No abstract

Endothelin-1 is an endothelium-derived vasoconstrictor peptide. Its circulating levels are below those known to evoke direct vascular effects. To study whether low concentrations of endothelin-1 potentiate the effects of other vasoconstrictor hormones, we suspended isolated human internal mammary and left anterior descending coronary artery rings in organ chambers for isometric tension recording. In mammary artery rings, the contractions to norepinephrine (3 x 10-8 M) were potentiated by threshold (3 X 10-10 M) and low concentrations (10`M) of endothelin-1 (96±35% and 149±58% increase from control; p<0.01 and 0.001; n=6). The inhibitor of endothelial nitric oxide formation L-NG-monomethyl arginine did not affect the potentiating effects of the peptide. The calcium antagonist darodipine (10`M) prevented the potentiation of the response to norepinephrine evoked by endothelin-1. Similarly, contractions to serotonin (10`or 3 x 10-8 M) were amplified by endothelin-1 (3 x 10-10 M) in the mammary (30±9%o) and in the coronary arteries (59±25%). Endothelin-1 (10-9 M) further potentiated the response (57±23% in mammary and 87±26% in coronary arteries;p <0.05; n=7 and 3). The sensitivity of mammary arteries to calcium chloride was markedly enhanced in the presence of endothelini1 (3 x 1010 M; concentration shift, eightfold; pc

The endothelium releases substances controlling vascular tone and platelet function. We investigated mediators of endothelium-dependent responses in human internal mammary arteries and saphenous veins. The inhibitor of nitric oxide formation, NG-monomethyl L-arginine, enhanced the sensitivity to norepinephrine (fivefold) and evoked more pronounced endothelium-dependent contractions in internal mammary arteries (19+6% of 100 mM KCI) than in saphenous veins (2±1%; p<0.005). In internal mammary arteries, NG-monomethyl L-arginine, but not indomethacin, markedly reduced endothelium-dependent relaxations to acetylcholine (from 95±2% to 39+7%; p<0.005) and prevented those to histamine (78±6% to 4+3%; p <0.005). In saphenous veins, endothelium-dependent relaxations to acetylcholine were weak (24+11%), while nitric oxide caused comparable relaxations (85+±3%) as in internal mammary arteries (80±5%; NS). NG-Monomethyl L-arginine prevented the relaxations to acetylcholine and unmasked endothelium-dependent contractions (30±10%o). Indomethacin and the thromboxane synthetase inhibitor CGS-13080 augmented relaxations of saphenous veins to acetylcholine from 24±11% to 46±91% (p<0.05). Histamine-evoked contractions were converted to endothelium-dependent relaxations by indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ-30741 (38+±3% and 40±+6%; p<0.05) but not CGS-13080. Thus, 1) nitric oxide mediates endothelium-dependent relaxations in human arteries and veins; 2) internal mammary arteries release more nitric oxide than do saphenous veins, and 3) in saphenous veins, the effects of nitric oxide are reduced by endothelium-derived contracting factors Received May 10, 1990; accepted August 9, 1990. um.3-9 In experimental animals, nitric oxide accounts at least in part for the biological activity of endothelium-derived relaxing factors released by acetylcholine and bradykinin.10,11 In endothelial cells, nitric oxide is cleaved from its precursor, the amino acid L-arginine, by specific enzymes.'2-14 By means of the methylated amino acid NG-monomethyl L-arginine (LNMMA), this pathway for the formation of nitric oxide can be inhibited.15-'7 In addition to nitric oxide, the endothelium can produce other relaxing factors such as prostacyclin1819 and yet unidentified substances such as endothelium-derived hyperpolarizing factor. [20][21][22][23][24] Furthermore, at least in blood vessels of dogs and rats, the endothelium can mediate contractions.25-33 While the endothelium-derived contracting factor released during hypoxia is resistant to most pharmacological interventions,26 the contractions to arachidonic acid and acetylcholine can be prevented by inhibitors of cyclooxygenase.28-31 The cyclooxygenase by guest on

Five to fifteen percent of patients undergoing aortic valve replacement (AVR) will have an ascending aortic aneurysm requiring a concomitant surgical procedure. On the other hand, a dilated ascending aorta is known to be a potential source of complications after AVR. From 1972 to 1988, 2278 AVR, either isolated or combined with a second cardiac procedure, were performed in our institution. In the same time interval, a dilated ascending aorta was treated in additional 291 consecutive patients during AVR. Three different surgical options were employed: aortic remodelling and external wall support in 164 patients (56.4%), composite graft replacement in 81 patients (27.8%) and a supracoronary graft in 46 patients (15.8%). Early mortality was 4.8%. Aortic remodelling plus external wall support had the lowest early mortality (1.8%) and the best 8-year survival (89.6%). Supracoronary grafting had a higher early mortality (6.4%) and lower 8-year survival (73.2%). The results of the composite graft were least favourable: early mortality was 9.8% and 8-year survival 76.5%. The results point out the necessity for instituting the appropriate surgical procedure for a dilated ascending aorta during AVR. They show that conservative aortic surgery with preservation of endothelial lining gives excellent early and late results.

The surgical treatment of aortopulmonary window has a low risk, even if associated with major cardiac anomalies. Prompt operative treatment achieves excellent long-term results.

A 26 year old man was admitted to hospital following a traffic accident. He had been sitting in the back of a car without wearing a seat belt. He suffered crush injuries on the anterior chest wall, trunk, and legs. On admission he was awake and cooperative, but restless, and obviously in severe pain. Radiography of the skull, facial bones, chest, spine, pelvis, and legs revealed a shaft fracture of the left femur and tibia and fracture of the 7th and 8th right ribs. The patient was transferred to the University Hospital of Zurich for further assessment and surgical repair of the lower limb fractures three days later. Because of worsening clinical condition with onset of partial respiratory insufficiency and new loud systolic murmur at the left sternal edge, a transthoracic echocardiography was performed, which showed an apical ventricular septal defect. Surgery was performed immediately. The ventricular septal defect was successfully repaired using a Teflon felt patch and interrupted sutures with pledgets, and sealed with glue. At six months' follow up the patient was doing well. Ventricular septal defects after blunt chest trauma occur either because of heart compression between sternum and the spine or because ofmyocardial infarction. In the present case the ventricular septal defect appeared three days after the accident, probably secondary to a post-traumatic myocardial infarction. Patients with blunt chest trauma and suspicion of cardiac contusion should be monitored carefully.

Tricuspid valve anomalies can be accurately identified by Doppler echocardiography. Surgical repair is the treatment of choice in patients with severe tricuspid regurgitation due to a congenital cleft of the anterior leaflet of the tricuspid valve.

A new in vitro flow system was developed to investigate the impact of laminar flow on extracellular matrix formation and tissue development. The dynamic in vitro system was designed to provide a cross flow arrangement of main flow induced by a dialysis roller pump (500 ml/min), and nutrition flow by a perfusion pump (3 ml/hr). Poly-L-lysine precoated polyglycolic acid (PGA) scaffolds (3.14 cm2) were seeded with myofibroblasts of human aortic origin (3.0 x 10(6) cells/ mesh) and incubated for 14 days under static conditions. The tissue was exposed to shear stress over a time period of 14 days (n = 4). The control group was seeded under static conditions (n = 4). To obtain a CO2 independent medium, 25 mM HEPES and 1 mM bicarbonate buffer was supplemented to modified MEM without bicarbonate. Gas samples were collected from the medium, and hydroxyproline assay was performed as a marker of collagen production. The newly developed flow system maintained stable cell culture conditions, with the hydroxyproline concentration significantly higher in group F (p< 0.05). These preliminary experiences with a new in vitro tissue culture system demonstrate the feasibility of using flow induced mechanical stress to enhance extracellular matrix formation.