Ultrastructural and cytochemical correlates of myocardial protection by cardiac hypothermia in man.

We report observations on ultrastructural and cytochemical changes in the myocardium after hypothermic protection in 21 patients who underwent cardiac operation. Two general categories of hypothermic protection were studied. (1) topical cooling during anoxic arrest and moderate general hypothermia (10 patients with aortic valve replacement, Group 1) and (2) intermittent perfusion during moderate general hypothermia combined with topical cooling (11 patients with multiple valve replacement, Group II). Transmural left ventricular biopsies were taken at the start of the cardiopulmonary bypass and shortly after the end of aortic cross-clamping. In Group I (cross-clamp time, 51 +/- 12 minutes) only minor pathologic changes of the myocardial fine structure were found, with no differences among the left ventricular layers. In most mitochondria, structure remained intact but the mitochondrial granules disappeared. Cytochrome-c-oxidase activity was unchanged. In Group II (total cross-clamp time, 83 +/- 16 minutes) the subendocardium was well preserved. Slight subcellular damage comparable with that of resulting from topical cooling was seen in all hearts even after a total cross-clamp period of 106 minutes. Cytochrome-c-oxidase activity was unchanged. In the subepicardium, however, a positive correlation was found between the severity of ultrastructural damage and total cross-clamp time (p less than 0.05). Matrix clearing, damage to the cristae and the mitochondrial membranes, and nuclear abnormalities occurred when the aorta was cross-clamped for morethan 60 minutes. Cytochrome-c-oxidase activities decreased in these samples. It is concluded that: (1) no significant subcellular injury was found in hearts cooled topically during 1 hour of anoxic arrest; and (2) in hearts protected by intermittent perfusion during moderate general hypothermia and additional external cooling, the subendocardium was well preserved for anoxic periods of up to 106 minutes. However, after 60 minutes of aortic cross-clamping subcellular damage increased progressively in the subepicardium.

The Björk-Shiley Monostrut valve. Clinical experience in 647 patients.

A total of 647 consecutive patients underwent valve replacement with a Björk-Shiley Monostrut valve (Shiley, Inc., Irvine, Calif.) from January 1, 1984, through December 31, 1988. A total of 135 patients (20.8%) had had a previous cardiac correction. Overall hospital mortality was 6.8%. Preoperative functional class, cardiopulmonary bypass time, aortic crossclamping time, and cause of valve replacement influenced in-hospital mortality significantly (univariate analysis). The median follow-up was 30 months. Overall actuarial survival was 81% +/- 4% at 6 years. Univariate and multivariate regression analysis showed that preoperative functional class, total cardiopulmonary bypass time, size of mitral prosthesis, and pure mitral insufficiency significantly influenced total mortality after valve replacement. Additional coronary bypass grafting and redo valve replacement did not. The actuarial rate of freedom from thromboembolism was 86% +/- 4% at 6 years. There were no cases of valve thrombosis. Patients having a thromboembolic event showed a higher probability of late death after native valve replacement.

Nifedipine as an adjunct to St. Thomas' Hospital cardioplegia. A double-blind, placebo-controlled, randomized clinical trial.

The cardioprotective effect of the addition of the slow calcium-channel blocker nifedipine to cardioplegic solution was tested in two double-blind placebo controlled randomized studies. The first study included 24 patients undergoing aortic-coronary bypass grafting, and the second included 24 patients undergoing aortic valve replacement. Nifedipine at a dose of 200 micrograms/L or placebo was added to St. Thomas' Hospital cardioplegic solution. The following markers of ischemia were used: adenosine triphosphate and its catabolites, creatine phosphate and inorganic phosphate, determined in transmural left ventricular biopsy specimens taken before, at the end of, and after aortic cross-clamping; hemodynamic recovery 15 minutes after cessation of cardiopulmonary bypass; clinical outcome in terms of the incidence of arrhythmias, low cardiac output, positive inotropic support immediately after operation, and follow-up at 15 months. The main difference between the two studies was that myocardial temperature during cross-clamping remained constant at 14 degrees C in coronary bypass grafting but increased to 25 degrees C in valve operations despite the application of the same amounts of cardioplegic solutions. This lower temperature resulted in better preservation of high-energy phosphates in coronary bypass operations as compared to the placebo group having valve replacement operations. According to analysis of variance, a drug effect could be demonstrated only in the aortic valve replacement study: Accumulation of breakdown products of the adenine nucleotide pool was less in the nifedipine group than in the placebo group (p less than 0.05). Adenosine triphosphate decreased only to 84% in the nifedipine group and to 72% in the placebo group. Despite this adenosine triphosphate-sparing effect, weaning from cardiopulmonary bypass was more difficult in the nifedipine group. Left ventricular stroke work index 15 minutes after bypass was decreased to 72% of the prebypass value in the nifedipine group (t test, p less than 0.01) and only to 86% in the placebo group (p = NS). In contrast, after the patients were admitted to the intensive care unit, the incidence of low cardiac output tended to be lower in the nifedipine group than in the placebo group: 33% versus 58% (p = NS). In conclusion, ischemia-induced degradation of nucleotides as it occurs when myocardial cooling is inadequate can be prevented by the addition of nifedipine to the St. Thomas' Hospital cardioplegic solution. This effect, however, is not associated with an improved clinical outcome.

Aortofemoral grafting: factors influencing late results.

During a 15-year period, the aortofemoral Dacron graft was used for revascularization of 615 limbs in 352 patients, with an overall operative mortality rate of 5.1% and a cumulative 10-year patency rate of 62%. The late complication rate was 27%, with late thrombosis being by far the most frequent complication (24%). Among several factors responsible for late occlusion, the presence of trifurcation disease and the site of the femoral anastomosis are by far the most important. Our procedure of choice for a thrombosed graft limb is thrombectomy and profundaplasty, which give a long-term patency rate of 68%.

The Ionescu-Shiley pericardial valve: results in 473 patients.

From January 1, 1980, through December 31, 1985, 473 patients underwent valve replacement with an Ionescu-Shiley valve. Overall hospital mortality was 7.8%. Major associated procedures and preoperative New York Heart Association (NYHA) Classes IV and V influenced hospital mortality significantly. The mean follow-up was 2.6 +/- 1.3 years. Late mortality was 5.9%. Overall actuarial survival was 81% at 5 years. A chief cause of reoperation was cusp rupture of a mitral prosthesis in 5 patients (all after aortic and mitral valve replacement). The overall actuarial reoperation-free incidence was 93% at 5 years. Thromboembolic (TB) phenomena occurred at a linear incidence of 1.4 +/- 0.3% per patient-year or an actuarial thromboembolism-free incidence of 92% at 5 years. Univariate and multivariate analyses showed that postoperative NYHA Class, rhythm at follow-up, and anticoagulant therapy significantly influenced the incidence of TE phenomena.

Nine years' experience with the Björk-Shiley prosthetic valve: early and late results of 932 valve replacements.

Between November, 1970, and December, 1977, 932 consecutive patients received the standard Björk-Shiley prosthesis. Operative mortality was 4.6% for aortic valve replacement (AVR; N = 364), 5.1% for mitral valve replacement (MVR; N = 313); 11.3% for multiple valve replacement (N = 194), and 13.7% for valve replacement combined with coronary artery bypass grafting (CABG; N = 51). Factors influencing hospital mortality included type of valve replacement, age at operation, whether the valve replacement was done as an emergency, and year of implantation. Complete follow-up (mean, 3.7 years) was achieved in 95% of the survivors. Actuarial survival was 82% for AVR patients at 8 years, 83% for MVR patients at 7 years, 72% for multiple valve replacement patients at 7 years, and 76% for those who had valve replacement with CABG at 3 years. No significant difference in late survival was found between patients with mitral insufficiency alone (p greater than 0.2) or aortic insufficiency alone (p greater than 0.9) and those with stenotic lesions only. Thromboembolic complications occurred at an incidence of 1.17% per patient-year, and Dicumarol-induced hemorrhages occurred at an incidence of 2.11% per patient-year. Twelve out of 13 patients survived operation for prosthetic valve thrombosis, indicating that this complication is not as catastrophic as many believe. The incidence of reoperation in anticoagulated patients was 0.63% per patient-year. All of these results are compared with data from the recent literature.

Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group.

BACKGROUND: The selection of stage IIIA N2 non-small cell lung cancer patients for primary surgical treatment remains controversial. METHODS: One hundred forty patients with resected non-small cell lung cancer who eventually proved to have pathologic N2 disease were studied with a univariate and multivariate analysis of prognostic factors. RESULTS: Nineteen patients had a positive mediastinoscopy; the others had a preoperative N0 or N1 stage. Complete resection rate was 80.7%. Five-year survival was 20.8% (95% confidence interval, 17.2% to 24.4%), 32.2% in mediastinoscopy-negative patients. In the univariate analysis, clinical N stage at mediastinoscopy, complete resection, performance status, T stage, number of metastatic levels in adenocarcinoma, and nodal capsule rupture were important factors. In a multivariate model, survival was worse in case of higher T stage (relative risk = 1.43), lower performance status (relative risk = 1.37), involvement of more than one node level (relative risk = 1.68), nonsquamous histology (relative risk = 1.29) and clinical N2 stage (relative risk = 1.43). Long-term survival was unlikely when lactic dehydrogenase or carcinoembryonic antigen levels were elevated. CONCLUSIONS: In clinical N0 or N1 cancer, complete resection resulted in reasonable survival prospects. In patients with N2 disease discovered at mediastinoscopy, surgical treatment was only worthwhile in case of minimal N2. Several unfavorable prognostic factors could be identified in the univariate analysis and confirmed in a multivariate Cox model.

St. Thomas cardioplegia versus topical cooling: ultrastructural and biochemical studies in humans.

Transmural left ventricular biopsies were studied from 28 patients undergoing cardiopulmonary bypass with anoxic cardiac arrest. The myocardium was protected by topical cooling (20 degrees C) (Group 1, 15 patients) or by cardioplegia with St. Thomas' solution (Group 2, 13 patients). Biopsies were taken at the start of bypass and 3 to 5 minutes after unclamping of the aorta. Mean cross-clamp time was not significantly different between the groups (50 minutes for Group 1 and 53 minutes for Group 2; p greater than 0.05). The ultrastructural changes induced by ischemia and subsequent reperfusion were almost exclusively related to the mitochondria. The degree of mitochondrial damage was evaluated by a semiquantitative analysis based on mitochondrial fine structure. The frequency of severe postischemic mitochondrial damage was significantly higher in Group 1 (20.1% versus 2.7% in Group 2; p less than 0.05). Biochemical analysis of the biopsies indicates that the myocardial concentration of creatine phosphate decreases by about 50% after topical cooling (p less than 0.05). With St. Thomas cardioplegia, no significant change in the tissue level of this high-energy phosphate takes place. The results show evidence of the superiority of the St. Thomas cardioplegia to topical cooling alone.

The Monostrut versus Medtronic Hall prosthesis: a prospective randomized study.

A prospective randomized study, comparing the clinical results between two groups of patients undergoing valve replacement with the Monostrut (MS) and Medtronic-Hall (MH) heart valve prosthesis was carried out between January 1985 and December 1988. A MS valve was implanted in 205, the MH in 198 patients selected randomly. Statistical analysis showed a perfect match between the two groups regarding preoperative and operative variables, including implantation site. All patients were given life-long anticoagulant therapy after operation. Follow up was 5.06 years (median) with a total of 1971.1 patient-years (pty) and 96.6% complete. The two groups showed no significant difference in the incidence of the following postoperative events: 30-day mortality, late mortality, reoperation, anticoagulant related bleeding, paravalvular leak, prosthetic valve endocarditis and thromboembolism (TE). Multivariate analysis indicated a borderline increased hazard of TE (2.1 +/- 0.4%/pty versus 0.7 +/- 0.2%/pty) (p = 0.0087, Bonferoni corrected significance) in the MS group. It is concluded that long term outcome is excellent with these two tilting disc valves. The marginally lower incidence of thromboembolism, however, favors the Medtronic Hall prosthesis.

Aneurysm of the left atrial appendage.

A 2-year old asymptomatic girl is presented in whom the chest x-ray film led to the discovery of a grossly distorted cardiac shadow. Angiocardiography showed a giant aneurysm originating from the left atrium. At operation an intrapericardial aneurysm of the left atrial appendage, measuring 12 X 4 X 4 cm, was found. It communicated with the left atrium through an orifice measuring 3 cm. The aneurysm was excised.

The spectrum of clinical manifestation of anomalous origin of the left coronary artery and surgical management.

Intercoronary collaterals play a major role in determining whether patients with the symptoms of anomalous left coronary artery will suffer infarction early in life with resultant complications or will survive to an older age before becoming symptomatic with angina. We believe that the definitive surgical treatment should be performed at the earliest age possible to avoid further damage to myocardial muscle.

Persistent atrio-ventricular canal. Case report of an unusual intermediate form.

A case is described, which presented the following combination of anomalies: An interatrial and interventricular septal defect, absence of a cleft in the aortic leaflet of the mitral valve and in the septal leaflet of the tricuspid valve. The latter leaflet was underdeveloped and presented several perforations. On the bases of the characteristic electrocardiographic, angiocardiographic and anatomical findings this anomaly was considered to be an intermediate form of a common atrioventricular canal. Total repair was successfully performed utilizing the technique of Rastelli and McGoon.

Total correction of tetralogy of Fallot following palliation.

Fifty three patients with Tetralogy of Fallot were totally corrected following palliation. Intracardiac repair was not adversely influenced by a Blalock Taussig shunt or a Waterston shunt which did not produce kinking of the RPA. The results were less satisfactory after correction following a Potts shunt or a Waterston shunt with kinking at the site of the anastomosis.

The expanded polytetrafluorethylene (PTFE) graft as a vascular substitute.

Ninety-one PTFE grafts (63 Gore-Tex and 28 Impragrafts) were used to bypass an occluded femoropopliteal artery in eighty-six patients. Ischemic rest-pain usually combined with ulcerative lesions or gangrene was the operative indication in 56 patients. In 58 percent the outflow was limited to at most 1 crural artery. The distal anastomosis was located to the distal popliteal artery in 38 reconstructions and to the tibioperoneal trunc or one of the crural arteries in 27 reconstructions. Postoperative angiography was performed in 18 patients. The incidence of early thrombosis is very high namely 47% within 3 months and 57% within 6 months. Limited outflow and thrombus apposition, as demonstrated by some angiograms, are the major reasons of the early occlusion.

The patient's perspectives after aortofemoral grafting for occlusive disease.

The late results of aortofemoral grafting for aortoiliac occlusive disease in 371 patients are presented. Late survival (30% after 15 years) was primarily dependent on age at the time of surgery and the presence of atherosclerotic heart disease on subinguinal atherosclerotic involvement. The majority of late deaths (42%) was due to atherosclerotic disease. With a mean follow-up period of 7 years the late complication rate was 29%. Late thrombosis was responsible for 66% of the late complications and a subsequent redo-operation was necessary in 24% of the patients. Age at the time of surgery and the presence of femoropopliteal occlusive disease were the most important factors. Regarding the late mortality rate of 45%, it is recommended that follow-up in these patients should be directed not only to late graft complications but also to other manifestations of generalized atherosclerosis.

Five-year survival in resected T3/N2 lung cancer.

The number of operated T3 lung cancers increases constantly. The absolute 5-year survival was 16.6% (9/54) and was only 9.5% (4/42) in resected N2 tumors.

Quantification of creatine phosphokinase and its isoenzyme MB, serum glutamic oxaloacetic transaminase and lactic dehydrogenase from different sources during aortic valve replacement procedure.

The diversity of conditions inducing an increase in CPK-MB, CPK, LDH and SGOT allows investigation of the quantitative evolution in cardiac patients during heart surgery. In nine patients submitted to valve replacement, three samples were taken respectively: one from the superior and the inferior caval veins and one another from the coronary sinus and immediately centrifuged. The sera were processed to quantitate the CPK, CPK-MB, LDH and SGOT through the three periods of observation. The three sites intended to explore the possible other sources of CPK-MB released at surgery: superior vena cava accounts for upper body regions, inferior vena cava for lower body regions and the coronary sinus for the heart itself. The three sites compared separately through the three periods did not show any significant differences. Only comparing the pre-CPK values to their homologous obtained during and after cardiopulmonary bypass, very evident differences could be registered (P less than 0,05 and less) for CPK, CPK-MB and LDH. While SGOT remained totally unchanged through the three periods. The evolutive CPK, CPK-MB and LDH increase accounted for high sensitivity of these enzymes to the variations of conditions during cardiac surgery. It is highly possible that other sources of CPK-MB could be dissiminated in the body and capable to produce valuable enzymatic amounts during and after cardiac surgery and that the heart is not exclusively alone in releasing this enzyme during cardiac ischemic arrest and in other circumstances. The real importance of CPK-MB principally and of CPK would be surestimated as conclusive parameters in diagnosis of myocardial damages during cardiac procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Five-year survival in operated lung cancer.

A total of 1,001 patients with a confirmed diagnosis of lung cancer were treated at the University Hospital Pellenberg - Leuven in the five-year period 1970-1974. One hundred and sixty-four patients (16.4%) were operated and 152 underwent surgical resection of their pulmonary lung lesion. The influence of factors as histology, type of resection, age, staging, anatomic localization of the tumor on the five year survival are considered. The survival was 34.2% for all types of resected tumors, ranging from 42.0% for the lobectomies in squamous cell carcinoma to 0% in small cell carcinoma. The operative (30 days) mortality is included in the statistical follow-up. This mortality was 8.6% for the pneumonectomies and 4.3% for the lobectomies.

Experience with 100 consecutive anterior mediastinotomies in lung cancer.

Between January 1978 and March 1981, 100 anterior mediastinotomies were performed in patients with proven or suspected lung cancer. It was done 72 times in patients with a tumor of the left lung, all presenting with a normal mediastinum. Of those 72 patients, 59 had a tumor in the left upper lobe: 30.5% of the latter were found to have involved mediastinal lymphnodes (our yield in this location was 15.1% when using the cervical mediastinoscopy); 16 patients with a left upper lobe tumor had both an anterior negative cervical mediastinoscopy followed by an anterior approach: 4 became positive (25%). The anterior mediastinotomy was performed two times in patients with a suspect mediastinum: the mediastinoscopy was once positive, and once negative. It was done 26 times in patients with a radiologically manifest enlarged mediastinum (7 on the right side, 19 on the left side); in 24 patients the histological diagnosis was unknown. The anterior mediastinotomy was positive in all 26 cases. For the whole group we found positive nodes in 10 of 26, i.e. 38.5% of the patients despite normal findings at cervical mediastinoscopy. We would therefore recommend an anterior mediastinotomy in every patient with a suspect or an enlarged superior mediastinum in order to establish an histological diagnosis or exceptionally to check the operability. If the mediastinum is radiologically normal, the anterior approach has much more chance to yield a positive result than the cervical one when the tumor is located in the left upper lobe.

[Surgical treatment of lungcancer five-year survival. Major surgical complications (author's transl)]. / Heelkundige behandling van het bronchuscarcinoom vijf-jaar overleving. Belangrijke heelkundige verwikkelingen.

In the period 1961--1971, 41 patients with a squamous-cell carcinoma were operated upon. The absolute 5-year survival is 47.6% for the lobectomy and 20% for the pneumonectomy. In the period 1971--1976 (6 years), 211 resections for carcinoma (all types) were performed including 19 cases of squamous cell carcinoma, operated in 1971 and also studied in the first part of the work. They represent only 15.2% of all the hospitalized lungcancer patients. The lobectomy/pneumonectomy ratio is 60/40. The postoperative mortality is respectively 4% and 9.5% and the major surgical complications (bleeding, broncho-pleural fistula, empyema) are 0.8% and 3.6%. The causes of postoperative death are examined. Remarkable is the low incidence of bronchial fistulisation: 1 in 211 resections for malignant tumors, i.e. 0.47%. These results are discussed and compared with the literature.