Biomedical subjects
Publications and source records attributed to T B Levine.
The authors describe two-dimensional echocardiographic features of an inferior venacaval filter that migrated to the right ventricle. As far as they can determine, this is the first description of the echocardiographic aspects of this clinical entity.
Although there is convincing evidence that prophylactic administration of high doses of the monoclonal antibody OKT3 predisposes patients to an increased prevalence of early posttransplantation malignancy, particularly posttransplantation lymphoproliferative disease, it is indeterminate whether polyclonal antilymphocyte globulin poses a similar hazard. We reviewed the outcome of 112 consecutive cardiac transplant recipients who received uniform immunosuppression, including induction therapy with antilymphocyte globulin, and were prospectively followed-up for a median duration of 41.5 months (range 1 to 81 months). No patients had posttransplantation lymphoproliferative disease. Nine malignant neoplasms (8%) were detected from 6 to 70 months after transplantation. Four patients with cutaneous neoplasms were alive and well at the time this article was written. Three patients died of disseminated adenocarcinoma 6 months, 17 months, and 60 months after transplantation. One patient was undergoing treatment of Kaposi's sarcoma at the time this article was written, and another was undergoing treatment of transitional bladder cell carcinoma. Actuarial survival for all patients was 88% at 1 year and 79% at 5 years. Moderate doses of induction antilymphocyte globulin may facilitate rapid reduction of maintenance cyclosporine and steroid doses, thereby decreasing the duration of intense immunosuppression and lowering the risk of posttransplantation lymphoproliferative disease. Testing this hypothesis would require the development of reliable and reproducible in vivo assays to prospectively assess immune status.
A 60 year male, orthotopic heart transplant recipient developed a fatal left ventricular outflow obstruction secondary to thrombus at 38 months post transplant. Although he had episodes of mild to moderate rejection at 2 and 16 months post transplant, subsequent biopsies were negative and annual cardiac catheterizations showed mild left ventricular hypokinesis and normal coronary arteries. This case represents a catastrophic complication of transplant rejection and illustrates the problems with identifying rejection using current diagnostic methods.
A group of orthotopic heart transplant (OHT, n = 28) and heart surgery (n = 19) patients, with similar ejection fractions and left ventricular end-diastolic pressures, were exercised to symptom-limited maximum to describe differences in cardiovascular and gas exchange responses. Testing was performed at a mean of 3 and 6 mo after surgery, respectively (P less than 0.05). OHT patients have a greater resting systolic and diastolic blood pressure (P less than 0.01) and a significantly greater (P less than 0.01) heart rate (HR) at rest in the supine and standing positions and during minutes 2 through 7 of supine recovery. Peak treadmill time was significantly less (P less than 0.01) in OHT patients. No significant differences were found for systolic blood pressure (SBP) during recovery, peak HR, ventilation, relative O2 uptake (VO2), body weight, ventilatory equivalents for O2 and CO2, O2 pulse, and HR-SBP product (peak HR x peak SBP). Peak pulse pressure, heart rate reserve, total VO2, and absolute VO2 at ventilatory threshold were significantly lower (P less than 0.01) in the OHT patients. We concluded that 1) complete cardiac decentralization is evident, 2) the significantly reduced VO2 at ventilatory threshold should be considered when activities of daily living are prescribed, and 3) SBP response is more appropriate than HR for assessing recovery of the decentralized heart after maximal exercise.
This study was performed to determine the diagnostic value of TEE in recipients of orthotopic heart transplantation. Findings on TEE were compared with those of TTE in 30 patients with orthotopic heart transplantation. Transesophageal echocardiography identified left atrial appendage and flow across the interatrial septum ... findings not detected by TTE. In addition, pronounced bulging of the interatrial septum was seen in six patients by TEE and not by TTE. Spontaneous echo contrast (smoke) in the atria was detected by TEE in 14 patients and by TTE in one patient. Abnormal geometry of the atria and donor-recipient atrial anastomosis was identified in all patients by TEE and TTE. Our findings suggest that TEE should be selectively utilized in the operating room, in patients with suspected atrial thrombi, and in those with clinically significant right ventricular volume overload to assess integrity of interatrial anastomosis.
Orthotopic heart transplantation (OHT) recipients often experience increased body weight (BW) following surgery. Using hydrostatic weighing (HW), this study assessed the body density (BD) and body composition of 17 white and seven black male OHT patients. It examined the cross-validity of the Jackson and Pollock seven and three site skinfold (SF) regression equations for predicting BD in these patients. We hypothesized that both prednisone (P) dose and months post-operative (MPO) would be inversely related to BD. The average of the last five of ten HW trials was used in computing BD. BW and % body fat (BF) were 88.5 +/- 17.8 kg (mean +/- SD) and 33.5 +/- 9.4%, respectively. The correlation coefficient between hydrostatically determined BD and BD determined via two of the three intercept revised Jackson and Pollock SF equations was r = 0.89, SE = 0.009. A polynomial regression model for BD using P dose and MPO provided a correlation coefficient of r = 0.71, SE = 0.015. Partial correlation techniques incorporating SF, age, MPO, and P dose indicated that neither P dose or MPO provided any significant additive effect, above SF and age, when predicting BD. We conclude that in OHT patients receiving glucocorticoids, the intercept revised Jackson and Pollock SF regression equations are generally applicable and associated with a SE of +/- 4 BF percentage points. Up to 49 months after OHT, both P dose and MPO are inversely related to BD but provide no additive value above SF for predicting BD.
A canine model of chronic heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Twenty closed-chest dogs underwent three to nine intracoronary embolizations performed 1-3 wk apart. Embolizations were discontinued when left ventricular (LV) ejection fraction was less than 35%. LV ejection fraction was 64 +/- 2% at baseline and decreased to 21 +/- 1% at 3 mo after the last embolization (P less than 0.001). During the same period, LV end-diastolic pressure increased from 6 +/- 1 to 22 +/- 3 mmHg (P less than 0.001); LV end-diastolic volume increased from 64 +/- 3 to 101 +/- 6 6 ml (P less than 0.001), and cardiac output decreased from 2.9 +/- 0.2 to 2.3 +/- 0.1 l/min (P less than 0.01). These changes were accompanied by significant increases of pulmonary artery wedge pressure and systemic vascular resistance. Plasma norepinephrine increased from 332 +/- 17 pg/ml at baseline to 791 +/- 131 pg/ml at 3 mo after the last embolization (P less than 0.01); plasma levels of atrial natriuretic factor increased from 12.7 +/- 10.0 to 28.8 +/- 8.6 pmol/l (P less than 0.01), whereas plasma renin activity remained unchanged. Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy. We conclude that multiple intracoronary embolizations with microspheres, separated in time, can lead to chronic heart failure in dogs. The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.
Orthotopic heart transplantation (OHT) represents an effective alternative for individuals with end-stage heart disease. The current literature reports only the responses of OHT patients to greater than or equal to 4 mo of exercise training (ET) and frequently lacks adequate controls. Most programs currently treating OHT patients usually provide 6-12 wk of ET. This study describes the effects of a 10-wk supervised ET program in 12 male OHT patients and 5 other male OHT patients who served as a comparison group. Graded exercise tests were performed before and after ET. After ET, maximal O2 consumption was significantly greater for the ET group than the comparison group (P less than 0.05) and the mean increase in peak heart rate was 18 +/- 4 and 6 +/- 4 (SE) min-1 for ET and comparison groups, respectively (P less than 0.05). Maximal ventilation was also significantly greater for the ET group at after ET, while resting heart rate and blood pressure and peak blood pressure, O2 pulse, respiratory rate, and ventilatory equivalents for O2 and CO2 were not significantly changed. We conclude that after OHT a 10-wk ET program improves maximal O2 consumption and, by improving peak heart rate, improves O2 delivery.
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Recent research indicates that neurohormonal responses after myocardial infarction may predict patient outcome, and alteration of this process may change etiologic factors and strengthen positive prognosticators. Because there are clinical similarities between acute myocardial infarction and heart failure, there appears to be justification for a unified treatment approach (i.e., therapies that have proved beneficial in the treatment of myocardial infarction have also showed promise in the treatment of heart failure). Conversely, some therapies that have benefited the patient with heart failure may benefit the patient who has had a myocardial infarction. For example, angiotensin-converting enzyme inhibitors have been proven to blunt detrimental neurohormonal activity seen after myocardial infarction. These therapies promise to reduce complications and improve survival.
Heart failure results not only in a fall in cardiac output but also in a redistribution of blood flow favoring some regional beds (the brain and the heart) at the expense of others (the kidney and working skeletal muscle). The chronic resting hypoperfusion of striated muscle is further compromised with exercise. Maladaptive vasoconstrictor control mechanisms prevent the redirection of blood flow from nonworking muscle and liver to working muscle. This inappropriate preservation of nonworking organ perfusion further compromises the functional capacity of working muscle and is associated with evidence for metabolic deconditioning with reduced oxygen extraction and impaired oxidative phosphorylation. It is becoming increasingly clear that the clinical response to the inotropic and vasodilator therapy used in heart failure is in part dependent on the differing regional blood flow profiles of the various agents studied. The ability of the angiotensin-converting enzyme inhibitors to redirect blood flow away from nonworking regional beds to exercising muscle, and thereby to reestablish an appropriate physiologic response to changing metabolic needs, may be the overriding reason for their long-term efficacy. Certainly in the future the comprehensive therapy of heart failure will have to take into consideration not only central hemodynamic but also regional blood flow/supply and demand issues.
Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.
Dobutamine was administered in a dose of 10 +/- 1 micrograms/kg/min to 13 patients with severe idiopathic or ischemic dilated cardiomyopathy. Acute hemodynamic improvement was noted in all patients. All patients had a significant decrease in plasma potassium (4.6 +/- 0.1 to 4.2 +/- 0.2 mEq/liter, p less than 0.0001) at peak infusion. The decrease in potassium persisted for at least 45 minutes after discontinuing the infusion. Three patients had exacerbation of baseline ventricular arrhythmias that resolved with infusion discontinuation. Changes in plasma norepinephrine could not explain the potassium decrease or arrhythmia production, which also significantly decreased in these patients (771 +/- 123 to 524 +/- 73 pg/ml, p less than 0.01). It is concluded that dobutamine causes a significant decrease in plasma potassium and that the decrease persists at least 45 minutes after the infusion is discontinued.
Lisinopril, a new converting enzyme inhibitor, was studied hemodynamically in 55 patients. The response to 2.5-, 5- and 10-mg doses showed significant increases in cardiac index and significant reductions in pulmonary artery wedge, right atrial, pulmonary arterial and systemic arterial pressures, as well as in systemic vascular resistance. Significant changes in most parameters were present at 24 hours. A dose-response relation for most parameters was noted. Over a 3-month period, 47 patients were followed up, with improvement in functional capacity and symptomatic status. Metabolic parameters did not change over time, although 26% showed evidence of reversible renal dysfunction. Only 3 patients (6.4%) required discontinuation because of adverse effects. A subgroup of patients reassessed at 3 months demonstrated maintenance of hemodynamic effects. The present study demonstrates that (1) the hemodynamic effects of lisinopril are of relatively long duration; (2) within certain limits, a dose-response relation can be defined; and (3) the drug has an acceptable long-term tolerability profile.
The hemodynamic effects of varying oral doses of the long-acting converting enzyme inhibitor lisinopril were studied in an acute, single-blind, parallel fashion in 55 patients with moderate to severe congestive heart failure. Doses of 2.5, 5.0, and 10 mg produced a significant increase in cardiac index and significant reductions in pulmonary capillary wedge, right atrial, pulmonary arterial, and systemic arterial pressures and systemic vascular resistance. The changes were present up to 24 hours after dosing for most parameters. There was a clear-cut dose-response relationship observed. Forty-seven patients were followed over a 3-month period, during which functional status and exercise tolerance improved. Although 26% showed some evidence of renal dysfunction with lisinopril, these changes could be normalized by decreasing either the lisinopril or the diuretic dose. These data demonstrate that the hemodynamic changes with the long-acting converting enzyme inhibitor lisinopril can be modulated with dose adjustment in patients with congestive heart failure. They also suggest that renal function changes may be normalized by adjustment of either the dose of lisinopril or the diuretic dose.
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To determine the biochemical basis of abnormal diastolic properties in human dilated cardiomyopathy calcium uptake by the sarcoplasmic reticulum in ventricular homogenates of biopsy specimens from 21 patients with dilated cardiomyopathy was compared with that in nine normal controls. As a group, patients with cardiomyopathy had considerably lower calcium uptake rates (3.3(0.6) nmol.mg-1.min-1 vs 6.5(0.5) nmol.mg-1.min-1, p less than 0.01). Calcium uptake rates correlated modestly with resting haemodynamic values and significantly with plasma noradrenaline concentrations but not with plasma renin activity. These results show that sarcoplasmic reticulum function is impaired in human dilated cardiomyopathy and that this impairment is related both to the severity of haemodynamic dysfunction and to the extent of sympathetic nervous system activation.
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