Critical limb-threatening ischaemia and microvascular transformation: clinical implications.

BACKGROUND AND AIMS: Clinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to characterize the role of the microvasculature in CLTI pathology. METHODS: Clinical high-resolution imaging of CLTI patients (n = 50) and muscle samples from amputated CLTI limbs (n = 40) were used to describe microvascular pathology of CLTI at the level of resting muscle blood flow and microvascular structure, respectively. Furthermore, a chronic, low arterial driving pressure-simulating ischaemia model in rabbits (n = 24) was used together with adenoviral vascular endothelial growth factor A gene transfers to study the effect of microvascular alterations on muscle outcome. RESULTS: Resting microvascular blood flow was not depleted but displayed decreased capillary transit time (P < .01) in CLTI muscles. Critical limb-threatening ischaemia muscle microvasculature also exhibited capillary enlargement (P < .001) and further arterialization along worsening of myofibre atrophy and detaching of capillaries from myofibres. Furthermore, CLTI-like capillary transformation was shown to worsen calf muscle force production (P < .05) and tissue outcome (P < .01) under chronic ischaemia in rabbits and in healthy, normal rabbit muscle. CONCLUSIONS: These findings depict a progressive, hypoxia-driven transformation of the microvasculature in CLTI muscles, which pathologically alters blood flow dynamics and aggravates tissue damage under low arterial driving pressure. Hypoxia-driven capillary enlargement can be highly important for CLTI outcomes and should therefore be considered in further development of diagnostics and treatment of CLTI.

Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease.

INTRODUCTION: The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades. METHODS: The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements. RESULTS: The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P < 0.001), bFGF (Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements. CONCLUSIONS: Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD.

Primary Aorto-Enteric Fistula With a Subsequent Secondary Aorto-Enteric Fistula.

Objective: Primary aorto-enteral fistula (PAEF) is a connection between the gastrointestinal tract and the aorta that occurs without previous aortic surgery. The aetiological factors include, but are not limited to, aneurysm, infection, and tumours. It is a life threatening condition if untreated and requires emergency vascular surgical repair. A secondary aorto-enteric fistula (AEF) can occur to a previously reconstructed aorta. This case report presents a unique case of a male patient who developed a primary AEF and subsequent secondary AEF with successful surgical outcomes, suggested to be due to tuberculous aortitis. Report: The patient was diagnosed and treated for tuberculosis and developed a saccular aneurysm within six months. The PAEF was surgically corrected with a tube graft using a bovine pericardial patch, the defect in duodenum was sutured, and a retrocolic omental flap was created between the duodenum and aorta. He developed a small stable pseudoaneurysm during follow up, and then a secondary AEF two and a half years later, in which a connection between the pseudoaneurysm and duodenum was corrected using a new bovine aorto-aortic interposition graft using a bovine pericardium patch. The defect in the duodenum was also sutured in two layers and a new omental flap was created. Discussion: The mortality rate of AEF is high and it is very unlikely that a patient will survive two AEFs without major complications. It is believed that there are extremely few double AEF cases described in the literature. The aetiological factor in the development of PAEF in this case was most likely the patient's aortic aneurysm, which was most likely of mycotic origin due to tuberculosis. The patient developed a pseudoaneurysm during follow up and it is uncertain whether the pulsatile pressure of the pseudoaneurysm led to the recurrence of the AEF.