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Biomedical subjects

R C Starling

Publications and source records attributed to R C Starling.

At least 55 records · Page 3Linked to original sources
PubMed1998

Partial left ventriculectomy and mitral valve repair for end-stage congestive heart failure.

OBJECTIVE: Partial left ventriculectomy (PLV), pioneered by Batista, has been proposed as an alternative treatment strategy in patients with refractory congestive heart failure. In order to analyze the midterm outcome of PLV and mitral valve (MV) repair and stratify patients according to risk, we prospectively studied 57 consecutive patients who underwent this procedure at the Cleveland Clinic Foundation (CCF). METHODS: Patients had a mean age of 53 years and were predominantly males (74%). In 95% the etiology of heart failure was idiopathic dilated cardiomyopathy. All patients had a left ventricular end diastolic diameter of >7cm and were in New York Heart Association (NYHA) functional classes III and IV. A total of 54 patients (95%) were awaiting heart transplantation. Preoperatively, requirements included inotropes in 23 (40%), intraaortic balloon pump counterpulsation in 3 (5.3%), and left ventricular assist device placement (LVAD) in 1 (1.8%). Concomitant procedures included MV repair (55 patients), MV replacement (2), tricuspid valve repair (34 patients), coronary artery bypass graft (CABG) (5), and aortic valve repair or replacement (1 patient each). RESULTS: Measurements preoperatively and at 3 months demonstrated improvement in left ventricular ejection fraction (14.4 +/- 7.7-23.2 +/- 10.7%, P < 0.001), left ventricular end diastolic volume (254 +/- 85-179 +/- 73 ml, P < 0.001) and left ventricular end diastolic diameter (8.4 +/- 1.1-6.3 +/- 0.9 cm, P < 0.001). Peak oxygen consumption (MVO2) increased from 10.6 +/- 3.9 to 15.3 +/- 4.5 ml/kg per min (P < 0.001). Cardiac index did not change (2.2 l/min per m2), although 40% had been on inotropes preoperatively and none were on inotropes at 3 months. NYHA functional class improved from 3.6 +/- 0.5 preoperatively to 2.2 +/- 0.9 at 3 months (P < 0.001). LVAD support was required as rescue therapy in 11 patients (17%). Actuarial freedom from procedure failure, defined as death or relisting for transplant, was 58% at 1 year. Hospital mortality was 3.5% (n = 2). On follow-up, there were 7 late deaths (including 3 sudden deaths) giving an actuarial survival of 82% at 1 year. Multivariate risk factor analysis revealed that age less than 40 years was associated with failure (P = 0.02). CONCLUSIONS: Although PLV with MV repair is now a surgical option in the treatment of end-stage congestive heart failure, caution is advised as early failures are unpredictable and mechanical support may be required as rescue therapy. Better risk stratification and patient selection may improve outcome. Further study is required to determine the procedure's exact role in the treatment of congestive heart failure.

Adolescent↗
PubMed1998

Vascular rejection post heart transplantation is associated with positive flow cytometric cross-matching.

OBJECTIVE: Use of flow cytometry cross-matching for measurement of donor-specific alloreactivity and monitoring anti-donor antibodies is well established. This study was performed to determine (1) its accuracy as a marker of vascular rejection, (2) its correlation with post-transplant outcome and (3) its ability to monitor highly sensitized patients requiring antibody removal with plasma exchange. METHODS: Serial serum samples from 99 heart transplant recipients were examined for the presence of anti-donor antibodies of the IgG class that were reactive with T and/or B cryopreserved donor lymphocytes. A sub-group of 20 HLA sensitized patients required plasma exchange to remove the anti-HLA antibodies and were monitored with flow cytometry cross-matching to assess the degree of antibody removal. RESULTS: Positive T-cell reactions were observed in 26 patients and positive B-cell reactions in 54. Twenty patients had vascular rejection. A significantly larger number of patients with a positive flow cytometry cross-match had vascular rejection (42% versus 12% for T-cell reactions, and 32% versus 7% for B-cell reactions; P = 0.002 each). Of the patients who had vascular rejection, 11 had a positive T-cell reaction (flow cytometry cross-match sensitivity of 55%), and 17 had a positive B-cell reaction (sensitivity of 85%). Of the 79 patients who did not develop vascular rejection, 64 had a negative T-cell reaction (specificity of 81%), and 42 had a negative B-cell reaction (specificity of 53%). The actuarial 2-year survival estimates were significantly higher in patients with negative T-cell reactions (90% versus 75%; P = 0.04), and B-cell reactions (95% versus 78%; P = 0.02). In the highly sensitized subgroup (n = 20) the effectiveness of plasma exchange to decrease anti-HLA antibody reactivity was a strong predictor of outcome. For patients in whom plasma exchange (PE) reduced anti-donor reactivity, 1-year survival was 87% compared to 25% in those whom PE did not reduce the level of antibody binding as assessed with flow cytometry cross-matching (P < 0.0001). CONCLUSIONS: Flow cytometry cross-matching provides a valuable marker for the detection of vascular rejection after cardiac transplantation. Quantitative measurements may allow evaluation of the efficacy of treatment modalities employed in the management of vascular rejection in an attempt to improve outcome.

Actuarial Analysis↗
PubMed1998

Human myocardial ATP content and in vivo contractile function.

The study was designed to characterize the relationship between the metabolite content of human cardiac muscle and in vivo cardiac function. ATP, total adenine nucleotides, and NAD were quantified in human myocardial biopsies using high performance liquid chromatography. Right ventricular endomyocardial biopsies were obtained from 43 patients with dilated cardiomyopathy, 6 with restrictive cardiomyopathy, 10 with normal systolic and diastolic function, and from 24 cold preserved human donor hearts. Transmural samples of failing right and left ventricular free walls were obtained during cardiac transplantation surgery in 8 patients. ATP, total adenine nucleotides, and NAD were similar in the cold-preserved donor hearts and in right ventricular endomyocardial biopsies from the 10 individuals with normal systolic and diastolic function. In contrast, these values were significantly depressed in tissue samples from patients with dilated or restrictive cardiomyopathy. There was a significant correlation between ATP and pulmonary capillary wedge pressures but not ejection fractions. Declines in the sizes of myocardial ATP, adenine nucleotide, and pyridine nucleotide pools in the human myocardium are associated primarily with diastolic but not systolic dysfunction.

Adenosine Triphosphate↗
PubMed1997

Morphometric analysis of neointimal formation in murine cardiac grafts: III. Dissociation of intestitial fibrosis from neointimal formation.

BACKGROUND: This study examined the relationship between transplant vascular sclerosis (TVS) and tissue fibrosis, features of chronic rejection that can develop rapidly in accepted heterotopic murine cardiac allografts. METHODS: The rate of development of interstitial fibrosis or TVS development was determined by computerized analysis of tissue sections from DBA/2-->C57BL/6 heterotopic cardiac allografts after immunosuppression with gallium nitrate. RESULTS: In accepted cardiac allografts, neointimal fibrosis developed by 30 days after transplant, whereas TVS was minimal by day 30, and maximal by day 60. Variable levels of fibrosis were found throughout the allografts. DBA/2-->DBA/2 cardiac isografts never displayed TVS in this time period, but displayed allograft-like fibrosis within 60 days of transplantation. CONCLUSIONS: Interstitial fibrosis can be dissociated from the TVS development in this experimental model of chronic cardiac allograft rejection. Apparently, it is caused, at least in part, by alloantigen-independent factors other than TVS-related tissue ischemia.

Animals↗
PubMed1997

Morphometric analysis of neointimal formation in murine cardiac allografts: II. Rate and location of lesion development.

BACKGROUND: Transplant vascular sclerosis (TVS) is manifested in transplanted human and murine hearts as a concentric, intimal lesion. The purpose of this study was to characterize the rate, location, and intensity of developing TVS lesions in murine cardiac allografts using quantitative morphometric analysis. METHODS: Murine cardiac allografts, treated with the immunosuppressant gallium nitrate, were explanted at 30, 60, and 90 days after transplant. The grafts were histologically stained and evaluated for intimal thickening by deriving a neointimal index (NI) using a computerized image-analysis system. RESULTS: In cardiac allografts, mild vascular lesions of varying NI were detectable by day 30 and lesion severity increased significantly by day 60. Thereafter, average lesion severity stabilized, although the percentage of affected vessels continued to increase from day 30 to day 90. In contrast, day-90 cardiac isografts showed little to no TVS development. Vascular lesions developed randomly without regard for vessel location or size. TVS developed more regularly in vessels of the interventricular septum than in the right or left ventricular walls. The degree of TVS development fluctuated along the length of individual vessels, even as late as 90 days after transplant. The smaller vessels (<85 microm in diameter) appeared to occlude more quickly than the larger vessels. CONCLUSIONS: TVS developed reproducibly in a random pattern throughout cardiac allografts over a 1-month to 3-month period after transplant. This development can be quantitatively monitored by computerized morphometric analysis. In general, under these experimental conditions, 30-day cardiac allografts seem to provide a useful experimental model for studying early aspects of TVS, whereas 60-day allografts may be better suited for analysis of advanced TVS.

Animals↗
PubMed1997

Morphometric analysis of neointimal formation in murine cardiac allografts.

BACKGROUND: Transplant vascular sclerosis is expressed in transplanted human and murine hearts as a concentric intimal thickening. The purpose of this study was to characterize the location, distribution, and intensity of transplant vascular sclerosis in murine cardiac allografts using computerized morphometric analysis. METHODS: Murine cardiac allograft recipients were treated with the immunosuppressant gallium nitrate to promote graft survival. The grafts were removed at 60 days after transplantation and histologically stained. The coronary arteries were analyzed for intimal thickening using a neointimal index (NI) derived with a computer imaging system. RESULTS: A cross-section taken from the middle of a cardiac allograft showed four major coronary arteries, each with widely different NI values (65, 0, 92, and 0). The same four vessels in two other grafts also showed highly variable NI values, but different patterns of vessel involvement. Next, NI values were determined along the length of a single vessel from aorta to apex. This revealed variable, fluctuating intimal thickening along the length of the vessel. In general, arteries from the aortic versus apical regions of the grafted hearts expressed similar amounts of intimal thickening (analysis of variance, P=0.4826). Finally, a method was devised to quantitate intimal thickening from a sampling of three tissue cross-sections taken from the middle of each cardiac allograft. This value was statistically indistinguishable from values obtained by analysis of intimal thickening in multiple sections covering the entire heart (P=0.6734, 0.9021, and 0.1474). CONCLUSIONS: Intimal thickening in the coronary arteries of murine cardiac allografts appears to be variable in terms of location, distribution, and intensity. This is true for different regions of the same vessel, different vessels in the same heart region, and the same vessels in different cardiac allografts.

Animals↗
PubMed1997

Permanent mechanical circulatory support with an implantable left ventricular assist device.

A 67-year-old man had end-stage ischemic cardiomyopathy. He had had two previous coronary bypass operations and a previous left ventricular aneurysmectomy. In December 1995 he underwent vented-electric HeartMate LVAD insertion as an alternative to transplantation. He was discharged from the hospital 13 days after the operation, and 5 months postoperatively he had returned to New York Heart Association functional class II.

Aged↗
PubMed1997

Early results with partial left ventriculectomy.

OBJECTIVE: We sought to determine the role of partial left ventriculectomy in patients with dilated cardiomyopathy. METHODS: Since May 1996 we have performed partial left ventriculectomy in 53 patients, primarily (94%) in heart transplant candidates. The mean age of the patients was 53 years (range 17 to 72 years); 60% were in class IV and 40% in class III. Preoperatively, 51 patients were thought to have idiopathic dilated cardiomyopathy, one familial cardiomyopathy, and one valvular cardiomyopathy. As our experience accrued we increased the extent of left ventriculectomy and more complex mitral valve repairs. For two patients mitral valve replacement was performed. For 51 patients the anterior and posterior mitral valve leaflets were approximated (Alfieri repair); 47 patients also had ring posterior annuloplasty. In 27 patients (51%) one or both papillary muscles were divided, additional left ventricular wall was resected, and the papillary muscle heads were reimplanted. RESULTS: Echocardiography showed a significant decrease in left ventricular dimensions after resection (8.3 cm to 5.8 cm), reduction in mitral regurgitation (2.8+ to 0), and increase in forward ejection fraction (15.7% to 32.7%). Cardiac index did not increase significantly (2.2 to 2.4 L/min per square meter). Eight patients (15%) required a perioperative left ventricular assist device; one died and was the only perioperative mortality (1.9%). At 11 months, actuarial survival was 87% and freedom from relisting for transplantation was 72%. CONCLUSIONS: Improved selection criteria are necessary to avoid early failures, and much more follow-up and analyses of data are mandatory. However, the operation may become a biologic bridge, or even alternative, to transplantation.

Cardiomyopathy, Dilated↗
PubMed1997

Radical alternatives to transplantation.

Because of the lack of donor hearts, thousands of patients annually die with end-stage heart failure. Surgical alternatives to transplantation include partial left ventricular resection, dynamic cardiomyoplasty, and left ventricular assist devices. Partial left ventricular resection is an innovative procedure in which the heart is surgically reduced in size and cardiac function is dramatically improved immediately after surgery. Long-term follow-up is required to determine the success of this procedure. Dynamic cardiomyoplasty has been in use for 12 years. In properly selected patients, it results in significant amelioration of symptoms and improvement in quality of life. Improved survival and objective physiologic improvement have not been documented. A randomized trial is now in progress to evaluate survival with surgical therapy versus survival with medical therapy. Left ventricular assist devices have been shown to be extremely effective as a short- and long-term "bridge" to heart transplantation in mortally ill patients. They are not approved for long-term support as an alternative to transplantation in the United States, but a randomized trial is now underway to compare the efficacy of these devices with the efficacy of medical therapy in New York Heart Association functional class IV patients.

Cardiomyoplasty↗
PubMed1996

Prospective study of the circadian pattern of blood pressure after heart transplantation.

BACKGROUND: Previous reports indicate that heart transplant recipients lack a normal nocturnal decline in blood pressure. This prospective study was designed to determine the evolution of circadian blood pressure patterns after heart transplantation. METHODS: Twenty-four-hour ambulatory blood pressure and heart rate was measured in eight heart transplant recipients early (47 +/- 35 days) and late (740 +/- 10 days) after transplantation. RESULTS: Early transplant recordings and the normal control group recordings showed similar daytime systolic blood pressure but had different nighttime systolic blood pressure (138 +/- 15 mm Hg versus 112 +/- 9 mm Hg, p = 0.0002). The percent nocturnal change in systolic blood pressure showed a nocturnal increase in blood pressure in the early recordings versus a decrease in the healthy subjects (+4 +/- 2.7 versus -13 +/- 5.4, p < 0.0001). The late recordings showed a significant decrease in the nighttime systolic blood pressure (138 +/- 15 mm Hg versus 119 +/- 7 mm Hg, p = 0.011). The percent nocturnal change in systolic blood pressure was also significantly different between the early and late recordings (+4 +/- 2.7 versus -9 +/- 9, p = 0.0082) indicating a return of a nocturnal decline in systolic blood pressure. Similar patterns in diastolic blood pressure were observed. No significant change in the percent nocturnal change in heart rate occurred (-10 +/- 4.1 versus -7 +/- 5.5). CONCLUSIONS: Prospective follow-up of this heart transplant population showed that diurnal blood pressure variation is restored in some patients; diurnal variation is not related to corticosteroids, cyclosporine, or heart rate.

Antihypertensive Agents↗
PubMed1996

Morphometric and immunocytochemical analysis of coronary arterioles in human transplanted hearts.

BACKGROUND: Heart transplant vascular sclerosis has been characterized in epicardial coronaries of human transplanted hearts. The purpose of this study was to analyze coronary arterioles (< 100 microns in diameter) within endomyocardial biopsy specimens from heart transplant recipients for the presence of disease. METHODS: The morphologic compartments of trichrome-stained vessels were quantified by means of computer imaging to measure the percentage of stenosis of 164 arterioles from 30 transplant recipients over time. The arterioles were divided into three groups based on their biopsy date after transplantation: early (0 to 6 months), middle (6 to 18 months), and late (18 to 36 months). The percentage of stenosis of arterioles from a control group of nondiseased hearts was compared with the grafts. Also, arterioles from heart transplant recipients were immunohistochemically labeled with an antibody, PC10, specific for proliferating cell nuclear antigen. The arterioles were immunocytochemically labeled with an antibody specific for vascular smooth muscle alpha-actin and the fluorescent signal was analyzed. RESULTS: The percentage of stenosis was not significantly different among the early, middle, late, and control groups. Vessels from the early, middle, and late groups did not show binding of the PCNA antibody. The antibody signal intensity and amount of alpha-actin within each vessel was significantly higher in the late groups as compared with the early and middle groups. CONCLUSIONS: The coronary microvasculature of human transplanted hearts does not exhibit intimal thickening or cellular proliferation within 3 years after transplantation. However, as shown by an increase of smooth muscle alpha-actin over time, vascular remodeling may occur in response to cytokines released as a result of injury.

Actins↗
PubMed1995

Response of failing canine and human heart cells to beta 2-adrenergic stimulation.

BACKGROUND: Failing human hearts lose beta 1- but not beta 2-adrenergic receptors. In canine hearts with tachypacing failure, the ratio of beta 2- to beta 1-adrenergic receptors is increased. The present study was designed to determine whether heart failure increases sensitivity to beta 2-adrenergic stimulation in isolated canine ventricular cardiomyocytes and to verify that myocytes from failing human ventricles contain functional beta 2-adrenergic receptors. METHODS AND RESULTS: Myocytes from healthy dogs, dogs with tachypacing failure, and human transplant recipients were loaded with fura 2-AM and subjected to electric field stimulation in the presence of zinterol, a highly selective beta 2-adrenergic agonist. Zinterol significantly increased [Ca2+]i transient amplitudes in all three groups. The failing canine myocytes were significantly more responsive than normal to beta 2-adrenergic stimulation. We also measured isotonic twitches, indo-1 fluorescence transients, and L-type Ca2+ currents in healthy canine myocytes. Zinterol (10(-5) mol/L) elicited large increases in the amplitudes of simultaneously recorded twitches and [Ca2+]i transients. Zinterol also increased L-type Ca2+ currents in the normal canine myocytes; this augmentation was abolished by 10(-7) mol/L ICI 118,551. cAMP production by suspensions of healthy and failing canine myocytes was not increased by zinterol (10(-9) to 10(-5) mol/L), nor did 10(-5) mol/L zinterol elicit phospholamban phosphorylation. CONCLUSIONS: Failing human ventricular cardiomyocytes contain functional beta 2-adrenergic receptors. Canine myocytes also contain functional beta 2-adrenergic receptors. The canine ventricular response to beta 2-agonists is increased in tachypacing failure. Positive inotropic responses to beta 2-stimulation are not mediated by increases in cAMP or cAMP-dependent phosphorylation of phospholamban.

Adrenergic beta-Agonists↗
PubMed1995

Left atrial volumes and function in orthotopic cardiac transplantation.

Early ventricular filling and therefore passive left atrial emptying may be impaired in patients with cardiac transplantation. As a result, left atrial function may be an important factor in maintaining stroke volume in recipients of orthotopic cardiac transplants. Left atrial volumes maximal (mitral valve opening), minimal (mitral valve closure), and onset of atrial systole (P wave on electrocardiogram) were determined by echocardiography using the biplane area-length method in 12 patients after cardiac transplantation and 12 control subjects. Maximal and minimal left atrial volumes and left atrial volumes at onset of atrial systole were larger in patients who had cardiac transplantation than in control subjects (89.8 vs 41.8 cm3, 48 vs 15.2 cm3, and 70.4 vs 27.0 cm3, respectively; p < 0.01). In patients undergoing cardiac transplantation, good correlations were found between left atrial maximal volume and left ventricular mass (r = 0.56) and between left atrial maximal volume and mean pulmonary capillary wedge pressure (r = 0.81). Left atrial passive emptying volume (maximal minus volume at P wave), was not statistically different between the two groups (19.3 in patients receiving transplants vs 14.7 cm3 in control subjects), but left atrial stroke volume (beginning atrial systole to minimal) was larger in patients receiving transplants than in control subjects (22.4 vs 11.8 cm3, respectively; p < 0.001). Thus left atrial contraction contributed 42% to the left ventricular stroke volume in patients who had cardiac transplantation but only 17% in control subjects (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Function, Left↗
PubMed1995

Neuropsychological function in patients with end-stage heart failure before and after cardiac transplantation.

This study was performed to examine cognitive function in patients with end-stage heart failure, to identify possible cardiovascular factors associated with cognitive function, and to evaluate changes in cognitive function in a subgroup of patients who received heart transplantation. An extensive battery of neuropsychological tests were given to 62 patients with end-stage cardiac failure as part of their evaluation for cardiac transplantation. Most patients were consecutive referrals, not selected because of cognitive complaints. A small subgroup of transplanted (n = 7) and non-transplanted (n = 4) patients received a repeat neuropsychological examination. At initial examination, approximately 50% of the patients met criteria for impairment in reference to normal control values. Higher stroke volume index and cardiac index and lower right atrial pressure were correlated with better cognitive function. In the subgroup of patients re-examined, the transplanted patients demonstrated significantly improved cognitive function, whereas the non-transplanted subjects were unchanged. These data indicate that in patients with end-stage heart failure there is a high prevalence of impaired cognitive function which is related to measures of cardiovascular efficiency. Preliminary evidence suggests that these impairments may be partially ameliorated by cardiac transplantation.

Adult↗
PubMed1993

Sustained augmentation of parasympathetic tone with angiotensin-converting enzyme inhibition in patients with congestive heart failure.

OBJECTIVES: The objective of this investigation was to evaluate the changes in parasympathetic tone associated with long-term angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure. BACKGROUND: Angiotensin-converting enzyme inhibitors provide hemodynamic and symptomatic benefit and are associated with improved survival in patients with congestive heart failure. Angiotensin II, whose production is ultimately inhibited by these agents, exerts significant regulatory influence on a variety of target organs including the central and peripheral nervous systems. Accordingly, it would be anticipated that angiotensin-converting enzyme inhibitors would significantly alter the autonomic imbalance characteristic of patients with congestive heart failure and that this influence over neural mechanisms of cardiovascular control may significantly contribute to the hemodynamic benefit and improved survival associated with angiotensin-converting enzyme inhibitor therapy. METHODS: In the current investigation, changes in autonomic tone associated with long-term administration of an angiotensin-converting enzyme inhibitor were measured using spectral analysis of heart rate variability in 13 patients with congestive heart failure who were enrolled in a double-blind randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor zofenopril. Both placebo and treatment groups were balanced at baseline study in terms of functional class, ventricular performance and autonomic tone. RESULTS: After 12 weeks of therapy with placebo, there was no change in total heart rate variability, parasympathetically governed high frequency heart rate variability or sympathetically influenced low frequency heart rate variability. In contrast, therapy with zofenopril was associated with a 50% increase in total heart rate variability (p = 0.09) and a significant (p = 0.03) twofold increase in high frequency heart rate variability, indicating a significant augmentation of parasympathetic tone. CONCLUSIONS: These results demonstrate that long-term treatment of patients having congestive heart failure with an angiotensin-converting enzyme inhibitor is associated with a restoration of autonomic balance, which derives in part from a sustained augmentation of parasympathetic tone. Such augmentation of vagal tone is known to be protective against malignant ventricular arrhythmias in patients with ischemic heart disease and therefore may have similar benefit in the setting of ventricular failure, thus contributing to the improved survival associated with angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗