The functional effect of adenoviral Na+/Ca2+ exchanger overexpression in rabbit myocytes depends on the activity of the Na+/K+-ATPase.

OBJECTIVES: The functional consequences of Na+/Ca2+ exchanger (NCX) overexpression in heart failure have been controversially discussed. NCX function strongly depends on intracellular sodium which has been shown to be increased in heart failure. METHODS AND RESULTS: We investigated the Na+/K+-ATPase (NKA) inhibitor ouabain (0.5-16 micromol/l) in electrically stimulated, isotonically contracting adult rabbit cardiocytes overexpressing NCX after adenoviral gene transfer (Ad-NCX-GFP, 48 h culture time). Myocytes transfected with adenovirus encoding for green fluorescent protein (Ad-GFP) served as a control. Contractions were analyzed by video-edge detection. In the Ad-NCX-GFP group, the maximum inotropic response was significantly reduced by 50.7% (P<0.05). This was a result of an enhanced susceptibility to contracture after exposure to the drug (median concentration (25-75%): 4 (4-8) vs. 8 (6-16) micromol/l, P<0.05). When analyzing relaxation before contracture, the maximum relaxation velocity was reduced (0.15+/-0.04 vs. 0.27+/-0.04 microm/s, P<0.05) and the time from peak shortening to 90% of relaxation was increased (298+/-39 vs. 185+/-15 ms, P<0.05). No differences in systolic and diastolic parameters were observed with the Na+ channel modulator BDF9198 (1 micromol/l). CONCLUSIONS: Inhibition of NKA by ouabain induces a combined diastolic and systolic dysfunction in NCX overexpressing rabbit myocytes. This may be the consequence of cytoplasmic Ca2+ overload due to inhibition of forward mode or induction of reverse mode Na+/Ca2+ exchange. In end-stage failing human myocardium and during digitalis treatment this mechanism may be of major importance.

Effect of sterile service on estrus duration, fertility and prolificacy in artificially inseminated dairy goats.

The effect of sterile service on estrus duration, fertility and prolificacy in artificially inseminated dairy goats during breeding season was studied. Nubian does (n=126) were divided into 2 equal groups: service and control. Estrus was synchronized with intravaginal sponges containing either fluorgestone acetate (FGA; 40 mg) or medroxiprogesterone acetate (MAP; 60 mg) for 12 or 14 d, respectively. Two vasectomized teaser bucks were used to detect estrus at 6-h intervals for 5 d after sponge removal (0600, 1200, 1800 and 2400 h). The teasers were fitted with aprons and permitted to mount all does in both groups, but to penetrate only the service does within the first 12 h of estrus. Does in both groups were inseminated twice at 12 and 24 h after estrus was first detected, using 1 straw per insemination containing 200 million of cooled spermatozoa from 1 buck. The semen was placed in mid-cervix. Estrus duration for the service and control does was (mean +/- SD) 29.4 +/- 6.5 and 41.8 +/- 9.6 h, respectively. Fertility for the service does was 73.7% (46/63); for control does it was 58.7% (37/63). Prolificacy was 2.1 (96/46) and 2.0 (74/37) for service and control does, respectively. Estrus duration (P<0.001) and fertility (P<0.05) differed between the service and control group, but prolificacy was similar (P>0.05). It is concluded that sterile service reduces the duration of estrus and increases fertility in artificially inseminated dairy goats.

Effect of a combined trenbolone acetate and estradiol implant on steady-state IGF-I mRNA concentrations in the liver of wethers and the longissimus muscle of steers.

Treatment of lambs (initial BW 28 kg) for 24 d with a combined implant containing 40 mg of trenbolone acetate (TBA) and 8 mg of estradiol (E2) increased ADG 25% (P < .05, n = 8) and feed efficiency 23% (P < .05, n = 2) compared with unimplanted lambs. By d 3 following implantation, sera from wethers implanted with TBA + E2 showed 32% (307 vs 233 ng/mL) increases (P < .001, n = 8) in IGF-I concentration compared with sera from unimplanted wethers. This increase was maintained throughout the entire 24-d study. Steady-state hepatic IGF-I mRNA levels were increased approximately 150% in implanted lambs compared with unimplanted lambs (P < .05, n = 4). These data suggest that liver may be the source of at least part of the increased circulating IGF-I in TBA + E2-implanted sheep. In steers implanted with Revalor-S (120 mg of TBA and 24 mg of E2) for 40 d, the steady-state concentration of IGF-I mRNA in the longissimus muscle was 68% greater than in the longissimus muscle of unimplanted steers (P = .013, n = 4). Consequently, increased local production of IGF-I by muscle tissue may play a role in increasing circulating IGF-I concentrations as well as an autocrine or paracrine role in stimulating muscle growth in steers implanted with Revalor-S.