Monitoring the effect of CPAP on left ventricular function using continuous mixed-blood saturation.

The hypothetic benefit of CPAP on cardiac performance and on a reduction in VO2 was tested in a patient before heart transplantation after acute myocardial infarction using continuous SvO2 monitoring. The CPAP added to inotropic support (enoximone plus dobutamine) and intraaortic balloon pumping dramatically increased SvO2 in relation to both an increase in cardiac output and a decrease in VO2 secondary to respiratory work reduction, validating the initial hypotheses.

Mechanical determinants of isotonic relaxation in isolated diaphragm muscle.

Determinants of lengthening velocity have not been investigated in the diaphragm muscle. This study was undertaken to define the mechanical determinants of isotonic relaxation rate over the entire load continuum in isolated rat diaphragm (n = 30). We tested the hypothesis that the determinants of lengthening could include loading conditions, namely, preload and afterload; abrupt changes of load during the contraction phase; end-shortening muscle length (ESL); extent of shortening (delta L); time; stimulation mode; and stimulation frequency. In afterloaded contractions preloaded at optimal initial length and stimulated in tetanus at 30 Hz, peak lengthening velocity (+dL/dtmax) was linearly related to delta L, ESL, and/or total load. Varying initial muscle length, ESL, afterload, or the load imposed on the muscle during the isotonic lengthening process did not modify +dL/dtmax vs. delta L relationship, whereas +dL/dtmax vs. load and +dL/dtmax vs. ESL relationships were modified by these procedures. For a given delta L, +dL/dtmax could be modified when lengthening was delayed by reversing the relaxation sequence and when twitch and tetanus modes were compared. In conclusion, our results demonstrate that in isolated diaphragm muscle, delta L is the main determinant of +dL/dtmax over a wide range of loads and under various experimental conditions, independent of ESL and initial muscle length and independent of the load imposed on the muscle during the lengthening process. Time and stimulation mode were also shown to modulate the lengthening rate in diaphragm muscle.

[Positive inotropic and lusitropic effect of RP 62719, a new class III antiarrhythmia agent]. / Action inotrope et lusitrope positive du RP 62719, une nouvelle molécule antiarythmique de classe III.

Antiarrhythmic drugs, especially the Class I family, exert a negative inotropic effect on the myocardium which is particularly undesirable in patients with depressed left ventricular function. Therefore, research has been directed to the development of new, more specific molecules of the Class III family. The authors studies the mechanical effects of RP 62719 on guinea pig left ventricular papillary muscle. This new molecule is a pure Class III antiarrhythmic, known to lengthen the duration of the cardiac action potential by selectively blocking the potassium current iK1 (inward rectifier K+ current). The mechanical parameters were determined during the phases of contraction and relaxation under isotonic and isometric conditions. At 0.2 and 2 microM concentrations, RP 62719 improved cardiac contraction under both isotonic and isometric conditions with an increase of about 30% of Vmax (p < 0.001), the maximum unloaded shortening velocity delta 1 (p < 0.001), the peak isometric active force normalized per cross-sectional area [AF/S (p < 0.001)]. At these two concentrations, a positive lusitropic effect (improved relaxation) was demonstrated by an increase in negative peak of derivative per mm2-dF/s and maximum lengthening velocity VR max (p < 0.01). At higher concentrations (20 microM), the inotropic and lusitropic effects were less marked with a bell-shaped form of the dose-effect curve. This study indicates that RP 62719 has moderate but significant positive inotropic and lusitropic effects. These actions could provide significant therapeutic advantages especially in patients cardiac failure.

Intrinsic alterations of diaphragm muscle in experimental cardiomyopathy.

Diaphragmatic function was investigated in the cardiomyopathic Syrian hamster (CSH) from the dilated Bio 53:58 strain, after long-term therapy with the angiotensin-converting enzyme inhibitor perindopril. Twenty-two 1-month old CSHs were treated during a 5-month period by either oral gavage with perindopril (1 mg/kg/day) (n = 11) or placebo (n = 11). Control hamsters from the F1B strain received placebo (n = 7). Mechanical properties were studied in isolated diaphragm strips electrically stimulated in both twitch and tetanic conditions. Compared with F1B control hamsters, peak active tension and positive (+dP/dtmax) and negative (-dP/dtmax) peaks of isometric tension derivative were significantly depressed in placebo treated CSHs. Compared with placebo-treated CSHs, peak active tension was significantly higher in perindopril-treated CSHs in both twitch (25 +/- 4 vs 16 +/- 1 mN/mm2; p < 0.01) and tetanus modes (56 +/- 4 vs 38 +/- 2 mN/mm2; p < 0.01). Moreover, +dP/dtmax and -dP/dtmax were improved significantly in twitch (p < 0.01 and p < 0.01, respectively) and tetanus modes (p < 0.05 and p < 0.01, respectively). We conclude that, in the CSH, long-term therapy with the angiotensin-converting enzyme inhibitor perindopril helped to preserve the diaphragmatic function.