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Biomedical subjects

M A Acker

Publications and source records attributed to M A Acker.

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

Development of donor-derived prostate cancer in a recipient following orthotopic heart transplantation.

OBJECTIVE: To report the development of metastatic prostate cancer in a heart transplant recipient without a primary focus in the recipient prostate gland; to present genetic evidence suggesting transplantation of the malignancy from the donor. DESIGN: Histological analysis of donor prostate and recipient prostate and rib. Molecular genetic analysis of prostate and kidney tissue from the donor and peripheral blood leukocytes and rib tissue from the transplant recipient. SETTING: University of Pennsylvania Medical Center. RESULTS: Multiple biopsies of recipient prostate were negative for malignancy but recipient rib contained prostatic adenocarcinoma with osteoblastic bone response. Molecular genetic analysis of recipient rib specimen, which contained both histologically normal and neoplastic cells, was shown to contain a combination of alleles from the donor and recipient at 4 loci. CONCLUSION: Although this is a single case report of an uncommon event, genotyping of polymorphic dinucleotide repeat elements from 4 different chromosomal regions provides strong evidence that the tumor cells arose from donor tissue and were transplanted along with the cardiac allograft.

Adenocarcinoma↗
PubMed1997

Dynamic cardiomyoplasty: its chronic and acute effects on the failing heart.

OBJECTIVES: Dynamic cardiomyoplasty is an alternative therapy for end-stage heart failure. We investigated the mechanisms, both acute and chronic, by which a synchronously stimulated conditioned muscle wrap affects left ventricular function in a chronic canine model of dilated cardiomyopathy. METHODS: Nineteen dogs underwent rapid ventricular pacing at a rate of 215 beats/min for 4 weeks to create a model of heart failure. Eight dogs were then randomly selected to undergo cardiomyoplasty, and all dogs received 6 additional weeks of rapid ventricular pacing. The cardiomyoplasty group also received a graded muscle conditioning protocol of synchronized burst stimulation to transform the muscle wrap. All dogs were studied with pressure-volume analysis and echocardiography at baseline and after 4 and 10 weeks of rapid ventricular pacing. Data in the cardiomyoplasty group were analyzed with the stimulator off, with it augmenting every beat (1:1), and with it augmenting only every other beat (1:2). RESULTS: Stimulator "of" data at 10 weeks of rapid pacing demonstrated chronic effects by enhanced ventricular function (end-systolic elastance = 1.80 after myoplasty vs 1.17 for controls, p = 0.005) and a stabilization of volumes and composite end-systolic and end-diastolic pressure-volume relations in the cardiomyoplasty group when compared with controls. Myoplasty stimulation increased apparent contractility (preload recruitable stroke work = 31.3 for stimulator "of" vs 40.6 for stimulator 1:2 assisted beats [p < 0.05] and vs 45.4 for stimulator 1:1 [p < 0.05]). CONCLUSIONS: Benefits from dynamic cardiomyoplasty are by at least two mechanisms: (1) the girdling effects of a conditioned muscle wrap, which halts the chronic remodeling of heart failure, and (2) active systolic assistance, which augments the apparent contractility of the failing heart.

Animals↗
PubMed1996

Circulatory management with retrograde cerebral perfusion for acute type A aortic dissection.

BACKGROUND: Cerebral circulation during urgent repair of acute type A aortic dissection has traditionally been managed with cardiopulmonary bypass and aortic cross clamping proximal to the innominate artery or by the use of hypothermic circulatory arrest (HCA). The more recently introduced retrograde cerebral perfusion (RCP) may confer additional cerebral protection during elective aortic arch reconstruction. The purpose of this study was to demonstrate the efficacy of RCP in the urgent repair of acute type A aortic dissection. METHODS AND RESULTS: We evaluated 60 consecutive patients who underwent repair of acute type A aortic dissection over a 6-year period. Patients were grouped according to intraoperative circulatory management strategies. Group 1 consisted of 41 patients operated on early in the series who were managed by cardiopulmonary bypass and standard aortic cross clamping (n = 21) with conversion to HCA (n = 20) if the intimal tear extended into the aortic arch. Since 1993, 19 patients, who make up group 2, were managed with routine open distal anastomosis and HCA with RCP. Data were analyzed for clinically evident, radiographically confirmed cerebrovascular accidents and 60-day mortality and evaluated by chi 2 analysis. Stroke and mortality rates of patients managed with either cardiopulmonary bypass or HCA were 26.3% and 29.3%, respectively. Patients undergoing RCP experienced statistically significant reductions in rates of confirmed cerebrovascular accidents (0%, P = .015) and mortality (5.3%, P = .04). CONCLUSIONS: We conclude that the introduction of circulatory management using RCP with HCA during urgent operative repair of acute type A aortic dissection has significantly improved both stroke and mortality rates.

Acute Disease↗
PubMed1996

Triiodothyronine optimizes sheep ventriculoarterial coupling for work efficiency.

BACKGROUND: Triiodothyronine (T3) administration after cardiopulmonary bypass has been shown to significantly improve cardiac performance. The present study was undertaken to elucidate the effects of T3, when administered as an intravenous bolus, on both cardiac energetics and stroke work-oxygen utilization (EW/LVVO2) efficiency. METHODS: In both unstressed and stressed hearts, energetics were evaluated at baseline and 2 hours after intervention in an in vivo sheep preparation. In the first group (n = 5) sheep received saline vehicle. In the second group (n = 9) sheep received an intravenous bolus of 1.2 micrograms/kg of T3. In the third group (n = 7) sheep received a 2-hour intravenous infusion of dobutamine at a rate of 5 micrograms/kg/min. RESULTS: In the unstressed heart, T3 improved cardiac function at no cost in oxygen consumption by decreasing afterload and hence improved EW/LVVO2 efficiency. In contrast, dobutamine improved unstressed cardiac function by increasing contractility at the cost of increased oxygen consumption and thus decreased EW/LVVO2 efficiency. Triiodothyronine optimized ventriculoarterial coupling for efficiency, but dobutamine optimized coupling for maximal work. In the stressed heart, T3 again improved EW/LVVO2 efficiency, but dobutamine had the opposite effect. CONCLUSIONS: The bolus administration of T3 improves unstressed cardiac performance through optimization of ventriculoarterial coupling for EW/LVVO2 efficiency, primarily through vasodilation. Triiodothyronine also increases efficiency in the stressed heart. This study supports the use of T3 in cardiac operations to improve cardiac performance with no cost in oxygen consumption characteristic of inotropic agents.

Animals↗
PubMed1996

Cortical blindness secondary to cyclosporine after orthotopic heart transplantation: a case report and review of the literature.

Cyclosporine neurotoxicity has been described after liver, kidney, and bone marrow transplantation and has been associated with a number of risk factors, including hypomagnesemia and low serum cholesterol levels. Reports in heart transplant recipients are less common. We present a patient with cortical blindness secondary to cyclosporine after orthotopic heart transplantation. The patient had confusion, focal visual field defects, and bilateral occipital lobe lesions shown on magnetic resonance imaging. Although he had significant clinical improvement with decreasing cyclosporine levels, residual computerized visual field defects and magnetic resonance imaging abnormalities were documented several months later.

Blindness↗
PubMed1995

Reverse remodeling from cardiomyoplasty in human heart failure. External constraint versus active assist.

BACKGROUND: Cardiomyoplasty (CM) is a novel surgical therapy for dilated cardiomyopathy. In this procedure, the latissimus dorsi muscle is wrapped around the heart and chronically paced synchronously with ventricular systole. While studies have found symptomatic improvement from this therapy, the mechanisms by which CM confers benefit remain uncertain. This study sought to better define these mechanisms by means of serial pressure-volume relation analysis. METHODS AND RESULTS: Serial pressure-volume studies were performed by the conductance catheter method in three patients (total to date) with dilated cardiomyopathy (New York Heart Association class III) who underwent CM. Data were measured at baseline (before surgery) and at 6 and 12 months after CM. Chronic left ventricular (LV) systolic and diastolic changes induced by CM were evaluated with the stimulator in its stable pacing mode (every other beat) and after temporarily suspending pacing. CM-stimulated beats were compared with pacing-off beats to evaluate active systolic assist effects of CM. In each patient, CM resulted in a chronic lowering of cardiac end-diastolic volume and an increased ejection fraction. Most notably, the end-systolic pressure-volume relation shifted leftward, consistent with reversal of chronic chamber remodeling. In contrast, the diastolic pressure-volume relation was minimally altered, and the loops shifted down along the same baseline relation. These marked chronic changes in LV function measurable with CM stimulation off contrasted to only minor acute effects observed when the muscle wrap was activated. This suggests that the benefit of CM derived less from active systolic assist than from remodeling, perhaps because of an external elastic constraint. CONCLUSIONS: These data, while limited to a small number of patients, suggest that CM can reverse remodeling of the dilated failing heart. While systolic squeezing assist effects of CM may play a role in some patients, our study found that this was not required to achieve substantial benefits from the procedure. We speculate that CM may act more passively, like an elastic girdle around the heart, to help reverse chamber remodeling.

Adult↗
PubMed1995

Acalculous candidal cholecystitis: a previously unrecognized complication after cardiac transplantation.

Acalculous cholecystitis is a life-threatening complication in critically ill surgical patients. Whereas Candida albicans and Torulopsis glabrata have been reported as the primary pathogens in 14 previous cases of acalculous cholecystitis, we report the first case of Candida parapsilosis as a biliary pathogen in a patient after cardiac transplantation. Although cardiac transplant recipients often have many of the risk factors for acalculous candidal cholecystitis, including major surgery, immunosuppression, antibiotic therapy, parenteral nutrition, and prolonged intensive care unit stay, this entity has not been previously reported in the cardiac transplant population. Although rare, acalculous candidal cholecystitis is associated with very high morbidity and a mortality rate of 40%. Early diagnosis necessitates an aggressive approach to the critically ill patient with abdominal complaints. Prompt drainage or cholecystectomy, if possible, represent the mainstays of therapy and offer the greatest chance for survival.

Candidiasis↗
PubMed1994

New method for mechanistic studies of cardiomyoplasty: three-dimensional MRI reconstructions.

The imaging modalities used to study the mechanism of cardiomyoplasty, such as echocardiography and radionuclide scintigraphy, are seriously limited by their two-dimensional format. Radiofrequency-pulse-tagged magnetic resonance imaging was used to generate three-dimensional reconstructions of the left ventricle throughout the cardiac cycle after cardiomyoplasty. In 2 dogs that had undergone conditioned, right anterior cardiomyoplasty, wrap stimulation with alternating heartbeats was found to produce marked translation of the left ventricle in the short-axis plane, rotation around the long axis, and displacement along the long axis with net long-axis compression; there was no augmentation of radial squeeze. The findings from this study suggest that any systolic augmentation produced by the right anterior wrap is due primarily to long-axis compression. Our study demonstrates a new, more accurate technique of assessing the mechanical effects of cardiomyoplasty in three dimensions, thus permitting a more rational optimization of wrap configurations, and emphasizes the perils of using standard two-dimensional imaging modalities in this setting of exaggerated three-dimensional motion.

Animals↗
PubMed1994

Intracardiac thrombus: a risk of incomplete anticoagulation for cardiac operations.

Mitral valve replacement was performed urgently in a patient with hemorrhagic brain lesions. To decrease the risk of intracranial hemorrhage, cardiopulmonary bypass was performed using a heparin-coated perfusion system and a reduced dose of heparin. The detection of an acute intracardiac thrombus by transesophageal echocardiography during cardiopulmonary bypass exposed a potential hazard of techniques employing reduced systemic anticoagulation for cardiac operations.

Acute Disease↗
PubMed1993

Pressure-volume analysis of changes in cardiac function in chronic cardiomyoplasty.

Reports of clinical improvement in human studies of dynamic cardiomyoplasty lack support by consistent objective hemodynamic evidence. Animal studies have also yielded conflicting results, likely due to nonuniform models, particularly the use of unconditioned wraps, and to limitations in commonly used study modalities caused by exaggerated heart motion during wrap stimulation. Our purpose was to assess the primary functional properties of the heart wrapped by conditioned muscle using pressure-volume relation analysis based on conductance catheter volume data. Compared with the unstimulated state, 1:1 stimulation caused an increase in contractility and decreases in end-diastolic volume and stroke work. Assisted beats during 1:2 stimulation showed an increase in contractility and a decrease in end-diastolic volume. Unassisted beats (1:2) showed decreases in end-diastolic volume and stroke work. There was no augmentation of cardiac output or ejection fraction with stimulation (1:1 or 1:2). We conclude that in the nonfailing heart, increased contractility does not augment cardiac output, ejection fraction, and stroke work because of a simultaneous decrease in end-diastolic volume. These changes in contractility and end-diastolic volume may prove therapeutic for dilated cardiomyopathy.

Animals↗
PubMed1988

Long-term neurostimulation of skeletal muscle: its potential for a tether-free biologic cardiac assist device.

Skeletal muscle has a tremendous capacity to adapt. This adaptive phenomenon is seen perhaps to the greatest extent when skeletal muscle is subjected to chronic low frequency stimulation via the motor nerve. There is a decrease in glycolytic enzymes and an increase in oxidative enzymes, as well as a change in the contractile proteins and an increase in the mitochondrial volume fraction of the muscle fiber. These adaptive changes result in a muscle that is considerably more fatigue-resistant. Specifically herein, we report on a pneumatic aortic counterpulsator device powered by skeletal muscle. These muscle pumps functioned continuously and pumped blood effectively in tether-free animals for several weeks.

Adaptation, Physiological↗
PubMed1988

In vivo 31P-NMR spectroscopy of chronically stimulated canine skeletal muscle.

Chronic stimulation converts skeletal muscle of mixed fiber type to a uniform muscle made up of type I, fatigue-resistant fibers. Here, the bioenergetic correlates of fatigue resistance in conditioned canine latissimus dorsi are assessed with in vivo phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After chronic electrical stimulation, five dogs underwent 31P-NMR spectroscopic and isometric tension measurements on conditioned and contralateral control muscle during stimulation for 200, 300, 500, and 800 ms of an 1,100-ms duty cycle. With stimulation, phosphocreatine (PCr) fell proportional to the degree of stimulation in both conditioned and control muscle but fell significantly less in conditioned muscle at all but the least intense stimulation period (200 ms). Isometric tension, expressed as a tension time index per gram muscle, was significantly greater in the conditioned muscle at the two longest stimulation periods. The overall small change in PCr and the lack of a plateau in tension observed in the conditioned muscle are similar to that seen in cardiac muscle during increased energy demand. This study indicates that the conditioned muscle's markedly enhanced resistance to fatigue is in part the result of its increased capacity for oxidative phosphorylation.

Animals↗
PubMed1988

Skeletal muscle grafts applied to the heart. A word of caution.

Latissimus dorsi pedicle grafts (LDPGs) were wrapped around the heart in eight dogs. In four dogs, the LDPGs were stimulated chronically; the remaining four dogs served as unstimulated controls. Right-sided cardiac filling pressures were normal in all dogs when measured 4 months after graft application. Mean tension generated by the viable LDPGs was 153 +/- 49.9 g. LDPGs contracting in synchrony with the heart did not increase cardiac output. In one dog, the aortic pressure changed from 140/100 to 155/85 mm Hg during synchronous contraction of the LDPG. Three dogs were placed on cardiopulmonary bypass, and their hearts were placed in fibrillation. The LDPGs were then stimulated at a burst frequency of 85 Hz and contracted vigorously. Under these conditions, the left ventricular pressure increased by an average of 15 mm Hg with each LDPG contraction; however, the mean aortic pressure was virtually unchanged. Left ventricular and aortic pressures of 125/20 and 125/65 mm Hg, respectively, could be obtained with manual compression of the fibrillating heart. This study indicates that although LDPGs can be made to contract chronically and in synchrony with the heart, they do not necessarily augment left ventricular performance.

Animals↗
PubMed1987

Skeletal muscle as the potential power source for a cardiovascular pump: assessment in vivo.

Skeletal muscle ventricles (SMVs) were constructed from canine latissimus dorsi and connected to a totally implantable mock circulation device. The SMVs, stimulated by an implantable pulse generator, pumped continuously for up to 8 weeks in free-running beagle dogs. Systolic pressures produced by the SMVs, initially of 139 +/- 7.2 mmHg and after 1 month of continuous pumping of 107 +/- 7 mmHg, were comparable to normal physiologic pressures in the adult beagles (114 +/- 21 mmHg). After 2 weeks of continuous pumping, the mean stroke work of the SMVs was 0.4 X 10(6) ergs, a performance that compares favorably with the animal's cardiac ventricles. This study shows that canine skeletal muscle which has not received prior training or electrical conditioning can perform sustained work at the high levels needed for an auxiliary cardiovascular pump. It might be possible eventually to use such muscle pumps in humans to assist the failing circulation and to provide support in children with certain types of congenital heart defects.

Adenosine Triphosphatases↗
PubMed1987

Canine diaphragm muscle after 1 yr of continuous electrical stimulation: its potential as a myocardial substitute.

Skeletal muscle has been rendered fatigue resistant by chronic stimulation and therefore has potential as an active substitute for damaged myocardium. It is therefore important to know whether stimulation produces any deleterious effects in the long term. Hemidiaphragm muscles of four dogs were examined after chronic stimulation for 1 yr at either 2 or 4 Hz. The stimulated hemidiaphragms appeared normal on gross inspection and were still contracting vigorously. By histochemical and immunohistochemical criteria, they had acquired a uniformly type I character, in contrast to the mixed fiber type composition of the unstimulated hemidiaphragms. This transformation was also reflected in their complement of myosin isozymes. There was some enzymatic evidence of an associated shift towards aerobic pathways of energy generation. Histological examination revealed no evidence of degenerative changes. Trends, observed in the shorter term (6-8 wk), toward a decrease in fiber area and an increase in connective tissue showed no further progression at 1 yr. Thus hemidiaphragm muscle stimulated at frequencies at or above the normal heart rate does not appear to undergo adverse long-term changes that would constrain its use in a myocardial assist role.

Animals↗
PubMed1987

Power output of skeletal muscle ventricles in circulation: short-term studies.

Skeletal muscle ventricles (SMVs) were constructed from preconditioned latissimus dorsi muscles in eight dogs and then connected to each animal's systemic arterial circulation in short-term experiments. The lengths of time that SMVs could produce hemodynamic work as left ventricular assist devices were recorded. After 4 hr of continuous pumping at approximately 55 beats/min, six of eight SMVs were able to generate systolic pressures of 128 +/- 23 mm Hg and flows of 340 +/- 31 ml/min, representing 20 +/- 4% of the animals' cardiac output. After 8 hr of continuous pumping, five of the eight SMVs generated pressures of 110 +/- 15 mm Hg and flows of 308 +/- 88 ml/min, or 15 +/- 7% of the animals' cardiac output. The stroke work produced by the SMVs was intermediate between that of the animals' left and right ventricles. Although the SMVs were stimulated to contract at only about one-third the heart rate, the power output of the SMVs approximated that of the right ventricles because of the greater stroke work of the SMVs. Two SMVs functioned as LVADs for 14 hr. Deterioration in SMV function eventually occurred. In each case, however, complications such as anemia, hypoxia, and hypotension, which are inherent to prolonged short-term experiments of this type, contributed to the deterioration of SMV function. The results presented here suggest that skeletal muscle has the potential to directly support the circulation; however, the length of time such muscle pumps are capable of functioning has yet to be determined.

Animals↗
PubMed1987

Skeletal muscle ventricles in circulation. One to eleven weeks' experience.

Skeletal muscle ventricles were constructed from canine latissimus dorsi and connected to the thoracic aorta in six dogs. These ventricles were stimulated to contract synchronously during diastole. The skeletal muscle ventricles were capable of continuous stroke work when placed within the arterial circulation for several weeks. Effective synchronous diastolic counterpulsation was produced. These results demonstrate that diastolic counterpulsators can be constructed from skeletal muscle and in the future may provide a feasible therapeutic alternative for the treatment of end-stage cardiac failure.

Animals↗