Biomedical subjects

P Gaudron

Publications and source records attributed to P Gaudron.

At least 37 records · Page 2Linked to original sources

PubMed1995

Investigation of coronary vessels in microscopic dimensions by two- and three-dimensional NMR microscopic imaging in the isolated rat heart. Visualization of vasoactive effects of endothelin 1.

BACKGROUND: Nuclear magnetic resonance (NMR) imaging of macroscopic coronary vessels is rapidly advancing, whereas little attention has focused on development of NMR techniques for investigation of coronary microvessels. Such techniques would be of particular importance, since conventional methods to visualize coronary microvessels have specific limitations. The aim of our study was to develop two- and three-dimensional (2D and 3D) high-resolution imaging of coronary microvessels. Quantitative analysis of vessel size was performed in tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1. METHODS AND RESULTS: Angiographic imaging was performed on an 11.75-T magnet by 2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this method in providing correct vessel size was tested by phantom experiments. Experiments were carried out in the isolated constant-pressure-perfused rat heart with continuous registration of coronary flow and left ventricular pressure. NMR pulse sequences were pressure-triggered in mid diastole. Four groups of hearts were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the long axis of the heart was performed. Cross sections of vessels with diameter > 140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n = 13), tomograms perpendicular to the long axis were obtained before and after administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3). Vehicle had no effect on vessel cross section. Endothelin 1, which decreased global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak but, on average, significant inverse correlation between area of cross section and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7 normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the entire coronary artery tree was obtained, revealing excellent agreement with anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery was demonstrated. CONCLUSIONS: Visualization and quantification of coronary microvessels are feasible by NMR microscopy. NMR microscopy bears the potential of becoming a powerful tool for the investigation of the coronary microcirculation.

Animals↗

PubMed1995

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress.

Adenosine Diphosphate↗

PubMed1994

Beta-blockers in cardiac failure.

The use of beta-blocking agents in patients with heart failure is still controversial. An activated sympatho-adrenal system in heart failure may support blood pressure and cardiac index, on the other hand, it increases cardiac load and myocardial oxygen consumption, reduces myocardial oxygen supply and may contribute to the high incidence of arrhythmias and sudden death. Today there is a certain awareness about the important role of the sympatho-adrenal system in CHF. Short-term studies failed to demonstrate a benefit of beta-blockers while long-term studies have proved major haemodynamic benefit and functional improvement in most patients. The haemodynamic benefit consists of a reduction of heart rate and left ventricular filling pressure and an improvement in exercise capacity. The mechanism of these actions of beta-blockers, with the exception of lowering heart rate, remains unclear. Energy metabolism of the failing heart, which is considered to be deficient, may beneficially be influenced by chronic beta-blocker treatment. Effects of beta-blockers on prognosis in patients with heart failure are also still controversial. Most recent trials (MDC Trial, CIBIS Trial) were inconclusive concerning mortality. Aetiology of heart failure may be important; however, observations on secondary prevention post-myocardial infarction also contradict heart failure studies. Thus, further efforts are urgently needed to define the mechanism of action of beta-blockers in patients with cardiac failure and to identify more clearly patients who benefit from this type of therapy.

Adrenergic beta-Antagonists↗

PubMed1994

Effects of LTD4 and its specific antagonist L-660,711 in isolated rat hearts with chronic myocardial infarction.

We investigated the effects of leukotriene (LT) D4 and its novel potent and selective antagonist L-660,711 on isolated rat hearts with chronic myocardial infarction. The left coronary artery was ligated permanently or for 30 or 60 min and followed by reperfusion. Hearts were isolated and perfused in the Langendorff mode 4 days, 4 wk, or 8 wk after the operation. Dose-response curves for LTD4 (12-240 ng/min) on coronary flow were shifted to the left in rats with permanent coronary occlusion for 8 wk or with coronary occlusion for 30 or 60 min and reperfusion for 4 wk. In contrast, dose-response curves were unchanged in rats 4 days after myocardial infarction. L-660,711 shifted dose-response curves for LTD4 on coronary flow to the right in all groups. The negative inotropic and chronotropic effects of LTD4 could be markedly attenuated by L-660,711 in all groups. Our findings suggest that the effect of LTD4 is enhanced in rat hearts with chronic myocardial infarction. L-660,711 effectively antagonized the vasoconstrictor effect of exogenous LTD4.

Angiotensin I↗

PubMed1994

Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction.

BACKGROUND: Remodeling of infarcted and noninfarcted ventricular regions, infarct expansion, shape distortion, and global left ventricular (LV) dilation influence LV performance and survival. The effect of chronic exercise, initiated early or later after infarction, on remodeling, hemodynamics, and survival has not been studied. METHODS AND RESULTS: A total of 156 rats were randomized after coronary artery occlusion or sham operation to remain sedentary or to start with swim training 4 days or 21 days after coronary occlusion, which was continued over 8 weeks (6 days per week, 90 minutes per day). These intervals after coronary artery ligation were chosen because final size of infarction is well reached after 4 days; histological evolution of scar healing is still in progress, and after 21 days, histological scar healing is completed. At 8 weeks, hemodynamics were measured and LV dilation quantitated by passive pressure-volume curves. In groups with small (< or = 35%) and large (> 35%) infarcts, the area enclosed by endocardial circumference, infarct size, LV diameter, scar thickness, and septal thickness were measured in stained transverse serial LV sections to assess aneurysmal shape distortion and the response of infarcted and noninfarcted myocardia. Survival was not influenced by infarction or exercise alone. In rats with small infarcts, LV volume and shape and long-term survival were not altered by chronic exercise initiated early or late after coronary artery ligation. Mortality rose in animals with large infarction as a result of exercise (P < .0001) and was 47.6% with early exercise and 26.7% with late exercise (P < .05, early versus late). Infarct size in rats with early exercise (48 +/- 3%) was similar compared with infarct size of rats with late exercise (46 +/- 2%, P = NS compared with early exercise). Exercise did not affect LV dysfunction (assessed by systolic and end-diastolic pressures and dP/dtmax) in survivors of small and large infarctions. LV volumes increased (P < .05) in sedentary rats by large infarction (n = 13, 0.48 +/- 0.04 mL) compared with volumes after sham operation (n = 33, 0.33 +/- 0.03 mL) and with exercise (early, n = 11, 0.56 +/- 0.04 mL; late, n = 11, 0.65 +/- 0.04; P < .05 versus sedentary). In nonsurvivors from early exercise, the area enclosed by LV endocardial circumference (which corresponds to LV volume) was increased by 195%, LV diameter was increased by 60%, and scar thickness was reduced by 37% (P < .05 versus respective control). Septal thickness increased in survivors by exercise (+25%) but decreased (-28.6%) in nonsurvivors (P < .0001 versus respective control). CONCLUSIONS: Endurance training in rats after small infarction, whether started early or late after left coronary artery ligation, was well tolerated without changes in LV volume, shape, hemodynamics, and long-term survival. Endurance training in rats with large infarction decreased overall survival (P < .0001). In survivors from late exercise, training caused aggravation of global LV dilation without additional shape changes. Endurance training after large infarction caused aggravation of remodeling to a degree that was not compatible with life in 27% of the rats with late exercise and in 48% with early exercise after coronary artery ligation, despite similar exercise. This was explained by extensive remodeling that was most pronounced in nonsurvivors from early exercise. In these rats, severe global LV dilation, distortion of LV shape, scar thinning, and a paradoxic reduction of septal thickness, ie, mismatch of infarcted and noninfarcted myocardia, were observed.

Animals↗

PubMed1994

[Indications for ACE inhibitors in the postinfarct period].

Prognosis of patients post-myocardial infarction depends largely on the degree of left ventricular dysfunction, which results from loss of contractile tissue and remodeling of infarcted and surviving myocardium. This remodeling process may result in chronically progressive dysfunction and ultimately in heart failure. Next to mechanical determinants humoral control of hypertrophy, dilatation and qualitative changes of surviving myocardium are discussed. A major determinant of the extent of remodeling is infarct size. Efficacy of angiotensin-converting enzyme (ACE) inhibitors on infarct size was tested in animal experiments with conflicting results. Recent clinical studies also report beneficial (GISSI-3 and ISIS-4) or no (CONSENSUS II) effects on survival post-myocardial infarction when ACE-inhibitors were used in the acute phase. Up to date it remains unsettled which patients may benefit from acute therapy with ACE-inhibitors. Three days after myocardial infarction hemodynamically stable patients with heart failure may be treated with ACE-inhibitors (AIRE study). Prognosis may be improved and manifestation of heart failure prevented or delayed also in patients without heart failure treated in this phase of myocardial infarction with ACE-inhibitors (SAVE study). Prevention of heart failure may also be observed in patients treated later (at least 4 weeks) after myocardial infarction (SOLVD prevention arm). It is essential for this indication that patients are carefully selected for treatment depending on left ventricular function. Duration of treatment in patients with severe left ventricular dysfunction probably has to be lifelong, the doses of ACE-inhibitors used have to be relatively high (e.g. 3 x 50 mg captopril or 2 x 10 mg enalapril).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Ventricular remodeling after myocardial infarction. Experimental and clinical studies.

Changes of ischemic myocardium following coronary occlusion, including active and passive functions, and adaptive changes of non-ischemic surviving myocardium have been summarized under the term "left ventricular remodeling" post myocardial infarction. An increase in left ventricular volume may be a consequence, and associated with an adverse prognosis. Although left ventricular dilatation may increase stroke volume and, thus, be compensatory at first, in about one-fifth of patients it ultimately results in progressive dysfunction and heart failure. Major determinants of this process are time, infarct size, infarct location, global left ventricular function assessed 4 days after infarction by radionuclide ejection fraction and right heart catheter (stroke volume), and morphology of the infarct-associated coronary artery. The surviving myocardium hypertrophies and may also dilate structurally. Depression of left ventricular ejection fraction chronically after the infarct is due to deterioration of wall motion of chamber segments initially classified normal by radionuclide analysis. Biochemical changes may also occur, including reduction of phosphocreatine, prolongation of time to peak Cai2+, and changes in myosin isoforms. Systemic or local humoral factors may be involved in these changes, however, clear evidence is still lacking. Perfusion of surviving myocardium may be altered under various conditions due to morphologic and functional changes of coronary vasculature. Successful prevention of heart failure and death by angiotensin converting enzyme inhibitors in asymptomatic patients with left ventricular dysfunction post-myocardial infarction has supported the pathophysiologic concepts of remodeling.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Aggravation of left ventricular dilatation and reduction of survival by a calcium channel blocker in rats with chronic myocardial infarction.

The mechanism of adverse effects of calcium channel blockade on cardiac performance and survival in patients with cardiac dysfunction after myocardial infarction is controversial. To test whether left ventricular dilatation and remodeling, as predictors of long-term survival and cardiac performance, are important, rats with healed infarcts received a vasodilating calcium channel blocker (anipamil) or placebo. After 8 weeks the mortality rate (total population n = 111) was 35% with calcium channel blockade and 4% with placebo in rats with infarction (p < 0.001). In survivors with large infarctions (44% +/- 12% of left ventricle, n = 9), calcium channel blockade did not aggravate left ventricular dysfunction and decreased chamber stiffness, but increased left ventricular volume (1.55 +/- 0.13 ml/kg, p = 0.03 vs placebo: 1.16 +/- 0.11 ml/kg; n = 11) (passive pressure-volume relationship) at persistently elevated volume/mass ratio. Thus this study shows for the first time that aggravation of left ventricular dilatation and remodeling is one important mechanism by which calcium channel blockade may reduce survival in the presence of ventricular dysfunction after myocardial infarction.

Animals↗

PubMed1993

Cardiac dysfunction and development of heart failure.

A major consequence of chronic cardiac dysfunction is chronic overload of contractile myocardium. Various aetiologies, in reaction to this, may induce compensatory mechanisms consisting of excentric (dilatation) and concentric hypertrophy. Chronic left ventricular dysfunction is caused most frequently by myocardial infarction. Left ventricular dilatation and hypertrophy occurs in patients with extensive infarction. Dilatation may at first be compensatory, restoring stroke volume within 4 weeks of the infarct. However, as dilatation progresses, left ventricular ejection fraction and stroke volume deteriorate during exercise and at rest, and finally pulmonary capillary wedge pressure increases and patients become symptomatic 1.5-3 years after the infarct. Major determinants of progressive left ventricular dilatation and deterioration of haemodynamics are a depressed left ventricular ejection fraction, angiographically determined infarct size, stroke volume early (4 days) after myocardial infarction, infarct location (anterior/inferior) and the grade (TIMI) of perfusion of the infarct-associated coronary artery. Chronic loading and unloading may accelerate or decelerate this process. Efficiency and energy reserve (phosphocreatine) of the dilated ventricles is reduced. Further intrinsic changes in surviving myocardium include morphological and functional disturbance of coronary microcirculation.

Cardiomegaly↗

PubMed1993

Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors.

BACKGROUND: Left ventricular enlargement and the development of chronic heart failure are potent predictors of survival in patients after myocardial infarction. Prospective studies relating progressive ventricular enlargement in individual patients to global and regional cardiac dysfunction and the onset of late chronic heart failure are not available. It was the aim of this study to define the relation between left ventricular dilatation and global and regional cardiac dysfunction and to identify early predictors of enlargement and chronic heart failure in patients after myocardial infarction. METHODS AND RESULTS: Left ventricular volumes, regional area shrinkage fraction in 18 predefined sectors (gated single photon emission computed tomography), global ejection fraction, and hemodynamics at rest and during exercise (supine bicycle, 50 W, 4 minutes, Swan-Ganz catheter) were assessed prospectively 4 days, 4 weeks, 6 months, and 1.5 and 3 years after first myocardial infarction. Seventy patients were assigned to groups with progressive, limited, or no dilatation. Patients without dilatation (n = 38) maintained normal volumes and hemodynamics until 3 years. With limited dilatation (n = 18), left ventricular volume increased up to 4 weeks after infarction and stabilized thereafter; depressed stroke volume was restored 4 weeks after infarction and then remained stable at rest. Wedge pressure during exercise, however, progressively increased. With progressive dilatation (n = 14), depressed cardiac and stroke indexes were also restored by 4 weeks but progressively deteriorated thereafter. Area shrinkage fraction as an estimate of regional left ventricular function in normokinetic sectors at 4 days gradually deteriorated during 3 years, but hypokinetic and dyskinetic sectors remained unchanged. Global ejection fraction fell after 1.5 years, whereas right atrial pressure, wedge pressure, and systemic vascular resistance increased. By multivariate analysis, ejection fraction and stroke index at 4 days, ventriculographic infarct size, infarct location, and Thrombolysis in Myocardial Infarction trial grade of infarct artery perfusion were significant predictors of progressive ventricular enlargement and chronic dysfunction. CONCLUSIONS: Almost 26% of patients may develop limited left ventricular dilatation within 4 weeks after first infarction, which helps to restore cardiac index and stroke index at rest and to preserve exercise performance and therefore remains compensatory. A somewhat smaller group (20%) develops progressive structural left ventricular dilatation, which is compensatory at first, then progresses to noncompensatory dilatation, and finally results in severe global left ventricular dysfunction. In these patients, depression of global ejection fraction probably results from impairment of function of initially normally contracting myocardium. Early predictors from multivariate analysis allow identification of patients at high risk for progressive left ventricular dilatation and chronic ventricular dysfunction within 4 weeks after acute infarction.

Aged↗

PubMed1993

[Epidemiology and prognosis of myocardial infarct and chronic heart failure].

The incidence of coronary heart disease and myocardial infarction fell gradually during the seventies. Reasons for this decline are not well understood. Speculations include changes of life style and health care. However, cardiovascular disease is still the leader of mortality in Western developed countries. Mortality of myocardial infarction has also declined. The major benefit was associated with broad establishment of coronary care units, smaller steps were achieved by various progresses in medical treatment. In contrast, the incidence of heart failure has increased. The major etiology of heart failure nowadays is coronary heart disease, especially large or recurrent myocardial infarction. The incidence of heart failure in patients having recovered from myocardial infarction is dramatically higher than in normal population. The Framingham Study showed an incidence of 14% in five years following a myocardial infarction. Prognosis of patients with manifestation of symptoms of heart failure is very poor. Patients with heart failure had an overall six years mortality of 55%. These observations suggest that coronary care units, thrombolysis and modern treatment as developed so far, suppressed in-hospital mortality and improved survival for the first year after a myocardial infarction. Thus, patients with larger infarcts who had succumbed early under previous regimens, survived. They carry, however, the burden of severely impaired left ventricular function, high probability to develop heart failure, and of a dubious long-term prognosis. Large efforts have put upon development of scores to estimate long-term prognosis after a myocardial infarction. With the development of techniques, composition of scores changed. However, residual ischemia, major left ventricular dysfunction, and ventricular arrhythmias are the basis of most scores indicating an adverse prognosis after an infarction. This review will be limited to the prognostic impact of left ventricular dysfunction and development of heart failure post myocardial infarction. A hypothetic cascade of events which may lead from myocardial infarction to heart failure and death is schematically outlined in Figure 1. Loss of contractile myocardium results in left ventricular dysfunction which may induce dilatation of the left ventricle, heart failure and ultimately death. This paper focuses on the evidence for the prognostic impact of the single steps and the whole cascade. Figure 1 shows in parenthesis the variables which were frequently measured to assess loss of contractile tissue, left ventricular dysfunction, and dilatation. Since heart failure is understood as a clinical syndrome of symptoms, it may only be semi-quantitated according to the classification of the New York Heart Association (NYHA).(ABSTRACT TRUNCATED AT 400 WORDS)

Cause of Death↗

PubMed1993

Adaptation to cardiac dysfunction after myocardial infarction.

Survival after myocardial infarction decreases with left ventricular dilatation, although dilatation at 4 weeks was found to be compensatory. To study this apparent discrepancy, prospective simultaneous volume and hemodynamic measurements at rest were extended in 39 patients with small and 37 with large myocardial infarctions from 4 days (range, 2-6 days) and 4 weeks (range, 3-5 weeks) to 6 months (range, 5-8 months) after infarction and were repeated during supine bicycle exercise at 50 W. In patients with small infarction, end-diastolic volume (mL/m2) decreased from 4 days to 6 months; ejection fraction (%), stroke volume (mL/m2), and end-systolic volume (mL/m2) remained unchanged. Stroke index rose during exercise at 4 weeks and 6 months. In patients after large infarction (n = 37), left ventricular end-systolic volume index (4 days, 38 +/- 3; 4 weeks, 47 +/- 3*; 6 months, 52 +/- 3*; *p < 0.05 versus 4 days) and end-diastolic volume indexes (4 days, 72 +/- 3; 4 weeks, 86 +/- 5*; 6 months, 92 +/- 5*; *p < 0.05 versus 4 days, +p < 0.05 versus 4 weeks) increased at constant wedge pressure. Stroke index remained restored beyond 4 weeks after infarction (4 days, 35 +/- 2; 4 weeks, 42 +/- 2*; 6 months, 42 +/- 2*; p < 0.05 versus 4 days) and rose during exercise at 4 weeks (rest, 45 +/- 2; exercise, 55 +/- 3; p < 0.05) but not at 6 months (rest, 42 +/- 3; exercise, 45 +/- 3; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1992

Compensatory and noncompensatory left ventricular dilatation after myocardial infarction: time course and hemodynamic consequences at rest and during exercise.

Survival after myocardial infarction decreases with left ventricular dilatation, although dilatation at 4 weeks was found to be compensatory. To study this apparent discrepancy, prospective simultaneous volume and hemodynamic measurements at rest were extended in 39 patients with small and 37 with large myocardial infarctions from 4 (range 2 to 6) days and 4 (range 3 to 5) weeks to 6 (range 5 to 8) months after myocardial infarction and were repeated during exercise. In small myocardial infarctions, end-diastolic volume index (EDVI) decreased from 4 days to 6 months; ejection fraction, stroke volume index (SVI), and end-systolic volume index (ESVI) remained unchanged. SVI increased during exercise at 4 weeks and at 6 months. In large myocardial infarctions (n = 37) ESVI (4 days = 38 +/- 3, 4 weeks = 47 +/- 3,* 6 months = 52 +/- 3*; *p less than 0.05 versus 4 days) and EDVI (4 days = 72 +/- 3, 4 weeks = 86 +/- 5,* 6 months = 92 +/- 5* ; *p less than 0.05 versus 4 days and p less than 0.05 versus 4 weeks) increased at constant wedge pressure. SVI remained unchanged beyond 4 weeks (4 days = 35 +/- 2, 4 weeks = 42 +/- 2*, 6 months = 42 +/- 2*; *p less than 0.05 versus 4 days) and increased during exercise at 4 weeks (rest = 45 +/- 2, exercise = 55 +/- 3; p less than 0.05) but not at 6 months (rest = 42 +/- 3, exercise = 45 +/- 3; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

PubMed1992

Determinants of coronary effects of atrial natriuretic factor in dogs.

The direct vascular action of atrial natriuretic factor (ANF) is unclear. In coronary vasculature, vasodilation has been reported as well as vasoconstriction. Doses of ANF, baseline plasma ANF levels and interference with the renin-angiotensin system might account for the controversy. We tried to further analyse determinants of the effect of ANF on coronary blood flow in anaesthetized dogs. The chest was opened and the left anterior descending coronary artery cannulated and perfused at constant normal (= 76 +/- 5 mmHg, n = 10) or reduced (= 37 +/- 3 mmHg, n = 10) pressure from the femoral arteries. At normal coronary perfusion pressure, ANF (1 ng kg-1 i.c.) reduced coronary flow from 30.7 +/- 4.2 to 26.9 +/- 4.0 ml min-1 (P less than 0.05). This effect was no longer significant at reduced coronary perfusion pressure (4.9 +/- 0.8 vs. 4.6 +/- 0.7 ml min-1). ANF (1 ng kg-1 i.c.) reduced coronary blood flow in correlation with baseline plasma ANF levels (r = 0.77, P less than 0.001). However the large variability of the constrictor effect of ANF in the rather small range of baseline plasma ANF, weakens the importance of this result and suggests other additional determinants. ANF (100 ng kg-1 i.c.) significantly increased coronary blood flow by 16-23% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

[Prevention with angiotensin-converting enzyme (ACE) inhibitors].

Preventive therapy by angiotensin-converting-enzyme (ACE) inhibitors is considered in hypertension and, more recently, in chronic heart failure. The mechanism of action of ACE-inhibitors is complex; most extensively studied, however, is their inhibitory effect on angiotensin-II production. ACE-inhibitors may act as vasodilators, reducing pre- and afterload. On the other hand, local renin-angiotensin systems may control growth processes both in myocardial and in smooth muscle cells. This may be another site of action for ACE-inhibitors. ACE-inhibitors are reliable antihypertensive drugs and may have additional specific effects on the heart and vascular smooth muscle. Clear evidence is, however, missing for their superiority above other drugs in preventing cardiovascular complications of hypertension. Most recently, the data of the "study of left-ventricular dysfunction" (SOLVD) and "survival and ventricular enlargement" (SAVE) study became available. These studies showed that ACE-inhibitors could prevent the incidence of heart failure in about one-third of patients with severe left-ventricular dysfunction during 3 years of observation when compared with placebo treated patients. A new indication, therefore, for ACE-inhibitors could be left ventricular dysfunction after myocardial infarction. It remains unclear 1) what could be the adequate diagnostic procedures to identify patients for preventive treatment, 2) when therapy should be started, 3) about the duration of therapy, 4) about the doses of ACE-inhibitors for this indication, 5) what will be the side-effects when used in a broader population, and 6) will this prevention of heart failure be a specific effect of ACE-inhibitors?

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

Serial changes in left ventricular size after acute myocardial infarction.

The prognosis is poor for patients with left ventricular enlargement associated with large infarcts. We studied 78 patients using gated single-photon emission computed tomography (SPECT, to assess left ventricular volumes), right heart catheterization (to measure pulmonary wedge pressure and cardiac output), and conventional planar radionuclide ventriculography (to estimate ejection fraction), 2-6 days, 3-5 weeks, and 5-8 months after their first myocardial infarction. Patients were assigned to a large or small infarct-size group based on creatine kinase analysis. In 37 patients with large infarcts, left ventricular volume increased and was greater than 27% after 5-8 months than after 2-6 days (p less than 0.05). Although ejection fraction remained significantly depressed, stroke volume, which initially declined, was restored as a result of dilation and thus returned to normal by 3-5 weeks, indicating that enlargement of the left ventricle compensated for the loss of contractile myocardium and depression of global ejection fraction. The progressive nature of left ventricular dilation suggested that this process is of major pathophysiologic importance and that it plays an etiologic role in the genesis of heart failure and perhaps of sudden death following myocardial infarction. Dilation preceded hemodynamic deterioration, which became evident on exercise after 5-8 months in patients with large infarcts.

Cardiac Volume↗

PubMed1991

Compensatory mechanisms for cardiac dysfunction in myocardial infarction.

Loss of contractile myocardial tissue by myocardial infarction would result in depressed cardiac output if compensatory mechanisms would not be operative. Frank-Straub-Starling-mechanism and increased heart rate and contractility due to sympathetic stimulation are unlikely to chronically compensate for cardiac dysfunction. Structural left ventricular dilatation may be compensatory, but results in increased wall stress and, ultimately, in progressive dilatation and heart failure. In patients with myocardial infarction, we have shown left-ventricular dilatation in dependence of infarct size and time after infarction. Dilatation is compensatory first and normalizes stroke volume. However, left ventricular dilatation progresses without further hemodynamic profit and, thus, may participate in development of heart failure.

Animals↗

PubMed1991

[Possibilities of ACE inhibitor therapy in acute myocardial ischemia].

Acute myocardial ischemia results from an increased cardiac workload in presence of a critical coronary stenosis (demand ischemia), coronary occlusion (supply ischemia) or a combination of both. It is complicated by cardiac arrhythmias and deterioration of function of ischemic myocardium and results in an increased load and dilatation of non-ischemic myocardium. Cardiac protection in acute myocardial ischemia can be related to preservation of coronary blood flow, function of ischemic and non-ischemic myocardium or prevention of cardiac arrhythmias. In control animals and humans, ACE-inhibitors have no major effect on coronary blood flow. Myocardial ischemia raises plasma-renin-activity, angiotensin I-conversion by passage through coronary circulation, and plasma-angiotensin-II-concentrations. ACE-inhibitors and angiotensin-II-receptor blockers increase coronary blood flow during myocardial ischemia. Other mechanisms (bradykinin potentiation) may be involved. We found a potentiation of the coronary dilatory effect of the neuropeptide neurotensin (which is probably mediated by prostaglandins) by ACE-inhibitor. ACE-inhibitor may delay infarct development in animal experiments and improve function of ischemic myocardium. The importance of early dilatation of non-ischemic myocardium is unknown and it is unclear whether it may be prevented by an ACE-inhibitor as was shown for late dilatation. Studies on the effect of ACE-inhibitors in exercise-induced angina pectoris are controversial. An antiischemic and coronary dilatory effect has been shown by invasive studies in patients. A preliminary study in unstable angina pectoris was positive. Beneficial hemodynamic and antiarrhythmic effects (as well as excessive hypotension, however) have been shown in patients with acute myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗