High Thoracic Epidural Anesthesia Does Not Inhibit Sympathetic Nerve Activity in the Lower Extremities

Background: Sympathetic nerve activity was recorded in the leg during high thoracic epidural anesthesia with a segmental sensory blockade of the upper thoracic dermatomes to test the hypothesis that the sympathetic blockade accompanying thoracic epidural anesthesia includes caudal parts of the sympathetic nervous system.

Methods: Experiments were performed on 10 patients scheduled for thoracotomy. An epidural catheter was inserted at the T3-T4 or T4-T5 interspace. In the main protocol (seven patients), blood pressure, heart rate, and skin temperature (big toe, thumb) were continuously monitored, and multiunit postganglionic sympathetic nerve activity was recorded with a tungsten microelectrode in a muscle-innervating fascicle of the peroneal nerve. After baseline data collection, muscle sympathetic nerve activity was recorded for an additional 45-min period after epidural injection of 4-6 ml bupivacaine, 5 mg/ml. In an additional three patients, the effects of thoracic epidural anesthesia on skin-innervating sympathetic nerve activity were qualitatively assessed.

Results: Activation of thoracic epidural anesthesia caused no significant changes in peroneal muscle sympathetic nerve activity (n = 7), blood pressure, or heart rate. Skin temperature increased significantly in the hand 15 min after activation of the blockade, from 32.7 +/- 2.4[degrees]C to 34.4 +/- 1.5[degrees]C (mean +/- SD), whereas no changes were observed in foot temperature. The sensory blockade extended from T1 (C4-T2) to T8 (T6-T11).     

Androgen-Receptor Blockade Does Not Impair Bone Mineral Density in Adolescent Females

The effect of peripheral androgen hypersensitivity on bone mineral density (BMD) was investigated in a group of adolescent women with idiopathic hirsutism (n= 17; mean age 17.0 ± 1.7 years). The effect of long-term androgen-receptor blockade with flutamide (500 mg daily in two divided doses for 12 months) on BMD was assessed too. BMD was measured at lumbar spine (L2–L4) by a dual energy X-ray densitometer. Before flutamide treatment, patient BMD (1.14 ± 0.07 g/cm²) was not significantly different from that of the control group (1.16 ± 0.12 g/cm², n= 22), and was normal for age and sex (BMD 0.14 ± 0.69 SDS, P= NS vs. 0). After 12 months of treatment, absolute BMD in patients increased (1.18 ± 0.08 g/cm², P < 0.002), but SDS BMD did not change (0.21 ± 0.72, P= NS vs. baseline). Flutamide treatment determined a clinical, marked improvement of androgen hypersensitivity (Ferriman–Gallwey score: before 22.0 ± 6.2; 6 months: 13.2 ± 6.4, P < 0.003; 12 months; 7.6 ± 4.1, P < 0.001; acne score: before 3.8 ± 0.8; 3 months 0.8 ± 0.5, P < 0.001; later disappeared). The serum levels of 3α-androstenediol-glucoronide decreased (before: 8.6 ± 1.1 μg/liter; 12 months: 7.2 ± 1.0 μg/liter, P < 0.02), whereas the other endocrinological parameters did not change. No relationship was found between BMD and clinical or biochemical parameters of hyperandrogenism. We concluded that in adolescent women, peripheral hyperandrogenism is not associated with abnormal BMD; long-term treatment with flutamide, which blocks the androgen receptor, does not alter their BMD. Received: 19 February 96 / Accepted: 31 December 96     

Sympathetic Nervous System Does Not Mediate Reflex Pupillary Dilation during Desflurane Anesthesia

Background: Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system. Noxious stimulation dilates the pupil in both unanesthetized and anesthetized humans. In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system. In contrast, pupillary dilation in cats given barbiturate or cloralose anesthesia is mediated solely by inhibition of the midbrain parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils during anesthesia in humans remains unknown. Accordingly, the authors tested the hypothesis that the pupillary dilation in response to noxious stimulation during desflurane anesthesia is primarily a parasympathetic reflex.

Methods: In six volunteers, the alpha-1 adrenergic receptors of the iris musculature were blocked by unilateral administration of topical dapiprazole; six other volunteers were given unilateral topical tropicamide to block the muscarinic receptors in the iris. Desflurane anesthesia was subsequently induced in all volunteers. Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane, and by a rapid 4%-to-8% step-up in the desflurane concentration. Pupil diameter and the change in pupil size induced by a light stimulus (light reflex amplitude) were measured with infrared pupillometry.

Results: Dapiprazole drops produced a Horner's miosis, but pupils were equally small after induction of anesthesia. Pupillary dilation after noxious stimulation and desflurane step-up was identical in the unblocked and dapiprazole-blocked pupils. After tropicamide administration, the pupil was dilated and the light reflex was completely inhibited. Noxious stimulation nonetheless produced a slight additional dilation.     

Signal-averaged P-wave Duration Does Not Predict Atrial Fibrillation after Thoracic Surgery

Background: Atrial fibrillation (AF) is the most common dysrhythmia seen early after major thoracic surgery but occurs infrequently after minor thoracic or other operations. A prolonged signal-averaged P-wave duration (SAPWD) has been shown to be an independent predictor of AF after cardiac surgery. The authors sought to determine whether a prolonged SAPWD alone or in combination with clinical or echocardiographic correlates predicts AF after elective noncardiac thoracic surgery.

Methods: Of the 250 patients enrolled, 228 were included in the final analysis. Preoperative SAPWD was obtained in 155 patients who had major thoracic surgery and in 73 patients undergoing minor thoracic or other operations who served as comparison control subjects. The SAPWD was recorded from three orthogonal leads using a sinus P-wave template. The filtered vector composite was used to measure total P-wave duration. Clinical, surgical, and echocardiographic parameters were collected and patients followed for 30 days after surgery for the development of symptomatic AF.

Results: Symptomatic AF developed in 18 of 155 (12%) patients undergoing major thoracic surgery and in 1 of 73 (1%) patients having minor thoracic or abdominal surgery, most commonly 2 or 3 days after surgery. In comparison with similar patients undergoing major thoracic surgery without AF, those who developed AF were older (66 +/- 8 vs. 62 +/- 10 yr; P = 0.04) but did not differ in SAPWD (145 +/- 17 vs. 147 +/- 16, ms) in standard electrocardiographic P-wave duration (105 +/- 7 vs. 107 +/- 10 ms), incidence of left-ventricular hypertrophy on 12-lead electrocardiography, male sex, history of hypertension, diabetes, or coronary heart disease. Thoracic-surgery patients at risk for postoperative AF did not differ from all other patients at low risk for AF in clinical or SAPWD parameters.     

Blockade of Macrophage Migration Inhibitory Factor Does Not Prevent Acute Renal Allograft Rejection

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory molecule involved in cell-mediated immunity and delayed-type hypersensitivity (DTH). We inhibited systemic and local MIF production to determine its contribution to acute rejection (AR). Skin DTH response and acute rejection of skin and kidney allografts were examined using MIF gene knockout (MIF -/-) and wild-type mice (MIF +/+) with anti-MIF or control antibody. MIF-Ab reduced skin DTH by 60% (p < 0.01), but absence of the MIF gene (MIF -/-) had no effect. Local absence of MIF had no effect on the survival of skin grafted onto BALB/c recipients. Similarly MIF +/+ and MIF -/- kidneys transplanted into BALB/c recipients showed a similar degree of histological rejection, graft dysfunction and cellular infiltrate suggesting that AR is not dependent on local MIF production. To investigate the influence of systemic MIF, BALB/c donor skin was grafted onto MIF +/+ and MIF -/- mice. The tempo of AR was not altered by systemic absence of MIF (MIF-Ab or MIF -/-). BALB/c kidneys transplanted into MIF +/+ (with or without MIF-Ab) and MIF -/- mice showed similar parameters of rejection. MIF blockade reduces the DTH response; however, neither local nor systemic MIF are required for the rejection of fully mismatched skin and renal allografts.     

Angiotensin Blockade Does Not Affect Fibrosis Progression in Recurrent Hepatitis C After Liver Transplantation

Background

Liver transplantation (LT) for hepatitis C virus (HCV)–related end-stage liver disease is impaired by universal disease recurrence and suboptimal response to antiviral therapy. Inhibition of angiotensin-II signalling by angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II receptor blockers (ARB) decreases hepatic stellate cell activation in vitro and hepatic fibrogenesis in animal models. A single-center retrospective analysis suggested that angiotensin blockade (AB) inhibits fibrosis progression in recurrent HCV post-LT. This study assessed the effect of AB on fibrosis progression in an independent patient cohort.

Methods

Chart review of all patients who underwent transplantation in our institution for HCV-related ESLD between January 2000 and February 2008 revealed 109 patients with ≥2 protocol liver biopsies and free of antiviral therapy post-LT up to the last biopsy analyzed; 27 of 109 patients were treated with ACE-I/ARB for ≥12 months, 82 were not. Fibrosis was staged using METAVIR.

Results

Live-donor LT was more frequent in controls than in the AB group (25% vs 11%; P < .05). However, parameters known to affect outcome of recurrent HCV, including donor age, prevalence of diabetes, acute cellular rejection, and immunosuppression, were similar in both groups. Time between first and last biopsy (median, 23 months), stage of fibrosis, fibrosis progression rates (median 0.47 vs 0.45 unit/y; P = .46), and time to develop fibrosis stage ≥2 did not differ between groups. Results held true if deceased-donor LT were analyzed separately.

Conclusion

Our study does not support the contention of a previous report that use of AB reduces fibrosis progression in recurrent HCV post-LT.     

Donor and Recipient Hepatitis C Status Does Not Affect Rejection in Thoracic Transplantation

BackgroundDonors with hepatitis C virus (HCV) have expanded the donor pool for heart and lung transplantation, but concerns have arisen about rejection. We examined the incidence of rejection after heart and lung transplantation in recipients of HCV-positive donors as well as HCV-positive recipients.MethodsAdults undergoing heart and lung transplantation from March 31, 2015 to December 31, 2019 were identified in the United Network for Organ Sharing/Organ Transplantation and Procurement Network Standard Transplant Analysis and Research file. Patients were stratified as donor–recipient HCV negative, donor positive, and recipient positive. Comparative statistics and a multilevel logistic regression model were used.ResultsMeeting the criteria were 10 624 heart transplant recipients. Donor-positive recipients were significantly associated with older age, blood group O, and shorter waitlist time. No significant differences existed with regards to treatment for rejection in the first year (negative, 19.5%; donor positive, 22.3%; recipient positive, 19.5%; P = .45) or other outcomes. On regression analysis HCV status was not associated with treated rejection; however center variability was significantly associated with treated rejection (median odds ratio, 2.18). Similarly, 9917 lung transplant recipients were identified. Donor-positive recipients were more commonly White and had obstructive disease and lower lung allocation scores. Both unadjusted (negative, 22.1%; donor positive, 23.0%; recipient positive, 18.6%; P = .43) and adjusted analyses failed to demonstrate a significant association between HCV status and treatment for rejection, whereas center variability remained significantly associated with treatment for rejection (median odds ratio, 2.41).ConclusionsUse of HCV donors has expanded the donor pool for heart and lung transplantation. HCV donor status was not associated with treatment for rejection in the first year, but center variability played a role in the incidence and treatment of rejection.     

Cerebral Blood Flow and Oxygen Consumption in Normocapnia and Hypercapnia: Modulating Influence of Paravertebral Sympathetic Blockade at the Low Thoracic Level

The objective of the present study was to explore whether the systemic consequences of sympathoadrenal activation influence the cerebral circulatory and metabolic effects of hypercapnia in the rat. To that end, a bilateral blockade of the sympathetic chain was performed at the low thoracic level by paravertebral injection of local anaesthetic. The injection was followed by a reduction in blood pressure and, in comparison to animals injected with local anaesthetic intramuscularly, those with paravertebral blockade showed lower blood and tissue concentrations of glucose and lactate. Overall ("cortical") CBF and CMRO2 were measured with a 133xenon modification of the Kety-Schmidt technique, and local CBF was estimated autoradiographically with 14C-iodoantipyrine as the diffusible tracer. Paravertebral blockade failed to modify the circulatory response to hypercapnia, nor did it prevent the increase in CMRO2d previously noted in this preparation. In animals maintained ventilated on 70% N2O, paravertebral blockade reduced overall CBF by 30% and local CBF by 30-40%, with a suggested but statistically nonsignificant reduction in CMRO2. In unparalysed, awake animals the blockade failed to affect local CBF. It is concluded, therefore, that blockade of the sympathetic chain causes a reduction of CBF only in the stressful conditions prevailing in paralysed and ventilated animals.