The effects of conjugated deferoxamine in porcine skin flaps.

BACKGROUND: The free radical scavenger, deferoxamine (DFO) has been shown to reduce skin flap necrosis; however, its shortcomings are its toxicity and short plasma half-life. METHODS: This study investigates the effects of the less toxic, longer acting conjugated form, DFO-Hespan (DFO-H), to ischemic porcine skin flaps. During the study, DFO-H plasma concentrations and flap viability were evaluated over 10 days. RESULTS: Steady DFO serum levels were maintained with no evidence of systemic side effects. However, DFO-H was not effective in increasing porcine skin flap viability. Mean treated flap viability (n = 18) was 36.2% +/- 1.7% (mean +/- SE ) vs control (n = 16) 35.8% +/- 2.6%, p =.9. CONCLUSION: DFO-H conjugation increases its half-life and its systemic tolerance for DFO. However, this conjugation may also reduce DFO's effectiveness to preserve flap survival probably by decreasing its ability to reach the intracellular oxygen free radicals. In addition, further studies are needed to investigate whether longer DFO administration given postoperatively can be more effective in reducing ischemic injury.

Vascular and epidermal effects of fibroblast growth factor on irradiated and nonirradiated skin flaps.

Head and neck cancer surgeons are often faced with the challenge of managing previously irradiated soft tissue that has poor vascularity and slower epithelialization. This study investigates the effect of supplemental basic fibroblast growth factor (bFGF) on flap vascularity, tissue oxygenation, and epidermal regeneration in nonirradiated (n = 40) and irradiated porcine skin flaps (n = 40). Supplemental bFGF increased vascularity in nonirradiated flaps by 80% (p = .005), with a trend to a higher tissue oxygen level by day 14. The irradiated bFGF-treated flaps did not show increased vascularity or higher tissue oxygen levels 2 weeks after surgery. However, in both irradiated and nonirradiated groups, epidermal regeneration increased by greater than 70% with supplemental bFGF (p < .002). The results of this study suggest that supplemental bFGF can increase tissue vascularity in nonirradiated tissues and epidermal regeneration in both nonirradiated and irradiated conditions.

Doxorubicin chemomyectomy: effects on evoked vocal fold tension and mucosal wave.

Chemomyectomy of the thyroarytenoid muscle is a potential alternative approach to the management of spasmodic dysphonia (laryngeal dystonia) that could provide a prolonged response. To be useful, chemomyectomy should produce weakening of vocal fold closure without disruption of the mucosal wave. Sixteen dogs were studied. In 8 animals, doxorubicin hydrochloride (3 mg) and verapamil hydrochloride (0.5 mg) were injected unilaterally into the thyroarytenoid muscle 2 months before evaluation. The remaining animals served as noninjected controls. Injection of doxorubicin and verapamil decreased the average evoked tension of the vocal fold by 74.7%, compared to an average side-to-side difference of 12.7% in the control group (p = .001). A mucosal wave was recognized bilaterally with videostroboscopy in all dogs. Doxorubicin did not significantly change the vocal fold appearance or mucosal wave amplitude. These results support further laboratory study of chemomyectomy as a potential alternative treatment for laryngeal dystonia.

Effect of sleep state on the laryngeal chemoreflex in neonatal piglets.

The laryngeal chemoreflex (LCR) is a brain stem-mediated response that is a potential mechanism for sudden infant death syndrome. The vast majority of sudden infant death occurs during sleep, yet it remains to be established whether there is a particular sleep state that makes an infant animal more susceptible to apneic events via the LCR. The purpose of this study was to investigate the LCR during different sleep states in the neonatal piglet. In this study, continuous physiologic monitoring and electroencephalographic, electro-oculographic, and electromyographic techniques were utilized to study neonatal piglets during a hypnotic induced sleep model. Propofol drip anesthetic was utilized to provide an anesthetic state and was titrated for dose-dependent sedation. The LCR was initiated in 11 animals during quiet sleep, rapid eye movement sleep, and the anesthetic state. Baseline respiratory and cardiovascular responses were measured. Durations of apnea were recorded and compared. This study found that despite known physiologic differences in respiratory control during different sleep states as compared to the anesthetic state, there appears to be no increased risk of profound apnea in one state versus another in piglets 19 to 28 days old.

Effect of antagonism at central nervous system M3 muscarinic receptors on laryngeal chemoresponse.

The laryngeal chemoresponse (LCR), comprising laryngeal adductor spasm, central apnea, and subsequent cardiovascular instability, is thought to be a factor in sudden infant death syndrome. A muscarinic subtype receptor, M3, appears to be involved in central respiratory drive and control. Both the duration of the LCR apnea and levels of M3 receptor messenger RNA in the brain stem change according to postnatal age. This study examined the effect of central nervous system antagonism at M3 receptors on the LCR with respect to animal age and dose of antagonist. Ten piglets in each of three age groups (group 1, 5 to 8 days; group 2, 18 to 21 days; and group 3, 40 to 43 days) received a series of four increasing doses of an M3 antagonist (p-fluoro-hexahydro-sila-diphenidol) by intracerebral ventricle injection. The LCR was evoked at baseline and after each dose of antagonist. An effect on susceptible animals (groups 1 and 2) was evident by the second antagonist dose, and persisted for the remainder of the experiment (2 hours). At completion of the experiment, mean apnea duration had decreased in group 1 (61%, p < .05), and group 2 (57%, p < .05), but was unchanged in group 3 (<10%, p not significant). Length of mean baseline apneas correlated directly with degree of apnea shortening. The reduction is not attributable to changes in arterial PO2 or PCO2 or baseline respiratory rate. These results support an age-related influence on the LCR by M3 receptors in younger animals that decreases with maturation.

Effect of topical diphenhydramine on the laryngeal chemoreflex.

OBJECTIVE: To study diphenhydramine nebulization as a clinically applicable method for blunting laryngeal chemoreflex (LCR)-associated apnea. INTERVENTIONS: Fourteen piglets aged 15 to 18 days were studied. In 7 piglets, diphenhydramine hydrochloride (5.0 mg/kg) was nebulized onto the laryngeal mucosa after a baseline response was obtained. RESULTS: After a 10-minute waiting period, the mean +/- SD LCR-induced apnea duration decreased from 29 +/- 13 seconds in the control animals to 15 +/- 5 seconds in the treated group (P = .02, 1-factor analysis of variance). After 1 hour, no treatment effect was seen. CONCLUSIONS: Nebulization of diphenhydramine can effectively reduce LCR-induced apnea for a short time. Nebulization of longer-acting agents may provide an effective prophylaxis of LCR-induced apnea.

Effect of a second laryngeal stimulation during recovery from the laryngeal chemoreflex.

The laryngeal chemoreflex is a potential mechanism for sudden infant death. In experimental protocols in which a full recovery is allowed between stimuli, no laryngeal chemoreflex responses result in a fatal outcome. In the clinical situation there are no controls to prevent repeated laryngeal stimulation before a full recovery. The effect of a laryngeal stimulus applied during or soon after a laryngeal chemoreflex-induced apnea was investigated. Eighteen piglets were divided into groups aged 10 to 12 days, 17 to 21 days, and 32 to 36 days. Laryngeal stimulation was performed under normoxic conditions with water applied to the mucosa. Baseline respiratory and cardiovascular response data were measured. After recovery an initial stimulation was applied, followed by a second stimulation during the apnea or 5, 30, 60, or 120 seconds after restoration of breathing. No profound apneas occurred with baseline laryngeal stimulation. In piglets aged 32 to 36 and 17 to 21 days, a second laryngeal stimulus resulted in a shortened apnea duration. The response varied in piglets aged 10 to 12 days with profound apneas observed in 2 of 6 subjects and 4 of 30 trials. Piglets aged 17 to 36 days are less susceptible to the laryngeal chemoreflex during the immediate recovery period. In piglets aged 10 to 12 days, the laryngeal chemoreflex response may be more severe after a second stimulus.