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Biomedical subjects

W W Monafo

Publications and source records attributed to W W Monafo.

At least 37 records · Page 2Linked to original sources

Regional spinal cord blood flow during local cooling.

We used the tissue distribution of [14C]butanol to quantitate regional blood flow in the spinal cord (RSCBF) of pentobarbital-anesthetized, normothermic rats in which segmental local cooling pentobarbital-anesthetized, normothermic rats in which segmental local cooling of the spinal cord (to 25-28 degrees C) at vertebral levels C4-C6 (n = 6) or T13-L1 (n = 6) was induced. Thirty minutes later, blood flow measurements were made at seven levels of the spinal cord and in the sciatic nerve trunks and biceps femoris muscles. Sham-cooled rats served as controls (n = 12). In control rats, RSCBF varied between 41.5 +/- 2.4 and 65.1 +/- 3.2 ml.min-1.100 g-1. Local cooling of the C4-C6 cord segment reduced RSCBF by 32%, from 65.1 +/- 3.2 to 44.4 +/- 3.5 ml.min-1.100 g-1 (P less than 0.01). Tissue vascular resistance (R) in the cooled C4-C6 segment was elevated versus control. There were no other changes in RSCBF at the other cord levels or in the cauda equina. Similarly, local cooling of the T13-L1 segment resulted in a 40% fall in RSCBF in that segment, from 57.1 +/- 2.4 to 34.1 +/- 4.3 ml.min-1.100 g-1 (P less than 0.001). R in the cooled T13-L1 segment was elevated versus control. RSCBF was reduced by 30% in the adjacent proximal T12 segment (P less than 0.001) and by 21% in the adjacent distal L2-L3 segment (P less than 0.05). R was increased in both of these adjacent segments. RSCBF was not altered elsewhere in the cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regional blood flow in transected rat spinal cord during hypothermia.

Regional blood flow (RBF) increases in the spinal cord and sciatic nerve of acutely hypothermic rats. To determine whether cord transection affects this response, we measured RBF in rat spinal cord and sciatic nerve 2 h after cord transection at vertebrae T8 (n = 18 rats) and T11 (n = 18 rats) using [14C]butanol distribution. Nine in each group were normothermic controls. In T11 transection-hypothermia (25-27 degrees C rectal temperature), RBF increased in the three rostral cord segments by 28-40% (P less than 0.05); caudally, cord RBF was depressed in two segments (P less than 0.05), unchanged in the other; RBF fell in nerve (P less than 0.05). In T8 transection-hypothermia, RBF was unchanged in the two rostral cord segments; caudally, RBF was depressed in one cord segment (P less than 0.05) and unchanged in the others; RBF was unchanged in nerve. We conclude that RBF does not rise in caudal spinal cord segments or in sciatic nerve during hypothermia in rats with prior spinal cord transection.

Animals↗

Current treatment recommendations for topical burn therapy.

Infections in burn patients continue to be the primary source of morbidity and mortality. Topical antimicrobial therapy remains the single most important component of wound care in hospitalised burn patients. The goal of prophylactic topical antimicrobial therapy is to control microbial colonisation and prevent burn wound infection. In selected clinical circumstances topical agents may be used to treat incipient or early burn wound infections. At the present time silver sulfadiazine is the most frequently used topical prophylactic agent; it is relatively inexpensive, easy to apply, well tolerated by patients, and has good activity against most burn pathogens. In patients with large burns the addition of cerium nitrate to silver sulfadiazine may improve bacterial control. Mafenide acetate has superior eschar-penetrating characteristics, making it the agent of choice for early treatment of burn wound sepsis. However, the duration and area of mafenide application must be limited because of systemic toxicity associated with prolonged or extensive use. Other agents, such as nitrofurazone or chlorhexidine preparations, may be useful in isolated clinical situations. The undesirable side effects of silver nitrate solution limit its use by most clinicians at the present time.

Administration, Topical↗

Regional blood flow in the brain and spinal cord of hypothermic rats.

[14C]butanol tissue uptake was used to measure simultaneously regional blood flow in three regions of the brain (cerebral and cerebellar hemispheres and brain stem) and in five levels of the spinal cord in 10 normothermic rats (group A) and in 10 rats in which rectal temperature had been lowered to 27.7 +/- 0.3 degrees C by applying ice to the torso (group B). Pentobarbital sodium anesthesia was used. Mean arterial blood pressure varied minimally between groups as did arterial pH, PO2, and PCO2. In group A, regional spinal cord blood flow (rSCBF) varied from 49.7 +/- 1.6 to 62.6 +/- 2.1 ml.min-1.100 g-1; in brain, regional blood flow (rBBF) averaged 74.4 +/- 2.3 ml.min-1.100 g-1 in the whole brain and was highest in the brain stem. rSCBF in group B was elevated in all levels of the cord by 21-34% (P less than 0.05). rBBF, however, was lowered by 21% in the cerebral hemispheres (P less than 0.001) and by 14% in the brain as a whole (P less than 0.05). The changes in calculated vascular resistance tended to be inversely related to blood flow in all tissues. We conclude that rBBF is depressed in acutely hypothermic pentobarbital sodium-anesthetized rats, as has been noted before, but that rSCBF rises under these experimental conditions. The elevation of rSCBF in hypothermic rats confirms our previous observations.

Animals↗

The effect of hypothermia on regional spinal cord blood flow in rats.

Spinal cord ischemia may accompany surgical procedures on the aorta or vertebral column. Regional spinal cord blood flow (SCBF) was measured at five vertebral levels in the spinal cords of pentobarbital-anesthetized rats based on the distribution of intravenously injected carbon-14-labeled butanol. In seven normal rats, mean SCBF (+/- standard error of the mean) ranged from 52.7 +/- 5.4 to 68.5 +/- 4.9 ml.min-1.100 gm-1 (depending on the level, being lowest at the thoracic levels) and mean arterial blood pressure (MABP) was 126 mm Hg. Corporal hypothermia (mean rectal temperature 28.1 degrees +/- 0.6 degrees C) was induced by cold exposure in seven other rats, and SCBF, measured immediately thereafter, was significantly elevated at all five levels by 52% to 69% compared to the normal group. However, MABP was elevated in the hypothermic group to 165 +/- 4 mm Hg (p less than 0.0001). Therefore, in seven additional hypothermic rats, MABP was maintained at the control level by withdrawal of arterial blood as necessary. In these animals, SCBF at all levels was still significantly elevated compared with the normal group and the values were nearly identical to those measured in the hypertensive hypothermic rats. It was concluded that hemodynamic autoregulation of SCBF is impaired in the presence of moderate systemic hypothermia in pentobarbital-anesthetized rats.

Animals↗

Topical silicone gel: a new treatment for hypertrophic scars.

A prospective, controlled clinical trial was designed to assess the efficacy of a new treatment of hypertrophic scars. Silicone gel sheeting was applied to 14 hypertrophic scars in 10 adults for 8 weeks. The treated scars and untreated, mirror-image or adjacent control scars were photographed, biopsy specimens were taken, and they were measured elastometrically before and after treatment. Photography and elastometry were repeated 4 weeks after treatment was discontinued. All the scars that had been treated for at least 12 hours a day were improved clinically after 4 weeks. There was further clinical improvement during the second 4 weeks of treatment. Elastometrically, the treated scars were improved significantly at 4, 8, and 12 weeks, compared with both their own treatment value and the control scars (p less than 0.05). Control scars were unchanged elastometrically. Clinical improvement persisted for at least 4 weeks after treatment was discontinued. The silicone gel sheeting was well tolerated, except for occasional transient rashes or superficial maceration--both of which resolved promptly when treatment was withdrawn. There was no histologic evidence of inflammation or foreign body reaction suggesting that silicone had entered the treated tissues. We conclude that this simple method of treating hypertrophic scar is efficacious, even in relatively chronic cases. The mechanism of action of silicone gel, which is apparently not related to compression, remains to be determined.

Administration, Topical↗

Regional blood flow in resting and stimulated sciatic nerve of diabetic rats.

The role of ischemia in the pathogenesis of diabetic peripheral neuropathy remains uncertain. We used the distribution of [14C]butanol to measure resting regional sciatic nerve blood flow in normal, anesthetized rats and in rats with acute experimental diabetes from streptozotocin administration. Regional flows in hind limb biceps femoris muscle and skin were simultaneously measured. In additional diabetic rats, these blood flows were compared in both limbs after proximal electrical stimulation of one sciatic trunk (10 shocks/s) for 15 min. One month after streptozotocin administration, 8 of 11 test rats were hyperglycemic. Resting nerve blood flow in the hyperglycemic rats--5.6 +/- 3.07 ml.min-1.100 g-1--was significantly less than that in the controls (9.4 +/- 3.9 ml.min-1.100 g-1, P = 0.002). Muscle blood flow was normal and skin blood flow decreased in these rats. Calculated tissue vascular resistances were elevated in all three tissues. Stimulation of one sciatic trunk in five other diabetic rats resulted in a stimulated nerve blood flow of 15.7 +/- 7.7 ml.min-1.100 g-1, and nerve blood flow in the resting control limb was 7.7 +/- 4.3 ml.min-1.100 g-1 (P = 0.009). Muscle blood flow increased approximately fourfold on the stimulated side but skin blood flow did not increase. Resting sciatic nerve blood flow is modestly decreased in acute streptozotocin-induced diabetes, but the neural blood vessels are still responsive to the increase in nerve metabolic activity associated with nerve stimulation.

Animals↗

[14C]butanol distribution: a new method for measurement of spinal cord blood flow.

[14C]butanol distribution was used to quantitate regional blood flow (SCBF) in the spinal cord (levels T3-5, T7-9, L1-2, L3-S) and in the sciatic nerves (NBF) of control pentobarbital sodium-anesthetized rats (group A), after 1 h of hemorrhagic hypotension (group B), after 15 min of stimulation of one sciatic nerve (group C-1), and after stimulation of one sciatic nerve plus hemorrhage, which maintained mean arterial pressure (MAP) at control (130 mmHg). Group A SCBF ranged from 52.3 +/- 3.5 (L3-S) to 67.4 +/- 2.7 (L1-2) ml.min-1.100 g-1. NBF was 8.0 +/- 0.9 ml.min-1.100 g-1. Group B SCBF was unchanged. NBF fell to 4.0 +/- 0.4 ml.min-1.100 g-1. Group C-1 SCBF was markedly elevated (range 122 +/- 23.1 to 150.1 +/- 18.7 ml.min-1.100 g-1). NBF was 33.5 +/- 4.1 ml.min-1.100 g-1 (stimulated side) and 14.7 +/- 1.4 ml.min-1.100 g-1 (nonstimulated). MAP was elevated (163 +/- 6 mmHg). In group C-2 (MAP was 130 +/- 4 mmHg), SCBF was still elevated at T3-5, L3-S, and marginally elevated at L1-2. NBF was 22.6 +/- 4.7 ml.min-1.100 g-1 (stimulated) but unchanged contralaterally. [14C]butanol distribution provides a sensitive reproducible measure of SCBF and NBF. Autoregulation of SCBF (but not of NBF) occurred in the range 60-160 mmHg MAP. Spinal cord stimulation via the sciatic nerve increased SCBF two- to threefold, but when hypertension was avoided by blood withdrawal, a modest (38%) increase in SCBF still occurred.

Animals↗

Elevated regional sciatic nerve blood flow in hypothermic anesthetized rats.

The effect of corporal hypothermia on regional blood flow in peripheral nerve is unknown. We compared blood flow in resting sciatic nerves of anesthetized, normothermic rats with that of rats whose rectal temperatures had been acutely lowered to 28 to 30 degrees C. Peripheral nerve regional blood flow in normothermic rats in which one hind limb was cooled was also measured, as were simultaneous flow changes in biceps femoris muscle and thigh skin. Flows were quantitated by the fractional distribution of [14C]butanol. Hypothermia was associated with increased peripheral nerve blood flow and a simultaneous decrease in muscle and skin blood flow. Nerve vascular resistance was not consistently altered in hypothermia, but muscle and skin vascular resistances were elevated. Topical cooling of one limb did not affect the tissue blood flows in either limb. The regulation of resting nerve blood flow in hypothermic rats differs appreciably from that in biceps femoris muscle and skin. Nerve blood flow did not increase with local cooling in normothermic rats. Central, neurally mediated mechanisms may be responsible for the increased regional nerve blood flow in hypothermic rats.

Animals↗

Sciatic nerve function following hindlimb thermal injury.

Peripheral neuropathy occurs in approximately 20% of patients with major burns and seriously impairs rehabilitation. We describe an experimental model which permits elevation of the tissue temperature in the region of the distal sciatic nerve trunk of rats at a reproducible rate to a predetermined level without inflicting concomitant major cutaneous injury. Radiofrequency current is delivered through parallel copper electrodes mounted in a chamber into which the limb has been inserted. In the present experiments, tissue temperature was arbitrarily elevated to 47 degrees C for 30 sec in 62 rats. There were 43 normal controls. The posterior tibial branch was the most intensively studied, as some of its conduction characteristics can be serially assessed percutaneously. Conduction block, which was apparently irreversible, was present in 67% of posterior tibials by 24 hr postinjury. In branches which were still excitable, prolongation of the absolute refractory period was the most consistent abnormality noted. Slowing of conduction, as evidenced by prolongation of inflection velocity or peak velocity, was never observed. However, this injury resulted in selective conduction failure of sural--but not of peroneal--fibers which conducted at 40 m/sec or greater. Fiber modality is an important determinant of the vulnerability to direct thermal injury of peripheral nerve in vivo.

Action Potentials↗

Topical therapy for burns.

Topical antimicrobial agents can prevent or minimize burn infections and should be used from the outset in all patients who are at significant risk from sepsis--either because of their wound severity or associated comorbid factors. All of the currently available topical agents have shortcomings; some of them have appreciable toxicity. The recent shift in emphasis toward early surgical closure of extensive deep burns in great part has resulted from appreciation of the inadequacies of currently available topical agents. Topical agents cannot substitute for timely and comprehensive physiologic support of burned patients.

Administration, Topical↗

Regional blood flow in sciatic nerve, biceps femoris muscle, and truncal skin in response to hemorrhagic hypotension.

Regional blood flow was measured simultaneously in rat sciatic nerves (NBF), truncal skin (SBF), and biceps femoris muscles (MBF) after graded hemorrhages. A modified 14C-butanol "indicator-fractionation" technique was used. In controls NBF was 11.4 +/- 1.38 ml X min-1 X 100 gm-1 and did not differ significantly between limbs. After hypotension, NBF was: 101 mm Hg, 7.7 +/- 1.3; 83 mm Hg, 5.3 +/- 0.6; 62 mm Hg, 4.1 +/- 0.6; 38 mm Hg, 3.1 +/- 0.3. The relationship between NBF and MAP was linear: (r = 0.56; p less than 0.001). SBF also declined linearly in hypotension (r = 0.54; p less than 0.01), but MBF did not change significantly. No significant change in nerve vascular resistance occurred with hypotension but muscle vascular resistance declined progressively. The data indicate a striking absence of autoregulation of NBF, but MBF, as expected, displayed close autoregulation. The vascular mechanisms which regulate resting NBF following hemorrhage differ from those in both muscle and skin: during hypotension, the calculated neurovascular resistance was unchanged, while the resistance in muscle fell and that in the skin increased.

Animals↗

Regional sciatic nerve blood flow response to limb movement.

The regional blood flow in the sciatic nerves (NBF), biceps femoris muscles (MBF), and hind limb skin (SBF) was measured simultaneously in anesthetized, normal rats, in other rats immediately after 15 min of electrical stimulation of one sciatic trunk (10 shocks/s), and in a group of similarly stimulated but previously curarized rats. These experiments were done to quantitate NBF during direct nerve stimulation in both the presence and absence of associated vigorous limb twitching, as these relationships have not previously been examined. Tissue blood flows were measured by an "indicator-fractionation" technic, using the distribution of [14C]butanol. NBF in normal controls was 11.1 +/- 1.4 ml X min-1 X 100 g-1; MBF was 6.8 +/- 0.6 ml X min-1 X 100 g-1. In the stimulated limb of noncurarized rats, NBF rose to 19.8 +/- 3.5 ml X min-1 X 100 g-1. MBF was elevated approximately tenfold. SBF also rose. In stimulated limbs of curarized rats, NBF was also approximately double the resting normal value, 23.2 +/- 4.8 ml X min-1 X 100 g-1, but MBF was then only slightly increased. We conclude that sciatic NBF increases appreciably when this nerve is stimulated, irrespective, for the most part, of whether limb motor activity is increased. The vascular mechanisms which regulate NBF differ from and are largely independent of those regulating MBF.

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Differential effects of in vitro heating on rat sciatic nerve branches and spinal nerve roots.

Locally applied heat induces nerve conduction block. Conflicting observations have been made regarding the relation of fiber conduction velocity to heat sensitivity. This study utilized sciatic nerve branches and spinal nerve roots which were heated until a substantial conduction block occurred. The results indicated that sensory fibers conducting at greater than 40 m/s are more heat-sensitive than motor fibers of the same conduction velocity.

Action Potentials↗

Potassium ion channel blockade restores conduction in heat-injured nerve and spinal nerve roots.

Compound action potentials were recorded in vitro from rat peroneal and sural nerves and from dorsal and ventral roots of the cauda equina before and after radiofrequency heating of 5-mm-length segments of these nerves to 41 to 45 degrees C. The heating was continued for intervals sufficient to reduce response amplitude by 50%. Inflection velocity, potential duration at 1/2 peak height, and the proportion of conducting A alpha fibers were also measured. The topical application of 4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA) to the previously heated segments immediately following the radiofrequency injury completely or near-completely restored amplitude height to the preheat value in all experiments. A alpha sensory fibers were the most susceptible to the conduction block. Conduction in these fibers was also the most readily restored by the application of 4-AP or TEA. The effects of TEA, but not of 4-AP, could be reversed by saline or buffer washing. Topical application of verapamil and of magnesium or calcium ions had no discernible effect on heated nerves. We suggest that the mechanism of heat-induced conduction block may be similar to that from early demyelination or stretch injury. Further, motor and sensory A alpha fibers differ both in their vulnerability to heat and in their subsequent response to the application of potassium channel blockers.

4-Aminopyridine↗

Regional sciatic nerve and muscle blood flow in conscious and anesthetized rats.

The regulation of peripheral nerve blood flow is incompletely understood. Regional blood flow in the rat sciatic nerve (NBF) and hamstring muscle (MBF) was measured in both conscious and anesthetized normal rats and in rats that had undergone surgical exposure of one sciatic nerve just prior to measurement. The distribution of [14C]butanol following its bolus intravenous injection was used to determine the flows in a modification of the "indicator fractionation" technique. NBF in normal rats was similar in limb pairs and was unaffected by pentobarbital sodium anesthesia. The pooled value was 12.5 +/- 1.1 ml X min-1 X 100 g-1. NBF was unaffected by sham operation in the conscious rats but was doubled in operated limbs of anesthetized rats (P less than 0.001). MBF in conscious normal rats was five times that measured during anesthesia. As in NBF, sham operation significantly increased MBF only in anesthetized rats (P less than 0.01). [14C]butanol distribution is a sensitive indicator of NBF and MBF. Mere surgical exposure of the nerve significantly increases NBF and MBF in anesthetized, but not in conscious rats.

Anesthesia↗

Protein dynamics in skeletal muscle after trauma: local and systemic effects.

Injury is attended by accelerated skeletal muscle proteolysis. Accurate definition of this hypercatabolic response and its mediation is requisite for specific therapy. We measured protein dynamics in the incubated and intact epitrochlearis and soleus muscles excised from both forelimbs and both hindlimbs of rats 4 days after injury by either a single hind limb scald (90 degrees C water for 3 seconds; metabolic rate (MR) + 15%, urinary urea nitrogen (UUN) + 10%) or a 5% excision (dorsal skin removed to fascia; MR + 40%, UUN + 90%). Protein synthesis (3H phenylalanine incorporation) increased only in the injured soleus from the scalded hind limb (+100%). Actin and myosin breakdown (3-methylhistidine release) increased in all muscles tested and was consistently larger in epitrochlearis than in soleus muscles. Breakdown of the mixed protein pool (tyrosine release) increased but less so than 3-methylhistidine and did not reach significance in the uninjured soleus muscle of scalded rats. With respect to fiber type, white fiber epitrochlearis muscle demonstrated a more pronounced elevation of both measures of breakdown but at a lower metabolic rate than did red fiber soleus muscle. Increasing MR was associated with a linear increase in soleus proteolysis but no further change in epitrochlearis breakdown. We conclude that protein breakdown is increased in skeletal muscle distant from injury; however, even when metabolic stress is severe, synthesis is unchanged. Muscles of different fiber composition are not equally labile. Furthermore, myofibrillar protein is more labile than the mixed protein pool.

Actins↗