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.

Post infarction ventricular septal defect - can we do better?

OBJECTIVE: To identify predictors of early and late outcome among 117 consecutive patients who underwent postinfarction ventricular septal defect (VSD) repair over a period of 12 years. METHODS: A retrospective analysis of clinical data was performed. Mean age was 65.5+/-7.8. There were 43 females. Full data were obtained in 110 patients. Of these, 76 patients presented with anterior and 34 with posterior VSD. Thirty-three patients were operated in cardiogenic shock. Mean time between myocardial infarction (MI) and VSD development was 5.6+/-7.8 days (median 4) and from VSD to surgery 9. 0+/-28.1 (median 2). Sixty-six patients had intraaortic balloon pump (IABP) inserted, and 15 were ventilated preoperatively. Logistic regression and Cox regression were used for multivariate analysis. RESULTS: Thirty days mortality was 37%. Among 110 patients, in whom complete analysis was possible, 38 died within 30 days (35%). Mortality in the posterior VSD group was 35% and in the anterior VSD group 34% (NS). In 44 patients (40%) a residual shunt was found on postoperative echocardiography. This required reoperation in 13 patients (four deaths). Cardiogenic shock prior to surgery adversely influenced early survival - odds ratio (OR) 5.7 (confidence interval (CI) 2.1-16.0) (P=0.0008). Deterioration of haemodynamic status in between admission and surgery was stronger predictor of mortality than shock on admission - OR 6.0 (CI 1.6-22.6) (P=0.008) vs. 3.1 (CI 1.0-9.3) (P=0.049). A longer time between MI and surgery favoured survival - OR 0.1 (CI 0.03-0.4) (P=0.002). The time period from the infarct to the septal rupture, but not from the rupture to surgery, appeared to be a significant predictor of survival - OR 0.2 (CI 0. 05-0.6) (P=0.008). Five years survival was 46+/-5%. Preoperative cardiogenic shock affected late survival - OR 2.7 (CI 1.5-4.9) (P=0. 001). Of 72 patients who survived 30 postoperative days, 12 (17%) were in New York Heart Association (NYHA) class III or IV and five (6.9%) in Canadian Cardiovascular Soceity (CCS) class III or IV at the last follow-up. CONCLUSIONS: Preoperative cardiogenic shock and early postinfarction septal rupture carry a grave prognosis. Achieving haemodynamic stability prior to surgery may be beneficial but prolonged attempts to improve patients' cardiovascular state are hazardous.

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.