Perivascular tissue mediated relaxation - a novel player in human vascular tone regulation.

Perivascular tissue (PVT) modulates vascular tone, releasing adventitia/adipocyte derived relaxing factor (ADRF). Its physiological role remains unclear. We studied isolated internal thoracic artery (ITA) segments obtained from 132 patients subjected to coronary artery bypass grafting. The vessels were skeletonized in vitro and the ITA rings and PVT were incubated in separate isolated organ baths. Skeletonized ITA segments were first precontracted with 10(-5.5)mol/L 5-hydroxytryptamine hydrochloride. The PVT was next transferred to the ITA tissue bath. This resulted in relaxation of ITA, presumably related to ADRF release from PVT which was floating freely in the tissue bath. The in-vitro relaxation responses were then correlated to patients' characteristics - including demographics, clinical and laboratory data, as well as therapy. Perivascular tissue transfer resulted in 49.7 ± 26.2% relaxation of precontracted ITA segments. In multiple linear regression modelling, the relaxation of ITAto PVT was negatively related to patient age (ß = -0.67; 95% CI -1.17 - -0.17; P = 0.009), symptoms of CCS class 4 angina (ß = -20.11; 95%CI -32.25 - -7.97; P = 0.001), and positively to body mass (ß = 0.37; 95%CI 0.08 - 0.67; P = 0.01) and lack of heart failure symptoms (NYHA class 1) (ß = 9.06; 95%CI 0.33 - 17.79; P = 0.04). The relaxation response to PVT was not related to patients' sex, diabetes, hypertension, lipid profile or therapy in both univariate and multivariate analysis. PVT might play an important role in regulating vascular tone in humans as exemplified by its changing physiological function with age and in atherosclerosis.

Mechanisms of vasodilatatory effect of perivascular tissue of human internal thoracic artery.

It has beed showed that perivascular adipose tissue (PVAT) of human internal thoracic artery (ITA) releases adventitia/adipocyte-derived relaxing factor (ADRF). The precise mechanism of vasodilatatory effect of ADRF is still unknown. It was suggested that various potassium channels may be involved in the action of ADRF. The aim of this study was to assess the involvment of potassium channels in the vasorelaxing properties of ADRF in human internal thoracic artery. Human ITA rings were studied in vitro. First the ability of perivascular tissue of human ITA to release ADRF to the bath was checked. In subsequent experiments two fragments of skeletonised ITA were used to assess the involvement of various potassium channels in vasorelaxing action of PVAT. Segment of ITA, precontracted with serotonin (10(-5.5)M), was relaxed by adding PVAT to tissue bath, first without and then in the presence of appropriate potassium channel blocker. Second segment served as a control (no addition of PVAT). The magnitude of relaxation was measured and compared between preparations. This protocol was used to analyze the influence of iberiotoxin (100 nM), apamin (1 uM), 4-aminopyridine (1 mM, 5 mM), BaCl2 (100 uM) and glibenclamide (10 uM). The addition of PVAT to precontracted skeletonized ITA caused significant vasorelaxation (54.6±8.03 mN versus 33.7±6.58 mN p=0.03). Similar effect was seen when 5 ml of aliquot from separate incubation of PVAT was added (36.3±5.45 mN versus 20.7±3.02 mN; p<0.001). PVAT dependent relaxation was blocked in the presence of Ca⁺² dependent potassium channel blocker iberiotoxin (47.4±16.67 mN versus 43.3±14.54 mN; p=0.36) and 4-aminopyridine (5 mM) (59.3±3.54 mN versus 51.6±4.77 mN; p=0.12). We conclude that perivascular adipose tissue of human ITA releases relaxing factor that seems to act with the involvement of Ca⁺² dependent potassium channels.

Ten-year probability of osteoporotic fracture in 2012 Polish women assessed by FRAX and nomogram by Nguyen et al.-Conformity between methods and their clinical utility.

PURPOSE: The aim of the cross-sectional study was to establish the degree of conformity between 10-year probability of osteoporotic fracture, assessed by FRAX, and using the nomograms, as proposed by Nguyen at al. METHODS: Postmenopausal Polish women (2012) were examined in their mean age of 68.5+/-7.9 years (age range 55-90 years). Fracture probability by FRAX was based on age, BMI, prior fracture, hip fracture in parents, steroid use, rheumatoid arthritis, alcohol use, secondary osteoporosis and T-score for femoral neck BMD. Fracture probability by Nguyen's nomograms was based on age, the number of prior fractures, the number of falls and T-score for femoral neck BMD. RESULTS: The mean conformity rate was 79.1% for any fracture risk (for threshold 20%) and 79.5% for hip fracture (threshold 3%). Any and hip fracture risks were significantly higher for both methods in women with fracture history in comparison to those without fracture and increased with ageing. The influence of prior fracture and ageing was more evident in Nguyen's nomograms. ROC analyses of any fracture risk in FRAX and Nguyen's methods demonstrated the area under curve (AUC) at 0.833 and 0.879, respectively. Similar analyses for hip fracture demonstrated AUCs for FRAX and Nguyen's technique at 0.726 and 0.850, respectively. The AUCs for Nguyen's nomograms were significantly larger than the AUCs for FRAX (p<0.0001). CONCLUSION: The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyen's nomograms seem to be more efficient in fracture risk assessment, especially for hip fractures, due to a higher accuracy of the method. The information on the number of falls during the last year and multiple fractures ought to be incorporated into the method of fracture risk prediction. MINI-ABSTRACT: The degree of conformity was assessed in a group of 2012 women between 10-year FRAX prognosis of fracture and Nguyen et al.'s nomograms. The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyen's nomograms seem to be more efficient in fracture risk assessment due to higher accuracy.

Intraoperative and laboratory evaluation of skeletonized versus pedicled internal thoracic artery.

BACKGROUND: The skeletonization of internal thoracic artery is postulated to improve graft length, early blood flow, sternal blood supply, and postoperative respiratory function. Concern exists that skeletonization may injure internal thoracic artery, precluding good results of surgery. Reports on endothelial function of skeletonized internal thoracic artery are lacking. METHODS: A prospective assessment of early clinical outcomes of 357 consecutive patients undergoing coronary artery bypass grafting was performed: 287 patients with nonskeletonized and 70 with skeletonized left internal thoracic artery (LITA). The lengths of LITA and of its discarded distal segment, as well as free LITA blood flow, were measured. The dose-effect relationship for relaxation to acetylcholine was studied in the organ bath. RESULTS: Apart from a higher incidence of breaching the pleura with nonskeletonized LITA the clinical outcomes were comparable. The length of skeletonized LITA was 17.8+/-1.14 cm versus 20.3+/-0.52 cm skeletonized (p = 0.11). The length of discarded LITA was shorter in nonskeletonized artery (0.8+/-0.28 cm versus 2.6+/-0.49 cm; p = 0.022). The free LITA blood flow was 66.3+/-7.42 mL/min in nonskeletonized vessel versus 100.3+/-14.84 mL/min in skeletonized (p = 0.048). The acetylcholine-induced relaxation was similar in both groups (maximal relaxation, 80.7%+/-5.95% in nonskeletonized versus 72.9%+/-9.11% in skeletonized; not significant; negative logarithm of half-maximal effect, 7.43+/-0.18 versus 7.1+/-0.10, respectively; p = 0.063). CONCLUSIONS: Skeletonization does not damage the endothelial function of the LITA. Higher free blood flow and available LITA length should encourage the use of skeletonized LITA in clinical practice.

Internal mammary artery graft function is not affected in hypertensive patients on therapy.

Results are presented which assess the reactivity of isolated human internal mammary artery fragments from non-hypertensive and treated hypertensive patients in vitro. Material from three patient groups was examined: group I, no hypertension; group II, arterial hypertension treated with ACE inhibitors; and group III, arterial hypertension treated with nifedipine. Responses to KCl, norepinephrine and acetylcholine, as well as the influence of N(G)-monomethyl-L-arginine (L-NMMA) on the effects of norepinephrine were tested. Response to KCl was highest in group III, while the contractile reactivity to norepinephrine was depressed in group II. Relaxation after acetylcholine was enhanced in groups II and III. Incubation of vessel fragments with L-NMMA sensitized the tissue to norepinephrine in the order of potency group II>group III>group I. Internal mammary artery function as the graft, and particularly in terms of endothelial function, is not adversely affected in arterial hypertension, although proper antihypertensive treatment may be essential.

The dihydropyridines modulate neurotensin inotropic action paradoxically.

The interaction of neurotensin and calcium channel modulators is examined in isolated electrically driven guinea pig left atrial appendages. Left guinea pig atria exposed to diltiazem become desensitised to neurotensin. There is no significant influence of verapamil pretreatment on the neurotensin inotropic action. Nifedipine pretreatment causes increase in the inotropic response of guinea pig atria to neurotensin. The regression line of neurotensin after pretreatment with nifedipine compared to the regression line of neurotensin alone has higher slope and is shifted to the left. The ED50 of neurotensin after nifedipine pretreatment compared with the ED50 of neurotensin alone results in potency ratio of 2.24. Bay K8644 significantly decreases the inotropic effect of ED100 of neurotensin. Results suggest that: (1) the mechanism of interaction of calcium channel modulators and neurotensin in the atrium does not depend on the calcium influx through calcium channel nor does it on the calcium channel itself; (2) the interaction of nifedipine and neurotensin is possibly dependent on dihydropyridine receptors, (3) the dihydropyridine binding site, possibly different from voltage-sensitive calcium channel, is somehow involved in the neurotensin action in guinea pig atria.

Reactivity of isolated human right atria to norepinephrine in various disease states.

The reactivity of isolated, electrically driven, right human atrial muscle to norepinephrine was studied in patients with coronary heart disease, with and without proximal right coronary artery occlusion, and in patients with mitral valve disease. The dose-effect curves for norepinephrine and ED50 doses for each group were compared. We found no difference in reactivity of atria from both coronary artery disease groups. The mitral valve disease group dose-effect curve was shifted to the right (potency ratio 3.98), and the maximal effect was significantly higher than in both coronary artery disease groups. We suggest that adrenoreceptor down regulation could account for observed ED50 difference. The difference in maximal responses could depend on more effective contraction mechanism in mitral valve disease myocardium. We conclude that occlusion of proximal right coronary artery does not necessarily mean ischaemia of right atrium and/or ischaemia does not change myocardium reactivity to norepinephrine.