Prompt improvement of left ventricular function and preservation of topography with combined reperfusion and intravenous nitroglycerin in acute myocardial infarction.

Reperfusion alone during acute myocardial infarction (AMI) preserves left ventricular (LV) topography but causes 'stunning', with delayed or no recovery of function. To determine whether adjunctive intravenous nitroglycerin (NTG) accelerates functional recovery, we prospectively measured function and topography by repeated two-dimensional echocardiography between 1 day and 6 months in 5 groups of patients (n = 73) with a first AMI: placebo (group 1), NTG alone (group 2), NTG combined with successful reperfusion after 4 h (group 3) or failed reperfusion (group 4), and successful reperfusion alone (group 5). Asynergy decreased promptly (p < 0.001) and ejection fraction improved (p < 0.001) between day 1 and 6 months in groups 2 and 3 compared to baseline and groups 1, 4 and 5. Infarct expansion and thinning found in group 1 were prevented in groups 2, 3, 4 and 5. Diastolic volume increased in the anterior subgroup 1 but not 2, 3, 4 and 5. This is the first demonstration that reperfusion combined with adjunctive NTG produces earlier, greater and persistent recovery of LV function in addition to attenuation of remodeling in patients after AMI.

Effect of long-term captopril therapy on left ventricular remodeling and function during healing of canine myocardial infarction.

To determine whether the long-term reduction of preload and afterload by captopril during healing after acute anterior myocardial infarction might attenuate left ventricular remodeling and improve function, 30 chronically instrumented dogs with infarction produced by left anterior descending coronary artery ligation were randomized 2 days later to oral therapy with placebo (n = 15) or captopril, 50 mg twice daily (n = 15), for 6 weeks. Serial hemodynamic as well as topographic and functional variables (two-dimensional echocardiography) were measured over 6 weeks. Scar topography (planimetry), occluded bed size (coronary arteriography) and collagen (hydroxyproline) content were measured at 6 weeks. Between 2 days and 6 weeks, captopril decreased (p less than 0.001) mean arterial pressure and mean left atrial pressure more than did placebo, but it did not influence heart rate. Infarct scar mass, transmurality and collagen content at 6 weeks were similar in the two groups but scars showed less (p less than 0.001) thinning and expansion with captopril than with placebo. Echocardiograms showed similar infarct expansion and thinning in the two groups at 2 days but less aneurysm with captopril at 6 weeks. Between 2 days and 6 weeks, expansion index (infarct-/noninfarct-containing segment length) decreased (p less than 0.001) with captopril but increased (p less than 0.001) with placebo. Also, thinning ratio (infarct/normal wall thickness) decreased (p less than 0.001) with placebo but did not change (p = NS) with captopril. By 6 weeks, left ventricular asynergy and volumes showed a greater decrease (p less than 0.01) and global ejection fraction a greater increase (p less than 0.05) with captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of left ventricular unloading with captopril on remodelling and function during healing of anterior transmural myocardial infarction in the dog.

OBJECTIVE: To determine whether left ventricular (LV) unloading with captopril between two days and six weeks during healing after transmural anterior acute myocardial infarction might prevent further LV remodelling and preserve function in the canine model. DESIGN: Serial LV topographic and functional parameters (two-dimensional echocardiograms) and hemodynamics over six weeks and scar topography (planimetry) and collagen (hydroxyproline) at six weeks were measured in 34 chronically instrumented dogs; 24 with anterior transmural acute myocardial infarction (coronary artery ligation and collateral obliteration) that had been randomized at two days post infarction to therapy with oral 50 mg bid placebo (n = 12) or captopril (n = 12) for six weeks, and 10 with sham infarction. MAIN RESULTS: At six weeks, captopril and placebo groups had similar scar mass (7.7 versus 8.1% LV), infarct hydroxyproline and transmurality but the captopril group showed significantly less (P less than or equal to 0.05) infarct expansion and thinning, cavity dilation, epicardial and endocardial bulge. Between two days and six weeks, captopril decreased mean left atrial and arterial pressures compared to placebo or sham. Echocardiograms at two days showed similar LV asynergy, ejection fraction, infarct expansion and thinning with placebo and captopril. In contrast, echocardiograms between two days and six weeks showed that: further expansion and thinning occurred with placebo but not captopril; LV volumes increased with placebo but decreased with captopril; total LV asynergy was unchanged with placebo but decreased with captopril; and LV ejection fraction was unchanged with placebo but increased with captopril. At six weeks, LV ejection fraction was 10% higher (45 versus 35%, P less than 0.001) and LV aneurysm was less frequent (33 versus 100%, P less than 0.005) with captopril compared to placebo. CONCLUSIONS: Chronic LV unloading with captopril therapy during healing after canine transmural anterior acute myocardial infarction limits further remodelling, decreases aneurysm formation and improves function.

Improved left ventricular function and topography by prolonged nitroglycerin therapy after acute myocardial infarction.

To determine whether decreasing preload and afterload by prolonged nitroglycerin therapy (NTG) after acute myocardial infarction (AMI) might improve left ventricular (LV) geometry and function, 43 patients with a first anterior transmural AMI (ATAMI) were given low-dose intravenous NTG infusion for the first 48 h and then randomized to buccal NTG (1-3 mg t.i.d., five hourly with an eight-h washout period to avoid vascular tolerance; dose titrated as for i.v. NTG for 10% decrease in blood pressure but not below 80 mm Hg) or placebo for six weeks. All patients had serial two-dimensional echocardiography for 12 weeks for regional LV function and topography: Expansion index = asynergic/non-asynergic endocardial segment length; Thinning ratio = asynergic/normal wall thickness. Asynergy was defined as akinesis + dyskinesis. Between initial and 12-week studies, expansion index did not change in the buccal NTG group (2.09 vs 2.28, N.S.; n = 23) but increased in the placebo group (2.10 vs 2.89, p less than 0.05; n = 20). Over the same period, thinning ratio was unchanged with buccal NTG (0.82 vs 0.77, N.S.) but increased with placebo (0.78 vs 0.66 p less than 0.05). Both expansion and thinning at 12 weeks were greater with placebo than buccal NTG (p less than 0.01). The results indicate that prolonged NTG therapy decreased infarct expansion and infarct thinning. Compared to placebo, the NTG group also showed improved hemodynamics, decreased LV volume and asynergy, and increased ejection fraction. Thus, prolonged NTG therapy after ATAMI preserves LV function and topography. The beneficial early and late remodeling with prolonged NTG therapy might prevent aneurysm formation.

Exercise training after anterior Q wave myocardial infarction: importance of regional left ventricular function and topography.

To determine whether the extent of left ventricular dysfunction and the degree of shape distortion can predict outcome in survivors of moderate-sized anterior Q wave myocardial infarction who are undergoing exercise training, these variables were measured by two-dimensional echocardiography before and after 12 weeks of a low level exercise training program starting 15 weeks after infarction in 13 patients (7 in group 1 and 6 in group 2) and 12 weeks apart in 24 matched control patients without training. By the end of training, the functional class score had increased in group 2 (from 2.25 to 2.67, p less than 0.005) but had not changed in group 1. Further discrimination of groups 1 and 2 was provided by an initial asynergy (akinesia or dyskinesia, or both) less than 18% or greater than or equal to 18%. Compared with group 1, group 2 had greater initial asynergy (32 versus 6%, p less than 0.001), expansion index (asynergic/normal endocardial segment length: 1.8 versus 1.6, p less than 0.025) and peak shape distortion index (12.2 versus 1.0 mm, p less than 0.005) but lower ejection fraction (43 versus 59%, p less than 0.05) and thinning ratio (asynergic/normal wall thickness: 0.61 versus 0.74, p less than 0.05). These variables did not change with training in group 1. However, in group 2, training caused significant increase in asynergy (from 32 to 40%, p less than 0.05), expansion index (from 1.8 to 2.0, p less than 0.01) and peak shape distortion (from 12.2 to 20.9 mm, p less than 0.05) associated with a decrease in thinning ratio (from 0.61 to 0.51, p less than 0.001) and ejection fraction (from 43 to 30%, p less than 0.005). Initial values for these variables were similar for corresponding control groups but did not change over the 12 weeks. Thus, patients with greater than or equal to 18% left ventricular asynergy on the initial echocardiogram showed more shape distortion, expansion and thinning before exercise training and developed further functional and topographic deterioration with training.

Role of infarct expansion in rupture of the ventricular septum after acute myocardial infarction: a two-dimensional echocardiographic study.

To verify the role of infarct expansion (IE) in ventricular septal rupture (VSR) after transmural acute myocardial infarction (TAMI), topographic parameters were measured using tomographic imaging with two-dimensional echocardiography (2-D echo) and computer-aided analysis in four groups of patients: 8 patients with VSR (Group 1); 24 patients with TAMI but no mechanical complications (Group 2); 11 normal athletes (Group 3); 5 adults with congenital ventricular septal defect (Group 4). Measurements made on end-diastolic outlines of mid-left ventricular (LV) short-axis images included: LV asynergy (akinesis and/or dyskinesis), expansion index (asynergy/nonasynergy-containing endocardial segment length), thinning ratio (asynergic/nonasynergic wall thickness), and new indexes of regional shape distortion (RSD) by quantifying the deviation of the actual asynergic segment from the ideal asynergic arc constructed using the nearly circular nonasynergic contour. In Group 1, clinical IE (hypotension, congestive heart failure, no signs of new infarction) preceded detection of the VSR and portable 2-D echo showed the VSR associated with LV asynergy, marked IE, and RSD. Although Groups 1 and 2 had similar LV asynergy (28.7 vs. 26.9% LV) and ejection fraction (38.9 vs. 41.8%), Group 1 had higher expansion index (1.50 vs. 1.17, p less than 0.05), lower thinning ratio (0.54 vs. 0.67, p less than 0.005), and higher RSD parameters (e.g., peak distortion, Pk or maximum radial distance from the ideal arc, 19.3 vs. 3.9 mm, p less than 0.01; area of distortion, Ad, 7.4 vs. 1.1 cm2, p less than 0.05) than Group 2. Groups 3 and 4 had normal regional and global function and no evidence of expansion, thinning, or RSD. Thus, IE with marked diastolic RSD on an early 2-D echo after TAMI might identify patients at risk for VSR.

Lysolecithin and acute coronary ligation in the anaesthetised dog.

The metabolism of lysolecithin by the normal and by the ischaemic heart was examined in eight anaesthetised dogs. Relative lysolecithin concentrations (%lysolecithin) were measured in arterial, local (ischaemic) venous and coronary sinus (nonischaemic) blood samples, withdrawn before and at 2, 6, 10, 15 and 20 min after ligation of the left anterior descending coronary artery. Before ligation, 9.0 +/- 0.8% of the arterial lecithin was in the form of the lyso-derivative. The heart extracted lysolecithin, as reflected by the positive arterio-venous difference of lysolecithin. Arterio-venous differences of %lysolecithin across both the ischaemic and nonischaemic myocardium tended to diminish after coronary ligation, whether or not the dogs developed ventricular fibrillation. These results do not support the view that the formation of lysolecithin during ischaemia precipitates arrhythmias, since lysolecithin levels do not reach those necessary to induce electrophysiological abnormalities in vitro. Nor will the uniform response of the ischaemic and nonischaemic tissue result in metabolic heterogeneity leading to electrophysiological heterogeneity, which is thought to be an important factor in the development of re-entry arrhythmias.

Single-dose i.v. Aldactone for congestive heart failure: a preliminary observation.

Aldactone (200 mg potassium canrenoate i.v.) was given in a single dose as the sole drug to 30 patients with congestive heart failure (CHF). Of these patients 21 were unresponsive to routine treatment. Clinical improvement was observed in 18 of 30 patients (60%) within 6 h after Aldactone injection. Good diuretic effect (urine volume over 500 ml/6 h) was achieved in 14 patients, including 7 cases who responded dramatically (diuresis 700-1500 ml in 6 h). Plasma aldosterone concentrations before the injection of Aldactone were variable in individual patients. An analysis of their diuretic response to the Aldactone injection within 6 h showed that responders had significantly higher initial plasma aldosterone level (312 +/- 108 pg/ml) than non-responders (152 +/- 31 pg/ml) (p less than 0.02). The same tendency was observed if good or poor clinical effects were considered. Aldactone caused a slight increase in plasma potassium level (0.20 mEq/1) (p less than 0.025). Aldactone given in a single dose i.v. to patients with CHF is a potent drug and can produce a dramatic response in some individuals who are refractory to routine therapy. The beneficial effects of Aldactone could be seen within the first 6 h especially in patients with secondary aldosteronism.

The renin-angiotensin--aldosterone system and the clinical course of acute myocardial infarction.

To determine whether the renin--angiotensin--aldosterone system is stimulated in myocardial infarction, plasma renin activity and serum aldosterone were measured by radioimmunoassay in 95 patients with acute infarction. Urinary catecholamines, and sodium and potassium levels in blood and urine were also determined. Plasma renin activity and aldosterone were insignificantly increased in mild myocardial infarction as compared to a reference group comprising patients with angina pectoris. In patients with a complicated course, however, they were greatly augmented. A close correlation was found between urine catecholamines and plasma renin activity and between urine noradrenaline and aldosterone. Aldosterone values were highly correlated with the urine potassium/sodium ratio.