Concentrate feeding strategy in lactating dairy cows: metabolic and endocrine changes with emphasis on leptin.

This study aimed to evaluate metabolic and endocrine adaptations to energy intake in multiparous Holstein cows (n = 90; mean 9434 kg energy-corrected milk yield/305 d) over the first 20 wk postpartum and to assess the association of leptin with metabolic, endocrine, and zootechnical traits. Concentrates were fed automatically for 24 h at 30% (C30) or 50% (C50) of total dry matter intake (DMI) from wk 1 to 10 postpartum and at linearly reduced amounts thereafter. Roughage was fed for ad libitum intake. The DMI was measured over 24 h; milk yield and body weight (BW), twice/d; milk composition, 4 times/wk; and milk acetone, weekly. Blood samples for determination of metabolite, hormone, and electrolyte concentrations and enzyme activities were obtained at wk 2 prepartum, and at wk 1 to 16 and at wk 20 postpartum from 0730 to 0900. Body condition scores (BCS) and backfat thickness were measured postpartum and during wk 1, 4, 8, 12, 16, and 20. Energy balance (EB) was considerably lower, but milk yield only slightly lower, in C30 than C50. Metabolic stress was more marked in C30 than C50, expressed by lower, glucose, insulin, insulin-like growth factor-1 (IGF-1), triiodothyronine, milk protein, and lactose concentrations, higher nonesterified fatty acid, beta-hydroxybutyrate, growth hormone, and milk acetone concentrations, and an accelerated decrease in BCS and backfat thickness. Nevertheless, C30 adapted successfully and thus maintained high milk yields despite negative EB. Leptin concentrations were lower in C30 than in C50 over the first 20 wk postpartum and were positively associated with BCS, EB, BW, cholesterol, albumin, insulin, and IGF-1; negatively associated with DMI and triiodothyronine; and were higher in cows calving in spring than in fall. Leptin is one among several factors involved in the regulation of energy metabolism and may be important for overall homeostatic and homeorhetic control of metabolism and thus for maintenance of performance.

Estimation of energy balance at the individual and herd level using blood and milk traits in high-yielding dairy cows.

This study aimed to estimate individual and herd-level energy balance (EB) using blood and milk traits in 90 multiparous high-yielding Holstein cows, held on a research farm, from wk 1 to 10 postpartum (p.p.) and to investigate the precision of prediction with successively decreased data sets simulating smaller herd sizes and with pooled samples. Dry matter intake, milk yield, and BW were measured daily from parturition through wk 10 p.p. Milk composition was determined 4 times per week, and milk acetone was measured weekly. Blood samples for the determination of metabolites, hormones, electrolytes, and enzyme activities were taken weekly from wk 1 to 10 p.p. between 0730 and 0900. Body condition scores and ultrasonic measurements of backfat thickness and fat depth in the pelvic area were evaluated in wk 1, 4, and 8 p.p. Concentrations of glucose, cholesterol, urea, insulin, insulin-like growth factor-1, triiodothyronine, and thyroxine (T4) in blood plasma and of lactose and urea in milk were positively correlated with EB, whereas concentrations of nonesterified fatty acids (NEFA), creatinine, albumin, beta-hydroxybutyrate, and growth hormone and enzyme activities in blood, and concentrations of fat, protein, fat:lactose ratio, and acetone in milk were negatively correlated with EB. Leptin concentration was not correlated to EB over the first 10 wk p.p. To estimate EB linear mixed-effects, models were developed by backward selection procedures. The most informative traits for estimation of EB were the fat:lactose ratio in milk and NEFA and T4 concentrations in blood. The precision of estimation of EB in individual cows was low. Using blood in addition to milk traits did not result in higher precision of estimation of herd-level EB, and decreasing sample sizes considerably lowered the precision of EB prediction. Estimation of overall mean herd-level EB over the first 10 wk p.p. using pooled samples was precise even with small sample sizes, but does not consider the level of EB in particular weeks. In conclusion, estimation of herd-level EB at individual weeks using milk traits only has practical implication with herd sizes of > or = 100 cows if calving is highly seasonal and of or = 400 cows if calving is uniformly distributed. Using blood in addition to milk traits does not improve precision of estimation of herd-level EB, regardless of sample size.

Alzheimer's disease-like cerebrovascular pathology in transforming growth factor-beta 1 transgenic mice and functional metabolic correlates.

Alzheimer's disease (AD) is frequently associated with cerebrovascular changes, including perivascular astrocytosis, amyloid deposition, and microvascular degeneration, but it is not known whether these pathological changes contribute to functional deficits in AD. To characterize the temporal relationship between amyloid deposition, cerebrovascular abnormalities, and potential functional changes, we studied transgenic mice that express transforming growth factor-beta 1 (TGF-beta 1) at low levels in astrocytes. TGF-beta 1 induced a prominent perivascular astrocytosis, followed by the accumulation of basement membrane proteins in microvessels, thickening of capillary basement membranes, and later, around 6 months of age, deposition of amyloid in cerebral blood vessels. At 9 months of age, various AD-like degenerative alterations were observed in endothelial cells and pericytes. Associated with these morphological changes were changes in regional cerebral glucose utilization. Preliminary results showed that TGF-beta 1 mice had significantly decreased glucose utilization in the mammillary bodies, structures involved in mnemonic and learning processes. Glucose utilization tended to be decreased in several other brain regions as well; however, in the inferior colliculus, it was markedly higher in TGF-beta 1 mice than in controls. We conclude that chronic overproduction of TGF-beta 1 triggers a pathogenic cascade leading to AD-like cerebrovascular amyloidosis, microvascular degeneration, and local alterations in brain metabolic activity. Similar mechanisms may be involved in AD pathogenesis.

Differentiated cerebrovascular effects of physostigmine and tacrine in cortical areas deafferented from the nucleus basalis magnocellularis suggest involvement of basalocortical projections to microvessels.

Cholinesterase inhibitors used to treat Alzheimer's disease according to the principle of cholinergic replacement therapy have proved to be less beneficial than expected. The present study was designed to investigate the cerebrovascular response to physostigmine and tacrine in the experimental model of lesioning of the nucleus basalis magnocellularis (NBM), a model involving a cholinergic deficit. Regional cerebral blood flow was measured by the [14C]iodoantipyrine tissue sampling technique in conscious rats infused with i.v. physostigmine (0.2 mg/kg/h), tacrine (8 mg/kg/h), or saline, 3-5 weeks after unilateral lesion of the NBM with ibotenic acid. Physostigmine and tacrine dose-dependently increased blood flow in most cortical and subcortical regions compared to the control group. However, physostigmine caused smaller blood flow increases in several areas, mostly cortical, of the lesioned compared to the intact hemisphere. The converse was observed with tacrine. A facilitated circulatory response appeared in cortical areas deafferented from the NBM, especially in the frontal cortex. These results provide evidence for distinct NBM-dependent components of the cortical cerebrovascular effects of physostigmine and tacrine. They suggest the involvement of different cellular postsynaptic targets of the NBM. The physostigmine-type effects could involve direct projects onto an inhibitory cortical interneuron supersensitized by deafferentation. This arrangement may explain why physostigmine and perhaps other cholinergic agonists are unable to specifically compensate for a deficit in NBM functioning. The tacrine-type effects presumably involve projections to the microvasculature, including perivascular astrocytes. The neurovascular junction would be sensitized by deafferentation from the NBM. Our data suggest that the regulatory mechanisms of blood flow originating in the NBM might constitute a target of neurodegenerative processes of Alzheimer's disease.

Dynamic in vivo measurement of erythrocyte velocity and flow in capillaries and of microvessel diameter in the rat brain by confocal laser microscopy.

A new method for studying brain microcirculation is described. Both fluorescently labeled erythrocytes and plasma were visualized on-line through a closed cranial window in anesthetized rats, using laser-scanning two-dimension confocal microscopy. Video images of capillaries, arterioles, and venules were digitized off-line to measure microvessel diameter and labeled erythrocyte flow and velocity in parenchymal capillaries up to 200 microm beneath the brain surface. The method was used to analyze the rapid adaptation of microcirculation to a brief decrease in perfusion pressure. Twenty-second periods of forebrain ischemia were induced using the tour-vessel occlusion model in eight rats. EEG, arterial blood pressure, and body temperature were continuously controlled. In all conditions, labeled erythrocyte flow and velocity were both very heterogeneous in capillaries. During ischemia, capillary perfusion was close to 0, but a low blood flow persisted in arterioles and venules, while EEG was flattening. The arteriole and venule diameter did not significantly change. At the unclamping of carotid arteries, there was an instantaneous increase (by about 150%) of arteriole diameter. Capillary erythrocyte flow and velocity increased within 5 seconds, up to, respectively, 346 +/- 229% and 233 +/- 156% of their basal value. No capillary recruitment of erythrocytes was detected. All variables returned to their basal levels within less than 100 seconds after declamping. The data are discussed in terms of a possible involvement of shear stress in the reperfusion period.

Directional variability of stimulation threshold measurements in isolated guinea pig cardiomyocytes: relationship with orthogonal sequential defibrillating pulses.

Reports on delivery of separated orthogonal pulses markedly improving cardiac defibrillation have suggested that the stimulation threshold of heart fibers varies in accordance with their orientation within the electric field. The present work was aimed at investigating the directional variability of stimulation thresholds in isolated guinea pig cardiomyocytes. This variability was measured in 48 single myocytes by rotating each one through a theta (theta) angle between two-fixed parallel electrodes 1.1 cm apart, thus making theta vary between the electric field and the myocyte axis. For theta = 0 degrees, the mean longitudinal current stimulation threshold was 16.92 +/- 4.20 mA (n = 48). When theta was increased by increments of 10 degrees up to 90 degrees, the stimulation threshold increased in an exponential way. For theta = 90 degrees, the mean transverse stimulation threshold was 63.13 +/- 13.30 mA. These results clearly demonstrate the dependence of isolated cardiomyocyte stimulation thresholds on their orientation within the electric field and may account for the improved efficacy of defibrillation previously observed after delivery of orthogonal pulses.

[Electrocoagulation of the His bundle node junction in dogs by a high-frequency current delivered by suction catheter]. / Electrocoagulation de la jonction nodo-hissienne chez le chien par un courant de hautes fréquences délivré avec cathéter à succion.

High-frequency currents constitute an attractive form of energy for transcutaneous myocardial destruction, but their potential for creating lesions varies with the nature of contact between electrode and skin. The adequacy of a suction catheter for electrocoagulation of the AV node-His bundle junction was assessed in 7 dogs. The high-frequency current (1.2 MHz) was delivered as bursts of 6 watts lasting 30 seconds, between the distal electrode of a bipolar catheter containing a central lumen (USCI 8F) and a wide skin electrode. During firing, an 80 kPa depression was applied to the lumen. Electrophysiological testing was performed before and immediately after firing. Continuous 24-hour Holter recording was carried out before, immediately after, then between the 2nd and 20th days post-firing. Following another electrophysiological study, the animals were killed on the 15th or 21st day for anatomical study. Complete atrioventricular block was obtained in all dogs during the first (n = 4) or second (n = 3) firing and persisted in 6 dogs up to the time of anatomical study. The atrial and right ventricular electrophysiological parameters remained unmodified after firing, and no severe ventricular arrhythmia was recorded during the study. The histological lesions were 4.7 +/- 0.7 mm in mean diameter and 3.1 +/- 0.6 mm in mean depth. It is concluded that electrocoagulation of the AV node-His bundle junction performed with high-frequency currents is a safe and selective technique. Using suction catheters makes this technique well reproducible with moderate amounts of energy. The development of preformed catheters should reduce the duration of the procedure.

Transcatheter radiofrequency ablation of atrial tissue using a suction catheter.

Closed chest ablative technique that avoid barotrauma would be attractive for ablation at thin walled cardiac structures, such as the atrial free wall or coronary sinus. Transcatheter radiofrequency (RF) currents produce tissue necrosis the size of which is dependent on the contact between the tissue and the electrode. In order to assess the effects of transvenous RF ablation of atrial free wall using a suction electrode catheter, we delivered in ten dogs, one single unmodulated RF pulse 1.2 MHz, in a unipolar mode, through the distal electrode of a lumen catheter (USCI 8F) (USCI, Billerica, MA USA) located in the right appendage. During the pulse an 80 KPa vacuum depression was applied to the lumen of the catheter. Each pulse had a 10 seconds duration and the mean delivered power was 4.3 +/- 1.4 W. Aortic pressure and electrocardiogram were monitored during the procedure. A right atrial electrophysiological study was performed at the ablated site, at control, after suction application and after RF pulse delivery. The animals were sacrificed after 14 or 21 days. Atrial pacing threshold values decreased after suction application in comparison to control values after the pulse (0.42 +/- 0.06 vs 0.60 +/- 0.23 mA, P less than O.05) but increased after the pulse delivery (2.60 +/- 1.85 mA, P less than 0.01). In contrast, the atrial effective refractory period did not significantly change after suction, nor after RF pulse delivery. Aortic pressure remained unchanged throughout the procedure. Complex arrhythmias were not observed during or after RF pulse delivery. One dog died suddenly at the first day after ablation, but this death was most probably unrelated to RF ablation. Anatomic lesions had a length of 8.8 +/- 3.3 mm, a width of 4.6 +/- 2.5 mm and a depth of 3.6 +/- 1.1 mm. They were transmural in nine of the ten dogs but without atrial wall perforation in any case. Lesions suggesting tissue volatilization were present in four dogs. These results demonstrate that low energy RF currents delivered with a suction electrode catheter can produce transmural necrosis of free wall, without risk of perforation. Such ablative technique would be of interest for ablation of right sided accessory pathways or atrial ectopic foci. Further experimental data are required in order to define the optimal energy level required to avoid tissue volatilization.

[Effect of the sinusal rate on experimental vagal atrial arrhythmia]. / Influence de la cadence sinusale sur les arythmies auriculaires vagales expérimentales.

Factors that facilitate the occurrence of cholinergic atrial arrhythmias were studied on 16 rabbit biatrial preparations in spontaneous rhythm. Sinus cycle length and characteristics of the atrial action potential were measured by the microelectrode technique in the basal state, then in the presence of acetylcholine at a concentration of 1.4 x 10(-5) M. Induction of arrhythmia was attempted by programmed stimulation, using an increasing number of extrastimuli. In the presence of acetylcholine the sinus cycle length increased by 106 +/- 63 p. 100 (p less than 0.0001) and the action potential duration, measured at 90 p. 100 repolarization (APD90) decreased from 60 +/- 15 ms to 40 +/- 11 ms (p less than 0.001). Reentrant activities, which had not been found in the basal state, were induced in 5 preparations. Under acetylcholine the sinus cycle of inducible preparations was shorter than that of non inducible preparations (663 +/- 272 ms vs 1218 +/- 531 ms, p less than 0.05). The percentage of sinus cycle lengthening was significantly smaller in inducible preparations (54 +/- 31 p. 100 vs 129 +/- 60 p. 100, p less than 0.05). Although sinus cycle lengthening was different in the two types of preparations, the APD90 was shortened in the same proportions. The vulnerability of the preparations seemed to depend mainly on a frequency effect. Vagal atrial arrhythmias occurred with a relatively small reduction in sinus rhythm. It is probable that an overpotent vagal effect is less arrhythmogenic because of its more homogeneous action on tissues.

[Electrophysiological, hemodynamic and histological effects of fulguration on the ventricular myocardium in the dog]. / Effets électrophysiologiques, hémodynamiques et histologiques de la fulguration sur le myocarde ventriculaire de chien.

The myocardial repercussions of endocavitary fulguration depend upon the interaction of different physical phenomena. We studied the influence of energy level on the one hand and of the physical properties of the catheter (Ct) on the other hand on the cardiac effects of right endoventricular fulguration in the dog. A monopolar anodal shock was delivered in 12 dogs. Two levels of energy were applied: 25 J (group A, n = 6) and 100 J (group B, n = 6), and three Ct were used which differed in resistance (R) and active surface (S): Ct 1 (R = 0.3 omega, S = 12 mm2), Ct 2 (R = 0.3 omega, S = 2 mm2) and Ct 3 R = 2 omega, S = 13 mm2). Immediately after fulguration a significant rise of the right ventricular effective refractory periods was observed in group B only (193 +/- 28 vs 174 +/- 19 ms; p less than 0.03). Compared to baseline values, the systolic and diastolic pressures fell by 12% (p less than 0.01) and 18% (p less than 0.01) respectively in group A and by 33% (p less than 0.05) and 34% (p less than 0.002) respectively in group B. In contrast, there was no significant difference between variations of these parameters with the three types of Ct. The incidence of complex ventricular arrhythmia was higher in group B (5/6) than in group A (1/6).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of physical parameters of fulguration on electrophysiological and anatomical properties of canine myocardium.

In order to determine the respective roles of catheter (Ct) physical properties and of energy levels in myocardial effects of fulguration, we delivered an electrical shock between the tip electrode of a Ct placed at the apex of the right ventricle and a large cutaneous cathodal electrode in 12 dogs. Two energy levels were used: Group A = 25 J (n = 6) and group B = 100 J (n = 6), and three Cts were studied. These Cts had different resistances (R) and active surface electrodes (S): Ct 1 (R = 0.3 omega, S = 12 mm2), Ct 2 (R = 0.3 omega, S = 2 mm2), Ct 3 (R = 2 omega, S = 13 mm2). Complex ventricular arrhythmias were observed in 5/6 cases at 100 J but only in 1/6 cases at 25 J and were independent of the Ct type. Following the shock, the effective ventricular refractory period (S1 S1 = 300 msec) increased significantly only at 100 J (11%, p = 0.03). Anatomical lesions were wider (10.6 vs. 5.2 mm, p less than 0.05) and deeper (100 vs. 55%, p less than 0.05) in the 100 J group. In contrast, there was no significant difference in the electrophysiological and anatomical changes between the three Cts. In conclusion, arrhythmogenic adverse effects of ventricular Ct fulguration are related to the delivered energy; on the contrary, they seem only slightly dependent on Ct physical properties at these energy levels; a 2 J/kg shock is not only effective but also seems to be safe.