Impending paradoxical embolism from atrial thrombus: correct diagnosis by transesophageal echocardiography and prevention by surgery.

During recovery from a posterolateral myocardial infarction, a 56 year old patient developed signs of deep vein thrombophlebitis and subsequently of pulmonary embolism. After conventional echocardiography showed masses in both atria, transesophageal two-dimensional echocardiography clearly revealed an elongated mass overriding an atrial septal defect. Impending paradoxical embolism was confirmed at surgery.

Ultrasonic tissue characterization with a real time integrated backscatter imaging system in normal and aging human hearts.

Experimental studies have shown that variation in the magnitude of integrated ultrasonic backscatter during the cardiac cycle represents acoustic properties of myocardium that are affected by pathologic processes; however, there are few clinical studies using integrated backscatter. Forty subjects without cardiovascular disease (aged 22 to 71 years, mean 41) were studied with use of a new M-mode format integrated backscatter imaging system to characterize the range of cyclic variation of integrated backscatter in normal subjects. Cyclic variation in integrated backscatter was noted in both the septum and the posterior wall in all subjects. The magnitude of the cyclic variation of integrated backscatter and the interval from the onset of the QRS wave of the electrocardiogram to the minimal integrated backscatter value were measured using an area of interest of variable size for integrated backscatter sampling and a software resident in the ultrasound scanner. The magnitude of cyclic variation was larger for the posterior wall than for the septum (6.3 +/- 0.8 versus 4.9 +/- 1.3 dB, p less than 0.01). The interval to the minimal integrated backscatter value was 328 +/- 58 ms for the septum and 348 +/- 42 ms for the posterior wall (p = NS). There was a weak correlation between the magnitude of cyclic variation of integrated backscatter and subject age for the posterior wall (r = -0.47, p less than 0.01), but this was not significant for the septum (r = -0.21) (partially because of inability to exclude specular septal echoes) and septal endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Left atrial spontaneous echo contrast in mitral valve disease: an indicator for an increased thromboembolic risk.

The incidence of left atrial spontaneous echo contrast was evaluated in 52 patients with isolated or predominant mitral valve stenosis (Group 1) and 70 other patients who had undergone mitral valve replacement (Group 2). All patients were studied by conventional transthoracic and transesophageal two-dimensional echocardiography. Spontaneous echo contrast could be visualized within the left atrium in 35 Group 1 patients (67.3%) (including 7 patients with sinus rhythm) and 26 Group 2 patients (37.1%) (all with atrial fibrillation). Patients with spontaneous echo contrast had a significantly larger left atrial diameter and a greater incidence of both left atrial thrombi and a history of arterial embolic episodes than did patients without spontaneous echo contrast. Association between spontaneous echo contrast and left atrial thrombi and a history of arterial embolization (considered individually or in combination) showed a high sensitivity and negative predictive value. It is concluded that spontaneous echo contrast is a helpful finding for identification of an increased thromboembolic risk in patients with mitral stenosis and after mitral valve replacement.

Lack of inotropic effect of cyclosporin A in isolated guinea pig left atria.

OBJECTIVE: Cyclosporin A is being widely used to prevent graft rejection in organ transplantation and to treat autoimmune diseases. Since various toxic side effects have been observed, the aim of this study was to look for even a subtle deleterious effect of cyclosporin A on cardiac inotropy in electrically stimulated guinea pig left atria. METHODS: The left atrial muscles of guinea pigs, in Tyrode's solution containing 2.7 or 5.4 mM potassium, were electrically stimulated by one of two methods: (1) continuously at 3 Hz, during which cyclosporin A was applied cumulatively (from 10(-9) to 10(-5) M); or (2) stimulated intermittently at 2.5 Hz in 5 mM cyclosporin A, with rest periods of 4 s duration interposed every 4 min. The effects of cyclosporin A on contractile force were observed for 150 min in the first stimulation method, and the effects on the steady state contractile force and amplitude of post-rest contraction were observed for 240 min in the second method. RESULTS: The steady state contractile force of the atria declined within the 4 h period at 2.7 mM potassium in Tyrode's solution both in the cyclosporin A group (n = 10) and in the control group (n = 5) to 68(SD 11)% and to 63(4)%, respectively. After 4 h the amplitudes of the post-rest contraction were 101(16)% and 101(4)% in cyclosporin A and control groups, respectively. At 5.4 mM potassium, the following values were obtained (cyclosporin A v control): steady state force 70(8)% (n = 11) v 69(8)% (n = 5); post-rest force 105(9)% v 102(7)%. CONCLUSIONS: Cyclosporin A does not influence the steady state contractile force or the amplitude of the post-rest contraction, suggesting the absence of inotropic effects on isolated guinea pig left atria.

Effects of acetylcholine on epicardial coronary arteries after cardiac transplantation without angiographic evidence of fixed graft narrowing.

The coronary response to acetylcholine was evaluated in 10 patients who had had cardiac transplantation 1 to 8 years earlier and in 4 patients who did not undergo transplantation. All 14 patients had no angiographic evidence of fixed coronary arterial narrowing. Acetylcholine was infused in 10-fold increasing concentrations (10(-6) to 10(-2) M) into the midpoint of the left anterior descending coronary artery by an infusion catheter. Administration was terminated when either vasoconstriction was noted at fluoroscopy or when the maximal acetylcholine concentration was reached. Vascular responses were evaluated by quantitative angiography. All 14 patients had a decrease in coronary lumen size in response to acetylcholine. The mean percentage of vasoconstriction was 37 +/- 24% (p less than 0.001). Combined infusion of nifedipine and the maximal vasoconstricting dose of acetylcholine did not result in a significant reversal of coronary vasoconstriction in all 10 cardiac transplantation patients. It was concluded that acetylcholine is a potent coronary vasoconstrictor in patients who had cardiac transplantation and possibly lacks vasodilating effects in most normal patients without angiographic evidence of coronary artery disease, thus suggesting that acetylcholine might not be a suitable pharmacologic agent for testing endothelial cell integrity.

Performance of a stentless xenograft aortic bioprosthesis up to four years after implantation.

Conventional biologic and mechanical prostheses have important limitations with regard to their hemodynamic characteristics and long-term durability. We evaluated the hemodynamic function of a stentless porcine aortic prosthesis in 10 patients by invasive pressure measurements and angiography with videodensitometry 8 +/- 4 days after operation, as well as by Doppler echocardiography 35 +/- 15 months after valve replacement. The early postoperative invasive study revealed a mean gradient of 8 +/- 6 mm Hg across the prosthesis, no regurgitation in eight patients, and mild regurgitation, defined as less than 20% regurgitant fraction, in the remaining two patients. The late postoperative Doppler echocardiographic study revealed a mean gradient across the aortic prosthesis of 6 +/- 3 mm Hg, mean Doppler-derived valve orifice area of 1.8 +/- 0.6 cm2, and color Doppler flow velocity mapping suggested no regurgitation in eight patients and mild regurgitation in two patients corresponding to early postoperative angiography. None of the 10 patients received anticoagulation therapy. The clinical course of all patients was without incident. This stentless aortic bioprosthesis may offer hemodynamic advantage; however, further studies are needed to allow comparison with conventional mechanical and biologic prostheses.

Natural history of a ventriculoatrial fistula after a gunshot injury in 1945.

We describe an exceptional case of a patient who suffered a penetrating heart injury from a gunshot wound in 1945 leading to a left ventricular-right atrial fistula. Despite the resulting left-to-right shunt the patient remained relatively asymptomatic for 50 years before the onset of congestive heart failure necessitated an operation.

Improvement in left ventricular diastolic filling by septal myectomy in hypertrophic cardiomyopathy.

Abnormalities in left ventricular diastolic function or filling are considered to be responsible for some of the symptoms in patients with hypertrophic cardiomyopathy. To clarify whether the abnormalities in left ventricular diastolic filling are improved by septal myectomy, 13 patients with hypertrophic cardiomyopathy and intracavitary pressure gradient were studied preoperatively and postoperatively by use of pulsed Doppler echocardiography. Peak early diastolic filling velocity (E), the ratio of peak early diastolic filling to peak atrial filling velocities (E/A ratio), and deceleration time were measured from the transmitral flow velocity pattern before and after septal myectomy. Although E and E/A ratio did not change after septal myectomy, deceleration time significantly shortened from 314 +/- 72 to 271 +/- 53 milliseconds (n = 10; p less than 0.05). Further, if seven patients with significant changes in heart rate (greater than 30%) or in the Doppler-determined severity of mitral regurgitation (more than one degree) were excluded (because these parameters may effect E and E/A ratio), there were also significant changes in E (81 +/- 21 versus 98 +/- 25 cm/sec, p less than 0.05) and in E/A ratio (0.84 +/- 0.17 versus 1.14 +/- 0.33, p less than 0.05). Because left ventricular systolic function has been demonstrated to remain constant or to decrease by most measures after septal myectomy, relief of some symptoms may be largely the result of the improvement in diastolic filling suggested by these criteria.

Doppler ultrasound of the subclavian artery as an aid to quantification of aortic insufficiency.

Aortic insufficiency (AI) induces backflow of blood in the arterial system that is most pronounced in the major arteries close to the heart. Assuming that the intensity of the arterial backflow of blood may reflect the severity of AI, the systolic and diastolic flow profiles of the subclavian artery were studied in 40 patients with and 10 patients without AI that was angiographically proved by use of continuous wave Doppler ultrasound (8 MHz transducer, supraclavicular approach). Patients with angiographically determined severe AI (n = 17) had significantly higher diastolic regurgitant flow velocities (V-max) than patients with only mild (n = 9) or moderate (n = 14) degrees of AI (Severe AI = 35.0 +/- 12.0 cm/sec, moderate AI = 16.8 +/- 3.9 cm/sec, mild AI = 7.4 +/- 2.6 cm/sec; p < 0.01) and also showed significantly higher values with regard to the time velocity integral of the regurgitant jet (severe AI = 13.8 +/- 5.6 cm; moderate AI = 5.7 +/- 2.4 cm, mild AI = 1.4 +/- 0.9 cm; p < 0.01). After classification by jacknife discrimination analysis, the Doppler ultrasound grading was compared with a corresponding three-point scale (mild, moderate, severe) from aortic root angiography. A correct estimation of the severity of AI was possible in 44 of 50 patients (88%; overestimation in one, underestimation in five) and in 41 of 50 patients (83%; overestimation in one, underestimation in eight) with regard to V-max and the time velocity integral of the regurgitant jet, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow velocity acceleration in the left ventricle: a useful Doppler echocardiographic sign of hemodynamically significant mitral regurgitation.

Doppler echocardiography is a sensitive method to detect mitral regurgitation in patients with both native and prosthetic valves. However, estimates of the amount of mitral regurgitation remain semiquantitative, and even severe mitral regurgitation may be underestimated in the presence of markedly eccentric regurgitant jets or acoustic shadowing of the left atrium by mitral or aortic prostheses. This report describes the Doppler findings in 10 patients with severe native valve mitral regurgitation (angiographic grade III or IV) and in 15 patients with severe bioprosthetic mitral regurgitation that required valve replacement. An increase in peak mitral flow velocity above normal values was seen in eight of 10 patients with severe native valve mitral regurgitation (greater than or equal to 130 cm per second) and 11 of 15 patients with severe prosthetic valve mitral regurgitation (greater than or equal to 210 cm per second). One of 10 patients with a native valve and four of 15 patients with a bioprosthetic valve appeared to have only a localized left atrial systolic flow disturbance, incorrectly suggesting that the mitral regurgitation was mild. However, in all patients with severe mitral regurgitation, a low velocity (less than 100 cm per second) flow signal could be recorded in the left ventricle that was directed toward the mitral valve in systole. This flow signal showed a gradual increase in velocity as the sample volume was moved toward the mitral valve, with an abrupt further increase on entry into the left atrium. This signal was continuous with antegrade mitral flow and had the same orientation as mitral regurgitation recorded by continuous wave technique from the apex. A similar flow signal was not recorded in the left ventricle of any individual in a control group of 30 patients who had no mitral regurgitation or who had angiographic grade I or II mitral regurgitation. These findings suggest that acceleration of left ventricle flow toward the mitral valve in systole is only recorded when there is hemodynamically significant mitral regurgitation that is approximately equal to angiographic grade III or IV. Recognition of this Doppler finding may help in the estimation of mitral regurgitation severity, especially in difficult diagnostic situations.

Evidence for partial sympathetic cardiac reinnervation following cardiac transplantation.

Heart transplantation causes total cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenal metabolite, dihydroxyphenylglycol (DOPEG, exclusively neuronal in origin), were used to examine the possibility of sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 15 heart transplant recipients (28-68 years of age at the time of transplantation with the transplant ageing from 0.5 to 4 years at the time of investigation) and in nine control patients (45-75 years of age). In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arteriovenous increment: 60 +/- 10%; P < 0.001). In the heart transplant recipients nine patients showed an arteriovenous increment in plasma DOPEG. For the mean group results it was found that the ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (r = 0.92; n = 5; P < 0.05). Thus, our data provide neurochemical evidence for partial sympathetic reinnervation in some of the heart transplants. Moreover, it is suggested that the time after transplantation is unlikely to be the only determinant for the occurrence and extent of sympathetic reinnervation.

Rest and exercise hemodynamics before and after valve replacement--a combined Doppler/catheter study.

BACKGROUND: Hemodynamic improvement is a common finding following valve replacement. However, despite a normally functioning prosthesis and normal left ventricular ejection fraction, some patients may show an abnormal hemodynamic response to exercise. METHODS: In a combined catheter/Doppler study, rest and exercise hemodynamics were evaluated in 23 patients following aortic (n = 12) (Group 1) or mitral valve (n = 11) (Group 2) replacement and compared with preoperative findings. Patient selection was based on absence of coronary artery disease and left ventricular failure as shown by preoperative angiography. Cardiac output, pulmonary artery pressure, pulmonary capillary pressure, and pulmonary resistance were measured by right heart catheterization, whereas the gradient across the valve prosthesis was determined by Doppler echocardiography. Postoperative evaluation was done at rest and during exercise. The mean follow-up was 8.2 +/- 2.2 years in Group 1 and 4.2 +/- 1 years in Group 2. RESULTS: With exercise, there was a significant rise in cardiac output in both groups. In Group 1, mean pulmonary pressure/capillary pressure decreased from 24 +/- 9/18 +/- 9 mmHg preoperatively to 18 +/- 2/12 +/- 4 mmHg postoperatively (p < 0.05), and increased to 43 +/- 12/30 +/- 8 mmHg with exercise (p < 0.05). The corresponding values for Group 2 were 36 +/- 12/24 +/- 6 mmHg preoperatively, 24 +/- 7/17 +/- 6 mmHg postoperatively (p < 0.05), and 51 +/- 2/38 +/- 4 mmHg with exercise (p < 0.05). Pulmonary vascular resistance was 109 +/- 56 dyne.s.cm-5 preoperatively, 70 +/- 39 dyne.s.cm-5 postoperatively (p < 0.05), and 70 +/- 36 dyne.s.cm-5 with exercise in Group 1. The corresponding values for Group 2 were 241 +/- 155 dyne.s.cm-5, 116 +/- 39 dyne.s.cm-5 (p < 0.05), and 104 +/- 47 dyne.s.cm-5. There was a significant increase in the gradients across the valve prosthesis in both groups, showing a significant correlation between the gradient at rest and exercise. No correlation was found between valve prosthesis gradient and pulmonary pressures. CONCLUSION: Exercise-induced pulmonary hypertension and abnormal left ventricular filling pressures seem to be a frequent finding following aortic or mitral valve replacement. Both hemodynamic abnormalities seem not to be determined by obstruction to flow across the valve prosthesis and may be concealed, showing nearly normal values at rest but a pathologic response to physical stress.

[Progression of coronary sclerosis. Studies in 19 patients over a 6-year period using quantitative coronary angiography]. / Zur Progression der Koronarsklerose. Untersuchungen bei 19 Patienten über 6 Jahre mittels quantitativer Koronarangiographie.

The characteristics of progressive coronary artery disease as judged from sequential angiography were quantitatively analysed in 19 patients with stable angina in whom coronary angiograms were repeated after 64-104 months (average 76.5 months). The diameters of at most 15 corresponding segments were measured with a vernier caliper (accuracy: 0.05 mm) at identical sites and in the same projections. Considering the error in measurement (less than 10%) and spontaneous changes in smooth muscle tone only a diameter decrease of greater than 20% and/or every transition to an occlusion were recorded as progression. The progression over a 6-year interval was predominately characterized by: A large amount of total occlusions (61% of all progressive stenoses), relatively independent of the initial degree of stenosis. A large amount of newly developed obstructions which are more severe in coronary arteries already segmentally diseased at the onset, indicating a diffuse intramural disease of the entire vessel. A different pattern of progression in the 3 main coronary arteries. No influence of risk factors on natural history.

[Importance of transesophageal echocardiography in the diagnosis of cardiac and paracardiac space-occupying processes]. / Bedeutung der transösophagealen Echokardiographie in der Diagnostik kardialer und parakardialer raumfordernder Prozesse.

The diagnostic value of transoesophageal echocardiography in the detection of cardiac and extracardiac masses has not yet been properly established. We therefore studied 23 patients (7 males, 16 females, mean age 54.7 years) using transoesophageal echocardiography in addition to conventional transthoracic echocardiography. Nine patients had an atrial thrombus, 6 an atrial myxoma and 8 extracardiac masses. The studies were performed without complications. Transthoracic as well as transoesophageal echocardiographic detection of atrial thrombus or myxoma (n = 15) was successful in all patients except 1 with a thrombus in the left atrial appendix, which could only be visualized by transoesophageal echocardiography. In contrast, accurate diagnosis of extracardiac masses could be established only by transoesophageal echocardiography in 5 of 8 patients (62.5%). In all 23 patients the judgement of the mobility of the tumor, as well as its acoustic properties and wall adherence was markedly facilitated by transoesophageal echocardiography. Thus, this method is a useful diagnostic tool for detection of extracardiac masses, whereas in patients with atrial thrombus or myxoma it can give important additional information.

Ultrastructural changes of human cardiac atrial nerve endings in diabetes mellitus.

BACKGROUND: Autonomic neuropathy resulting from long-term diabetes mellitus may affect heart innervation. However, so far diabetes induced morphological changes of cardiac nerves are not well-known. In this study human cardiac atrial tissue from diabetic patients was analysed by electron microscopy for structural alterations as a result of diabetic neuropathy. METHODS: In coronary bypass surgery, an edge of the right auricle was routinely resected for reason of extracorporal circulation. Thin cardiac tissue sections of 100 nm were studied by electron microscopy. Atrial tissue samples were collected from 5 patients with long-standing diabetes (for at least 8 years) and compared to atrial tissue samples from 5 patients without diabetes, equally undergoing coronary bypass surgery. RESULTS: In all atria-free nerve endings with unmyelinized, axons were observed. Cross sections of 479 axons from diabetic patients were compared to 419 axons of nondiabetic patients. The number of altered axons was significantly higher in cardiac tissue of diabetic patients (32%) in comparison to normal subjects (17%). In diabetic patients, 20% of the intra-axonal mitochondria were condensed or hydropic, whereas in nondiabetic patients only 4% of the mitochondria were altered. Membrane fragments were present in 21% of the axons in atria of diabetic patients compared to 10% in nondiabetic subjects. Only in cardiac axons from diabetic patients there were lamellar bodies, dissolved axoplasma and junctions between neighbouring axons in a minor number. Few vacuoles were present in axons of both groups. CONCLUSION: In myocardial atrial-free nerve fibre bundles of diabetic patients, the amount of degenerative changes was higher in comparison to atrial cardiac tissue from nondiabetic subjects. These morphological alterations may indicate manifestation of diabetic neuropathy and might contribute to the impairment of autonomic neural control affecting the heart in long-standing diabetes mellitus.

[Acquired heart valve defects. Diagnostic and therapeutic strategies]. / Erworbene Herzklappenfehler. Diagnostische und therapeutische Strategien.

BACKGROUND: Diagnostic and therapeutic strategies in patients with acquired valvular heart disease, are determined by clinical symptoms, hemodynamics and empirical information. DIAGNOSIS: A quantitative assessment of cardiac disease can made largely on the basis of echocardiography or Doppler echocardiography with consideration also being given to the results of clinical findings. As a rule, cardiac catheterization should be done only once, immediately prior to operation. OUTLINE OF THERAPY: In chronic mitral and aortic valve insufficiency, the surgical indication is based primarily on the clinical symptoms, while in aortic and mitral valve stenosis, it is based primarily on the hemodynamic findings. Promising interventional procedures such as balloon valvuloplasty, represent useful alternatives to valve replacement in the case of mitral valve stenosis alone. In the event of significant aortic valve stenosis alone. In the event of significant aortic valve stenosis, balloon valvuloplasty is not a promising procedure. In patients with aortic or mitral valve insufficiency, but normal left ventricular function, medical treatment should first be attempted.

[Unstable angina pectoris: disease picture and study of its course]. / Instabile Angina pectoris: Krankheitsbild und Verlauf neu überprüft.

The object of the present study is to analyse the history of patients with typical unstable angina. For this purpose the data of all patients admitted to the Hannover Medical School between 1977 and 1983 and taken to the CCU because of proven unstable angina (history, duration of symptoms, intrahospital mortality, incidence of infarction, medical or surgical therapy, coronary pathomorphology, mortality after release from hospital, late incidence of infarction and rehospitalization) were documented and stored on a data bank for statistical analysis. 123 patients were entered into the study (97 males, 26 females; average age 58.4 +/- 9.2 years); during hospitalization all patients had angina at rest, 94% had transient ECG-changes (ST-segment changes, BBB etc.). The average follow-up was 4.2 +/- 2.0 years. 80 patients of the whole study population were treated medically, 43 underwent early bypass surgery. The two groups were different with respect to coronary pathomorphology (number of diseased vessels) as well as left ventricular wall motion, which was significantly more impaired in the surgical group (p less than 0.05). The hospital-mortality in the surgical group amounted to 9.3% (n = 4), the incidence of infarction to 18.6% (n = 8); the hospital mortality in medically treated patients was 2.5% (n = 2), the incidence of infarction 7.5% (n = 6). During the whole study period (average follow-up 4.2 years) the overall mortality amounted to 21%, the infarction rate was 23.5%: The cumulative survival rates revealed no significant difference between the 2 groups: after 3 years 84% of all patients were still alive, 65% without new infarction during the observation period; the rate of rehospitalization amounted to 50%. At the end of the study class III or IV angina (NYHA-criteria) was much more common in the medically treated than in the surgically treated group (NYHA mean 2.5 versus 2.0; p less than 0.5). The relatively high rate of perioperative death and myocardial infarction in the surgical group is based on the selection of patients according to coronary pathomorphology and the clinical status.

Mitral prosthesis malfunction. Comparative Doppler echocardiographic studies of mitral prostheses before and after replacement.

To assess the influence of mitral prosthesis malfunction on various Doppler echocardiographic indexes, we studied the changes in the peak mitral flow velocity during early diastolic filling phase (Vmax), the mean transprosthesis pressure drop from the simplified Bernoulli equation, the mitral valve area by the pressure half-time method, and the left ventricular isovolumic relaxation time in 15 patients before and after replacement of the malfunctioning mitral prosthesis using continuous wave Doppler echocardiography. Examination of the 15 replaced prostheses revealed a torn or perforated leaflet in 12 valves and a sewing ring dehiscence in one valve. Additional restricted leaflet motion (classified as mild obstruction) was seen in three of these 13 valves. In the remaining two valves, severe prosthesis obstruction was noted. Changes in the Doppler indexes between the preoperative and postoperative study were present in all patients regarding Vmax (mean, 2.2 +/- 0.3 versus 1.6 +/- 0.2 m/sec; p less than 0.001), mean gradient (mean, 9 +/- 5 versus 5 +/- 0.8 mm Hg; p less than 0.001), and isovolumic relaxation time (mean, 47 +/- 12 msec versus 80 +/- 13 msec; p less than 0.001). The mean mitral valve area remained virtually unchanged (2.3 +/- 0.9 versus 2.6 +/- 0.3 cm2; p = NS) but increased postoperatively in each patient with preoperative mild or severe prosthesis obstruction without concomitant aortic regurgitation. Our conclusion is that the peak mitral flow velocity, the mean gradient, and the isovolumic relaxation time are useful parameters in the differentiation of normal and abnormal mitral prosthesis function but may not define the underlying lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

[Change in the diameter of the coronary vessels following sublingual or intravenous nifedipine administration correlated with the plasma level]. / Koronarweitenänderung nach sublingualer und intravenöser Nifedipinapplikation in Korrelation zu Plasmaspiegeln.

UNLABELLED: The diameter changes of angiographically normal epicardial coronary arteries were studied in 25 patients in correlation to nifedipine plasma levels. In group 1 (15 patients) 20 mg of s.l. nifedipine were administered. Measurements of the coronary lumen size (automated contour detection system, accuracy 0.12 mm) and detection of plasma levels (gas-chromatography) were done before and 10, 20 and 30 min after drug administration. According to the slope of nifedipine plasma levels, patients were divided into group 1 A (n = 4) and 1 B (n = 11). Plasma levels in both groups were: at 10 min, 27.8 +/- 9.8 and 13.5 +/- 4.5 ng/ml resp.; P less than 0.05; at 20 min, 54.0 +/- 11.7 and 21.7 +/- 6.6 ng/ml resp.; P less than 0.001; at 30 min, 79.1 +/- 9.3 and 28 +/- 9.8 ng/ml resp.; P less than 0.001. The corresponding diameter changes in A and B were: 7.3 +/- 5.1%/.-5.6 +/- 9.0% resp.; P less than 0.01; 11.4 +/- 4.1% and -4.5 +/- 11.3% resp.; P less than 0.01; 14.5 +/- 5.9% and 0.5 +/- 13.6% resp.; P less than 0.05. In group 2 (10 patients) 1 mg nifedipine was administered intravenously within 4 min. Measurements were done at 1 min intervals during infusion as well as 7 and 15 min after beginning and compared to a placebo group (n = 10). Peak plasma levels amounted to 16.7 +/- 5.7 ng/ml after 7 min. The maximum coronary dilation was reached after 4 min (verum 5.0 +/- 6.8%; placebo 3.2 +/- 3.6%). Significant differences between both groups were observed after 7 min (verum 4.1 +/- 5.3%; placebo -3.1 +/- 5.8%, P less than 0.05) and 15 min (verum 1.2 +/- 3.2%; placebo -6.2 +/- 8.4%; P less than 0.05). CONCLUSION: based on significantly different plasma levels following sublingual application of 20 mg nifedipine a classification of patients into "early-" and "late-coronary-responders" could be established. After intravenous infusion of 1 mg nifedipine peak plasma levels were much lower than after sublingual application of 20 mg and coronary diameters showed only a mild increase.

[Progression and regression of coronary sclerosis in the angiographic image]. / Progression und Regression der Koronarsklerose im angiographischen Bild.

The natural history of coronary artery disease has to be studied by comparing coronary angiograms of the same patient taken at different times. However, conclusions from repeated angiographic studies are fraught with substantial errors mainly because of: 1. patients selection, 2. variable time interval and 3. technical pitfalls. Despite this bias published interval studies demonstrate that coronary atherosclerosis predominantly is a progressive disease: after 2-3 years 50% to 60%, after 3-4 years 60% to 70% and after 5 years more than 80% of patients demonstrate progressive coronary artery disease at angiography. In addition, quantitative evaluation of coronary angiograms reveals that progression of coronary artery disease: 1. has a variable pattern and pace in each coronary artery and 2. predominantly involves initially normal coronary artery segments. From all clinical and angiographic parameters under scrutiny progressive coronary artery disease is significantly correlated to: abnormal lipid levels at the time of the first angiogram, a period of unstable angina pectoris, interval myocardial infarction and initial severity of coronary artery obstruction. It has to be emphasized, however, that in the individual patient the speed of progression is highly variably supporting the concept of different underlying pathophysiological mechanisms (primary/secondary progression). Regression or coronary stenosis is a rare phenomenon which may occur spontaneously and is anecdotally reported in patients after vigorous treatment of severe hyperlipoproteinemia.