Björn Wohlfart

The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder.

Brain-derived neurotrophic factor (BDNF) and other neurotrophins are believed to play an important role in affective disorders. In this study we investigated plasma-BDNF response during an incremental exercise test in 18 patients suffering from moderate major depressive disorder (MDD) and 18 controls. The patients were not treated with antidepressants or neuroleptics. Possible associations between plasma plasma-BDNF levels, dexamethasone suppression test cortisol levels and Montgomery-Asberg Depression Rating Scale (MADRS) scores were also tested. No difference in basal BDNF levels between patients and controls was found. BDNF increased significantly during exercise in both male and female patients as well as in male controls, with no significant differences between the groups. BDNF levels declined after exercise, but after 60 min of rest BDNF levels showed tendencies to increase again in male patients. No correlation between BDNF and cortisol or MADRS scores was found. We conclude that unmedicated patients with moderate depression and normal activity of the hypothalamic-pituitary-adrenal axis do not have a disturbed peripheral BDNF release during exercise. The BDNF increase 60 min after interruption of exercise in male patients might indicate up-regulated BDNF synthesis, but this needs to be further investigated in future studies.

Velocity of sarcomere shortening in rat cardiac muscle: relationship to force, sarcomere length, calcium and time.

The relation between force and velocity was determined in sixteen trabeculae of rat right ventricle as a function of time during a twitch, of sarcomere length and of external Ca2+ concentration, [Ca2+]o. The trabeculae were studied in modified Krebs‐Henseleit solution at 25 degrees C. Force was measured with a semiconductor strain gauge. Sarcomere length was measured with a laser diffraction system. A servomotor system was used in which control could be switched between sarcomere length, muscle length and force. Force‐velocity relations were derived from load clamps and from contractions in which sarcomere length was initially held constant followed by a quick release and slower release of the sarcomeres at controlled velocity. Force‐velocity relations were fitted by Hills equation (Hill, 1938), (Po‐P) b = (P+a) V, where P = force, V = velocity, Po = isometric force in mN/mm2 and a and b are constants. For [Ca2+]o = 2.5 mM, with both interventions the values (mean +/‐ S.D.) were: b = 1.00 +/‐ 0.45 micron/s; a = 9.52 +/‐ 5.60 mN/mm2; Vo measured = 13.6 +/‐ 3.0 micron/s; Vo calculated = 13.4 +/‐ 3.4 micron/s; Po measured = 96.5 +/‐ 25.0 mN/mm2; Po calculated = 119.3 +/‐ 34.5 mN/mm2. Vo rose with [Ca2+]o to a maximum at [Ca2+]o = 1.2 mM when Po was about 50% of maximum, while Po rose with [Ca2+]o to a maximum at above 2.5 mM. Vo rose with time during the twitch to a maximum at 25 ms following onset of contraction; Po was then about 50% of the maximum that was obtained at 120 ms. Vo increased with sarcomere length from zero at a sarcomere length of 1.6 micron to a maximum at 1.85 micron. Between 1.85 micron and 2.3 micron, Vo was constant. At 1.85 micron, Po was about 60% of maximum Po. These results are compatible with the hypothesis that Vo is more sensitive than Po to the amount of Ca2+ bound to the contractile proteins, and that Vo reaches a maximal value with an amount of Ca2+ bound to the contractile proteins at which Po has obtained only about 50% of its maximal value.

Relation between cardiac dimensions and peak oxygen uptake

BackgroundLong term endurance training is known to increase peak oxygen uptake () and induce morphological changes of the heart such as increased left ventricular mass (LVM). However, the relationship between and the total heart volume (THV), considering both the left and right ventricular dimensions in both males and females, is not completely described. Therefore, the aim of this study was to test the hypothesis that THV is an independent predictor of and to determine if the left and right ventricles enlarge in the same order of magnitude in males and females with a presumed wide range of THV.Methods and ResultsThe study population consisted of 131 subjects of whom 71 were athletes (30 female) and 60 healthy controls (20 female). All subjects underwent cardiovascular MR and maximal incremental exercise test. Total heart volume, LVM and left- and right ventricular end-diastolic volumes (LVEDV, RVEDV) were calculated from short-axis images. was significantly correlated to THV, LVM, LVEDV and RVEDV in both males and females. Multivariable analysis showed that THV was a strong, independent predictor of (R2 = 0.74, p < 0.001). As LVEDV increased, RVEDV increased in the same order of magnitude in both males and females (R2 = 0.87, p < 0.001).ConclusionTotal heart volume is a strong, independent predictor of maximal work capacity for both males and females. Long term endurance training is associated with a physiologically enlarged heart with a balance between the left and right ventricular dimensions in both genders.

The action-potential duration and contractile response of the intact heart related to the preceding interval and the preceding beat in the dog and cat

1. Simultaneous measurements were made in anaesthetized dogs of monophasic action potentials from the right ventricle and of the maximum rate of rise of left ventricular pressure (dPlv/dtmax). Atrio‐ventricular dissociation was induced and the heart paced via right ventricular electrodes.

Effects of low temperature on contraction in papillary muscles from rabbit, rat, and hedgehog.

During hibernation the body temperature may fall to only a few degrees above 0 degree C. The heart of the hedgehog continues to function whereas the hearts of nonhibernating mammals stop beating. The present study was performed to investigate and compare the mechanical responses to hypothermia in rabbits, rats, and hedgehogs. Isometric force was recorded from papillary muscles mounted in an organ bath and effects of hypothermia on the mechanical restitution curve were also compared. A reduction of bath temperature from 35 degrees C caused an increase in peak developed force. Maximum force was seen at 20 degrees C in the rabbit, 15 degrees C in the rat, and 10 degrees C in the hedgehog preparations. In all the species there was a similar prolongation of time to peak force and of time from peak to half-relaxation as temperature was lowered. An increase in resting force and after-contractions were recorded in the rabbit and rat muscles at temperatures below 15 and 10 degrees C, respectively. The rabbit and rat preparations became inexcitable at temperatures below 10 and 5 degrees C, respectively. The hedgehog papillary muscle, on the other hand, still contracted at 0 degree C and did not show increased resting force nor after-contractions. The results are consistent with the hypothesis that there is a calcium overload in cardiac cells from rabbit and rat at low temperatures but there is no calcium overload in the hedgehog muscle during hypothermia.

Temperature effects on the Na and Ca currents in rat and hedgehog ventricular muscle

Cardiac transmembrane potentials and Na and Ca currents were recorded at different temperatures in rat and hedgehog ventricular muscle. At 35 degrees C in both species resting potential was about -80 mV and upstroke velocity (Vmax) of the action potential above 100 V/s. The shape of the action potential in hedgehog ventricular cells at 35 degrees C was similar to that in the rat showing a fast repolarization phase. When temperature was decreased, the membrane resting potential depolarized and action potential amplitude and Vmax declined. In rat ventricular cells at 10 degrees C, the resting potential was about -40 to -50 mV and Vmax was reduced to about 5 V/s. In hedgehog ventricular cells, however, the transmembrane potentials and Vmax were better maintained at low temperature. Phase 3 of the action potential was markedly prolonged below 20 degrees C in hedgehog but not in rat ventricular cells. When temperature was decreased to 10 degrees C the availability curve of the Na current shifted toward more negative potentials and ICa.peak declined in rat ventricular cells. In hedgehog cardiac preparations, the Na current was less influenced by the cooling and ICa.peak did not change very much at low temperatures. A transient inward current usually considered to induce cardiac arrhythmias could be recorded in rat ventricular cells below 20 degrees C but not in hedgehog preparations. These features of hedgehog cardiac membranes may contribute to the cold tolerance and the resistance to ventricular fibrillation during the hypothermia in mammalian hibernators.

Manual versus mechanical cardiopulmonary resuscitation. An experimental study in pigs

BackgroundOptimal manual closed chest compressions are difficult to give. A mechanical compression/decompression device, named LUCAS, is programmed to give compression according to the latest international guidelines (2005) for cardiopulmonary resuscitation (CPR). The aim of the present study was to compare manual CPR with LUCAS-CPR.Methods30 kg pigs were anesthetized and intubated. After a base-line period and five minutes of ventricular fibrillation, manual CPR (n = 8) or LUCAS-CPR (n = 8) was started and run for 20 minutes. Professional paramedics gave manual chest compressions alternating in 2-minute periods. Ventilation, one breath for each 10 compressions, was given to all animals. Defibrillation and, if needed, adrenaline were given to obtain a return of spontaneous circulation (ROSC).ResultsThe mean coronary perfusion pressure was significantly (p < 0.01) higher in the mechanical group, around 20 mmHg, compared to around 5 mmHg in the manual group. In the manual group 54 rib fractures occurred compared to 33 in the LUCAS group (p < 0.01). In the manual group one severe liver injury and one pressure pneumothorax were also seen. All 8 pigs in the mechanical group achieved ROSC, as compared with 3 pigs in the manual group.ConclusionsLUCAS-CPR gave significantly higher coronary perfusion pressure and significantly fewer rib fractures than manual CPR in this porcine model.

Vectorcardiographic loop alignment and the measurement of morphologic beat-to-beat variability in noisy signals

The measurement of subtle morphologic beat-to-beat variability in the electrocardiogram (ECG)/vectorcardiogram (VCG) is complicated by the presence of noise which is caused by, e.g., respiration and muscular activity. A method was recently presented which reduces the influence of such noise by performing spatial and temporal alignment of VCG loops. The alignment is performed in terms of scaling, rotation and time synchronization of the loops. Using an ECG simulation model based on propagation of action potentials in cardiac tissue, the ability of the method to separate morphologic variability of physiological origin from respiratory activity was studied. Morphologic variability was created by introducing a random variation in action potential propagation between different compartments. The results indicate that the separation of these two activities can be done accurately at low to moderate noise levels (less than 10 /spl mu/V). At high noise levels, the estimation of the rotation angles was found to break down in an abrupt manner. It was also shown that the breakdown noise level is strongly dependent on loop morphology; a planar loop corresponds to a lower breakdown noise level than does a nonplanar loop.

Repeatability of measurements of oxygen consumption, heart rate and Borg's scale in men during ergometer cycling

The coefficient of repeatability (COR), expressed as 2 SD of differences, was calculated between two measurements of oxygen consumption ( ), heart rate (HR) and rating of perceived exertion (RPE) during ergometer cycling by men. The two sets of measurements were performed 5 to 6 weeks apart. Nineteen healthy men performed an incremental maximal exercise test on an ergometer cycle. The load started at 50 W and increased by 5 W 20 s−1 until exhaustion was reached. At 40% of the individual maximum load of the pretest, the load was kept constant for 4 min in order to reach steady state. Gas measurements were recorded continuously by computerized instrumentation. The HR was monitored with electrocardiography (ECG) and the perceived exertion was evaluated using Borgs scale. The COR of at sub‐maximal load was 14% and at maximum load 11%. The values in absolute figures were 209 and 332 ml min−1. The corresponding COR of the HR was 16% at sub‐maximum load and 6% at maximum load, and an evaluation of the perceived exertion yielded CORs in absolute values of 4·8 and 1·3, respectively. The COR for , HR and ratings of perceived exertion when cycling on an ergometer cycle thus indicate a better agreement between the measurements at maximum load. The COR of the heart at sub‐maximal loads must be kept in mind when using HR for estimation of . The reported findings should be considered when using tests on an ergometer cycle for evaluating exercise capacity.

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion.

Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP‐reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.