Diastolic abnormalities in systemic sclerosis: evidence for associated defective cardiac functional reserve.

OBJECTIVE: To investigate the pattern of diastolic abnormalities in patients with systemic sclerosis (SSc) and the relationship between impaired ventricular filling and systolic function. METHODS: Twenty four patients with SSc underwent M-mode and two dimensional echocardiography using echo-Doppler and gated blood pool cardiac angiography, both at rest and after exercise. RESULTS: An impaired diastolic relaxation of the left ventricle was detected in 10 of the 24 patients with SSc. Left ventricular ejection fraction at rest in these 10 patients with impaired ventricular filling did not differ from that in the remaining 14 patients, but eight of the 10 failed to increase their ejection fraction during exercise, compared with two of the 14 with normal ventricular filling (p = 0.003). CONCLUSION: Impaired relaxation of the left ventricle is a recently described feature of scleroderma heart disease. Diastolic dysfunction in SSc could depend on myocardial fibrosis or myocardial ischaemia, or both. It was found to be associated with a defective cardiac functional reserve. However, its prognostic significance remains to be clarified.

Effects of intravenous digoxin on pulmonary venous and transmitral flows in patients with chronic heart failure of different degrees.

Acute effects of digoxin on diastole were evaluated noninvasively by combining data simultaneously obtained by Doppler echocardiograms (echo-Doppler) of transmitral and pulmonary venous flow curves in 38 patients with dilated and failing hearts, who had been stable for at least 7 days before the study. According to the resting ejection fraction (EF), patients were subdivided into Group 1 (EF < 30%: n = 20, mean EF values 23 +/- 8%) and Group 2 (EF > or = 30%: n = 18, mean EF values 40 +/- 3%). Significant differences were observed at rest between the two groups in both transmitral (shorter deceleration time and isovolumic relaxation time and increased peak E and E/A ratio in Group 1 vs. Group 2) and transpulmonary (reduced systolic forward component and systolic fraction of the flow curves in Group 1 compared with Group 2 and control subjects) parameters. Digoxin (1 mg subdivided into two doses, each infused over a 15-min period with 2 h between the doses) significantly modified the diastolic profile in Group 1 patients in the absence of statistically relevant changes in EF: a significant decrease of transmitral peak E (from 76 +/- 17 to 60 +/- 15 cm/s, p < 0.05) and E/A ratio (from 2.5 +/- 1 to 1.6 +/- 0.6; p < 0.05) and a significant lengthening of deceleration time (from 115 +/- 20 to 160 +/- 18 ms; p < 0.05) were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of short-term oral digoxin on left ventricular diastolic filling in patients with ventricular dysfunction. An echo-Doppler study.

34 patients with ventricular dysfunction (18 in NYHA class II and 16 in NYHA class III heart failure) whose clinical status was stabilized by diuretics and systemic vasodilators, entered a randomized trial to compare the effects of short-term oral digoxin and active placebo on left ventricular diastolic function, non invasively evaluated by echo-Doppler transmitral left ventricular filling flow. At baseline patients were subdivided by reversal--the ratio of peak early (E) and late (A) transmitral filling velocities--E/A < 1 (group I) or normal--E/A > or = 1 (group II) echo-Doppler E/A ratio; group II exhibited a shorter deceleration time (125 +/- 20 ms vs 198 +/- 38 ms, p > 0.05) and isovolumic relaxation time (64 +/- 15 ms vs 93 +/- 10 ms; p < 0.05) as well as a higher peak E velocity (85 +/- 28 cm/s vs 54 +/- 20 cm/s; p < 0.05), ("restrictive" left ventricular filling pattern). After 4 weeks, no changes in all echo-Doppler parameters were noted in group I in response to either oral digoxin or active placebo. Clinical amelioration (defined as reduction by at least one functional class) was observed in 3 patients after digoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac involvement in rheumatoid arthritis: an echocardiographic study.

Thirty-nine consecutive patients with rheumatoid arthritis (RA) and 40 control subjects were studied by echocardiography in order to assess the incidence of cardiac involvement in this disease. The occurrence of anatomic lesions in our series was lower than that observed in other studies. No differences in mean values of left and right ventricular diastolic function indexes obtained by Doppler echocardiography were found between patients and controls. However, in 26% of patients with RA, left ventricular abnormalities probably secondary to myocardial fibrosis were observed.

Left ventricular diastolic function with epirubicin therapy: an echodoppler study.

Thirty patients undergoing epirubicin therapy for primary lung cancer were studied by echocardiography and Doppler echocardiography. 2 D ejection fraction (EF) and Doppler left ventricular filling parameters (peak E, peak A, E/A ratio) were calculated before and after the completion of therapy. No differences in the mean values of these parameters were observed. However, 6 out of 30 patients (20%) showed left ventricular filling abnormalities; in 2 of them a slight reduction of EF was also noted. These abnormalities seem to be dose related. A longer term prospective study will be required to evaluate whether these findings are irreversible and to establish the clinical implications of our observations.

Human basophil/mast cell releasability. V. Functional comparisons of cells obtained from peripheral blood, lung parenchyma, and bronchoalveolar lavage in asthmatics.

Releasability of human basophils and mast cells is an important parameter in allergic disorders. We compared IgE- and non-IgE-mediated releasability of human peripheral blood basophils with that of mast cells obtained from lung parenchyma (isolated by mechanical or enzymatic dissociation) and from bronchoalveolar lavage of normal and asthmatic donors. In a first study, the response to anti-IgE, Staph A, Con A, f-met peptide, and Ca2+ ionophore A23187 of basophils obtained from 52 donors was compared with that of mast cells isolated enzymatically (PMCE) or mechanically (PMCM) from lung parenchyma obtained during surgery. The histamine content of basophils (1.1 +/- 0.1 pg/cell) was significantly lower than that of PMCE (4.1 +/- 0.3 pg/cell; p less than 0.001) and PMCM (3.7 +/- 0.3; p less than 0.001). The maximal percent anti-IgE-induced histamine secretion in basophils (41.3 +/- 3.6) was higher than in PMCE (17.5 +/- 1.8) and in PMCM (13.8 +/- 1.5). Similarly, the response to Staph A and Con A was higher in basophils (29 +/- 3.9 and 31.6 +/- 4.9, respectively) than in PMCE (3.5 +/- 0.6 and 3.3 +/- 0.8, respectively) and PMCM (5.1 +/- 1.3 and 8.8 +/- 2.2, respectively). A positive correlation between the maximal percent of histamine release induced by anti-IgE and Staph A was found in basophils (rs = 0.61; p less than 0.001), whereas there was a negative correlation between the reactivity of PMCE (rs = 0.67; p less than 0.001) and PMCM (rs = -0.40; p less than 0.001) to anti-IgE and their reactivity to Staph A.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin A inhibits the release of histamine and peptide leukotriene C4 from human lung mast cells.

We investigated the effect of cyclosporin A (CsA) on in vitro release of chemical mediators from mast cells purified from human lung tissues. CsA (3 X 10(-2) to 1 microgram/ml) dose-dependently inhibited IgE-mediated release of histamine and peptide leukotriene C4 (LTC4) from human lung mast cells. The same concentrations of CsA also inhibited the release of histamine from lung mast cells challenged with the Ca2+ ionophore A23187. Therefore, CsA in pharmacological concentrations inhibits the IgE- and non-IgE-mediated release of inflammatory mediators from mast cells purified from human lung tissues.

IgE-mediated activation of human heart in vitro.

We used human cardiac tissue from the right atrial appendages of patients undergoing corrective heart surgery to study content and de novo synthesis of mediators in the human heart. Human heart tissue contained 1.7 +/- 0.1 micrograms/g wet weight of histamine (mean +/- S.E.M.) and spontaneously produced 6-keto-PGF1 alpha (38.4 ng/g wet weight/min), PGF1 alpha (1.9 ng/g wet weight/min), PGE (1.7 ng/g wet weight/min) and thromboxane B2 (TxB2) (1.7 ng/g wet weight/min). Spontaneous release of PGD2, leukotriene C4 and histamine was negligible. Rabbit anti-human IgE (1-10 micrograms/ml) dose-dependently induced the release of histamine (5 to 15% of the total histamine content) and of PGD2 (5 to 100 ng/g of wet tissue). The effect of anti-IgE was dose-related and reached a maximum after 30-45 min of incubation. A significant linear correlation (rs = 0.90; p less than 0.001) was found between de novo synthesis of PGD2 and the secretion of histamine induced by anti-IgE challenge of human heart. These results support the concept that PGI2 is the main, but not the sole, product of arachidonic acid metabolism synthesized by human heart in vitro. Additionally, anti-IgE challenge of human heart in vitro induces the release of histamine and PGD2. The local concentrations of these mediators appear high enough to play some role in the modulation of several cardiac functions in vivo.