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Biomedical subjects

S P Nolan

Publications and source records attributed to S P Nolan.

At least 19 recordsLinked to original sources

Distribution of low density lipoprotein in the branch and non-branch regions of the aorta.

Atherosclerosis occurs focally in branch segments of the artery. Understanding why these segments are more susceptible to the development of the disease is at the root of understanding atherogenesis. We investigated accumulation of low density lipoprotein (LDL) in the branch and non-branch regions of the aorta to determine why the disease develops in branch regions. Abdominal aortas and their major branches were harvested from 36 rabbits. Rabbit LDL was prepared from whole blood and radiolabeled with 125I. The aorta was incubated with radiolabeled LDL in the lumen at 37 degrees C, under intraluminal pressure of 2-3 mmHg, for 1 h. Disks of 1.8 mm diameter were punched from the branch and non-branch regions of the aorta, cryosectioned and the sections counted in a gamma counter. Protein bound radioactivity was determined by TCA precipitation. LDL accumulation was highest towards the aortic intima and declined sharply towards the media. LDL accumulation at any given depth was higher in the branch than non-branch region. LDL accumulation in the intimal-medial sections was 87% higher in the branch than non-branch region. Total LDL accumulation in the branch was almost twice that in the non-branch region. Mean LDL accumulation was also greater in the branch than non-branch region. The aorta was significantly thicker at the branch. LDL distribution profiles indicate that LDL is present in a greater concentration and over a greater depth in the branch than non-branch region. The tendency of the branch region to accumulate LDL in greater amounts may explain its susceptibility to atherosclerotic lesion development.

Animals

A mathematical model for the quantification of mitral regurgitation. Experimental validation in the canine model using contrast echocardiography.

BACKGROUND: Because the clearance of contrast from the left atrium (LA) relative to the left ventricle (LV) depends on the degree of mitral regurgitation (MR), we hypothesized that a mathematical model can be developed that would provide a quantitative estimation of MR from the washout of contrast from these chambers. METHODS AND RESULTS: After mathematically developing the model, we performed experiments in two groups of dogs with the use of contrast echocardiography. Group 1 consisted of nine dogs in which different degrees of MR were produced by creating ischemic LV dysfunction. Contrast was injected into the LV, and MR was graded visually on a scale of from 0 to 4+. Videointensity plots generated from the LA and LV were provided to the model. There was excellent correlation between visual assessment of MR and model-derived regurgitant fraction in the 33 stages: y = 0.16x + 0.002 (r = 0.97, p less than 0.001, SEE = 0.06). To obtain a more quantitative validation, we placed electromagnetic flow probes on the aorta and just cephalad to the mitral annulus in six dogs (group 2) during cardiopulmonary bypass. Different degrees of MR were produced by chordal traction and/or myocardial ischemia. Regurgitant fraction was calculated at each stage from the flow probe and videointensity data. There was excellent correlation between flow probe and model-derived regurgitant fraction (y = 0.90x + 0.03; r = 0.96, p less than 0.001, SEE = 0.06), and close interobserver and intraobserver correlations were noted using flow probe and contrast echocardiographic data. CONCLUSIONS: A mathematical model that uses the clearance of contrast from the LA relative to the LV can be used to accurately measure the severity of MR. These findings may have important practical implications for the quantification of MR.

Animals

Change in endothelial cell morphology at arterial branch sites caused by a reduction of intramural stress.

Arterial branch sites have very high intramural stresses at physiologic intraluminal pressures; the same sites have a predilection for atherosclerosis. The effect of intramural stress on endothelial cell morphology was investigated. Five rabbits had permanent casts placed around a segment of the abdominal aorta-left renal artery branch area during controlled hypotension, thus reducing intramural stress without narrowing the lumen. These five animals, and three normal rabbits, were sacrificed after 4-8 weeks, and the vessels were perfused with buffered 2.5% glutaraldehyde for 2 h at 100 mm Hg pressure. The aortas were examined by scanning electron microscopy. In normal aortas, the distal region of the ostia of the left renal and celiac arteries just beyond the flow divider displayed many morphologically altered endothelial cells ranging from spindle shape to cobble-stone shape. The same aortic area of casted rabbits, as well as the straight abdominal aorta in all rabbits, showed a smooth surface of endothelial cells with intact cell borders and no morphologically altered cells. At branch sites, the occurrence of morphologically altered endothelial cells may be due to increased intramural stress. When intramural stress is reduced, the morphology of branch endothelial cells changes to resemble that of the unbranched regions. In conclusion, endothelial cell morphology changes in response to changes in intramural stress.

Animals

Four years' experience with fibrin sealant in thoracic and cardiovascular surgery.

A single-donor fibrin sealant system was used in 689 thoracic and cardiovascular surgical procedures over the 4-year period between April 1, 1985, and March 31, 1989. An excellent overall success rate (646/689, 94% effective) was achieved with specific applications, including reduction of leakage of air (29/33, 88% effective), blood (595/634, 94% effective), and fluid (14/14, 100% effective), as well as positioning of anatomical structures such as coronary bypass grafts (8/8, 100% effective). Application methods included use of spray bottles (477/497, 96% effective), syringes (165/186, 89% effective), and a Silastic cannula through the flexible fiber-optic bronchoscope (4/6, 67% effective). The system was used in a wide variety of cardiac, pulmonary, esophageal, and vascular procedures to seal staple lines, suture lines, anastomoses, conduits, fistulas, and raw surfaces. No complications with this single-donor system secondary to blood-borne disease have been documented. Overall infection occurred at a nominal rate (16/689, 2%). Thus, fibrin sealant has been a useful tool to control the leakage of air, blood, and fluid during a wide variety of thoracic and cardiovascular procedures and may be of benefit to other surgeons.

Aerosols

Incidence and risk of reintervention after coarctation repair.

We examined the need for intervention after coarctation repair in a retrospective study of 197 procedures performed between 1967 and 1989. Reintervention was required in 23 patients. No technique of coarctation repair was free from complications. Although there were only two stenoses in the group receiving Dacron patch angioplasty, only seven of these procedures were performed in children under the age of 1 year. The risk of stenosis was inversely correlated to the age at primary repair, with children less than 1 year old being at greater risk than those more than 1 year of age (p less than 0.05). Subclavian flap angioplasty had a lower risk of reoperation than end-to-end anastomosis (p less than 0.02). Formation of true aneurysms was confined to the Dacron patch angioplasty group. The morbidity and mortality for reintervention was low in all groups, with only one procedure-related death and no incidence of paraplegia. Although no technique is free from risk, subclavian flap angioplasty leads to fewer reinterventions in younger patients.

Adolescent

Mediastinal fibrin glue: hemostatic effect and tissue response in calves.

There is continued controversy regarding the effectiveness and potential adverse effects of fibrin glue. Thus, we chose to evaluate it in a model of experimental calf aortic valve replacement that has been previously well established. Concentrated fibrinogen and topical thrombin were sprayed to form a thin layer of fibrin glue over the mediastinal tissues of 20 consecutive calves undergoing aortic valve replacement. Chest tube outputs of these animals were compared with those of the preceding 20 consecutive calves undergoing aortic valve replacement without fibrin glue. All procedures were performed by the same surgeon, and no other technical changes were made between the two series. Total postoperative chest tube output (mean +/- standard error) was 553 +/- 50 mL for the calves treated with fibrin glue and 1,155 +/- 103 mL for the control calves (p less than 0.001). On histological examination of mediastinal tissues from 5 treated calves killed 6 weeks after operation, there was no evidence of inflammation, fibrosis, or residual fibrin. To our knowledge, this is the first controlled laboratory study to show that fibrin glue spray is an effective hemostatic agent and that it produces no long-term tissue reaction.

Animals

Repair of large muscular ventricular septal defects in infants employing left ventriculotomy.

The approach to muscular ventricular septal defect has been controversial. Traditional approaches have included pulmonary artery banding or right ventriculotomy. Left ventriculotomy has been employed in older children because of the ease of exposure in the absence of trabeculations, but concern has been raised regarding potential loss of left ventricular function. Four infants less than 4 months of age underwent repair of a large muscular ventricular septal defect by left ventriculotomy. One infant had no associated defects; 2 had undergone previous coarctation repair (1 with pulmonary artery banding); and 1 had a large secundum atrial septal defect. All had congestive heart failure refractory to maximal medical management. All patients survived, and there was no myocardial dysfunction. Echocardiographic indices of ventricular function 3 to 24 months postoperatively were normal (mean shortening fraction, 32.5%). Left ventriculotomy with patch closure of the ventricular septal defect provides a simple approach to a large muscular ventricular septal defect in infants with heart failure.

Cardiopulmonary Bypass

Pulmonary artery banding revisited.

Pulmonary artery (PA) banding to reduce pulmonary blood flow was described by Muller and Dammann in 1952. This review describes the outcome of 170 children who had PA banding at the University of Virginia Medical Center between 1955 and 1988. One hundred and one of the patients were banded between 1958 and 1970; fewer bands were placed in later years because early total correction was feasible for certain conditions. When analyzed by preoperative diagnoses, the data reveal that children with a single ventricle undergoing banding had a significantly lower 30-day mortality rate of 12% compared to other preoperative diagnoses, including atrioventricular canal, truncus arteriosus, and ventricular septal defect (VSD) at 30% (p less than 0.05). The late overall mortality for all patients was approximately 10%, an attrition rate of 1% per year. PA banding still has a role in management of patients with congenital heart disease, particularly for infants with a single ventricle. Actuarial survival at 10 years for patients with this condition is 92%. Interestingly, this indication for pulmonary banding is the same one cited in the original report.

Aortic Coarctation

Coronary revascularization rather than cardiac transplantation for chronic ischemic cardiomyopathy.

Patients with very poor ventricular function have been thought to be highly vulnerable to elective myocardial revascularization. Ischemic cardiomyopathy is now the major indication for cardiac transplantation. The 2-year survival of medically treated patients with ejection fractions less than 20%, but who are not sufficiently symptomatic for cardiac transplantation, is less than 25%. At our institution we have taken an aggressive approach by using myocardial revascularization for chronic ischemic cardiomyopathy. Between 1983 and 1988, 39 patients with preoperative ejection fractions less than 20% underwent coronary artery bypass. Patients were excluded if they had valvular heart disease other than mild to moderate mitral regurgitation, required resection of a left ventricular aneurysm, or required emergency operation for acute coronary occlusion. Mean age was 63.3 years (range, 43 to 80 years) and 31 were men. Mean preoperative ejection fraction was 18.3% (range, 10% to 20%) and the mean preoperative left ventricular end diastolic pressure was 22 mm Hg (range, 8 mm Hg to 38 mm Hg). There was one operative death (2.6%). Mean follow-up was 21 months (range, 3 to 60 months) with eight late deaths (a total mortality rate of 21%). Seven deaths were due to arrhythmias. Three patients continued to have severe heart failure, one of whom underwent successful cardiac transplantation. By life table analysis, there was a 3-year survival rate of 83%. With the present shortage of cardiac transplant donors, myocardial revascularization for ischemic cardiomyopathy is a reasonably effective means for preserving residual ventricular function.

Adult

Successful use of fibrin glue during 2 years of surgery at a university medical center.

A method for producing concentrated fibrinogen, an essential component of fibrin glue, from individually stored, single-donor units of human plasma is reported. The plasma is screened for hepatitis B antigen and HIV-1 virus to reduce the risk of transmission of hepatitis and acquired immunodeficiency syndrome (AIDS). This material is routinely stocked in some operating rooms. It is thus readily available when requested by a surgeon for use in combination with topical bovine thrombin to produce fibrin glue. From April 1985 to March 1987 this material was used by surgeons from eight different surgical specialties on 413 patients with a 91 per cent success rate (376/413). Uses have included sealing vascular suture lines, reinforcing pulmonary and esophageal staple lines, closing dural cerebrospinal fluid leaks, fixing split-thickness skin grafts, reducing lymphatic leakage, and controlling bone bleeding. Additional uses include closure of bronchopleural fistulas by means of the flexible bronchoscope, reduction of perioperative hemorrhage by spraying fibrin glue on the anterior mediastinum during cardiac surgery, and reduction of bleeding during debridement of burn eschars. Careful monitoring and patient follow-up detected no cases of transmission of blood-borne diseases. Only one complication, a local wound infection, has been documented. This material has been an important adjunct for the surgical services and may be safely used at hospitals with local blood bank facilities.

Aprotinin

The reversal of amiodarone-induced perioperative reduction in cardiac systolic reserve in dogs.

There is controversy about the myocardial depressant effects of amiodarone in patients with decreased cardiac function undergoing surgery. Some surgeons believe that these effects complicate the discontinuation of cardiopulmonary bypass. Accordingly, the hemodynamic effects of amiodarone were evaluated in two groups of anesthetized mongrel dogs that had undergone a median sternotomy. A control group of 10 dogs and an amiodarone-treated group (15 mg/kg per day for 3 weeks) of 10 dogs were studied, and serum (0.26 to 1.09 micrograms/ml) and tissue (cardiac 2.97 to 11.60 micrograms/ml) levels of amiodarone were measured by liquid chromatography. Hemodynamic measurements were made at baseline and after administration of routine therapeutic intravenous doses of dobutamine (10 micrograms/kg per min), isoproterenol (0.06 micrograms/kg per min) and epinephrine (2 micrograms/min). The amiodarone-treated dogs had a smaller increase in cardiac output compared with baseline than did control dogs. For each drug when the amiodarone-treated group was compared with the control group, increases in cardiac output (liters/min) were: dobutamine, 1.32 +/- 0.24 versus 1.73 +/- 0.31; isoproterenol, 0.84 +/- 0.26 versus 1.43 +/- 0.28; epinephrine, 0.25 +/- 0.15 versus 0.44 +/- 0.53. Amiodarone-treated dogs were also given higher doses of drugs, dobutamine (50 micrograms/kg per min), isoproterenol (1.2 micrograms/kg per min) and epinephrine (20 micrograms/min). Increases in cardiac output were 1.24 +/- 0.24, 1.62 +/- 0.25 and 2.82 +/- 0.64, respectively. All cardiac outputs were significantly increased from the baseline values (p less than 0.05) except those measured in the amiodarone group receiving the lower dose of epinephrine. Thus, amiodarone-treated dogs have a relative reduction of perioperative cardiac systolic reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone

Success of internal mammary bypass grafting can be assessed intraoperatively using myocardial contrast echocardiography.

To determine whether the success of internal mammary artery bypass grafting can be assessed intraoperatively using myocardial contrast echocardiography, sonicated Renografin-76 was injected into the aortic root of 11 dogs during the delivery of cardioplegic solution. Studies were performed with the left anterior descending coronary artery patent and totally occluded, and after internal mammary artery bypass grafting distal to the occluded vessel. Flow rate during cardioplegia was constant for all three stages in each experiment. Myocardial contrast echocardiography clearly demonstrated homogeneous myocardial perfusion with the left anterior descending coronary artery patent, lack of perfusion in the left anterior descending artery bed during its occlusion and excellent perfusion of the occluded bed after internal mammary artery bypass grafting distal to the occlusion in 10 of the 11 dogs. In one dog, the bypass graft was technically inadequate and contrast opacification was not noted in the left anterior descending artery bed after internal mammary artery bypass grafting. The exponential function C(t) = Ae-alpha t + Be-beta t was fitted to computer-derived time-intensity curves from the myocardium, where alpha denotes contrast washout and beta denotes contrast appearance. Respective values for alpha and beta (mean + 1 SD) were similar for the patent left anterior descending coronary artery and after internal mammary artery bypass grafting distal to the occluded artery (0.11 +/- 0.10 versus 0.10 +/- 0.10, and 2.5 +/- 2.4 versus 1.1 +/- 0.56). In conclusion, myocardial contrast echocardiography has potential for intraoperative assessment of the adequacy of coronary artery bypass grafting.

Animals

Structure, stress, and tissue repair in aortic valve leaflets.

During the normal cyclic operation of the aortic valve its leaflets are subjected to continual bending, shearing, and membrane stresses. In vivo studies of marked leaflets have shown that the bending stresses are greatest where leaflets are attached to the aortic wall. Pressure stresses during diastole also appear to be high in this region. The internal shearing stresses are difficult to predict because of the semifluid nature of the tissue in the attachment zone. In the present study a model of the attachment region incorporated measurements of leaflet motion from dogs in vivo and from histological sections. From these measurements bending and membrane stresses were derived in order to estimate the total stresses. In this region the total stresses in systole were negligible because membrane stresses are essentially zero, but those in diastole ranged from 76 to 95 g.mm-2 in the circumferential direction and from 37 to 44 g.mm-2 in the radial direction. The calculated stress suggests that excessive tissue wear and valve failure could occur in the absence of tissue replacement. From radioautographic studies of rat valves, proteins and complex sugars of the valve connective tissues were found to be regularly replaced in patterns predictable from the level of stresses.

Animals

Atrial extension of mitral annular calcification mimicking intracardiac tumor.

Liquefaction necrosis of mitral annular calcification occurs in 3% of autopsied cases. The liquified material can spread intramurally in various directions creating suspicious appearing mass lesions on chest x-ray or echocardiography. An incidential finding of an echogenic left atrial calcified mass in a 57-year-old woman was suspected to be an intracardiac tumor for which she underwent exploratory cardiotomy. Instead, culture-negative liquified pasty material was removed from the posterior left atrial wall adjacent to the calcified mitral annulus. This case illustrates that liquefaction necrosis of mitral annular calcification may spread to contiguous structures and masquerade as an intracardiac tumor. This relatively unknown aspect of mitral annular calcification should be considered in the differential diagnosis of echogenic left atrial mass lesions.

Calcinosis

Reduction of perioperative hemorrhage by anterior mediastinal spray application of fibrin glue during cardiac operations.

A variety of published techniques for the production of concentrated fibrinogen from units of screened single-donor human plasma have led to increasing clinical use of fibrin glue in the United States. We have adapted a method of applying this material with a disposable plastic sprayer. In 20 consecutively treated patients, fibrin glue was sprayed on the anterior mediastinum before closure of the median sternotomy incision. A control group of 20 patients undergoing the identical cardiac operations (13 coronary artery bypass grafting procedures [CABG], 4 valve replacements [including 1 reoperative procedure], and 3 combined valve replacements and CABG) by the same surgeon within a one-year period was chosen for comparison of chest tube outputs. Specifically, chest tube outputs were as follows for treated and untreated patients, respectively: at 12 hours, 461 +/- 40 ml (mean +/- 1 standard error of the mean versus 731 +/- 80 ml; at 24 hours, 714 +/- 73 ml versus 1,016 +/- 109 ml; and at 48 hours, 863 +/- 93 ml versus 1,187 +/- 137 ml. The differences between control and spray chest tube output are statistically significant by unpaired t test (p less than 0.05) at both 12 and 24 hours. Thus, this method can reduce perioperative hemorrhage from the anterior mediastinum after cardiac operations.

Aerosols

Anterolateral thoracotomy as an alternative to repeat median sternotomy for replacement of the mitral valve.

Median sternotomy is the most common approach for repeat cardiac surgery despite the potential complications of cardiac injury. Right anterolateral thoracotomy has been recommended as an alternative for patients undergoing mitral valve replacement, but data supporting one approach over the other do not exist. To compare these procedures, the records of 43 patients who had had a previous median sternotomy and who underwent mitral valve replacement were reviewed. No statistically significant differences between patients undergoing repeat median sternotomy (33 patients) and those undergoing right anterolateral thoracotomy (10 patients) were demonstrable when compared for age, gender, New York Heart Association Functional Class, other diseased valves, urgency of operation, indication for operation, type of valve removed, type of valve implanted, length of postoperative hospitalization, length of operation, days of ventilatory support, length of intensive care unit stay, and survival (90% for thoracotomy group; 76% for median sternotomy group; p, NS). Significant differences between the two groups, favoring right anterolateral thoracotomy, were apparent when comparisons were made for length of perfusion (means, 94.8 min, thoracotomy group; 121.4 min, sternotomy group; p = .03), incidence of reexploration (0%, thoracotomy group; 13%, sternotomy group; p = .001), and blood transfusion (means, 5.3 units, thoracotomy group; 11.4 units, sternotomy group; p = .003). Right anterolateral thoracotomy is an effective alternative to repeat median sternotomy for replacement of the mitral valve in patients who have had a previous median sternotomy.

Heart Valve Prosthesis