Pathophysiology and prevention of acute renal failure associated with thoracoabdominal or abdominal aortic surgery.
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Acute Kidney Injury↗
Biomedical subjects
D C Miller
Publications and source records attributed to D C Miller.
A prospective, randomized study of the effects of prostacyclin on neuropsychologic dysfunction after coronary artery operation.
This randomized, double-blind study was designed to evaluate the effect of prostacyclin (epoprostenol) on the incidence and severity of postoperative neuropsychologic dysfunction in patients undergoing coronary artery operation. Four days before operation and 1 week after operation, 100 patients having coronary artery bypass grafting underwent detailed neurologic and psychologic examinations and computed tomographic scans of the brain. The psychologic examination was repeated 2 months after operation. During cardiopulmonary bypass, all patients received 300 U/kg of heparin and then either buffer-diluent or prostacyclin (12.5 ng/kg/min from the time of heparinization until onset of cardiopulmonary bypass and 25 ng/kg/min during cardiopulmonary bypass). No deaths or major neurologic complications occurred in this series. Ninety-six patients completed the psychologic and neurologic evaluations 1 week after operation; 74 of these patients were evaluated psychologically 2 months after operation. Psychologic testing demonstrated similar declines in postoperative performance in both the prostacyclin-treated and the control groups; these changes were no longer present in either group 2 months after operation. Results of neurologic examinations and computed tomographic scans of the brain were unchanged. We conclude that the administration of prostacyclin during cardiopulmonary bypass in patients undergoing routine coronary artery operation has no effect on perioperative cognitive changes.
Adult↗
Aneurysms of ascending thoracic aorta and transverse aortic arch.
Recent chapters in the relatively brief history of surgical treatment of patients with ascending aortic aneurysms and aortic arch aneurysms continue to be punctuated by substantial clinical improvements. More precise diagnostic methods, increased awareness of the dismal natural history of patients with these aneurysms, improved methods of myocardial and cerebral protection, refined vascular grafts and prosthetic valves, widespread availability of specific coagulation components, more sophisticated anesthetic and postoperative management, and more timely referral of patients (prior to rupture or irreversible deterioration of left ventricular function, or both) have all been instrumental in promoting these improving results. The thrust of future efforts should be directed to the appropriate identification, diagnosis, and treatment of remote aneurysms and atherosclerotic disease in the cerebral and coronary circulation, detection of patients predisposed to aortic dissection, and ultimately to the development of pharmacologic methods to prevent aortic dissection and atherosclerotic aneurysm development. Eventually, it is hoped, more complete understanding of the genetics, molecular biology, and biochemistry of both acquired and congenital degenerative thoracic aortic aneurysms will also lead to preventive measures for these patients.
Aorta↗
Primary cardiac neoplasms. Early and late results of surgical treatment in 42 patients.
Forty-two patients underwent resection of primary cardiac neoplasms at Stanford University Medical Center and the Palo Alto Veterans Administration Medical Center between 1961 and 1986. A total of 27 atrial myxomas, seven benign nonmyxomatous tumors, and eight malignant tumors were resected. The mean age was 47 years (range 8 to 79) in 27 female and 15 male patients. The clinical presentations included congestive heart failure in 24 patients, palpitations in nine, neurologic symptoms in six, recurrent cardiac tamponade in three, vasculitis in two, and chest pain in two. Thirty-one of 34 benign lesions were completely resected, although one patient required cardiac transplantation to resect completely an "inoperable" benign tumor. All gross tumor was resected in four of eight patients with malignant lesions. All patients survived operation, but three with malignant disease died within 30 days. Late outcome was known for 41 of 42 (98%) patients. Total follow-up for the series was 200.1 patient-years, for an average of 4.7 years (range 1 month to 18 years). Excellent early and late results were obtained in patients with benign lesions, as there was no known tumor recurrence even if resection was incomplete. Effective palliation and local control of disease is possible with extensive resection of malignant primary tumors, but more effective adjuvant therapy will be necessary to improve long-term prognosis.
Adolescent↗
Clinical, hemodynamic, and angiographic predictors of operative mortality in patients undergoing single valve replacement. Veterans Administration Cooperative Study on Valvular Heart Disease.
Preoperative characteristics of 964 patients in the Veterans Administration Cooperative Study on Valvular Heart Disease undergoing single valve replacement were examined to determine predictors of operative mortality. The operative mortality rate was 8.3% in 661 patients having isolated aortic valve disease and 7.5% in 239 patients having isolated mitral valve disease, but 12.5% in 64 patients with multivalve disease undergoing single valve replacement. For the aortic valve replacement subgroup, three-vessel coronary artery disease, left ventricular systolic pressure, prior cardiac operation, body surface area, and cardiac index were related to operative mortality. In the mitral valve replacement group, there was a strong association of operative mortality with advanced age, exertional dizziness, reduced cardiac index, left ventricular contraction grade, ST segment depression on the resting electrocardiogram, and pleural effusion. The risk of operative death for an individual patient undergoing aortic or mitral valve replacement may be estimated with the use of independent risk factors.
Adult↗
Relative contributions of the anterior and posterior mitral chordae tendineae to canine global left ventricular systolic function.
The relative importance of the anterior and posterior mitral chordae tendineae to global left ventricular performance, independent of load, was determined by sequentially measuring the slope of the left ventricular peak isovolumetric pressure-volume relation in a canine model with the chordae of both, either, and neither mitral leaflet(s) intact. The order in which the chordae were severed was randomly assigned. Compared to baseline values (both chordae intact), severing the chordae of the anterior leaflet (posterior leaflet chordae intact) reduced the slope of the pressure-volume relation by 27% (p = 0.005) in 10 dogs; the slope decreased by an additional 16% (p = 0.017) when the posterior chordae were subsequently severed in this group. In 10 dogs randomized to the reverse order, the slope of the pressure-volume relation decreased by 17% (p = 0.021) after the posterior chordae were severed (anterior leaflet chordae intact); an additional 24% decrease in the slope (p = 0.001) occurred when the chordae of the anterior leaflet were subsequently severed in this group. The chordae of the anterior and posterior mitral leaflets have an additive, but statistically indistinguishable (p = 0.140), influence upon global left ventricular systolic performance; however, the contribution of the anterior chordae tends to be more important. Thus preservation of the anterior mitral leaflet and its chordal attachments to the papillary muscles during mitral valve replacement may have an equal or greater impact upon postoperative left ventricular function than mitral valve replacement with preservation of the posterior chordae; however, severing either the anterior or posterior chordae appears to be detrimental.
Animals↗
Myoventriculoplasty and neoventricle myograft cardiac augmentation to establish pulmonary blood flow. Preliminary observations and feasibility studies.
In 10 dogs, a latissimus dorsi muscle (myograft) was neuroelectrically stimulated at 120 cycles/min for as long as 80 days. The higher thresholds and multiple lead penetrations required of direct muscle stimulation for muscle conditioning were avoided. Vascular delay and protective wrapping of the myograft in four dogs resulted in rapid seroma and fibrous sheath formation, which precluded further study. Of the six other myografts that were stimulated, two were used as functional right ventricular myoventriculoplasties and four were employed as neoventricle myografts with inflow and outflow valved conduits that were used to provide total pulmonary blood flow. Myoventriculoplasty produced functional enlargement of the right ventricle with synchronously contractile muscle. Neoventricles provided hemodynamically stable total pulmonary blood flow for as long as 20 hours, until internal chamber thrombus formed. Transpulmonary blood pressure generation by the neoventricle was found to be programmable up to physiologic systemic pressures by modulation of chamber preload and burst stimulation frequency at 50 msec intervals, delivered 120 times per minute. Synchronization capabilities for implantable burst pulse generators would further improve the efficacy of these myograft techniques designed to augment or supplant ventricular function, particularly to provide transpulmonary blood flow at programmable pressures.
Animals↗
The interaction of hematoporphyrin derivative, light, and ionizing radiation in a rat glioma model.
The effects of hematoporphyrin derivative, light, and cobalt 60 (60Co) irradiation were studied in a rat glioma model using an in vivo and an in vitro clonogenic assay. There was no effect on tumor growth by visible light or by a single dose of 60Co irradiation at 4 Gy or 8 Gy, whereas 16 Gy inhibited tumor growth to 40% versus the control. Hematoporphyrin derivative alone slightly stimulated growth (P less than 0.1). Light in the presence of 10 mg hematoporphyrin derivative/kg inhibited tumor growth to 32%. 60Co irradiation in the presence of hematoporphyrin derivative produced a significant tumor growth inhibition (P less than 0.02). This growth inhibition was directly related to the concentration of hematoporphyrin derivative. The addition of 60Co to light in the presence of hematoporphyrin derivative produced a greater growth inhibition than light or 60Co irradiation alone. This effect was most pronounced when light was applied 30 minutes before 60Co irradiation. Our experiments in a subcutaneous rat glioma model suggest a radiosensitizing effect of hematoporphyrin derivative. Furthermore, the photodynamic inactivation is enhanced by the addition of 60Co irradiation. These findings may be of importance in planning new treatment modalities in malignant brain tumors.
Animals↗
Autologous pericardium versus a xenograft substitute in myocardial wound healing.
This study compared repair of myocardial wounds covered with autologous pericardium to healing of wounds covered with glutaraldehyde-preserved bovine pericardium in an experimental canine model. Right (RV) and left (LV) full thickness ventriculotomies were made and closed. In the control group (n = 12), the pericardium was closed over the wound; in the experimental group (n = 12), wounds were covered with bovine pericardium. Animals were sacrificed at 14, 21, 28, and 42 days. After excising the pericardium, 6 mm punch biopsies of normal RV, RV wound, normal LV, and LV wound were assayed for hydroxyproline (HPro). Both autologous and bovine pericardium became densely adherent to the wounds. Bovine pericardium was mildly adherent over unwounded areas, while autologous pericardium was usually free. Normal RV contained more than twice as much HPro as normal LV (5.4 +/- 0.57 micrograms/mg vs 1.7 +/- 0.35 micrograms/mg, P less than 0.0002). A gradual rise in HPro over time was seen in both groups, but this increase was statistically significant only at 42 days (P less than 0.05). There was no significant difference in HPro between wounds covered with autologous pericardium and those covered with bovine grafts (P = 0.13) at any of the sample times in this study. In this experimental canine model, the pericardium does not appear to play a prominent role in myocardial wound healing by contributing collagen-producing fibroblasts. Furthermore, the bovine pericardial xenograft becomes densely adherent to LV and RV incisions. In the clinical setting, such may make reoperation more hazardous when the heart has been previously incised or coronary bypass grafts have been constructed.
Animals↗
A reconsideration of cerebral perfusion in aortic arch replacement.
Ten patients underwent aortic arch replacement for aneurysmal disease from 1970 to 1985 using a simplified cardiopulmonary bypass (CPB) technique with partial brachiocephalic perfusion, low CPB flow (30 to 50 ml/kg/min), moderate systemic cooling (26 degrees to 28 degrees C), and topical hypothermic myocardial protection. The arterial line from a single pump head has a Y shape to perfuse the femoral artery (20F cannula) and either the innominate or left carotid artery (14F). Of the 10 patients (mean age, 58 years) with arch aneurysm (6 atherosclerotic, 2 dissections, and 2 degenerative), 3 had previously undergone major cardiovascular operations. Concomitant procedures included aortic valve replacement in 4 and coronary artery bypass grafting in 3. Eight patients survived the procedure, and 1 died three weeks after operation of a ruptured abdominal aneurysm. Among the survivors, CPB time was 119 +/- 36 minutes (+/- standard deviation), myocardial ischemia time was 79 +/- 32 minutes, and intraoperative blood requirement was 5.9 +/- 3.4 units. There were no postoperative strokes. Neurological complications were only minor and included an asymptomatic miosis and ulnar nerve paresthesias in 1 patient and transient vocal cord palsy in another. Applicable in most patients undergoing elective resection of degenerative and atherosclerotic arch aneurysms and in selected patients with arch dissections, this simplified technique of brachiocephalic perfusion without circulatory arrest provides an attractive and safe alternative; the potential advantages are technical simplicity, reduced CPB and operating times, and satisfactory cerebral protection.
Adult↗
Pharmacological, hematological, and physiological effects of a new thromboxane synthetase inhibitor (CGS-13080) during cardiopulmonary bypass in dogs.
The hematological and pharmacological effects of a new thromboxane synthetase inhibitor, CGS-13080 (imidazo[1,5-alpha]pyridine-5-hexanoic acid), were investigated during cardiopulmonary bypass in a blinded, randomized manner in dogs. Compared with placebo, CGS-13080 suppressed thrombin-stimulated platelet thromboxane B2 production by 90% during cardiopulmonary bypass (p less than .001), an effect that persisted for two hours after stopping the infusion. In the CGS-13080-treated group, plasma 6-keto-prostaglandin F1 alpha levels significantly increased over time (p less than .03) and were somewhat higher when compared with those in the placebo-treated group. This observation suggests that an "endoperoxide shunt" may have occurred. In the control group, an inverse correlation between platelet count and level of thromboxane B2 per platelet following in vitro thrombin stimulation (r = .5, p less than .001) was apparent, but there was no correlation between these two variables (r = .18, p less than .10) in the CGS-13080-treated group. No adverse hemodynamic or other effects attributable to CGS-13080 occurred during or immediately following cardiopulmonary bypass. These results suggest that CGS-13080 is an effective inhibitor of thromboxane B2 production during cardiopulmonary bypass in dogs and has no adverse physiological effects.
6-Ketoprostaglandin F1 alpha↗
Prosthetic graft infection: limitations of indium white blood cell scanning.
The lack of a rapid, noninvasive, and accurate method to confirm or rule out prosthetic graft infection continues to constitute a compelling and vexing clinical problem. A host of adjunctive diagnostic techniques has been used in the past, but early promising results subsequently have usually not yielded acceptable sensitivity (reflecting false negatives) and specificity (reflecting false positive) data. White blood cell (WBC) indium 111 scanning has recently been added to this list. The utility and accuracy of 111In WBC scans were assessed by retrospective review of WBC scan results in 70 patients undergoing evaluation for possible prosthetic graft infection over a 7-year period. Operative and autopsy data (mean follow-up, 18 months for survivors with negative scans) were used to confirm the 22 positive, 45 negative, and three equivocal WBC scans. The false positive rate (+/- 70% confidence limits) was 36% +/- 6% (n = 8) among the 22 patients with positive scans (44% +/- 6% [11 of 25] if the three equivocal scans are included as false positive), yielding a specificity of 85% +/- 5% and an overall accuracy rate of 88% +/- 4% (80% +/- 5% and 84% +/- 5%, respectively, if the three equivocal cases are considered as false positive). All three patients with equivocal scans ultimately were judged not to have prosthetic graft infection. As implied by the high accuracy rate, the sensitivity of the test was absolute (100% [14 of 14]); there were no false negative results. (ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Biochemical (functional) adaptation of "arterialized" vein grafts.
Canine venous autografts and allografts were interposed in the femoral and carotid arterial positions in 29 dogs; grafts were harvested at three postoperative intervals (1-2 weeks, 4-6 weeks, and 8-10 weeks) for light and scanning electron (SEM) microscopy and lumenal surface prostacyclin (PGI2) production. Normal veins and arteries were used as controls. Radioimmunoassay for tritiated 6-k-PGF1 alpha, the stable metabolite of PGI2, was performed using a flow surface template incubation chamber during basal and arachidonic acid stimulated conditions. Using SEM, the autografts revealed normal endothelial cell (EC) surfaces at all time intervals; conversely, allografts exhibited extensive EC loss at 1-2 weeks with gradual reparation by 10-12 weeks (such that the EC surface was virtually indistinguishable from that of control veins or autografts). PGI2 production was significantly greater in control arteries than veins (p = 0.0001). At 1-2 weeks and 4-6 weeks, lumenal production of PGI2 in both the autografts and allografts was not significantly different from control vein; however, PGI2 production after 10-12 weeks was identical to normal arterial levels (and significantly [p less than 0.0044] higher than venous levels) in both basal and stimulated conditions. Although the mechanisms responsible for this functional (biochemical) "arterialization" process remain conjectural, increased biosynthesis and/or release of PGI2 by endothelial cells, acute phase inflammatory cells (allografts) mediated by interleukin-1 or myointimal cells seems most likely. Further elucidation of these sources of PGI2 is necessary, but these data demonstrate for the first time that venous grafts placed in the arterial circulation undergo complete functional adaptation (in addition to the well known morphological changes).
Adaptation, Physiological↗
Repair of ascending aortic aneurysms and dissections.
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Acute Disease↗
Hormonal modulation of Schwann cell tumors. I. The effects of estradiol and tamoxifen on methylnitrosourea-induced rat Schwann cell tumors.
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Animals↗
Valvular-ventricular interaction: importance of the mitral apparatus in canine left ventricular systolic performance.
As the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressure-volume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 +/- 3.35 (+/- SD) to 6.38 +/- 0.96 mm Hg/ml (p less than .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tense may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.
Animals↗
Use of the intra-aortic balloon pump after valve replacement. Predictive indices, correlative parameters, and patient survival.
Intra-aortic balloon pump counterpulsation required as an adjunct during weaning from cardiopulmonary bypass or for circulatory support in the immediate postoperative period was analyzed in 2,498 patients undergoing valve replacement between December, 1972, and September, 1981. A total of 140 successful insertions were performed in 155 attempts. Ninety-five of these patients were from a homogeneous cohort of 1,908 patients undergoing valve replacement with porcine xenografts and were analyzed for factors that might be useful predictors of the need for balloon pump support. Univariate analysis of individual factors delineated preoperative characteristics in patients having mitral valve replacement and intraoperative factors in all patients that correlated with use of the balloon pump. Multivariate analysis revealed a subset of male patients with mitral valve and coronary disease most likely to require counterpulsation. Overall survival rate was markedly reduced at 30 days (balloon counterpulsation plus valve replacement, 50% +/- 5%; valve replacement only, 96% +/- 5%; p less than 0.001) and at 1 year (balloon counterpulsation plus valve replacement, 38% +/- 5%; valve replacement only, 89% +/- 1%, p less than 0.001) if balloon pumping was required. The entire group of 140 patients were retrospectively analyzed for factors predictive of survival. Patients requiring balloon pumping who had a preoperative diagnosis of aortic regurgitation had a lower 1 year survival rate (13% +/- 9%) than the total subgroup undergoing balloon counterpulsation (36% +/- 4.0%) (p = 0.002). Similarly patients treated by balloon counterpulsation who had postoperative renal failure had a significantly lower 1 year survival rate (17% +/- 5%) than those without renal failure (66% +/- 6%) (p = 0.003). The survival rate of patients who required this therapeutic modality after valve replacement is poor. Other methods of hemodynamic support are necessary.
Aortic Valve↗
A prospective, randomized study of the effects of prostacyclin on platelets and blood loss during coronary bypass operations.
A randomized, double-blind study was designed to evaluate the therapeutic effect and safety of prostacyclin (epoprostenol) in patients undergoing cardiopulmonary bypass. One hundred patients having isolated coronary bypass grafting received 300 units/kg of heparin and then either prostacyclin (12.5 ng/kg/min from heparinization until cardiopulmonary bypass, 25 ng/kg/min during bypass) or buffer/diluent in a similar manner. Standardized anesthetic, perfusion, and surgical techniques were used. Drug and placebo groups were similar in demographic data and bypass times, and there were no deaths. Activated coagulation time and platelet count were significantly higher during cardiopulmonary bypass in patients receiving prostacyclin. Platelet count remained significantly higher 24 hours after bypass in the active drug group. Immediately after operation, there was significantly less prolongation of bleeding time (1.3 versus 2.9 minutes; p = 0.009) in the patients receiving prostacyclin. Blood loss was significantly reduced during the first 4 hours postoperatively in the prostacyclin group (261 +/- 159 versus 347 +/- 197 ml; p = 0.02). There was no significant difference between the groups when total blood loss was compared (710 +/- 351 versus 869 +/- 498 ml; p = 0.07). Patients receiving prostacyclin required an average of 257 ml less blood transfused in the intensive care unit (p = 0.02). We conclude that the clinical impact of prostacyclin in patients undergoing coronary artery operations was demonstrable, but small. Prostacyclin may provide clinical benefits in patients undergoing cardiopulmonary bypass when there are contraindications to or other difficulties with blood transfusion. With prostacyclin, reduced heparin dose is possible and therefore reduced protamine requirement would offer a potential benefit of less cardiovascular depression immediately after bypass. However, the advantages offered by prostacyclin are not sufficient to recommend its routine use during cardiopulmonary bypass.
Adult↗