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Biomedical subjects

G Gherardini

Publications and source records attributed to G Gherardini.

At least 19 recordsLinked to original sources

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.

Animals↗

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 microM), 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.

Animals↗

Calcitonin gene-related peptide improves skin flap survival and tissue inflammation.

The effects of systemic administration of calcitonin gene-related peptide (CGRP) on survival and inflammation of experimental skin flaps subjected to prolonged arterial ischemia were studied. An island groin flap was elevated in the rat. The femoral artery was occluded for 8, 10, 12 or 14 h in four groups of 10 rats. In a group of 10 sham-operated control animals, the femoral artery was not occluded. After ischemia, blood flow was restored and flap survival evaluated at day 7. Following 12 h of ischemia, three flaps (30%) survived, compared with 100% survival of the control group. In the second part of the study the effects of CGRP on flap survival were assessed. Eighty flaps were rendered ischemic for 12 h, and received systemic CGRP (10(-7), 10(-8), 10(-9), 10(-10) M) or saline (control) at the end of the ischemia period. Administration of CGRP (10(-7) M) significantly increased the number of flaps surviving compared with the control. The effect of systemic pretreatment of the animals with the CGRP receptor antagonist CGRP8(-37), followed by CGRP (10(-7) M) treatment was also evaluated in 10 flaps. Flap survival in this group was 10%. In the third part of the study the anti-inflammatory effects of CGRP were evaluated. Forty rats were subjected to arterial ischemia for 12 h, and received systemic CGRP (10(-7) M), or saline at the end of the period of ischemia. The animals were sacrificed at 24 h and flap tissue samples were obtained. Myeloperoxidase (MPO) analysis was used as marker of neutrophil accumulation. CGRP (10(-7) M) significantly reduced the 24 h MPO accumulation in the flap, compared with saline treatment. A group of animals was pretreated with CGRP8(-37), followed by CGRP (10(-7) M), and a significant increase of MPO accumulation was seen, compared with the group treated only with CGRP. This study suggests that CGRP has a beneficial effect on survival of the rat ischemic groin flap, and diminishes the inflammatory response to the ischemic insult.

Animals↗

Venous flap ischemia: microcirculatory changes in experimental flaps in a rabbit model.

This study was designed to investigate the simultaneous changes in blood flow and microcirculation in an island flap during venous occlusion (venous ischemia), in an ischemia/reperfusion injury model in the rabbit. An island groin flap based on the inferior epigastric vessels was harvested in 15 rabbits. The flap was rendered ischemic for 3 hr (n = 5) or 4 hr (n = 10, 5 heparinized and 5 not), by applying a microvascular clamp to the inferior epigastric vein. Transonic Doppler and laser Doppler were used to monitor blood flow in the epigastric artery and microcirculation of the flap for 1 hr after flap elevation, 1 hr after occlusion, and for 3 hr at the end of the ischemic period. Venous occlusion was followed by a rapid decrease of blood flow and microcirculation readings. After ischemia, both blood flow and microcirculation readings in the flap were significantly decreased, compared to pre-ischemic values in all groups. In the 3-hr ischemia group, blood flow readings returned to pre-stress values, while microcirculation remained significantly lower. In the 4-hr ischemia group treated with heparin, blood flow in the artery settled at levels significantly lower than pre-stress readings; however, microcirculation of the flap was ultimately fully restored to pre-ischemic values. In the 4-hr ischemia group, both blood flow and microcirculation in the flap settled at levels significantly lower than pre-stress values. The authors concluded that tolerance for venous ischemia is time-dependent in this model and that venous ischemia is more deleterious than global ischemia. Administration of heparin may alter the time frame of ischemia/reperfusion injury and may prevent the harmful effects of injury at the microcirculatory level.

Animals↗

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

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 gene-related 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.

Aged↗

Laparoscopic harvesting of jejunal free flaps for esophageal reconstruction.

Endoscopic harvest of the jejunum is indicated for the reconstruction of complex defects of the head and neck and specifically the reconstruction of circumferential defects of the esophagus. However, open laparotomies are associated with systemic and local morbidity and are often seen as prohibitively invasive procedures. Laparoscopy for intra-abdominal procedures is a proven technique that yields less morbidity and provides an anatomical exposure similar to that of the open approach. We report on 11 consecutive clinical cases of free jejunal flap harvesting with the laparoscopic technique and show that the procedure is feasible.

Adult↗

Fat necrosis in free and pedicled TRAM flaps.

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.

Abdominal Muscles↗

Blood flow and microcirculatory changes in an ischemia-reperfusion injury model: experimental study in the rabbit.

This is the first in a series of studies designed to investigate the simultaneous changes in blood flow and microcirculation in an island flap during ischemia, in an ischemia-reperfusion model in the rabbit. An island groin flap based on the inferior epigastric vessels was harvested in 17 rabbits. The flap was rendered ischemic for 4 (n = 4), 6 (n = 4), and 16 (n = 9) hr by applying a microvascular clamp to both the inferior epigastric artery and vein. The blood flow in the epigastric artery and the microcirculation of the flap were monitored for 1 hr before the ischemia and for 3 hr after the ischemia period, using a transonic Doppler and a laser Doppler, respectively. Both the blood flow and the microcirculation of the flap were found significantly increased immediately after the ischemia in the 4- and 6-hr ischemia groups, compared to the pre-ischemic values. In the same groups, blood flow and microcirculation remained elevated over pre-ischemic levels, indicating a hyperemic response. In the 16-hr ischemic group, blood flow and microcirculation values remained significantly lower than the pre-ischemic readings at all points in time, demonstrating ischemia-reperfusion injury.

Animals↗

Drug-induced vasodilation: the effects of sodium nitroprusside, hydralazine, and cromakalin on the rabbit carotid artery: in vitro and in vivo study.

Extreme arterial and venous constructions are common problems in microvascular surgery, often leading to tissue injury and flap failure. The ideal pharmacologic tool to counteract ischemia should exert its action both locally and distally in the microcirculation of the flap. In this study, the vascular properties of sodium nitroprusside, hydralazine, and cromakalin were evaluated and compared in in vitro and in vivo models in the rabbit carotid artery. In the in vitro study, 20 rings from the rabbit carotid artery were bathed in Krebs-Ringers solution, stretched progressively to an optimal tension of 3.7 to 4.2 gm, and their isometric contractile activity was measured. The specimens were precontracted with norepinephrine (1 microM) and a dose-response curve was established by adding cumulatively either sodium nitroprusside (n = 7), cromokalin (n = 7), or hydralazine (n = 7) at increasing concentrations. In the in vivo study, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 19 animals using 9-0 nylon suture and standard microsurgical techniques. In each animal, one side was treated with heparinized sodium chloride, and served as control. The other side was treated blindly with the topical application of 1 ml of either sodium nitroprusside (10 mg/ml, n = 5), hydralazine (20 mg/ml, n = 5), or cromakalin (25 mg/ml, n = 4), during and after the anastomoses. Blood-flow changes in the vessels were continuously monitored with the transonic Doppler applied to both carotid arteries for 60 min after the procedure. Sodium nitroprusside and cromakalin elicited a concentration-dependent relaxation of norepinephrine-precontracted carotid artery rings in vitro. Sodium nitroprusside was significantly more effective than cromakalin in inducing relaxation. Hydralazine elicited a biphasic response, with low concentrations (1.5 x 10(-5) to 1.5 x 10(-3) M) potentiating the norepinephrine-induced contraction, and high concentrations relieving this contraction. Microsurgical anastomosis in the rabbit carotid artery-produced a significant decrease of blood flow through the vessel as measured by the transonic Doppler for 30 min. Topical application of heparinized saline did not significantly change the blood flow after the microvascular anastomosis. Topical application of sodium nitroprusside and cromakalin significantly increased the blood flow in the vessel after the anastomosis; however, the topical hydralazine did not significantly alter blood flow, but demonstrated a trend toward increased flow values. The data support the conclusion that sodium nitroprusside and cromakalin could be used to relieve vascular constriction. It is suggested that further studies on the clinical use of these drugs in microsurgery is warranted.

Animals↗

Cell adhesion and short-term patency in human endothelium preseeded 1.5-mm polytetrafluoroethylene vascular grafts: an experimental study.

It has been shown that endothelialization improves short-term patency of 1.5-mm expanded polytetrafluoroethylene vascular grafts. A model for endothelialization of 1.5-mm expanded polytetrafluoroethylene vascular grafts with human endothelial cells is described. In this model, the adherence of endothelial cells was increased significantly in grafts coated with serum proteins and collagen. By means of this protocol, graft patency was tested after implantation in two animal models: the rat aorta and the rabbit common carotid artery. Anastomosis was performed with a 3M Precise Microvascular Anastomotic System. In both animal models, no significant loss of endothelial cells in the precoated grafts (rat, n = 8) were noted 1 hour after blood flow restoration. All uncoated grafts showed significant endothelial cell loss. In the rabbit model, all nonendothelialized grafts (n = 8) clotted 5 to 25 minutes after flow restoration. Seven (n = 8) endothelialized grafts showed no clotting during 1 hour's observation: one clotted immediately for a patency rate of 87.5 percent. These results indicate that endothelialization of 1.5-mm grafts is practical. Furthermore, adhesion of endothelial cells to the graft walls is not affected by short-term, pulsatile, high-pressure blood flow.

Animals↗

Standardization in photography for body contour surgery and suction-assisted lipectomy.

Despite the existence of basic clinical standards in plastic surgery, specific guidelines for body contour photography have not been detailed previously. In this report we propose standard and supplemental views for positioning of the subject for suction-assisted lipectomy and body contour surgery. Also demonstrated are specialty views for the face, where liposuction has become an integral component of the procedures. Finally, recommendations for photographic documentation of skin "textural" changes and "cellulite" improvement with liposuction, as well as regions requiring lipectomy, are discussed. A professional photographic studio and a model were utilized. Proper lighting, equipment, and backgrounds are described to achieve such standards. General principles for clinical photography are reviewed. We present standard and supplemental views for suction-assisted lipectomy and body contour surgery, with an emphasis on methods to address advanced liposuction techniques (i.e., superficial suction lipectomy) that may affect texture and contour of the skin. These techniques provide consistency for all practitioners, allowing comparison of results and techniques.

Female↗

Peripheral nerve regeneration: the effects of postoperative irradiation.

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.

Animals↗

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

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 microM), 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 concentration-dependent 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.

Administration, Topical↗

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 because 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 bands 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 bands in normal skin allows for the US to be more reliably used for assessment of skin disorders.

Adult↗

Congenital syndromes associated with nonmelanoma skin cancer.

Syndromes associated with nonmelanoma skin cancer are part of a group of inherited disorders characterized by a wide variety of clinical manifestations including palmar and plantar pitting, calcification of the dura, jaw cysts, and skeletal abnormalities. The syndromes have in common skin lesions progressing to basal or squamous cell cancers. In addition to skin tumors, bone and visceral tumors are common. Early diagnosis, genetic counseling, and treatment of skin lesions are appropriate tools for the management of patients with these syndromes. Surgical procedures generally involve total resection combined with reconstructive efforts.

Basal Cell Carcinoma↗

Comparison of vascular effects of calcitonin gene-related peptide and lidocaine on human veins.

Arterial and venous constriction during microsurgery are among the leading causes of flap failure. So far, pharmacologic tools have been proposed only for arterial constriction, and local anesthetics are commonly used to counteract the vascular spasm. The purpose of this study was to investigate the vascular effects of two known arterial vasodilators on human veins, in order to evaluate the possibility of their potential use during microsurgery. In vitro experiments were performed on 31 greater saphenous vein (SV) rings obtained from 20 patients and on 12 cephalic vein (CV) rings from 7 patients. The rings were mounted in organ baths and their isometric contractile activity was measured. Experiments were conducted by cumulatively adding calcitonin gene-related peptide (CGRP) or lidocaine to the organ baths. The endothelium was mechanically removed in 18 SV rings and in 6 CV rings. Results demonstrated that in vitro CGRP produced vasodilation only; no constrictive effects were seen. Lidocaine produced a biphasic response with contraction at low concentrations (1.5 x 10(-5) M, 1.5 x 10(-3) M) and release of the maximal contraction at higher concentrations, similar to that observed in arteries. Removal of the endothelium did not significantly affect contractile activity in either CGRP- or lidocaine-treated vessels. The data supported the conclusion that CGRP could be used to relieve venous constriction, and it is suggested that further studies on the clinical use of CGRP in microsurgery is warranted.

Calcitonin Gene-Related Peptide↗

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.

Animals↗