In vivo influx of free and esterified plasma cholesterol into human aortic tissue without atherosclerotic lesions.

In order to determine the in vivo influx of plasma cholesterol into human aortic intimamedia tissue, specimens of the ascending aortic wall without visible atherosclerosis were obtained from patients undergoing aortic valve replacement. Before the operation the patients were intravenously injected with autologous plasma in which the lipoproteins were labeled with radioactive cholesterol. The influence of the duration of the exposure time (0.3-114 h) and of the distribution of radioactivity between free and esterified cholesterol in plasma on the amount of radioactivity found in the arterial wall was studied by the simultaneous use of 3H- and 14C-cholesterol. It was shown that the influx of free and esterified cholesterol into the intima-media layer of the tissue could be calculated from a set of linear equations that relate the labeled sterols in the tissue to the average specific activities in plasma. In nine patients between 50 and 70 yr of age with 4.2-5.9 mM total cholesterol in plasma, the influx of free cholesterol and of esterified cholesterol was 1.2-8.8 and 1.0-12.5 nmol X cm-2 X d-1, respectively. Both hydrolysis and esterification of the sterol fractions in the aortic tissue and exchange of free cholesterol between the plasma lipoproteins and the tissue were demonstrated. The cholesterol content of the intima-media layer was 0.6-2.3 mumol X cm-2. This corresponds to the influx of esterified cholesterol during a period of only 0.1-3.5 yr, which is short compared with the lifespan of the patient. Our data thus suggest that removal of esterified cholesterol from aortic tissue without visible atherosclerosis represents a major importance for the cholesterol concentration in the tissue.

A surgical model to study in vivo efflux of cholesterol from porcine aorta. Evidence for cholesteryl ester transfer through the aortic wall.

We describe a surgical procedure in pigs which makes it possible to follow the influx into, the penetration through and the efflux from the arterial wall of labeled lipoproteins. After 4 h exposure of the luminal side of the arterial wall to labeled lipoproteins, labeled esterified cholesterol was found in all layers of the aortic wall, whereas labeled free cholesterol gained access only to the most luminal layer. The data suggest that at least 40%, if not 80-90%, of the cholesteryl ester that enters the aortic wall from the luminal side, passes through the entire wall and leaves the aortic wall through vasa vasorum and lymphatics. They also suggest that free cholesterol in the lipoproteins exchanges extensively with cellular free cholesterol while the lipoproteins penetrate through the most luminal layer. More than 90% of the labeled cholesteryl ester disappeared from the arterial wall during a cold chase period of 4 days. By the simultaneous use of [3H]cholesterol and [14C]cholesterol it was shown that only 10-20% of this disappearance can be explained by cholesteryl ester hydrolysis in the arterial wall.

Brain hyperperfusion during cardiac operations. Cerebral blood flow measured in man by intra-arterial injection of xenon 133: evidence suggestive of intraoperative microembolism.

Cerebral blood flow (CBF) was measured by intra-arterial injection of xenon 133 in 29 patients during cardiac operations. Marked changes occurred in all patients. A normal and significant correlation with temperature and plasma PCO2 (p less than 0.01) support the reliability of the method. Mean CBF measured between sternotomy and the onset of extracorporeal circulation (ECC) was 38 ml/100 gm . min. The first minute of ECC was associated with a decrease in CBF in nine of 12 patients (p less than 0.02). During steady-state hypothermic ECC (temperature 29 degrees C), CBF increased unexpectedly to 64 ml/100 gm . min (p less than 0.01). Following rewarming steady-state normothermic ECC, mean CBF decreased to 42 ml/100 gm . min with signs of impairment of cerebral autoregulation. Ten and 20 minutes after termination of ECC, mean CBF was 40 and 41 ml/100 gm . min, respectively. Arterial PCO2 was found to be important in regulating CBF. The cerebral autoregulation maintained CBF down to arterial pressures of around 55 mm Hg. Below this level, CBF was significantly correlated with perfusion pressure (p less than 0.01). Multiple small emboli with a hyperemic border zone could cause a brain hyperperfusion, as seen in our patients during bypass. Measurements of CBF during ECC hold promise as a guide toward safer cardiac operations.

Study of autologous pericardial patch-grafts in the right ventricular outflow tracts in growing and adult dogs.

The effects of growth and hemodynamic load on autologous pericardial grafts in the right ventricular outflow tract were studied in adult dogs (nine) and pups (12); ten of the 21 also had bands around the main pulmonary artery. All grafts functioned without radiographic evidence of abnormality for up to 14 months. At necropsy small central aneurysms were found in patches in three pups. Fibrous organization extending from the margins and adventitial aspect considerably thickened each patch. Cartilaginous metaplasia was evident in the ingrowing host tissue in many animals (57%). Small foci of necrotic pericardium and dystrophic calcification were evident in half of the grafts in pups but not in those in adult dogs. Patches in animals with normal pressures showed a reduction (p < 0.05) in the axis which lay in the direction of blood flow but no increase in the transverse axis. Only those patches subjected to elevated pressures in adult dogs showed an increase in patch size. These findings indicate that autologous pericardium is a suitable material for use in the surgical enlargement of the right ventricular outflow tract.

Experimental evaluation of aortic homograft valves mounted on flexible support frames and comparison with glutaraldehyde-treated porcine valves.

The durability of the aortic homograft valve, when mounted in a rigid support frame, has been limited in some cases by aortic wall detachment from the frame in the commissure buttress area. To investigate the effects of frame flexibility, a stent was designed which was suitable for canine aortic valves of selected sizes. Of the two materials tested, acetal copolymer was found to be superior to polypropylene, as stents made from the latter material were permanently deformed as a result of polymer creep under the action of a cyclic load. Observations of a commercially available glutaraldehyde-treated heterograft mounted on a polypropylene frame indicated that stent flexibility was less important than had been suggested in earlier reports. It is considered that the glutaraldehyde preservation and the method of mounting this valve in the frame are major factors in prolonging the life of the implant.

Histological evaluation of transannular autografts of pericardium placed in the right ventricular outflow tract of dogs.

Autografts of pericardium were inserted as patches into incisions across the annulus of the pulmonary valve in 12 adult dogs and 12 pups. In order to accommodate for possible effects of pulmonary hypertension which pertains in many clinical circumstances, constricting teflon bands were placed around the main pulmonary artery in half of the animals. Samples of tissue from the patches were examined by light and scanning electron microscopy from 6 to 14 mth later. The eventual thickness of the insertion site of the patches was found to become 2-14 times greater than the initial autograft due to apposition of layers of collagenous tissue on the endocardial and epicardial surfaces of the autografts. Three pups showed small, angiographically undetected central aneurysms in their patches but the tissue in their base was 5 or more times thicker than control pericardium. Cartilaginous metaplasia was evident at the margins of 57% of the patches, necrotic remnants of parts of the autograft were evident in 38% and foci of dystrophic calcification in 24% of them. Whereas smooth muscle cells sometimes extended into the repair tissue (19%), elastic fibres were not present in the patches. Thus pericardial autografts in the right ventricular outflow tract seem unlikely to develop clinically significant abnormalities.

Intravascular air after fibrin sealing by spray gun in cardiovascular surgery.

During an operation for an ascending aortic aneurysm with implantation of a saphenous vein graft to the left coronary artery into a prosthesis, we occasionally observed air bubbles in the graft after application of fibrin glue to the anastomosis to control bleeding. In an experimental study in a pig, a vascular prosthesis was anastomosed to the descending aorta. The aorta and the prosthesis were transected and reanastomosed. Air bubbles were collected in a glass flask placed at the end of the prosthesis. Fibrin glue was applied with a spray catheter on all anastomoses at varying distances and with different air pressures. Small amounts of air were collected in the glass flask when an air pressure of 3 or 4 bar was used. This study demonstrates that the use of fibrin glue in cardiovascular surgery can introduce air into the vascular system with subsequent air emboli as a possible side-effect.

Gastric intrinsic factor production and vitamin B12 absorption after oesophageal resection using stomach as substitute.

OBJECTIVE: To investigate whether the use of the stomach as a substitute after oesophageal resections causes disturbances in vitamin B12 absorption due to deficient intrinsic factor (IF) production. MATERIAL AND METHODS: Eleven patients operated upon with oesophageal resection a.m. Ivor Lewis, for malignant (10) or benign (1) conditions of the oesophagus were examined with a postoperative dual isotope technique 11-41 months (mean 25 months) after operation. RESULTS: In two patients the test showed abnormally low absorption of vitamin B12. One of these probably due to incomplete urine collection during the test period. However, no patient showed deficient intrinsic factor production with absorption ratios between vitamin B12 +/- IF of 0.87-1.14 (reference interval: 0.70-1.20). CONCLUSION: Deficiency of intrinsic factor is neither an obligatory nor a common occurrence after oesophageal resection with gastric substitute. However, vitamin B12 absorption may be low due to other factors, and should be looked for in all patients surviving more than a couple of months postoperatively.

An experimental study of hot air thermocoagulation in cardiac surgery.

Recently a thermocoagulator using hot air has been developed. It has been used for haemostatic purposes in a number of cases of liver, pulmonary and retroperitoneal cancer surgery. An experimental animal study was undertaken to evaluate the use of the thermocoagulator during cardiac surgery. Since the thermocoagulator produces coagulation necrosis, the epi-/myocardium including the epicardial coronary arteries was investigated microscopically for acute and chronic histopathological changes. The investigation demonstrated that the thermocoagulator is an effective hemostatic tool during cardiac surgery. The histological examination of the hearts has shown that the technique does not damage the myocardium or the coronary arteries neither at the time of application nor in the long term.

Aneurysm of the ductus arteriosus. A review of the literature and the surgical implications.

One hundred and forty-four cases of aneurysms of the ductus arteriosus (DAA) have been reported in the literature of which 106 appeared spontaneously and 38 followed surgical treatment of a patent ductus arteriosus (PDA). Within the last few years there has been an increasing number of reported spontaneous DAA. However, the real incidence is presumably still underestimated. Aortography is a well established diagnostic method. In neonates, transthoracic echocardiography has shown convincing potential, whereas in older children and adults, transoesophageal echocardiography has yielded very promising results. Serious complications following spontaneous DAA are rupture, erosion, infection and thromboembolism. In infants younger than 2 months of age, the complication rate is 31%, in children between 2 months and 15 years, 66%, in adults, 47%. The rate of complications following postoperative DAA is even higher: 91% of the unoperated cases died due to rupture or infection. The operative mortality in children older than 2 months and adults is low. In the neonate group, 2 of 8 died during operation. The operative mortality in patients with postoperative DAA was 26%. Based on information from the literature, we suggest prompt surgical treatment of all spontaneous DAA in patients older than 2 months of age, and in all patients with postoperative DAA. In infants, a DAA should be closely followed with echocardiography, as spontaneous regression has been reported in this age group. If no regression is seen within a few days, it should be surgically corrected.

CABG shortly after AMI treated with thrombolysis: an analysis of the surgical group and a comparison with PTCA in the DANAMI study. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction.

OBJECTIVE: To present surgical results of the DANAMI study comparing conservative and invasive treatment of postinfarction myocardial ischaemia and to compare these with percutaneous transluminal angioplasty (PTCA) which was the alternative invasive treatment in that study. METHODS: A group of 413 patients with verified acute myocardial infarction treated with thrombolysis within 12 h of the onset of symptoms, who demonstrated postinfarction myocardial ischaemia were treated with coronary artery bypass grafting (CABG) or PTCA. Patients with left main lesions, three-vessel disease, two-vessel disease with more than three stenoses and patients with occlusions of a non-infarct related vessel had primary CABG. Patients with 1- and 2-vessel disease with not more than a total of three stenoses had PTCA. In case of failed PTCA patients had secondary CABG. The median distance from AMI to CABG was 45 days. PTCA was performed at a mean of 39 days after the infarction. RESULTS: A total of 147 patients had CABG and 266 had PTCA. The operative mortality for CABG was 1.4%. No PTCA patients died in relation to the procedure, 0.8% developed acute myocardial infarction as a consequence of the procedure, 1.5% had acute CABG and 3.5% elective CABG due to failed PTCA. In spite of more severe coronary artery disease among the CABG patients there was no difference in survival at 2.4 years. The CABG group had significantly fewer episodes of unstable angina, 10.2% versus 25.6% (P = 0.0002). No CABG patients had re-do revascularisation at 2.4 years follow-up versus 15.4% of the PTCA patients. At 3 years 80% of the CABG patients were free of angina compared to the 61% of the PTCA group (P < 0.0001). CONCLUSION: Low morbidity and mortality justifies the deferred elective revascularisation in patients with postinfarction myocardial ischaemia even in patients with silent ischaemia. There is no difference in survival at 2.4 years between CABG and PTCA but CABG offers more lasting results concerning incidence of stable and unstable angina than PTCA, which, however, is a valuable alternative in patients with less severe coronary artery disease.

Myocardial protection in coronary artery bypass surgery. A study comparing cold cardioplegia and intermittent aortic cross clamping.

Twenty patients having elective coronary artery bypass surgery were randomized for myocardial protection during cardiopulmonary bypass with cold cardioplegia and topical deep hypothermia with the Bretschneider solution in one group and intermittent aortic cross clamping at 30 degrees C in another group. The cardioplegic group showed more consistent results with lower CK-MB elevations both in terms of peak values and areas under the time-enzyme activity curves, although no statistical significance was obtained. There were significantly more infarct suspect time-enzyme activity curves in the intermittent cross clamping group (4 vs. O), and therefore, cold cardioplegia is advocated in preference to intermittent cross clamping in coronary artery bypass surgery.

Continuous suture technique in prosthetic aortic valve replacement.

Among 80 patients having aortic valve replacement using a continuous suture technique the occurrence of periprosthetic leak was 8.8%. There is a statistically significant difference in the occurrence of the periprosthetic leak in patients having pure stenosis (o) of combined stenosis and insufficiency, and patients having pure insufficiency (26%). Continuous suture technique reduces cross clamp time and by-pass time significantly but should be used routinely only in stenotic lesions. In pure insufficiency the method of suture should be considered separately in each case. Interrupted suture technique should be used if one or more of the known factors predisposing to perivalvular leak are present.

In vivo transfer of cholesterol from plasma into human aortic tissue.

It has recently become possible to measure the in vivo flux of cholesteryl ester from plasma into human aortic tissue by use of labeled cholesterol in patients undergoing reconstructive aortic surgery. For the ascending thoracic aorta without visible atherosclerotic lesions the influx was 4.5 +/- 1.4 nmol X cm-2 X day-1 (means +/- SEM, n = 9). For the abdominal aorta with severe atherosclerosis the influx of cholesteryl ester was 45 +/- 5 nmol X cm-2 X day-1 (n = 12). In both types of tissues the influx of cholesteryl ester from HDL was 2-3 times higher than the influx of cholesteryl ester from LDL and VLDL compared with the concentration of these fractions in plasma. This is in accordance with an aortic influx-mechanism which depends on the sizes and the concentration of the lipoproteins in plasma. The transfer of plasma lipoproteins into human aortic tissue shows a number of similarities with the transfer of plasma lipoproteins into the aortic wall of cholesterol-fed rabbits and also with the transfer of other plasma macromolecules across various capillaries. The cholesterol content in intima-media tissue without lesions corresponded in some of the patients to less than one year of continuous influx of cholesteryl ester from plasma. This time is short compared with the age of the patients. It suggests that removal of cholesterol from the aortic wall represents a major importance in prevention of cholesterol accumulation in that tissue.

[Results with the Ionescu-Shiley bioprosthesis]. / Resultater med Ionescu-Shiley bioproteser.

During the period 1.1.1982-31.12.1987, 61 patients were submitted to operative introduction of the Ionescu-Shiley pericardial xenograft. The indications were anticipated brief survival or conditions which rendered anticoagulation therapy undesirable. Because of this, the operative lethality was high (12/61). No thromboembolic complications were observed during a period of observation of up to five years and no cases of primary destruction of valvular tissue.

[Reoperation because of mechanical heart valve prosthesis dysfunction]. / Reoperation på grund af dysfunktion af mekaniske hjerteklapproteser.

Thromboembolism, haemolysis, prosthetic endocarditis and paravalvular leakage are the commonest complications of introduction of mechanical heart valve prosthesis. Malfunction of the cusps inside the sewing ring is a rare but serious condition, which is due to partial or total prevention of the free movements of the cusps or valves resulting in symptoms of valvular stenosis or incompetence. Twenty-six valvular prosthesis (2.3%) were replaced on account of malfunction. Fifteen out of the 26 patients were submitted to emergency operation and 11 to elective intervention. Four out of the 26 patients died preoperatively or during the postoperative course, corresponding to a lethality of 15%. The operative lethality was associated with emergency operations exclusively. The authors conclude that patients with previously well functioning valvular prosthesis who develop symptoms of cardiac failure should be referred to the cardiological centre where the operation was carried out as rapidly as possible instead of institution of traditional medical treatment.

[Aortic dissection--a life-threatening condition requiring immediate treatment]. / Aortadissektion--en livstruende tilstand der kroever hurtig behandling.

We present a retrospective examination of 70 consecutive patients (median age 55 years, range 20-71 years) operated for aortic dissection from January 1981 to October 1992. Four of these patients were operated twice, making a total of 74 operations. The operations were grouped according to the Stanford classification in Type A-acute (53%), type A-chronic (11%), type B-acute (26%) and type B-chronic (10%). Fifty-seven patients were males (81%) and 90% of the operations were performed as emergencies. Eleven percent of the patients had Marfan Syndrome. The peroperative mortality was 23% and the perioperative mortality was 39%. The 10 year survival including the perioperative mortality was 39%. The frequency of operative complications lasting for more than one month was 12% and some of these complications were caused rather by the aortic disease rather than the operation. Further improvement depends on the referral of these patients to cardio-thoracic surgical units on near suspicion of the condition for the earliest possible treatment. Furthermore, patients must be followed lifelong for recurrences in progression of chronic AD.

[Diaphragm pacing by electric stimulation of the phrenic nerves]. / Diafragma-pacing ved elektrisk stimulation af nn. phrenici.

Artificial ventilation by electric stimulation of the phrenic nerves has become clinically significant within the past 20 years and, in the world as a whole, approximately 700 patients have been treated with implanted diaphragmatic pacemakers. The two first patients in whom diaphragmatic pacemakers were implanted in Denmark, had sustained accidental fractures of the second cervical vertebra with subsequent high cervical spinal cord lesions with not only tetraplegia but also respiratory arrest. In both patients, diaphragmatic pacemakers were implanted bilaterally and these were employed for 12-14 hours daily while ventilation with a respirator was employed at night. The main indications for diaphragmatic pacing are paralysis of respiration following high cervical spinal traumata and the chronic central hypoventilation syndrome (sleep apnoea of Undine's curse). Diaphragmatic pacing may improve the mode of ventilation and the quality of life for patients with tetraplegia and respiratory insufficiency. On account of the potential technical problems, the risk of complications and the limited number of patients in whom this operation is suitable, implantation of diaphragmatic pacemakers should be concentrated in a few centres and probably only one in Denmark.

[Surgical treatment of cancer of the cardia and the esophagus]. / Kirurgisk behandling af cancer cardiae og cancer esophagi.

During the period 1977 to 1989, 379 patients with cancer cardiac and cancer esophagi were admitted. The ages ranged from 18-88 years with an average of 65 years. The treatment concept was basically unchanged during the study period. Resection as described by Ivor Lewis was employed as palliative or curative treatment when resection was considered possible. Intubation of the esophagus was employed when no other treatment was considered possible. Resection was employed in 251 patients, eight of these emergencies on account of perforation or haemorrhage. Bypass operations were employed in five patients, intubations in 63 and no surgical treatment was undertaken in 60 patients. The all over operative mortality for resections was 11.2% and for elective operations 9.9%. The operative mortality increased with the TNM stage of the tumour and was 3.2% for stages I + II, 8.2% for stage III and 24.4% for stage IV. The complication ration was 42%. 15% of the patients submitted to resection required reoperation. Anastomotic leaks were encountered in 18 patients and nine of these died. Pulmonary complications were the most frequent and resulted in ten early postoperative deaths. The mortality connected with intubations was 15%. The over all five-year survival rate after resections was 10.4%. In stages I + II this was 42% and 8% in stage III. None of the patients in stage IV survived for two years. The longest survival after intubation was less than one year.

[DANAMI. A Danish study of invasive versus conservative treatment of patients with post-infarction ischemia who had received thrombolytic therapy]. / DANAMI. En dansk undersøgelse af invasiv versus medicinsk behandling af trombolysebehandlede patienter med postinfarkt iskaemi.

INTRODUCTION: To compare an invasive strategy employing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass grafting (CABG) with a medical strategy in patients who had received thrombolytic treatment for first acute myocardial infarction (AMI), and with signs of inducible ischaemia. METHODS: In a prospective study 1008 patients were randomized, 503 to invasive treatment, of whom 266 (52.9%) had PTCA, and 147 (29.2%) CABG, 505 to conservative treatment, of whom eight (1.6%) were revascularized within two months. RESULTS: After a median follow-up of 2.4 years the mortality in the invasive group was 3.6% vs. 4.4% (p = 0.45) in the conservative group, re-infarction incidence was 5.6% vs. 10.5% (p = 0.0038) and percentage of admissions with unstable angina was 17.9% vs. 29.5% (p < 0.00001). DISCUSSION: We conclude that post-infarct patients with inducible ischaemia should be referred to coronary angiography and revascularised accordingly.