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Biomedical subjects

S R Arthur

Publications and source records attributed to S R Arthur.

5 recordsLinked to original sources

Effects of chronic angiotensin-converting enzyme inhibition on left ventricular and myocyte structure and function during recovery from chronic rapid pacing.

LV and myocyte function and angiotensin converting enzyme (ACE) activity with ACE inhibitor (ACEI) treatment were examined in four groups of dogs (n = 6 each): (1) control; (2) with 4 weeks of recovery from chronic rapid pacing (REC: 216 beats/min), (3) ACEI for the first 14 days of REC (ACEI--14), and (4) ACEI for 28 days of REC (ACEI--28). Three additional control dogs were administered ACEI for 28 days. LV mass increased with REC compared to control (146 +/- 6 v 92 +/- 3 g, P < 0.05), was unaffected with ACEI--14, and was decreased with ACEI--28 compared to REC (111 +/- 8 g, P < 0.05). Myocyte function was decreased in REC compared to controls (43 +/- 3 v 63 +/- 3 microns/s, P < 0.05) and was similarly reduced with ACEI--14. However, with ACEI--28, myocyte shortening velocity was increased compared to REC (56 +/- 1 microns/s, P < 0.05). Myocyte beta-adrenergic response was decreased with REC and ACEI--14 compared to controls (53 +/- 9 and 57 +/- 14, respectively v 127 +/- 14 microns/s, P < 0.05). ACEI--28 resulted in a normalization of myocyte beta-adrenergic responsiveness (108 +/- 3 microns/s). LV myocardial ACE activity increased in REC compared to control (5.82 +/- 0.21 v 3.51 +/- 0.15 nmol/mg/min, P < 0.05). With ACEI--14 or ACEI--28, myocardial ACE activity was decreased compared to REC (4.16 +/- 0.06 and 4.08 +/- 0.23 nmol/mg/min; P < 0.05). In control dogs administered ACEI, there were no differences in any of these parameters compared to controls. The unique findings in this study were: (1) effects of ACEI treatment in this model of LV hypertrophy were time dependent with respect to LV mass and LV and myocyte function; and (2) the effect of ACEI treatment on the degree of LV hypertrophy appears to not be solely due modulation of myocardial ACE activity.

Adrenergic beta-Agonists↗

Cellular basis for improved left ventricular pump function after digoxin therapy in experimental left ventricular failure.

OBJECTIVES: The present study examined left ventricular (LV) and myocyte contractile performance and electrophysiologic variables after long-term digoxin treatment in a model of LV failure. BACKGROUND: A fundamental therapeutic agent for patients with chronic LV dysfunction is the cardiac glycoside digoxin. However, whether digoxin has direct effects on myocyte contractile function and electrophysiologic properties in the setting of chronic LV dysfunction remains unexplored. METHODS: Left ventricular and isolated myocyte function and electrophysiologic variables were examined in five control dogs, five dogs after the development of long-term rapid pacing (rapid pacing, 220 beats/min, 4 weeks) and five dogs with rapid pacing given digoxin (0.25 mg/day) during the pacing period (rapid pacing and digoxin). RESULTS: Left ventricular ejection fraction decreased in the dogs with rapid pacing compared with that in control dogs (30 +/- 2% vs. 68 +/- 3%, p < 0.05) and was higher with digoxin than that in the rapid pacing group (38 +/- 3%, p = 0.038). Left ventricular end-diastolic volume increased in the rapid pacing group compared with the control group (84 +/- 6 ml vs. 59 +/- 7 ml, p < 0.05) and remained increased with digoxin (79 +/- 6 ml). Isolated myocyte shortening velocity decreased in the rapid pacing group compared with the control group (37 +/- 1 microns/s vs. 59 +/- 1 microns/s, p < 0.05) and increased with digoxin compared with rapid pacing (46 +/- 1 microns/s, p < 0.05). Action potential maximal upstroke velocity was diminished in the rapid pacing group compared with the control group (135 +/- 6 V/s vs. 163 +/- 9 V/s, p < 0.05) and increased with digoxin compared with rapid pacing (155 +/- 12 V/s, p < 0.05). Action potential duration increased in the rapid pacing group compared with the control group (247 +/- 10 vs. 216 +/- 6 ms, p < 0.05) and decreased with digoxin compared with rapid pacing (219 +/- 12 ms, p < 0.05). CONCLUSIONS: In this model of rapid pacing-induced LV failure, digoxin treatment improved LV pump function, enhanced isolated myocyte contractile performance and normalized myocyte action potential characteristics. This study provides unique evidence to suggest that the cellular basis for improved LV pump function with digoxin treatment in the setting of LV failure has a direct and beneficial effect on myocyte contractile function and electrophysiologic measures.

Action Potentials↗

LV and myocyte structure and function after early recovery from tachycardia-induced cardiomyopathy.

Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals during the progression of tachycardia-induced dilated cardiomyopathy (DCM) and during a 1-mo recovery period from DCM (post-DCM). LV end-diastolic volume and LV wall stress increased and LV ejection fraction decreased with each week of pacing. Despite the increased LV wall stress, LV mass did not change during the progression of tachycardia DCM. One week post-DCM resulted in an improved LV ejection fraction and normalization of neurohormonal profiles. However, 1 wk post-DCM was accompanied by a 26% increase in LV mass and persistent LV chamber dilation. Isolated myocyte function was examined and compared with that in six normal control dogs. Myocyte percent and myocyte velocity of shortening were 19 and 32% lower, respectively, in the post-DCM group compared with controls. Thus termination of the tachycardia subsequent to the development of DCM resulted in persistent LV chamber dilation and abnormalities in myocyte contractile function. The improved LV pump function with early recovery from tachycardia-induced DCM was mediated by LV hypertrophy and a subsequent reduction in LV wall stress rather than a normalization of LV geometry and myocyte contractile function.

Animals↗

Restricted energy intake and elevated calcium and phosphorus intake for gilts during growth. III. Characterization of feet and limbs and soundness scores of sows during three parities.

Gilts that had previously been fed ad libitum or 75% ad libitum intake and 100 or 150% National Research Council recommended daily Ca and P from weaning to 100 kg were used in a reproductive study in which a 14% protein diet was fed. Foot and leg measurements, subjective toe scores and structural soundness scores were taken at each of three parities, 21 d postweaning. Sows previously ad libitum-fed generally had larger front toes than limit-fed sows; whereas, hind toes were larger for sows previously fed 150% Ca and P levels than sows fed 100% Ca and P. Sows previously fed the ad libitum-150% Ca and P diet had the largest toes. Front inside toes were larger than hind inside toes, but the reverse was observed for front and hind outside toes, with the magnitude of the difference between the inside and outside toes greater for the hind foot. Toe size increased over parities with the greatest increase from parity 2 to 3. Incidence and severity of toe pad and horn scores were generally unaffected by previously fed energy and Ca and P levels and were not correlated to toe size. Hind feet exhibited a larger number of lesions than front feet and outside toes exhibited a larger number of lesions than inside toes, with the hind outside toe exhibiting the greatest number of lesions. In general, incidence and severity of toe lesions decreased or were unchanged from parity 1 to 3. Structural soundness scores were unaffected by previously fed energy or Ca and P levels, but were quadratically affected by parity, with a small increase (poorer) from parity 1 to 2 and a large improvement from parity 2 to 3. Soundness scores were not related to any of the feet or leg measurements and characteristics. Restricting growth rate and feeding elevated Ca and P levels during growth had no effect on incidence and severity of lesions on the toes and overall structural soundness of sows kept for three parities.

Animals↗

Restricted energy intake and elevated calcium and phosphorus intake for gilts during growth. IV. Characterization of metacarpal, metatarsal, femur, humerus and turbinate bones of sows during three parities.

The effect of early nutrition on subsequent bone development was studied using gilts that had previously been fed ad libitum or 75% ad libitum intake and 100 or 150% National Research Council-recommended daily Ca and P from weaning to 100 kg. During the three-parity reproductive study, sows were fed a 14% protein diet. Metacarpals and metatarsals were taken from sows culled due to lameness or failure to breed and from sows after completing three parities. Femur and humerus articular cartilage and turbinates were described at necropsy. Metacarpals and metatarsals were heavier and tended to have thicker walls when sows were previously fed ad libitum or fed 150% Ca and P. Energy intake produced the greater response. Metacarpal breaking strength was greatest for sows previously fed ad libitum. Metatarsals were not affected by energy intake. Stiffness, Young's modulus of elasticity (YME) and flexural modulus for metacarpals and metatarsals were not affected by energy intake. Previously fed Ca and P intakes did not affect any of the mechanical bone characteristics. Metacarpals were heavier, had a greater breaking strength, were more elastic and exhibited slightly less resistance to bending than the metatarsals. The ether extract, ash, Ca and P content and the Ca:P ratio of metacarpals and metatarsals were not affected by previously fed energy or Ca and P intakes. The ether extract content tended to decrease and the ash, Ca and P content tended to increase with age. Articular cartilage and turbinate scores were not influenced by previously fed energy or Ca and P intakes. The YME and flexural modulus were the only bone characteristics that were even poorly correlated (average r = .25) with soundness scores, suggesting that high values result in poorer soundness scores. Energy and Ca and P intakes during growth and development had only minimal effects on bone characteristics and no apparent effect on structural soundness and longevity of sows kept for three parities.

Animals↗