Search PubMed⌕ Search

Biomedical subjects

F W Smart

Publications and source records attributed to F W Smart.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cyclosporine-induced hypertension in cardiac transplantation.

Cyclosporine-induced hypertension occurs in more than 90% of patients following cardiac transplantation. This article underlines the clinical characteristics as well as the mechanisms that can be associated with the development of cyclosporine-induced hypertension. In addition, the clinical trials up to date for the treatment of hypertension following cardiac transplantation are discussed. However, in view of the possible long-term sequelae associated with cyclosporine-induced hypertension, further studies to evaluate the long-term efficacy and safety of antihypertensive agents and finally the long-term effects of hypertension on the cardiac allograft are needed.

Antihypertensive Agents↗
PubMed1997

Heterogeneity of cardiac allograft vasculopathy: clinical insights from coronary angioscopy.

OBJECTIVES: With this study, we sought to examine the heterogeneity of cardiac allograft vasculopathy in vivo using coronary angioscopy as an adjunct to intravascular ultrasound, and we evaluated the clinical relations of immunologic and nonimmunologic risk factors with the different forms of cardiac allograft vasculopathy detected angioscopically. BACKGROUND: Intravascular ultrasound detects vascular intimal proliferation accurately but is limited in its ability to delineate morphologic characteristics. Coronary angioscopy can evaluate intimal surface morphology by direct visualization and can differentiate pathologically distinct forms of plaque topography on the basis of color and contour. METHODS: We studied 107 consecutive heart transplant recipients with intravascular ultrasound and angioscopy at the time of their annual angiogram, and we assessed the relation of nonimmunologic and immunologic risk factors to the development of cardiac allograft vasculopathy distinguished angioscopically into a pigmented (yellow) or nonpigmented (white) intimal thickening. We further evaluated the clinical differences in cardiac events among these two forms of angioscopically heterogeneous forms of cardiac allograft vasculopathy. RESULTS: Significant clinical predictors of nonpigmented intimal thickening were advanced donor age and lower mean cyclosporine levels, whereas hyperlipidemia, cumulative prednisone dose and time since transplantation correlated with pigmented intimal hyperplasia. In addition, comparisons between the two angioscopic groups revealed increased intimal thickening, serum cholesterol, low density lipoprotein cholesterol, acute allograft rejection and time since transplantation in the group with pigmented intimal thickening (p < 0.05). With regard to cardiac events, nonpigmented plaque was more frequently found in the sudden death group (53% vs. 20%, p = 0.05), whereas the nonsudden cardiac event group had a significantly higher prevalence of pigmented plaque (80% vs. 47%, p = 0.07). CONCLUSIONS: These findings indicate that cardiac allograft vasculopathy is a heterogeneous disease with varied morphologic expressions with different clinical implications. Furthermore, this investigation provides insight into the cohesive, yet diverse influences of various factors, particularly immunosuppression, in these forms of cardiac allograft vasculopathy.

Adult↗
PubMed1997

Implications for the vascular surgeon with prolonged (3 to 89 days) intraaortic balloon pump counterpulsation.

PURPOSE: The intraaortic balloon pump (IABP) is useful in the treatment of failing hearts. Although most experience with IABPs has been with acute short-term use, the safe duration of therapy and possible complications of long-term IABP use are uncertain. We evaluated the feasibility, management, and complications associated with long-term IABP therapy. METHODS: Fifty consecutive patients with 87 IABPs were evaluated retrospectively. All patients had IABP support for greater than 72 hours. Results and complications were evaluated. RESULTS: The mean duration of IABP support was 23.2 days. There were 21 IABP-related complications in 16 patients: (16 ischemic, three infections, two hemorrhage). The rate of complications was 0.13 per patient-week of support. Significant predictors of complications were total days of IABP support (p < 0.0001), use of multiple IABPs (p < 0.0001), and attempted but unsuccessful percutaneous insertions (p < 0.001). Complications led to 14 vascular procedures (five patch angioplasties, four bypass procedures, two major amputations, one fasciotomy, one groin exploration for hemorrhage, and one removal of an infected Dacron patch). Percutaneous removals had a 14% complication rate compared with none after operative removal (p = 0.02). Thirty-two patients survived (64%). Of the survivors, 27 underwent transplant. CONCLUSIONS: Prolonged IABP therapy is feasible and is associated with an acceptable rate of complications. Operative removal is superior to percutaneous removal. Percutaneous removal should be limited to short-term therapy. There is no need for mandatory removal or site rotation based solely on indwelling time.

Adult↗
PubMed1997

The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation.

OBJECTIVE: The authors present their experience with patients having undergone orthotopic heart transplantation (OHT) in whom surgical conditions subsequently developed that required operative intervention. The incidence, morbidity, and mortality of these procedures are reported. SUMMARY BACKGROUND DATA: Several studies have evaluated the management options of biliary tract disease after OHT. Multiple reports of patients having undergone OHT who subsequently underwent peripheral vascular reconstructions, plastic reconstructive, and thoracic procedures also have been published. METHODS: A chart review of 349 patients who underwent OHT between 1985 and 1996 was conducted to identify surgical procedures that were required in the post-transplant period. Their outcomes are reported. RESULTS: Of 349 patients who underwent OHT, conditions requiring 94 surgical procedures developed in 54 patients (15%). Biliary tract disease developed in 17 patients (5%) who required cholecystectomy, 2 of the 5 patients with acute cholecystitis died. Eight patients (2%) underwent orthopedic procedures with no operative mortality. Flap advancements for sternal wound infections were performed in five patients and four deaths occurred. Seventeen thoracic procedures were performed in 11 patients with an overall mortality of 45%. Twenty-one vascular procedures were performed on 17 patients with 1 delayed death due to a malignancy. Seven patients underwent procedures of the colon and rectum with no mortality. Seven patients underwent repair of inguinal or incisional hernias with no mortality. Various infections occurred with one resultant death after operative intervention. Six procedures were performed for diseases of the small intestine with no resultant mortalities. CONCLUSIONS: Patients having undergone OHT and chronic immunosuppression are at increased risk of having complications develop from infection. Acute cholecystitis and sternal wound infection caused an inordinate risk of complications and death. Malignancies developed in four patients who required surgical intervention. A heightened awareness of coexisting peripheral vascular disease in patients transplanted for ischemic cardiomyopathy should exist. Close screening before surgery and surveillance after surgery to identify risk factors for infection and vascular disease and to screen for malignancies are essential.

Adult↗
PubMed1997

The prognostic impact of immunosuppression and cellular rejection on cardiac allograft vasculopathy: time for a reappraisal.

BACKGROUND: Our current immunosuppressive strategies have made little impact on the development of cardiac allograft vasculopathy, the leading cause of long-term allograft loss. This study sought to evaluate the relationship of cellular rejection and immunosuppressive therapy with the development of morbid events resulting from cardiac allograft vasculopathy. METHODS: The study population consisted of 163 consecutive patients who received heart transplants between January 1990 and May 1994. Data regarding nonimmunologic risk factors (lipids, obesity indexes, hypertension, donor age and sex, cytomegalovirus infection, diabetes mellitus, time after transplantation, and cold ischemic time), immunologic factors (histocompatibility, episodes of treated rejection, and average first-year biopsy rejection score), and immunosuppressive regimens (cumulative prednisone dose, average daily prednisone dose, mean cyclosporine level, average cyclosporine daily dose, cumulative azathioprine dose, and average daily azathioprine dose) were collected and analyzed in all patients. The diagnosis of cardiac allograft vasculopathy was established in all patients by a combination of necropsy, angiography, and intravascular ultrasound examination of the allograft vasculature. Cardiac events were defined as sudden death, myocardial infarction, and need for revascularization. RESULTS: Of all variables assembled, stepwise logistic regression recognized cumulative prednisone dose > 15 gm (relative risk [RR] 5.7; p = 0.01), donor age > 35 years (RR 3.73; p < 0.05), and average biopsy rejection score > 1 (RR 2.77; p < 0.05) as independent adverse predictors of cardiac events. In distinction, average daily cyclosporine dose > 4.5 mg/kg/day was found to confer a protective effect (RR 0.16; p = 0.03). CONCLUSIONS: The development of cardiac events as a result of cardiac allograft vasculopathy is influenced by the interdependence of allograft rejection and the balance of immunosuppression. The clinical implications of these findings point to the need for a reappraisal of our traditional approach to using corticosteroids (acute and maintenance) and cyclosporine (maintenance) in heart transplantation.

Adult↗
PubMed1997

Mechanisms of hypertension in cardiac transplantation and the role of cyclosporine.

The use of cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Several mechanisms, including endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in nitric oxide, and altered cytosolic calcium translocation, have been proposed to underlie cyclosporine-induced hypertension. In addition, other studies have shown activation of the sympathetic nervous system and the renin-angiotensin system, as well as abnormalities in prostaglandin metabolism, as culpable mechanisms. Hemodynamic features of cyclosporine-induced hypertension consist of elevated peripheral vascular resistance, ventricular vascular uncoupling contributing to left ventricular hypertrophy, and abnormalities in the diastolic function of the allograft. Combined calcium-channel blockers and angiotensin-converting enzyme inhibitors have been used for this treatment of this clinical problem, and they achieve blood pressure control in 65% of patients. Moreover, these agents may also be beneficial in preventing development of cardiac allograft vasculopathy, a long-term nemesis in cardiac transplantation.

Animals↗
PubMed1996

Risk factors for early, cumulative, and fatal infections after heart transplantation: a multiinstitutional study.

BACKGROUND AND METHODS: By multivariable analysis, risk factors were identified for initial infection of any type, cumulative infections during the first 6 months and fatal infection among 2210 heart transplant recipients at 30 institutions. RESULTS AND CONCLUSIONS: Of the 1218 infections in 695 patients, bacterial infections were most frequent (47%), followed by viral (42%), fungal (8%), and protozoal (4%). Risk factors for earlier infection included older recipient age (p < 0.0001), ventilator support at time of transplant (p < 0.0001), ventricular assist device at time of transplant (p = 0.02), OKT3 induction therapy (p < 0.0001), donor black race (p = 0.0007), and positive donor cytomegalovirus serology (for cytomegalovirus infection) (p = 0.0007). Cumulative infections during the first 6 months were increased by older recipient age (p < 0.0001), ventilator support at transplant (p = 0.0004), ventricular assist at transplant (p = 0.009), Black donor (p = 0.03), female donor (p = 0.03), and OKT3 induction therapy (p = 0.005). The actuarial freedom from fatal infection was 96% at 1 year and 95% at 3 years. Risk factors for death from infection included very old (p = 0.002) and very young recipients (p = 0.004), ventilator support at time of transplant (p = 0.004), older donor (p < 0.0001), and longer donor ischemic time (p = 0.02). The risk of death from infection within the first 3 months exceeded 20% among older recipients (> 55 years) on ventilator support at time of transplantation who received an older (> 50 years) donor heart.

Actuarial Analysis↗
PubMed1996

Adenovirus-mediated in vivo gene transfer in a rabbit model of allograft vasculopathy.

BACKGROUND: The long-term success of heart transplantation continues to be in jeopardy because of the development of accelerated vascular myointimal proliferation. Transfer of genes encoding products that can modulate the adverse consequences of phenomena that cause myointimal proliferation, into the allograft vessel wall, may modify these pathologic processes. The purpose of this study was to assess the feasibility of gene transfer and to evaluate the duration of gene expression in a rabbit heterotopic aortic transplant model of allograft vasculopathy. METHODS: The abdominal aortas of 32 outbred New Zealand rabbits were harvested and cross-sectionally bisected (n = 64). Six donor and recipient animals were used in a preliminary study to examine neointimal proliferation without accompanying gene transfer. Of the remaining 26 rabbits (52 allografts), one half of each allograft aorta was administered a control solution, while the other half was incubated with a replication-defective, recombinant, adenoviral vector-encoding, cytomegalovirus promoter-regulated beta-galactosidase. After a 20-minute incubation period, bilateral aorto-carotid transplantations were performed in 26 recipient rabbits. All animals received cyclosporine immunosuppression (10 mg/kg/day subcutaneously). The allografts were harvested at 3, 7, 10, 21, and 28 days after transplantation and assayed for beta-galactosidase activity. RESULTS: Neointimal areas showed an initially slow increase for the first 10 days, followed by a rapid increase up to 21 days, and tended to plateau thereafter. Significant beta-galactosidase was apparent in aortic sections dissected from host rabbits for all time points, except at 28 days. At the 21-day time point, the aortic section from one rabbit was positive, whereas the other two remained negative. However, the one positive section showed intense beta-galactosidase activity, suggesting variability in the experimental model. At 28 days, all aortic sections were negative. CONCLUSIONS: Our findings confirm that genes delivered by this method are expressed for the duration of early rapid intimal proliferation in this heterotopic rabbit model of aortic allograft vasculopathy. These findings suggest that this animal model can be used to assess the therapeutic potential of gene transfer at the time of vascular transplantation and may provide a novel therapeutic approach to prevent or ameliorate the genesis of allograft vasculopathy.

Adenoviruses, Human↗
PubMed1995

Predictive model to assess risk for cardiac allograft vasculopathy: an intravascular ultrasound study.

OBJECTIVES: This study was performed to assess the influence and interdependence of immunologic and nonimmunologic risk factors in the development of cardiac allograft vasculopathy. Another primary objective was to establish a clinically useful model for risk assessment of cardiac allograft vasculopathy that would facilitate identifying those heart transplant recipients likely to have severe intimal proliferation and thereby at greater risk for adverse clinical events. BACKGROUND: To our knowledge, no comprehensive intravascular ultrasound study has assessed the relative influences of both nonimmunologic and immunologic factors in the development of cardiac allograft vasculopathy, currently the major limitation to long-term cardiac allograft survival. METHODS: Using a computer-assisted model of stepwise logistic regression, immunologic and nonimmunologic risk factors were evaluated to help identify the development of severe intimal thickening in 101 subjects who underwent intravascular ultrasound. Prospective validation of the findings was performed in a separate consecutive cohort of 37 heart transplant recipients, and the accuracy of this model to predict a relative risk > 1 for the development of severe intimal hyperplasia was assessed. RESULTS: Significant independent predictors of severe intimal hyperplasia in this model included a donor age > 35 years, a first-year mean biopsy score > 1 (a measure not only of severity of rejection, but also of frequency of insidious rejection) and hypertriglyceridemia at two incremental levels of risk (150 to 250 mg/dl [1.70 to 2.83 mmol/liter] and > 250 mg/dl [2.83 mmol/liter]). Based on the absence (0) or presence (1) of these factors, 12 individual categories of risk were ascertained with increasing relative risks and predicted probabilities for severe intimal hyperplasia. Prospective validation of this model revealed a sensitivity and specificity of 70% and 90%, respectively, and the positive and negative predictive values were 85% and 80%, respectively. Additionally, subjects with severe intimal thickening had a four-fold higher cardiac event rate than those without severe intimal proliferation on intravascular ultrasound. CONCLUSIONS: This study establishes a clinically useful predictive model that can be applied to individual heart transplant recipients to assess their risk for developing significant cardiac allograft vasculopathy and, thus, aids in the identification of patients at risk for cardiac events in whom closer surveillance and risk factor modification may be warranted.

Adult↗
PubMed1995

Cardiac allograft vasculopathy: current concepts.

The major cause of late death in cardiac transplant recipients is cardiac allograft vasculopathy, also referred to as cardiac transplant atherosclerosis, which occurs in 15% to 20% of transplant recipients. It differs from traditional atherosclerosis in that it is a concentric and diffuse intimal hyperplastic process; the internal elastic lamina remains intact; calcification is rare; and the disease tends to develop rapidly. Although no definitive reason for cardiac allograft vasculopathy has been established, it has been suggested that it may be caused by a combination of immunologic and nonimmunologic damage to endothelial cells that results in myointimal proliferation. Intravascular ultrasound and coronary angioscopy are more sensitive diagnostic measures of cardiac allograft vasculopathy than coronary angiography. Although retransplantation currently seems to be the only definitive therapy for cardiac allograft vasculopathy, it has shown only fair results.

Coronary Artery Disease↗
PubMed1995

Potentiation of endothelium-dependent hyperpolarization to serotonin by dietary intake of NC 020, a defined fish oil, in the porcine coronary artery.

The membrane potential of vascular smooth muscle cells of the porcine coronary artery was measured to examine whether serotonin evokes endothelium-dependent hyperpolarization, and if it does, whether the electrical responses are modulated by the chronic dietary intake of NC 020, a defined fish oil. Serotonin induced transient, concentration-dependent hyperpolarizations of coronary arterial smooth muscle cells. The hyperpolarization was observed in tissues with, but not in those without endothelium. In coronary arteries obtained from pigs fed chronically with NC 020, serotonin induced significantly larger hyperpolarizations than those observed in control arteries. These results suggest that endothelium-dependent hyperpolarization may contribute to the endothelium-dependent relaxation evoked by serotonin and to its potentiation by the dietary intake of fish oil (NC 020).

Animals↗
PubMed1995

New developments in the diagnosis and management of cardiac allograft vasculopathy.

The major cause of late death in cardiac transplant recipients is cardiac allograft vasculopathy, also referred to as cardiac transplant atherosclerosis, which occurs in as many as 45% of transplant recipients who survive longer than 1 year. It differs from typical atherosclerosis in that intimal hyperplasia is concentric and diffuse, the internal elastic lamina remains intact, calcification is rare, and the disease tends to develop rapidly. Intravascular ultrasound and coronary angioscopy are more sensitive diagnostic measures of cardiac allograft vasculopathy than is coronary angiography. Although retransplantation at present seems to be the only definitive therapy for cardiac allograft vasculopathy, it has shown only fair results. Recent studies have suggested that calcium entry blockers and angiotensin-converting enzyme inhibitors may play a beneficial role in delaying the progression of cardiac allograft vasculopathy.

Angioplasty, Balloon, Coronary↗
PubMed1995

Lung transplantation in Louisiana: report of the first twenty lung transplants performed in the state.

Lung transplantation is a successful alternative treatment for a variety of end-stage lung diseases. The first 20 lung transplants performed in Louisiana between November 1990 and July 1994 are reported from Ochsner Foundation Hospital. Transplant procedures included 1 heart-lung, 11 bilateral sequential lung, and 8 single-lung transplants in 8 males and 11 females (1 retransplantation). The average age was 38 years (range 7-60), and the median waiting time was 34.5 days (range 1-329). Indications for transplant included emphysema, pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. Overall 1-year and 3-year survival were 65.0% and 58.5%, respectively. Infection was the major cause of morbidity and mortality. Rejection episodes were observed but treated successfully in all 20 patients. Lung transplantation has proved to be a successful treatment for a variety of severely limiting and terminal pulmonary conditions for patients in our state.

Adolescent↗
PubMed1994

Cardiac allograft vasculopathy assessed by intravascular ultrasonography and nonimmunologic risk factors.

The genesis of cardiac allograft vasculopathy has been linked to nonimmunologic endothelial injury. Studies evaluating the role of nonimmunologic risk factors have thus far been limited to angiographic assessment. Intravascular ultrasound can detect cardiac allograft vasculopathy before it becomes angiographically evident. To assess the influence of nonimmunologic risk factors in the development of cardiac allograft vasculopathy, we studied 101 consecutive cardiac transplant recipients who underwent intracoronary ultrasound imaging during routine, annual coronary angiography. Based on the severity of intimal thickening, patients were divided into 2 groups: group 1 = minimal, mild, or moderate intimal thickness; and group 2 = severe intimal thickness. Cardiac transplant recipients with severe intimal thickness had higher levels of total cholesterol (267 +/- 70 vs 227 +/- 41 mg/dl, p = 0.0008), low-density lipoprotein cholesterol (187 +/- 47 vs 139 +/- 31 mg/dl, p = 0.0001), and triglycerides (237 +/- 75 vs 182 +/- 88 mg/dl, p = 0.0004), a higher percentage of weight gain (12 +/- 4% vs 8 +/- 5%, p = 0.0001), a larger body mass index (30 +/- 4 vs 25 +/- 3, p = 0.0001), and older donor age (27 +/- 5 vs 23 +/- 7 years, p = 0.005) than recipients with mild or moderate intimal thickness. Multiple regression analysis established that total cholesterol, low-density lipoprotein cholesterol, triglyceride levels, obesity indexes, donor age, and years following cardiac transplantation (p < 0.01) were independent predictors of the severity of intimal thickening, and thus the severity of cardiac allograft vasculopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Exploring the minimal dose of amiodarone with antiarrhythmic and hemodynamic activity.

Amiodarone in doses of 200 to 400 mg/day has shown promise in secondary prevention trials for reducing mortality in patients surviving myocardial infarction who have complex ventricular ectopy or nonsustained ventricular tachycardia, or both. In an attempt to explore the lowest dose of amiodarone with antiarrhythmic and hemodynamic activity, we studied 48 patients (mean age 53 +/- 11 years, ejection fraction 23 +/- 9%, clinical heart failure in 85%) with nonsustained ventricular tachycardia. This was a 3-month, randomized, parallel, double-blind pilot study comparing placebo (n = 16) with amiodarone 50 mg/day (n = 15) and 100 mg/day (n = 17). Patients randomized to amiodarone received a mean loading dose of 422 mg/day for the first study week. At the end of the 12 weeks, amiodarone (100 mg) significantly reduced ventricular premature complexes (177 +/- 64 to 98 +/- 38/hour), couplets (8 +/- 3 to 4 +/- 2/hour), and runs of nonsustained ventricular tachycardia (13 +/- 7 to 3 +/- 2/day), all p < 0.01 versus baseline. In addition, 10 of 14 patients taking 100 mg/day had total suppression of nonsustained ventricular tachycardia compared with 4 of 15 taking placebo, p = 0.021. Left ventricular ejection fraction improved by > or = 7% (absolute) in 11 of 29 patients taking amiodarone as compared with only 1 of 15 placebo patients (p = 0.02). In these 11 patients with the greatest measurable hemodynamic improvement, amiodarone significantly increased ejection fraction (21 +/- 7% to 33 +/- 11%, p < 0.01), stroke volume index (28 +/- 9 to 40 +/- 7 ml/m2, p < 0.01) and decreased end-systolic volume index (116 +/- 48 to 92 +/- 44 ml/m2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

High-risk surgery as an alternative to transplantation.

Between April 1992 and April 1994, 185 patients were waiting for a cardiac transplant at our institution. Transplantation was performed in 118 of these patients. Twenty-six patients (14%) died while awaiting a donor heart: 13 of these were in the intensive care unit on multiple inotropic medications, mechanical support, or both; another 13 were either in the hospital on a single inotropic medication or at home with or without inotropic support. The remaining 41 patients were still awaiting transplantation at the end of the study period. During the same interval, 20 comparably ill patients who were referred to our institution for transplantation were considered for high-risk conventional surgical procedures. These patients underwent clinical evaluation to determine whether they had viable muscle that was salvageable and electrophysiologic status that was alterable. On this basis, these 20 patients underwent a variety of combined high-risk procedures. Two patients died; the operative mortality was 5% and the cumulative mortality was 10%. We conclude that these initial results support our original impression that mortality rates are higher in patients waiting for cardiac donation than in patients undergoing high-risk surgical procedures. Therefore, we will continue to investigate high-risk conventional surgery as an alternative to cardiac transplantation.

Aged↗