J. Adam van der Vliet

Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis.

Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eight studies which met our inclusion criteria. We extracted data for serum creatinine, blood urea nitrogen and histological renal damage, as well as study quality indicators. Meta-analysis showed that IPC reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD 1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89, 1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were the window of protection (<24 h = early vs. ≥24 h = late) and animal species (rat vs. mouse). No difference in efficacy between local and remote IPC was observed. In conclusion, our findings show that IPC effectively reduces renal damage after IRI, with higher efficacy in the late window of protection. However, there is a large gap in study data concerning the optimal window of protection, and IPC efficacy may differ per animal species. Moreover, current clinical trials on RIPC may not be optimally designed, and our findings identify a need for further standardization of animal experiments.

Intestinal permeability is increased after major vascular surgery

PURPOSE In experimental animals increased intestinal permeability has been demonstrated after ischemia and reperfusion injury. In this study we determined intestinal permeability in patients after elective or emergency aortic aneurysm repair; the latter patients were in severe shock on hospital admission. METHODS A dual sugar absorption test, with lactulose and mannitol as markers, was used to measure intestinal permeability on the second day between 24 and 30 hours after hospital admission. RESULTS The lactulose/mannitol excretion ration was 0.012 +/- 0.005 in seven healthy control subjects, 0.118 +/- 0.116 in seven patients having elective operation, and 0.098 +/- 0.093 in eight patients having emergency operation, indicating a significant increase of intestinal permeability in both patient groups (p < 0.01). No significant difference was found in intestinal permeability between patients of the elective and emergency groups. CONCLUSIONS A significant increase in intestinal permeability commonly occurs in patients after elective and emergency major vascular surgery. It is suggested that this is mainly due to reperfusion injury rather than the ischemic period of the intestine itself.

The Effect Of Pancreas Transplantation On Diabetic Polyneuropathy

Neuromuscular function was evaluated in long-term type I diabetic patients who retained a functioning pancreas graft. A group of 34 patients was examined at 1 year and another group of 11 patients at 2 years after pancreas transplantation. In this report the clinical and electrophysiological course of motor features of poly-neuropathy are described. Before pancreas transplantation, clinical evidence of polyneuropathy was present in all patients. The mean motor nerve conduction velocities (NCV) were below normal and the mean amplitude of the evoked muscle action potentials (MAP) were in the low normal range. The observed abnormalities of muscle strength and tendon reflexes had not progressed in these intervals. Motor NCV improved slightly and MAP amplitude was essentially unchanged. These preliminary results indicate that the progression of diabetic polyneuropathy may be halted by successful pancreas transplantation.

Chlamydia pneumoniae in Abdominal Aortic Aneurysms : Abundance of Membrane Components in the Absence of Heat Shock Protein 60 and DNA

In this article, we describe the results of a comparative study for the detection of Chlamydia pneumoniae in abdominal aortic aneurysm specimens of 19 patients through the use of immunocytochemistry (ICC), in situ hybridization (ISH), and polymerase chain reaction (PCR), along with the detection of cytomegalovirus (CMV) and herpes simplex virus (HSV) by ICC and PCR. C pneumoniae-specific membrane protein was detected in specimens of all 19 (100%; 95% confidence interval [CI] 82% to 100%) and of 15 (79%; 95% CI 54% to 94%) patients with monoclonal antibodies RR-402 and TT-401, respectively. Chlamydial lipopolysaccharide was detected in specimens of 15 (79%; 95% CI 54% to 94%) patients when the results of 4 different monoclonal antibodies were combined. Surprisingly, chlamydial heat shock protein 60 was not detected in any of the specimens by ICC. Furthermore, C pneumoniae DNA was not detected by ISH when a C pneumoniae major outer membrane protein gene fragment was used as probe, nor was it reproducibly detected by PCR on extracted DNA. These results may be explained either by different kinetics of degradation of the different components of C pneumoniae after infection of the vessel wall or by the involvement of other Chlamydia-like microorganisms. Coexistence of C pneumoniae antigens and HSV antigens but not CMV antigens was observed in specimens from 10 of 18 (56%; 95% CI 31% to 78%) patients by ICC. CMV and HSV DNAs were not detected by PCR. In conclusion, we have demonstrated the presence of antigens of C pneumoniae in the absence of specific DNA in abdominal aortic aneurysms, suggesting persistence of the antigens rather than a persistent infection.

Influence of prolonged cold ischemia in renal transplantation

van der Vliet JA, Warlé MC, Cheung CLS, Teerenstra S, Hoitsma AJ. Influence of prolonged cold ischemia in renal transplantation. 
Clin Transplant 2011: 25: E612–E616.

Overexpression of Angiopoietin-Like Protein 4 Protects Against Atherosclerosis Development

Objective—Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized the regulation of Angptl4 expression in macrophages and examined the impact of Angptl4 on atherosclerosis development. Approach and Results—Macrophage activation elicited by pathogen-recognition receptor agonists decreased Angptl4 expression, whereas lipid loading by intralipid and oxidized low-density lipoprotein increased Angptl4 expression. Consistent with an antilipotoxic role of Angptl4, recombinant Angptl4 significantly decreased uptake of oxidized low-density lipoprotein by macrophages, via lipolysis-dependent and -independent mechanisms. Angptl4 protein was detectable in human atherosclerotic lesions and localized to macrophages. Transgenic overexpression of Angptl4 in atherosclerosis-prone apolipoprotein E*3-Leiden mice did not significantly alter plasma cholesterol and triglyceride levels. Nevertheless, Angptl4 overexpression reduced lesion area by 34% (P<0.05). In addition, Angptl4 overexpression decreased macrophage content (−41%; P<0.05) and numbers of monocytes adhering to the endothelium wall (−37%; P<0.01). Finally, plasma Angptl4 was independently and negatively associated with carotid artery sclerosis measured by 3-T MRI in subjects with metabolic syndrome and low-grade systemic inflammation. Conclusions—Angptl4 suppresses foam cell formation to reduce atherosclerosis development. Stimulation of Angptl4 in macrophages by oxidized low-density lipoprotein may protect against lipid overload.

Assessing endovascular skills using the Simulator for Testing and Rating Endovascular Skills (STRESS) machine.

OBJECTIVES Endovascular techniques are an integral part of modern-day vascular surgery practice and training. Nevertheless, validated in vitro assessment tools for these skills are scarce. This study describes the development and pilot testing of the Simulator for Testing and Rating Endovascular Skills (STRESS machine). DESIGN The design was kept straightforward and compact, without the need for contrast or fluoroscopy. A specific technical skill score was designed analogous to the Imperial College Evaluation of Procedural Skill (ICEPS), an assessment score for open surgical skill. This score was combined with an already validated global rating assessment to form the total score (TS). METHODS A pilot study was carried out on 18 candidates of varying levels of expertise: novice, intermediate and expert, who were assessed by two independent observers to test inter-observer reliability. RESULTS Inter-observer reliability was excellent, Cronbachs alpha coefficient of the TS was 0.94 (95% confidence interval: 0.84-0.97). A one-way analysis of variance (ANOVA) showed a significant difference between the novice and expert groups (p<0.001), between the novice and intermediate groups (p<0.01) and between the intermediate and expert groups (p<0.05). CONCLUSION The STRESS machine, in combination with the specific technical skill score and global rating assessment, provides a reliable method of discriminating between the novice, intermediate and expert candidates with excellent inter-observer variability.

Unilateral vascular reconstruction for iliac obstructive disease

PURPOSE Controversy exists regarding the extent of vascular reconstructive surgery in the presence of unilateral symptomatic iliac obstructive disease. This study reviews the results of unilateral iliac reconstruction, with special emphasis on the need for consecutive contralateral intervention. METHODS The outcomes of 184 unilateral and 350 aortobilateral reconstructions for obstructive disease performed during the same period were retrospectively analyzed. Treatment allocation was based on hemodynamic parameters. Unilateral reconstruction was performed by a way of a retroperitoneal approach through a pararectal incision and bilateral reconstruction by way of a transperitoneal approach through a midline abdominal incision. RESULTS Symptom relief, improvement of noninvasively measured parameters, and graft patency were similar after unilateral and bilateral reconstruction. Both groups had a 10-year primary patency rate greater than 80%. There were no differences in morbidity rate, although respiratory complications occurred more often after bilateral reconstruction. Mortality rates were 1.6% after unilateral reconstruction and 4.9% after bilateral reconstruction. Secondary contralateral reconstruction was performed in only 6% of the patients who underwent an initial unilateral operation. CONCLUSIONS The unilateral vascular reconstruction for iliac obstructive disease is a well-tolerated procedure with an excellent long-term outcome. It is a valuable alternative to conventional aortobilateral reconstruction in carefully selected patients. Prophylactic reconstruction of an asymptomatic iliac stenosis without signs of significant hemodynamic impairment is most often not indicated.

Treatment of recurrent varicose veins of the great saphenous vein by conventional surgery and endovenous laser ablation

OBJECTIVE Varicose vein recurrence of the great saphenous vein (GSV) is a common, costly, and complex problem. The aim of the study was to assess feasibility of endovenous laser ablation (EVLA) in recurrent varicose veins of the GSV and to compare this technique with conventional surgical reintervention. METHODS Case files of all patients treated for GSV varicosities were evaluated and recurrences selected. Demographics, duplex scan findings, CEAP classification, perioperative data, and follow-up examinations were all registered. A questionnaire focusing on patient satisfaction was administered. RESULTS Sixty-seven limbs were treated with EVLA and 149 were surgically treated. General and regional anesthesia were used more in the surgery group (P < .001). Most complications were minor and self-limiting. Wound infections (8% vs 0%; P < .05) and parasthesia (27% vs 13%; P < .05) were more abundant in the surgery group, whereas the EVLA-treated patients reported more delayed tightness (17% vs 31%; P < .05). Surgically-treated patients suffered less postoperative pain (P < .05) but reported a higher use of analgesics (P < .05). Hospital stay in the surgery group was longer (P < .05) and they reported a longer delay before resuming work (7 vs 2 days; P < .0001). Patient satisfaction was equally high in both groups. At 25 weeks of follow-up, re-recurrences occurred in 29% of the surgically-treated patients and in 19% of the EVLA-treated patients (P = .511). CONCLUSION EVLA is feasible in patients with recurrent varicose veins of the GSV. Complication rates are lower and socioeconomic outcome is better compared to surgical reintervention.

Humoral signalling compounds in remote ischaemic preconditioning of the kidney, a role for the opioid receptor

BACKGROUND Renal ischaemia-reperfusion injury (IRI) is a common clinical problem associated with significant mortality and morbidity. One strategy to reduce this damage is remote ischaemic preconditioning (RIPC), in which brief ischaemia of a limb protects the kidney against a prolonged ischaemic insult. The mechanism of renal RIPC has not yet been elucidated. Here, we address the gap in our understanding of renal RIPC signalling, using a rat model of renal IRI and RIPC by brief hind limb ischaemia. METHODS Rats were treated with either no RIPC, RIPC+vehicle or RIPC+ an inhibitor or antagonist of one of the following candidate signalling molecules: noradrenalin, cannabinoids, glucocorticoids, inducible nitric oxide synthase, calcitonin gene-related peptide, ganglion-mediated signalling, haem oxygenase and free radicals. Subsequently, the animals underwent 25 min of renal ischaemia and 2 days of reperfusion, after which renal function and damage were assessed. RESULTS RIPC by three 4 min cycles of hind limb ischaemia effectively reduced renal IRI. Pre-treatment with the opioid receptor antagonist naloxone completely blocked this protective effect, when compared with animals treated with RIPC+vehicle; serum creatinine and urea increased (307.8±43.7 versus 169.5±16.7 µmol/L and 42.2±4.9 versus 27.6±2.2 mmol/L, respectively), as did the renal histological damage (score 4.2±0.7 versus 2.8±0.5) and expression of kidney injury molecule-1 (KIM-1; relative-fold increase in mRNA expression 164±18 versus 304±33). All other antagonists were without effect. CONCLUSIONS Renal RIPC by brief hind limb ischaemia may be the result of endorphin release from the hind limb. The importance of opioid signalling in renal RIPC provides vital clues for its successful translation to the clinical setting.