Y. Lecarpentier

Effect of beta adrenoceptors and thyroid hormones on velocity and acceleration of peripheral arterial flow in hyperthyroidism.

Brachial artery flow patterns were studied in 10 hyperthyroid and 10 normal subjects. Mean blood velocity and flow were evaluated by pulsed Doppler, and peak systolic acceleration was calculated by computer-assisted digitization of the instantaneous velocity curve. Compared to control subjects, hyperthyroid patients had higher velocity and flow (p less than 0.01, p less than 0.02) and higher peak systolic acceleration (p less than 0.01). In hyperthyroid patients, measurements were repeated after (1) mechanical exclusion of the hand from brachial circulation, (2) short-term beta-blocker treatment and (3) inducement of the euthyroid state. Exclusion of the hand reduced velocity and flow (p less than 0.001) but did not change peak systolic acceleration. Beta blockade induced disparate changes of velocity and flow but reduced peak systolic acceleration (p less than 0.05). In the euthyroid state, decreased blood velocity (p less than 0.01), flow (p less than 0.02) and acceleration (p less than 0.02) were observed. A hyperkinetic arterial circulation consisting of an increase in both velocity and acceleration is thus observable in hyperthyroidism. Hand exclusion showed that velocity seems to be influenced by peripheral factors while beta blockade suggests that acceleration is dependent of beta 1 adrenoceptors. Comparison between euthyroidism and hyperthyroidism indicates that both mean blood velocity and peak systolic acceleration are influenced by thyroid hormones.

Species-dependent changes in mechano-energetics of isolated cardiac muscle during hypoxia.

Abstract The present study investigates the mechanical and energic changes induced by hypoxia in isolated cardiac muscles of different species characterized by different myosin isoforms. Classic mechanical parameters of contraction and energetic parameters derived from the tension-velocity relationship were studied in rat and guinea pig left ventricular papillary muscles and in frog ventricular strips before and after 15 min hypoxia (n = 8 in each group) The isomyosin pattern is predominantly V1 with high ATPase activity in rat and V3 with low ATPase activity in guinea pig and frog heart ventricles. At baseline, cardiac mechanical performace was greater in rat than in guinea pig and frog muscle, but the economy of tension generation did not differ significantly between the three species. Hypoxia significantly decreased myocardial mechanical performance in al three groups. Mechanical impairment was more marked in rat than in the other two species and was intermediate in guinea pig. The energetic consequences of hypoxia differed according to species and in a different manner from the mechanical parameters. Hypoxia decreased the economy of tension generation in rat heart, in contrast to no change in guinea pig and frog muscle. These results suggest that in terms of mechano-energetic properties, cardiac muscles with V1 isomyosin were more sensitive to hypoxia than those containing V3 isomyosin.

Lusitropic effect and modifications of contraction-relaxation coupling induced by α-adrenergic stimulation in rat left ventricular papillary muscle

Phenylephrine (PE) and metaraminol (MR) were studied alone at 2 x 10(-5) M and at 4 x 10(-5) M respectively. These drugs were also used both in the presence of either propranolol (PR) at 4 x 10(-7) M (PE/PR and MR/PR groups) or prazosin (PZ) at 2 x 10(-7) M (PE/PZ and MR/PZ groups). Specific alpha-adrenergic stimulation (AS) was induced in the PE/PR and MR/PR groups. These AS were evaluated in isotonic and isometric conditions on rat left ventricular papillary muscle. Peak shortening velocity (Vcmax) and peak lengthening velocity (Vrmax) were calculated from the twitch with preload only. Positive (+dF/dtmax) and negative (-dF/dtmax) peak derivative forces were calculated from the isometric twitch. Two coefficients R1 and R2 were used to measure the coupling between contraction and relaxation at low and heavy load, respectively: R1 = Vcmax/Vrmax and R2 = (+dF/dtmax)/(-dF/dtmax). In all groups, there was a significant positive inotropic effect. As compared to control values before AS, R1 significantly decreased in all groups, (PE/PR: -15%; MR/PR: -18%; PE/PZ: -8%; MR/PZ: -23%; PE: -19%; MR: -32%). On the other hand, R2 significantly decreased only in three groups (PE/PZ: -5.4%; MR/PZ: -16.5%; MR: -12.0%) whereas it did not significantly change in the three other groups (PE/PR; MR/PR; PE). In all groups, and at low load, Vrmax increased more than Vcmax (positive relaxant effect i.e. R1 decreased). At heavy load, despite the positive inotropic effect, there was no significant relaxant effect after predominent alpha-AS. These results indicate that alpha-AS modified the coupling between contraction and relaxation differently, depending on the level of load.

Myocardial contractility, lusitropy and calcium responsiveness in young (50 days) and hypertrophied (180 days) cardiomyopathic hamsters

Contractility, lusitropy and responsiveness to the increase of external Ca2+ concentration were studied in left ventricular papillary muscles of normal and cardiomyopathic Syrian hamsters (SCH) from the UM-X 7.1 strain, both at the onset of myolysis (50-day-old animals) and at the cardiac hypertrophy stage (180-day-old animals) in the absence of congestive heart failure. A marked decrease in all indices of systolic performance was observed in 180-day-old myopathic hamsters as compared to age-matched controls. This was associated with (1) an impairment of the relaxation phase, (2) a loss of the load sensitivity of relaxation, and (3) a decrease in the inotropic and lusitropic responsiveness to Ca2+. On the other hand, when some indices of contraction and the inotropic response to Ca2+ were impaired in 50-day-old myopathic hamsters as compared to age-matched controls, relaxation phase and the lusitropic response to Ca2+ did not alter. This study shows that, in the UM-X 7.1 myopathic hamsters at the earlier stage of the disease, alterations in calcium homeostasis and contraction seem to be the first determinant factors of the development of heart failure when relaxation is not impaired. Conversely, when cardiac hypertrophy has developed, impaired relaxation may worsen heart failure.

Mechanics and energetics of myosin molecular motors from nonpregnant human myometrium

Mechanical properties of spontaneously contracting isolated nonpregnant human myometrium (NPHM) were investigated throughout the whole continuum of load from zero load up to isometry. This made it possible to assess the three-dimensional tension-velocity-length (T-V-L) relationship characterizing the level of contractility and to determine crossbridge (CB) kinetics of myosin molecular motors. Seventy-seven muscle strips were obtained from hysterectomy in 42 nonpregnant patients. Contraction and relaxation parameters were measured during spontaneous mechanical activity. The isotonic tension-peak velocity (T-V) relationship was hyperbolic in 30 cases and nonhyperbolic in 47 cases. When the T-V relationship was hyperbolic, the Huxley formalism could be used to calculate CB kinetics and CB unitary force. At the whole muscle level and for a given isotonic load level, part of the V-L phase plane showed a common pathway, so that a given instantaneous length corresponded to only one possible instantaneous velocity, independent of time and initial length. At the molecular level, rate constants for CB attachment and detachment were dramatically low, ∼100 times lower than those of striated muscles, and ∼5 to 10 times lower than those of other smooth muscles. The CB unitary force was ∼1.4 ± 0.1 pN. NPHM shared similar basic contractile properties with striated muscles, reflected in the three-dimensional T-V-L relationship characterizing the contractile level. Low CB attachment and detachment rate constants made it possible to generate normal CB unitary force and normal muscle tension in NPHM, even though it contracted extremely slowly compared with other muscles.