Intracoronary prostaglandin E1 plus streptokinase in acute myocardial infarction

Fourteen patients with acute myocardial infarction (duration of chest pain 5 ± 2 hours) received intracoronary infusion of prostaglandin E₁ (PGE₁) and streptokinase. Intracoronary PGE₁ was followed by intracoronary streptokinase in 10 patients (group A), with successful recanalization in all patients. Of 4 patients in whom recanalization failed with intracoronary streptokinase given first (group B), 2 had successful recanalization after addition of intracoronary PGE₁. Immediately after successful recanalization, left ventricular ejection fraction increased from 50 ± 9% to 62 ± 10% (p < 0.0008), left ventricular end-diastolic pressure decreased from 20 ± 10 to 16 ± 10 mm Hg (p < 0.05) and stroke volume index increased from 34 ± 10 to 44 ± 12 ml/m² (p < 0.02). Infarct segment shortening improved from 9 ± 5 to 18 ± 4% (p < 0.0002). Transient hypotension in 1 patient was the only complication. Follow-up catheterization in recanalized patients at 2 to 10 days showed maintained improvement in left ventricular global and infarct segment function. Reocclusion occurred in 1 patient. Thus, intracoronary infusion of PGE₁ was effective in establishing reperfusion in all patients when followed by streptokinase and was associated with immediately improved left ventricular global and regional function. PGE₁ deserves further evaluation in acute myocardial infarction.     

Residual exertional ischemia and unfavorable left ventricular remodeling in patients with systolic dysfunction after anterior myocardial infarction

Objectives. This study investigated whether exercise-induced myocardial ischemia influences left ventricular remodeling after anterior myocardial infarction.

Background. The effects of acute and recurrent ischemia on ventricular function are well established. However, to our knowledge the role of exertional ischemia in the remodeling response after infarction has not been investigated.

Methods. Ninety-one patients with a first anterior Q wave myocardial infarction were studied at 5 weeks by rest echocardiography and exercise scintigraphy. The echocardiographic examination was repeated 6 months later. On the basis of the presence and extent of reversible perfusion defects on exercise scintigraphy, patients were assigned to groups with no exertional ischemia (group 1, n = 20 [22%]), mild to moderate ischemia (group 2, n = 45 [49%]) and severe exertional ischemia (group 3, n = 26 [29%]).

Results. Initial left ventricular volumes were similar, and no differences were found among the three groups in the remodeling response over the 6-month period of the study. However, patients in groups 2 and 3 with an ejection fraction ≤40% showed significant (p < 0.01) ventricular enlargement over time, which was similar between the two groups (end-diastolic volume [mean ± SD] from 74 ± 13 to 80 ± 17 ml/m² in group 2 and from 72 ± 11 to 81 ± 19 ml/m² in group 3; regional dilation from 42 ± 16% to 52 ± 22% in group 2 and from 38 ± 18% to 46 ± 27% in group 3). In contrast, ventricular dimensions did not change in group I patients with an ejection fraction ≤40% as well as in patients in all three groups with an ejection fraction >40%.

Conclusions. Exercise-induced myocardial ischemia may contribute to progressive ventricular enlargement in patients with poor left ventricular function after a large interior myocardial infarction.     

Heterogeneous fate of perfusion and contraction after anterior wall acute myocardial infarction and effects on left ventricular remodeling

After acute myocardial infarction, patency of infarct vessel and extent of left venticular (LV) dysfunction are major determinants of ventricular remodeling. Spontaneous, delayed reperfusion in the infarct zone occurs in a sizeable number of patients well after the subacute phase. The aim of this study was to determine the relation between the occurrence of this spontaneous, delayed reperfusion and LV remodeling. In 84 patients, resting LV volumes, topography, regional function, and perfusion were quantitatively evaluated by 2-dimensional echocardiography and sestamibi tomography 5 weeks (study 1) and 7 months (study 2) after anterior Q-wave infarction. At study 2, LV end-diastolic volume increased by >15% in 17 patients (20%, LV remodeling); they had already had at study 1 significantly larger LV volumes, more severe hypoperfusion and wall motion abnormalities, and greater regional dilation than patients with stable LV volumes. Delayed reperfusion occurred in 8 of 17 patients with and in 42 of 67 patients without LV remodeling (47% vs 63%; p = NS). At study 2, LV regional dilation and end-diastolic volumes were stable in patients with, but increased in patients without, spontaneous reperfusion (from 25 ± 24% to 29 ± 26% at study 2 [p<0.05] and from 65 ± 14 to 68 ± 18 ml/m² [p <0.05]). At multivariate analysis, however, regional ventricular dilation at study 1 was the sole predictor of further LV remodeling. Thus, after acute myocardial infarction, spontaneous reperfusion occurring after 5 weeks plays only a minor role in influencing LV remodeling. Benefits from delayed reperfusion seem limited to patients with preserved LV volumes; patients with an enlarged left ventricle 5 weeks after acute infarction are prone to further LV remodeling, irrespective of delayed reperfusion.     

Acute and short-term effects of partial left ventriculectomy in dilated cardiomyopathy: assessment by pressure-volume loops

OBJECTIVES

The aim of this study was to evaluate the short-term effects of partial left ventriculectomy (PLV) on left ventricular (LV) pressure-volume (P-V) loops, wall stress, and the synchrony of LV segmental volume motions in patients with dilated cardiomyopathy.

BACKGROUND

Surgical LV volume reduction is under investigation as an alternative for, or bridge to, heart transplantation for patients with end-stage dilated cardiomyopathy.

METHODS

We measured P-V loops in eight patients with dilated cardiomyopathy before, during and two to five days after PLV. The conductance catheter technique was used to measure LV volume instantaneously.

RESULTS

The PLV reduced end-diastolic volume (EDV) acutely from 141 ± 27 to 68 ± 16 ml/m² (p < 0.001) and to 65 ± 6 ml/m² (p < 0.001) at two to five days postoperation (post-op). Cardiac index (CI) increased from 1.5 ± 0.5 to 2.6 ± 0.6 l/min/m² (p < 0.002) and was 1.8 ± 0.3 l/min/m² (NS) at two to five days post-op. The LV ejection fraction (EF) increased from 15 ± 8% to 35 ± 6% (p < 0.001) and to 26 ± 3% (p < 0.003) at two to five days post-op. Tau decreased from 54 ± 8 to 38 ± 6 ms (p < 0.05) and was 38 ± 5 ms (NS) at two to five days post-op. Peak wall stress decreased from 254 ± 85 to 157 ± 49 mm Hg (p < 0.001) and to 184 ± 40 mm Hg (p < 0.003) two to five days post-op. The synchrony of LV segmental volume changes increased from 68 ± 6% before PLV to 80 ± 7% after surgery (p < 0.01) and was 73 ± 4% (NS) at two to five days post-op. The LV synchrony index and CI showed a significant (p < 0.0001) correlation.

CONCLUSIONS

The acute decrease in LV volume in heart-failure patients following PLV resulted at short-term in unchanged SV, increases in LVEF, and decreases in peak wall stress. The increase in LV synchrony with PLV suggests that the transition to a more uniform LV contraction and relaxation pattern might be a rationale of the working mechanism of PLV.     

Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol

OBJECTIVES

The purpose of this study was to analyze whether long-term treatment with the nonselective beta-adrenergic blocking agent carvedilol may have beneficial effects in patients with dilated cardiomyopathy (DCM), who are poor responders in terms of left ventricular (LV) function and exercise tolerance to chronic treatment with the selective beta-blocker metoprolol.

BACKGROUND

Although metoprolol has been proven to be beneficial in the majority of patients with heart failure, a subset of the remaining patients shows long-term survival without satisfactory clinical improvement.

METHODS

Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction ≤40%) and reduced exercise tolerance (peak oxygen consumption <25 ml/kg/min) despite chronic (>1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n = 16, mean dosage 142 ± 44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n = 14, mean dosage 74 ± 23 mg/day).

RESULTS

At 12 months, patients on carvedilol, compared with those continuing on metoprolol, showed a decrease in LV dimensions (end-diastolic volume −8 ± 7 vs. +7 ± 6 ml/m², p = 0.053; end-systolic volume −7 ± 5 vs. +6 ± 4 ml/m², p = 0.047), an improvement in LV ejection fraction (+7 ± 3% vs. −1 ± 2%, p = 0.045), a reduction in ventricular ectopic beats (−12 ± 9 vs. +62 ± 50 n/h, p = 0.05) and couplets (−0.5 ± 0.4 vs. +1.5 ± 0.6 n/h, p = 0.048), no significant benefit on symptoms and quality of life and a negative effect on peak oxygen consumption (−0.6 ± 0.6 vs. +1.3 ± 0.5 ml/kg/min, p = 0.03).

CONCLUSIONS

In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption.     

Effects of partial left ventriculectomy on left ventricular performance in patients with nonischemic dilated cardiomyopathy

Objectives. This study sought to assess the effects of partial left ventriculectomy (PLV) on left ventricular (LV) performance in a series of consecutive patients with nonischemic dilated cardiomyopathy.

Background. Reduction of LV systolic function in patients with heart failure is associated with an increase of LV volume and alteration of its shape. Recently, PLV, a novel surgical procedure, was proposed as a treatment option to alter this process in patients with dilated cardiomyopathy.

Methods. We studied 19 patients with severely symptomatic nonischemic dilated cardiomyopathy, before and 13 ± 3 days after surgery, and 12 controls. Single-plane left ventriculography with simultaneous measurements of femoral artery pressure was performed during right heart pacing.

Results. The LV end-diastolic and end-systolic volume indexes decreased after PLV (from 169 to 102 ml/m², and from 127 to 60 ml/m², respectively, p < 0.0001 for both). Despite a decrease in LV mass index (from 162 to 137 g/m², p < 0.0001), there was a significant decrease in LV circumferential end-systolic and end-diastolic stresses (from 277 to 159 g/cm², p < 0.0001 and from 79 to 39 g/cm², p = 0.0014, respectively). Ejection fraction improved (from 24% to 41%, p < 0.0001); the stroke work index remained unchanged.

Conclusions. The PLV improves LV performance by a dramatic reduction of ventricular end-systolic and end-diastolic stresses. Further studies are needed to assess whether this effect is sustained during long-term follow-up and to define the role of PLV in the treatment of patients with dilated cardiomyopathy.     

Dissociation Between Changes in Intramyocardial Function and Left Ventricular Volumes in the Eight Weeks After First Anterior Myocardial Infarction

Objectives. We sought to examine the relation between regional changes in intramyocardial function and global left ventricular (LV) remodeling in the first 8 weeks after reperfused first anterior myocardial infarction (MI).

Background. Because of limitations in imaging methods used to date, this relation has not been thoroughly evaluated.

Methods. We studied 26 patients (21 men, 5 women; mean age 51 years) by magnetic resonance imaging (MRI) on day 5 ± 2 (mean ± SD) and week 8 ± 1 after their first anterior MI. All patients had single-vessel left anterior descending coronary artery disease and although they had received reperfusion therapy, all had regional LV dysfunction and an initial ejection fraction (EF) ≤50%. Short-axis magnetic resonance tagging was performed spanning the LV. Percent intramyocardial circumferential shortening (%S) on a topographic basis, LV mass index, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index and LV ejection fraction (LVEF) were measured.

Results. Left ventricular mass index tended to decrease, whereas the LVEDVI increased from 82 ± 24 to 96 ± 27 ml/m² (p = 0.002). Left ventricular end-systolic volume index remained unchanged, whereas LVEF increased from 39 ± 12% to 45 ± 14% (p = 0.002). Apical %S improved from 9 ± 6% to 13 ± 5% (p < 0.0001), as it did in the midanterior (6 ± 6% to 10 ± 7%, p < 0.02) and midseptal regions (8 ± 7% to 12 ± 6%, p < 0.02). Early dysfunction in remote midinferior and basal lateral regions resolved by 8 weeks. By multivariate analysis, the only significant predictor of an increase in LVEDVI over the study period was peak creatine kinase (p = 0.04).

Conclusions. In the first 8 weeks after a large, reperfused anterior MI, %S improved in the apex, midanterior and midseptal regions and normalized in remote noninfarct-related regions, but LV end-diastolic volumes also increased. This increased LVEDVI correlated with infarct size by peak creatine kinase and was not related to changes in global and regional LV function.     

Association of beta2-adrenoceptor Gln27Glu variant with body weight but not hypertension.

β₂-Adrenoceptor (β₂-ADR)-mediated vasodilatation decreases vascular reactivity and blood pressure (BP) and chromosome 5 where its gene (ADRB2R) resides and shows linkage to hypertension (HT). A Gln27Glu ADRB2R variant confers resistance to agonist-induced desensitization and enhanced vasodilator response to isoprenaline. Therefore, we carried out a case-control study in a cohort of HT and normotensive (NT) Anglo-Celtic Australian white subjects whose parents had a similar BP status as the subjects. Glu27 frequency was 0.41 in 108 HT and 0.42 in 141 NT (χ² = 0.05, P = .82). Within the HT group, the Glu27 allele was more prevalent in 61 subjects who were overweight (body mass index [BMI] ≥ 25 kg/m²) compared with 41 who were lean (BMI <25 kg/m²); ie, 0.49 v 0.31, respectively (χ² = 6.4, P = .012). Furthermore, Glu27 tracked with elevation in BMI in these subjects: 24 ± 4 kg/m², 27 ± 5 kg/m², and 28 ± 5 kg/m² for Gln/Gln, Gln/Glu, and Glu/Glu, respectively (P = .0058 by one-way ANOVA). Thus, the Gln27Glu β₂-ADR variant is excluded in HT, but might influence body weight.     

Lack of correlation between left ventricular mass and diameter of left coronary artery main trunk in hypertensive patients

The study was designed to evaluate whether the increase in left ventricular (LV) mass in essential hypertensives (H) is associated with a proportional increase in diameter of the left coronary artery (LCA) trunk. Twenty-six hypertensives, 14 with left ventricular hypertrophy (LVH) (left ventricular mass index [LVMI] ≥>134 g/m² in men and ≥110 g/m² in women) and 12 without LVH, and 10 normotensive controls (C) underwent clinical laboratory and echocardiographic transthoracic examination. LV dimensions were measured according to the Penn convention and LV mass calculated by the formula of Devereux. The LCA main trunk was visualized by two-dimension short axis view at the level of the great vessels section, and the diameter measured as intima–intima distance at end-diastole. Hypertensives with and without LVH and C had similar age, sex, and body surface area distribution. LVMI was, by definition, significantly higher in H with LVH than in H without LVH and in C (144 ± 21, 113 ± 13, and 98 ± 10 g/m², P < .01), whereas the diameter of the LCA trunk was similar in all groups (0.48 ± 0.1, 0.48, and 0.46 cm, respectively). There was no significant correlation between LVMI and LCA diameter in H (r = 0.21, P = not significant). The diameter of LCA trunk was significantly correlated only with BSA (r = 0.5, P < .01), LV end-systolic and end-diastolic diameters (r = 0.5 and r = 0.4, P < .05). Our data suggest that in H the increase in LVM is not associated with a concomitant increase of epicardial coronary artery diameter, and this finding may account in part for the impairment of coronary blood flow reserve in LVH.     

Increased myocardial ultrasonic reflectivity is associated with extreme hypertensive left ventricular hypertrophy: A tissue characterization study in humans

We assessed myocardial reflectivity pattern in a large spectrum of left ventricular mass values, covering the extremes from absent to severe myocardial hypertensive hypertrophy.

Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to the morphometrically evaluated collagen content in humans.

We enrolled 88 essential hypertensives. With an echo prototype implemented in our Institute, integrated values of the radiofrequency signal of myocardial walls were obtained and normalized for those of the pericardium (Integrated Backscatter Index, IBI, %). Left ventricular mass index (LVMI) was measured by Devereux formula.

There was a weak correlation between septal IBI and LVMI (r = 0.35; P < .001). On the basis of LVMI values, three groups of hypertensives were identified, with absent (Group I, n = 23; LVMI < 125 g/m²), mild to moderate (Group II, n = 44; LVMI from 125 to 174 g/m²), or severe (Group III, n = 21; LVMI > 175 g/m²) left ventricular hypertrophy. The Integrated Backscatter Index in the septum was lower in patients of Group I (IBI = 23.3% ± 3.6%) and II (IBI = 26.5 ± 7.6; P = NS v Group I), in comparison with patients of Group III (IBI = 31.1 ± 5.9; P < .02 v II; P < .0001 v I).

An increased myocardial wall reflectivity is detectable only in the presence of extreme forms of hypertensive left ventricular hypertrophy.     

Effect of increasing heart rate in patients with aortic regurgitation: Effect of incremental atrial pacing on scintigraphic, hemodynamic and thermodilution measurements

This study was performed to assess the effect of pacing-induced tachycardia in patients with aortic regurgitation. In 12 patients (5 men and 7 women with a mean age of 53 years) with aortic regurgitation, left ventricular end-diastolic and end-systolic volume indexes were measured with multigated equilibrium blood pool imaging, and forward cardiac index was determined with thermodilution, both at rest (mean heart rate ± standard deviation 72 ± 8 beats/min) and during atrial pacing at 100 and 120 beats/min. Pacing caused a decremental reduction in left ventricular end-diastolic and end-systolic volume indexes and radionuclide-determined stroke volume index but no change in radionuclide-determined cardiac index or left ventricular ejection fraction. Forward cardiac index increased incrementally from the baseline value at rest to that at 120 beats/min despite a decremental reduction in stroke volume index. There was a stepwise decrease in regurgitant volume/stroke (46 ± 20 ml/m² at baseline, 27 ± 15 at 120 beats/min; p < 0.05) but no change in regurgitant volume/min (3.38 ± 1.80 Iiters/min per m² at baseline, 3.22 ± 1.78 at 120 beats/min; difference not significant [NS]) or regurgitant fraction (0.54 ± 0.13 at baseline, 0.49 ± 0.13 at 120 beats/min; NS). Mean femoral arterial, pulmonary arterial and pulmonary capillary wedge pressures did not change with pacing.     

Results of partial left ventriculectomy for dilated cardiomyopathy: hemodynamic, clinical and echocardiographic observations

OBJECTIVES

The study was done to prospectively measure the echocardiographic, hemodynamic and clinical outcomes after partial left ventriculectomy (PLV).

BACKGROUND

Although PLV can improve symptoms of advanced heart failure, immediate postoperative echocardiographic findings remain abnormal.

METHODS

Fifty-nine patients with cardiomyopathy and advanced heart failure underwent PLV and concomitant mitral valve surgery between May 1996 and December 1997. Thirty-nine percent were on inotropic therapy. All were New York Heart Association (NYHA) functional class III or IV. Mechanical circulatory support (LVAD) and transplant were provided for rescue therapy when hemodynamic compromise occurred. Patients were followed for a mean of 405 ± 168 days, and clinical, echocardiographic and hemodynamic measures were obtained preoperatively, immediately postoperatively, and at 3 and 12 months prospectively.

RESULTS

Comparing preoperative and 12-month postoperative values in event-free survivors, we found: NYHA functional class improved from 3.6 to 2.1, p < 0.0001; peak oxygen consumption increased from 10.8 to 16.0 ml/kg/min, p < 0.0001; LV ejection fraction increased from 13 ± 6.0% to 24 ± 6.9%, p < 0.0001; LV end diastolic diameter decreased from 8.2 ± 1.03 to 6.2 ± 0.64 cm, p < 0.0001, and volume was reduced from 167 ± 60 to 105 ± 38 ml/m², P = 0.02. Central hemodynamics did not normalize after surgery.

CONCLUSIONS

Partial left ventriculectomy can provide structural remodeling of the heart that may result in temporary improvement in clinical compensation. However, perioperative failures and the return of heart failure limit the propriety of this procedure.     

Computer analysis of left ventricular dynamic geometry in man

Analysis of left ventricular performance in 20 normal patients was undertaken using biplane cineangiography and a semiautomatic computer image processing system. The analysis included evaluation of volumes, ejection fraction, regional shortening, patterns of ejection and filling and, when simultaneous left ventricular pressure was recorded, stroke work, stroke power, wall stress and internal myocardial work. All of these data were calculated from digitized images stored permanently on digital magnetic tape, and can be reproduced without reanalysis of the cine film. Normal left ventricular function is described by an end-diastolic volume index of 82 ± 3 ml, an ejection fraction of 60 ± 2 percent, left ventricular mass index of 97 ± 6 g/m², peak first derivative of volume (dV/dt) of 485 ± 28 ml/sec, anterior shortening of 48 ± 2.3 percent, inferior shortening of 33 ± 1.7 percent, lateral shortening of 29 ± 1.5 percent, anterior mean shortening velocity (Vcf, in percent of end-diastolic length [L]/sec) of 1.5 ± 0.1 L/sec, inferior Vcf of 1.1 ± 0.06 L/sec and lateral Vcf of 0.94 ± 0.2 L/sec, stroke work of 1.33 ± 0.21 joules, mean stroke power of 3.7 ± 0.62 joules/sec, integrated left ventricular pressure (tension-time index) of 2,866 ± 340 mm Hg-sec, and integrated stress (stress-time index) of 7,260 ± 765 (× 10³) dynes sec/cm². Internal myocardial work was calculated from the strain energy. More Internal work was expended in circumferential than longitudinal shortening (circumferential, 0.69 ± 0.1 joules; longitudinal, 0.41 ± 0.08, P < 0.01), because hoop stress was greater than meridian stress (hoop, 201 ± 20 dynes/cm³ × 10³; meridian, 126 ± 13, P < 0.001). This analysis of left ventricular performance provides a reliable means for identifying abnormal ventricular function and may be more sensitive than any one measurement alone. The use of digital image processing makes this complex functional analysis of left ventricular performance feasible.     

Effects of intravenous administration of nicorandil on cardiovascular hemodynamics and left ventricular function

The effects of the intravenous administration of the antianginal drug, nicorandil, 50 μg/kg administered over 2 minutes, were investigated during pacing-induced ischemia in 8 patients with coronary artery disease. Hemodynamic parameters were measured and single-plane left ventriculograms were obtained in control and postpacing periods both before and after pretreatment with nicorandil. Regional wall motion of the left ventricle was assessed by measuring shortening of the radial axes originating from the center of gravity of the end-diastolic silhouette. Heart rate, left ventricular (LV) systolic pressure and end-diastolic volume index did not change in the immediate postpacing period with or without medication. LV end-diastolic pressure decreased with nicorandil, from 22.0 ± 3.4 to 17.0 ± 2.3 mm Hg (mean ± standard error of the mean) (p < 0.05), and LV systolic volume index, from 39.6 ± 8.0 to 30.4 ± 6.8 ml/m² (p < 0.05). Ejection fraction increased from 55.2 ± 5.0 to 64.3 ± 3.8% (p < 0.05). Stroke index and cardiac index (calculated from heart rate and stroke index) did not change significantly. Rapid right ventricular pacing increased the extent and degree of dyskinesia of the left ventricle, but premedication with nicorandil improved the wall motion. Thus, nicorandil has salutary effects on ventricular contractile and hemodynamic responses to transient ischemia induced by pacing stress.     

Effects of the angiotensin II antagonist losartan on endothelin-1 and norepinephrine plasma levels during cold pressor test in patients with chronic heart failure

We evaluate the acute hemodynamic and neurohormonal effects of losartan in 15 patients with symptomatic chronic heart failure (CHF), mean age 72 ± 8 years, which were classified in two subgroups: (A) Patients with left ventricular ejection fraction (LVEF) ≤0.35 (n = 7); (B) subjects with LVEF >0.35 (n = 8). Sympathetic reactivity (blood pressure, heart rate and plasma norepinephrine) and plasma endothelin-1 (ET-1) were evaluated by a cold pressor test (CPT). Single doses of losartan (50 mg p.o.) lowered delta DBP in both subgroups (A, 8 ± 9 to 0 ± 5 mmHg, P < 0.05; B, 10 ± 6 to 3 ± 4 mmHg, P < 0.05) and attenuated the rise of HR in patients with mild (4 ± 6 to −1 ± 2 bpm, P < 0.05) but not with severe (4 ± 5 to 2 ± 5 bpm, n.s.) impairment of left ventricular function. Losartan blunted the response (delta) of PNE during CPT (A, 142 ± 131 to 10 ± 74 pg/ml, P < 0.05; B, 129 ± 72 to 1 ± 144 pg/ml, P < 0.01). A significant rise in plasma ET-1 was observed during CPT in patients from subgroup B (0.64 ± 0.40 to 0.81 ± 0.40 fmol/ml, P < 0.05) but not in patients with LVEF ≤0.35 (1.79 ± 0.44 to 1.51 ± 0.66 fmol/ml, n.s.). Losartan attenuated the rise in ET-1 during CPT in patients with LVEF >0.35 (delta ET-1 0.17 ± 0.86 to 0.03 ± 0.11 fmol/ml, P < 0.05), with no significant changes in subgroup A. Acute effects of losartan were characterized by a more favorable hemodynamic and neurohumoral response in patients with chronic heart failure and preserved systolic ventricular function related to subjects with lower ejection fractions.     

Effects of intravenously administered digoxin on mild left ventricular failure in acute myocardial infarction in man

Studies were made in 10 patients with early mild left ventricular failure in acute myocardial infarction to determine the hemodynamic correlates of the condition and evaluate the effects of intravenously administered digoxin. Studies were performed within 72 hours of infarction. Patients with basilar rales, tachycardia and ventricular (S₃) gallop sound were selected for study. Findings during the control period were consistent with mild left ventricular failure. Stroke index was below normal (28 ± 7.1 ml/m²), but cardiac index was within normal limits (3.22 ± 0.60 liters/min per m²) because of tachycardia. Stroke work index was low (39 +- 13.7 g-m/m²), and pulmonary arterial end-diastolic pressure was minimally increased (15.2 ± 3.5 mm Hg).

After intravenous administration of digoxin (0.75 mg in 7 patients, 1.0 mg in 3 patients), there were no statistically significant changes in any of the measured variables when the whole group was considered. Relating stroke work index to pulmonary arterial diastolic pressure, 2 types of responses were found. Four patients had a distinct inotropic response; the other 6 patients had no significant change, or a worsening of function. The reasons for a variable response in the early phase of infarction may be related to the regional nature of infarction or possibly to humoral factors influencing myocardial performance. Data suggest that digitalis is of limited value during this stage of infarction. Further studies and more precise characterization of patients may provide insight into the role of digitalis in the early phases of acute infarction.     

Hemodynamic results of percutaneous aortic balloon valvuloplasty as assessed by sequential Doppler echocardiographic studies

We determined the sequential hemodynamic changes after percutaneous aortic balloon valvuloplasty by means of two-dimensional and Doppler echocardiographic examinations in 25 patients immediately before, immediately after, and 24 to 36 hours after valvuloplasty. An aortic valve area was determined at all three time periods by using the continuity equation from the Doppler velocity profiles. The aortic valve area by Doppler echocardiography immediately before valvuloplasty correlated with that determined by cardiac catheterization (r = 0.85, SEE = 0.08 cm²). The mean aortic valve gradient by Doppler echocardiography was 50 ± 22 mm Hg before the procedure, decreasing to 29 ± 12 mm Hg (P < 0.001), with a small, but significant, increase 1 day later to 33 ± 13 mm Hg (P < 0.001). The mean subvalvular velocity increased from 0.44 ± 0.13 to 0.52 ± 0.15 m/sec immediately after valvuloplasty (P < 0.001), increasing further to 0.60 ± 0.16 m/sec 1 day later (P < 0.001). The resultant aortic valve area increased from 0.45 ± 0.11 to 0.73 ± 0.18 cm² immediately after (P < 0.05). One day later, the aortic valve area increased further to 0.86 ± 0.19 cm² (P < 0.05). Because of the dynamic changes occurring during the first 24 to 36 hours after balloon valvuloplasty, hemodynamic measurements taken immediately after the procedure may underestimate the efficacy of this technique.     

Effect of very early angiotensin-converting enzyme inhibition on left ventricular dilation after myocardial infarction in patients receiving thrombolysis: results of a meta-analysis of 845 patients. FAMIS, CAPTIN and CATS Investigators

OBJECTIVES

We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition <9 h after myocardial infarction (MI) on left ventricular (LV) dilation in patients receiving thrombolysis.

BACKGROUND

The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism.

METHODS

The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective.

RESULTS

The ACE inhibitor was started 3.2 ± 1.7 h after the patients’ first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m² (95% confidence interval [CI] −1.5 to 2.5, P = 0.61), and the systolic volume index by 0.5 ml/m² (95% CI −1.0 to 1.9, P = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients.

CONCLUSIONS

We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI.     

Diadenosine Polyphosphates’ Action on Calcium and Vessel Contraction

The effects of the endogenous, platelet-derived vasoactive compounds, diadenosine tetraphosphate (AP₄A), diadenosine pentaphosphate (AP₅A), and diadenosine hexaphosphate (AP₆A) on the vasoconstriction of isolated rat renal resistance vessels and rat aortic strips were measured using a vessel myograph. In addition, the effects of AP₄A, AP₅A, and AP₆A on the cytosolic free calcium concentration ([Ca²⁺]_i) were evaluated in cultured rat vascular smooth muscle cells (VSMC) using the fluorescent dye technique. Diadenosine polyphosphates dose-dependently increased the force of renal resistance vessels and isolated aortic strips. The administration of 10 μmol/L AP₄A, AP₅A, or AP₆A significantly increased the force of isolated renal resistance vessels by 3.48 ± 0.43 mN (n = 8), 2.14 ± 0.40 mN (n = 12), or 2.70 ± 0.31 mN (n = 11, each P < .01 compared with resting tension), respectively. The administration of 10 μmol/L AP₄A, AP₅A, or AP₆A significantly increased the force of isolated aortic strips by 2.45 ± 0.97 mNewton (n = 10), 2.70 ± 0.30 mN (n = 6), or 1.48 ± 0.20 mN (each P < .01 compared with resting tension), respectively. The administration of 10 μmol/L AP₄A, AP₅A, or AP₆A significantly increased [Ca²⁺]_i in VSMC to a peak concentration of 314 ± 60 nmol/L (n = 6), 247 ± 25 nmol/L (n = 15), or 332 ± 100 nmol/L (n = 5), respectively (each P < .01 compared with resting value). Both the diadenosine polyphosphate-induced vasoconstriction and [Ca²⁺]_i increase was significantly reduced in the absence of extracellular calcium or after administration of a specific inhibitor of P2 purinoceptors. It is concluded that diadenosine polyphosphates increase [Ca²⁺]_i and hence cause vessel constriction.     

Reactive oxygen species in essential hypertension and non–insulin-dependent diabetes mellitus

To evaluate whether increased levels of reactive oxygen species (ROS) are involved in the pathogenesis of essential hypertension (EH) and non–insulin-dependent diabetes mellitus (NIDDM), both resting and stimulated levels of intracellular ROS were measured in lymphocytes from patients with EH (n = 10), NIDDM (n = 16) and age-matched healthy individuals (control subjects, n = 19). ROS was monitored with the dye, dihydrorhodamine-123 (DHR; 1 μmol/L) in the presence or absence of superoxide dismutase (superoxide scavenger), sodium azide (singlet oxygen/hydrogen peroxide scavenger), genistein (tyrosine kinase inhibitor), or bisindolylmaleimide (protein kinase C inhibitor). Simultaneous monitoring of cytosolic [Ca²⁺]_i was done with fura-2. Resting ROS levels were significantly higher in NIDDM (4.71 ± 0.25 nmol/10⁶ cells; mean ± SEM, P < .05) compared with EH (4.03 ± 0.22 nmol/10⁶ cells) or controls (4.05 ± 0.15 nmol/10⁶ cells). The formyl-Met-Leu-Phenylalanine-(fMLP)–induced ROS generation was significantly higher in NIDDM (21.92 ± 2.23 nmol/10⁶ cells; P < .05) compared with EH (14.58 ± 1.90 nmol/10⁶ cells) or control (16.06 ± 1.22 nmol/10⁶ cells). The fMLP-induced ROS increase was significantly reduced in the presence of sodium azide in all groups (P < .01) but was largely unaffected in the presence of SOD. Genistein and bisindolylmaleimide significantly inhibited the fMLP-induced ROS in all groups. The fMLP-induced [Ca²⁺]_i increase was significantly higher in NIDDM (71 ± 12 nmol/L, P < .01) compared with EH (42 ± 4 nmol/L) and control subjects (35 ± 3 nmol/L). Phytohemagglutinin was more effective in increasing [Ca²⁺]_i than ROS. It is concluded that ROS may play a role in the metabolic syndrome of NIDDM but not in EH.