Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans.

OBJECTIVES: The expression of endothelial adhesion molecules and their functional significance in leukocyte adhesion to human myocardial blood vessels in acute myocardial infarction (AMI) were studied. BACKGROUND: Leukocyte extravasation, mediated by specific adhesion molecules, exacerbates tissue injury after restoration of blood supply to an ischemic tissue. Experimental myocardial reperfusion injury can be alleviated with antibodies that block the function of adhesion molecules involved in leukocyte emigration, but the relevant molecules remain poorly characterized in human AMI. METHODS: Semiquantitative immunohistochemistry and in vitro adhesion assays were used to study the expression and granulocyte binding abilities of different endothelial adhesion molecules in human AMI. Changes in the molecular nature of vascular adhesion protein-1 (VAP-1) were evaluated using immunoblotting. RESULTS: Certain endothelial adhesion molecules (intercellular adhesion molecule [ICAM-2], CD31 and CD73) were expressed in myocardial blood vessels homogeneously in normal and ischemic hearts, whereas others (E-selectin and peripheral lymph node addressin) were completely absent from all specimens. The synthesis of ICAM-1 was locally, and that of P-selectin regionally, upregulated in the infarcted hearts when compared with nonischemic controls. Vascular adhesion protein-1 showed ventricular preponderance in expression and alterations in posttranslational modifications during ischemia-reperfusion. Importantly, P-selectin, ICAM-1 and VAP-1 mediated granulocyte binding to blood vessels in the ischemic human heart. CONCLUSIONS: Human P-selectin, ICAM-1 and VAP-1 appear to be the most promising targets when antiadhesive interventions preventing leukocyte-mediated tissue destruction after myocardial ischemia are planned.

Human vascular adhesion protein-1 in smooth muscle cells.

Human vascular adhesion protein-1 (VAP-1) is a dual-function molecule with adhesive and enzymatic properties. In addition to synthesis in endothelial cells, where it mediates lymphocyte binding, VAP-1 is expressed in smooth muscle cells. Here we studied the expression, biochemical structure, and function of VAP-1 in muscle cells and compared it to those in endothelial cells. VAP-1 is expressed on the plasma membrane of all types of smooth muscle cells, but it is completely absent from cardiac and skeletal muscle cells. In tumors, VAP-1 is retained on all leiomyoma cells, whereas it is lost in half of leiomyosarcoma samples. In smooth muscle VAP-1 predominantly exists as a approximately 165-kd homodimeric glycoprotein, but a trimeric (approximately 250 kd) form of VAP-1 is also found. It contains N-linked oligosaccharide side chains and abundant sialic acid decorations. In comparison, in endothelial cells dimeric VAP-1 is larger, no trimeric forms are found, and VAP-1 does not have N-glycanase-sensitive oligosaccharides. Unlike endothelial VAP-1, VAP-1 localized on smooth muscle cells does not support binding of lymphocytes. Instead, it deaminates exogenous and endogenous primary amines. In conclusion, VAP-1 in smooth muscle cells is structurally and functionally distinct from VAP-1 present on endothelial cells.

Angiographic changes in saphenous vein grafts and atherosclerosis risk factors. A 5-year study with serial measurements of serum lipids and lipoproteins.

The association between cardiovascular risk factors and stenosis or occlusion of saphenous vein grafts was analysed in a prospective 5-year study of 176 unselected patients with coronary artery bypass grafting (CABG). Methods included serial measurements of serum lipids and lipoproteins, determination of apolipoprotein E phenotype, lipoprotein (a) levels 5 years postoperatively, and subcutaneous fat biopsy to determine the fatty acid composition before and one year after CABG. Graft angiography with quantitative analysis of angiograms was performed at the end of follow-up. A coronary artery with diameter < or = 1.5 mm was associated with occlusion of vein grafts (p < 0.01). The mean levels of serum lipids and lipoproteins, other traditional risk factors for atherosclerosis, and subcutaneous fatty acid composition were similar in patients with and without graft occlusion, and similar when the maximum diameter of non-occluded grafts was < 50% vs > or = 50%, and < 25% vs > or = 25%. High lipoprotein (a) concentration tended to be associated with obstructive changes in vein grafts. Our data indicate that, because lipids, lipoproteins and other traditional cardiovascular risk factors do not predict occlusion or stenosis of saphenous vein grafts five years after CABG, it is not currently possible to predict directly from the levels of these risk factors which patients are likely to benefit from pharmacological or other interventions.

Toremifene concentration and multidrug resistance in lung tumors.

In this pharmacokinetics study, concentrations of toremifene (TOR), a new antiestrogen, were measured after a 7-day oral treatment in serum, lung, and tumor tissue to determine the optimal dose of TOR for the modulation of clinical multidrug resistance in patients with lung cancer. Target levels of the antiestrogen were based on previous in vitro studies. Altogether, 18 patients with operable lung tumors were studied. TOR was given in an open, nonrandomized, phase I study at three different dose levels. The medication consisted of oral TOR given for 7 days at either 240, 480, or 600 mg/day before surgical removal of the tumor. At least five patients were scheduled to be included at each dose level, with all five receiving the full course of therapy before escalation of the dose. Blood samples for serum TOR concentration measurements were taken on days 0 and 7. Specimens of tumor and normal lung tissue of approximately 0.5 g were taken on day 7. The concentrations of TOR and its metabolites were determined in serum, lung, and tumor tissue at different dose levels. Altogether, 12 evaluable patients completed the scheduled treatment. The concentrations measured in serum, lung, and tumor tissue increased along with the dose used, such that the highest TOR values were achieved at 600 mg/day, with mean values being 4.9 mumol/l, 175.0 mumol/g, and 122.7 mumol/g, respectively. The concentrations of TOR and its metabolite N-demethyltoremifene were highest in lung tissue, but the values measured in tumor specimens were also well above the respective concentrations detected in serum samples. The TOR doses of 240 and 480 mg/day were well tolerated. One patient in the group treated at 600 mg/day had to discontinue the treatment because of headache and nausea. TOR given at doses ranging from 480 to 600 mg/day for 7 days will produce serum, lung, and tumor concentrations of the parent drug and its metabolites that have been shown to reverse multidrug resistance of cancer cells in vitro. As the 480-mg/day dose of TOR produced tumor concentrations high enough to reverse multidrug resistance without producing adverse drug reactions, the dose recommended for the foreseen clinical trials in the reversal of multidrug resistance would be 480 mg/day for 7 days.

Acute dissection of ascending aortic aneurysm in a patient with previous coronary artery bypass grafting.

Six years after coronary artery bypass grafting, a 61-year-old man underwent emergency surgery for annulo-aortic ectasia and acute dissection. The aneurysmal tissue and aortic valve were excised and reconstruction was achieved with a composite graft. The patent vein grafts were attached to the composite graft and the original coronary orifices were closed.

Composite graft in annulo-aortic ectasia. Nineteen years' experience without graft inclusion.

OBJECTIVE: The original Bentall procedure for the surgery of annulo-aortic ectasia (AAE) includes the risk of leakage and pseudo-aneurysm formation in the coronary anastomosis. To avoid the complications mentioned above we have used the open technique without the graft inclusion. In this study we evaluate our early and late results. MATERIAL AND METHODS: One hundred consecutive patients with annuloaortic ectasia underwent surgical repair with composite graft between December 1975 and February 1994. In all cases the aneurysmal tissue was radically resected and the origins of the coronary arteries were directly reimplanted to the tube prosthesis. No wrapping was used. Twenty-two patients met the clinical criteria of Marfan syndrome. Thirteen of the patients underwent an emergency operation, because of a rupture of aneurysm in 2 cases and an acute dissection in 11 cases. Additional procedures were performed in 16 patients: mitral valve replacement in 2, coronary artery bypass grafting in 12 patients and in 2 cases the tube prosthesis included aortic arch, too. RESULTS: The overall hospital mortality was 3.0% (3/100). In the elective group there was one hospital death (1/87; 1.1%). In the emergency group two patients died in the operation room (2/13; 16.7%). There have been 13 late deaths among the 97 hospital survivors (13.4%). Four of the late deaths were surgery related. Routine control angiography was performed in all patients 6 months after surgery. Sixty patients who had lived at least 3 years after surgery were called to reangiography and 53 of them came. No pseudo-aneurysm or leakage at distal anastomosis or coronary anastomosis could be seen. A slight dilatation of one or both coronary origins was observed on 15 patients; 9 of whom had Marfan syndrome. CONCLUSIONS: The open technique is simple and can be used in all anatomical variations of the annulo-aortic ectasia. The early and late results are at least comparable with those achieved by other techniques.

Use of the polymerase chain reaction and DNA sequencing for detection of Bartonella quintana in the aortic valve of a patient with culture-negative infective endocarditis.

We used the polymerase chain reaction (PCR) and broad-range bacterial primers, combined with DNA sequencing, to identify Bartonella quintana as the etiologic agent in a case of culture-negative infective endocarditis; all blood cultures, as well as the bacterial cultures of the resected aortic valve and vegetations, remained negative. PCR was used to amplify bacterial 16S rDNA from a template prepared from the aortic valve vegetation. The amplified 16S rDNA produced a nucleotide sequence that was 99.79% identical to the B. quintana rDNA sequence. The patient had a highly elevated level of serum antibodies to Bartonella antigen (1:8,192).

Myocardial reperfusion after coronary bypass surgery. Suture of only distal or all anastomoses with the aorta cross-clamped?

Sixty patients undergoing elective coronary artery bypass grafting were randomly allocated into two groups, each of 30 patients and similar as regards age, sex, number of coronary artery bypasses and left ventricular ejection fraction. In group A the proximal anastomoses of vein grafts were sutured after aortic declamping during partial occlusion of the aorta, and in group B these anastomoses were done during aortic cross-clamping. The aortic cross-clamp time was significantly longer in group B than in group A (72 vs 57 min, p < 0.0001). Myocardial cooling and rewarming and the number of sustained or possible perioperative myocardial infarctions were equal in both groups. Central haemodynamics showed no intergroup difference, before or after induction of anaesthesia or at the end of surgery. Conduction disturbances were more common in group A than in group B (12 vs 3, p = 0.0246), and transient external pacing was more often required in group A (9 vs 2, p = 0.0534). Myocardial reperfusion via native coronary arteries and bypass grafts gives better protection against conduction disturbances than does reperfusion via only native arteries, despite longer aortic cross-clamping time.

Tonometric assessment of sigmoid perfusion during aortobifemoral reconstruction for arteriosclerosis.

OBJECTIVE: To assess the effect of inferior mesenteric artery reimplantation on perfusion of the mucosa of the sigmoid colon in patients undergoing aortobifemoral reconstruction for arteriosclerotic disease. DESIGN: Random control study. SETTING: University hospital. SUBJECTS: 8 Men and 2 women with peripheral vascular disease and angiographically patent superior and inferior mesenteric arteries. INTERVENTIONS: Patients were randomised to have the inferior mesenteric artery reimplanted in the Y-graft or not. Sigmoid perfusion was measured with a tonometer and expressed as the intramucosal pH (pHi) during operation (baseline) and for four days afterwards. MAIN OUTCOME MEASURES: Measurements of pHi, arterial blood gases, and acid base balance, and signs of ischaemia of the gut. RESULTS: In both groups the pHi was reduced after clamping the aorta, but returned to baseline on the first postoperative day. One patient had a cardiac arrest from which he was resuscitated and his pHi measurements were subsequently low. CONCLUSION: pHi does seem to reflect changes in the circulation of the sigmoid mucosa. Even if the inferior mesenteric artery is patent, reimplantation is only rarely indicated in patients undergoing aortobifemoral reconstruction.

Cardiac rehabilitation and return to work after coronary artery bypass surgery.

The work situation of 66 male patients who underwent elective coronary artery bypass surgery (CABS) and who had been randomly allocated to receive cardiac rehabilitation (group R) was compared with the work situation of 59 similar patients allocated to receive only standard care (group H). The follow-up time was one year. The proportions of subjects working in groups R and H were 26% and 20% (p = ns) before the CABS, 45% and 34% (p = ns) 6 months and 56% and 38% (p = ns) 12 months after the CABS, respectively. The increase in proportion of subjects who worked was significant in both groups at both 6 and 12 months after the CABS (p < 0.05 for all changes). The increases were not significantly different between the whole groups, but in patients younger than 55 years of age, return to work was more frequent in group R than in group H (at 12 months 60% vs. 35%, p for the difference in change = 0.02). Stepwise logistic regression analysis of the factors influencing return to work showed that a patient's judgement of his own working capacity as good 6 months after CABS (odds ratio (OR) 8.5, confidence interval (CI) 2.3-32.0), functional class I 6 months after the CABS (OR 6.7, CI 1.8-24.5), his desire to work (OR 6.4, CI 1.6-26.0) and absence from work of less than 3 months before the CABS (OR 4.9, CI 1.2-20.2) were significant positive predictors of return to work 1 year after the CABS.

Coronary heart disease risk factors before and after bypass surgery: results of a controlled trial on multifactorial rehabilitation.

The effect of a three-phase multifactorial institution-based rehabilitation programme on coronary heart disease (CHD) risk factors was studied in an open randomised trial comprising 228 patients undergoing coronary artery bypass surgery allocated into a rehabilitation (R) group (n = 119) and a hospital (H = control) group (n = 109). Follow-up examinations were performed at 6 and 12 months. Serum total cholesterol and triglyceride levels decreased significantly in both groups during follow-up. These decreases were not significantly different between the R and H groups. Serum high density lipoprotein (HDL) cholesterol level increased significantly at 6 and 12 months in the R group, but not in the H group. The differences in the changes between the groups were not significant. The ratio of serum HDL cholesterol to total cholesterol increased significantly in the R group from the preoperative value of 0.154 to 0.179 (P less than 0.001) at 6 months and to 0.180 (P less than 0.001) at 12 months. In the H group these values were 0.152, 0.166 (P less than 0.001) and 0.168 (P less than 0.001), respectively. The significance of the differences in the changes between the groups were P = 0.01 at 6 months and 0.06 at 12 months. These differences were more obvious in patients aged 55 years or under. There was a significant decrease (P = 0.005) in the proportion of smokers in the R group and a significant increase in the proportion of patients taking regular exercise in both groups as assessed by questionnaire.(ABSTRACT TRUNCATED AT 250 WORDS)

When is routine operative cholangiography necessary? An evaluation of 200 consecutive patients operated on for gallbladder stones.

Operative cholangiography (OC) was performed during open standard cholecystectomy in 195 of 200 consecutive patients. The cholangiography was considered suspicious for choledochal stones in 28 patients (14%). Both choledochotomy and choledochoscopy were carried out. Stones in the biliary tree were found in 17 patients and in 11 cases choledochotomy was negative. Cholecystectomy was performed on an emergency basis in 46 patients, 15 of them underwent choledochotomy and in 11 (24%) bile duct stones were found. In 154 electively operated patients six (4%) had choledochal stones. Based on preoperative history choledochal stones were suspected in 30 electively operated patients but only eight had stones in the biliary tree at the time of operation. The percentage of false positive cholangiograms was 6% in the whole material, and unsuspected choledochal stones were diagnosed in 5% respectively. It is recommended that operative cholangiography should be performed routinely in patients subjected to emergency cholecystectomy. In elective operations selective use is acceptable.

Early and late results of aortic valve replacement. A series of 510 patients.

Aortic valve replacement was performed in 510 patients (Björk-Shiley valves in 93%), with concomitant surgical procedures in 146 cases. The patients were grouped according to technique of myocardial protection: Group I (n = 98) selective coronary perfusion, group II (n = 82) topical cooling, and group III (n = 330) cold crystalloid cardioplegia and topical cooling. The early mortality rate was 5.7% overall: Among patients with isolated aortic valve replacement in groups I, II and III it was 8.4, 1.7 and 1.3%, respectively, and among those with additional surgery 40.0, 12.5 and 8.4%. Myocardial infarction and low cardiac output were responsible for 65.5% of the early deaths. Follow-up ranged from 2 months to 16 11/12 years, totalling 2,859 patient years. In patients with isolated aortic valve replacement and Björk-Shiley prosthesis, the incidence of valve-related late complications/100 patient years was 0.49 for thromboembolism, 0.82 for anticoagulant-related haemorrhage and 0.49 for prosthetic valve endocarditis. There was no thrombotic encapsulation in aortic position. Survival at 5 and 10 years was 83% and 72%. Aortic valve replacement is a safe procedure and concomitant operations do not unreasonably increase risks.

Prosthetic valve endocarditis.

Prosthetic valve endocarditis is an infrequent but serious complication of valve surgery. It occurred in 25 (3.2%) of 772 patients who received aortic, mitral or double valve replacement in 1971-1987. The total follow-up time was 3,976 patient years, giving an incidence of 0.63/100 patient years. Staphylococci were the most common of the cultured organisms in early and late infections-60% and 64%, respectively. The endocarditis was disclosed at autopsy in two cases. Treatment was antibiotics alone in 11 cases, and surgery was required in 12, the indication always being congestive heart failure. C-reactive protein level fell more rapidly than erythrocyte sedimentation rate in response to antibiotic or surgical management. The mortality rate was 73% in the antibiotic group and 33% in the surgical group. The findings demonstrated that an infected valve prosthesis should be replaced without delay if complications develop.

The proportion of patients with cognitive impairment after coronary artery bypass surgery: an 8-month follow-up study.

The aim of this study was to investigate cognitive function after coronary artery bypass surgery and the association of this with surgical variables. All male patients scheduled for elective surgery, aged 40-64 years, mean age 54 +/- 6 (n = 104), and participating in a randomized rehabilitation study, were included. A comprehensive psychodiagnostic examination was conducted preoperatively, 2, and 8 months postoperatively. The assessment of change was conducted using tertiles, defined according to population norms. More patients revealed improvement than impairment, and practically no significant associations with surgical variables were found.

Results of multiple valve repair. A clinical study of 81 patients.

A report is presented of 50 men and 31 women, mean age 50.3 years, who underwent surgery for multivalvular cardiac disease in 1973-1987. NYHA function class was III-IV in 88% of the patients. The most common procedures were aortic + mitral valve replacement (81%), aortic + mitral valve replacement + coronary artery bypass grafting (5%), aortic valve replacement + tricuspid valvuloplasty (5%) and mitral valve replacement + tricuspid valvuloplasty (5%); 95% of the implanted valves were of Björk-Shiley disc type. Nine patients died perioperatively, six due to myocardial infarction and/or low cardiac output. Postoperative bleeding necessitated resternotomy in three cases. Follow-up was complete, with a mean observation time of 4.5 years (a total of 323 patient years). The incidence of thrombotic valve encapsulation was 0.6/100 patient years. Corresponding figures for anticoagulant-related haemorrhage, prosthetic valve endocarditis and paraprosthetic leakage were 0.9, 1.2 and 1.2. In our experience, the rate of late complications after multivalvular reconstruction using Björk-Shiley prosthesis is acceptable if anticoagulant therapy is correctly employed.

Surgical treatment of active native valve endocarditis.

A report is presented of 24 patients (23 male), mean age 38 years, who underwent surgery for active native valve endocarditis of the left heart in 1975-1988. The aortic valve was affected in all patients, and also the mitral valve in five. Pre-existing aortic valve disorder was present in 17 cases (13 congenitally bicuspid 4 rheumatic affection). There were five hospital deaths (20.8%). Staphylococci as causal organism and extensive infection predicted the highest mortality and morbidity. The mean follow-up time was 39.7 (range 2-114) months. Two reoperations because of prosthetic valve dehiscence revealed endocarditis of the implanted valve. Strong correlation was found between favourable postoperative course and rapid normalization of C-reactive protein levels, which did not fall in patients with persistent infection. Early surgery is recommended if the course of bacterial endocarditis is severely complicated.