Tissue optical perfusion pressure: a simplified, more reliable, and faster assessment of pedal microcirculation in peripheral artery disease.

Oscillometry is an alternative to continuous-wave Doppler (cw-Doppler) to determine peripheral artery disease (PAD) severity using the ankle-brachial index (ABI). cw-Doppler ABI differentiates systolic pressure of ATP and ADP where either one of both values in most patients is higher (high) and the other value is lower (low). In contrast, oscillometric ABI measures the strongest signal and hence misses the lower value. Both do not take pedal perfusion into consideration. Simultaneous determination of tissue microperfusion cares for pedal PAD. ABI was determined by cw-Doppler and oscillometry. Tissue optical perfusion pressure (TOPP) was taken from the first toe using photoplethysmography. 323 patients were evaluated retrospectively in 3 independent groups. group 1 (99 patients) compared TOPP and oscillometric ABI with systolic cw-Doppler-pressure and cw-Doppler ABI. In group 2 (103 patients) TOPP was compared with toe pressure (TP). In group3 (121 symptomatic patients) TOPP and ABI at rest and after stress were compared (ultrasound examination and magnetic resonance angiography (MRA) or computer tomography angiography (CTA) as control). Bland-Altman-plot analysis presented no significant difference between oscillometric ABI and the high cw-Doppler ABI (group 1). TOPP showed a difference of 26mmHg to the low cw-Doppler-pressure and none to the high cw-Doppler-pressure. In group 2 TOPP correlates to TP but presented a difference of 37 mmHg. group 3 showed weak or no correlation between ABI and walking distance. Oscillometric ABI correlates significantly to TOPP. To conclude, data after stress present a better correlation than at rest. We conclude that TOPP provides absolute values of pedal macro-/microcirculation at rest and after stress tests.NEW & NOTEWORTHY This new application of photoplethysmography investigated the microcirculation in peripheral artery disease at the level of the toe pad and determined the tissue optical perfusion pressure as the first pulsatile signal during automatic cuff deflation at the ankle. It is the first time that this method has been integrated for simultaneous routine examination in an automatic oscillometric ankle-brachial index (ABI) system. This quick and simple measurement technique provides clinical information on the microcirculation downstream the routine ABI measurement at rest and in particular after stress test.

Serial assessments of microvascular obstruction by contrast-enhanced magnetic resonance predict contractile recovery and clinical outcome after reperfused acute myocardial infarction.

AIMS: The purpose of the study was to investigate, using cardiac magnetic resonance (CMR), the presence and time course of microvascular obstruction (MO) in patients with acute myocardial infarction (AMI), and to test its relationship with cardiac remodeling and clinical outcomes. METHODS AND RESULTS: 53 patients with AMI and successful percutaneous reperfusion underwent CMR examination at four separate timepoints: within the first 48 hours, at 10 days, at six and twelve months after infarction. MO was quantified immediately (early imaging) and 10 minutes (late imaging) after contrast administration in each session. The extent of MO decreased from early to late imaging at both the first and the second CMR exam (p≤0.001). Early MO was absent in 18(36%) patients both at 48 hours and 10 days after AMI. At 1 year follow-up, LVEF in these patients improved to normal (median = 62% (53-70)). Early MO was present in the first but not in the second CMR in 13 (26%) patients; LVEF at one year in these patients reached a median = 52% (47-61). Finally, Early MO was present in both exams in 19 (38%) patients, who at 1 year after infarction had a LVEF of median = 49% (42-54, P≤0.001 across groups). The time course of MO was a predictor of prognosis upon Kaplan-Meier analysis (P = 0.035). The presence of MO at 10 days after AMI was associated with a higher risk of MACE during a 5-years follow-up. CONCLUSIONS: The presence of MO within 48 hours after AMI, and its time course in the following ten days, provides complementary information on both functional myocardial recovery and long-term outcome.

Off-pump coronary artery bypass prevents visceral organ damage.

OBJECTIVES: Visceral malperfusion after coronary artery bypass grafting (CABG) results in high morbidity and mortality. This study was designed to evaluate the effect of CABG performed by surgical techniques on visceral perfusion and function. METHODS: Pigs (n = 28) were studied in four groups: I. Sham; II. Off-pump coronary artery bypass grafting (OPCAB): 1 h stabilizer with 40 min intracoronary shunt; III. Extracorporeal circulation (ECC): 1 h ECC with 40 min aortic cross-clamping and cardioplegic arrest; IV. Impella: 1 h left ventricular blood-pump support and stabilizer with 40 min intracoronary shunt. A left internal mammary to left anterior descending coronary artery bypass was performed in Groups II-IV. All animals were observed for a further 240 min. During the experiment haemodynamics, creatinine clearance, intestinal fatty acid binding protein (iFABP), pancreatic (lipase and amylase) and liver enzymes (α-glutathione s-transferase, glutamate-oxaloacetate transaminase (GOT), gamma-glutamyl transferase (GGT), glutamate dehydrogenase and glutamate-pyruvate transaminase (GPT)) were measured. Visceral perfusion (VP) was assessed in both kidneys, intestine, pancreas, liver and spleen with 15 µm fluorescent microspheres. RESULTS: During OPCAB surgery, VP decreased slightly. Renal functional parameters, iFABP, pancreatic and liver enzymes remained unchanged. ECC and Impella led to significantly reduced renal, pancreatic and intestinal blood flow (P < 0.05). Creatinine clearance, pancreatic and liver (GPT, GGT) enzymes were significantly decreased only after ECC (P < 0.05). ECC and Impella resulted in a significantly increased iFABP level (P < 0.05). GOT was elevated significantly after surgery in Groups II, III and IV (P < 0.05). CONCLUSIONS: CABG with ECC or Impella leads to impaired visceral blood flow and function. OPCAB minimizes these procedure associated alterations.

Novel ß-amino acid derivatives as inhibitors of cathepsin A.

Cathepsin A (CatA) is a serine carboxypeptidase distributed between lysosomes, cell membrane, and extracellular space. Several peptide hormones including bradykinin and angiotensin I have been described as substrates. Therefore, the inhibition of CatA has the potential for beneficial effects in cardiovascular diseases. Pharmacological inhibition of CatA by the natural product ebelactone B increased renal bradykinin levels and prevented the development of salt-induced hypertension. However, so far no small molecule inhibitors of CatA with oral bioavailability have been described to allow further pharmacological profiling. In our work we identified novel ß-amino acid derivatives as inhibitors of CatA after a HTS analysis based on a project adapted fragment approach. The new inhibitors showed beneficial ADME and pharmacokinetic profiles, and their binding modes were established by X-ray crystallography. Further investigations led to the identification of a hitherto unknown pathophysiological role of CatA in cardiac hypertrophy. One of our inhibitors is currently undergoing phase I clinical trials.

Continuous regional myocardial blood flow measurement: validation of a near-infrared laser Doppler device in a porcine model.

OBJECTIVE: RMBF measurement is a major concern in various clinical and experimental settings, but no validated device for RMBF is currently available. METHODS: An LVP-triggered laser Doppler to measure RMBF was validated by simultaneous fluorescent MS RMBF in a porcine LAD flow reduction model (n = 10 pigs). The laser probe was positioned on the left ventricle's anterior wall. LAD blood flow reduction was achieved by a shaft-driven occluder positioned proximal to the transit-time flow meter measuring coronary blood flow. RMBF was measured at baseline; after the reduction of LAD blood flow to 70% and 30% of baseline; at 20 and 120 minutes of reperfusion; and, finally, 15 minutes after LAD occlusion. RESULTS: Laser Doppler RMBF (LDU) correlated strongly with MS RMBF under all tested conditions: baseline (epicardial 194.7 ± 41.9, endocardial 130.2 ± 29.2); 70% baseline-flow (epicardial 160.4 ± 27.7, endocardial 112.1 ± 15.1); 30% baseline-flow (epicardial 44.3 ± 5.5, endocardial 32.9 ± 9); 20 minutes reperfusion (epicardial 175.8 ± 33.6, endocardial 126.5 ± 30); 120 minutes reperfusion (epicardial 146.3 ± 31.1, endocardial 107.1 ± 29.7); and complete LAD occlusion (epicardial 10.5 ± 5.8 endocardial 1.4 ± 0.3) (r = 0.986-0.962, p < 0.001). CONCLUSIONS: This new blood pressure waveform-triggered laser Doppler probe is able to measure RMBF at different depths online in the beating heart.

Gene therapy with iNOS enhances regional contractility and reduces delayed contrast enhancement in a model of postischemic congestive heart failure.

AIMS: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. METHODS: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. RESULTS: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. Wall thickness at end-systole (6.8 mm vs. 5.9 mm, p < 0.001) and at end-diastole (5.4 mm vs. 4.2 mm, p < 0.001) were significantly higher in the therapy group. Additionally, the regional wall motion at the level of the ischemic region was 3.5 mm in the therapy group while it was significantly less (3.0 mm, p < 0.001) in the control group. CONCLUSIONS: Our findings demonstrate that transient iNOS overexpression potentially leads to a significant decrease of regional late enhancement with a positive effect on regional cardiac function in the ischemic area in a large animal model of postischemic heart failure.

Comparison of the quantitative first pass myocardial perfusion MRI with and without prospective slice tracking: comparison between breath-hold and free-breathing condition.

Physiologic motion of the heart is one of the major problems of myocardial blood flow quantification using first pass perfusion-MRI method. To overcome these problems, a perfusion pulse sequence with prospective slice tracking was developed. Cardiac motion was monitored by a navigator directly positioned at heart's basis to overcome no additional underlying model calculations connecting diaphragm and cardiac motion. Additional prescans were used before the perfusion measurement to detect slice displacements caused by remaining cardiac motion between navigator and the perfusion slice readout. The pulse sequence and subsequent quantification of myocardial blood flow was tested in healthy pigs with and without prospective slice tracking under both free-breathing and breath-hold conditions. To avoid influences by residual contrast agent concentration time courses were analyzed. Median myocardial blood flow values and interquartile ranges with prospective slice tracking under free-breathing and in a breath-hold were (1.04, interquartile range = 0.58 mL/min/g) and (1.20, interquartile range = 0.59 mL/min/g), respectively. This is in agreement with published positron emission tomography values. In measurements without prospective slice tracking (1.15, interquartile range = 1.58 mL/min/g), the interquartile range is significantly (P < 0.012) larger because of residual cardiac motion. In conclusion, prospective slice tracking reduces motion-induced variations of myocardial blood flow under both during breath-hold and under conditions of free-breathing.

Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.

BACKGROUND: This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. METHODS AND RESULTS: Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-transfer was demonstrated for up to 7 days by reverse transcriptase-polymerase chain reaction in preliminary studies. Four weeks after iNOS transfer, magnetic resonance imaging showed no effect of iNOS overexpression on cardiac contractility at rest and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P = ns). Late enhancement, infarct size, and the amount of fibrosis were similar between groups. Although perfusion and perfusion reserve in response to adenosine and dobutamine were not significantly modified by iNOS-transfer, both vessel number and diameter were significantly increased in the ischemic area in the iNOS-treated group versus control (point score: control 15.3, iNOS 34.7; P < 0.05). CONCLUSIONS: Our findings demonstrate that transient iNOS overexpression does not aggravate cardiac dysfunction or postischemic fibrosis, while potentially contributing to neovascularization in the chronically ischemic heart.

Usefulness of MRI to differentiate between temporary and long-term coronary artery occlusion in a minimally invasive model of experimental myocardial infarction.

The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusion was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 +/- 4.4%; p = 0.008) and group 2 (9.4 +/- 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 +/- 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 +/- 0.3, 5.9 +/- 0.7, and 6.1 +/- 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 +/- 2.1%) compared to group 1 (5.3 +/- 5.4%; p = 0.003) and group 2 (9.7 +/- 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development.

Long term follow up after percutaneous closure of PFO in 357 patients with paradoxical embolism: Difference in occlusion systems and influence of atrial septum aneurysm.

BACKGROUND: Percutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA is an alternative to medical therapy especially in patients with atrial septal aneurysm (ASA). The differences in time to complete occlusion for various closure devices in PFO alone and PFO plus ASA are of natural interest. METHODS AND RESULTS: Between January, 1st 1998 and November, 30th 2006 percutaneous PFO closure was performed in 357 patients with a history of > or =1 paradoxical embolism using three different devices: Amplatzer PFO-(n=199), Starflex-(n=48) and Helex Occluder (n=110). All patients were assigned to a post-interventional protocol with contrast-enhanced transesophageal echocardiography (TOE) at 1 and 6 months and every 6 to 12 months in case of incomplete closure. Definite closure was confirmed in at least two consecutive TOE studies. The closure time curves between the three devices were significantly different (p=0.0072). Devices of 25 mm or less had a better occlusion rate. The difference between the closure time curves of PFO and PFO+ASA concerning each device type was significant for Helex (p=0.006) and Starflex (p=0.030). In regard to the occlusion time for large devices Helex succeeded later than Amplatzer and Starflex (p=0.0029). Concerning the cumulative follow up period of 1265 patient years the recurrence/re-event rate of cerebral and peripheral thromboembolic events was 0.7% per patient year. No relation to residual PFO shunting or to thrombus formation was seen. There were no peri-interventional technical complications. In five patients of the Starflex group thrombi were detected in the four week TOE controls. CONCLUSION: The closure rate is dependent on occluder size and type plus the occurrence of an atrial septum aneurysm.

Critical single proximal left arterial descending coronary artery stenosis to mimic chronic myocardial ischemia: a new model induced by minimal invasive technology.

BACKGROUND/AIMS: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. METHODS: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. RESULTS: Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 +/- 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 +/- 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. CONCLUSION: The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease.

Quantitative myocardial perfusion imaging using different autocalibrated parallel acquisition techniques.

PURPOSE: To compare three different autocalibrated parallel acquisition techniques (PAT) for quantitative and semiquantitative myocardial perfusion imaging. MATERIALS AND METHODS: Seven healthy volunteers underwent myocardial first-pass perfusion imaging at rest using an SR-TrueFISP pulse sequence without PAT and while using GRAPPA, mSENSE, and TSENSE. signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), normalized upslopes (NUS), and myocardial blood flow (MBF) were calculated. Artifacts, image noise, and overall image quality were qualitatively assessed. Furthermore, the relation between signal intensity (SI) and contrast medium (CM) concentration was determined in phantoms. RESULTS: Using PAT the linear range of the SR-TrueFISP sequence was increased about 40%. All three PAT methods introduced significant loss in SNR and CNR. GRAPPA yielded slightly better values then mSENSE and TSENSE. Both SENSE techniques introduced significantly residual aliasing artifacts. Image noise was increased with all three PAT methods. However, overall image quality was reduced only with mSENSE. Even though GRAPPA yielded smaller NUS values than non-PAT, mSENSE, and TSENSE, no differences were found in MBF between all applied techniques. CONCLUSION: Quantitative and semiquantitative myocardial perfusion imaging can benefit from PAT due to shorter acquisition times and increased linearity of the pulse sequence. GRAPPA and TSENSE turned out to be well suited for quantitative myocardial perfusion imaging.

Resistance of the internal mammary artery to restenosis: a histomorphologic study of various porcine arteries.

BACKGROUND/AIMS: Restenosis after percutaneous transluminal angioplasty (PTA) of the internal mammary artery (IMA) grafts is much less pronounced than in other arteries and venous grafts. The aim of the study was to test whether various arteries respond differently to dilatation. METHODS: PTA of the IMA, carotid, renal and circumflex coronary (RCx) arteries was performed in 9 pigs (balloon to artery ratio of 1:1.5). After 8 weeks, angiography was repeated and vessels prepared for histological analysis. Immunohistochemical staining was done to examine proliferative activity (Ki67) and to identify the vasa vasorum of the adventitia (F VIII-RA). RESULTS: The intima-media ratio after PTA was lowest in the IMA (0.06), followed by the carotid (0.27) and renal arteries (0.49) and the RCx (0.69). Proliferation of the intima was seen at 287 degrees of the vessel circumference in the RCx, at 286 degrees in the renal and at 166 degrees in the carotid artery. No proliferative activity was seen in the IMA. The intima-adventitia ratio was lower in the IMA than in the RCx and renal arteries (p < 0.05). CONCLUSION: Intima proliferation after PTA varies between the different vessels, with best results seen in the IMA. There are differences in remodeling after PTA between muscular, muscular/elastic and elastic arteries.

Inflammatory pathways in patients with heart failure and preserved ejection fraction.

UNLABELLED: Immune activation is well established in patients with chronic heart failure and reduced ejection fraction (HF and reduced EF) and is associated with an impaired prognosis. Patients with heart failure and preserved ejection fraction (HF and preserved EF) have an impaired prognosis as well. It is not known whether they have signs of immune activation. METHODS: We studied patients with HF and preserved EF (n=17, NYHA II [n=7]/III [n=10]) and patients with HF and reduced EF (n=17 NYHA II [n=1]/III [n=16]) and 20 controls. Echocardiography demonstrated preserved ejection fraction (LVEF 59+/-9%), but LV hypertrophy in patients with preserved EF as compared with patients with reduced EF (LVEF 23+/-5%). We evaluated levels of TNFalpha, its receptors (sTNFR-1 and 2), IL-6, IL-10 and NT-proBNP. RESULTS: TNFalpha, was highest in HF with reduced EF (2.87+/-0.65 vs 1.67+/-0.58 pg/mL, p<0.001) compared to preserved EF and similar between HF with preserved EF and controls. However, sTNFR1 (1618+/-384 vs 1017+/-302 pg/mL, p<0.001) and sTNFR2 levels (3554+/-916 vs 2041+/-586 pg/mL, p<0.001) in HF with preserved EF were significantly higher compared with controls. The same was true for IL-6, IL-10 and NT-proBNP. The highest cytokine and NT-proBNP levels were present in HF with reduced EF. There was a negative correlation between TNFalpha, and LVEF (r=- 0.700; p<0.0001) and positive correlations between sTNFR1 and 2 with NT-proBNP. CONCLUSION: Patients with HF and preserved EF already show signs of systemic-immune activation which may contribute to the impaired prognosis and the progression to HF with reduced EF.

Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization in a porcine model.

BACKGROUND AND PURPOSE: Emboli and proinflammatory mediators are suspected of generating cerebral edema after coronary surgery. In contrast to cardiopulmonary bypass (CPB), off-pump coronary artery bypass surgery (OPCAB) reduces microemboli count and proinflammatory mediator release but carries the risk of hemodynamic instability. A microaxial blood pump can augment cardiac output. METHODS: Coronary bypasses were constructed in pigs with CPB and cardioplegia (n=9), OPCAB (n=9), or blood-pump support CAB (n=9). Nine animals underwent sham operation. Embolus count was monitored and regional cerebral blood flow was assessed with microspheres in 21 brain specimens per animal (n=189 per group). Interleukins 6 and 8 and tumor necrosis factor-alpha concentrations were determined. These variables were studied before, during, and for 4 hours after surgery. Finally, cerebral water content was determined. RESULTS: During CPB and blood-pump CAB, a significant number of emboli were counted in contrast to OPCAB and controls (P<0.05). During CPB, regional cerebral blood flow was affected (32 of 189) and showed reactive hyperemia except in 10 specimens after aortic cross-clamp release. This impairment persisted in 20 specimens. During and after OPCAB, regional cerebral blood flow remained nearly unchanged but showed low flow during (58 of 189) and after (35 of 189) the blood-pump run. A significant increase in proinflammatory mediators was observed only in the CPB group. CPB and blood-pump CAB significantly increased cerebral water content (P<0.05). A strong correlation between embolic load and cerebral water content was observed in all groups. No correlation between proinflammatory mediator release and cerebral water content was detected. CONCLUSIONS: Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization.

Monocyte-derived dendritic cells of patients with coronary artery disease show an increased expression of costimulatory molecules CD40, CD80 and CD86 in vitro.

BACKGROUND: Atherosclerosis is a disease triggered by diverse exogenous stimuli and sustained by chronic inflammatory processes. Dendritic cells (DCs) are key regulatory antigen-presenting cells and play a crucial role in regulating the adaptive and innate immune system in any chronic inflammatory process. DCs are present in atherosclerotic lesions in the areas of the highest T-cell density. So far, their role in atherosclerosis has not been fully elucidated. We investigated the phenotypic properties of DCs in patients with coronary artery disease (CAD) in comparison to healthy individuals. METHODS: Peripheral blood monocytes were isolated from 50 patients with CAD and 19 healthy individuals and differentiated over 9 days to immature and mature DCs. Analysis of the distribution of important stimulatory and costimulatory molecules on the surface of immature and mature DCs was performed by flow cytometry. RESULTS: We observed no changes between the groups concerning cell numbers or expression of CD1a or HLA-DR on DCs. Patients with CAD, however, showed a significant upregulation of the costimulatory molecules CD80, CD86 and CD40 as compared with healthy controls. Expression of CD40, CD80 and CD86 on DCs partly correlated with smoking, family history of CAD, as well as with C-reactive protein levels. High-density lipoprotein cholesterol was inversely associated with the expression of CD40 and CD80 on mature DCs (P<0.05). CONCLUSION: Upregulation of important costimulatory molecules on monocyte-derived DCs of CAD patients, is influenced multifactorially. Our results show notable differences between CAD patients and healthy individuals, possibly contributing to the pathophysiological processes in atherogenesis.

Comparison of three accelerated pulse sequences for semiquantitative myocardial perfusion imaging using sensitivity encoding incorporating temporal filtering (TSENSE).

PURPOSE: To investigate the parallel acquisition technique sensitivity encoding incorporating temporal filtering (TSENSE) with three saturation-recovery (SR) prepared pulse sequences (SR turbo fast low-angle shot [SR-TurboFLASH], SR true fast imaging with steady precession [SR-TrueFISP], and SR-prepared segmented echo-planar-imaging [SR-segEPI]) for semiquantitative first-pass myocardial perfusion imaging. MATERIALS AND METHODS: In blood- and tissue-equivalent phantoms the relationship between signal intensity (SI) and contrast-medium concentration was evaluated for the three pulse sequences. In volunteers, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and normalized upslopes (NUS) were calculated from signal-time curves (STC). Moreover, artifacts, image noise, and overall image quality were qualitatively evaluated. RESULTS: Phantom data showed a 40% increased linear range of the relation between SI and contrast-medium concentration with TSENSE. In volunteers, TSENSE introduced significantly residual artifacts and loss in SNR and CNR. No differences were found for NUS values with TSENSE. SR-TrueFISP yielded highest SNR, CNR, and quality scores. However, in SR-True-FISP images, dark-banding artifacts were most pronounced. NUS values obtained with SR-TrueFISP were significantly higher and with SR-segEPI significantly lower than with SR-TurboFLASH. CONCLUSION: Semiquantitative myocardial perfusion imaging can significantly benefit from TSENSE due to shorter acquisition times and increased linearity of the pulse sequences. Among the three pulse sequences tested, SR-TrueFISP yielded best image quality. SR-segEPI proved to be an interesting alternative due to shorter acquisition times, higher linearity and fewer dark-banding artifacts.

C1-esterase inhibitor reverses functional consequences of superior mesenteric artery ischemia/reperfusion by limiting reperfusion injury and restoring microcirculatory perfusion.

Activated complement contributes significantly to reperfusion injury after ischemia. This study explores functional consequences of C1-esterase inhibitor (C1-INH) treatment after superior mesenteric artery occlusion (SMAO)/reperfusion using intravital microscopy. Thirty anesthetized, spontaneously breathing, male Sprague-Dawley rats underwent SMAO for 60 min followed by reperfusion (4 h). C1-esterase inhibitor (100 and 200 IU/kg body weight) or saline (0.9%) was given as a single bolus before reperfusion. Sham-operated animals (n = 10) without SMAO served as controls. Systemic hemodynamics were monitored continuously, arterial blood gases analyzed intermittently, and leukocyte/endothelial interactions in the mesenteric microcirculation quantified at intervals using intravital microscopy. Ileal lipid-binding protein (I-LBP) levels were determined from serum samples with an enzyme-linked immunosorbent assay at the end of the experiments. C1-esterase inhibitor restored microcirculatory perfusion to baseline levels in a dose-dependent manner and reduced adherent leukocytes after SMAO/reperfusion to similar levels in both C1-INH-treated groups during reperfusion. Furthermore, C1-INH treatment efficiently prevented metabolic acidosis, reduced the need for intravenous fluids to support blood pressure, and decreased I-LBP levels in a dose-dependent manner. Survival rates were 100% in controls and after 200 IU/kg C1-INH, 90% after 100 IU/kg C1-INH, and 30% in saline-treated animals. C1-esterase inhibitor bolus infusion efficiently blunted functional consequences of mesenteric ischemia/reperfusion with I-LBP, proving to be a valuable serum marker mirroring the effect of ischemia/reperfusion and treatment at the end of the experiments.

Shunting of the microcirculation after mesenteric ischemia and reperfusion is a function of ischemia time and increases mortality.

OBJECTIVE: Shunting of the microcirculation contributes to the pathology of sepsis and septic shock. The authors address the hypothesis that shunting of the microcirculation occurs after superior mesenteric artery occlusion (SMAO) and reperfusion, and explore functional consequences. METHODS: Spontaneously breathing animals (rats) (n = 30) underwent SMAO for 0 (controls), 30 (SMAO_30) or 60 min (SMAO_60) followed by reperfusion (4 h) with normal saline. Leukocyte-endothelial interactions in mesenteric venules were quantified in an exteriorized ileal loop using intravital microscopy. Abdominal blood flow was recorded continuously, and arterial blood gases were analyzed at intervals. The above groups were matched by comparable groups with continuous superior mesenteric artery blood flow measurements and without exteriorizing an ileal loop (controls*, SMAO_30*, SMAO_60*). RESULTS: Adherent leukocytes increased shortly after reperfusion in ischemia groups, and plateaued in these groups. Centerline velocity in the recorded venules was significantly reduced after reperfusion down to low-flow/no-flow in SMAO_60 as compared to SMAO_30 and controls, whereas perfusion of the SMA and ileal vessels persisted. The microcirculatory changes in SMAO_60 were accompanied by progressive metabolic acidosis, substantially larger volumes of intravenous fluids needed to support arterial blood pressure and significantly reduced survival (30%). SMA blood flow increased in relation to abdominal blood flow after reperfusion in SMAO_60*, and remained constant in SMAO_30* and controls*. Survival was 80% in SMAO_60*. CONCLUSION: Shunting of the microcirculation can be observed after SMAO for 60 min and reperfusion, and contributes significantly to the pathology of mesenteric ischemia and poor outcome.

Anti-inflammatory treatment with standardized human serum protein solution reduces local and systemic inflammatory response after hemorrhagic shock.

OBJECTIVE: Reperfusion after hemorrhagic shock leads to local and systemic inflammatory response. This study evaluates the effect of a short-term treatment with standardized human serum protein solution (SPS) on the local and systemic inflammatory response in the mesenteric microcirculation in the rat. METHODS: Spontaneously breathing animals underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume-controlled hemorrhagic shock was set by arterial blood withdrawal (2.5 ml/100 g body weight for 60 min), followed by reperfusion for 4 h. SPS (n = 10) or saline 0.9% (controls, n = 10) was given intravenously as a continuous infusion for 30 min at the beginning of reperfusion ('pre-hospital'). This was followed in both groups by substitution of blood and normal saline to support blood pressure ('in-hospital'). Systemic hemodynamics, mesenteric microcirculation and arterial blood gases were monitored before, during and after shock, and for 4 h after initiation of reperfusion. RESULTS: SPS treatment markedly reduced leukocyte/endothelial interaction, and reduced the need for intravenous fluids compared to controls. For the entire observation period, blood pH was unchanged from baseline only in SPS-treated animals. The improvement of base excess and abdominal blood flow persisted for 2 h after SPS infusion. CONCLUSION: Short-term SPS treatment of hemorrhagic shock improved mesenteric microcirculation, arterial blood gases and global hemodynamics, and attenuated the inflammatory response to reperfusion. It may provide clinical benefit when applied at an early phase of reperfusion after hemorrhagic shock.