Giulio Gherardini

Fat necrosis in free and pedicled TRAM flaps.

&NA; One purported advantage of the free transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction is that, compared with the conventional TRAM flap, it has a better blood supply and therefore a lower incidence of fat necrosis. We tested this claim by reviewing the incidence of fat necrosis, both clinically and mammographically, in a group of 110 patients with 116 TRAM flap breast reconstructions who had undergone mammography of their reconstructed breasts. Of the 49 breasts reconstructed with free TRAM flaps, 4 (8.2 percent) had clinically evident fat necrosis, and 1 (2.0 percent) had fat necrosis that was detectable by mammography. Of the 67 breasts reconstructed with conventional TRAM flaps, 18 (26.9 percent) had clinically detectable fat necrosis, and 9 (13.4 percent) had fat necrosis that was detectable mammographically. Both of these differences were statistically significant (p = 0.0113 for clinical fat necrosis; p = 0.031 for mammographic fat necrosis). Fat necrosis was more common in patients who were obese or had a history of smoking, but neither association was statistically significant. We conclude that the use of the free TRAM flap reduces the incidence of fat necrosis in the reconstructed breast. (Plast. Reconstr. Surg. 102: 1502, 1998.)

Comparison of vascular effects of ropivacaine and lidocaine on isolated rings of human arteries.

Ropivacaine is a new local anaesthetic agent. Previous animal studies have indicated that vasoconstrictor effects are elicited by ropivacaine in vitro and subcutaneously and that it produces blanching of the skin if injected subcutaneously in humans.

Spinal cord stimulation improves survival in ischemic skin flaps: an experimental study of the possible mediation by calcitonin gene-related peptide.

Currently, spinal cord stimulation is used to treat ischemia and ischemic pain, with the best results observed in vasospastic cases. It was earlier demonstrated that spinal cord stimulation may attenuate experimentally induced vasospasm in an island flap in the rat. The present study was designed to investigate whether preemptive spinal cord stimulation could increase long-term flap survival and to explore the neurohumoral mediation of the effect. A total of 56 rats were implanted with chronic spinal cord stimulation systems. Three days later, a groin flap based on the superficial epigastric vessels was harvested, and the single feeding artery was occluded by a detachable microvascular clip. After 12 hours, the clip was removed. Flap survival was evaluated after 7 days. Immediately before flap surgery, two groups of animals received 30 minutes of stimulation using current clinical parameters and with stimulation amplitudes of 70 (n = 10) or 90 percent (n = 8) of that evoking muscular contractions. The outcomes in these groups were compared with those in two control groups (n = 20; n = 10). In one group, an additional calcitonin gene-receptor peptide (CGRP) antagonist was intravenously injected before stimulation (n = 8). In the control groups without stimulation, virtually all flaps necrotized. In treated groups, flap survival was 60 percent at the lower intensity and almost 90 percent at the higher one. The administration of a CGRP antagonist before treatment reduced its efficacy to below 40 percent survival. The differences between the untreated and treated groups were significant. The decrease in survival after CGRP-receptor block was significant in one of two tests. Preemptive spinal cord stimulation increases survival of skin flaps with critical ischemia. The effects are dependent on the stimulation intensity and are possibly mediated by the release of CGRP in the periphery.

Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery.

&NA; Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs‐Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 &mgr;M), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9‐0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentrationdependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re‐evaluated, since this substance may act as a partial agonist. (Plast. Reconstr. Surg. 100: 1475, 1997.)

Venous ulcers : Improved healing by iontophoretic administration of calcitonin gene-related peptide and vasoactive intestinal polypeptide

&NA; A study on the effects of iontophoretic administration of calcitonin gene‐related peptide and vasoactive intestinal polypeptide on the healing of venous stasis ulcers of the extremities was carried out on 66 patients. Two randomized groups of patients were compared, one receiving standard treatment plus iontophoresis of calcitonin generelated peptide and vasoactive intestinal polypeptide, and the other receiving standard treatment plus placebo iontophoresis. Calcitonin gene‐related peptide and vasoactive intestinal polypeptide were administered locally by iontophoresis for 20 min three times weekly for 12 weeks. To determine the effects of the two treatments, the percentage surface area of ulcer healed and the number of healed ulcers were compared after 2, 4, 6, 8, and 12 weeks of treatment. The results demonstrate that there were significant improvements of the healing process in the group treated with calcitonin gene‐related peptide and vasoactive intestinal polypeptide when compared with placebo iontophoresis, and support the use of iontophoresis administration of calcitonin gene‐related peptide and vasoactive intestinal polypeptide in the treatment of venous ulcers. (Plast. Reconstr. Surg. 101: 90, 1998.)

Drug‐induced vasodilation: In vitro and in vivo study on the effects of lidocaine and papaverine on rabbit carotid artery

Flap ischemia is often encountered during pedicled and free tissue transfer. In this study, the vascular effects of varying doses of lidocaine, papaverine, and a combination of the two agents were evaluated and compared in an in vitro and in vivo model in the rabbit carotid artery. In the in vitro study, 14 rings from the rabbit carotid artery were bathed in Krebs‐Ringers solution and stretched progressively to an optimal tension of 3.7–4.2 grams. Their isometric contractile activity was measured. The specimens were precontracted with norepinephrine (1 μM), and a dose response curve was established by adding cumulatively either lidocaine (to 7 arterial rings) or papaverine (to 7 arterial rings) at increasing concentrations. In the in vivo study, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 30 animals using 9–0 nylon suture and standard microsurgical techniques. In each animal, one side was treated with heparinized sodium chloride and served as the control. The other side was treated blindly, during and after the anastomoses, with a topical application of 1 ml of either lidocaine 2% (n = 5), lidocaine 20% (n = 5), papaverine (30 mg/ml, n = 5), lidocaine 2% combined with papaverine (30 mg/ml, n = 5), or lidocaine 20% combined with papaverine (30 mg/ml, n = 5). For 30–60 minutes after the procedure, blood flow changes in the vessels were continuously monitored with a transonic doppler applied to both carotid arteries. The 20% lidocaine group was flushed with saline at the end of the first hour and monitored for an additional 60 minutes. Papaverine elicited a concentration‐dependent relaxation of norepinephrine precontracted carotid artery rings in vitro. Lidocaine elicited a biphasic response, with low concentrations (10−6–10−4 M) increasing the norepinephrine‐induced contraction and high concentrations (10−4–10−2 M) relieving this contraction. Microsurgical anastomosis produced a significant decrease of blood flow through the rabbit carotid artery as measured by the transonic doppler. Drug application did not alter the systemic blood pressure of the animals. Topical application of lidocaine 2% did not significantly change the blood flow after microvascular anastomosis. Topical application of lidocaine 20%, papaverine (30 mg/ml), or lidocaine (2% or 20%) combined with papaverine significantly increased the blood flow in the rabbit carotid artery. In the lidocaine 20% group, the blood flow remained significantly increased after the drug was flushed with heparinized saline solution. These results demonstrate that topical lidocaine 20%, papaverine, and lidocaine 2% or 20% combined with papaverine significantly increase blood flow in the rabbit carotid artery after microvascular anastomosis. The data confirm the use of papaverine and lidocaine 20%, alone or in combination, as spasmolytics during clinical microsurgery. This suggests that lidocaine 2% alone is not the ideal drug to relieve vascular constriction, and further studies on the clinical use of low concentrations of topical lidocaine in microsurgery is warranted.

Peripheral nerve regeneration: The effects of postoperative irradiation

&NA; The purpose of this study was to evaluate the effects of postoperative external cobalt‐60 beam irradiation on nerve regeneration. Sixty‐five 250‐gm male Sprague‐Dawley rats were studied. Peripheral nerve regeneration was measured by walking track analysis and histomorphology of the proximal, graft, and distal nerve segments. These 65 animals underwent a 1.5‐cm interpositional nerve graft into the right posterior tibial nerve. The left leg served as a control. Each animal was then randomly allocated into one of four groups. Group 1 served as control. Groups 2 through 4 were subjected to external cobalt‐60 gamma‐ray irradiation through a 2.5‐cm circular portal for a total fractionated dose of 30, 50, and 70 Gy beginning on postoperative day 3. Radiation was administered in 2‐Gy fractions, 5 fractions per week, with a top‐up dose of 16 Gy given at the end of the fractionated irradiation. Walking track analysis was performed at 30, 60, 90, and 120 days after nerve grafting. At the conclusion of 120 days, sections of the proximal, grafted, and distal nerve were harvested, stained, and examined histomorphologically. Hematoxylin and eosin stains also were obtained. Evaluation of the print‐length index demonstrated no statistical difference between the unirradiated controls and the irradiated groups. The total number of axons per square millimeter and nerve fiber density per square millimeter were significantly decreased in the distal segment of all the irradiated groups when compared with controls. Despite the reduction in myelinated regenerating fibers, no reduction in function was observed, as measured by walking track analysis. We would therefore recommend immediate reconstruction of peripheral nerve defects in the face of postoperative irradiation. (Plast. Reconstr. Surg. 100: 375, 1997.)

The histological interpretation of high frequency cutaneous ultrasound imaging.

BACKGROUND High frequency, high resolution B‐scan ultrasound imaging (US) has been used to assess skin. The use of US is limited became of difficulty interpreting the various echoes. OBJECTIVES To correlate the appearance of constant US echoes with histology in normal human skin. METHODS Normal skin from eight volunteers was scanned with US at a frequency of 20–25 MHz, prior to excision for clinical reasons. The echogenic hands of the skin and histological measurements of various layers were related statistically. RESULTS Three constant echogenic bands were identified, which correlated with skin surface, dermis, and subcutaneous fascia. CONCLUSION The correct interpretation of echogenic hands in normal skin allows for the US to be more reliably used for assessment of skin disorders.

Polyacrylamide Gel Injection for Treatment of Human Immunodeficiency Virus-Associated Facial Lipoatrophy: 18 Months Follow-Up

BACKGROUND Lipoatrophy of the face affects the quality of life and body image of individuals receiving antiretroviral therapy. The objective of this study was to assess the safety and efficacy of a permanent nonbiodegradable polyacrylamide gel filler, used for facial wasting rehabilitation. METHODS Thirty‐two individuals positive for the human immunodeficiency virus (HIV) were enrolled in the study between January 2007 and January 2009 and treated using nonbiodegradable polyacrylamide gel injections for a facial wasting rehabilitation. RESULTS Local infection, foreign body reaction, and migration of the product were not observed during follow‐up (18 months). Small, palpable, nonvisible nodules were recorded in 13 cases at the end of follow‐up. CONCLUSIONS Polyacrylamide hydrogel is an appropriate treatment option in restoring facial contours in immunocompromised people with HIV. Injections of large volumes of polyacrylamide gel (8 to 12 mL) are not associated with a high rate of complications such as infection and foreign body reaction and allow improvement in quality of life in a limited time. The authors have indicated no significant interest with commercial supporters.

Calcitonin gene-related peptide in experimental ischemia. Implication of an endogenous anti-ischemic effect

Ischemia resulting from flap harvesting and vascular manipulation during microsurgery may be responsible for flap ischemic sufferance and, ultimately, necrosis. Recently, the regulatory role of the sensory nervous system in ischemia has attracted much interest. Calcitonin gene-related peptide (CGRP), a neuropeptide, is a naturally occurring vasodilator with no constrictive effects. In the present study, we developed a model of partial, chronic ischemia in the rat epigastric flap and investigated the effects of ischemia on concentrations of CGRP-like immunoreactivity (-LI) in ischemic skin and in different regions of the rat brain (striatum, hippocampus, pituitary, hypothalamus, and frontal and occipital cortex). A neurovascular island flap based on the superficial epigastric vessels was raised in 10 animals. Ischemia of the flap was obtained by ligating the feeding artery so that the blood flow was reduced to 25% of the normal circulation. An electromagnetic Doppler positioned on the artery was used to monitor the blood flow reduction. Ten nonoperated animals were used as controls. Ten days after the operation, CGRP-LI was significantly increased in five of six brain regions analyzed (striatum excepted). Significantly decreased concentrations of CGRP-LI were found in seven ischemic flaps, as opposed to the control group. In the remaining three flaps, no significant changes in CGRP concentration were observed. The highest blood flux values (detected using a laser Doppler) in the flaps correlated positively with the highest concentrations of CGRP-LI in the flap tissue. The results of the present study suggest that endogenous CGRP may be involved in the adaptive response to ischemia.