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D D Stapleton

Publications and source records attributed to D D Stapleton.

At least 37 records · Page 2Linked to original sources
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

Autoradiographic assessment of blood flow heterogeneity in the hamster heart.

OBJECTIVE: Provide regional flow measurement in the hearts of small mammals using a new, higher-resolution technique based on the deposition of a molecular marker. METHODS: We determined the instantaneous extraction and retention of the "molecular microsphere" radiolabeled desmethylimipramine in retrogradely perfused hamster hearts. In a separate series of experiments, autoradiography was used to measure regional myocardial deposition densities in hamster hearts of about 0.5 g with spatial area resolution of 16 x 16 microns. RESULTS: Radiolabeled desmethylimipramine is almost 100% extracted during a single transcapillary passage and is retained in the tissue for many minutes. Autoradiographic images demonstrated a spatial flow heterogeneity with standard deviations of 31 +/- 4% of the mean flow (N = 5) in 16 x 16 x 20-micronm3 voxels. This is equivalent to the projections made using fractal relationships from cruder observations obtained with microspheres in the hearts of baboons, sheep, and rabbits. CONCLUSIONS: Autoradiography using a molecular deposition marker provides quantitative information on myocardial flow heterogeneities with resolution at the size of cardiac myocytes. Because the regions resolved are smaller than the volume of regions supplied by single arterioles, the results must slightly exaggerate the true heterogeneity of regional flows.

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↗
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

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↗
PubMed1994

Influence of donor and recipient gender on cardiac allograft vasculopathy. An intravascular ultrasound study.

BACKGROUND: Cardiac allograft vasculopathy remains the leading limitation to long-term survival after cardiac transplantation. While the influence of donor and recipient gender in the pathogenesis of cardiac vasculopathy is still poorly understood, studies have indicated that female allografts may be at higher risk for the development of cardiac allograft vasculopathy. The purpose of this study was to characterize the influence of donor and recipient gender on the early genesis of cardiac allograft vasculopathy by using intravascular ultrasound. METHODS AND RESULTS: Thirty-six consecutive cardiac transplant recipients were divided into three groups on the basis of donor and recipient gender as follows: group 1, female donor and male recipient (n = 8); group 2, male donor and female recipient (n = 7); and group 3, male donor and male recipient (n = 21). The three groups were similar with regard to donor and recipient age, weight, body surface area, serum lipids, left ventricular function, histocompatibility, cellular and vascular rejection, and cytomegalovirus infection. To precisely quantitate the extent of cardiac allograft vasculopathy, intravascular ultrasound was performed in all patients at the time of first annual angiography. Intimal thickening and intimal index were accurately quantitated by intravascular ultrasound. Intimal thickening was significantly greater in group 1 (0.55 +/- 0.15 mm) than in group 2 (0.18 +/- 0.04 mm) or group 3 (0.29 +/- 0.05 mm) (P < .05). In addition, the intimal index was greater in group 1 (0.20 +/- 0.04) than in group 2 (0.07 +/- 0.02) or group 3 (0.15 +/- 0.02) (P < .01, group 1 versus group 2). CONCLUSIONS: Male recipients of female allografts have a higher degree of vascular intimal hyperplasia detected by intravascular ultrasound at 1 year after heart transplantation. These findings indicate that donor and recipient gender influences the early genesis of cardiac allograft vasculopathy.

Age Factors↗
PubMed1994

Cardiovascular adaptation to cyclosporine-induced hypertension.

Arterial hypertension is a complication of cyclosporine therapy in heart transplant recipients. We studied cardiovascular adaptation to cyclosporine-induced hypertension by determining haemodynamic and echocardiographic indexes in 25 cardiac transplant recipients matched by mean arterial pressure, age, sex, height and weight to 25 patients with established essential hypertension. Twenty-five normotensive subjects matched by age, sex and body habitus were used as controls. Systemic vascular resistance was 15% higher (P = 0.07) and cardiac and stroke volume indices were 20% and 25% lower (P < 0.01), respectively, in the hypertensive cardiac transplant recipients compared with patients with essential hypertension. Patients with essential hypertension and hypertensive cardiac transplant recipients had greater posterior wall thickness and left ventricular mass index than normotensive subjects (P < 0.01); however, hypertensive cardiac transplant recipients had a greater left ventricular mass (245 +/- 7 vs. 223 +/- 8 g, P < 0.05) than patients with markedly established essential hypertension. Left ventricular ejection fraction was significantly lower in hypertensive cardiac transplant recipients when compared with either normotensives or patients with established essential hypertension. These results indicate that established essential and cardiac transplant hypertension are associated with markedly increased systemic vascular resistance. However, after heart transplantation, hypertension is associated with higher systemic vascular resistance, lower cardiac output, stroke volume and stroke work compared with patients with established essential hypertension at the same level of mean arterial pressure. The cardiac adaptation to cyclosporine-induced hypertension has more severe concentric left ventricular hypertrophy and impaired left ventricular systolic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Assessment of intracoronary morphology in cardiac transplant recipients by angioscopy and intravascular ultrasound.

Percutaneous coronary angioscopy and intravascular ultrasound are sensitive intravascular imaging methods for detecting early changes in coronary morphology in cardiac transplant recipients. To compare the 2 imaging modalities, 29 consecutive cardiac transplant recipients underwent percutaneous coronary angioscopy and intravascular ultrasound during annual coronary angiography. Surface morphology, presence of plaque, and percent area stenosis were determined with each procedure. Percutaneous coronary angioscopy was more sensitive in detecting the presence of plaque and stenosis than was coronary angiography (plaque: 79 vs 10% [p < 0.001]; and stenosis: 24 vs 3% [p < 0.01]). Intravascular ultrasound was also more sensitive in detecting plaque (76 vs 10%; p < 0.001) and stenosis (45 vs 3%; p < 0.001) than was coronary angiography. Although both angioscopy and ultrasound identified atherosclerotic plaque, only percutaneous coronary angioscopy could show luminal surface morphology and pigmentation of the plaque. Conversely, ultrasound could detect calcification and presence of intimal thickening, and was more accurate in assessing the severity of stenosis (45 vs 24%; p < 0.01). In conclusion, percutaneous coronary angioscopy and intravascular ultrasound, in conjunction, provide information not only regarding the appearance of the luminal surface, but also quantitative information regarding the structure and extent of the disease in the coronary artery wall.

Adult↗
PubMed1993

Prior arterial injury enhances luciferase expression following in vivo gene transfer.

We determined the time course of gene expression following DNA/Lipofectin transfection of normal or previously injured arterial segments using direct intraluminal infusion following surgical exposure. Constructs possessing the firefly luciferase cDNA regulated by Simian virus 40, Rous sarcoma virus, or alpha-actin promoter were incubated together with Lipofectin for 30 minutes. Arterial segments were assayed for luciferase activity following harvest at 2-21 days. Without prior injury, luciferase activity was only 2.5-fold greater than background two days following gene transfer. Arterial injury three days before gene transfer resulted in luciferase activity 12.5-fold over background levels. This observation has clinical implications with regard to gene therapy following angioplasty, a procedure that is associated with endothelial cell denudation and smooth muscle cell proliferation. Maintenance of gene expression for several days could ameliorate the early smooth muscle migration and proliferation following arterial injury.

Actins↗
PubMed1993

Induction immunosuppression with the monoclonal antibody OKT3 after cardiac transplantation.

The routine use of monoclonal induction immunosuppression with OKT3 after orthotopic heart transplantation remains controversial. This study examined the clinical response of prophylactic monoclonal induction immunosuppression versus standard triple-drug immunosuppression in 41 patients who underwent orthotopic heart transplantation from January 1989 to December 1990 at this institution. Of these, eight received monoclonal induction immunosuppression for a period of 10 to 14 days. All patients received identical triple-drug immunosuppression with the exception of cyclosporine starting on the fifth postoperative day in those who received OKT3. At 6 months the duration of hospitalization, freedom from rejection, incidence of infection requiring hospitalization, and serum creatinine in the monoclonal induction immunosuppression and triple-drug groups were compared. It was found that the length of hospital stay in the OKT3 group was 14.3 +/- 4.5 days, compared with 14.7 +/- 4.7 days in the triple-drug group and that freedom from rejection was 66% in the OKT3 group compared with 75% in the triple-drug group. In addition, it was found that the incidence of infection was 36% in the OKT3 group compared with 38% in the triple-drug group and that serum creatinine at 6 months was 1.36 +/- 0.26 mg/dl in the OKT3 group compared with 1.45 +/- 0.73 mg/dl in the triple-drug group. Finally, patient survival at 1 year for the monoclonal induction immunosuppression group was 100% compared with 91% for the triple-drug group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1993

Cyclosporine-induced hypertension. Efficacy of omega-3 fatty acids in patients after cardiac transplantation.

BACKGROUND: Cyclosporine-induced hypertension may be related to vasoconstriction of the afferent arterioles in the glomeruli caused by changes in the prostaglandin profile. omega-3 Fatty acids have demonstrated vasodilatory properties related to a favorable effect in the prostaglandin profile. The purpose of this study was to evaluate the antihypertensive effects of oral supplementation with omega-3 fatty acids in cyclosporine-treated cardiac transplant recipients. METHODS AND RESULTS: The study consisted of 20 orthotopic cardiac transplant recipients with hypertension who were prospectively randomized in a double-blind fashion to receive either omega-6 fatty acids (placebo group, n = 10) or omega-3 fatty acids (treatment group, n = 10). Blood pressure, systemic hemodynamics, two-dimensional guided M-mode and Doppler echocardiography, and laboratory values (serum creatinine, lipid profile) were recorded at baseline and at 12 weeks. The treatment group demonstrated a significant reduction in mean arterial pressure (120 +/- 7 versus 102 +/- 7 mm Hg; P = .0001) associated with a decrease in systemic vascular resistance (2107 +/- 45 versus 1426 +/- 60 dynes.sec.cm-5; P = .0001). No changes in indexes of left ventricular structure and function occurred, except for a modest decrease in deceleration time (211 +/- 10 versus 182 +/- 12 milliseconds; P = .05), an index of left ventricular diastolic function. CONCLUSIONS: omega-3 Fatty acids (3 g/d) reduce blood pressure by decreasing systemic vascular resistance and, therefore, can be used as an adjuvant for the treatment of hypertension in cyclosporine-treated cardiac transplant recipients. Their vasodilatory effect may be related to a beneficial change in the prostaglandin profile.

Antihypertensive Agents↗
PubMed1993

Cardiac transplantation: an overview of recipient selection.

Cardiac transplantation is an accepted treatment for end-stage heart disease. Potential recipients are carefully screened in order to best place the short supply of donor organs with the best recipient. The success of heart transplantation in the United States today is directly related to careful donor and recipient selection criteria and improvements in immunosuppression.

Age Factors↗
PubMed1993

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, and calcification is rare. The distal portion of the coronary vessel is the earliest to occlude, with occlusion occurring rapidly. Sometimes a low grade vasculitis is also present. There is no definitive reason for cardiac allograft vasculopathy occurring though it has been suggested that it may actually be caused by immunologic and nonimmunologic damage to endothelial cells resulting in myointimal proliferation. Intravascular ultrasound and coronary angioscopy seem to be a more sensitive diagnostic measure of cardiac allograft vasculopathy than coronary angiography. To date, retransplantation seems to be the only definitive therapy for cardiac allograft vasculopathy. But only fair results are being seen with this procedure.

Coronary Artery Disease↗
PubMed1992

Current issues in advanced heart failure.

In the past 50 years, an increased understanding of the pathophysiologic mechanisms associated with the development of heart failure has produced a more precise treatment of this syndrome. The effects of the agents used for the treatment of patients with advanced heart failure have been summarized in this article and demonstrate the importance of vasodilatory drugs on the survival and progression of dilated cardiomyopathy.

Cardiomegaly↗
PubMed1992

Cardiac transplantation: clinical aspects of recipient selection.

The improved outcome following cardiac transplantation has produced changes in the traditional criteria for potential candidates. We have analyzed these changes and the clinical aspects involved in the selection process, which are of critical importance to assure an excellent result of cardiac transplantation in patients with advanced heart failure.

Contraindications↗
PubMed1991

Cardiac transplantation. How recipients are selected.

Your patients with heart disease may ask about transplantation. Those who are potential candidates need a physician who knows enough about the selection system to get them into it. For other patients, an explanation of why the procedure is contraindicated in their case can help them refocus on compliance with recommended therapy. The authors discuss the principles of recipient selection.

Age Factors↗