Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca2+ handling.

Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by analyzing myocardial contractility and Ca2+ handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca2+) transients, sarcoplasmic reticulum (SR) Ca2+ content and SR Ca2+ leak (as Ca2+ sparks). Reactive oxygen species (ROS), as superoxide anion (O2•-) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca2+ transients and SR Ca2+ content and increased diastolic SR Ca2+ leak. Decay of twitch and caffeine-induced Ca2+ transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca2+ content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca2+ leak leading to reduced SR Ca2+ content and reduced Ca2+ transients. TBT-induced myocardial ROS production, may destabilize the SR Ca2+ release channel RyR2 and reduce SR Ca2+ pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects.

Exercise tolerance in patients with mitral stenosis before and after acute percutaneous mitral valvuloplasty. Role of lung diffusing capacity limitation?

The aim of this study was to specify in patients with tight mitral stenosis whether lung diffusing capacity could play a role in their exercise intolerance. A similar study was recently carried out in patients with moderate chronic heart failure. Ten patients with tight mitral stenosis were studied before and 6 months after successful percutaneous transvenous balloon valvuloplasty and compared to six control subjects. Measurements of diffusing capacity, evaluated by the lung transfer factor (TLCO) and by the transfer coefficient (TLCO/VA), obtained at rest and during early recovery after cardiopulmonary exercise testing were performed. Cardiac output was determined non-invasively, both at rest and during exercise, using the carbon dioxide exponential rebreathing technique. Prior to valvuloplasty, TLCO and TLCO/VA were not different at rest between the two groups. During exercise, patients differed from control subjects, with lower oxygen uptake (P < 0.001) and lower cardiac output at peak exercise (P < 0.001). These values at peak exercise were significantly correlated (P = 0.02; r = 0.75). Moreover, patients differed from control subjects at early recovery after peak exercise with an absence of increase in TLCO (P < 0.05). Six months after valvuloplasty, a decrease of both TLCO (P < 0.01) and TLCO/VA (P < 0.05) was observed at rest. During exercise, comparison of patients demonstrated a significant increase of both peak exercise oxygen uptake (SLVO2, P < 0.01) and cardiac output (P < 0.001). At early recovery after peak exercise there was a significant increase in TLCO (P < 0.05) and TLCO/VA (P < 0.01), such that a delta TLCO and a delta TLCO/VA appeared (P < 0.05) identical to that observed in control subjects. Moreover, delta SLVO2 was significantly correlated in patients with delta Q+ delta TLCO/VA (P = 0.02; r = 0.72). In conclusion, this study suggests a role, at least partial, of lung diffusing capacity in exercise intolerance in patients with tight mitral stenosis and in the improvement of their aerobic exercise capacity demonstrated after successful percutaneous balloon valvuloplasty.

Exercise intolerance in patients with chronic heart failure: role of pulmonary diffusing limitation.

In order to test the hypothesis of pulmonary diffusing capacity involvement in exercise limitation in subjects with chronic heart failure (CHF), lung transfer factor (TLCO), oxygen saturation (SaO2), cardiac output (CO) and gas exchange were studied over the course of an incremental exercise test in 10 patients and 10 controls. The TLCO and transfer coefficient for carbon monoxide (TLCO/VA) were measured at rest and during recovery by the single breath method. The SaO2 was followed non-invasively with a finger oximeter and CO was determined according to the carbon dioxide rebreathing method. Analysis of respiratory variables at maximal effort showed significantly lower values in patients with CHF as regards peak oxygen uptake (VO2), minute ventilation (VE), heart rate (HR), oxygen pulse (O2 pulse), and CO with higher ventilatory reserve (VR) than controls. At a comparable workload (30 W), patients with CHF demonstrated higher values for VE and lower values for CO than controls. The TLCO, expressed as percent of predicted values, was significantly lower in CHF patients than controls, respectively, at rest (90.5 +/- 3.75% vs 106.8 +/- 3.8%) and within 5 min after maximal exercise (87 +/- 4.4% vs 117.4 +/- 3.81%). The TLCO/VA showed comparable data between the two groups at rest (81.7 +/- 3.28 vs 90.3 +/- 2.86%). However, significantly lower values of TLCO/VA were obtained for CHF after maximal exercise in comparison to control subjects (77.5 +/- 3.85% vs 96.3 +/- 3.95%). These results confirm the alteration of the main variables in relation to cardiopulmonary exercise limitation in-tHF, and indicate a significant decrease in TLCO and TLCO/VA after maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary exercise testing. Determinants of dyspnea due to cardiac or pulmonary limitation.

The aim of this study was to bring to light new and simple criteria, obtained during cardiopulmonary exercise testing, in order to demonstrate in patients the cardiac or the pulmonary origin of a comparable exertional dyspnea. Forty male subjects were compared, who exercised with a 30-W/3-min protocol and were divided into three groups: the cardiac heart failure (CHF) group (n = 15), the chronic obstructive lung disease (COLD) group (n = 15), and the control group (n = 10). The two groups of patients differed totally from the control group concerning their spirometric values at rest and a clear inability during effort which was confirmed by all the studied cardiopulmonary parameters at maximal exercise. The CHF and COLD groups differed slightly concerning their maximum symptom-limited oxygen uptake, only when related to body mass (13.26 +/- 0.69 ml/kg/min in CHF group, 17.05 +/- 1.59 ml/kg/min in COLD group; p < 0.05), and concerning their maximum ventilatory equivalent for oxygen which tended to be higher in the CHF group in comparison with the COLD group (p = 0.082). Furthermore, and as foreseen, the two groups of patients clearly differed at maximum exercise concerning the ventilatory reserve respiratory parameter (49.73 +/- 3.18 percent in CHF group, 8.38 +/- 5.85 percent in COLD group; p < 0.01). On the other hand, they did not differ concerning cardiac parameters or those considered as such (maximum heart rate [HR], HR reserve, HR response, maximum O2 pulse measurement). While their maximum ventilation was similar in the CHF and COLD groups, a difference in adaptation during exercise was found by observing their breathing pattern. In the CHF group, this was demonstrated by a significantly lower breathing frequency at maximum exercise (31.24 +/- 1.53 beats/min vs 37.75 +/- 2.24 beats/min; p < 0.05) and a tidal volume that tended to be higher at maximum exercise (p = 0.077) and significantly higher at 60-W work load (p < 0.05). This work shows that the study of ventilatory reserve and breathing pattern during exercise testing allows one to discriminate if dyspnea on exertion in patients is due to cardiac or respiratory disease.

Doppler echocardiographic evaluation of the Omnicarbon cardiac valve prostheses.

Comprehensive 2 D/Doppler examination of 98 patients (mean age 56), implanted between September 1984 and February 1991, with normally functioning aortic (n = 49) and mitral (n = 49) Omnicarbon valves (OC) were analyzed in order to characterize the normal hemodynamic profiles of the OC valves. The mean time from implantation was 36.4 months (range 6 to 78). The following parameters were assessed (average of 5 measurements): peak transvalvular velocity (peak V), peak instantaneous gradient (peak G), mean transvalvular gradient (mean G), effective aortic valve area (ef Va), modified aortic valve area (m Va), aortic permeability index (PI), mitral valve area (Mit Va). Doppler data were correlated to prosthetic sizes (ranging from 21-29 mm for aortic OC and from 23-31 mm for mitral OC). The study establishes normal Doppler hemodynamics for each size (especially in aortic position) of OC valves and shows excellent performance. Significant correlations between peak G, mean G, Pl, and prosthetic aortic valve size (AS) were moderate. By contrast there were strong relationships between AS and ef Va (r = 0.56, p < 0.001) or mVa (r = 0.55, p < 0.001). These data should be helpful to identify OC prosthetic dysfunction.