Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries.

Stress-induced release of IL-1alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P < 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P < 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P < 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P < 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.

In vitro validation of volumetric blood flow measurement using Doppler flow wire.

Determination of any volumetric blood flow requires assessment of mean blood flow velocity and vessel cross-sectional area. For evaluation of coronary blood flow and flow reserve, however, assessment of average peak velocity alone is widely used, but changes in velocity profile and vessel area are not taken into account. We studied the feasibility of a new method for calculation of volumetric blood flow by Doppler power using a Doppler flow wire. An in vitro model with serially connected silicone tubes of known lumen diameters (1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 mm) and pulsatile blood flow ranging from 10 to 200 mL/min was used. A Doppler flow wire was connected to a commercially available Doppler system (FloMap(R), Cardiometrics) for online calculation of the zeroth (M(0)) and the first (M(1)) Doppler moment, as well as mean flow velocity (V(m)). Two different groups of sample volumes (at different gate depths) were used: 1. two proximal sample volumes lying completely within the vessel were required to evaluate the effect of scattering and attenuation on Doppler power, and 2. distal sample volumes intersecting completely the vessel lumen to assess the vessel cross-sectional area. Area (using M(0)) and V(m) (using M(1)/M(0)) obtained from the distal gates were corrected for scattering and attenuation by the data obtained from the proximal gates, allowing calculation of absolute volumetric flow. These results were compared to the respective time collected flow. Correlation between time collected and Doppler-derived flow measurements was 0.98 (p < 0.0001), with a regression line close to the line of equality indicating an excellent agreement of the two measurements in each individual tube. The mean paired flow difference between the two techniques was 1.5 +/- 9.0 mL/min (ns). Direct volumetric blood flow measurement from received Doppler power using a Doppler flow wire system is feasible. This technique may potentially be of great clinical value because it allows an accurate assessment of coronary flow and flow reserve with a commercially available flow wire system.

[Long-term results after successful mitral valvuloplasty: comparison of Inoue and double balloon technique]. / Langzeitverlauf nach erfolgreicher Mitralvalvuloplastie: Vergleich der Inoue- mit der Doppelballontechnik.

UNLABELLED: Mitral balloon valvuloplasty is the treatment of choice for severe mitral stenosis in young patients with a minimally calcified and pliable mitral valve. The present study reports the results of the first 65 patients undergoing mitral valvuloplasty in Zurich with the double-balloon or Inoue-balloon technique. Early outcome and late follow-up over 4.1 +/- 2.5 years were evaluated in these patients. PATIENTS: Percutaneous mitral valvuloplasty was performed in 65 patients (48 females and 12 males, mean age 41 +/- 11 years). The double-balloon technique was used in 25 and the Inoue-balloon technique in 40 patients. Left ventricular pressure as well as pressure gradient and valve area were calculated before and after the intervention. Mitral valvuloplasty was considered to be successful when the valve area was > or = 1.5 cm2 and the pressure gradient < or = 8 mm Hg. RESULTS: Mitral valvuloplasty was successful in 22 patients of group 1 and 39 patients of group 2. Acute complications were observed in 4 patients (6%), i.e. 1 perforation of the left atrium, 1 perforation of the left ventricle, 1 peripheral embolisation and 1 rupture of the mitral leaflet. Mitral valve area increased from 1.0 to 1.9 cm2 with the double-balloon and from 1.0 to 2.0 cm2 with the Inoue-balloon technique. The pressure gradient over the mitral valve dropped significantly from 11 to 4 mm Hg in group 1 and from 15 to 5 mm Hg in group 2. Left ventricular ejection fraction remained unchanged but left atrial pressure decreased significantly in the first group from 20 to 9 mm Hg and in the second group from 22 to 12 mm Hg. Long-term follow-up over 4.1 years showed a mild (not significant) decrease in valve area from 1.7 to 1.6 cm2 in both groups, with NYHA class unchanged and bicycle exercise capacity increased from 76 to 82%. CONCLUSIONS: Mitral valvuloplasty with either the double-balloon or Inoue-balloon technique provides excellent clinical, echocardiographic and haemodynamic results. The long-term follow-up demonstrated a mild decrease in mitral valve area but clinical symptomatology and physical exercise capacity remained unchanged. From a technical standpoint the Inoue-balloon technique is easier to use and has a lower complication rate (2.5%) compared to the double-balloon technique (12%). Thus, in the last few years the double-balloon technique has been replaced by the Inoue-balloon technique, with a good long-term outcome over the first 4-5 years of follow-up.

High level of cholesterol increases coronary vasomotor tone during exercise.

BACKGROUND: Coronary vasomotor tone plays an important role in the regulation of myocardial perfusion and influences ischemic threshold significantly. Endothelial dysfunction occurs in the presence of coronary risk factors and is closely linked to the development of atherosclerosis affecting myocardial perfusion and decreasing ischemic threshold. OBJECTIVE: To study the effect of hypercholesterolemia on coronary vasomotor tone in normal and stenotic coronary arteries at rest and during exercise. PATIENTS AND METHODS: In total 48 patients were included in the present analysis. Patients were divided into two groups according to the actual levels of serum cholesterol: 18 patients had normal (mean 181 +/- 28 mg%; group 1) and 30 had elevated (mean 263 +/- 46 mg%; group 2) levels of serum cholesterol according to the 4S criteria with a cutoff level of 213 mg% (5.5 mmol/l). Coronary vasomotor tone at rest and during supine bicycle exercise was calculated by dividing mean aortic pressure by radius of coronary vessel obtained using biplanar quantitative coronary angiography. A normal as well as a stenotic vessel segment in each patient were studied. RESULTS: Normal vessel segments in patients with normal levels of cholesterol (group 1) exhibited no exercise-induced change in coronary vascular tone (+3%, NS), whereas a significant increase in tone (+24%, P < 0.01 versus rest) occurred in those with high levels of cholesterol (group 2). In contrast, stenotic segments in members of both groups exhibited an increase in vascular tone irrespective of the actual level of serum cholesterol. CONCLUSIONS: Hypercholesterolemia causes a pathologic increase in coronary vasomotor tone of angiographically normal vessel segments during exercise. A similar pathologic response occurs in stenotic arteries, but this is independent of the actual level of serum cholesterol. These findings suggest that hypercholesterolemia influences vasomotor tone of the nonstenosed coronary arteries in patients with coronary artery disease probably through the occurrence of endothelial dysfunction.

Impact of exercise-induced coronary vasomotion on anti-ischemic therapy.

Coronary vasomotion has an important role in the regulation of myocardial perfusion. During dynamic exercise, normal coronary arteries dilate, whereas stenotic arteries constrict. This exercise-induced vasoconstriction has been associated with the occurrence of myocardial ischemia and has been believed to be the result of endothelial dysfunction, with a reduced release or production of EDRF, increased sympathetic stimulation, enhanced platelet aggregation with release of thromboxane A2 and serotonin, or a passive collapse of the disease-free wall segment within the stenosis (the Bernoulli effect), or a combination of any of these. More recently, it has been realized that pharmacological treatment might prevent exercise-induced vasoconstriction and, thus, reduce myocardial ischemia and the occurrence of angina pectoris. Vasodilators such as nitrates, calcium antagonists or alpha-receptor blockers dilate the coronary arteries and prevent coronary stenosis narrowing during exercise. In contrast, beta-blocking agents are associated with coronary vasoconstriction at rest, but--conversely--can induce coronary vasodilatation during exercise. Pharmacological treatment in patients with stable angina pectoris may improve myocardial ischemia by reducing pre- and afterload, myocardial contractility, oxygen consumption, and vasomotor tone. However, coronary collateral perfusion can modify these effects by shunting blood from the non-ischemic to the ischemic region (collateral flow) or by shunting blood from the ischemic to the non-ischemic zone (coronary steal phenomenon). Typically, a steal phenomenon has been reported in patients receiving either dipyridamole or calcium antagonists, whereas a reversed steal has been described after beta-blockade, with an increase in contralateral tone shunting blood from the non-ischemic to the ischemic zone (reverse steal phenomenon).

Diastolic heart failure.

Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or increased stiffness. These conditions result typically in an upward displacement of the diastolic pressure-volume relationship with increased end-diastolic, left atrial and pulmo-capillary wedge pressure leading to symptoms of pulmonary congestion. Diagnosis of diastolic heart failure requires three conditions: (1) presence of signs or symptoms of heart failure; (2) presence of normal or slightly reduced LV ejection fraction (EF > 50%) and (3) presence of increased diastolic filling pressure. Assessment of diastolic function can be performed with several non-invasive (2D- and Doppler-echocardiography, color Doppler M-mode, Doppler tissue imaging, MR-myocardial tagging, radionuclide ventriculography) and invasive techniques (micromanometry, angiography, conductance method). Doppler-echocardiography is the most useful tool to routinely measure diastolic function. Different techniques can be used alone or in combination to assess LV diastolic function, but most of them are dependent on heart rate, pre- and afterload. The transmitral flow pattern remains the starting point, since it is easy to acquire and rapidly categorizes patients into normal (E > A), delayed relaxation (E < A), and restrictive (E >> A) filling patterns. Invasive assessment of diastolic function allows determination of the time constant of relaxation from the exponential pressure decay during isovolumic relaxation, and the evaluation of the passive elastic properties from the slope of the diastolic pressure-volume (= constant of chamber stiffness) and stress-strain relationship (= constant of myocardial stiffness). The prognosis of diastolic heart failure is usually better than for systolic dysfunction. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and AT2-blockers as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.

Effect of NO donors on LV diastolic function in patients with severe pressure-overload hypertrophy.

BACKGROUND: Previous experimental studies have shown that nitric oxide (NO) modulates cardiac function by an abbreviation of systolic contraction and an enhancement of diastolic relaxation. However, the response to NO donors of patients with severe pressure-overload hypertrophy and diastolic dysfunction is unknown. METHODS AND RESULTS: Intracoronary NO donors were given to 17 patients with severe aortic stenosis. A dose-response curve was obtained with nitroglycerin (30, 90, and 150 microg) in 11 patients and sodium nitroprusside (1, 2, and 4 microg/min) in 6. Left ventricular (LV) high-fidelity pressure measurements with simultaneous LV angiograms were performed at baseline and after the maximal dose of NO. The dose-response curve for intracoronary NO donors showed a marked fall in LV end-diastolic pressure, from 23 to 14 mm Hg (-39%; P<0.0001), whereas LV peak systolic pressure fell only slightly, from 206 to 196 mm Hg (-4%; P<0.01). End-diastolic chamber stiffness decreased from 0.12 to 0.07 mm Hg/mL (P<0.0001) and end-systolic stiffness from 1.6 to 1.3 mm Hg/mL (P<0.01). Heart rate, right atrial pressure, LV ejection fraction, the time constant of isovolumic pressure decay (tau), and LV filling rates remained unchanged. CONCLUSIONS: In patients with severe pressure-overload hypertrophy, intracoronary NO donors exert a marked decrease in LV end-diastolic pressure without affecting LV systolic pump function. Thus, the hypertrophied myocardium appears to be particularly susceptible to NO donors, with a marked improvement in diastolic function.

Alpha-adrenoceptor blockade prevents exercise-induced vasoconstriction of stenotic coronary arteries.

OBJECTIVES: The study aimed to evaluate the role of alpha-adrenergic mechanisms during dynamic exercise in both normal and stenotic coronary arteries. BACKGROUND: Paradoxical vasoconstriction of stenotic coronary arteries has been reported during dynamic exercise and may be due to several factors such as alpha-adrenergic drive, a decreased release of nitric oxide, platelet aggregation with release of serotonin, or a passive collapse of the vessel wall. METHODS: Twenty-six patients were studied at rest, during two levels of supine bicycle exercise and after 1.6 mg sublingual nitroglycerin. The alpha-blocker phentolamine was given to 16 patients before exercise, five of whom had also taken a beta-adrenergic-blocker the same morning. Ten patients served as controls. The cross-sectional areas of a normal and a stenotic coronary vessel were determined by biplane quantitative coronary arteriography. RESULTS: In the normal vessel segments, coronary cross-sectional area did not change after phentolamine injection, but increased in all patient groups similarly during exercise. Although coronary vasoconstriction existed in stenotic vessel segments in control patients, phentolamine-treated patients showed exercise-induced vasodilation without difference in patients with and without chronic beta-blockade. CONCLUSIONS: Exercise-induced vasoconstriction of stenotic coronary arteries is prevented by intracoronary administration of phentolamine. There was no difference in coronary vasomotion between patients receiving phentolamine alone and patients receiving phentolamine in addition to a beta-blocker. This finding suggests that exercise-induced vasoconstriction is mediated not only by endothelial dysfunction but also by alpha-adrenergic mechanisms.

Reversal of increased diastolic stiffness in mitral stenosis after successful balloon valvuloplasty.

BACKGROUND AND AIM OF THE STUDY: Abnormal passive elastic properties have been reported in patients with severe mitral stenosis and have been attributed to either: (i) chamber atrophy due to unloading; (ii) myocardial fibrosis; (iii) right and left ventricular (LV) interaction; or (iv) internal restrictions due to the rigid mitral valve apparatus. The study aim was to evaluate the effect of percutaneous mitral balloon valvuloplasty (PMV) on passive elastic properties in 19 patients with severe mitral stenosis. Ten patients with normal coronary arteries and LV function served as controls. METHODS: LV high-fidelity pressure measurements and simultaneous biplane LV angiograms were obtained before and after PMV (n = 11). The constant of chamber stiffness (b; ml(-1)) was calculated from the diastolic pressure-volume relationship and the constant of myocardial stiffness (beta) from the diastolic stress-strain relationship. The time constant of relaxation (T; ms) was calculated from the LV pressure decay during isovolumic relaxation. Regional ejection fraction (radial axis system) was determined in six regions of the right anterior oblique (RAO) and left anterior oblique (LAO) angiographic projections. RESULTS: Mitral valve area was increased from 1.0 to 2.2 cm2 after PMV, whereas diastolic pressure gradient was reduced from 14 to 4 mmHg. Global LV ejection fraction (EF) was slightly reduced (57% versus 63%; p<0.05) before valvuloplasty and normalized thereafter. Regional EF increased significantly (p<0.05) in the posterolateral region of the LAO projection after intervention. Myocardial stiffness was increased before, and decreased significantly after balloon valvuloplasty (from 16 to 11; p<0.05). The rate of relaxation and chamber stiffness remained unchanged. CONCLUSIONS: Myocardial stiffness is increased in patients with mitral stenosis, but normalized after successful PMV. The improvement in passive elastic properties after valvuloplasty can be explained by the mobilization of the subvalvular apparatus with an improvement in regional LV function.

[Diagnosis and indication for aortic valve replacement in asymptomatic and symptomatic patients with aortic regurgitation]. / Diagnostik und Indikation zum Klappenersatz bei asymptomatischer und symptomatischer Aorteninsuffizienz.

Chronic volume overload is associated with dilatation and eccentric hypertrophy of the left ventricle (= ventricular remodeling). With the dilatation of the left ventricle and the shift of the pressure-volume-relationship to the right, the filling pressures can be kept normal despite severe regurgitation. Therefore, the patient with aortic regurgitation can remain asymptomatic over many years. Thus, the indication for aortic valve replacement in patients with severe aortic regurgitation is sometimes difficult and may lead to problems to choose the optimal time point for operation. As a general rule, symptomatic patients with severe aortic regurgitation should be operated as soon as possible. In asymptomatic patients with significant dilatation of the left ventricle and reduction of systolic pump function the therapy of choice is aortic valve replacement. Asymptomatic patients with normal left ventricular function have usually a good prognosis with a yearly mortality rate of approximately 0.04%. However, in the presence of significant dilatation of the left ventricle, i.e. enddiastolic chamber diameter more than 70 mm respectively endsystolic diameter more than 50 mm, patients have to be checked on a regular basis, i.e. in yearly intervals to detect left ventricular dysfunction in due time. According to the literature, asymptomatic patients with severe aortic regurgitation develop left ventricular dysfunction in a yearly rate of 4%. However, approximately 50% of all patients are even after 10 years asymptomatic. The indication for aortic valve replacement is given when the patient shows a deterioration of left ventricular function or becomes symptomatic. Valve replacement is also indicated in patients with an ejection fraction below 50% and/or endsytolic chamber diameter of more than 55 mm. Therapy of choice in symptomatic patients with severe aortic regurgitation is aortic valve replacement. In asymptomatic patients, operation depends on the degree of chamber dilatation respectively the severity of left ventricular dysfunction. In patients with severe aortic regurgitation but without clinical symptoms and moderate enlargement of the left ventricle regular check-ups in yearly intervals are indicated. In the presence of severe left ventricular dilatation check-ups should be performed on a half-year basis to prevent irreversible damage to the heart muscle.

Influence of the culprit lesion on clinical symptoms of coronary artery disease, with special emphasis on exercise data.

BACKGROUND: Clinical symptoms have been found to correlate only poorly with the severity of the culprit lesion in coronary artery disease. The purpose of the present study was to evaluate the influence of the culprit lesion and its change during exercise on clinical symptoms in patients with this condition. METHODS: Minimal luminal area was determined using biplane quantitative coronary angiography in 42 patients (aged 53 +/- 8 years) with coronary artery disease. Percent diameter stenosis and minimal luminal area and its change during exercise were assessed in all patients and compared with clinical symptoms judged according to the functional classification of the New York Heart Association (NYHA). Coronary dimensions were determined with the patient at rest, during supine bicycle exercise and after sublingual administration of 1.6 mg glyceryl trinitrate. RESULTS: Exercise-induced vasoconstriction of the culprit lesion was found in all patients (-14.0% at 102 W), but there was exercise-induced vasodilatation in the normal vessel segments (+13.0%). However, only minimal vasoconstriction was found in groups 1 (NYHA I: -0.5%, NS) and 2 (NYHA II: -4.7%, NS), but significant constriction in groups 3 (NYHA II-III: -18.0%, P < 0.01) and 4 (NYHA III: -31.4, P < 0.01). Vasodilatation of the normal vessel segments was similar in the four groups. The observed inverse relationship between exercise-induced changes in minimal luminal area and NYHA classification was stronger than the relationship between NYHA and minimal luminal area when the patient was at rest. There was no correlation between glyceryl trinitrate-induced vasodilatation and NYHA classification. CONCLUSIONS: The more severe the culprit lesion, the more pronounced the exercise-induced vasoconstriction. This effect of the culprit lesion was reflected by the clinical symptoms: the greater the exercise-induced vasoconstriction, the higher the NYHA classification. Thus the anatomy of the lesion (= severity) and the functional integrity of the endothelium (= exercise-induced vasomotion) are two major determinants of clinical symptoms.

Reversal of abnormal coronary vasomotion by calcium antagonists in patients with hypercholesterolemia.

BACKGROUND: It has been shown that exercise-induced coronary vasodilation of angiographically normal coronary vessels is reduced in hypercholesterolemic patients. The purpose of this study was to evaluate the effect of calcium channel blockers on coronary vasomotion of angiographically smooth coronary arteries in hypercholesterolemic patients. METHODS AND RESULTS: A total of 57 patients were included in the present analysis. Vasomotion of angiographically normal coronary arteries was evaluated in 37 control subjects (group 1) without and 20 patients (group 2) with calcium blocker administration before physical exercise. Both groups were subdivided into subgroup A (normal cholesterol values: < or = 5.5 mmol/L or 212 mg%) and subgroup B (elevated cholesterol values: >5.5 mmol/L or 212 mg%). Coronary luminal area at rest and during exercise was assessed by biplane quantitative coronary angiography. The normal vessels showed a significant increase in coronary luminal area during exercise in subgroup A (n=13) with normal cholesterol values (31%; P<.05) but not in subgroup B (n=24; 13%; P=NS). In contrast, all patients in group 2 showed similar vasodilation during exercise, namely, 22% (P<.05) in subgroups A (n=8) and B (n=12) (P<.05). Independent of the actual cholesterol level, the stenotic lesions showed coronary vasoconstriction during exercise in group 1 but vasodilation in group 2 after pretreatment with calcium antagonists. CONCLUSIONS: Coronary vasomotor response to exercise is inversely related to actual serum cholesterol level in angiographically normal vessels. Administration of calcium antagonists normalizes exercise-induced vasodilation and thus eliminates cholesterol-induced abnormal vasomotion, probably by a direct effect on the smooth muscles of the vasculature.

Flow-dependent vasodilation in the coronary circulation: alterations in diseased states.

Flow-dependent vasodilation has been recognized to play an important role in the perfusion of the myocardium and the occurrence of myocardial ischaemia. In the past few years, the role of the endothelium in the regulation of coronary artery dimensions has gained a lot of attraction. Changes in coronary artery size are caused through the contraction and relaxation of the smooth musculature within the vessel wall. Vasoactive substances released from the endothelium play a crucial role in the regulation of vessel size and coronary vasomotor tone. During physiologic exercise, normal coronary arteries dilate, whereas stenotic arteries constrict. This abnormal behaviour of the stenotic artery has been associated with the occurrence of myocardial ischaemia, and has been thought to be either due to: endothelial dysfunction with reduced release or production of the endothelial derived relaxant factor (EDRF); an increased sympathetic stimulation during exercise; enhanced platelet aggregation with release of thromboxane A2 and serotonin; and/or a passive collapse of the disease-free vessel segment within the stenosis when blood-flow velocity increases during exercise. Thus, a diseased coronary endothelium may have a dramatic effect on the function of the coronary arteries, and may cause or contribute to the occurrence of myocardial ischaemia under high-demand situations, e.g. physical exercise or mental stress. Changes in flow-dependent vasodilation have been described in various disease states, e.g. hypercholesterolaemia, hypertension, diabetes mellitus, but also in valvular heart disease, heart failure and transplantation. Most of these alterations are due to functional changes of the endothelium, but vascular remodelling of the coronary arteries with thickening of the intima and an enlargement of the artery may affect these functional changes importantly.

Enhanced coronary vasoconstriction after PTCA in patients with acute ischemia.

UNLABELLED: Coronary vasoconstriction of the distal vessel segment has been reported after percutaneous transluminal coronary angiography (PTCA), which was explained by increased vasoconstrictor influences. In patients with acute ischemia these changes may be even enhanced. Thus, vasomotion of the epicardial coronary arteries was studied before and after PTCA in patients with acute ischemia due to unstable angina or acute infarction. METHODS: 52 patients were divided into 2 groups: Group 1 (controls) consisted of 31 patients who underwent elective (PTCA) and group 2 of 21 patients who underwent emergency PTCA for unstable angina or acute infarction. Coronary artery dimensions proximal and distal to the culprit lesion were determined by quantitative coronary angiography before and after PTCA as well as after 0.2 mg nitroglycerin i.c. at the end of the procedure. RESULTS: Stenosis severity was similar before and after PTCA in both groups (before, 91 +/- 8% in group 1 vs 90 +/- 9% in group 2; after, 28 +/- 9% vs 23 +/- 10%, resp.). Heart rate and mean blood pressure remained unchanged. In the group with acute ischemia no vasodilation of the proximal (2 +/- 3%) and distal vessel (-1 +/- 4%) occurred after PTCA, whereas in the control group significant vasodilation of both vessel segments (11 +/- 2% resp. 13 +/- 3%) was found. The response to nitroglycerin was maintained in both groups. In the control group there was a significant correlation between stenosis severity and percent diameter change of the distal vessel segment. However, in the acute ischemic group this relationship was shifted downwards suggesting an enhanced vasoconstrictor response in these patients. CONCLUSIONS: Epicardial coronary arteries in patients with acute ischemia show an enhanced vasoconstriction after PTCA. Nevertheless, the response to nitroglycerin is maintained suggesting that functional (endothelial dysfunction) rather than structural factors are responsible for this phenomenon.

Coronary vasomotion after percutaneous transluminal coronary angioplasty depends on the severity of the culprit lesion.

OBJECTIVES: This study sought to evaluate coronary vasomotor response to percutaneous transluminal coronary angioplasty (PTCA) and its influence on proximal and distal vessel diameters with regard to stenosis severity and coronary blood flow. BACKGROUND: Coronary vasoconstriction of the distal vessel segment has been reported after PTCA. This vasoconstrictive effect was thought to be due to balloon-induced injury of the vessel wall, with release of local vasoconstrictors or stimulation of the sympathetic system with release of catecholamines, or both. METHODS: Thirty-nine patients were prospectively studied before and after PTCA. Patients were classified into two groups according to the severity of the culprit lesion: group 1 = > or = 70% to < or = 85% diameter stenosis (n = 23); and group 2 = > 85% to < or = 95% diameter stenosis (n = 16). The coronary vessel diameter of the proximal and distal vessel segments as well as the minimal lumen diameter were determined by quantitative coronary angiography. In a subgroup of 16 patients, basal and maximal coronary flow velocity was measured before and after PTCA with the Doppler FloWire system. RESULTS: The groups were comparable with regard to age, gender, serum cholesterol levels and medical therapy. The proximal vessel segment remained unchanged after PTCA in group 1 ([mean +/- SD] 0.9 +/- 3.5%, p = 0.8) but showed vasodilation in group 2 (+13.7 +/- 3.6%, p < 0.05). However, the distal segment showed vasoconstriction in group 1 (-6.7 +/- 2.0%, p < 0.01) and vasodilation in group 2 (+31 +/- 8.0%, p < 0.01). A significant correlation was found between the change in distal vessel diameter after PTCA and stenosis severity (r = 0.61, p < 0.0001). Changes in blood flow were directly correlated to stenosis severity (r = 0.85, p < 0.002); that is, rest flow increased after PTCA in narrow lesions but remained unchanged in moderate lesions. The diameter changes in the distal vessel segment after PTCA were significantly related to flow changes (r = 0.90, p < 0.0001). Coronary distending pressure of the distal vessel segment increased significantly in both groups; however, this increase was significantly greater in group 2 than in group 1 (55 +/- 4 vs. 14 +/- 3 mm Hg, p < 0.0001). CONCLUSIONS: Coronary vasomotion of the proximal and distal vessel segments after PTCA depends on the severity of the culprit lesion; that is, vasoconstriction of the distal segment is found in patients with moderate lesions and vasodilation in those with severe lesions. Thus, vasomotion of the post-stenotic vessel segment depends on the severity of the culprit lesion and is influenced by changes in coronary flow or distending pressure, or both.

[Diuretics in the treatment of heart failure: current pathophysiological aspects]. / Diuretika in der Behandlung der Herzinsuffizienz: neue pathophysiologische Aspekte.

From a pathophysiologic point of view heart failure can be divided into systolic and diastolic dysfunction. Systolic dysfunction is characterized by a decreased ejection fraction and increased chamber volume which can be typically found in young people with congestive cardiomyopathy. Diastolic dysfunction is associated with an enhanced filling pressure but with a normal systolic pump function. This disorder can be typically found in elderly patients with myocardial hypertrophy. Treatment of congestive heart failure includes. 1.) reduction of central blood volume (preload reduction) 2.) decrease of peripheral resistance afterload reduction) 3.) regression of myocardial hypertrophy (improving myocardial stiffness) 4.) maintenance of atrial contraction (atrial kick) 5.) decrease of heart rate (prolongation of diastolic filling time and increase in contractility) 6.) improvement of LV relaxation (positive lusitropic effect) and 7.) prevention of myocardial ischemia (improvement in contractility and relaxation). The primary goal of medical therapy is symptomatic improvement. Reduction in morbidity and mortality is only a secondary consideration. To achieve this goal ACE-inhibitors and in certain cases betablockers (cave: neg. inotropic action) are suited best. Additionally, digitalis-especially in the presence of atrial fibrillation- and vasodilators can be used to further improve quality of life. In the case of severe heart failure with or without atrial fibrillation oral anticoagulation is indicated to prevent systemic embolication. Diuretics are often used for symptomatic improvement but have no effect on long-term survival. Aldosterone antagonists (e.g, spironolactone) have a beneficial effect on LV remodeling and probably also on mortality. The role of endothelin antagonists and atriopeptidase inhibitors in the treatment of heart failure are not yet clear.

[Anemia and heart function]. / Anämie und Herzfunktion.

Anemia typically leads to a state of hyperkinetic circulation with tachycardia, reduced peripheral resistance, increased stroke volume chamber dilatation, and finally to the development of left ventricular hypertrophy. These changes are usually well tolerated by patients with a healthy heart. In patients with heart diseases, however, anemia may lead to deterioration of ventricular performance and to increased morbidity and mortality respectively. Specific changes in cardiac function may arise depending on the causes of anemia such as myocardial iron deposition and dilatative cardiomyopathy in hemolytic anemia or alterations of homeostasis and reduction of cardiac function in renal anemia. With respect to cardiac function the cause of anemia must be corrected as far as possible and hemoglobin kept over a level of 10 g/dl. As far as renal anemia is concerned this goal can be reached by regular administration of erythropoietin and/or iron respectively.

[Function of the residual myocardium after infarct and prognostic significance]. / Funktion des Restmyokards nach Infarkt und dessen prognostische Bedeutung.

Changes of the left ventricle after myocardial infarction are characterized by geometric, structural, and vascular alterations, which have been summarized under the term "remodeling". This process takes place in the infarct region as well as in the surviving myocardium. Depending on to the size of infarction and the degree of neurohumoral activation, the left ventricle demonstrates diastolic dysfunction which may finally lead to systolic failure. The residual myocardium develops progressive myocyte hypertrophy and interstitial fibrosis. These structural alterations are due to changes in loading conditions and stimulation of the neurohumoral system with an activation of local paracrine and autocrine factors. Myocardial function can be assessed by different non-invasive (echocardiography, radionuclide ventriculography, magnetic resonance imaging, etc.) or invasive methods (e.g., simultaneous pressure-volume measurements). "Myocardial tagging" based on magnetic resonance imaging allows the assessment of 3D-motion of the left ventricle by labelling specific myocardial regions with a rectangular grid. A systolic "wringing" motion with clock-wise rotation at the base and counter-clockwise rotation at the apex has been described in normal subjects. In the ischemic myocardium, delayed relaxation with a prolonged back-rotation (untwisting) has been reported during early diastole, whereas decreased systolic contraction with delayed diastolic rotation has been observed in non-Q-wave infarction. In patients with anterolateral aneurysms, a complete loss of systolic rotation has been demonstrated. The prognostic significance of LV "remodeling" has been emphasized by several authors: The size of infarction, LV volume, LV ejection fraction, as well as the degree of neurohumoral activation have been identified as being associated with an unfavorable clinical outcome. Yearly mortality rates have been reported to range between 15 and 17% in patients with large infarcts and marked LV dilatation and between 3 and 7% in patients with small to medium-sized infarcts.