Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers.

Clenbuterol, a beta 2-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especially at the single-fiber level, have not been fully characterized. Male C57BL/10 mice were allocated to three groups: Control-Treated mice were administered clenbuterol (2 mg.kg-1. day-1) via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases in Ca2+ sensitivity. Endurance exercise offset clenbuterol's effects, demonstrated by similar Ca2+ sensitivities in the Trained-Treated and Control groups. Long-term clenbuterol treatment did not affect the normalized maximal tension of fast or slow fibers but increased the proportion of fast fibers in the soleus muscle. Training increased the proportion of fibers with high and intermediate succinate dehydrogenase activity in the EDL and soleus muscles, respectively. If clenbuterol is to be used for treating muscle-wasting disorders, some form of low-intensity exercise might be encouraged such that potentially deleterious slow-to-fast fiber type transformations are minimized. Indeed, in the mouse, low-intensity exercise appears to prevent these effects.

When does a random flap die?

A random flap can be constructed, its circulation determined, and the ischemic portion identified. Left untreated for a period, the critical ischemia time, the ischemic portion will die and is clinically recognized several days later. What is not known is when this tissue, destined to die, actually dies. To ascertain this time, we compared the percent necrosis of a distal 3 x 3 cm segment of a 10 x 3 cm reverse McFarlane random flap with a known distribution of necrosis to the percent necrosis of the distal 3 x 3 cm of full-thickness skin grafts taken from a similar reverse McFarlane flap at 0, 4, 8, 12, and 16 hours after pedicle construction. Implicit in this experiment is the assumption that necrosis of the full-thickness skin grafts in excess of that of control animals represented skin no longer viable. Sometime between 8 and 12 hours, the percent necrosis of the full-thickness skin grafts surpassed that of the control, and it was concluded that this graft was dead prior to grafting. Thus it is suggested that critical ischemia time and death of the flap tissue are nearly identical, and the latter occurs at between 8 and 12 hours.

Fluorometric analysis of an attempt to reclaim ischemic flaps in rats with Fluosol.

An experiment was designed to answer two questions as they apply to random skin-flap survival: Is there a therapy that can improve random skin-flap survival when given postoperatively? And if so, when does one start such a therapy? Fluosol-DA 20% (Fluosol) has increased random skin-flap survival when given preoperatively in our laboratory. An experiment was devised to see if it could rescue failing flaps. One-hundred Sprague-Dawley rats were divided into a control (N = 25) and five experimental groups (N = 15). All had 10 X 13 cm reverse McFarlane random flaps raised and reinset. The experimental groups underwent hemodilution with either Ringer's lactate or Fluosol at 4, 8, and 12 hours after flap elevation. All were kept in 50% oxygen for 72 hours postoperatively. The flaps and their corresponding necrotic areas were measured on day 7. As to when to institute a therapy, we simultaneously evaluated the use of a microfluorometer as a monitor of flap survival. Analysis of flap survival showed little difference between control and experimental Ringer's lactate or Fluosol groups. Analysis of the microfluorometric data led to the following points. First, as a monitor of flap viability, it is limited by a lack of specificity and sensitivity. Second, comparison of the data from portions of the flap destined to live with those destined to die suggests that it may not be failure of circulatory inflow that leads to flap death.

The school-police partnership. Identifying at-risk youth through a truant recovery program.

A substantial amount of research has established that truancy is a consistent at-risk indicator of future criminality. This article studies the experiences of 178 juveniles targeted by the Truant Recovery Program, a collaborative and nonpunitive school-law enforcement effort, and considers questions regarding its impact through examination of juvenile justice and school information in the years before and after the truancy sweep. In particular, the article suggests that intensive cooperative efforts between school and police may be effective in identifying troubled youth and raises questions about appropriate school and justice system responses for children who demonstrate at-risk behavior.

Dermofluorometric prediction of flap survival.

Techniques to predict flap survival would help the reconstructive surgeon, but while various modalities exist, none is consistently accurate. The standard clinical method of fluorescein visualization by ultraviolet light requires such a high dose that it precludes rapid repetition. Recently, assessment of cutaneous fluorescein with the dermofluorometer has allowed mini-dose fluorescein, quantification, and repetition. The fiberoptic dermofluorometer was tested on experimental and clinical flaps. An experiment was devised to determine if the dermofluorometer could accurately predict flap survival. Modified McFarlane flaps were raised in 10 250- to 300-g female Sprague-Dawley rats and divided into 10 1-cm grids. A dermoviability index was calculated for each grid. A reading below 30% correlated with flap necrosis. Our clinical experiences were less predictive.

Endurance training effects on the contractile activation characteristics of single muscle fibres from the rat diaphragm.

1. Considerable debate exists as to whether the properties of diaphragm muscles can be modified by training. As the diaphragm is chronically activated during normal respiration, it is of interest to determine whether this muscle is resistant to further modification by exercise. The aim of this study was to investigate the contractile activation characteristics of single skinned muscle fibres from the diaphragm of both CONTROL and TRAINED rats. 2. Male rats were subjected to a 20 week high-intensity endurance exercise training programme that consisted of running on a motorized treadmill, 5 days/week, 90-120 min/day, 27-30 m/min, up a 20 degrees incline. At the conclusion of training, rats were killed with an overdose of ether and costal regions of the diaphragm were removed and stored in a glycerol-based skinning solution at -20 degrees C. 3. Single skinned (membrane-permeabilized) diaphragm muscle fibres were attached to a sensitive force transducer and activated in Ca(2+)- and Sr(2+)-buffered solutions in order to determine relative force-pCa and force-pSr characteristics. Fibres were allocated into discrete groups (population I, population II, intermediate, mixed) on the basis of their physiological (contractile) properties. 4. Population I (slow-twitch) fibres from the diaphragm of TRAINED rats exhibited a reduced sensitivity to Ca2+ (indicating a rightward shift of the force-pCa relationship) compared to those diaphragm fibres from CONTROL animals. An increased number of population II (fast-twitch) fibres were sampled from TRAINED rats, however, training did not affect the activation properties of these fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Contractile activation characteristics of single permeabilized fibres from levator palpebrae superioris, orbicularis oculi and vastus lateralis muscles from humans.

1. We investigated the contractile activation characteristics of single membrane-permeabilized fibres from the following muscles from humans: the levator palpebrae superioris (LPS), an extraocular muscle; the orbicularis oculi (OO), a facial muscle; and the vastus lateralis (VL), a major muscle of the thigh. 2. Single permeabilized muscle fibres were isolated from each of the different muscles, attached to a sensitive force transducer and activated by rapid immersion in buffered solutions of varying [Ca2+] and [Sr2+]. Fibres were allocated into discrete populations based on their contractile characteristics, including their differential force responses during Ca2+ and Sr2+ activation. 3. With the exception of one fibre from the LPS, all 152 fibres sampled from the three different human muscles could be classified into either population I (slow, type I) or population II (fast, type II) based on their force-pCa(pSr) relations. The LPS muscle fibre which was unable to be classified into the two major fibre populations displayed a combination of the typical force-pCa(pSr) relations for mammalian fast and slow muscle fibres. 4. Although fibres from the LPS, OO and VL muscles had similar differential sensitivities to Ca2+and Sr2+, the steepness of the force-pCa(pSr) curves for fibres from the LPS and OO muscles were highly variable compared with those for fibres from the VL muscle. Specific forces (N cm-2) of the smaller diameter fibres from the LPS and OO muscles were significantly lower than those of fibres from the VL muscle. 5. The differences in the contractile activation characteristics between fibres from the VL muscle and those of fibres from facial (OO) muscles and extraocular (LPS) muscles, reflect the differences in their fibre composition that are responsible for their functional specificity.