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Biomedical subjects

D C Miller

Publications and source records attributed to D C Miller.

At least 271 records · Page 15Linked to original sources
PubMed1988

Effects of aspirin, dipyridamole, and cod liver oil on accelerated myointimal proliferation in canine veno-arterial allografts.

The effects of the administration of aspirin (ASA), dipyridamole (DPM), and cod liver oil (CLO) on graft patency rate and degree of intimal hyperplasia were investigated in a canine, hypercholesterolemic veno-arterial allograft model in an attempt to modify this immunologically mediated vascular injury. The drug regimens were ASA 1 mg/kg/day, DPM 10 mg/kg/day, combined ASA and DPM (ASA + DPM), and CLO (1.8 g/day eicosapentanoic acid [EPA] and 1.2 g/day docosahexanoic acid [DHA]), and control. The early angiographic patency rate (1-3 weeks) was 81% +/- 10% (+/- 70% confidence limits); the 90-day overall patency rate was 60% +/- 4% (87/144), with no statistically significant differences among the groups (range 46 +/- 10-71 +/- 9%). Qualitatively, there was no difference in luminal thrombus, intimal hemorrhage, or lesion eccentricity. Considering the relatively short time of graft implantation, an extensive amount of microscopic disease was observed; quantitatively, the mean intimal thickness was 515 +/- 17 microgram overall but was not statistically different between the groups. The fraction of potential lumenal area occupied by intimal thickening was 0.37 +/- 0.01 but again did not differ significantly between the groups. These doses of ASA, DPM, ASA + DPM, and CLO did not alter graft occlusion or retard the marked degree of subintimal myointimal cell hyperplasia that was generated in this hypercholesterolemic canine veno-arterial allograft preparation. Possible explanations for these negative findings include inadequate dosage or form of omega-3 fatty acids and the antiplatelet drugs administered, excessive variability in graft response due to uncharacterized immunologic histocompatibility, and the possible influence of non-platelet-mediated mechanisms. Nevertheless, this preparation is attractive as a reproducible model of accelerated (immunologically mediated) experimental arteriosclerosis.

Animals↗
PubMed1988

A simple technique for aortic valve replacement using freehand allografts.

Given the recent resurgence of interest in the use of "fresh" and cryopreserved allograft valves for aortic valve replacement, the fact that many cardiac surgeons were not exposed to the operative techniques involved in freehand implantation of allograft valves during their residency training, and the paucity of teaching materials that clearly portray such techniques, details of a simplified method of subcoronary, freehand allograft valve implantation in the aortic position are described and illustrated.

Aortic Valve Stenosis↗
PubMed1988

Valvular-ventricular interaction: the importance of the mitral chordae tendineae in terms of global left ventricular systolic function.

While conventional mitral valve replacement (MVR) for patients with chronic mitral regurgitation has been associated with relatively high operative mortality rates and incidence of late postoperative left ventricular (LV) failure and death, chordal-sparing mitral valve operations (valve repair/reconstruction or MVR with preservation of the chordae tendineae) subjectively appear to portend lower operative morbidity and mortality rates, better functional results, and improved long-term survival rates. Such empirical clinical observations have provided the basis for the concept of valvular-ventricular interaction, namely, that the intact mitral chordae are important mediators of more efficient and forceful ventricular contraction that enhances LV performance. This paper reviews the pertinent basic physiology and dynamics of the chordae tendineae and papillary muscles and examines critically the available experimental and clinical data regarding valvular-ventricular interaction. The problems inherent in quantifying LV contractility are central to this discussion and are also examined. While earlier experimental studies have produced conflicting results, more recent experiments utilizing load-independent measures of ventricular performance (particularly in isovolumic preparations) have conclusively demonstrated the importance of chordal integrity for optimal LV systolic function in normal animal hearts. The balance of the clinical evidence is also suggestive (although by no means conclusive) regarding the importance of valvular-ventricular interaction. Recent experimental evidence suggests that the mitral chordae enhance LV systolic function by means of regional afterload reduction. The mechanism(s) responsible for valvular-ventricular interaction, however, remains incompletely characterized at the present time, which underscores the urgent need for further experimental and, most importantly, clinical studies.

Animals↗
PubMed1988

Torsional deformation of the left ventricular midwall in human hearts with intramyocardial markers: regional heterogeneity and sensitivity to the inotropic effects of abrupt rate changes.

The spiral orientation of left ventricular (LV) fibers suggests that twisting about the ventricular long axis of the apex with respect to the base, i.e., torsional deformation, may be characteristic of LV contraction. To demonstrate this twisting motion, 10 orthotopic human cardiac allograft recipients were studied with biplane cineradiography of tantalum helices implanted within the LV midwall at 12 specific sites. Counterclockwise twisting about the LV long axis (as reviewed from apex to base) accompanied ventricular ejection in all patients. Torsional deformation angles, measured relative to a reference minor axis at the base, were substantially smaller in the anteroapical wall, as compared with counterparts in the apical third of the inferior and lateral walls (anterior = 13.3 +/- 6.0 degrees, inferior = 18.7 +/- 6.3 degrees, and lateral = 23.4 +/- 10.7 degrees). Torsional angles at the midventricular level were roughly half as much and exhibited similar regional variabilities (anterior = 7.6 +/- 3.3 degrees, inferior = 9.0 +/- 3.3 degrees, lateral = 10.7 +/- 5.2 degrees, and septal = 8.8 +/- 3.8 degrees). Comparison of control beats and the initial beat after abrupt cessation of rapid atrial pacing (126 +/- 10 beats/min) with return to the control heart rate (96 +/- 9 beats/min) permitted the mild positive inotropic effect of tachycardia to be assessed at similar levels of ventricular load. Torsional deformation of the anteroapical and inferoapical sites increased significantly (p less than 0.05) over control values to 15.6 +/- 7.5 degrees and 21.2 +/- 5.5 degrees, respectively. In contrast, torsional deformation of the lateral wall was essentially unchanged. These data provide direct evidence for torsional deformation of the left ventricle in humans, demonstrate that torsion of the LV chamber is nonuniform, and suggest a dependence of LV torsion upon contractile strength that is attenuated in the lateral wall.

Heart↗
PubMed1988

Increased elastin mRNA levels associated with surgically induced intimal injury.

Quantitative levels of mRNAs coding for elastin, types I and III procollagen and gamma-actin were measured in porcine vascular material following balloon catheterization. A balloon catheter was introduced into the thoracic aorta and jugular vein of 3-6 week old pigs; following distention and six days of postoperative recovery, tissue samples were obtained for histopathology, electron microscopy, RNA extraction and mRNA quantitation. Using a series of mammalian cDNA clones and the procedure of slot blot hybridization, we have shown that elastin and types I and III procollagen mRNA levels rose significantly during the postoperative period following vascular distention. The increase correlated with an increase in the cell mass present in both the venous and arterial intimal layers. Changes in gamma-actin mRNA levels were also associated with this rapid proliferative response but in arterial tissue only.

Actins↗
PubMed1988

Primary central nervous system lymphoma.

Primary lymphoma of the central nervous system (CNS), including reticulum cell sarcoma, microglioma, and histiocytic lymphoma, represents less than 1% of all primary brain tumors. In the last 10 years, this tumor has tripled in frequency in the nonimmunosuppressed population. By 1991, the tumor will be the most common neurological neoplasm by virtue of the increase in sporadic occurrence and in the acquired immunodeficiency syndrome (AIDS) population. Three percent of AIDS patients will develop this tumor either prior to AIDS diagnosis or during their subsequent course. In addition to acquired immunosuppression, patients with inherited disorders (such as Wiskott-Aldrich syndrome, severe combined immunodeficiency, and X-linked immunodeficiency) and other acquired disorders of the immune system are predisposed to the development of CNS lymphoma. Immunological studies have suggested a role for Epstein-Barr virus in the production of this tumor. Although subtypes exist, non-Hodgkin's lymphoma of the CNS most commonly consists of histiocytic cells or large immunoblastic cells bearing B cell surface markers in close proximity to the lateral and third ventricles. Sixty percent of these deposits are multiple, and subarachnoid invasion is seen in one-quarter of patients. Vitreous involvement of the eye occurring prior to and during the course of CNS lymphoma has been noted in up to 25% of patients. The involvement of multiple areas of the neuraxis, the eye, and multiple intracranial sites often occurs in the absence of obvious systemic lymphoma. Therapeutic trials of brain radiation therapy are associated with median survivals of less than 1 year. Uniform complete responses of intracranial deposits are recorded following chemotherapy with high-dose intravenous methotrexate, CHOP (cyclophosphamide, hydroxydaunomycin/doxorubicin, Oncovin (vincristine), and prednisone), high-dose cytosine arabinoside, and intra-arterial methotrexate with barrier modification.

Central Nervous System Diseases↗
PubMed1988

Inhibition of vein graft intimal thickening by eicosapentanoic acid: reduced thromboxane production without change in lipoprotein levels or low-density lipoprotein receptor density.

Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.

Animals↗
PubMed1988

Restoration of left ventricular systolic performance after reattachment of the mitral chordae tendineae. The importance of valvular-ventricular interaction.

Clinical studies suggest that chorda-sparing mitral valve replacement techniques are associated with superior postoperative outcome, and several animal experiments have shown that disruption of the mitral subvalvular apparatus is followed by deterioration of left ventricular systolic function. One essential element, however, underlying the importance of chordal integrity for left ventricular function remains unproved: All investigators heretofore have been unable to demonstrate that left ventricular systolic performance can be restored by chordal reattachment after disruption of annular-papillary continuity. Therefore, we studied the effects of chordal detachment and subsequent chordal reattachment on left ventricular systolic performance using an in situ, isovolumic heart preparation in 10 halothane-anesthetized swine. The slope and left ventricular volume intercept of the isovolumic peak pressure-volume relationship were measured to assess global left ventricular systolic performance independent of load. Coronary perfusion pressure was maintained constant (95 +/- 6 mm Hg [+/- standard deviation]), and heart rates were in the physiologic range (133 +/- 26 min-1). Slope changed significantly (repeated measures analysis of variance, p = 0.0002), decreasing by 29% (from 4.74 +/- 0.94 to 3.37 +/- 0.87 mm Hg/ml, p less than 0.001) after chordal detachment and then returning to baseline (6.05 +/- 2.38 mm Hg/ml, p = 0.001) after chordal reattachment. Slope after chordal reattachment was not significantly different from the baseline value (p = 0.074). Volume intercept did not change significantly (p = 0.44) at any time. We conclude that the acute decrease in left ventricular contractility associated with surgical interruption of annular-ventricular continuity can, in fact, be reversed by chordal reattachment in this experimental model (isovolumically contracting normal porcine hearts). These data provide concrete confirmation of the concept of valvular-ventricular interaction; if these findings can be corroborated in the dilated, human left ventricle, such would strongly support efforts to preserve the mitral chordae tendineae during clinical mitral valve replacement to optimize postoperative left ventricular function.

Animals↗
PubMed1988

Operative mortality in patients undergoing single valve replacement in teaching institutions--early mortality as a function of resident versus staff surgeon.

Nine hundred sixty-four patients undergoing single valve replacement (SVR) procedures alone or in combination with other cardiac surgical procedures were analyzed prospectively to determine whether the risks of operative mortality (OM) are different when the operation is performed by a resident under direct supervision of an attending surgeon (group I, 49.5%) or by an attending surgeon (group II, 50.5%). The overall OM rate was 8.4% (7.2% for group I and 9.7% for group II, which was not significant). Fifty-eight clinical, angiographic, and hemodynamic variables were analyzed to adjust statistically for differences in patient characteristics in each group. For aortic valve replacement, group II patients had smaller valve area and a higher incidence of three-vessel coronary artery disease, and more patients required resection of an ascending aortic aneurysm, whereas group I patients had higher incidence of peripheral edema and S3 gallop. For mitral valve replacement, more patients in group II had pleural effusion, previous cardiac operations, higher mean pulmonary artery pressures, mitral insufficiency due to coronary artery disease, and were in New York Heart Association (NYHA) functional class 3 and 4, whereas the group I patients had higher incidence of S3 gallop and elevated serum creatinine. Expected OM for each group was derived from a multivariate logistic model. Ratio of observed-to-expected (O/E) OM was calculated to adjust observed OM according to the risk of patients. There was no difference in O/E mortality ratio between the two groups. We conclude that OM probability is not increased when the SVR procedure is performed by residents under direct supervision of attending surgeons when adjusted for patient- and disease-related risk factors. These findings also constitute compelling evidence that patient care does not suffer when resident teaching experience is enhanced in teaching institutions.

Aortic Valve↗
PubMed1987

Central nervous system neoplasm in a young man with Martin-Bell syndrome--fra(X)-XLMR.

A 17-year-old retarded male developed unilateral leg weakness with foot drop, pain, and incontinence. Workup disclosed a cauda equina tumor which, on surgical exploration, was demonstrated to merge with the conus medullaris. Pathological examination of the subtotally resected tumor led to a diagnosis of malignant ganglioglioma. Further evaluation of the patient documented marginal macro-orchidism, and chromosome studies showed fragile X. Since some neoplasms are known to be associated with chromosomal deletions and other abnormalities, we suggest that the occurrence of this tumor in this patient indicates a more than coincidental relationship between the two diagnoses.

Adolescent↗
PubMed1987

A tri-institutional comparison of tissue and mechanical values using a patient-oriented definition of "treatment failure".

Selection of valve type for predominant usage is obscured by limiting the analysis to prosthesis-related rather than patient-oriented failure modes. In this report, "treatment failure" is defined as a valve-related death or permanent patient disability; successful reoperations are excluded, and emboli with permanent residua are included. Results with the Starr-Edwards Silastic ball valve (Oregon) and the Hancock (Stanford) and Carpentier-Edwards (Vancouver) porcine valves are compared using this new definition of treatment failure. Evaluated according to structural failure, the mechanical valve is superior to the tissue valve, and using the Stanford definition of valve failure, it becomes so between 5 and 10 years. Using treatment failure, tissue valves are superior at 5 years; at 10 years in the aortic position, the results are comparable; and in the mitral position at 8 to 10 years, tissue valves show a continued but small advantage.

Aortic Valve↗
PubMed1987

When should Doppler-determined valve area be better than the Gorlin formula?: Variation in hydraulic constants in low flow states.

In low flow states, underestimation errors occur when the Gorlin formula is used to calculate valve area. A model of valvular stenosis designed to examine changes in the hydraulic discharge coefficient (Cd) and coefficient of orifice contraction (Cc) may explain these errors. Unsteady flow was examined in a pulsatile pump model and in a dog model. Valve areas were calculated from pressure and flow data using: a modified form of the Gorlin formula (assuming constant values for Cd and Cc) and a corrected formula (with values of Cd and Cc obtained from steady state data). Valve area was also calculated using the continuity equation with velocity and flow data (constant Cc). Flow velocities were measured using a newly designed ultrasound Doppler catheter capable of resolving flow velocities of up to 5.5 m/s. Both the corrected formula and continuity equation were highly predictive of actual valve area (r = 0.99, slope or M = 0.96 and r = 0.99, M = 1.06, respectively). The modified Gorlin equation was less accurate and tended to underestimate valve areas (r = 0.87, M = 0.83). This underestimation was most notable at low rates of flow (Gorlin: r = 0.94, M = 0.53; continuity: r = 0.93, M = 0.81 and r = 0.94, M = 0.89, respectively) more accurately than the modified Gorlin formula (r = 0.69, M = 0.49). In patients with low cardiac output, hemodynamic formulas, such as the Gorlin formula, which assume a constant value for the hydraulic discharge coefficient (Cd), may be less accurate than formulas using either a corrected value of Cd or Doppler-determined flow velocity and mean systolic flow.

Animals↗
PubMed1987

Incomplete biochemical adaptation of vein grafts to the arterial environment in terms of prostacyclin production.

Biochemical (or functional) adaptation of venoarterial grafts has been demonstrated recently. We reexamined one aspect of this biochemical "arterialization" process: prostacyclin (PGI2) production by canine venoarterial autologous grafts and the responsiveness of this biosynthetic pathway to maximal stimulation with substrate enhancement. Four reversed autologous grafts (femoral vein) were interposed into both carotid and femoral arteries in eight dogs. After 12 weeks, the grafts were removed, and radioimmunoassay was used to determine luminal surface production of 6-keto-PGF1 alpha (the stable metabolite of PGI2) in both the basal and stimulated (27 mumol/L arachidonic acid [AA]) states. PGI2 production by the venous autologous grafts was compared with that of control native artery and vein. We confirmed that PGI2 production (measured in nanograms per milliliter) by control artery was greater than vein under both basal conditions (5.8 +/- 0.4 [+/- SEM] vs. 2.7 +/- 0.5, p less than 0.001) and stimulated conditions (8.8 +/- 0.8 vs. 5.5 +/- 0.4, p = 0.002); moreover, AA stimulation significantly increased PGI2 production in both native artery and vein compared with basal PGI2 production. Under basal conditions, graft PGI2 production (6.3 +/- 1.6 ng/ml) was not significantly different than basal arterial levels (p = 0.8) but was higher than basal venous levels (p = 0.05). However, in marked contrast to both native artery and vein, the vein graft flow surface showed no significant response to substrate enhancement with AA: basal (6.3 +/- 1.6 ng/ml) vs. stimulated (5.9 +/- 0.9 ng/ml) (p = 0.8). These observations confirm that canine venoarterial autologous grafts undergo biochemical "arterialization"; however, this process appears to be an incomplete one.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1987

Cardiac cryolesions as an experimental model of myocardial wound healing.

The standard coronary ligation model for experimental myocardial infarction results in variable areas and patterns of necrosis; therefore, the healing of such infarctions is also variable. The authors developed an experimental myocardial injury model using simple cryoinjury, which allows standardization of the size, depth, and location of the wound. Thirty-eight left ventricular cryolesions were created in 19 dogs, which were then killed from 3 to 35 days after injury. A consistent decrease in the depth of scar (p less than 0.005) and accumulation of collagen (p less than 0.0001) over time characterized this healing myocardial wound. Histologic examination revealed that the cellular pattern of healing myocardial cryolesions is similar to that of a healing myocardial infarction but with less variability. The authors advocate the use of cardiac cryolesions as a model of experimental myocardial wound healing.

Animals↗
PubMed1987

"Fresh" aortic allografts: long-term results with free-hand aortic valve replacement.

Renewed interest in the use of "fresh" and cryopreserved allograft valves for aortic valve replacement (AVR) prompted an updated analysis of the long-term results of our old experience (1964-1971) with free-hand AVR. Eighty-three patients received "fresh" (antibiotic stored at 4 degrees C for intervals between 24 hrs and 18 days), free-hand allograft valves. Current (1986) follow-up was 96% complete; cumulative follow-up included 773 patient-years (pt-yr) and averaged 9 yrs. Importantly, 37 patients were still at risk with their original allograft valve at ten yrs, and 12 patients at 17 yrs. Standard conservative criteria were used to assess valve-related complications. Thromboembolism (TE) occurred at a linearized incidence of 1.0%/pt-yr, anticoagulation-related hemorrhage (ACH) at 0.2%/pt-yr), and fatal prosthetic valve endocarditis (PVE) at 0.5%/pt-yr. In actuarial terms, the incidence of degenerative valve failure was 30 +/- 6% (+/- SEM) at ten yrs and 40 +/- 7% at 15 yrs. Valve failure due to all causes (including sudden, unexplained deaths and PVE) occurred in 38 +/- 6% of patients at ten yrs and 57 +/- 7% after 15 yrs. The incidence of fatal valve failure was 11 +/- 4% at six yrs (the time of the last event). The rate of reoperation was 33 +/- 6% at ten yrs and 52 +/- 7% at 15 yrs. Given the relatively crude methods of allograft valve preparation and storage during this remote era, we believe that these long-term results with free-hand allograft AVR are satisfactory, albeit far from optimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Effect of acute human cardiac allograft rejection on left ventricular systolic torsion and diastolic recoil measured by intramyocardial markers.

Left ventricular systolic torsion and diastolic recoil were quantified in 12 human cardiac transplant recipients with surgically implanted intramyocardial markers with the use of computer-aided analysis of biplane cineradiographic images. Measurements were performed between 6 and 16 weeks after surgery and related to the presence or absence of rejection as determined by cardiac biopsy. Torsional deformation, defined as twisting about the left ventricular long axis of the apical region with respect to the base, was characterized in terms of the rate and amplitude of systolic torsion and the rate of diastolic recoil by means of an internal reference system. Comparison of measurements before, during, and after recovery from 14 rejection episodes allowed assessment of the effects of acute reversible cardiomyopathy on left ventricular torsion and recoil. Compared with prerejection values, the amplitude of torsional deformation in the maximally deforming segment (theta max) decreased by 25% from 21.1 +/- 15.2 to 16.0 +/- 5.7 degrees (p less than .005) during acute rejection with myocyte necrosis; this was associated with significant (p less than .05) decreases in the peak systolic torsion rate (+d theta/dtmax), whereas the peak diastolic recoil rate (-d theta/dtmax) was unchanged. This suggests that the stiffness of elastic components of the myocardium may have increased, maintaining the rate of diastolic recoil when these elements are stretched less. With successful treatment of rejection episodes, the torsional deformation characteristics normalized. Heart rate, mean arterial pressure, left ventricular end-diastolic volume, stroke volume, ejection fraction, and peak left ventricular filling rate were unchanged with rejection episodes, whereas left ventricular end-systolic volume increased (p less than .05) during acute rejection and returned to normal with resolution of the rejection process. These data suggest that left ventricular torsional deformation amplitude and rate are sensitive to episodes of subclinical left ventricular dysfunction and that such intramyocardial marker techniques may provide new insights regarding the elastic properties of the ventricular myocardium and their impact on left ventricular mechanics.

Acute Disease↗