Regional tissue oximetry reflects changes in arterial flow in porcine chronic heart failure treated with venoarterial extracorporeal membrane oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in treatment of decompensated heart failure. Our aim was to investigate its effects on regional perfusion and tissue oxygenation with respect to extracorporeal blood flow (EBF). In five swine, decompensated low-output chronic heart failure was induced by long-term rapid ventricular pacing. Subsequently, VA ECMO was introduced and left ventricular (LV) volume, aortic blood pressure, regional arterial flow and tissue oxygenation were continuously recorded at different levels of EBF. With increasing EBF from minimal to 5 l/min, mean arterial pressure increased from 47+/-22 to 84+/-12 mm Hg (P<0.001) and arterial blood flow increased in carotid artery from 211+/-72 to 479+/-58 ml/min (P<0.01) and in subclavian artery from 103+/-49 to 296+/-54 ml/min (P<0.001). Corresponding brain and brachial tissue oxygenation increased promptly from 57+/-6 to 74+/-3 % and from 37+/-6 to 77+/-6 %, respectively (both P<0.01). Presented results confirm that VA ECMO is a capable form of heart support. Regional arterial flow and tissue oxygenation suggest that partial circulatory support may be sufficient to supply brain and peripheral tissue by oxygen.

Heterogenic endothelial responses to inflammation: role for differential N-glycosylation and vascular bed of origin.

BACKGROUND: Endothelial cell responses during inflammation are heterogeneous and key for selectivity in how leukocytes hone in on specific sites and why vascular diseases are highly bed specific. However, mechanisms for this specificity remain unclear. METHODS AND RESULTS: Here, we exposed human endothelial cells isolated from 5 systemic arterial beds from 1 donor (to overcome donor-to-donor genetic/epigenetic differences), the umbilical vein, and pulmonary microvasculature to TNF-α, LPS, and IL-1ß and assessed acute (ERK1/2 and p65) and chronic (ICAM-1, VCAM-1 total and surface expression) signaling responses and assessed changes in surface N-glycans and monocyte adhesion. Significant diversity in responses was evident by disparate changes in ERK1/2 and p65 NF-κB phosphorylation, which varied up to 5-fold between different cells and in temporal and magnitude differences in ICAM-1 and VCAM-1 expression (maximal VCAM-1 induction typically being observed by 4 hours, whereas ICAM-1 expression was increased further at 24 hours relative to 4 hours). N-glycan profiles both basally and with stimulation were also bed specific, with hypoglycosylated N-glycans correlating with increased THP-1 monocyte adhesion. Differences in surface N-glycan expression tracked with dynamic up- or downregulation of α-mannosidase activity during inflammation. CONCLUSIONS: These results demonstrate a critical role for the vascular bed of origin in controlling endothelial responses and function to inflammatory stimuli and suggest that bed-specific expression of N-linked sugars may provide a signature for select leukocyte recruitment.

Postacute C-reactive protein levels are elevated in cervical artery dissection.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) is associated with atherogenesis and stroke in mostly elderly subjects. We tested whether elevated CRP may also be linked to spontaneous cervical artery dissection (CAD) and cryptogenic stroke. METHODS: We investigated high-sensitivity CRP levels in 62 patients <60 years of age experiencing cerebral ischemia resulting from large artery atherosclerosis (LAA; n=21), CAD (n=21), or cryptogenic etiology (n=20) >9 months ago, and in 54 sex- and age-matched population controls. Receiver operating characteristic curve was used to identify the best CRP cutoff level for dichotomization. RESULTS: CRP was elevated above control levels (0.54 [0.33 to 0.84] median, interquartile range mg/L) in patients with LAA (2.59 [0.56 to 3.99] mg/L; P<0.001) and with CAD (2.37 [0.57 to 4.78] mg/L; P=0.0013) but not in patients with cryptogenic etiology (0.74 [0.14 to 7.86] mg/L). CRP levels above the cutoff level of 0.71 mg/L were independently associated with former CAD (P=0.005) but not with former LAA after adjustment for age, gender, and conventional risk factors. CONCLUSIONS: Our results strongly suggest that CRP is associated with CAD, independent from conventional risk factors, and that inflammatory mechanisms may play a role in its pathogenesis. This finding should be confirmed by larger studies.

TNFalpha increases the inflammatory response to vascular balloon injury without accelerating neointimal formation.

There is now clear evidence for a contributory role of inflammatory processes to restenosis following vascular balloon injury and stent implantation. The aim of the present study was to study the effects of TNFalpha, administered locally in vivo immediately following balloon angioplasty, on the leukocyte adhesive response and extent of neointimal formation in a rabbit model of subclavian artery injury. Initial in vitro studies were performed with normal isolated artery rings to assess the vascular adhesive response to TNFalpha or IL-1beta. Pre-incubation with either cytokine prior to addition of (51)Cr-labelled leukocytes enhanced the adhesion of leukocytes to the artery in both a time- and concentration-dependent manner. Although both cytokines induced an increase in the expression of the adhesion molecules ICAM-1 and VCAM-1, only antibodies to ICAM-1 blocked the enhanced adhesion induced by the cytokines. In artery segments retrieved from rabbits that had previously undergone subclavian artery angioplasty either 24 h or 8 days previously, there was an injury-induced increase in adhesion of leukocytes assessed ex vivo. In segments obtained from rabbits that received a 15 min local infusion of TNFalpha (2 ng/min) to the injured artery immediately after the angioplasty procedure, leukocyte adhesion assessed ex vivo was further significantly enhanced. The pro-adhesive effect of TNFalpha was associated with an increased expression of both ICAM-1 and VCAM-1. However, TNFalpha administration did not alter the extent of neointimal formation observed 8 days after injury. These findings suggest that while TNFalpha may play a role following vascular injury, it does not act alone to induce neointimal formation. Thus anti-inflammatory strategies targeted at multiple cytokines may be more appropriate than targeting a single cytokine to reduce the response to vascular injury.

Correlation of changes in nitric oxide synthase, superoxide dismutase and nitrotyrosine with endothelial regeneration and neointimal hyperplasia in the balloon-injured rabbit subclavian artery.

OBJECTIVES: Alterations in nitric oxide (NO) and superoxide production within the wall of injured vessels may modulate the development and eventual extent of neointima after balloon injury. METHODS: In this study we have characterized a rabbit model of subclavian artery injury and have used immunocytochemistry to detect NO synthase (NOS) isoforms, Cu-Zn superoxide dismutase (SOD) and nitrotyrosine in the injured vessel from 2 h to 28 days after injury. RESULTS: At 48 h after injury, when cellular proliferation that will ultimately form the neointima is commencing, there was upregulation of inducible NOS, Cu-Zn SOD and nitrotyrosine. Recovery of endothelial NOS occurred at 28 days after injury, when the neointima is stabilizing and cellular proliferation has slowed down. There was no increase in neuronal NOS at any time point studied. CONCLUSIONS: NO may serve to limit the development of neointima while superoxide may attenuate the effect of NO by formation of peroxynitrite, detected as increased nitrotyrosine staining. Upregulation of Cu-Zn SOD would limit superoxide both at sites of inflammation in the vessel wall from 48 h and in the adventitia up to 28 days after injury. Very early intervention to protect NO may reduce neointimal size.

Carbon dioxide in the aortic arch: coronary effects and implications in a swine study.

PURPOSE: CO2 angiography is considered dangerous in the aortic arch where bubbles may cause critical cerebral and cardiac ischemia. We investigated CO2 distribution, physiologic effects in the heart, methods of detection and treatments. METHODS: Eight pigs had CO2 and iodinated contrast arch angiograms in supine and both lateral decubitus positions. An electrocardiogram, physiologic data and cardiac ultrasound were obtained. Therapies included precordial thumps and rolls to lateral decubitus positions. RESULTS: Supine high descending aorta CO2 injections floated retrograde up the arch during diastole and preferentially filled the right coronary artery (RCA): mean score 3.5 (of 4), innominate artery 2.4, left coronary artery 1.2; n = 17; p = 0.0001. Aortic root injections preferentially filled the RCA when the animal was supine, left coronary in the right decubitus position, and showed a diffuse pattern in the left decubitus position. Right decubitus rolls filled both coronaries causing several lethal arrhythmias. Precordial thumps successfully cleared CO2. Ultrasound is a sensitive detector of myocardial CO2. CONCLUSION: Arch distribution of CO2 primarily involves the RCA. Diagnostic ultrasound detects cardiac CO2 well. Precordial thumps are an effective treatment.

Role of the subchondral vascular system in endochondral ossification: endothelial cell-derived proteinases derepress late cartilage differentiation in vitro.

Endochondral ossification in growth plates proceeds through several consecutive steps of late cartilage differentiation leading to chondrocyte hypertrophy, vascular invasion, and, eventually, to replacement of the tissue by bone. The subchondral vascular system is essential for this process and late chondrocyte differentiation is subject to negative control at several checkpoints. Endothelial cells of subchondral blood vessels not only are the source of vascular invasion accompanying the transition of hypertrophic cartilage to bone but also produce factors overruling autocrine barriers against late chondrocyte differentiation. Here, we have determined that the action of proteases secreted by endothelial cells were sufficient to derepress the production of the hypertrophy-markers collagen X and alkaline phosphatase in arrested populations of chicken chondrocytes. Signalling by thyroid hormones was also necessary but endothelial factors other than proteinases were not. Negative signalling by PTH/PTHrP- or TGF-beta-receptors remained unaffected by the endothelial proteases whereas signalling by FGF-2 did not suppress, but rather activated late chondrocyte differentiation under these conditions. A finely tuned balance between chondrocyte-derived signals repressing cartilage maturation and endothelial signals promoting late differentiation of chondrocytes is essential for normal endochondral ossification during development, growth, and repair of bone. A dysregulation of this balance in permanent joint cartilage also may be responsible for the initiation of pathological cartilage degeneration in joint diseases.

Correlation of leukocyte adhesiveness, adhesion molecule expression and leukocyte-induced contraction following balloon angioplasty.

1. The aim of this study was to examine the changes in leukocyte adhesion and leukocyte-induced contraction in balloon-injured rabbit subclavian artery and to correlate these changes with vessel morphology and expression of adhesion molecules on the injured arteries. 2. Rabbits were anaesthetized and their left subclavian arteries were injured by balloon inflation and withdrawal followed by sacrifice at 2, 24, 48 h or 8 days after injury. The left and right subclavian arteries were removed and leukocytes were isolated from autologous rabbit blood. Leukocyte-induced contraction was measured in 5-HT precontracted artery rings and leukocyte adhesion was measured using (51)Cr-labelled leukocytes. Immunocytochemistry using paraffin-embedded tissue was employed to detect changes in the expression of adhesion molecules on injured arteries. 3. Autologous leukocytes caused a contraction of rabbit subclavian artery rings, which was prevented by L-NAME (10(-3) M). Balloon-induced injury abolished the contractile response to leukocytes, which correlated with loss of carbachol-induced relaxation 4. Balloon injury markedly enhanced the adhesiveness of the subclavian artery for leukocytes, most notably at 24 and 48 h after injury (1.7 and 1.8 fold respectively). Increased leukocyte adhesion at these two time points correlated with an upregulation of E-selectin, P-selectin and VCAM-1 expression on the remaining endothelium of the injured artery. 5. Vessel morphology revealed that balloon inflation had induced an infiltration of inflammatory cells into the vessel wall, the greatest increase being seen at 24 h after injury. 6. It is concluded that an increase in the expression of E-selectin, P-selectin and VCAM-1 following balloon-induced injury leads to enhanced leukocyte adhesion and migration into the injured vessel.

Extraaortic intimomedial mucoid degeneration: a clinicopathological study.

Six black patients with extraaortic intimomedial mucoid degeneration of the major arterial branches of the aorta are reported. Five patients presented with aneurysmal dilatation of the arterial wall as a result of the intimomedial mucoid degeneration, and the sixth patient had superimposed occlusive thrombosis. The ages ranged from twenty to fifty years. Five patients were female. Two were hypertensive. All patients in this study underwent reconstructive vascular surgery. The clinical and histopathologic findings are discussed.

Influence of diabetes on arteriosclerosis.

The cholesterol contents of the posterior cerebral, subclavian, left common carotid, coronary, superior mesenteric and renal arteries were determined in 6 nondiabetic and 21 diabetic autopsy subjects. The dry weight of the arteries per length was 1.40 to 2.96 times greater in the diabetic group than in the nondiabetic group. The contents of cholesterol in the arteries of the diabetic group were also 1.07 to 4.10 times greater than those of the nondiabetic group. Statistically significant correlation was demonstrated between the dry weight of the arteries per length in the nondiabetic group and the contents of cholesterol in the arteries of the nondiabetic group and the diabetic group. Relation between the cholesterol content (x) in the artery of nondiabetic group and ratio (y) of the cholesterol content in the artery of the diabetic group to the nondiabetic group could be expressed by the following regression equation; y = 4.303 - 0.558 x (r = -0.843, p less than 0.002). Most of correlation coefficients between dry weight of each artery, or between the cholesterol content of each artery were low. These results suggest that arteriosclerosis is enhanced in the diabetics, especially in smaller artery where the cholesterol content is low, and arteriosclerosis in the diabetics develops not uniformly.

Histochemical study of polysaccharides in some arteries of the region of the heart of black vulture (Coragyps atratus).

A comparative histochemical study of polysaccharides in some arteries of the region of the heart of black vulture was performed. With some exceptions, no variation in polysaccharides composition in all arteries studied were shown. Arterial walls present a sialo-mucopolysaccharidic complex and it is composed of: sialic acid, neutral mucopolysaccharides, hyaluronic acid and chondroitin sulfates. The concentration of these carbohydrates, mainly of the acidic ones, decrease from the inner portions of the media toward the adventitia.