after an initially successful PTCA was almost exclusively necessary in patients with intracoronary thrombus formation (p < 0.001). Univariate analysis demonstrated the following factors to be significantly associated with intracoronary thrombus formation: Irregular lumen of stenosis (p = 0.006), stenosis at branch point (p = 0.012) and unstable angina pectoris (p = 0.001). Patients with intracoronary thrombus formation did not show a worse long-term prognosis regarding clinical events compared with a matched group (average follow-up of 20 months). CONCLUSION: Luminal irregularities within the stenosis to be dilated and the clinical syndrome of unstable angina pectoris are predisposing factors for PTCA-induced intracoronary thrombus formation, suggesting that preexisting local activation of the coagulation system plays an independent role for intracoronary thrombus formation during PTCA. Although intracoronary thrombus formation increases the risk for acute complications during PTCA, the long-term result is not adversely affected.

[The potential significance of early effort myocardial scintigraphy following PTCA]. / Aussagemöglichkeiten der frühen Belastungsmyokardszintigraphie nach PTCA.

Exercise 201Tl scintigraphy before and after successful PTCA was evaluated in 69 patients with coronary stenosis > 60%. Mean luminal stenosis was found reduced from 74 +/- 10% to 31 +/- 11% (58% reduction). Scintitomographic examination within 3 weeks following intervention showed a reduction of the exercise perfusion defect from 17.00 +/- 14.6 to 5.8 +/- 7.8 arbitrary units (66% reduction). Angiographically, re-stenosis was identified in 22/41 patients (54%) after 6 months. Unexpectedly, re-stenosis could not be predicted by early 201Tl scintigraphy (positive and negative predictive value in patients with single-vessel disease: 61% and 41%, resp.). Nevertheless, evaluation of PTCA results was possible (sensitivity 83%). However, postinterventional transient defects, indicating ischemia, were often seen (all patients: 43/69; patients with single-vessel disease: 31/55) and not indicative of failure of the intervention. Thus, post-PTCA scintigrams should be compared with scintigrams recorded before the intervention to ensure reliable follow-up control.

Percutaneous mitral balloon valvuloplasty--a comparative evaluation of two transatrial techniques.

The efficacy and safety of two different percutaneous transfemoral mitral balloon valvuloplasty procedures were evaluated in 45 patients. A double-balloon technique with Mansfield balloons was applied in the first 22 patients (group A), and an Inoue single-balloon technique was used in the subsequent 23 patients (group B). Mean diastolic gradient decreased from 17 +/- 7 mm Hg to 8 +/- 3 mm Hg (p < 0.001) in group A and from 13 +/- 4 mm Hg to 8 +/- 3 mm Hg (p < 0.001) in group B. The mitral orifice area increased from 1.1 +/- 0.3 cm2 to 2.2 +/- 0.8 cm2 (p < 0.001) in group A and from 1.2 +/- 0.4 cm2 to 1.7 +/- 0.7 cm2 (p < 0.001) in group B. The length of the total procedure and the total fluoroscopy time were considerably shorter in group B (86 +/- 24 minutes and 18 +/- 7 minutes) compared with group A (128 +/- 38 minutes and 35 +/- 14 minutes; p < 0.001). Mitral regurgitation (grade 3/4) was observed after the procedure in two patients in group A but in nine patients in group B. Cardiac tamponade occurred in two patients in group A, but no major complications were seen in group B. The Inoue single-balloon technique seemed to be safe, easier to perform, and equally effective.

Three-dimensional and four-dimensional transesophageal echocardiographic imaging of the heart and aorta in humans using a computed tomographic imaging probe.

We evaluated the clinical applicability of a prototype tomographic transesophageal echocardiographic (TEE) system, which not only provides conventional TEE images but also three-dimensional tissue reconstruction and four-dimensional display capabilities. The probe was used in 16 patients in the echocardiographic laboratory, intensive care unit, and the operating room. The instrument is a 5-MHz, 64-element, phased array unit mounted on a sliding carriage within a casing. After appropriate probe placement within the esophagus, the probe is straightened, a balloon surrounding the probe is inflated, and data acquisition begun with ECG and respiration gating. With computer controlled transducer movement at 1-mm increments, a complete cardiac cycle is recorded at each tomographic level. These are processed using a dedicated four-dimensional software, and displayed as a dynamic three-dimensional tissue image of the heart. We were able to see the dynamic motion of the ventricles and all the valves in the four-dimensional format. In addition to four-dimensional display, we were able to cut and visualize the heart in dynamic mode in any desired plane and also in multiple planes. Patients tolerated the procedure well. We conclude that this tomographic four-dimensional approach, which does not require tedious off-line processing, can easily be performed in patients and has a strong clinical potential.

Reduction of the risk of surgery for abdominal aortic aneurysms by extended coronary diagnostics and therapy.

The morbidity and mortality in the surgery of abdominal aortic aneurysms are essentially determined by the coronary risk profile of the patient. Preoperative coronary artery diagnostics with the potential consequence of a coronary revascularization as procedure before the aneurysmectomy seems to be mandatory to decrease the risk of treatment. Out of 223 patients treated at our institution for abdominal aortic aneurysm, 68 (30.5%) had to undergo extended cardiological diagnostic procedures, and 37 (16.6%) needed a coronary angiography; in 23 patients (10.3%) myocardial revascularization was performed prior to the aneurysmectomy. Since routinely performing this thorough investigation of the coronary risks, the mortality of surgery for aortic aneurysm has been clearly reduced.

Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis.

BACKGROUND: The vascular endothelium is capable of regulating tissue perfusion by the release of endothelium-derived relaxing factor to modulate vasomotor tone of the resistance vasculature. METHODS AND RESULTS: To test whether atherosclerosis is associated with a functional abnormality of endothelium-mediated microvascular relaxation affecting coronary blood flow regulation, we compared coronary blood flow responses with cold pressor testing with the response of the coronary vasculature to acetylcholine (an endothelium-dependent vasodilator) and to papaverin (a direct dilator of vascular smooth muscle) in 12 normal control patients and in 19 patients with non-flow-limiting epicardial atherosclerosis (CAD). The drugs were subselectively infused into the left anterior descending coronary artery via a Doppler catheter, and the response in coronary blood flow was assessed by measuring intracoronary blood flow velocity and cross-sectional arterial area (quantitative angiography). Coronary vascular resistance decreased in all normal control patients by -24.1 +/- 5.5% (mean +/- SD) during the cold pressor test, whereas the CAD patients demonstrated a variable coronary vascular resistance response to cold pressor testing despite comparable changes in the rate-pressure product. The slopes of the acetylcholine dose-blood flow response (percent change in coronary blood flow/dosage of acetylcholine) were significantly reduced in the CAD patients with 38.5 +/- 24.8 compared with the normal patients (80.8 +/- 28.1; p less than 0.001). Although coronary blood flow responses to papaverin were slightly but significantly (p less than 0.05) reduced in the CAD patients, the response to the endothelium-dependent dilator acetylcholine was considerably out of proportion to the papaverin response in these patients compared with the normal patients. The capacity of the coronary system to increase blood flow in response to acetylcholine expressed as relative proportion of the maximal papaverin response was 52.5 +/- 18.2% in the normal control patients but only 33.6 +/- 23.6% in the CAD patients (p less than 0.025 versus normals). There was a significant negative correlation (r = -0.69; p less than 0.0001) between cold pressor test-induced changes in coronary vascular resistance and the capacity of the coronary system to increase blood flow in response to acetylcholine. CONCLUSIONS: Early stages of epicardial atherosclerosis are associated with an impairment in endothelium-dependent dilation of the coronary microvasculature, indicating that the pathophysiological consequences of atherosclerosis may extend into the human coronary microcirculation. The correlation between cold pressor test-induced coronary vascular resistance changes and the extent of endothelial dysfunction suggests a relation between endothelial function of the microvasculature and coronary blood flow regulation during sympathetic stimulation associated with increased myocardial work.

Intracoronary thrombus formation causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease.

BACKGROUND: Experimental studies have demonstrated that intracoronary platelet aggregation and thrombus formation may induce marked vasoconstriction of epicardial arteries with endothelial injury. METHODS AND RESULTS: To examine the effects of intracoronary thrombus formation on coronary vasomotor tone of human epicardial arteries in vivo, we studied 15 patients who developed intracoronary thrombi adherent to the guide wire during balloon dilatation. Epicardial artery luminal area was evaluated by quantitative coronary angiography proximal and distal to the site of intracoronary thrombus formation and in a reference vessel before and after thrombus formation as well as after intracoronary injection of 0.2-0.3 mg nitroglycerin. All artery segments distal to the site of thrombus formation showed vasoconstriction with a luminal area reduction of -27.4 +/- 17.1% (p less than 0.001), whereas proximal vessel segments and reference vessels not manipulated during percutaneous transluminal coronary angioplasty did not demonstrate any significant luminal area changes during thrombus formation. Angiographic measurements after advancing the guide wire with the adherent thrombus (performed in six of the 15 patients) revealed in all patients that vasoconstriction did develop at a new site distal to the thrombus persistence of the initial vasoconstriction now residing proximal to the thrombus. Thus, there was a sequential association between thrombus formation and subsequent distal vasoconstriction. Intracoronary injection of nitroglycerin abolished the thrombus-induced vasoconstriction. No significant luminal area changes were observed in 20 patients without angiographic evidence of intracoronary thrombus formation. CONCLUSIONS: Intracoronary thrombus formation during percutaneous transluminal coronary angioplasty causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. Although caution must be advised in the extrapolation of this phenomenon, which was observed in a manipulated artery during coronary angioplasty, the vasoconstrictor response to intracoronary thrombus formation in vivo may play an important role in the dynamic mechanisms of acute coronary heart disease syndromes.

Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis.

The endothelium plays a critical role in the control of vasomotor tone by the release of vasoactive substances. Because endothelial injury or dysfunction is considered important very early in atherogenesis, we hypothesized that abnormal endothelial function precedes the angiographic detection of coronary atherosclerosis in the human coronary circulation. The coronary vasomotor responses to three different endothelium-mediated stimuli (intracoronary infusion of acetylcholine 10(-8) to 10(-6) M, increase in blood flow to induce flow-dependent dilation, and sympathetic stimulation by cold pressor testing) were assessed by quantitative angiography and subselective intracoronary Doppler flow velocity measurements within the left anterior descending coronary artery in 38 patients. All three stimuli elicited epicardial artery dilation in all 11 patients with smooth coronary arteries and absence of risk factors for coronary artery disease (group 1). All nine patients with smooth coronary arteries but with hypercholesterolemia (group 2) demonstrated a selective impairment in endothelial function with vasoconstriction (35 +/- 12.7% decrease in mean luminal area) in response to acetylcholine but showed a preserved flow-dependent dilation (15.5 +/- 4.4% increase in mean luminal area) and vasodilation in response to cold pressor testing (14.2 +/- 4.6% increase in mean luminal area). In all nine patients with an angiographically defined smooth coronary artery segment but with evidence of atherosclerosis elsewhere in the coronary system (group 3), both acetylcholine and cold pressor testing induced vasoconstriction (26.2 +/- 8.7% and 18.7 +/- 7.9% decrease in mean luminal area, respectively), whereas flow-dependent dilation was preserved (20.4 +/- 8.7% increase in mean luminal area). In the nine patients with angiographic evidence of wall irregularities (group 4), flow-dependent dilation was also abolished and vasoconstriction occurred in response to acetylcholine and cold pressor testing (34.5 +/- 10.7% and 19.9 +/- 6.3% decrease in mean luminal area, respectively). All coronary artery segments dilated in response to nitroglycerin, suggesting preserved function of vascular smooth muscle. Despite similar reductions in coronary vascular resistance in response to the smooth muscle relaxant papaverin, patients with hypercholesterolemia demonstrated a selective impairment of vasodilation of the resistance vasculature in response to acetylcholine (p less than 0.05 versus groups 1, 3, and 4). Thus, there is a progressive impairment of endothelial vasoactive functioning in coronary arteries of patients with different early stages of atherosclerosis, beginning with a selective endothelial dysfunction in angiographically defined normal arteries in patients with hypercholesterolemia and progressively worsening to a complete loss of endothelium-mediated vasodilation in angiographically defined atherosclerotic coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)