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In conclusion, we have shown that microemboli appear to be a universal phenomenon during PTMC. Because none of our patients had any apparent sequelae, these microemboli may be harmless. Further investigations are required to determine the nature of these microemboli and to ascertain whether subtle neurologic deficits have occurred.

Impaired long-axis motion is a sensitive marker of systolic myocardial dysfunction, but no data are available that relate long-axis changes in systole with those in diastole, particularly in subjects with diastolic dysfunction and a 'normal' left ventricular (LV) ejection fraction. A total of 311 subjects (including 105 normal healthy volunteers) aged 20-89 years with variable degrees of systolic function (LV ejection fraction range 0.15-0.84) and diastolic function were studied using tissue Doppler echocardiography and M-mode echocardiography to determine mean mitral annular amplitude and peak velocity in systole and early and late diastole. The LV systolic mitral annular amplitude (S(LAX), where LAX is long-axis amplitude) and peak velocity (S(m)) correlated well with the respective early diastolic components (E(LAX) and E(m)) and late diastolic (atrial) components (A(LAX) and A(m)). A non-linear equation fitted better than a linear relationship (non-linear model: S(LAX) against E(LAX), r(2)=0.67; S(m) against E(m), r(2)=0.60; S(LAX) against A(LAX) and S(m) against A(m), r(2)=0.42). After adjusting for age, sex and heart rate, linear relationships of early diastolic (E(LAX), r(2)=0.70; E(m), r(2)=0.60) and late diastolic (A(LAX), r(2)=0.61; A(m), r(2)=0.64) long-axis amplitudes and velocities with the respective values for S(LAX) and S(m) were found, even in those subjects with apparently 'isolated' diastolic dysfunction. Long-axis changes in systole or diastole did not correlate with Doppler mitral velocities. We conclude that ventricular long-axis changes in early diastole are closely related to systolic function, even in subjects with diastolic dysfunction. 'Pure' or isolated diastolic dysfunction is uncommon.

A 60 year old man presented with recurrent near syncope preceded by fast palpitation for six months. Investigations showed normal left and right ventricles. Programmed electrical stimulation (PES) was able to induce clinical arrhythmia of cycle length 250 ms with left bundle branch block pattern and inferior axis, suggesting right ventricular outflow tract (RVOT) ventricular tachycardia (VT). Blood pressure dropped to 60/40 mm Hg during tachycardia with notable dizziness. Overdrive pacing was successful in terminating the arrhythmia. The clinical arrhythmia was …

Power spectral analysis of heart rate variability is frequently used as an easy non invasive method for assessing autonomic tone. However changes in respiratory rate are frequently ignored and these may have an important effect on the measurements of spectral components, especially in heart failure. We have assessed the effect of different respiratory rates (10, 15, 20 min -1 and spontaneous) on low frequency (LF) and high frequency (HF) components of HR variability in 11 heart failure pts (CCF) (EF = 40 ± 4%; 9 males) and 9 normal subjects (5 males). Results LF a HF spectral power in normalized units (%); S = spontaneous (mean ± SEM) LF10 HF10 LF15 HF15 LF20 HF20 LFS HFS Supine CCF 19 ± 8 63 ± 9 * 18 ± 5 54 ± 7 13 ± 4 47 ± 8 * 16 ± 6 49± 8 Normal 14 ± 6 68 ± 8 18 ± 6 58 ± 10 15 ± 6 70 ± 5 22 ± 9 55 ± 10 Stand CCF 15 ± 7 66 ± 6 19 ± 7 46 ± 8 30 ± 10 51 ± 9 7 ± 5 31 ± 10 Normal 28 ± 9 55 ± 8 30 ± 9 42 ± 9 58 ± 10 27 ± 5 50 ± 12 17 ± 5 * p l 0.05 Supine HF power falls with increasing respiratory rate in most CCF pts and this effect is similar to that seen in normals on standing (i.e. at increased sympathetic levels). An improvement in clinical state of CCF pts will lower respiratory rate and this effect alone will increase HF power rather than any therapy.

Although the technique of transdermal iontophoretic drug delivery has been known for many years, its use has been limited clinically to those applications for which a brief drug delivery period is adequate (e.g., delivery of pilocarpine in the diagnosis of cystic fibrosis). For most therapeutic applications, however, it is necessary to have an extended, if not continuous, drug delivery regimen. The use of iontophoresis has been limited in these applications by side effects, primarily skin trauma, associated both with the current density and the total amount of current passed. A mechanism for these side effects will be proposed and techniques to mitigate them will be presented. Many of these techniques involve ways in which the drug formulation can be designed to maximize the fraction of current carried by the drug species. These methods include the following: control of the pH in the bulk solution and in the boundary layer without using conventional buffers; taking advantage of polarization effects; and enhancing the permselectivity of skin. In this way, the therapeutic dose or optimal infusion rate of drug can be achieved with the minimum current and, therefore, the minimum number of side effects.

OBJECTIVESTo evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia.BACKGROUNDHyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known.METHODSAdults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 ± 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 ± 2.8 μmol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation.RESULTSCompared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 ± 7.0 vs. 29.7 ± 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 ± 3.1 vs. 9.5 ± 2.5 μmol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 ± 1.6% vs. 6 ± 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed.CONCLUSIONFolic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.

Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often complain of breathlessness and/or fatigue, and most have reduced exercise capacity.1 Patients with nHCM typically exhibit diastolic dysfunction, which is thought to contribute significantly to the genesis of breathlessness in these patients. Active relaxation is slowed and filling rate is typically diminished at rest in nHCM patients.2 Furthermore, we previously showed that there is frequently a failure of the normal increase in rate of active relaxation (as measured by time to peak filling) on exercise; indeed, in some patients, active relaxation paradoxically slowed on exertion.1 Resting echocardiographic Doppler parameters of left ventricle (LV) filling have been used to measure diastolic function.3 However, these parameters are dependent on loading conditions. The LV twists during systole as a result of counterclockwise rotation of the apex and clockwise rotation of the base with corresponding untwisting during diastole. The resulting untwisting may represent a useful marker of diastolic function.4,5 The velocity of LV untwisting has been correlated with invasive measurements of LV relaxation under a variety of loading and inotropic conditions in animal models. Dong et al6 confirmed that LV untwisting is a measure of LV relaxation that is independent of preload as reflected in left atrial (LA) pressure. The development of speckle tracking echocardiography (STE) has allowed LV strain, twisting, and untwisting rates to be measured relatively easily with reasonably high temporal resolution.7 In this study, we used STE to measure LV strain, strain rate, and twist and untwist rates in nHCM patients and controls; and we sought to assess their relationship with exercise capacity.

OBJECTIVES We sought to compare the effects of two different beta-blockers, carvedilol and metoprolol, to an angiotensin-converting enzyme (ACE) inhibitor (captopril) on myocardial collagen deposition during healing and ventricular remodeling after myocardial infarction (MI). BACKGROUND Beta-adrenergic blockade has been shown to be beneficial post-MI and in chronic heart failure. Carvedilol is a new-generation vasodilating beta-blocker with additional alpha1-adrenoceptor antagonism and an antiproliferative action, but it is not known if it is more beneficial than standard selective beta-blockers. METHODS Using a rat model of MI, induced by left coronary ligation, we studied the effects of 11 weeks of therapy with oral carvedilol, metoprolol or captopril on hemodynamics, tissue weights, collagen volume fraction and hydroxyproline content. RESULTS Both beta-blockers caused similar decreases in heart rate and LVEDP compared with untreated post-MI rats. At equivalent beta-adrenoceptor blocking doses, however, carvedilol, but not metoprolol, attenuated the increase in collagen content in noninfarcted regions and prevented the increase in right ventricular weight/body weight (all p < 0.05), and its effect was similar to captopril. Metoprolol treatment tended to increase right ventricular weight and heart weight (p < 0.05). There were no differences in infarct size between the groups. CONCLUSIONS Long-term treatment with both beta-blockers, as well as an ACE inhibitor, benefited the healing process in rats post-MI. At equivalent myocardial beta-adrenoceptor blocking doses, however, carvedilol significantly reduced myocardial collagen in the noninfarcted myocardium and cardiac hypertrophy in the right ventricle, whereas metoprolol had no effect on myocardial collagen deposition.

ObjectivesThis study sought to investigate the incremental prognostic value of non-invasive measures of early myocardial relaxation and left ventricular diastolic pressure (LVDP) in patients with impaired left ventricular (LV) systolic function.BackgroundThe early diastolic mitral annulus velocity (Em) reflects myocardial relaxation, and the combined ratio of the early transmitral flow velocity (E) to Em (E/Em) >15 correlates well with elevated mean LVDP. It is unknown if these new indexes will predict poorer survival in patients with LV systolic dysfunction.MethodsEchocardiograms were prospectively obtained in 182 patients with impaired LV systolic function, defined as an LV ejection fraction 15 (p = 0.038).ConclusionsEarly diastolic mitral annulus velocity is a powerful predictor of cardiac mortality in patients with LV systolic impairment; Em

Using a newly developed iontophoretic delivery device, a novel inotropic catecholamine, pharmacologically similar to dobutamine, has been successfully administered to dogs by noninvasive transdermal infusion for periods of up to 1.5 h. The technique was compared with intravenous infusion and shown to be capable of achieving the same degree of cardiac contractility and steady-state plasma concentrations of the inotrope. There was also a good linear relationship between the applied current and the resulting steady-state plasma concentrations of the inotrope. Approximately 2 mA of applied current during transdermal iontophoresis produced a response equivalent to an intravenous infusion of 1 micrograms/kg/min of the drug.

Idiopathic dilated cardiomyopathy (IDC) is a common clinical problem in Africa. To determine if there is a defect of immune regulation in patients with IDC, the percentage of total T-cells (OKT3 positive), helper/inducer cells (OKT4 positive) and suppressor/cytotoxic cells (OKT8 positive) were measured using monoclonal antibodies in 20 patients with IDC and in 20 age-matched normal control subjects. The percentage of helper/inducer cells was significantly higher in the IDC patients (45 ±2% mean ± standard error) than in the normal subjects (33 ± 2%) and 8 of the 20 IDC patients had a helper/suppressor cell ratio ( OKT4 OKT8 ) higher than the normal range. Of the 8 patients with this abnormality, 7 were studied within 3 months of the onset of their illness. Results suggest that an excessive immune reaction is part of the pathogenesis of IDC in Africans.

Cardiac valve calcification (VC) has long been regarded as a consequence of aging and abnormal calcium-phosphate metabolism in uremic patients. In view of the recent recognition of association among inflammation, malnutrition, and atherosclerosis, the possible role of inflammation and malnutrition in VC was investigated. Inflammatory markers (including C-reactive protein [CRP], fibrinogen, and basal metabolic rate) and nutritional status (assessed using serum albumin, subjective global nutrition assessment, and handgrip strength) were examined, in addition to calcium phosphate parameters and other traditional cardiovascular risk factors, including gender, smoking habits, BP, and lipid profile, in relation to VC in 137 patients who were on continuous ambulatory peritoneal dialysis. Compared with patients with no VC, patients with VC not only were older (60 [10] versus 54 [12] yr; P = 0.005), had higher plasma phosphate (1.89 [0.52] versus 1.64 [0.41] mmol/L; P = 0.003), and had higher parathyroid hormone (83 [40, 145] versus 38 [16, 71] pmol/L; P = 0.001) but also had higher CRP (4.5 [0.1, 13.4] versus 0.2 [0.1, 4.4] mg/L; P = 0.004), had higher fibrinogen (6.6 [1.9] versus 5.7 [1.3] g/L; P = 0.002), and had lower serum albumin (26 [4] versus 29 [3] g/L; P = 0004). Twenty-three percent of patients with VC versus 17% of patients with no VC were moderately to severely malnourished according to subjective global nutrition assessment (P = 0.05). Even after adjustment for patients' age, duration of continuous ambulatory peritoneal dialysis, diabetes, and calcium x phosphate product, cardiac VC remained strongly associated with CRP (odds ratio, 1.05; P = 0.026) and albumin (odds ratio, 0.85; P = 0.01). The data suggest that VC not only is a passive degenerative process but also involves active inflammation, similar to that seen in atherosclerosis. The presence of uncontrolled hyperphosphatemia and hyperparathyroidism further accelerates the progression of calcification. The data also indicate that VC and atherosclerosis should be considered as associated syndromes, sharing similar pathogenic mechanisms, namely active inflammation.

In order to demonstrate the potential therapeutic effect of two flavonoids, Baicalein and Wogonin, on suppression of pathological myocardial fibrosis in hypertension, we investigated their in vitro effects on collagen expression in primary cultured cardiac fibroblasts isolated from neonatal normotensive (WKY) and hypertensive (SHR) rats. Our results showed that over-expression of collagen mRNA and protein induced in cardiac fibroblasts by angiotensin (AngII) could be attenuated significantly by both flavonoids at an optimal dosage (30 microM; P < 0.01). Results of immunoblots showed that expression of 12-LO level, p-ERK/ ERK ratio and MMP-9 in AngII|-stimulated SHR cardiac fibroblasts were significantly down-regulated by both flavonoids. Our results show that both Baicalein and Wogonin can suppress collagen deposition in AngII-stimulated SHR and WKY cardiac fibroblasts.

We have compared the cardiac performance of four groups of rats: normotensive control rats (NCR) and spontaneously hypertensive rats (SHR) not drinking alcohol, and NCR and SHR drinking 20% alcohol (NCR-A and SHR-A, respectively), over a period of 6-9 months.