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Biomedical subjects

E D Verrier

Publications and source records attributed to E D Verrier.

At least 55 records · Page 3Linked to original sources

CD18-independent mechanism of neutrophil emigration in the rabbit lung after ischemia-reperfusion.

BACKGROUND: Reperfusion of ischemic lung causes an inflammatory pulmonary vascular injury characterized by increased vascular permeability and migration of inflammatory cells into the alveoli. Migration of neutrophils into the alveolus during reperfusion after 24 hours of unilateral pulmonary artery occlusion has been shown to be in part dependent on the CD18 adhesion molecule on the cell surface. The current study investigated whether reperfusion lung injury after a 1-hour period of complete lung ischemia was CD18 dependent. METHODS: Eighteen rabbits were assigned to one of three groups. Groups 1 and 2 were subjected to one hour of in situ right hilar occlusion followed by 2 hours of reperfusion. Group 3 was subjected to identical surgical dissection but the right hilum was never occluded. Group 1 rabbits received saline solution (1 mL/kg) before hilar occlusion and group 2 rabbits, monoclonal antibody 60.3, a blocking antibody for the CD18 adhesion molecule on the neutrophil surface (2 mg/kg). In 3 of the antibody-treated rabbits, flow cytometry was performed on blood neutrophils before and after administration of the antibody and 120 minutes after reperfusion. RESULTS: The rabbits in groups 1 and 2 had significantly increased alveolar neutrophil infiltrate and increased pulmonary vascular resistance compared with the rabbits in group 3. However, there was no significant difference between group 1 (saline solution treated) and group 2 (antibody treated). Antibody treatment did not block migration of neutrophils into the alveoli. Flow cytometry of circulating neutrophils demonstrated that CD18 was upregulated after reperfusion and that CD18 was fully blocked after antibody treatment for the duration of the study. CONCLUSIONS: We conclude that a 1-hour period of warm ischemia followed by reperfusion results in upregulation of CD18 but that emigration of the neutrophils into the alveoli is not CD18 dependent in this injury.

Animals↗

Modified conduit preparation creates a pseudosinus in an aortic valve-sparing procedure for aneurysm of the ascending aorta.

Mechanical valved conduit replacement of the aortic root is a durable and appropriate procedure for many diseases of the ascending aorta, but may sacrifice an anatomically salvageable aortic valve. For young active patients and for patients with "systemic" arterial disease (atherosclerosis, Marfan's syndrome) who may require future operations, life-long anticoagulation with its attendant thromboembolic versus hemorrhagic risks is not ideal. Several techniques have been suggested as aortic valve-sparing options. Recently, a procedure was described that combines the freehand homograft techniques with the standard Bentall techniques (David procedure). This innovative technique replaces the ascending aorta with a Dacron cylinder, spares the aortic valve, and restores competence and thus offers an excellent alternative. The durability of this procedure that places the aortic valve inside a cylindrical conduit without sinuses of Valsalva is unknown. In selected patients, we have used this technique to spare the aortic valve. On the basis of experimental data and preliminary computer modeling, with the hope of improving the durability, we have modified the conduit to create a "pseudosinus" in our most recent nine patients. We have done the David procedure in 10 patients. The pseudosinus modification was done in the most recent nine patients. Patients' ages ranged from 37 to 71 years (mean 49.9 years). There were five female and five male patients. Five patients had Marfan's syndrome and five patients had annuloaortic ectasia. There has been no mortality and all patients have had both early and late follow-up echocardiography. Five patients have zero to trace aortic insufficiency, four patients have trace to mild aortic insufficiency, and one patient has mild or "1+" aortic insufficiency. Aortic insufficiency has not progressed in any patient during the 18 months of follow-up. The patient with 1+ aortic insufficiency has no activity limits, good ventricular function, and no evidence of congestive symptoms. One patient who had extensive thoracoabdominal aneurysmal disease has undergone subsequent replacement of the descending aorta to the level of the renal arteries and has done well. Aortic valve-sparing replacement of the aortic root is an excellent procedure for any patient with an ascending aortic aneurysm and an anatomically salvageable valve. We believe that by modifying the proximal conduit and creating a "pseudosinus" into which the leaflets can retract without contact of the cylindrical conduit we may increase the longevity of the native aortic valve in this procedure.

Aorta↗

Hypothermia reversibly inhibits endothelial cell expression of E-selectin and tissue factor.

Hypothermia frequently accompanies cardiopulmonary bypass (CPB) and myocardial protection strategies during cardiac surgery. With CPB, the blood/artificial surface interface activates components of the humoral and cellular inflammatory cascades and may contribute to postoperative end organ dysfunction including the heart or multiple other organ systems. The endothelial cell (EC) monolayer normally mediates components of solute transport, vasomotor function, coagulation, cell differentiation/growth, and immune/inflammatory processes. E-selectin is a vascular adhesion molecule that mediates neutrophil adherence and that is inducible in ECs by inflammatory mediators such as cytokines. Tissue factor (TF) is similarly an inducible procoagulant factor in ECs that contributes to thrombosis. The induction, transcription, and expression of both molecules were studied in cultured human umbilical vein cells at normothermic (37 degrees), hypothermic (25 degrees), and rewarmed (37 degrees) conditions after stimulation with the cytokines tumor necrosis factor alpha and interleukin-1. Hypothermia reversibly inhibits the transcription and expression but not the induction of both E-selectin and TF.

E-Selectin↗

Individual variations in the fibrinolytic response during and after cardiopulmonary bypass.

The purpose of this study was to determine whether individual patients show different patterns of fibrinolytic response to cardiopulmonary bypass (CPB) and whether preoperative or intraoperative parameters were predictive of these different patterns. Active t-PA, active PAI-1 and total t-PA antigen were measured in plasma samples obtained from 38 subjects, age 32 to 85 (median 69 years), before, during and after CPB. Four patterns of fibrinolytic response were noted: 1) 40% of patients showed the "typical" response, a rapid rise in active and total t-PA during CPB followed postoperatively by elevated PAI-1 and reduced t-PA, 2) 10% showed no change in t-PA or PAI-1 during or after CPB, 3) 24% showed no change in t-PA with an increase in PAI-1 postoperatively, and 4) 26% showed an increase in t-PA during CPB with no change in PAI-1 postoperatively. When present, the t-PA response was rapid, occurring within the first 30 min of CPB and was more common in patients undergoing valve surgery than in coronary artery bypass grafting (p < 0.005). Increased levels of PAI-1 postoperatively were associated with ischemic times greater than 70 min (p = 0.003) but not with the total length of CPB. Age, sex, CPB temperature, total CPB time and preoperative levels of t-PA and PAI-1 were not associated in the intra- or postoperative fibrinolytic response pattern. We conclude that the fibrinolytic response to CPB is heterogeneous. Further studies will be needed to determine whether different response patterns are clinically significant.

Adult↗

Acquired immunodeficiency syndrome-related lymphoma of the lung presenting as empyema thoracis.

B-cell lymphoma in patients infected with the human immunodeficiency virus is usually a disseminated process that occasionally involves the lungs. Surgical diagnosis is often necessary to distinguish this from other neoplasms or opportunistic infections of the lung. We report a case of pulmonary B-cell lymphoma in a patient infected with human immunodeficiency virus who presented with a left empyema thoracis and an associated left lower lobe abscess secondary to bronchial obstruction. Resection was performed and the patient subsequently recovered from the acute process and survived an additional 6 months. This report demonstrates that surgical intervention may be necessary for both the diagnosis of pulmonary lymphoma and the definitive management of infectious complications that may arise as a result of pulmonary neoplastic disease in patients with acquired immunodeficiency syndrome.

Adult↗

Inhibition of neutrophil adhesion does not prevent ischemic spinal cord injury.

Paraplegia may occur after transient aortic occlusion as a consequence of primary ischemia to the spinal cord or injury during the reperfusion period. In animal models of ischemia/reperfusion there is evidence that reperfusion injury may be modulated partially by neutrophils. The efficacy of the neutrophil adherence blocking murine monoclonal antibody (MAb 60.3) was assessed in spinal cord ischemia/reperfusion in rabbits. Spinal cord ischemia was accomplished by balloon catheter occlusion of the infrarenal aorta. Neurologic assessment was graded as normal, partial neurologic deficit, or complete paralysis. Electrophysiologic monitoring with somatosensory evoked potentials was used to determine the optimal length of time of occlusion. Animals were treated randomly with 2 mg/kg of intravenous Mab 60.3 (n = 8) or saline solution (n = 9) with the investigator unaware of treatment. Mean occlusion times were no different between groups (control, 32.7 +/- 3.6 minutes versus MAb, 32.4 +/- 6.0 minutes). Five (55%) saline-treated and four (50%) MAb 60.3-treated animals became paraplegic. Animals with initial paraparesis all progressed to flaccid paraplegia within 24 hours. We conclude that spinal cord injury after transient aortic occlusion is independent of the CD11/CD18 glycoprotein complex of the neutrophil. Injury in this setting may occur during ischemia and thus may not be dependent on neutrophils or reperfusion.

Animals↗

Schwannoma of the left atrium: diagnostic evaluation and surgical resection.

A case of primary benign schwannoma of the left atrium is reported. A 35-year-old man presented with new onset atrial fibrillation. Noninvasive evaluation revealed a 4 x 7-cm mediastinal mass either directly posterior to or involving the left atrium. The histologic diagnosis and specific location of the mass were established by incisional biopsy through a left thoracotomy. On cardiopulmonary bypass the tumor was resected by widely excising the posterior left atrium. The residual 20-cm2 left atrial defect was patched with pericardium. This unusual case illustrates that left atrial tumors originating near the pulmonary veins may be nonmyxomatous neoplasms of neural origin. Diagnosis may be difficult and require a surgical transthoracic approach.

Adult↗

Expression of E-selectin on coronary endothelium after myocardial ischemia and reperfusion.

Neutrophils localize in ischemic or infarcted myocardium and thus are implicated in playing a role in myocardial reperfusion injury and stunning. We studied one of the mechanisms by which neutrophils are recruited into the region of ischemic myocardium. Anesthetized adult rhesus monkeys (n = 2) underwent ligation of one of the obtuse marginal coronary arteries for 90 minutes followed by 5 hours of reperfusion. Tissues from the normal perfused area of the heart and from the ischemic area were preserved in methacarn fixative after sacrificing the animal at the end of the reperfusion period. Immunohistochemical staining showed that E-selectin is not constitutively expressed on coronary endothelium in vivo. E-selectin, however, was upregulated in selective endothelial cells located in the postcapillary coronary venules in response to ischemia and reperfusion. The presence of E-selectin in this setting suggests that it may have a similar role as in the recruitment of neutrophils into other inflamed or damaged tissues.

Animals↗

Maximal vascular conductance in right ventricular myocardial circulation.

With acutely increasing right ventricular (RV) hypertension, failure eventually occurs because of RV ischemia. This study examines the effects of RV hypertension on the diastolic right coronary circulation. Conscious dogs instrumented to measure right coronary artery pressure and blood flow were studied after maximal coronary vasodilation with chromonar. Diastolic coronary pressure-flow relations, described by slope (conductance) and zero-flow, pressure axis intercept (Pf = 0), were generated before and during RV hypertension. Diastolic Pf = 0 increased from 11.8 +/- 6.5 to 17.1 +/- 7.1 (means +/- SD, P < 0.01) Torr, with no change in conductance. During RV hypertension, RV diastolic pressure increased. To examine possible mechanisms for the increase in Pf = 0, pressure-flow relations were generated before and after volume loading, without systolic hypertension. Diastolic Pf = 0 increased from 15.5 +/- 3.1 to 20.8 +/- 4.1 Torr, suggesting that changes in Pf = 0 with RV hypertension were mediated by increased filling pressures. Pressure flow relations were derived from mean right coronary flow and RV driving pressure before and during RV hypertension. Under these conditions, Pf = 0 is close to zero; the use of RV driving pressure provides a method for calculating maximal right coronary conductance.

Animals↗

Dependence of Gorlin formula and continuity equation valve areas on transvalvular volume flow rate in valvular aortic stenosis.

BACKGROUND: Valve areas derived by the Gorlin formula have been observed to vary with transvalvular volume flow rate. Continuity equation valve areas calculated from Doppler-echo data have become a widely used alternate index of stenosis severity, but it is unclear whether continuity equation valve areas also vary with volume flow rate. This study was designed to investigate the effects of changing transvalvular volume flow rate on aortic valve areas calculated using both the Gorlin formula and the continuity equation in a model of chronic valvular aortic stenosis. METHODS AND RESULTS: Using a canine model of chronic valvular aortic stenosis in which anatomy and hemodynamics are similar to those of degenerative aortic stenosis, each subject (n = 8) underwent three studies at 2-week intervals. In each study, transvalvular volume flow rates were altered with saline or dobutamine infusion (mean, 10.3 +/- 5.1 flow rates per study). Simultaneous measurements were made of hemodynamics using micromanometer-tipped catheters, of ascending aortic instantaneous volume flow rate using a transit-time flowmeter, and of left ventricular outflow and aortic jet velocity curves using Doppler echocardiography. Valve areas were calculated from the invasive data by the Gorlin equation and from the Doppler-echo data by the continuity equation. In the 24 studies, mean transit-time transvalvular volume flow rate ranged from 80 +/- 33 to 153 +/- 49 mL/min (P < .0001). Comparing minimum to maximum mean volume flow rates, the Gorlin valve area changed from 0.54 +/- 0.22 cm2 to 0.68 +/- 0.21 cm2 (P < .0001), and the continuity equation valve area changed from 0.57 +/- 0.18 cm2 to 0.70 +/- 0.20 cm2 (P < .0001). A strong linear relation was observed between Gorlin valve area and mean transit-time volume flow rate for each study (median, r = .88), but the slope of this relation varied between studies. The Doppler-echo continuity equation valve area had a weaker linear relation with transit-time volume flow rate for each study (median, r = .51). CONCLUSIONS: In this model of chronic valvular aortic stenosis, both Gorlin and continuity equation valve areas were flow-dependent indices of stenosis severity and demonstrated linear relations with transvalvular volume flow rate. The changes in calculated valve area that occur with changes in transvalvular volume flow should be considered when measures of valve area are used to assess the hemodynamic severity of valvular aortic stenosis.

Animals↗

Anatomic basis for mitral valve modelling.

The increasing popularity of mitral valve repair and current interest in replacement with a mitral homograft or heterograft warrant a new look at the normal functional anatomy of the system. We conducted a detailed review of the anatomic structure of both the intact and excised mitral apparatus of porcine and human species. The following intact structural dimensions were measured: total annular length, anterior and posterior annular length. Excised measurements included: total annular length, anterior and posterior annular lengths, leaflet edge lengths, leaflet heights, and anterolateral and posteromedial commissural heights. Leaflet area was calculated from planimetric measurements. Chordal lengths were measured and distribution recorded. The majority of leaflet measurements were not statistically different between groups. For both groups, the measured annular length increased significantly upon valve excision. In both groups, the posterior leaflet area was significantly larger than the anterior leaflet area, and the area of each leaflet alone was significantly greater than the calculated orifice area. Chordal length was not significantly different between groups, however, distribution varied slightly with the ratio of origins to insertions being 8:1 (porcine) and 5:1 (human). The results are consistent with previous studies of the human mitral valve. This study showed little difference between human and porcine data, and the porcine valve was identified as an appropriate model for further investigation of the mitral valve system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Aortic root and valve relationships. Impact on surgical repair.

A surgical procedure has recently been described for patients with aortic incompetence caused by annular dilation, but with normal aortic leaflets. The dilated aortic root is replaced with a Dacron graft, and the native aortic valve is resuspended within the graft. Matching the size and shape of the graft to the size of the leaflets may have significant effects on valve closure and leaflet stress and thus on the longevity of the repair. To define the relationship of native aortic root structure to leaflet size, we morphologically examined normal human aortic roots (n = 10) and valve leaflets and applied mathematic analyses to the results. Our data show that the root has a consistent shape with varying size and that there is a definable mathematic relationship between root diameter and clinically measurable leaflet dimensions. We derived an equation that allows calculation of the appropriate diameter of the root at the sinus of Valsalva level from leaflet heights and perimeters. The diameter of the graft at the sinotubular junction and base should follow the relationship of the normalized root dimensions, either by tailoring of the graft or by new graft design. The current data imply that the graft should incorporate sinuses for proper valve closure and for sharing stress with the leaflets. Application of these results will allow prosthetic graft design to more closely resemble the native aorta. These new grafts should improve physiologic function of the valve, reduce leaflet stress, and increase the durability of the repair.

Adolescent↗

Pyoderma gangrenosum after coronary artery bypass grafting.

Pyoderma gangrenosum is a rare cutaneous disorder that may complicate recovery after a cardiac operation. The lesions appear to represent a necrotizing infection; however, they do not respond to surgical debridement and antibiotic therapy. The treatment is based on high-dose corticosteroids and concomitant treatment of any underlying systemic disease.

Aged↗

Clonidine improves perioperative myocardial ischemia, reduces anesthetic requirement, and alters hemodynamic parameters in patients undergoing coronary artery bypass surgery.

The purpose of this study was to determine if clonidine reduces myocardial ischemia or alters anesthetic requirement and perioperative hemodynamic parameters during coronary artery bypass grafting (CABG) surgery. Forty-three patients were randomized in a prospective, double-blind fashion to receive either clonidine (5 micrograms/kg) or placebo. Anesthetic induction and maintenance was accomplished with intravenous sufentanil-midazolam (S-M) in a 1:20 ratio; up to 1.0% enflurane was added during surgery when repeated boluses of S-M failed to maintain the blood pressure within 20% of preinduction values. Continuous ST segment analysis of leads II and V5 was performed throughout surgery with maximal ST segment deflection from baseline recorded every 5 minutes. Catecholamine levels were measured intermittently throughout the perioperative period and myocardial lactate use or excretion was determined just prior to cardiopulmonary bypass (CPB) and at 1, 5, 10, 30, and 60 minutes after release of the aortic cross-clamp. Patients who received clonidine required significantly less sufentanil for their surgical procedure (11.82 +/- 0.66 micrograms/kg v 14.55 +/- 0.90 micrograms/kg, P < 0.05) and also needed less enflurane for blood pressure control, particularly during CPB (P < 0.05). Baseline hemodynamic parameters were similar for both groups prior to induction. In the period between anesthetic induction and the initiation of CPB, patients treated with clonidine had a significantly slower heart rate (HR) (P < 0.01), a lower cardiac output (CO) (P < 0.05), and transiently higher systemic vascular resistance (SVR) (P < 0.05) than placebo-treated patients. Immediately after CPB, patients receiving clonidine continued to have a significantly lower CO (P < 0.01) and a higher SVR (P < 0.01) than placebo-treated patients. Clonidine treatment significantly increased the percentage of patients who required pacing after CPB (P < 0.05). In the intensive care unit, clonidine-treated patients displayed a persistently increased requirement for pacing (P < 0.01), decreased systolic blood pressures, and reduced sodium nitroprusside requirements relative to patients treated with placebo. Epinephrine and norepinephrine levels were lower in clonidine-treated patients throughout the perioperative procedure with significant differences noted immediately following sternotomy and release of the aortic cross-clamp (P < 0.05). Critical ST segment depression was significantly less in clonidine-treated patients for the period from sternotomy until application of the aortic cross-clamp (P < 0.01). Following CPB, absolute deviation of ST segments from isoelectric baseline was significantly less in the clonidine-treated group (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, Intravenous↗

Potential role of neutrophil anti-adhesion therapy in myocardial stunning, myocardial infarction, and organ dysfunction after cardiopulmonary bypass.

When activated neutrophils are recruited and bind to endothelial tissues, they release leukotrienes, proteolytic enzymes, and free radicals. The latter has been implicated in myocardial stunning following periods of ischemia and reperfusion, as may occur following cardiopulmonary bypass (CPB). The neutrophil surface complex CD11/CD18 promotes the neutrophil-endothelial adhesion process. Monoclonal antibodies have been developed that can block neutrophil adhesion to the endothelium by preventing CD11/CD18 binding to adhesion molecules (ICAM-1 or ELAM-1) located on endothelial cells. We used monoclonal IgG antibody 60.3 to block neutrophil adherence and thereby potentially reduce myocardial stunning. Pretreatment of rabbits subjected to myocardial ischemia/reperfusion with either monoclonal 60.3 or saline resulted in only a small increase in the rate of recovery of preload recruitable stroke work index during reperfusion. More severe occlusion may have been needed to see significant results. We also evaluated the effects of anti-neutrophil therapy in animal models of CPB. Rhesus monkeys were subjected to deep hypothermia and CPB, followed by 24 hours of fluid resuscitation. Animals receiving monoclonal 60.3 (N = 3) showed less weight gain, less infused resuscitative fluid, and higher terminal hematocrit and PaO2 than controls (N = 3). Antineutrophil therapy may prevent multiorgan system failure in certain high risk patients.

Animals↗

Echocardiographic volume flow and stenosis severity measures with changing flow rate in aortic stenosis.

The anatomy of degenerative valvular aortic stenosis has been poorly represented in animal models, limiting the evaluation of noninvasive echo-Doppler measures of transvalvular volume flow rate and stenosis severity during progressive disease evolution or under conditions of changing volume flow rates. To study these issues, chronic valvular aortic stenosis, characterized by stiff leaflets without commissural fusion, was created in nine adult mongrel dogs by suturing pericardial covered Teflon-felt pads into the sinuses of Valsalva below the coronary ostia during hypothermic cardiac arrest. In the eight surviving dogs, echo-Doppler examinations were performed weekly for up to 8 wk postoperatively. Simultaneous invasive micromanometer pressure data were collected at 2-wk intervals in all subjects, with simultaneous ascending aortic transit time-volume flow measurement in four subjects. Volume flow rates were altered with saline and dobutamine infusions during invasive studies for comparison of echo-Doppler and invasive pressure gradients, volume flow, and valve areas. Serial echo-Doppler follow-up (39 +/- 11 days) demonstrated that, from baseline to final study, mean transvalvular pressure gradient increased (4 +/- 1 to 38 +/- 7 mmHg, P = 0.001), continuity equation aortic valve area decreased (2.06 +/- 0.18 to 0.54 +/- 0.04 cm2, P < 0.0001), and progressive left ventricular hypertrophy developed (62 +/- 6 to 114 +/- 9 g, P = 0.0003). Echo-Doppler and invasive data correlated well for measures of transvalvular pressure gradients (n = 98, maximum instantaneous gradient r = 0.95, mean gradient r = 0.91), volume flow (n = 75, stroke volume r = 0.86, cardiac output r = 0.86), and valve area (n = 73, r = 0.73) despite acute alterations in volume flow and progressive disease evolution. This chronic canine model, with anatomy and hemodynamics similar to clinical degenerative valvular aortic stenosis, should provide a valuable tool for investigating clinically relevant new measures of stenosis severity with use of invasive or noninvasive techniques.

Analysis of Variance↗