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Biomedical subjects

W S Ring

Publications and source records attributed to W S Ring.

At least 37 records · Page 2Linked to original sources

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

The effect of aspartate and glutamate on myocardial function during reperfusion is controversial. A beneficial effect has been attributed to altered delivery of carbon into the citric acid cycle via substrate oxidation or by stimulation of anaplerosis, but these hypotheses have not been directly tested. 13C isotopomer analysis is well suited to the study of myocardial metabolism, particularly where isotopic and metabolic steady state cannot be established. This technique was used to evaluate the effects of aspartate and glutamate (amino acids, AA) on anaplerosis and substrate selection in the isolated rat heart after 25 min of ischemia followed by 30 or 45 min of reperfusion. Five groups of hearts (n = 8) provided with a mixture of [1,2-13C]acetate, [3-13C]lactate, and unlabeled glucose were studied: control, control plus AA, ischemia followed by 30 min of reperfusion, ischemia plus AA followed by 30 min of reperfusion, and ischemia followed by 45 min of reperfusion. The contribution of lactate to acetyl-CoA was decreased in postischemic myocardium (with a significant increase in acetate), and anaplerosis was stimulated. Metabolism of 13C-labeled aspartate or glutamate could not be detected, however, and there was no effect of AA on functional recovery, substrate selection, or anaplerosis. Thus, in contrast to earlier reports, aspartate and glutamate have no effect on either functional recovery from ischemia or on metabolic pathways feeding the citric acid cycle.

Acetyl Coenzyme A↗

Differential collagen distribution in the mitral valve and its influence on biomechanical behaviour.

Surgical repair of the mitral valve primarily involves endogenous valve tissue, however, the intrinsic mechanical behaviour of the tissue is not well described. To address this issue, porcine mitral valve leaflets were examined histologically and engineering concepts were applied to understand the mechanical behaviour of the layered tissue. Rectangular portions were excised from the anterior and posterior leaflets, either parallel or perpendicular to the annulus, and sections were stained for collagen (Masson's trichrome). The cross sectional layers of the valve (atrialis/spongiosa, fibrosa, and ventricularis) were identified by differences in cellularity and collagen density. The fibrosa is composed of dense collagen, while the atrialis/spongiosa and ventricularis are composed of loose collagen. Layer thicknesses were recorded digitally across the section. These values were averaged within tissue groups to determine changes in layer thickness over the length of the sample and average thickness of each layer. In all tissue groups, the fibrosa was the thickest layer, and the atrialis/spongiosa layer was thicker than the ventricularis layer. The total and fibrosa layer thicknesses of the anterior leaflet were significantly thicker than in the posterior leaflet. Mechanical engineering analysis of the layered structures under tension indicated that the anterior leaflet would be able to support greater tensile loads than the posterior leaflet. The layered arrangement was then examined as a beam in bending, and was shown to decrease the resistance of leaflets to bending, and decrease the overall bending stresses on the leaflet. This type of analysis may be extrapolated to gain insight into changes in function in diseased valves as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Finite element analysis of the mitral valve.

A finite element model was developed to examine deformation and stress patterns in the mitral valve under systolic loading conditions. This is the first three-dimensional finite element model of the mitral valve, incorporating all essential anatomic components, regional tissue thickness, collagen fiber orientation and related anisotropic material properties. A non-linear, transient, dynamic analysis was performed which included time-dependent loading, leaflet and chordal mass inertial effects and chordal element bi-linearity. The model was first analyzed without either annular or papillary muscle contraction and then with either or both. The hypothesis was that the combination of annular and papillary muscle contraction would have a beneficial effect on valve function. In all models, the computed anterior leaflet principal stresses were tensile and of greater magnitude than those in the posterior leaflet. The principal stress directions were observed to correlate well with collagen fiber orientation. Earlier leaflet coaptation was demonstrated with annular contraction, promoting valve closure, while papillary muscle contraction increased the stress on the chordae tendineae and both leaflets, tending to pull the latter apart. The combination of the two combined these effects, and showed the most even stress distribution. The effects of annular and papillary muscle contraction on valve function were shown to be beneficial by this model, and they can be further elucidated by varying the extent and timing of the individual contractions. This model can be used to examine the effects of pathologic changes, surgical manipulations and proposed material replacements. It can thus aid both the surgeon and the biomedical engineer in improving the materials and techniques available for the repair and/or replacement of mitral valve system components.

Animals↗

Changes in plasma atrial natriuretic peptide concentration during heart transplantation.

Examination of changes in plasma atrial natriuretic peptide (ANP) concentrations during heart transplantation may provide important information about factors influencing plasma ANP in patients with severe heart failure. Serial changes in plasma ANP during heart transplantation, and atrial content of ANP in native and donor atria, were measured in 12 patients. Preoperative plasma ANP was elevated in all patients (387 +/- 77 pg/mL), whereas atrial content of ANP in native atria was reduced (0.36 +/- 0.082 micrograms/mg protein). Preoperative plasma ANP did not correlate with hemodynamics, but was negatively correlated with creatinine clearance (r = -0.76, P < .01). Intraoperative plasma ANP prior to transplantation was strongly correlated with intraoperative plasma ANP after transplantation (r = 0.84, P < .001). Although postoperative plasma ANP was reduced from preoperative plasma ANP by 75%, these two measurements were also significantly correlated (r = 0.70, P < .02). Postoperative plasma ANP was not correlated with hemodynamics, but was negatively correlated with both creatinine clearance (r = -0.65, P < .05) and content of ANP in the native atria (r = -0.75, P < .01). Multiple linear regression analysis suggested that up to 85% of the variability of early postoperative plasma ANP could be accounted for by the variability in these latter two parameters. The decrease in native atrial ANP content, in the context of elevated plasma ANP concentration, is consistent with prior animal studies suggesting that severe heart failure induces cellular adaptations favoring accelerated ANP synthesis and secretion (with resultant reduction in tissue content).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pheochromocytoma with extension into the inferior vena cava: a case report.

Eleven cases of pheochromocytoma with extension into the inferior vena cava have been reported previously. This report describes a case of a right adrenal pheochromocytoma with extension into the inferior vena cava that was removed with the aid of cardiopulmonary bypass and circulatory arrest.

Adrenal Gland Neoplasms↗

Heart transplantation in children: an international survey.

A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor.

Actuarial Analysis↗

Coronary artery disease in pediatric cardiac transplant recipients receiving triple-drug immunosuppression.

Although triple-drug immunosuppression (cyclosporine, azathioprine, and prednisone) has reduced the incidence of acute rejection after pediatric cardiac transplantation, its effect on the development of coronary artery disease, which may be the major determinant of long-term survival in these patients, is not well defined. We reviewed 42 coronary angiograms obtained annually in 17 cardiac transplant recipients, aged 6 months to 18 years (mean, 12.4 years) at the time of transplantation, who had been maintained on triple-drug immunosuppression and had survived at least 1 year after transplantation. Each angiogram was reviewed for luminal irregularities or discrete stenoses, for the loss of third-order branching, and for the presence of myocardial bridging or calcification of vessels. Patient files were reviewed for donor and recipient age, sex, and ABO blood group, for postoperative episodes of rejection or cytomegalovirus infection, for hypertension, and for cholesterol and triglyceride values. No recipient in our series has died or undergone retransplantation because of coronary artery disease. Six of 17 (35%) patients have developed angiographically identifiable coronary artery abnormalities: four by the first year and two additional recipients by the second and third years, respectively, after transplantation. Development of coronary artery abnormalities approached a significant correlation when related to posttransplantation cytomegalovirus infection (p = 0.11) and older recipient age (p = 0.056) but not to any other factors studied, including episodes of rejection (p = 1.0). Angiographically identifiable coronary artery abnormalities can occur in pediatric recipients within the first year after cardiac transplantation in spite of a low incidence of acute rejection. Although the abnormalities may be mild initially, they can progress and require intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Rejection and infection after pediatric cardiac transplantation.

Cardiac transplantation has only recently become an accepted therapeutic modality for children and adolescents with end-stage cardiomyopathy. Long-term survival, the incidence of rejection, and the incidence of infection are still being defined. From 1985 to 1989, 21 children aged 6 months to 19 years (average age, 11.2 years) underwent cardiac transplantation at our institutions. Eighteen survived the operative period and have been followed for 5 to 49 months (average follow-up, 24 months). All operative survivors have received triple-drug immunosuppression consisting of cyclosporine, azathioprine, and prednisone. During follow-up, 7 patients have been treated on 12 occasions for rejection as documented by endomyocardial biopsy. Eight (67%) of the 12 episodes of rejection occurred in the presence of subtherapeutic cyclosporine levels. Two of the 7 patients treated for rejection have subsequently died of ongoing cardiac rejection and arrhythmia. There have been no perioperative or late deaths from infection. Bacterial sepsis was identified and treated twice during follow-up, viral infections on five occasions, and fungal infection once. Actuarial 1-year survival and 3-year survival of the 18 operative survivors are 94% and 78%, respectively. In the first 7 months after cardiac transplantation, 73% of patients were free from rejection and 83% were free from serious bloodborne infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Sepsis-induced diastolic dysfunction in chronic canine peritonitis.

A chronic canine model of hyperdynamic sepsis was achieved by cecal ligation and puncture (SEP) in conjunction with continuous high-volume fluid resuscitation. Cardiac function was evaluated using ultrasonic cardiac crystals placed across the major, minor, and wall thickness axes of the left ventricle, together with simultaneous arterial and ventricular pressure measurement. Seven to 10 days after crystal implantation, animals were randomized to either SEP (n = 10) or sham laparotomy control (n = 7). SEP dogs became febrile and lethargic, with elevated leukocyte counts and positive blood cultures for enteric organisms. They were also hyperdynamic, with significant increases in heart rate and cardiac output and a fall in systemic vascular resistance. Systolic blood pressure, stroke volume, and ejection fraction remained stable. Relative to control, the SEP group demonstrated a significant reduction in intrinsic contractility during systole, as measured by the heart rate and load-independent index of left ventricular performance Emax (P less than 0.01), confirming the observations of others. In addition, however, diastolic function also became markedly abnormal with a progressive increase in unstressed and end-diastolic ventricular volumes (P less than 0.05) and a significant decrease in myocardial compliance as quantitated by transmural pressure vs. volume-strain analysis. It is hypothesized that this increase in diastolic volume helps to maintain global cardiac performance during the hyperdynamic response to sepsis in the presence of adequate volume support.

Animals↗

Five-year experience with triple-drug immunosuppressive therapy in cardiac transplantation.

Although triple-drug immunosuppression with a combination of cyclosporine, prednisone, and azathioprine has been shown to improve short-term survival after cardiac transplantation, its long-term effects still are unknown. From December 1983 through December 1988, all patients (N = 139) who underwent orthotopic cardiac transplant at our institution received triple-drug immunosuppressant therapy. Follow-up averaged 32.2 +/- 15.8 months. Twenty-one patients died; 134 survived more than 30 days. Actuarial survival was 92% at 1 year, 85% at 3 years, and 78% at 5 years. Twenty-five episodes of acute graft rejection were diagnosed in 21 of the 139 recipients (0.18 episode per patient). In patients, the incidence of infection was 0.82 episode; 72% of infections were viral, with 10% due to cytomegalovirus. The incidence of coronary artery disease was 10% at 1 year, 25% at 3 years, and 36% at 5 years. Coronary artery disease was responsible for 60% of late deaths. Arterial hypertension developed in 81% of patients, despite relatively well-maintained renal function (serum creatinine, 1.7 +/- 0.3 mg/dl). Skeletal complications occurred in 15.8% and lymphoma in 1.4% of recipients. Complete long-term rehabilitation was achieved in all but two of the surviving patients. These data support the short- and long-term effectiveness of triple-drug therapy. This regimen reduces the incidence of rejection, infection, and lymphoma, as well as the degree of renal failure. However, the incidence of posttransplant coronary artery disease has not been reduced, and graft atherosclerosis represents the major cause of late graft failure and death.

Actuarial Analysis↗

Myocardial carnitine in end-stage congestive heart failure.

To test the hypothesis that carnitine is decreased in the myocardial tissue of patients with end-stage congestive heart failure (CHF), left ventricular myocardial carnitine was measured in 51 patients undergoing orthotopic cardiac transplantation. The study group included patients with idiopathic dilated cardiomyopathy, coronary artery disease, myocarditis and rheumatic heart disease. Myocardial carnitine varied in different cardiac chambers. In normal control hearts, the left and right ventricular total carnitine was similar, but the ventricles had higher levels than the atria (p less than 0.005); in 30 hearts in CHF, the left ventricular total carnitine was higher than in the right ventricle (p less than 0.001) and both ventricles had higher total carnitine than the atria (p less than 0.005). Only 7 of 51 patients with CHF had low myocardial carnitine, whereas plasma carnitine was elevated in all diagnostic groups of end-stage CHF studied.

Adolescent↗

Occult pulmonary artery associated with failure to thrive and recurrent pneumonia--a case report.

Occult pulmonary artery is an uncommon cardiovascular defect. Associated symptoms include recurrent pulmonary infections and congestive heart failure. The authors describe a one-year-old boy initially diagnosed as having broncho-pulmonary dysplasia who developed severe failure to thrive, recurrent pneumonias, and pulmonary hypertension. The presence of an occult right pulmonary artery was suspected by lung perfusion scan and diagnosed by cardiac catheterization and angiography. After surgical repair, his clinical course improved and his growth and development were normal. This case demonstrates the importance of including occult pulmonary artery in the differential diagnosis of infants with failure to thrive associated with recurrent pulmonary infection.

Blood Vessel Prosthesis↗

Coronary artery disease in cardiac transplant patients receiving triple-drug immunosuppressive therapy.

Although triple-drug immunosuppression with cyclosporine, prednisone, and azathioprine has reduced the incidence of acute graft rejection after cardiac transplant, its effect on the development of coronary artery disease is unknown. We have followed up 74 cardiac transplant recipients with yearly coronary angiograms. The probability of acute rejection was 10.8% at 1 year. The incidence of coronary artery disease was 8% at 1 year (six of 74 patients) and 24% at 2 years (11 of 30 patients). In patients who developed posttransplant coronary artery disease, there was a slightly higher, but not statistically significant, incidence of acute graft rejection and pretransplant idiopathic cardiomyopathy. No correlation was found between the incidence of coronary artery disease and recipient age, human leukocyte antigen (HLA) type, hypertension, diabetes, cholesterol level, triglyceride levels, weight gain after transplant, and smoking. These data indicate that triple-drug immunosuppression, despite having produced a significant reduction in the episodes of acute graft rejection, has not decreased the incidence of posttransplant coronary artery disease. Common risk factors for coronary disease and HLA mismatch are probably not important in the pathogenesis of coronary atherosclerosis after cardiac transplantation, whereas the risk for coronary artery disease may be increased by acute graft rejection and pretransplant idiopathic cardiomyopathy.

Azathioprine↗

15- to 30-year follow-up of patients undergoing repair of ruptured congenital aneurysms of the sinus of Valsalva.

Rupture of a congenital aneurysm of the sinus of Valsalva is a rare congenital cardiac malformation. Between 1956 and 1971, we operated on 14 patients aged 9 to 36 years (median, 20 years) for repair of a ruptured aneurysm of the sinus of Valsalva, and have followed each patient to the present. Two operative and 4 late deaths occurred, 3 following a second cardiac operation and the other from dysrhythmia. Late complications have included development of complete heart block in 2 patients (necessitating permanent pacemaker insertion 11 and 24 years after initial repair), progression of aortic regurgitation in 2 (necessitating valve replacement 9 and 13 years after initial repair), and endocarditis in 1 patient 20 years after repair. Four of the 8 remaining long-term survivors (followed for 15 to 30 years [mean, 23.6 years]) are in New York Heart Association (NYHA) Class I, and the other 4 are in NYHA Class II. Three of the 5 patients with suture closure (no pledgets or adjacent ventricular septal defect repair) of the ruptured aneurysm of the sinus of Valsalva sustained recurrent rupture and required repeat closure. Whether the lack of prosthetic material to bolster the repair or inadequate resection of redundant aneurysmal fibrous tissue was responsible for these recurrences cannot be stated. Operative management of patients with ruptured congenital aneurysms of the sinus of Valsalva is discussed.

Adolescent↗

The effects of verapamil on left ventricular function in the presence of beta-adrenergic blockade.

Supraventricular tachyarrhythmias frequently complicate myocardial revascularization. Intravenous administration of verapamil has been effective in terminating these arrhythmias. To determine the effects of verapamil on left ventricular systolic function, we implanted ultrasonic dimension transducers in dogs and, after they had recovered from the operation, studied them while they were awake and unsedated. Intravenous administration of verapamil (0.2 mg/kg) resulted in an elevation of cardiac output above baseline because of reflex-induced tachycardia. Contractility, as measured by the load-independent end-systolic pressure-volume relationship, remained unchanged. When the animals were pretreated with atropine and propranolol, verapamil resulted in a fall in cardiac output and contractility. The intact animal responded to the vasodilatory effect of verapamil by releasing catecholamines to maintain cardiac output and hemodynamic stability. Only when this compensatory mechanism was blocked by a beta-adrenergic blocker do the inherently negative inotropic and chronotropic effects of verapamil become apparent. The clinical ramifications of this finding are of greater importance to the surgeon as more patients receive beta-adrenergic blocking agents up to the time of the immediate preoperative period. We conclude that verapamil should be administered with caution to patients with supraventricular tachyarrhythmias who have been receiving beta-adrenergic blocking agents.

Adrenergic beta-Antagonists↗

Role of extrastimulus site and tachycardia cycle length in inducibility of atrial preexcitation by premature ventricular stimulation during reciprocating tachycardia.

Preexcitation of the atria during reciprocating tachycardia (RT) by a premature ventricular complex occurring when the His bundle is refractory provides direct evidence of the presence of accessory atrioventricular (AV) connection. The impact of ventricular stimulation site and RT cycle length on inducibility of atrial preexcitation was assessed in 38 patients with RT utilizing a single accessory AV connection (right free wall in 5 patients, left free wall in 21 and posterior septal/paraseptal in 12). Extrastimuli were inserted at right ventricular (RV) apical, left ventricular (LV) septal and LV free wall sites. Inducibility of and magnitude of atrial preexcitation increased as stimulation site approached accessory AV connection site. Thus, for RV free wall connections, RV extrastimuli preexcited the atria in 5 of 5 patients, LV septal in 1 of 5 and LV free wall in 0 of 4. For LV free wall accessory connections, RV extrastimuli preexcited the atria in only 3 of 21 patients, compared with 12 of 17 with LV septal and 20 of 21 with LV free wall stimulation. Additionally, the magnitude of atrial preexcitation achieved was related to RT cycle length, diminishing as cycle length shortened. Finally, in a few instances both RV apical and LV free wall extrastimuli failed to elicit preexcitation in patients with a posterior septal connection. Thus, ventricular pacing site and RT cycle length contribute importantly to induction of atrial preexcitation by ventricular extrastimulation technique and should be considered during evaluation of patients with RT in whom accessory AV connections may be present.

Adolescent↗

Heterogeneous myocardial catecholamine concentrations in patients with congestive heart failure.

Left ventricular catecholamine and plasma norepinephrine levels were assayed in 39 patients undergoing cardiac transplantation to test the hypothesis that in congestive heart failure (CHF) the normally high concentration of myocardial norepinephrine is depleted while dopamine is increased because dopamine conversion to norepinephrine is the rate-limiting step in norepinephrine synthesis. Plasma norepinephrine was elevated in all patients (average 741 +/- 472 micrograms/ml), but myocardial norepinephrine was variable, ranging from 79 to 2,127 ng/g (average 512 +/- 392). Myocardial dopamine also varied considerably (range 0 to 713 ng/g, average 143 +/- 150). Nineteen patients had the expected pattern of low cardiac norepinephrine and elevated dopamine levels. However, myocardial catecholamine levels were normal (high norepinephrine, low dopamine) in 7 patients; both norepinephrine and dopamine were low in 6 patients; and norepinephrine levels were preserved but dopamine high in 7 patients. Cardiac norepinephrine level correlated only weakly with peripheral vascular resistance (r = 0.39, p less than 0.05), and examination of multiple other variables failed to reveal likely causes of the differences in cardiac norepinephrine and dopamine between patients. Thus, myocardial norepinephrine is not uniformly reduced in patients with severe CHF, and further attempts to delineate the factors regulating myocardial catecholamine concentration and adrenergic function in such patients are needed.

Adult↗

Echocardiographic versus cardiac catheterization diagnosis of infants with congenital heart disease requiring cardiac surgery.

The success of noninvasive preoperative evaluation of infants with congenital heart disease using cardiac ultrasound depends not only on diagnostic accuracy, but also on risk of morbidity and mortality as compared with infants who undergo cardiac catheterization. Fifty-six infants (age 10 weeks or younger) with coarctation of the aorta (n = 16), coarctation with ventricular septal defect (n = 12), valvar aortic stenosis (n = 10) or total anomalous pulmonary venous connection (n = 18) were examined. Thirty-one underwent noninvasive preoperative assessment and 25 underwent evaluation including cardiac catheterization. Age, level and duration of support, pH, renal function, mortality, complications of cardiac catheterization and errors of diagnosis were compared. Significant differences between the 2 groups were more frequent preoperative use of prostaglandin E1 and shorter hospital stay in the noninvasively evaluated coarctation group. Of the infants with coarctation and ventricular septal defect, 1 who had cardiac catheterization required renal transplantation and 1 evaluated noninvasively required surgery at age 3 months for mitral stenosis not discovered on preoperative evaluation. One noninvasively evaluated infant with total anomalous pulmonary venous connection had a stenotic communication between the pulmonary venous confluence and the left atrium not detected by ultrasound. Surgery was successful in the latter 2 infants. Noninvasive preoperative diagnosis of some infants with congenital heart disease can be performed without increasing the risk of operative morbidity and mortality. Eliminating cardiac catheterization reduces hospital costs, decreases total numbers of catheterizations performed and influences the structure of training programs.

Cardiac Catheterization↗