Determinants of left ventricular untwisting behaviour in patients with dilated cardiomyopathy: analysis by two-dimensional speckle tracking.

BACKGROUND/OBJECTIVE: Left ventricular (LV) untwisting velocity has emerged as a novel index of LV diastolic function since it is thought to be related to LV diastolic suction. However, the pathophysiology of LV untwisting behavior has not been fully investigated. The aim of this study was to investigate the determinants of LV peak untwisting velocity in patients with dilated cardiomyopathy (DCM). METHODS: 101 patients with DCM (mean age 60 (SD 13) years) and 50 control subjects were evaluated. After a standard echocardiographic examination, peak torsion and peak untwisting velocity were measured using two-dimensional speckle-tracking imaging. Radial dyssynchrony was assessed by speckle-tracking radial strain analysis. Tissue Doppler derived systolic (Ts-SD) and diastolic (Te-SD) dyssynchrony indices were also assessed. RESULTS: The patients with DCM had significantly smaller peak torsion (p<0.001) and peak untwisting velocity (p<0.001) and greater radial dyssynchrony (p<0.001) and Ts-SD (p<0.001) and Te-SD (p = 0.001) compared with the control subjects. The peak untwisting velocity was correlated with end-systolic volume index (r = 0.524, p<0.001), E/e' (r = 0.365, p<0.001), radial dyssynchrony (r = 0.578, p<0.001), Ts-SD (p<0.001), Te-SD (p<0.001) and peak torsion (r = -0.635, p<0.001) in patients with DCM(. )Multivariate analysis revealed that peak torsion, radial dyssynchrony and E/e' were independent predictors of peak untwisting velocity in patients with DCM (standard coefficient -0.483, p<0.001, 0.330, p<0.001 and 0.241, p = 0.001, respectively). CONCLUSION: These results suggest that strain-based LV radial dyssynchrony and E/e' as well as LV torsion are related to diastolic untwisting behaviour in patients with DCM.

Possible link between large artery stiffness and coronary flow velocity reserve.

BACKGROUND: Population studies have shown that increased large artery stiffness is an independent predictor of cardiovascular events. Experimental studies have shown that a stiff aorta is associated with decreased coronary blood flow. However, a link between large artery stiffness and coronary microvascular function in the clinical setting has not been demonstrated previously. OBJECTIVE: To evaluate the relationship between large artery stiffness and coronary flow velocity reserve (CFVR). PATIENTS AND METHODS: 102 consecutive subjects (mean (SD) age 62 (10) years) without coronary and peripheral arterial disease were enrolled in the study. After 15 minutes' rest, measurements were obtained of brachial-ankle pulse wave velocity (baPWV), augmentation index (AIx) from a carotid pulse tracing, and transthoracic echocardiographic measures, including coronary flow velocity in the left anterior descending coronary artery. In addition, coronary flow velocity during hyperaemia was measured during an intravenous infusion of adenosine triphosphate. CFVR was defined as the ratio of hyperaemic to basal coronary velocity. RESULTS: Subjects with decreased CFVR (< 2.5; n = 40) had significantly higher baPWV (1848 (369) cm/s vs 1548 (333) cm/s; p<0.001), greater AIx (25.3 (11.0)% vs 16.3 (20.0)%; p = 0.01) and greater pulse pressure (PP) (64 (13) mm Hg vs 54 (13) mm Hg; p<0.001) than those with normal CFVR (> or = 2.5; n = 62). Multivariate analysis showed that AIx and PP were independent predictors of CFVR (r = -0.32, p<0.001 and -0.25, p = 0.02, respectively). CONCLUSIONS: The data suggest that large artery stiffening is linked to a reduction of CFVR, which may partially explain the higher cardiac event rate in patients with increased large artery stiffness.

Usefulness of selective myocardial contrast echocardiography in percutaneous transluminal septal myocardial ablation: a case report.

A 67-year-old woman with hypertrophic obstructive cardiomyopathy that was refractory to medical treatment underwent percutaneous transluminal septal myocardial ablation (PTSMA). The septal branch supplying the myocardium involved in the left ventricular outflow tract (LVOT) obstruction was identified by selective myocardial contrast echocardiography (MCE). MCE for the third and largest septal branch opacified the right side of the mid-septal myocardium and MCE for the second septal branch opacified the right side of the basal portion of the septal myocardium. Finally, contrast agent was injected into the first, small branch, which opacificied the myocardium protruding into the LVOT. Subsequently, septal myocardial ablation for this vessel with intracoronary alcohol was performed, followed by a reduction of the LVOT gradient and successful, dramatic improvement in the patient's clinical condition. Selective MCE was very useful to identify the appropriate septal branch for PTSMA and enabled maximal effect of this treatment with minimal myocardial damage.

Site-directed mutagenesis of the putative distal helix of peroxygenase cytochrome P450.

CYP152A1 is an unusual, peroxygenase enzyme that catalyzes the beta- or alpha-hydroxylation of fatty acids by efficiently introducing an oxygen atom from H2O2 to the fatty acid. To clarify the mechanistic roles of amino acid residues in this enzyme, we have used site-directed mutagenesis of residues in the putative distal helix and measured the spectroscopic and enzymatic properties of the mutant proteins. Initially, we carried out Lys-scanning mutagenesis of amino acids in this region to determine residues of CYP152A1 that might have a mechanistic role. Among the Lys mutants, only P243K gave an absorption spectrum characteristic of a nitrogenous ligand-bound form of a ferric P450. Further investigation of the Pro243 site revealed that a P243H mutant also exhibited a nitrogen-bound form, but that the mutants P243A or P243S did not. On the hydroxylation of myristic acid by the Lys mutants, we observed a large decrease in activity for R242K and A246K. We therefore examined other mutants at amino acid positions 242 and 246. At position 246, an A246K mutant showed a roughly 19-fold lower affinity for myristic acid than the wild type. Replacing Ala246 with Ser decreased the catalytic activity, but did not affect affinity for the substrate. An A246V mutant showed slightly reduced activity and moderately reduced affinity. At position 242, an R242A showed about a fivefold lower affinity than the wild type for myristic acid. The Km values for H2O2 increased and Vmax values decreased in the order of wild type, R242K, and R242A when H2O2 was used; furthermore, Vmax/Km was greatly reduced in R242A compared with the wild type. If cumene hydroperoxide was used instead of H2O2, however, the Km values were not affected much by these substitutions. Together, our results suggest that in CYP152A1 the side chain of Pro243 is located close to the iron at the distal side of a heme molecule; the fatty acid substrate may be positioned near to Ala246 in the catalytic pocket, although Ala246 does not participate in hydrophobic interactions with the substrate; and that Arg242 is a critical residue for substrate binding and H2O2-specific catalysis.

Structure and function of the left ventricle and carotid artery in hemodialysis patients.

Hemodialysis patients frequently show associated hypertension, which can lead to a number of cardiovascular complications. The aim of this study was to assess the effects of hypertension on the structure and function of the carotid artery and left ventricle (LV) in hemodialysis patients. In addition, we investigated the contribution of hemodialysis and other risk factors. Fifty-two hemodialysis patients, 71 hypertensive patients (HT group) and 30 normotensive subjects (NT group) were included in this study. Hemodialysis patients were divided into two groups: 35 patients with hypertension (HDHT group), and 17 patients without hypertension (HDNT group). We measured intima-media thickness (IMT), plaque score, end-diastolic diameter, and stiffness index beta of the carotid artery by ultrasonography, and LV mass index (LVMi), endocardial fractional shortening (FS), and midwall FS (MWS) by echocardiography. A multiple stepwise regression analysis including hemodialysis, hypertension, diabetes mellitus, and other risk factors was also performed. IMT was significantly higher in the HT and HDHT groups than in the NT group. Plaque score and diameter of the carotid artery were higher in the HDHT group than in the other three groups. The stiffness index beta was higher in the HDHT group than in the non-hemodialysis groups. In multivariate analysis, IMT was independently correlated with age and hypertension. Plaque score and stiffness index beta were independently associated with age, hypertension, and hemodialysis. LVMi was higher in HT and hemodialysis-patients groups than in the NT group. Hypertension and hemodialysis were strong and independent predictors of LVMi. FS showed no significant differences among the four groups, but MWS was significantly lower among the hemodialysis patients than in the NT group. MWS was independently correlated with hemodialysis and diabetes. In conclusion, hemodialysis per se advanced both atherosclerosis and arteriosclerosis of the carotid artery. Moreover, it increased LVMi and caused cardiac dysfunction. Associated hypertension might thus accelerate the progression of atherosclerosis and arteriosclerosis of the carotid artery and the increase of LVMi.

[Relationship between the fecal mutagenicity and metal content, smoking habit and dietary intake].

OBJECTIVE: The study was carried out to collect basic data on exposure of mucous cells of the large intestine to mutagens by investigating the genotoxicity of fecal samples from the urban population. Simultaneously, relations with food intake (food groups and nutritive components), lifestyle factors and fecal metal content was investigated. METHODS: A total of 199 self-collected fecal samples from middle aged healthy volunteer living in urban areas of Osaka city were freeze-dried and ground in a mill. The mutagenicity of aqueous extracts of the ground samples was measured by the umu-test. Metal content of the feces was analysed by atomic absorption spectrophotometlly. On the day previous to the feces collection, the contents of meals were recorded and confirmed by interview with a dietitian. Quantification of nutritive components was carried out using the 4th edition of the Japan Food Standard Vomposition Table. RESULTS: Mutagenicity of feces was higher in males than in females, and in those aged 40-49 years than 50-69 years in males but not females. Large differences were found for content of 8 metals in the feces; concentrations were in the decreasing order of calcium, potassium, magnesium, sodium, zinc, iron, manganese and copper, the highest being 20.4 mg for calcium and the lowest was 53.5 micrograms for copper. Between the metal contents and mutagenicity, values for zinc and iron showed positive correlations and for sodium a negative correlation under S9(+) conditions. A weak but significant correlation was observed between the numbers of cigarettes smoked per day and S9 (+) mutagenicity. However we could not find any relation with food groups or nutritive components. CONCLUSION: It is well known that human feces contain many mutagens and carcinogens and that these can act directly on the mucous membrane of large intestine. Therefore, it is very important to estimate exposure levels. From the present data we can conclude that relations between mutation-activity of the feces and diet are complex. Their elucidation will require a large number of volunteers who have similar living conditions to obtain appropriate data.

Effect of angiotensin-converting enzyme inhibitor on cardiopulmonary baroreflex sensitivity in patients with acute myocardial infarction.

We evaluated the effect of angiotensin-converting enzyme inhibition (quinapril) on cardiopulmonary baroreflex sensitivity in 30 patients with uncomplicated myocardial infarction (quinapril group, 15 patients; placebo group, 15 patients) at 5 and 10 days after the onset of myocardial infarction. This study indicates that quinapril improved cardiopulmonary baroreflex and thus reduced sympathetic outflow in patients with acute myocardial infarction.

Fatty acid-specific, regiospecific, and stereospecific hydroxylation by cytochrome P450 (CYP152B1) from Sphingomonas paucimobilis: substrate structure required for alpha-hydroxylation.

Fatty acid alpha-hydroxylase from Sphingomonas paucimobilis is an unusual cytochrome P450 enzyme that hydroxylates the alpha-carbon of fatty acids in the presence of H2O2. Herein, we describe our investigation concerning the utilization of various substrates and the optical configuration of the alpha-hydroxyl product using a recombinant form of this enzyme. This enzyme can metabolize saturated fatty acids with carbon chain lengths of more than 10. The Km value for pentadecanoic acid (C15) was the smallest among the saturated fatty acids tested (C10-C18) and that for myristic acid (C14) showed similar enzyme kinetics to those seen for C15. As shorter or longer carbon chain lengths were used, Km values increased. The turnover numbers for fatty acids with carbon chain lengths of more than 11 were of the same order of magnitude (10(3) min(-1)), but the turnover number for undecanoic acid (C11) was less. Dicarboxylic fatty acids and methyl myristate were not metabolized, but monomethyl hexadecanedioate and omega-hydroxypalmitic acid were metabolized, though with lower turnover values. Arachidonic acid was a good substrate, comparable to C14 or C15. The metabolite of arachidonic acid was only alpha-hydroxyarachidonic acid. Alkanes, fatty alcohols, and fatty aldehydes were not utilized as substrates. Analysis of the optical configurations of the alpha-hydroxylated products demonstrated that the products were S-enantiomers (more than 98% enantiomerically pure). These results suggested that this P450 enzyme is strictly responsible for fatty acids and catalyzes highly stereo- and regioselective hydroxylation, where structure of omega-carbon and carboxyl carbon as well as carbon chain length of fatty acids are important for substrate-enzyme interaction.

Infection of left atrial thrombus associated with mitral stenosis: A case report.

We describe the first reported case of an infected left atrial thrombus. The case of the 65-year-old male patient in this report was associated with mitral stenosis and involved Escherichia coli, and was treated successfully with surgical resection of the infected thrombus. This case suggests that such infection should be considered as a possible complication of intracardiac thrombus when bacteremia is present.

Characterization of the ybdT gene product of Bacillus subtilis: novel fatty acid beta-hydroxylating cytochrome P450.

We have characterized the gene encoding fatty acid alpha-hydroxylase, a cytochrome P450 (P450) enzyme, from Sphingomonas paucimobilis. A database homology search indicated that the deduced amino acid sequence of this gene product was 44% identical to that of the ybdT gene product that is a 48 kDa protein of unknown function from Bacillus subtilis. In this study, we cloned the ybdT gene and characterized this gene product using a recombinant enzyme to clarify function of the ybdT gene product. The carbon monoxide difference spectrum of the recombinant enzyme showed the characteristic one of P450. In the presence of H2O2, the recombinant ybdT gene product hydroxylated myristic acid to produce beta-hydroxymyristic acid and alpha-hydroxymyristic acid which were determined by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry. The amount of these products increased with increasing reaction period and amount of H2O2 in the reaction mixture. The amount of beta-hydroxyl product was slightly higher than that of alpha-hydroxyl product at all times during the reaction. However, no reaction products were detected at any time or at any concentration of H2O2 when heat-inactivated enzyme was used. HPLC analysis with a chiral column showed that the beta-hydroxyl product was nearly enantiomerically pure R-form. These results suggest that this P450 enzyme is involved in a novel biosynthesis of beta-hydroxy fatty acid.

Angioplasty-bypass surgery combination therapy: case study of an elderly patient with unstable angina and colon cancer.

An 83-year-old man was admitted with refractory unstable angina and severe anemia. Colonofiberscopy revealed hemorrhagic colon cancer in the transverse colon. Coronary angiography showed total occlusion of the right coronary artery (RCA), diffuse, calcified 90% stenosis of the middle portion of the left anterior descending artery (LAD); and fair collaterals from the LAD to the RCA. Coronary revascularization was considered prior to colectomy, but because of the patient's advanced age and hemorrhagic cancer, conventional coronary aorta bypass grafting (CABG) using extracorporeal circulation, as well as coronary stenting requiring antiplatelet therapy, were regarded as inadvisable. Percutaneous transluminal coronary angioplasty (PTCA) for the LAD carried the risk of suboptimal coronary stenting. Thus, the patient was first treated with PTCA for the occluded RCA, followed 7 days later by a left internal thoracic artery graft to the LAD on the beating heart without extracorporeal circulation. The patient was stable thereafter. This approach to coronary revascularization may be suitable for patients for whom anticoagulation or antiplatelet therapy are contraindicated, or when complete revascularization would be difficult with CABG or PTCA alone.

Importance of intrinsic calf vasodilator capacity in determining distribution of skeletal muscle perfusion during supine bicycle exercise in patients with left ventricular dysfunction.

BACKGROUND: Distribution of skeletal muscle perfusion during exercise is an important factor in determining exercise capacity and is markedly impaired in patients with cardiac disease. This study examined the importance of intrinsic calf vasodilator capacity in determining distribution of skeletal muscle perfusion during supine bicycle exercise in patients with left ventricular dysfunction. METHODS: We studied 19 patients with left ventricular dysfunction (left ventricular ejection fraction <45%) after myocardial infarction. All the patients underwent cardiopulmonary exercise testing with measurements of central hemodynamics, leg blood flow (LBF), and the percentage of cardiac output distributed to both legs (%LBF). Calf reactive hyperemic flow (RH) was measured by venous occlusive plethysmography at supine rest. RESULTS: LBF at peak exercise was closely related to peak cardiac output and RH. Furthermore, %LBF at peak exercise had modest correlation with peak cardiac output and good correlation with RH. Although peak cardiac output and RH were independent determinants of LBF at peak exercise by multiple regression analysis, RH had higher correlation with %LBF at peak exercise than peak cardiac output. Despite marked changes in other hemodynamic variables, nonleg blood flow during exercise was constantly maintained at a level identical to resting value. CONCLUSIONS: Calf vasodilator capacity, which was the major determinant of distribution of skeletal muscle perfusion during exercise, may have contributed to maintaining perfusion of important nonexercising regions during exercise in patients with left ventricular dysfunction.

Phytanic acid alpha-hydroxylation by bacterial cytochrome P450.

Fatty acid alpha-hydroxylase, a cytochrome P450 enzyme, from Sphingomonas paucimobilis, utilizes various straight-chain fatty acids as substrates. We investigated whether a recombinant fatty acid alpha-hydroxylase is able to metabolize phytanic acid, a methyl-branched fatty acid. When phytanic acid was incubated with the recombinant enzyme in the presence of H2O2, a reaction product was detected by gas chromatography, whereas a reaction product was not detected in the absence of H2O2. When a heat-inactivated enzyme was used, a reaction product was not detected with any concentration of H2O2. Analysis of the methylated product by gas chromatography-mass spectrometry revealed a fragmentation pattern of 2-hydroxyphytanic acid methyl ester. By single-ion monitoring, the mass ion and the characteristic fragmentation ions of 2-hydroxyphytanic acid methyl ester were detected at the retention time corresponding to the time of the product observed on the gas chromatogram. The Km value for phytanic acid was approximately 50 microM, which was similar to that for myristic acid, although the calculated Vmax for phytanic acid was about 15-fold lower than that for myristic acid. These results indicate that a bacterial cytochrome P450 is able to oxidize phytanic acid to form 2-hydroxyphytanic acid.

Spontaneous spinal subarachnoid hematoma of unknown pathogenesis: case reports.

OBJECTIVE AND IMPORTANCE: The occurrence of spontaneous spinal subarachnoid hematoma of unknown pathogenesis is extremely rare. In the cases reported to date, the hematoma, located dorsal to the spinal cord (dorsal type), has caused paraplegia and has required emergency surgical intervention. CLINICAL PRESENTATION: We examined two patients who sustained spontaneous spinal subarachnoid hematoma. Both experienced sudden back pain, but there were no symptoms of spinal cord compression. Magnetic resonance imaging revealed spinal subarachnoid hematoma located ventral to the spinal cord (ventral type). INTERVENTION: Both patients were treated conservatively, and follow-up examinations have revealed that they have remained neurologically normal for 7 years and 6 months, respectively. CONCLUSION: We postulate that there are two types of spontaneous spinal subarachnoid hematoma of unknown pathogenesis (ventral and dorsal types), each of which presents a distinct clinical picture and prognosis. Ventral type hematoma may be one of the causes of acute back pain, and because of its benign prognosis, surgical treatment may not be necessary.

Plasma adrenomedullin concentrations and cardiac and arterial hypertrophy in hypertension.

It has been reported that plasma concentrations of adrenomedullin (AM), a novel vasodilator peptide, are higher in patients with essential hypertension than those in normotensive subjects. To clarify the clinical significance of increased levels of AM in patients with essential hypertension, in this study we examined the relationship between plasma concentrations of AM and the structure of the left ventricle or carotid artery. Plasma AM concentrations; renin activity; and norepinephrine, epinephrine, and creatinine concentrations in 50 patients with untreated essential hypertension without renal dysfunction and heart failure were measured. We also measured the mean wall thickness of the left ventricle and left ventricular mass index by M-mode echocardiography and intimal-medial thickness and arterial distensibility of the carotid artery by ultrasonography. Hypertensive patients were divided into two groups: hypertensives with and those without left ventricular hypertrophy. Plasma AM concentrations in hypertensive patients with left ventricular hypertrophy were significantly higher than in hypertensive patients without left ventricular hypertrophy (7.87+/-2.70 vs 5.74+/-1.65 fmol/mL, P<.01). In all hypertensive patients, plasma AM concentrations were not correlated with blood pressure, plasma renin activity, plasma norepinephrine, plasma epinephrine, or plasma creatinine concentration. Plasma AM concentrations were positively correlated with left ventricular mass index or mean wall thickness (r=.37, P=.009; r=.40, P=.004, respectively) and inversely correlated with carotid artery distensibility (r=-.33, P=.02), whereas plasma AM concentrations were not correlated with intimal-medial thickness. These results suggest that the observed elevation of plasma AM in patients with essential hypertension with normal renal function may be partly related to cardiac hypertrophy and decreased carotid artery distensibility.

Left atrial function as a reliable predictor of exercise capacity in patients with recent myocardial infarction.

STUDY OBJECTIVE: To examine the relation between left atrial (LA) function and exercise performance. DESIGN AND SETTING: Retrospective study at a referral cardiopulmonary exercise laboratory in a university hospital. PATIENTS: Forty-one patients with recent myocardial infarction. INTERVENTIONS: M-mode echocardiography and cardiopulmonary exercise testing combined with radionuclide ventriculography. MEASUREMENTS AND RESULTS: Hemodynamic measurements were obtained at rest and peak exercise. LA fractional shortening at rest was used as an index of global LA function. LA fractional shortening had fair correlations with peak oxygen consumption (r=0.67, p<0.01) and exercise duration (r=0.71, p<0.01). Although there were no significant relations between LA fractional shortening and hemodynamic measurements at rest, LA fractional shortening was positively related to peak cardiac output (r=0.61, p<0.01) and peak stroke volume (r=0.57, p<0.01), and negatively related to peak pulmonary arterial wedge pressure (r=-0.44, p<0.05). In addition, LA fractional shortening correlated significantly with an increase in left ventricular (LV) end-diastolic volume from rest to peak exercise (r=0.48, p<0.02), but did not correlate with the changes in ejection fraction and end-systolic volume during exercise. An increase in LV end-diastolic volume during exercise was significantly related to peak oxygen consumption (r=0.46, p<0.02), peak cardiac output (r=0.60, p<0.01), and peak stroke volume (r=0.53, p<0.01), whereas the changes in ejection fraction and end-systolic volume during exercise were not related to these indexes. CONCLUSIONS: Exercise capacity and LV performance during exercise were mainly dependent on LV diastolic filling rather than systolic contraction during exercise. LA fractional shortening at rest reflected LV diastolic filling during exercise and, therefore, predicted cardiac output and stroke volume responses to exercise and exercise capacity in patients with recent myocardial infarction.

Effects of ACE inhibitors versus calcium antagonists on left ventricular morphology and function in patients with essential hypertension.

We compared the effects of two long-term antihypertensive treatments (ACE inhibitors vs. Ca antagonists) on left ventricular hypertrophy (LVH) and LV function in patients with essential hypertension and LVH. After a washout period of at least 4 wk, ceronapril or delapril was administered to 18 patients and nifedipine or nicardipine to 15 patients for 6 months. Mean blood pressure (MBP), LV mass (LVM), LV fractional shortening (FS), systolic time intervals (ejection time/pre-ejection period ratio = ET/PEP), and isovolumic relaxation time (IRT) were examined in the pretreatment phase and after 6 months of treatment. MBP and LVM significantly and similarly decreased after treatment in both groups (ACE inhibitors vs. Ca antagonists, delta MBP: -17.1 +/- 1.3 vs. -16.9 +/- 1.6%; delta LVM: -11.7 +/- 2.7 vs. -10.0 +/- 3.8%, both p = not significant). ACE inhibitors produced significant beneficial changes in FS, ET/PEP, and IRT after treatment as compared with Ca antagonists (ACE inhibitors vs. Ca antagonists, delta FS: 11.8 +/- 3.3 vs. 5.1 +/- 4.1%, p < 0.05; delta ET/PEP: 11.9 +/- 2.3 vs. 4.7 +/- 6.4%, p < 0.05; delta IRT: -12.0 +/- 3.4 vs. -3.8 +/- 6.1%, p < 0.05). The results indicate that both ACE inhibitors and Ca antagonists induce significant and similar reductions in blood pressure and LVM in hypertensive patients. ACE inhibitors produce significant improvements in LV function in both systolic and diastolic phases as compared with Ca antagonists.

Both a calcium antagonist and ACE inhibitor reverse hypertrophy in hypertension but a calcium antagonist also depresses contractility.

The aim of this study was to compare the effects of a calcium antagonist, nicardipine SR, with an angiotensin-converting enzyme (ACE) inhibitor, alacepril, on the regression of left ventricular hypertrophy (LVH) and function. Twenty patients with LVH, aged 42-78 years, were treated with nicardipine SR or alacepril. Ten patients were treated with nicardipine SR (40-80 mg) for 21 months, and the other 10 patients were treated with alacepril (25-100 mg) for 18 months. All patients underwent echocardiography to assess left ventricular structure and function before and after the treatment. After nicardipine SR or alacepril treatment, blood pressure was decreased significantly from 176.0 +/- 13.9/97.0 +/- 5.3 mmHg to 140.0 +/- 14.0/77.4 +/- 7.2 mmHg and from 168.2 +/- 22.3/99.0 +/- 5.5 mmHg to 138.4 +/- 12.5/85.2 +/- 9.7 mmHg, respectively (both p < 0.01), whereas heart rate did not change (73.8 +/- 14.6 beats/min vs. 69.9 +/- 13.5 beats/min and 71.6 +/- 9.7 vs. 65.8 +/- 8.1 beats/min, respectively). The left ventricular mass index decreased significantly from 133.2 +/- 11.7 g/m2 to 114.4 +/- 15.7 g/m2 with nicardipine SR and from 137.1 +/- 14.8 g/m2 to 99.3 +/- 23.0 g/m2 with alacepril (both p < 0.01). The fractional shortening, peak shortening rate, and peak lengthening rate all improved significantly after each treatment. The end-systolic wall stress/left ventricular end-systolic volume index, as an index of left ventricular contractility, was decreased significantly after treatment with nicardipine SR but was not changed after treatment with alacepril. In conclusion, both nicardipine SR and alacepril similarly reduced LVH and improved left ventricular systolic and diastolic function. However, alacepril did not alter left ventricular contractility, whereas nicardipine SR decreased left ventricular contractility.

Effects of left ventricular peak filling rate on exercise capacity 3 to 6 weeks after acute myocardial infarction.

STUDY OBJECTIVES: To investigate the importance of early left ventricular (LV) diastolic filling on maintenance of exercise performance, we examined peak filling rate and its relation to exercise capacity during upright bicycle exercise in patients with recent myocardial infarction. DESIGN: Retrospective analysis of data of cardiopulmonary exercise testing characteristics in patients with recent myocardial infarction. SETTING: Coronary care unit in a university hospital. PATIENTS: Fifty-one patients 3 to 6 weeks after acute myocardial infarction. INTERVENTIONS: Upright bicycle exercise using a symptom-limited graded exercise protocol. MEASUREMENTS AND RESULTS: Peak filling rate increased significantly from 1.55 +/- 0.52 at rest to 3.43 +/- 1.1 end-diastolic volume per second at peak exercise. Despite no significant relation between peak filling rate at rest and peak oxygen consumption, peak filling rate at peak exercise correlated significantly with peak oxygen consumption (r = 0.50; p < 0.002), stroke volume (r = 0.51; p < 0.002), and cardiac output (r = 0.56; p < 0.002) at peak exercise. Although both end-systolic and end-diastolic volumes increased from rest to peak exercise, the increases in end-systolic volume correlated inversely with the changes in peak filling rate during exercise (r = -0.45; p < 0.02), but the increases in end-diastolic volume did not. CONCLUSIONS: During maximal upright bicycle exercise, exercise capacity and exercise hemodynamic responses were mainly dependent on early LV diastolic filling, and preserved LV systolic contraction, resulting in a cardiac suction effect following early diastole, seemed to have an important role in the enhancement of early LV diastolic filling in patients with recent myocardial infarction.