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Biomedical subjects

R M Bolman

Publications and source records attributed to R M Bolman.

At least 127 records · Page 7Linked to original sources
PubMed1988

Noninvasive assessment of treatment of cardiac allograft rejection with indium-111-labeled lymphocytes.

We have shown previously that cardiac allograft rejection can be detected noninvasively with gamma scintigraphy after administration of indium-111 (111In)-labeled lymphocytes. To determine whether this technique could be used to monitor salvage immunosuppressive therapy in reversing rejection, 5 dogs were studied after thoracic heterotopic cardiac transplantation. Initial postoperative immunosuppression was maintained with cyclosporine (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 7 days after transplantation and then discontinued. Scintigraphy after administration of labeled lymphocytes was performed during initial immunosuppression and every 3 days after its termination. Endomyocardial biopsies were obtained on each day scintigraphy was performed. Once scintigraphic criteria for rejection were met (111In-lymphocyte uptake greater than mean +/- 2SD of normal myocardium), animals were treated with high dose methylprednisolone and cyclosporine. Myocardial 111In-lymphocyte activity compared with that in blood was 0.7 +/- 0.8 during initial immunosuppression, increased to 5.7 +/- 3.5 after termination of therapy (P less than 0.01), and diminished with salvage immunosuppressive therapy to 0.5 +/- 0.8 (P = NS compared with native hearts or allografts during initial immunosuppression). Scintigraphy accurately predicted all but one episode of biopsy-documented rejection and accurately detected reversal of rejection during salvage. Thus, scintigraphy with 111In-labeled lymphocytes should facilitate noninvasive monitoring of antirejection therapy in patients.

Animals↗
PubMed1988

Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy.

Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

Animals↗
PubMed1987

Effects of transplantation on atrioventricular nodal accommodation and hysteresis.

In the present study, atrioventricular nodal accommodation and hysteresis characteristics were evaluated in awake, unsedated dogs, before (n = 10) and after cardiac transplantation (n = 10). Chronically instrumented animals were atrially paced at a cycle length (CL) of 400 ms, followed by an abrupt decrease in pacing CL to 300 ms, followed by an abrupt return in pacing CL to 400 ms (with pacing sustained for 60 s at each CL). Atrioventricular nodal conduction characteristics (assessed by AH intervals) were simultaneously monitored. Under control conditions, AH intervals lengthened rapidly after an abrupt decrease in pacing CL [mean time for AH interval lengthening to stabilize (Tonset) = 2 +/- 1 s], whereas AH intervals lengthened more slowly (P less than 0.05) after transplantation (Tonset = 41 +/- 4 s). Similarly, after an abrupt increase in pacing CL, control AH intervals shortened rapidly [mean time for AH interval to return to base line (Tonset) = 5 +/- 1 s], whereas AH intervals shortened more slowly (P less than 0.05) after transplantation (Tonset = 42 +/- 5 s). Thus accommodation appears to be an intrinsic atrioventricular nodal response (present after cardiac denervation by transplantation) to abrupt, sustained atrial CL changes. Furthermore equivalence (P = NS) in atrioventricular nodal accommodation responses to symmetric CL decreases and increases after transplantation suggests that hysteresis [i.e., nonequivalence (P less than 0.05) in atrioventricular nodal accommodation responses], as seen under control conditions, results primarily from extrinsic (neural) modification of intrinsic atrioventricular nodal responses to symmetric CL changes.

Adaptation, Physiological↗
PubMed1987

Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes.

To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 (111In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous 111In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed (p less than .01). In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures.

Animals↗
PubMed1987

Potentiation of cardiac electrophysiologic effects of verapamil after autonomic blockade or cardiac transplantation.

Cardiac electrophysiologic effects of verapamil in vivo are the result of both direct and indirect actions on the heart (the latter due to augmentation of sympathetic neural tone, diminution of parasympathetic neural tone, and increased circulating catecholamines). In this study we assessed the interaction of verapamil's direct and indirect actions on electrophysiologic properties of the heart in awake, previously instrumented, unsedated dogs. After administration of intravenous verapamil (0.2 mg/kg), electrophysiologic effects were assessed serially over a 1 hr period in 10 awake dogs before (group 1 studies) and during pharmacologic autonomic blockade (group 2 studies), and in a subset of these dogs (n = 5) after orthotopic cardiac transplantation (group 3 studies). In group 1 dogs, sinus cycle length (SCL) initially shortened after verapamil (postverapamil 379 +/- 50 msec vs baseline of 494 +/- 72 msec, p less than .001) and subsequently gradually prolonged. In groups 2 and 3, transient SCL shortening was absent. SCL prolonged promptly after verapamil, and sinus arrest developed in two of 10 group 2 and two of five group 3 animals. Verapamil exerted a negative dromotropic effect on atrioventricular node conduction in all three experimental groups, as assessed by drug-induced changes in minimum cycle length with sustained 1:1 atrioventricular conduction and measurements of atrioventricular node effective and functional refractory period. However, compared with findings in group 1, this negative dromotropic effect occurred more rapidly and was markedly potentiated in groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Anti-B-mediated rejection of an ABO-incompatible cardiac allograft despite aggressive plasma exchange transfusion.

A group A recipient received a group B cardiac allograft. Aggressive plasma exchange with replacement by group AB FFP initially reduced the recipient's anti-B titer to a low level. Once a secondary anti-B response was mounted, plasma exchange was ineffective and IgM and IgG anti-B titers rose to high levels. Associated with the increased anti-B titers, cardiac function deteriorated and on day 13 the group B heart was replaced by a group A allograft. The compatible allograft functioned well initially but was eventually rejected, and the patient died 51 days after the initial transplantation. Histologic examination of the first allograft revealed a delayed form of typical antibody-mediated rejection with destruction of the microvasculature associated with antibody deposition and acute inflammation. By contrast, the histopathology of the second compatible allograft was typical of cell-mediated allograft rejection. Extracts of myocardium from the incompatible heart contained IgM and IgG anti-B, while no anti-B alloantibody was demonstrable in the extracts of the ABO-compatible allograft and a control heart. The utility of plasma exchange with group AB FFP replacement in such a circumstance requires further study.

ABO Blood-Group System↗
PubMed1986

Endomyocardial biopsy in the cardiac allograft recipient. A review of 570 biopsies.

The morphologic abnormalities present in 570 endomyocardial biopsies from 39 cardiac allograft recipients and 16 autopsy hearts are described, and criteria pertinent to the diagnosis of rejection discussed. Entirely normal myocardium was apparent in 16% of the biopsies. Abnormalities related to biopsy of previous biopsy site occurred in 69%, and mononuclear infiltrates of varying intensity were present in 64% of the biopsies. Acute rejection was diagnosed in 17 (43.6%) patients in 32 (5.6%) of the biopsies and five hearts at autopsy. Seven of the biopsies with acute rejection were follow-up biopsies after a previous diagnosis of acute rejection and represented ongoing acute rejection. Similarly, three patients with rejection at autopsy died with ongoing rejection. The overall frequency of acute rejection was thus 0.70 episodes per patient. The most reliable histologic feature in the diagnosis of acute rejection in cyclosporine immunosuppressed recipients was a diffuse mononuclear infiltrate, apparent at low magnification. Myocyte necrosis, said to be critical in the diagnosis of rejection in cyclosporine-treated patients, was not a reliable indicator in the authors' experience.

Adolescent↗
PubMed1985

Kinetics of electrophysiologic changes during oral loading of amiodarone and after withdrawal of amiodarone in the unsedated dog.

We examined the temporal kinetics of onset and offset of the cardiac electrophysiologic effects of orally administered amiodarone in chronically instrumented, unsedated adult dogs (n = 8). Right atrial (RA), atrioventricular nodal (AVN), and right ventricular (RV) effective refractory period (ERP), and AVN functional refractory period (FRP), were determined daily for 21 days during amiodarone loading (24 mg/kg/day) and for 21 days after cessation of amiodarone. Left ventricular (LV) ERP was assessed in four of eight animals. Group mean RA-ERP peaked and plateaued early during amiodarone loading (time to reach one-half observed peak change [t1/2 onset] = 1.2 +/- 0.5 days) and rapidly returned toward baseline after cessation of drug (decay time to one-half peak value [t1/2 offset] = 2.0 +/- 1.7 days). Group mean RV-ERP rose in a linear manner throughout the loading period (t1/2 onset = 9.3 +/- 2.1 days) and remained elevated after cessation of drug (t1/2 offset greater than 21.0 days). Group mean AVN-ERP and FRP exhibited temporal kinetics intermediate between those of the RA-ERP and RV-ERP, both during amiodarone loading and after cessation of the drug. Group mean LV-ERP onset kinetics (assessed in a limited number of animals, n = 4) appeared to differ from RV-ERP onset kinetics (t1/2 onset = 2.5 +/- 2.5 days), whereas LV-ERP and RV-ERP offset kinetics appeared similar (t1/2 offset greater than 21 days). In summary, our findings demonstrate that during oral loading, the temporal sequence of onset of amiodarone-induced electrophysiologic effects is site dependent. Similarly, after cessation of amiodarone, the persistence of drug-induced electrophysiologic effects is both variable and site dependent.

Administration, Oral↗
PubMed1985

Concomitant pulmonary and cerebral arteriovenous fistulae.

The previously unreported occurrence of concomitant pulmonary and cerebral arteriovenous fistulae was found in an individual with severe neurologic complications. Both polycythemia and paradoxical embolization were implicated in the genesis of the cerebral symptoms while the cerebral fistulae were asymptomatic. An improved method of therapeutic embolization was used to treat the pulmonary lesions, avoiding surgical resection.

Adult↗
PubMed1985

Improved immunosuppression for heart transplantation.

Since 1981, at the University of Minnesota, and more recently at Washington University in St. Louis, cyclosporine has been used as the main immunosuppressive agent for heart transplantation. It was initially combined with prednisone and given in a manner similar to that described at Stanford. In late 1983, concern regarding the nephrotoxic side effects of cyclosporine were heightened due to the fact that a potential recipient had chronic renal insufficiency secondary to renal damage suffered during previous heart surgery. In this patient it was decided to use lower doses of cyclosporine and to add azathioprine to maintain adequate immunosuppression. Initially, the same prednisone therapy was employed. This patient had an uncomplicated course following heart transplantation and was discharged with a normal renal function. This experience was the origin of a trial consisting of using cyclosporine, azathioprine, and prednisone as immunotherapy for heart transplantation. This report describes the results of this therapy in 17 patients.

Azathioprine↗
PubMed1984

Early mechanical function in the heterotopic heart transplant.

The characteristics of left ventricular (LV) function in the nonimmunosuppressed heterotopic heart transplant (TX) with less than 3 hr of cold preservation, were studied in 12 awake chronically instrumented dogs prior to TX (control), 1-12 hr post TX (P1), 12-24 hr post TX (P2), and 24-48 hr post TX (P3). Micromanometers measured LV transmural pressure and ultrasonic transducers measured ventricular dimension in order to allow calculations of myocardial mechanical properties. Immediately after transplant (P1) there was significant (P less than 0.05) depression noted in both diastolic function and systolic function (peak LV pressure, 137 +/- 5 vs 80 +/- 10 mm Hg; dp/dtmax, 2642 +/- 170 vs 1038 +/- 98 mm Hg/sec; maximum velocity of minor axis shortening, 4.46 +/- 0.50 vs 2.41 +/- 0.56; and Emax, 6.5 +/- 1.2 vs 2.0 +/- 1.4 mm Hg/ml). However, the contractility reserve (studied in six dogs) as estimated by postextrasystolic potentiation ratio was maintained (1.41 +/- 0.07 vs 1.37 +/- 0.15), suggesting reversibility of the depressed function. Over the next 2 days the diastolic function and the systolic function (at P3: 109 +/- 6 mm Hg, 1842 +/- 450 mm Hg/sec, 5.54 +/- 0.77 cm/sec, and 4.5 +/- 1.3 mm Hg/ml, respectively) gradually improved toward control. Microscopic examination of the autopsied hearts did not show significant evidence of rejection. Thus, the early depression of function in the heart TX appeared to be the result of ischemia from preservation and surgical trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Cardiac operations in patients with functioning renal allografts.

The Transplant Service at the University of Minnesota Hospitals has performed over 2,000 kidney transplants. Fourteen of these patients have developed cardiac conditions necessitating surgical intervention at intervals of 9 to 144 months (mean 67 months) following their transplantation. These individuals had a mean age of 42 years, and five (36%) were diabetic. All patients had functioning renal allografts with preoperative serum creatinine levels ranging from 1.0 to 1.8 mg/100 ml (mean 1.4 mg/100 ml). Ten patients underwent aorta-coronary saphenous vein bypass grafting. One patient underwent bypass grafting and concomitant left ventricular aneurysmectomy. Native valvular endocarditis developed in two patients. One had tricuspid valve debridement for fungal endocarditis and the other had aortic valve replacement for bacterial endocarditis. The final patient had calcific aortic stenosis and coronary artery disease necessitating aortic valve replacement and coronary bypass. Two patients (14%) died perioperatively. One was a young woman with juvenile-onset diabetes and preinfarction angina who died suddenly several days after the operation; at autopsy, she was found to have an occluded graft to the right coronary artery and extensive infarction. The other was a 54-year-old woman with calcific aortic stenosis, coronary artery disease, and unstable angina who died perioperatively of uncontrollable arrhythmias. Autopsy suggested that she may have had an unsuspected infarction 1 to 2 days before the operation. The remaining 12 patients had uneventful postoperative courses and returned to Class I functional status from a cardiac standpoint. There has been one late death (7%), 45 months after successful coronary artery bypass grafting, as a result of complications attendant to a perforated gastric ulcer. The remaining 11 patients are alive and well at intervals of 8 to 93 months (mean 31 months) after operation. Postoperative serum creatinine levels at hospital discharge averaged 1.6 mg/100 ml, not significantly changed from preoperative levels. Cardiac operations can be performed safely in patients with functioning renal allografts. Patient survival is acceptable and preservation of renal function has been uniformly successful in surviving patients.

Adult↗
PubMed1983

Elevated left ventricular myocardial dopamine in preterminal idiopathic dilated cardiomyopathy.

The adrenergic nervous system is chronically activated in patients with congestive heart failure (CHF). One consequence of this is depletion of the normally high levels of myocardial norepinephrine. In this study, myocardial norepinephrine and dopamine concentrations from the left ventricular walls of 3 patients undergoing cardiac transplantation for severe refractory CHF are reported. The dopamine/norepinephrine ratios were high in all 3 patients (29, 58 and 26%). This finding supports data from animal studies suggesting a change in the rate-limiting step for myocardial norepinephrine synthesis in CHF. Conversion of tyrosine to dopa by tyrosine hydroxylase is replaced as the rate-limiting step by inability to hydroxylate dopamine to norepinephrine. Thus, dopamine accumulates while norepinephrine is depleted.

Adult↗
PubMed1981

Surgical management of chronic relapsing pancreatitis.

Chronic relapsing pancreatitis is a syndrome usually associated with chronic alcohol abuse, and is characterized by pain in the upper abdomen and back, weight loss, and disturbances in function of the endocrine and exocrine pancreas. A surgical attack on this disorder can be traced to the turn of the century, when experimental work suggested the feasibility of operations of the pancreas. In 1911 Link performed pancreatostomy for this disease and achieved an excellent long-term result. Later, partial or total pancreatectomy was introduced in the management of this condition. With pathologic evidence of pancreatic duct dilatation, attempts at retrograde drainage of the duct into the gastrointestinal tract were introduced in the 1950s, with encouraging results. The recent advent of diagnostic modalities capable of more precise definition of ductal anatomy allows more discriminate application of the two major surgical approaches of resection and internal drainage. In this review, the literature concerning this interesting subject is surveyed and the favored diagnostic and surgical methods are assessed.

Alcoholism↗
PubMed1980

Improved management of pancreatic lesions in children aided by ERCP.

Internal pancreatic fistulas have only recently been recognized as distinct entities in children. Unless their pathophysiology is understood they can present the clinician with a diagnostic dilemma. Recently, these entities have been better defined in the adult literature and significant improvement made in treatment. We report a case of a child with pancreatic ascites in whom endoscopic retrograde cholangiopancreatography significantly aided the diagnosis and the operative management. An outline of recommended management of pancreatic lesions in children is presented including internal pancreatic fistulas.

Ascites↗