Gender-specific ischemic tissue tolerance in critically perfused skin.

Purpose: The purpose of this study is to determine gender-specific differences in the development of necrosis in persistent ischemic tissue and to analyze whether differences are due to gender-specific loss of vascular reactivity or change in ischemic tolerance.

Methods: Hairless mice (skh-1) of both genders were assigned to three groups of adolescent, adult, and senescent age. Critical ischemia was induced by transection of the two distal pedicles of the animal's ear.

Erythropoietin reduces necrosis in critically ischemic myocutaneous tissue by protecting nutritive perfusion in a dose-dependent manner.

Background: Erythropoietin (Epo), the primary regulator of erythropoiesis, has recently been shown to exert antiinflammatory and antiapoptotic properties in neuronal and myocardial tissue. We herein studied whether Epo pretreatment can reduce cell death and ischemic necrosis in a chronic in vivo model.

Methods: C57BL/6 mice were treated daily for 3 consecutive days with either 500 IU EPO/kg body weight (bw) (group Epo 500, n = 8) or 5000 IU EPO/kg bw (group Epo 5000, n = 8) administered intraperitoneally 24 hours before surgery.

Erythropoietin protects critically perfused flap tissue.

Objective: The objective of this study was to analyze whether erythropoietin (EPO) protects from necrosis of critically perfused musculocutaneous tissue and the mechanisms by which this protection is achieved.

Background: EPO is the regulator of erythropoiesis and is used to treat patients with anemia of different causes. Recent studies suggest that EPO has also other tissue-protective effects, irrespective of its erythropoietic properties.

Ischemia-induced up-regulation of heme oxygenase-1 protects from apoptotic cell death and tissue necrosis.

Background: Tissues are endowed with protective mechanisms to counteract chronic ischemia. Previous studies have demonstrated that endogenous heme oxygenase (HO)-1 may protect parenchymal tissue from inflammation- and reoxygenation-induced injury. Nothing is known, however, on whether endogenous HO-1 also plays a role in chronic ischemia to protect from development of tissue necrosis.

Microdialysis of the rectus abdominis muscle for early detection of impending abdominal compartment syndrome.

Objective: To investigate whether microdialysis is capable of assessing metabolic derangements during intra-abdominal hypertension (IAH), and whether monitoring of the rectus abdominis muscle (RAM) by microdialysis represents a reliable approach in the early detection of organ dysfunctions in abdominal compartment syndrome (ACS).

Design: Prospective, randomized, controlled animal study.

Setting: University animal research facility.

Selective blockade of endothelin-B receptor improves survival of critically perfused musculocutaneous flaps.

Background And Aims: Insufficient perfusion of distal flap areas, which may lead to partial necrosis, still represents a challenge in reconstructive surgery. In the process of microvascular and endothelial dysfunction, endothelins (ETs) and their receptors may play an important role. Therefore, the aim of the study was to investigate in a chronic in vivo model the effect of various ET-receptor antagonists in critically perfused flap tissue.

A new model for the study of the abdominal compartment syndrome in rats.

Background: The purpose of the present study was to develop of a rodent model of abdominal compartment syndrome (ACS), which allows detailed analysis of intra-abdominal hypertension (IAH)- and decompression-associated reperfusion injury.

Methods: In 20 anesthetized and ventilated Sprague-Dawley rats an IAH of 20 mmHg was induced for 3 h by intraperitoneal infusion of gelatin polysuccinate. After decompression, an additional 3-h period of reperfusion was studied.

Aging is associated with an increased susceptibility to ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance.

In the present study in a murine model of chronic ischaemia, we analysed: (i) whether aging was associated with an increased susceptibility to ischaemic necrosis, and (ii) whether this was based on microvascular dysfunction or reduced ischaemic tolerance. An ischaemic pedicled skin flap was created in the ear of homozygous hairless mice. The animals were assigned to three age groups, including adolescent (2+/-1 months), adult (10+/-2 months) and senescent (19+/-3 months).

Impact of severity of local soft-tissue trauma on long-term manifestation of microcirculatory and microlymphatic dysfunctions.

Background: The present study aimed at quantitatively evaluating the impact of severity of local trauma on manifestation of soft-tissue injury-associated microcirculatory and microlymphatic dysfunctions in a chronic model that allowed repeated analyses by intravital fluorescence microscopy.

Methods: C57BL/6 mice were chronically instrumented with dorsal skinfold chambers and subjected to mild (180 J/m2, n = 6), moderate (270 J/m2, n = 6), or severe trauma (450 J/m2, n = 6; 540 J/m2, n = 6). Nontraumatized animals served as controls (sham; n = 8).

Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes.

Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure.

Heat shock preconditioning reduces ischemic tissue necrosis by heat shock protein (HSP)-32-mediated improvement of the microcirculation rather than induction of ischemic tolerance.

Introduction: Supraphysiologic stress induces a heat shock response, which may exert protection against ischemic necrosis. Herein we analyzed in vivo whether the induction of heat shock protein (HSP) 32 improves survival of chronically ischemic myocutaneous tissue, and whether this is based on amelioration of microvascular perfusion or induction of ischemic tolerance.

Methods: The dorsal skin of mice was subjected to local heat preconditioning (n = 8) 24 hours before surgery.

Effect of systemic hypothermia on local soft tissue trauma-induced microcirculatory and cellular dysfunction in mice.

Objective: Changes in body temperature occur as a systemic reaction to severe trauma; however, its role in the manifestation of injury remains unclear. Thermoregulatory responses vary considerably from fever to hypothermia. Although hypothermic trauma patients seem to have a worse prognosis, there is the question whether hypothermia per se or the severity of trauma producing the hypothermia is responsible for aggravated injury and increased mortality rate.

Evolution of a "falx lunatica" in demarcation of critically ischemic myocutaneous tissue.

Using intravital microscopy in a chronic in vivo mouse model, we studied the demarcation of myocutaneous flaps and evaluated microvascular determinants for tissue survival and necrosis. Chronic ischemia resulted in a transition zone, characterized by a red fringe and a distally adjacent white falx, which defined the demarcation by dividing the proximally normal from the distally necrotic tissue. Tissue survival in the red zone was determined by hyperemia, as indicated by recovery of the transiently reduced functional capillary density, and capillary remodeling, including dilation, hyperperfusion, and increased tortuosity.

Mechanism of the delay phenomenon: tissue protection is mediated by heme oxygenase-1.

Induction of the "delay phenomenon" by chronic ischemia is an established clinical procedure, but the mechanisms conferring tissue protection are still incompletely understood. To elucidate the role of heme oxygenase-1 [HO-1 or heat shock protein-32 (HSP-32)] in delay, we examined in the skin-flap model of the ear of the hairless mouse, 1) whether chronic ischemia (delay) is capable to induce expression of HO-1, and 2) whether delay-induced HO-1 affects skin-flap microcirculation and survival by either its carbon monoxide-associated vasodilatory action or its biliverdin-associated anti-oxidative mechanism. Chronic ischemia was induced by transsection of the central feeding vessel of the ear 7 days before flap creation.

p-[123I]iodo-L-phenylalanine for detection of pancreatic cancer: basic investigations of the uptake characteristics in primary human pancreatic tumour cells and evaluation in in vivo models of human pancreatic adenocarcinoma.

Pancreatic cancer is associated with the worst 5-year survival rate of any human cancer. This high mortality is due, in part, to difficulties in establishing early and accurate diagnosis. Because most tumours share the ability to accumulate amino acids more effectively than normal tissues and any other pathology, assessment of amino acid transport in tumour cells using radiolabelled amino acids has become one of the most promising tools for tumour imaging.

Experimental models to study microcirculatory dysfunction in muscle ischemia-reperfusion and osteomyocutaneous flap transfer.

Background: During the past decade, experimental studies have provided convincing evidence that microcirculatory dysfunction plays a pivotal role in the manifestation of tissue injury in ischemia-reperfusion and osteomyocutaneous flap transfer. The study of the mechanisms of injury, however, requires sophisticated experimental in vivo models. With the use of microsurgical techniques, osteomyocutaneous flap transfer can successfully be performed in rat hind limbs, allowing in vivo fluorescent microscopic analysis of post-ischemic microcirculatory dysfunction in all tissues involved, including periosteum, striated muscle, subcutis and skin.

Heme oxygenase and nitric oxide synthase mediate cooling-associated protection against TNF-alpha-induced microcirculatory dysfunction and apoptotic cell death.

Local cooling protects against TNF-alpha-induced injury by attenuating inflammation-associated microcirculatory dysfunction and leukocytic response. Mechanisms of protection, however, are not fully understood. We studied whether the metabolites of the HO and NOS pathway, exerting potent vasodilatory, antioxidant, and anti-apoptotic properties, are involved in tissue cryoprotection.