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Biomedical subjects

C W Christensen

Publications and source records attributed to C W Christensen.

48 records · Page 3Linked to original sources
PubMed1976

Possible association of increased rat behavioral effects and increased striatal dopamine and norepinephrine levels during the DOPA-potentiation test.

Previous reports have indicated that alpha-MSH release inhibiting hormone (MIF-1) increased the behavior occurring as a result of the dihydroxyphenylalanine (DOPA) potentiation test [3,7]. This study was undertaken to see whether dopamine (DA) or norepinephrine (NE) levels likewise increased in the test animals. The DOPA potentiation test was performed as follows: 2-4 hr before behavior measurement, 40 mg/kg of the monoamine oxidase inhibitor pargyline HCl was given orally. Two hr later this was followed by the intraperitoneal (IP) injection of MIF-1 at doses of 0.1, 0.3 or 1.0 mg/kg. Behavioral measurement was begun after the IP injection of 200 mg/kg of dl-DOPA 1-2 hr after the MIF-1. The parameters included social interaction, aggressiveness, fighting, ataxia, jumping, defecation, urination and salivation. The animals were beheaded while the behavior was still increased and the striatal area removed, placed in aluminum foil, and kept at -50 degrees C until assayed. In general, especially among the younger animals, a significant correlation (p=0.05 to p=0.01) was found between the increased behavioral responses to MIF-I and the rise in DA. Because of a few exceptions to this correlation the possibility is suggested that MIF-I might also affect behavior by acting directly on the postsynaptic membrane thus bypassing any change in NE or DA which is known to increase cycli AMP in the striatum.

Animals↗
PubMed1976

Effects of L-prolyl-L-leucyl-glycine amide (MIF-I) on dopaminergic neurons.

In an attempt to determine the mechanism of action of L-proly-L-leucyl-glycine amide (MIF-I) in the treatment of Parkinson's disease, various parameters of dopaminergic neuronal function were studied in rats. It was found that the active uptake of 3H-dopamine (3H-DA) by synaptosome-rich homogenates of the striatum of rats treated with MIF-I (1 mg/kg IP X 3, 24 hr intervals) was unaltered 1 hr after final treatment with MIF-I. Also, neither tyrosine hydroxylase nor dopa decarboxylase activity was altered in the striatum and substantia nigra of rats treated with MIF-I (20 mg/kg IP X 3, 24 hr intervals). Thus, vital functional processes associated with dopaminergic neurons apparently are not altered by MIF-I under the conditions studied. These findings illustrate the importance of concurrent DOPA administration in observing an effect of MIF-I on dopaminergic neuronal function.

Animals↗
PubMedDate not supplied

Tolerance to cadmium in the abdominal stretch response: a comparative study of cadmium and acetic acid.

The intraperitoneal injection of cadmium (Cd) in mice produces a characteristic abdominal stretch response similar to that observed with acetic acid. Morphine, clonidine, and tripelennamine ED50 values were the same for inhibition of the response to Cd and to acetic acid. The ED50 values for aspirin and indomethacin were lower against the Cd than the acetic acid response. On repeated injections, Cd did but acetic acid did not produce tolerance to itself. Furthermore, the mice made tolerant to Cd were not cross-tolerant to acetic acid, but the acetic-acid-treated mice were cross-tolerant to Cd. These results suggest that Cd and acetic acid may produce the stretch response through different mechanisms, and the Cd-induced response might serve as a screening test for aspirin-like agents.

Abdominal Muscles↗
PubMedDate not supplied

Experimental studies of pulsatile flow and endothelial cell adaptation in ventricle shaped cell culture chambers.

The authors' long-term research goal is to minimize the risk of thromboembolic complications in cardiac prostheses by lining blood contacting surfaces with a functional monolayer of autologous endothelial cells. These cells recognize changes in hemodynamics and can adapt effectively to experimentally manipulated flow conditions. By implication, the morphology of endothelial cells, in conjunction with their function, might serve as an indicator of the flow patterns in a particular location. It was hypothesized that, by understanding flow patterns at a given site, the local morphology and function of the endothelial cells in such a region could be predicted. To test this hypothesis, a series of ventricle shaped flow chambers were designed and perfused with pulsatile flow. The flow field in the chambers was studied by computer aided dye visualization and nuclear scintigraphy. The results showed that the large scale motion of the fluid in the cavity was highly coherent and consisted of distinct flow patterns. The temporal and spatial characteristics of the flow patterns, and their implications with respect to endothelial cell endurance in this in vitro environment, were examined in detail.

Adaptation, Physiological↗
PubMedDate not supplied

In vitro assessment of the Milwaukee Heart and right to left balance.

A new, electrically powered, total artificial heart, the Milwaukee Heart, has been developed. This device is undergoing testing in vitro. The unidirectional motion of the brushless DC motor (BDCM) affords easier motor control and reduces energy demand. Motors with a unidirectional motion have a longer life than those with bidirectional motion. This device requires less power due to the highly efficient mechanical design. It consumes 6.5 W of power at an average flow of 5 L/min into 100 mmHg of mean aortic pressure and 20 mmHg of mean pulmonary pressure. Pumping at 8 L/min it requires 9.6 W of power. The maximum pump flow is 10 L/min and overall efficiency is 20%. A slotted optocoupler is used to determine the position of the pusher plate at the start of left systole. The number of revolutions that the BDCM makes is counted from this position. There are 50 revolutions of the BDCM per stroke (using a 50:1 gear reducer connected to the motor). The position of the pusher plate is determined from the number of BDCM revolutions. Based on where the pusher plate encounters resistance from the bladder, the force on the left pump is increased or decreased. Left to right balance has been achieved by reducing the size of the right pusher plate in conjunction with varying right stroke volume. In vitro tests show that this new, electrically powered artificial heart provides reliable performance and satisfactory hemodynamic results.

Biomechanical Phenomena↗
PubMedDate not supplied

Is it possible to perform immediate cardiac assist using untrained latissimus dorsi muscle in a work-rest regimen?

The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.

Animals↗
PubMedDate not supplied

Force enhancement of skeletal muscle used for dynamic cardiomyoplasty and as a skeletal muscle ventricle.

Some patients with pre end-stage congestive heart disease do not receive a significant hemodynamic benefit from dynamic cardiomyoplasty because, during prolonged preoperative immobilization, their latissimus dorsi muscle (LDM) becomes extremely weak. It is the authors' hypothesis that the local administration of an anabolic steroid into an electrically stimulated LDM will produce a thicker and stronger muscle with significant resistance to fatigue. The electrical stimulation training protocol of sheep continued for 8 weeks. For localized anabolic steroid administration an osmotic pump was placed in a subcutaneous pocket and the catheter was introduced into the LDM. The contractile force of electrically stimulated and unstimulated control muscle was studied. Control data were calculated as 100% and all other data were corrected to control. After 4 weeks there was no decrease in contractile force. The change seen was from 88 to 100% with different preloads (10, 15, and 20 g/kg) and amplitudes of impulses (5 and 10 V). After 8 weeks, the LDM was more powerful than before electrical stimulation, with a change of 97-133%. Usually after 8 weeks of electrical stimulation alone, contractile force decreases to 70-75%. During a fatigue test (30 min, 100 bursts per minute, 10-25 Hz, ripple frequency, 10 V impulse amplitude) after 4 and 8 weeks of our protocol, the LDM lost only 12% of its initial force, whereas control muscle lost 40%. Thus local anabolic steroid administration makes the LDM stronger and more useful for cardiomyoplasty.

Animals↗
PubMedDate not supplied

Skeletal muscle of a growing organism has a greater transformation after electrical stimulation than adult skeletal muscle.

Six adult sheep and four newborn lambs (5 days old) were implanted with stimulator leads into the latissimus dorsi muscle and connected to a Myostim 7220 pacing system (Telectronics Pacing Systems, Inc., Englewood, CO). Electrical stimulation was started immediately after the operation. After 8 weeks of electrical stimulation, contractile force (CF) in adult sheep decreased to 76-81%, and to 78-82% in lambs. After 2 weeks' delay, CF in adults was 96-98%, and only 89-93% in lambs. After a 30 min intensive stress test, unconditioned control muscle lost 39% in lambs and 43% in adults. Muscle conditioned for 8 weeks lost 7-8% CF. However, after 2 weeks' delay, CF in adult muscle lost 33%, but only 12% in lambs. After cessation of electrical stimulation, the LDH-5 and LDH-1 + 2 fractions reverted to initial levels in adults, whereas in lambs, these levels continued to follow trends established during electrical stimulation. In both adults and lambs, the percent area occupied by the mitochondria increased during electrical stimulation by 6.9% in adults and 6.5% in lambs. After electrical stimulation cessation, the percent area in adults returned to baseline levels, whereas it continued to be elevated in lambs (3.3% vs 5.1%, respectively). The transformed muscle of the lamb did not revert to baseline levels after a delay period.

Adaptation, Physiological↗
PubMedDate not supplied

Effects of nicorandil and nifedipine on protection of ischemic myocardium.

The effects of nicorandil and nifedipine on ischemia--reperfusion-induced myocardial infarct size following a 2-h occlusion and 30-min reperfusion period of the left anterior descending coronary artery (LAD) were compared in anesthetized dogs. Myocardial blood flow was measured using the radioactive microsphere technique, and infarct size was determined using triphenyl tetrazolium chloride histochemical stain. Vehicle, nicorandil (100-micrograms/kg bolus followed by 25 micrograms/kg/min), or nifedipine (10-micrograms/kg bolus followed by 1 microgram/kg/min) was administered intravenously 10 min after LAD occlusion and infused throughout the occlusion and reperfusion periods. Nicorandil and nifedipine reduced mean arterial blood pressure similarly (15 mm Hg) during infusion. However, neither drug altered collateral blood flow to the ischemic region during occlusion. In all three groups, left ventricular mass, area at risk mass, percentage of the left ventricle at risk, and retrograde flow during occlusion were similar. As compared with the control group, nicorandil reduced myocardial infarct size as determined by absolute mass, percentage of the area at risk infarcted, and percentage of the left ventricle infarcted. Nifedipine had no significant effect on infarct size. This beneficial effect of nicorandil was not related to an improvement in myocardial blood flow or a change in global hemodynamics.

Animals↗
PubMedDate not supplied

Application of a new nuclear scintigraphy camera to evaluate flow and mechanical pumping of artificial hearts.

To assist in the development of an artificial blood pump, The Milwaukee Heart (MH-1), a new nuclear scintigraphy camera was used to study the wash-in and wash-out patterns of the MH-1. These studies indicate the MH-1 has an ejection fraction of 59.3%, with a stroke volume of 72 +/- 3 ml, and an afterload of 130 mmHg. Flow through the device is highly uniform, with no areas of stagnation. Regional ejection fraction images demonstrate homogeneous ejection from apex to base. The ability to scan through the first pass images allows study of wash-in, mixing, and wash-out of the tracer. In conclusion, this technique may provide a new approach to evaluating artificial heart pumps.

Blood Flow Velocity↗
PubMedDate not supplied

Morphology and integrity of endothelial cell monolayers inside a ventricle shaped perfusion chamber.

The long-term maintenance of patients with failing hearts on cardiac prostheses requires prevention of device related thromboembolic events. This challenge is being addressed by endothelialization of the blood sacs. However, the practice of establishing and maintaining a durable endothelial cell monolayer inside a beating prosthesis has not been fully realized. Thus, before exposing endothelial cell monolayers to the hemodynamics inside an artificial heart, the authors studied the effect of various flow patterns in a ventricle shaped chamber on the integrity and morphology of the endothelium. After 20 hours of superfusion by pulsatile flow, there were no denudation signs in the jet, where shear stress was 1.5 dynes/cm2. However, there was measurable damage to the monolayer close to the periphery of the eddies (turbulent flow) at 0.15 dynes/cm2. In either case, there were no signs of cell alignment with the flow, but there were changes in cell morphology compared with that of static control. These findings suggest that adjustment of endothelial cells in response to frictional forces occurs even at low shear stresses and that random velocity fluctuations might jeopardize the integrity of endothelial cell monolayers.

Animals↗