Local fluid transfer regulation in heart extracellular matrix

The interstitial myocardial matrix is a complex and dynamic structure that adapts to local fluctuations in pressure and actively contributes to the heart's fluid exchange and hydration. However, classical physiologic models tend to treat it as a passive conduit for water and solute, perhaps because local interstitial regulatory mechanisms are not easily accessible to experiment in vivo. Here, we examined the interstitial contribution to the fluid-driving pressure ex vivo. Interstitial hydration potentials were determined from influx/efflux rates measured in explants from healthy and ischemia-reperfusion-injured pigs during colloid osmotic pressure titrations. Adaptive responses were further explored by isolating myocardial fibroblasts and measuring their contractile responses to water activity changes in vitro. Results show hydration potentials between 5 and 60 mmHg in healthy myocardia and shifts in excess of 200 mmHg in edematous myocardia after ischemia-reperfusion injury. Further, rates of fluid transfer were temperature-dependent, and in collagen gel contraction assays, myocardial fibroblasts tended to preserve the micro-environment's hydration volume by slowing fluid efflux rates at pressures above 40 mmHg. Our studies quantify components of the fluid-driving forces in the heart interstitium that the classical Starling's equation does not explicitly consider. Measured hydration potentials in healthy myocardia and shifts with edema are larger than predicted from the known values of hydrostatic and colloid osmotic interstitial fluid pressures. Together with fibroblast responses in vitro, they are consistent with regulatory mechanisms that add local biological controls to classic fluid-balance models (AU)

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Local fluid transfer regulation in heart extracellular matrix.

The interstitial myocardial matrix is a complex and dynamic structure that adapts to local fluctuations in pressure and actively contributes to the heart's fluid exchange and hydration. However, classical physiologic models tend to treat it as a passive conduit for water and solute, perhaps because local interstitial regulatory mechanisms are not easily accessible to experiment in vivo. Here, we examined the interstitial contribution to the fluid-driving pressure ex vivo. Interstitial hydration potentials were determined from influx/efflux rates measured in explants from healthy and ischemia-reperfusion-injured pigs during colloid osmotic pressure titrations. Adaptive responses were further explored by isolating myocardial fibroblasts and measuring their contractile responses to water activity changes in vitro. Results show hydration potentials between 5 and 60 mmHg in healthy myocardia and shifts in excess of 200 mmHg in edematous myocardia after ischemia-reperfusion injury. Further, rates of fluid transfer were temperature-dependent, and in collagen gel contraction assays, myocardial fibroblasts tended to preserve the micro-environment's hydration volume by slowing fluid efflux rates at pressures above 40 mmHg. Our studies quantify components of the fluid-driving forces in the heart interstitium that the classical Starling's equation does not explicitly consider. Measured hydration potentials in healthy myocardia and shifts with edema are larger than predicted from the known values of hydrostatic and colloid osmotic interstitial fluid pressures. Together with fibroblast responses in vitro, they are consistent with regulatory mechanisms that add local biological controls to classic fluid-balance models.

Ameliorating Spinal Cord Injury in an Animal Model With Mechanical Tissue Resuscitation.

BACKGROUND: Traumatic spinal cord injury (SCI) is a major worldwide cause of mortality and disability with limited treatment options. Previous research applying controlled negative pressure to traumatic brain injury in rat and swine models resulted in smaller injuries and more rapid recovery. OBJECTIVE: To examine the effects of the application of a controlled vacuum (mechanical tissue resuscitation [MTR]) to SCI in a rat model under several magnitudes of vacuum. METHODS: Controlled contusion SCIs were created in rats. Vacuums of -50 and -75 mm Hg were compared. Analysis included open-field locomotor performance, magnetic resonance imaging (in vivo T2, ex vivo diffusion tensor imaging and fiber tractography), and histological assessments. RESULTS: MTR treatment significantly improved the locomotor recovery from a Basso, Beattie, and Bresnahan score of 7.8 ± 1.9 to 11.4 ± 1.2 and 10.7 ± 1.9 at -50- and -75-mm Hg pressures, respectively, 4 weeks after injury. Both pressures also reduced fluid accumulations > 10% by T2-imaging in SCI sites. The mean fiber number and mean fiber length were greater across injured sites after MTR treatment, especially with treatment with -50 mm Hg. Myelin volume was increased significantly by 60% in the group treated with -50 mm Hg. CONCLUSION: MTR of SCI in a rat model is effective in reducing edema in the injured cord, preserving myelin survival, and improving the rate and quantity of functional recovery. ABBREVIATIONS: BBB, Basso, Beattie, and BresnahanDTI, diffusion tensor imagingFA, fractional anisotropyMTR, mechanical tissue resuscitationMTR50, mechanical tissue resuscitation with 50-mm Hg subatmospheric pressureMTR75, mechanical tissue resuscitation with 75-mm Hg subatmospheric pressureROI, region of interestSCI, spinal cord injury.

Mechanical tissue resuscitation (MTR): a nonpharmacological approach to treatment of acute myocardial infarction.

BACKGROUND AND AIM: Myocardial ischemia-reperfusion injury is known to trigger an inflammatory response involving edema, apoptosis, and neutrophil activation/accumulation. Recently, mechanical tissue resuscitation (MTR) was described as a potent cardioprotective strategy for reduction of myocardial ischemia-reperfusion injury. Here, we further describe the protective actions of MTR and begin to define its therapeutic window. METHODS: A left ventricular, free-wall ischemic area was created in anesthetized swine for 85 minutes and then reperfused for three hours. Animals were randomized to two groups: (1) untreated controls (Control) and (2) application of MTR that was delayed 90 minutes after the initiation of reperfusion (D90). Hemodynamics and regional myocardial blood flow were assessed at multiple time points. Infarct size and neutrophil accumulation were assessed following the reperfusion period. In separate cohorts, the effect of MTR on myocardial interstitial water (MRI imaging) and blood flow was examined. RESULTS: Both groups had similar areas at risk (AAR), hemodynamics, and arterial blood gas values. MTR, even when delayed 90 minutes into reperfusion (D90, 29.2 ± 5.0% of AAR), reduced infarct size significantly compared to Controls (51.9 ± 2.7%, p = 0.006). This protection was associated with a 33% decrease in neutrophil accumulation (p = 0.047). Improvements in blood flow and interstitial water were also observed. Moreover, we demonstrated that the therapeutic window for MTR lasts for at least 90 minutes following reperfusion. CONCLUSIONS: This study confirms our previous observations that MTR is an effective therapeutic approach to reducing reperfusion injury with a clinically useful treatment window.

The Use of Brainlab Navigation in Le Fort III Osteotomy.

Le Fort III osteotomy is commonly used in the surgical correction of midface hypoplasia, specifically in patients with syndromic craniosynostosis. These osteotomies can be associated with significant complications, which are often the result of incomplete or inaccurate osteotomies. Brainlab, a technology first developed for neurosurgery, has been applied to numerous surgical subspecialties. The aim of this study was to report our initial experience using the Brainlab VectorVision2 and Brainlab Curve (Brainlab, Westchester, IL) as an intraoperative guidance system for osteotomy placement during Le Fort III advancement. Three pediatric patients with syndromic craniosynostosis and midface hypoplasia scheduled to undergo Le Fort III advancement were scanned preoperatively with 0.6-mm computed tomography cuts, which were then uploaded to the Brainlab system. All surgeries commenced with rigid fixation of the Brainlab registration device to the patient's skull. The navigation system was used intraoperatively to accurately determine osteotomy sites and trajectories. External distractors were placed without complication. Mean length of surgery was 331 minutes, and mean estimated blood loss was 500 mL. No transfusion was required with a mean postoperative hemoglobin of 8.3 g/dL. The application of Brainlab technology to Le Fort III advancement proved useful in establishing precise osteotomy lines and trajectories. Looking forward, this technology could be applied to a minimal dissection technique in order to avoid extensive blood loss. Further study would be needed to determine possible benefits such as reduced complications or operative time when using an intraoperative navigation system for image-guided osteotomy placement during Le Fort III advancement.

Mechanical tissue resuscitation protects against myocardial ischemia-reperfusion injury.

BACKGROUND AND AIM: Reperfusion injury is a complex inflammatory response involving numerous mechanisms and pathways. Mechanical tissue resuscitation is a newly described therapeutic strategy that reduces reperfusion injury. This study further investigates potential mechanisms for the protective effects of mechanical tissue resuscitation while utilizing a bio-absorbable matrix. METHODS: Anesthetized swine were subjected to 80 minutes of coronary ischemia and three hours of reperfusion. An absorbable matrix was used to cover the ischemic-reperfused myocardium and apply the mechanical tissue resuscitation (-50 mmHg) throughout reperfusion. Infarct size, myocardial blood flow (microspheres), apoptosis, edema, and hemodynamics were analyzed. RESULTS: Both control and treated groups displayed similar hemodynamics and physiologic parameters. Mechanical tissue resuscitation significantly reduced early infarct size (16.6 ± 3.8% vs. 27.3 ± 2.5% of area at risk, p < 0.05). This reduction of infarct size was accompanied by reduced edema formation in both epicardial (27% reduction) and endocardial (58% reduction) samples. Histological examination of both epicardial and endocardial tissues also revealed a reduction in apoptosis (80% and 44% reductions) in MTR-treated hearts. CONCLUSIONS: Treatment with mechanical tissue resuscitation during reperfusion reduces both early cell death and the delayed, programmed cell death after ischemia-reperfusion. This cardioprotection is also associated with a significant reduction in interstitial water. Additional cardioprotection may be derived from mechanical tissue resuscitation-induced increased blood flow. Mechanical tissue resuscitation, particularly with a resorbable device, is a straightforward and efficacious mechanical strategy for decreasing cardiomyocyte death following myocardial infarction as an adjunctive therapy to surgical revascularization.

Vacuum-assisted closure for complex cranial wounds involving the loss of dura mater.

The aim in this study was to describe the safety and efficacy of vacuum-assisted closure (VAC) in patients with complex cranial wounds with extensive scalp, bone, and dural defects who were not candidates for immediate free tissue transfer. Five patients (4 men and 1 woman) ages 24-73 years with complex cranial wounds were treated with VAC at Wake Forest Baptist Medical Center. Etiologies included trauma, squamous cell carcinoma, and malignant meningioma. Cutaneous wound defects measured as large as 15 cm in diameter. Four of the 5 patients had open skull defects with concomitant dural defects, and 1 patient had dural dehiscence. After surgical debridement, all 5 patients were treated with the direct application of a VAC device to a reapproximated dura mater (1 patient), to a pericranial flap (1 patient), or to a regenerative tissue matrix overlying CNS tissue (3 patients). In all cases involving open cranial wounds, the VAC device promoted granulation tissue formation over the dural substitute, prevented CSF leakage, and kept the wounds free from local infection. The duration of VAC therapy ranged from 16 to 91 days. Although VAC therapy was intended as a temporary measure until these patients could be stabilized for larger tissue transfer procedures or they succumbed to their primary pathology, 1 patient had a successful skin graft following VAC therapy. Hydrocephalus requiring shunt placement developed in 2 patients during VAC therapy. The VAC dressings applied to a tissue matrix or other barrier over brain tissue in extensive cranial wounds are safe and well tolerated, providing a functional barrier and preventing infection.

Influence of frontosphenoidal suture synostosis on skull dysmorphology in unicoronal suture synostosis.

Severity of the Harlequin deformity seen in unicoronal synostosis may be augmented when frontoparietal suture synostosis has an associated fusion of the frontosphenoidal suture or in cases of isolated frontosphenoidal synostosis. The purpose of the current study is to characterize various suture fusion patterns along the coronal ring using a modified orbital index (MOI), orbital angle (OA), and endocranial base (EB) angle.This study is a retrospective single institution cohort study. Charts were reviewed over the past 12 years; patients with isolated UCS were included. MOI, OA, and EB were used to identify 3 groups of UCS patients.Twenty-one patients were identified for inclusion in skeletal dysmorphology analysis using MOI, OA, and EB measures. Frontoparietal synostosis patients were diagnosed at significantly younger ages than frontoparietal + frontosphenoidal patients (P = 0.0001). Ipsilateral MOI measures were more severe for frontoparietal patients compared with frontoparietal + frontosphenoidal patients (P = 0.0239). There was a trend for more severe ipsilateral OA measures in frontoparietal patients compared with frontoparietal + frontosphenoidal patients (P = 0.181).Modified orbital index, OA, and EB measurements are useful in the diagnosis of suture fusion patterns in UCS patients. Frontoparietal synostosis has more severe Harlequin deformity compared with frontoparietal + frontosphenoidal patients. Frontosphenoidal fusion coinciding with frontoparietal synostosis may blunt the severity of skeletal dysmorphology in UCS patients and be associated with a delayed diagnosis. Attention must be paid to assessing the frontosphenoidal suture to assure adequate surgical release.

AlloDerm revision for failed pharyngoplasty.

Velopharyngeal insufficiency (VPI) occurs in more than 20% of patients with a cleft palate after primary palatoplasty. Surgical treatment focuses on pharyngoplasty to narrow the nasopharyngeal space and to decrease the distance needed for palatal closure. Persistent VPI after pharyngoplasty affects more than 20% of patients.From September 2007 to December 2009, 16 children (10 boys and 6 girls) with a mean age of 9.5 years (4-15 years) underwent surgical revision using an AlloDerm sling for persistent VPI after at least 1 previous failed pharyngoplasty. Ten children had previous sphincter pharyngoplasties, and 6 had previous pharyngeal flaps. Surgical technique involves creation of a submucosal tunnel through the limbs of the previous pharyngoplasty or pharyngeal flap. A strip of AlloDerm is threaded circumferentially, and the port is adjusted to the desired aperture.All patients underwent preoperative and postoperative analysis of VPI, including oral pharyngeal and perceptual speech examination by speech pathology with a mean follow-up of 441 days. Acoustic nasometry was used to objectively compare preoperative and postoperative nasalance values. A significant improvement in perceptual resonance was seen in 93.8% of patients, and 87.5% of patients improved to normal or mild resonance (P < 0.001). There was a significant mean reduction of nasalance using the MacKay-Kummer Simplified Nasometric Assessment Procedure test (P < 0.001). Two patients developed postoperative flap dehiscence, with one being revised ultimately to have normal speech resonance.Revision pharyngoplasty using an AlloDerm sling can safely and effectively improve speech in patients with persistent VPI after failed pharyngoplasty. Long-term follow-up studies are ongoing.

A new method for modulating traumatic brain injury with mechanical tissue resuscitation.

BACKGROUND: Traumatic brain injuries remain a treatment enigma with devastating late results. As terminally differentiated tissue, the brain retains little capacity to regenerate, making early attempts to preserve brain cells after brain injury essential. OBJECTIVE: To resuscitate damaged tissue by modulating edema, soluble cytokines, and metabolic products in the "halo" of damaged tissue around the area of central injury that progressively becomes compromised. By re-equilibrating the zone of injury milieu, it is postulated neurons in this area will survive and function. METHODS: Mechanical tissue resuscitation used localized, controlled, subatmospheric pressure directly to the area of controlled cortical impact injury and was compared with untreated injured controls and with sham surgery in a rat model. Functional outcome, T2 magnetic resonance imaging hyperintense volume, magnetic resonance imaging spectroscopy metabolite measurement, tissue water content, injury cavity area, and cortical volume were compared. RESULTS: There were significant differences between mechanical tissue resuscitation treated and untreated groups in levels of myoinositol, N-acetylaspartate, and creatine. Treated animals had significantly less tissue swelling and density than the untreated animals. Nonviable brain tissue areas were smaller in treated animals than in untreated animals. Treated animals performed better than untreated animals in functional tests. Histological analysis showed the remaining viable ipsilateral cerebral area was 58% greater for treated animals than for untreated animals, and the cavity for treated animals was 95% smaller than for untreated animals 1 month after injury. CONCLUSION: Mechanical tissue resuscitation with controlled subatmospheric pressure can significantly modulate levels of excitatory amino acids and lactate in traumatic brain injury, decrease the water content and volume of injured brain, improve neuronal survival, and speed functional recovery.

Giant facial lymphangioma.

Lymphatic malformation (LM) is a benign cystic entity resulting from aberrant lymphatic drainage. Often evident at birth, most LMs have declared themselves by 2 years of age. They can be concerning when they occur near vital structures such as the airway or orbit. The natural history varies considerable from spontaneous gradual regression to long-term growth and debilitation. Depending on the location, structures involved, and clinical course of the LM, therapeutic options include observation, intralesional sclerosis, laser therapy, and surgical excision. The literature provides guidelines for treatment options that must be carefully applied to the facial region. We present a newborn infant who presented to our institution with giant facial lymphangioma who underwent a combination of sclerosis, laser ablation, and surgery with reconstruction.

Development of a biodegradable foam for use in negative pressure wound therapy.

Treatment of wounds using negative pressure wound therapy (NPWT) uses a nondegradable polyvinyl alcohol (PVA) foam in the application of negative pressures typically for 1-3 days. The purpose of this study was to construct and test biodegradable poly(ε-caprolactone) (PCL) foam as a substitute for the PVA foam. Such a foam would be left within the wound until healing was achieved and form a biodegradable matrix into which tissue would grow. The use of such foam would obviate the need for any serial foam changes and a final foam removal, thus making patient care much easier and more economical. PCL foams were prepared by salt leaching and phase separation. Morphological and mechanical properties of the foams were characterized and compared to PVA foam. PCL and PVA foams were tested on the uncut surface of a pig liver maintained in a hydration chamber continuously replenished with saline under the conditions of negative pressure of 50 mm Hg for 72 h. The results demonstrated that PCL foam made from phase separation had the similar properties and function as the PVA foam. The results demonstrate that PCL foam is an appropriate substitute for currently used nondegradable PVA foam in NPWT applications.

Time-dependent perioperative anesthetic management and outcomes of the first 100 consecutive cases of spring-assisted surgery for sagittal craniosynostosis.

BACKGROUND: The anesthetic risks and outcomes of the first 100 consecutive spring-assisted surgeries (SAS) for cranial expansion from a single institution are reported. The effect of number of procedures was also tested on hematocrit postoperative day 1 (POD1), anesthesia time, and surgery time of the first procedure. METHODS: The records of 100 consecutive patients undergoing SAS were reviewed. Anesthesia management and related complications are presented. Time series linear regression analysis was performed on hematocrit POD1, anesthesia time, and surgery time of the first procedure. RESULTS: The average age of the first insertion procedure was 4.4 and 9.0 months for the second removal procedure. Two patients were inadvertently extubated during positioning. Thirty-eight children had a decrease in blood pressure >20% from baseline. No child was admitted to the intensive care unit. No patient received any blood or blood product transfusion. Anesthesia time, surgery time, and hematocrit POD1 were correlated with procedure number or experience. CONCLUSIONS: Changes in anesthetic management resulted from changing the procedure. The reduction in volume resuscitation reduces the need for invasive monitoring. Facility and comfort with the surgical procedure increase with time and number of procedures performed. This experience further reduces blood loss and risk of transfusion.

Congenital pyriform aperture stenosis.

Neonates rely on the nasal airway for their source of air; thus, any compromise in the ability to inhale will dramatically alter their ability to breathe. Congenital nasal pyriform aperture stenosis is a rare yet serious form of airway obstruction due to overgrowth of the maxilla at the medial nasal process. Infants typically present with difficulty feeding and obvious difficulty breathing. Radiologic imaging aids in confirming the diagnosis and assists in operative planning to open the medial nasal process to reduce airway resistance. Further corrective surgery is often needed and is planned commensurate with facial growth. We present a novel case of a child diagnosed with congenital nasal pyriform aperture stenosis who has performed extraordinarily well intellectually and has achieved an excellent cosmetic and physiological reconstruction of the nose and airway.

The local pathology of interstitial edema: surface tension increases hydration potential in heat-damaged skin.

The local pathogenesis of interstitial edema in burns is incompletely understood. This ex vivo study investigates the forces mediating water-transfer in and out of heat-denatured interstitial matrix. Experimentally, full-thickness dermal samples are heated progressively to disrupt glycosaminoglycans, kill cells, and denature collagen under conditions that prevent water loss/gain; subsequently, a battery of complementary techniques including among others, high-resolution magnetic resonance imaging, equilibrium vapor pressure and osmotic stress are used to compare water-potential parameters of nonheated and heated dermis. The hydration potential (HP) determined by osmotic stress is a measure of the total water-potential defined empirically as the pressure at which no net water influx/efflux into/from the dermis is detected. Results show that after heat denaturation, the HP, the intensity of T2-weighed magnetic resonance images, and the vapor pressure increase indicating higher water activity and necessarily, smaller contributions from colloidosmotic forces to fluid influx in burned relative to healthy dermis. Concomitant increases in HP and in water activity implicate local changes in interfacial and metabolic energy as the source of excess fluid-transfer potential. These ex vivo findings also show that these additional forces contributing to abnormal fluid-transfer in burned skin develop independently of inflammatory and systemic hydrodynamic responses.

Aplasia cutis congenita: clinical management of a rare congenital anomaly.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital disorder characterized by absence of skin and adjacent tissue that usually affects the scalp, but any part of the body may be affected. Although ACC is more often superficial and small, it can be large and involve the underlying structures such as skull and dura, thus increasing the risk of hemorrhage, infection, and mortality. Controversy exists regarding nonsurgical versus surgical intervention for this condition. This study reviews indications and modalities for treatment of this rare congenital anomaly. RESULTS: Management of this anomaly depends on size, location, and structures at risk. Small lesions with intact underlying structures and lesions affecting extremities are treated in a conservative fashion with dressings and ointments followed by delayed scar excision. Aplasia cutis congenita scar excision often requires complex tissue rearrangement, tissue expansion, or skin grafting. Larger ACC lesions or lesions with exposure of vital structures require early surgical intervention. Initially, exposed vital structures and bony ridges can be protected using conservative measures. Delayed definitive repair can then be performed using scalp flaps, split- and full-thickness skin grafts, cultured epithelial autografts, delayed split rib cranioplasty, tissue expansion, and composite cranioplasty. CONCLUSIONS: Aplasia cutis congenita should be individually evaluated based on size, depth, location, and tissues involved. Using conservative and surgical modalities, one can achieve complete closure of the defect, thus avoiding risks of infection, hemorrhage, and further trauma.

Increased incidence of metopic suture abnormalities in children with positional plagiocephaly.

Metopic craniosynostosis has traditionally been reported to be the third most common form of single-suture synostosis. The purposes of this article were to analyze the relationship between metopic craniosynostosis and positional plagiocephaly and to define more clearly the differences between the changes seen with true suture fusion compared with metopic abnormalities secondary to positional changes. This is an institutional review board-approved retrospective review of three-dimensional computed tomographic scans for abnormalities of the metopic suture in all children treated at our institution for positional plagiocephaly between 1997 and 2007. We also independently reviewed the images of all patients treated for metopic synostosis for evidence of positional plagiocephaly during the same period. Among the positional plagiocephaly group, 39% were noted to have some form of metopic suture abnormality. Of the children treated for metopic craniosynostosis, a much smaller percentage also was noted to have evidence of positional plagiocephaly. Between 1997 and 2007, we treated 93 patients (50%) for sagittal synostosis, 41 patients (22%) for unicoronal, 41 patients (22%) for metopic, 4 patients (2%) for lamdoid, and 7 patients (4%) with multiple-suture involvement. This study demonstrates an increasing trend toward metopic suture abnormalities during the past 10 years, which corresponds to the same time interval of an increased incidence of positional abnormalities. It is postulated that some of these abnormalities are related to deformational forces resulting from posterior pressure. Altered mechanical forces from supine infant positioning may be associated with early metopic suture ridging and dysmorphology distinct from true craniosynostosis.

Loxoscelism and negative pressure wound therapy (vacuum-assisted closure): an experimental study.

Brown recluse spider (Loxosceles) bites cause lesions ranging from chronic necrotic ulcers to acute life-threatening sepsis. Based on our experience in treating acute and chronic wounds with negative pressure, we postulated that vacuum-assisted closure (VAC) would be valuable in this application. Chester pigs were procured and injected with purified brown recluse spider venom, 1 µl of venom in two anterior sites and 0·1 µl of venom in two posterior sites on their dorsum. For each concentration of venom, treatment consisted of either VAC or dry, non adherent dressings (control group). Each day, the wounds were inspected and measured. For wounds receiving 1·0 µl of venom, the control wounds decreased in surface area to 50% of initial size after 7 days and none had healed, whereas VAC-treated wounds were less than 50% after 48 hours and completely healed and reepithelialised after 8 days. Wounds with 0·1 µl of venom had 50% reduction after 5 days with no complete healing for control wounds, and the VAC wounds were 50% after 48 hours and all had closed and reepithelialised after 5 days. Our experimental study showed an accelerated healing time in the animals treated with the VAC as compared with controls.

Reduction of myocardial ischemia-reperfusion injury by mechanical tissue resuscitation using sub-atmospheric pressure.

BACKGROUND: Reperfusion-induced injury after myocardial infarction is associated with a well-defined sequence of early and late cardiomyocyte death. Most present attempts to ameliorate this sequence focus on a single facet of the complex process in an attempt to salvage cardiomyocytes. We examined, as proof of concept, the effects of mechanical tissue resuscitation (MTR) with controlled negative pressure on myocardial injury following acute myocardial infarction. METHODS: Anesthetized swine were subjected to 75 minutes of left coronary artery occlusion and three hours of reperfusion. Animals were assigned to one of three groups: (A) untreated control; treatment of involved myocardium for 180 minutes of MTR with (B) -50 mmHg, or (C) -125 mmHg. RESULTS: All three groups were subjected to equivalent ischemic stress. Treatment of the ischemic area with MTR for 180 minutes significantly (p < 0.001) reduced infarct size (area of necrosis/area at risk) in both treatment groups compared to control: 9.3 +/- 1.8% (-50 mmHg) and 11.9 +/- 1.2% (-125 mmHg) versus 26.4 +/- 2.1% (control). Total area of cell death was reduced by 65% with -50 mmHg treatment and 55% in the -125 mmHg group. CONCLUSIONS: Treatment of ischemic myocardium with MTR, for a controlled period of time during reperfusion, successfully reduced the extent of myocardial death after acute myocardial infarction. These data provide evidence that MTR using subatmospheric pressure may be a simple, efficacious, nonpharmacological, mechanical strategy for decreasing cardiomyocyte death following myocardial infarction, which can be delivered in the operating room.