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Biomedical subjects

R A Jonas

Publications and source records attributed to R A Jonas.

At least 109 records · Page 6Linked to original sources
PubMed1995

Structure-function correlations in cryopreserved allograft cardiac valves.

This communication briefly summarizes a morphologic investigation of explanted cryopreserved heart valves and discusses the findings in the context of ongoing debates regarding modes of failure, cellular viability, durability of the extracellular matrix, and the contribution of immune responses. We studied 20 cryopreserved human heart valve allografts functioning up to 9 years as either orthotopic aortic valves/root replacements or right ventricle-to-pulmonary artery conduits explanted for valve failure, infection, or growth-related conduit or valve stenosis. Implanted valves had progressively severe loss of normal layered structure and were devoid of stainable deep connective tissue cells. Inflammation was minimal. Other late findings included minimal inflammation, mild cuspal hematomas, mural thrombus, and calcification, most prominent in the aortic wall. Transmission electron microscopy of late explants revealed nonviable cells and their debris, and a collagenous skeleton that was largely intact. We conclude that cryopreserved allograft heart valves have minimal, if any, viable cells, but largely retain the original collagen network; preservation of the autolysis-resistant collagenous skeleton likely provides the structural basis of function. Our results also suggest that immune responsiveness has little, if any, impact on late allograft function or degradation.

Adolescent↗
PubMed1995

Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants.

BACKGROUND: Cerebral protection during deep hypothermic circulatory arrest is predicted on efficient and complete cerebral cooling. Institutions approach cooling quite differently. We compared two different cooling strategies in terms of measured jugular venous bulb saturations in 39 infants undergoing deep hypothermic cardiopulmonary bypass to evaluate the effect of institutional cooling practices on jugular venous bulb saturation, an indirect measure of cerebral cooling efficiency. METHODS: The patients were grouped based on the method of core cooling. In group A (n = 17), core cooling was achieved rapidly by setting the water bath temperature of the heat exchanger at 4 degrees to 5 degrees C, and the patient was cooled until rectal temperature and nasopharyngeal temperature were 15 degrees C or lower. In group B (n = 22), the heat exchanger was initially set at 18 degrees C and slowly lowered to 12 degrees C. Hypothermic temperatures of 12 degrees C were maintained until the nasopharyngeal temperature was 18 degrees C or less and the rectal temperature was 20 degrees C or lower. Once cooling was complete, blood samples were analyzed by cooximetry for determination of arterial oxygen saturation and jugular venous bulb saturation. RESULTS: In group A, the measured jugular venous bulb saturation was 98.0% +/- 0.9% and the oxygen saturation to jugular venous bulb saturation difference was 0.3% +/- 0.5%, measured at the time that institutional cooling objectives were achieved (total cooling time, 15.0 +/- 0.45 minutes). In group B, jugular venous bulb saturation was 86.2% +/- 12% and the oxygen saturation to jugular venous bulb saturation difference was 10.8% +/- 12.2%, measured at the time that institutional cooling objectives were achieved (total cooling time, 17.5 +/- 1.1 minutes (p < 0.01). CONCLUSIONS: Differences in cardiopulmonary bypass cooling techniques may alter the rate at which jugular bulb saturations rise. We believe this represents an indirect measure of the efficiency of brain cooling and therefore of cerebral protection.

Body Temperature↗
PubMed1995

University of Wisconsin cerebroplegia in a piglet survival model of circulatory arrest.

BACKGROUND: Previous acute studies in immature piglets at our institution have demonstrated improved recovery of cerebral blood flow, intracellular pH, and high-energy phosphates with the administration of multidose University of Wisconsin solution as cerebroplegia during a period of deep hypothermic circulatory arrest (HCA). In an effort to define further the clinical applicability of this technique, we have developed a survival model of swine cardiopulmonary bypass (CPB) and HCA. METHODS: 12 Yorkshire pigs (age 4 to 5 weeks) were placed on CPB via the right femoral artery and right atrium. Animals were cooled to a rectal temperature of 15 degrees C and submitted to 90 minutes of HCA. Group UW (n = 6) received a single infusion of 50 mL/kg of 4 degrees C University of Wisconsin solution delivered antegrade to the cerebral circulation. The control group (n = 6) received no intervention. Animals were reperfused, rewarmed to 35 degrees C, and weaned from CPB. Neurologic assessments using neurologic deficit scoring (0 = normal, 500 = brain death) and overall performance categories (1 = normal, 5 = brain death) were performed at 24-hour intervals for 5 days. On the 5th postoperative day all brains were perfusion-fixed and examined for histologic evidence of neuronal injury (0 = normal, 5 = severe injury). RESULTS: All animals were extubated 18 to 20 hours postoperatively. There was no significant difference between the mean neurologic score of the two groups. The mean day 5 neurologic deficit score was 108 for the UW group and 68 for the control group (p > 0.05). The day 5 overall performance category was 2.8 for the UW group and 2.0 for the control group (p > 0.05). Three of the UW animals but none of the control animals experienced generalized seizures. Histologic examination revealed more severe damage in UW animals, primarily in the cerebral cortex. Injury was more widespread in UW animals, involving cerebellum and hippocampus. The mean histologic injury score was 3.8 for UW animals and 2.4 for the control group (p = 0.06). CONCLUSIONS: A clinically relevant survival model of CPB with HCA in immature swine is feasible. Cold UW solution as single-dose cerebroplegia is not beneficial, and may be injurious to the immature swine brain subjected to CPB and HCA. Further studies are indicated to determine optimal composition and administration of cerebroplegic solutions.

Animals↗
PubMed1995

pH strategies and cerebral energetics before and after circulatory arrest.

The pH-stat strategy compared with the alpha-stat strategy provides more rapid recovery of brain high-energy phosphate stores and intracellular pH after 1 hour of hypothermic circulatory arrest in pigs. Possible mechanisms for this difference are (1) improved oxygen delivery and homogeneity of brain cooling before deep hypothermic circulatory arrest and (2) greater cerebral blood flow and reduced reperfusion injury owing to extracellular acidosis during the rewarming phase. To identify which of these mechanisms is predominant, we studied 49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest. Four groups were defined according to cooling/rewarming strategy: alpha/alpha, alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate levels and intracellular pH were measured by magnetic resonance spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25 animals cerebral blood flow was measured by labeled microspheres, cerebral metabolic rate by oxygen and glucose extraction, and the redox state of cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6). Cerebral blood flow was greater with pH-stat than alpha-stat during cooling (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p < 0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the initial 45 minutes of reperfusion was more rapid in group pH/pH compared with that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in the initial 30 minutes was faster in group pH/pH compared with that in group alpha/alpha (p = 0.026). Intracellular pH became more acidic during early reperfusion only in group alpha/alpha, whereas it showed continuous recovery in the other groups. This study suggests that there are mechanisms in effect during both the cooling and rewarming phases before and after deep hypothermic circulatory arrest that could contribute to an improved cerebral outcome with pH-stat relative to more alkaline strategies.

Adenosine Triphosphate↗
PubMed1995

Factors influencing early and late outcome of the arterial switch operation for transposition of the great arteries.

Between January 1983 and January 1992, 470 patients underwent an arterial switch operation at our institution. An intact (or virtually intact) ventricular septum was present in 278 of 470 (59%); a ventricular septal defect was closed in the remaining 192. Survivals at 1 month and 1, 5, and 8 years among the 470 patients were 93%, 92%, 91%, and 91%, respectively. The hazard function for death (at any time) had a rapidly declining single phase that approached zero by one year after the operation. Risk factors for death included coronary artery patterns with a retropulmonary course of the left coronary artery (two types) and a pattern in which the right coronary artery and left anterior descending arose from the anterior sinus with a posterior course of the circumflex coronary. The only procedural risk factor identified was augmentation of the aortic arch; longer duration of circulatory arrest was also a risk factor for death. Earlier date of operation was a risk factor for death, but only in the case of the senior surgeon. Reinterventions were performed to relieve right ventricular and/or pulmonary artery stenoses alone in 28 patients. The hazard function for reintervention for pulmonary artery or valve stenosis revealed an early phase that peaked at 9 months after the operation and a constant phase for the duration of follow-up. Incremental risk factors for the early phase included multiple ventricular septal defects, the rapid two-stage arterial switch, and a coronary pattern with a single ostium supplying the right coronary and left anterior descending, with a retropulmonary course of the circumflex. The need for reintervention has decreased with time. The arterial switch operation can currently be performed early in life with a low mortality risk (< 5%) and a low incidence of reintervention (< 10%) for supravalvular pulmonary stenosis. The analyses indicate that both the mortality and reintervention risks are lower in patients with less complex anatomy.

Child, Preschool↗
PubMed1995

Advances in surgical care of infants and children with congenital heart disease.

Recent important technical developments in the field of surgery for congenital heart disease have included the Ross pulmonary autograft replacement of the aortic valve, video-assisted thoracoscopic surgery, and the double-switch and switch-Rastelli procedure for congenitally corrected transposition. Although the growth potential of the pulmonary autograft has been confirmed, an important incidence of late aortic regurgitation has been noted. Expanding indications for video-assisted thoracoscopic surgery have been described, including division of the vascular ring. Late hemodynamic assessment after the double-switch or switch-Rastelli procedure will encourage increased application of this repair. Both clinical and laboratory studies have focused on neurologic and developmental outcome after cardiac surgery. Perioperative seizures in young infants have been found to be associated with impaired psychomotor development at 1 year of age. In the area of perioperative management, the antifibrinolytic agents tranexamic acid, epsilon-aminocaproic acid, and aprotinin have been found to be useful in reducing postoperative hemorrhage. Nitric oxide is useful in reducing postoperative pulmonary hypertension. Late clinical follow-up studies of patients with single ventricle have revealed an important incidence of pulmonary arteriovenous malformations after a bidirectional Glenn shunt and atrial flutter after a Fontan procedure. Late assessment of patients after the arterial switch procedure for transposition has revealed preservation of ventricular function and an extremely low incidence of late arrhythmias.

Antifibrinolytic Agents↗
PubMed1995

Anti-CD18 attenuates deleterious effects of cardiopulmonary bypass and hypothermic circulatory arrest in piglets.

Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest induce leukocyte and platelet activation and cytokine production as part of the inflammatory response to bypass. These events are thought to be responsible for producing at least some of the morbidity of bypass. We studied the effects of a monoclonal antibody to a specific leukocyte adhesion integrin, CD18, on the deleterious effects of CPB and circulatory arrest in piglets using techniques from infant heart surgery. Seventeen immature piglets were subjected to CPB, cooling, 1 hour of circulatory arrest at 15 degrees C, and subsequent reperfusion and rewarming. Nine piglets received anti-CD18 monoclonal antibody (group MAb), and eight randomly selected control piglets received none (group C). Monoclonal antibody to leukocyte integrin CD18 significantly decreased deleterious effects of CPB and hypothermic circulatory arrest in our immature animal model. This study suggests that antiadhesion therapy that alters fundamental leukocyte/endothelial interactions during open heart surgery may be protective against some deleterious effects of bypass and circulatory arrest in infants.

Animals↗
PubMed1995

Neurologic and developmental outcomes following pediatric cardiac surgery.

The successful early repair of congenital heart disease has placed the focus on the long-term outcome for surviving patients. This article reviews the neurologic risks of cardiopulmonary bypass, deep hypothermia, and circulatory arrest. Potential neurologic and developmental sequelae in both the immediate postoperative period and the long term are discussed, with a review of current, research-based literature.

Age Factors↗
PubMed1995

Pathological considerations in cryopreserved allograft heart valves.

Since structure-function correlations have not been determined for cryopreserved allograft heart valves, we studied 20 explanted valves in place several hours to nine years, as either orthotopic aortic valves/root replacements or right ventricle to pulmonary artery conduits. They were explanted primarily due to growth-related conduit or valve stenosis, valve regurgitation, or infection. Controls included seven unused cryopreserved allograft valves and 16 aortic valves removed from transplanted allograft hearts obtained at either autopsy (n = 15) or retransplantation (n = 1), two days to four years postoperatively, following myocardial rejection (n = 4), graft coronary arteriosclerosis (n = 4), and other (n = 8). Analysis included gross inspection, radiography, light microscopy, electron microscopy, and immunohistochemical studies (to allow identification/localization of endothelial cells, mononuclear inflammatory cells, and T and B lymphocyte subsets). Cryopreserved allograft valves implanted more than one day had progressively severe loss of normal structure and were devoid of surface endothelium and stainable deep connective tissue cells. Inflammatory cellularity varied from none (most valves) to prominent (primarily T lymphocytes in one valve). Transmission electron microscopy of three long term valvular allografts revealed no viable cells, remarkable preservation of the collagenous valve matrix and focal cell-oriented calcification. In contrast, aortic valves from transplanted hearts showed remarkable structural preservation, including layered architecture, endothelium and deep connective tissue cells; inflammatory infiltrates were generally sparse, even in cases with fatal myocardial rejection. We conclude that cryopreserved allograft valves are morphologically non-viable valves, whose structural basis for function seems primarily related to the largely preserved collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗
PubMed1994

Maturational and hemodynamic factors predictive of increased cyanosis after bidirectional cavopulmonary anastomosis.

Bidirectional cavopulmonary anastomosis (BCA) is thought to be beneficial in the palliation of patients with univentricular congenital heart disease considered at high risk for Fontan repair. Experience with patients undergoing BCA suggested that those who were older or larger at the time of surgery tended to be more cyanotic postoperatively than their younger and smaller counterparts. This study was designed to identify correlates of systemic arterial oxygen saturation after BCA. Specifically, it was postulated that maturational changes in blood flow distribution might be associated with decreasing arterial oxygen saturation. Database records of all 110 patients undergoing BCA at our institution from June 1988 until the end of 1991 were reviewed. Postoperative catheterization data were available for 66 patients. Twenty-one patients were excluded because they had potentially reversible causes of cyanosis yielding inestimable degrees of error in hemodynamic calculations. In the remaining 45 patients, univariate and multivariate regression analyses were used to identify correlates of systemic arterial oxygen saturation. Growth and maturation as represented by body surface area exhibited a highly significant inverse correlation with arterial oxygen saturation (p = 0.005), as did pulmonary vascular resistance (p = 0.003). Patients who underwent BCA when > 3.9 years of age or with body surface area > 0.65 m2 were at significantly increased risk for excessive postoperative cyanosis, defined as systemic arterial oxygen saturation < or = 75% (p < 0.005). The interval between surgery and catheterization correlated directly with arterial oxygen saturation (p = 0.002), indicating a tendency toward earlier study of more cyanotic patients. None of the other variables examined correlated significantly with arterial oxygen saturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Dilation of intra-atrial baffle fenestrations: results in vivo and in vitro.

Spontaneous closure of intra-atrial baffle fenestrations occurred early postoperatively following a Fontan procedure in three patients (ages 0.8-2 yr) and were reopened using transvenous balloon dilation. Following this clinical experience with this complication we studied the effects of high pressure balloons of different sizes on fenestrations created in polytetrafluoroethylene (PTFE) patches. The intra-atrial baffle fenestration was found closed within hours after surgery in two patients and 32 days postoperatively in the other. Increasing edema, chest tube drainage, and renal dysfunction ensued rapidly. At catheterization the balloon dilation in two patients reduced the elevated right atrial pressure, edema, and pleural effusion and allowed an acceptable arterial saturation. In the other patient, with acidosis and a low cardiac output, transient cardiac arrest occurred following passage of the catheter through the fenestration and during later unsuccessful operation the fenestration, although open, was traversed by strands of clot. In the experimental study, a total of 45 fenestrations 4 mm in diameter were dilated with 5, 6, 7, 8, and 9 mm balloons. The fenestration areas remained increased significantly during the 14 days of observation in room air, with the larger balloons producing larger holes. Balloon dilation may be effective for spontaneous fenestration closure occurring in the early postoperative period after a fenestrated Fontan procedure. Our experimental data may be useful in selecting the balloon size in this setting.

Cardiac Surgical Procedures↗
PubMed1994

Total anomalous pulmonary venous drainage in newborns with visceral heterotaxy.

Children with visceral heterotaxy often present with total anomalous pulmonary venous drainage (TAPVD) associated with univentricular congenital heart disease. We reviewed our experience with the primary surgical management of this lesion under these circumstances. Over a recent 10-year span, 38 patients within the first 3 days of life were admitted to our institution and underwent primary palliation. Twenty-one of them had TAPVD, 18 to a systemic vein. Twelve (67%) of these 18 were seen with obstruction of the anomalous connection and underwent emergency operation. In 7 patients, repair of TAPVD was combined with a systemic-pulmonary artery shunt because of additional obstruction of the pulmonary blood supply, with two deaths. One patient had primary shunting and then repair of TAPVD. Four patients underwent repair of TAPVD alone. Two of them then showed signs of insufficient pulmonary blood flow, received a shunt in a second procedure, and subsequently died. Early mortality in the group with obstructed TAPVD was thus 4 (33%) of 12 patients. Statistical analysis of all 38 patients (univariate analysis, chi 2 testing) showed that neither the presence of TAPVD (p = 0.7) nor TAPVD repair alone (p = 0.8) or with shunting (p = 0.8) was a definite risk factor for early death. The performance of a shunt during the first operation, however, was associated with lower early mortality (p = 0.03). Total anomalous pulmonary venous drainage is a common finding in newborns with visceral heterotaxy. Its presence and its subsequent early repair (requiring cardiopulmonary bypass) do not increase the mortality risk. The need of a concomitant shunt in obstructed TAPVD can initially be underestimated.

Heart Defects, Congenital↗
PubMed1994

Effects of aprotinin on acute recovery of cerebral metabolism in piglets after hypothermic circulatory arrest.

Brain protection during cardiopulmonary bypass and hypothermic circulatory arrest is incomplete. Activation of blood protease cascades may contribute to cellular injury under these conditions. To test this hypothesis, effects of the protease inhibitor aprotinin on recovery of brain energy metabolism after hypothermic circulatory arrest were studied in the piglet. Twenty-four 4-week-old piglets (10 aprotinin-treated and 14 control) underwent core cooling, 1 hour of circulatory arrest at 15 degrees C, reperfusion and rewarming (45 minutes), and normothermic perfusion (3 hours) on cardiopulmonary bypass. Cerebral high-energy phosphate concentration and intracellular pH were studied by phosphorus-31 magnetic resonance spectroscopy in 12 animals. In the remaining animals cerebral and regional blood flow were measured with radioactive microspheres and carotid artery blood flow was measured with an electromagnetic flowmeter. Cerebral oxygen and glucose extraction were measured, and vascular resistance responses to endothelium-dependent (acetylcholine) and -independent (nitroglycerin) vasodilators were calculated. Recovery of cerebral adenosine triphosphate (p = 0.02) and intracellular pH (p = 0.04) in the initial 30 minutes of reperfusion was accelerated in the aprotinin-treated piglets. These piglets showed a greater in vivo cerebral and systemic endothelium-mediated vasodilation (acetylcholine response: cerebral p < 0.01, systemic p = 0.04) after reperfusion. The response to endothelium-independent vasodilation (nitroglycerin) was the same in both groups. Carotid blood flow tended to be greater at 20 minutes of reperfusion and less during 45 to 80 minutes after reperfusion in the aprotinin-treated animals. Brain water content postoperatively was 0.8077 in the aprotinin group and 0.8122 in control animals (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Downsizing of valve allografts for use as right heart conduits.

In recent years, there has been a worsening shortage of small and intermediate-sized aortic and pulmonary allografts for use as right ventricular-to-pulmonary artery conduits in infants and children. However, there is a surfeit of large pulmonary and aortic allografts from adult donors. The feasibility of reducing a large allograft to a more useful size was examined using human pulmonary and aortic allografts. Eleven pulmonary allografts (11 to 26 mm in diameter) and nine aortic allografts (5 to 27 mm in diameter) were studied. Valve competence before downsizing was tested with a column of saline to a static pressure equivalent to the normal pulmonary pressure (20 mm Hg). Regurgitant flow was measured for 15 minutes. One complete cusp of the valve was excised, together with a longitudinal strip of the arterial wall. A bicuspid valved conduit was created by suturing the allograft longitudinally. The diameter of the bicuspid valve was measured with a dilator. A nomogram was constructed that predicts the size of the bicuspid allograft based on the size of the original allograft. The competence of the bicuspid allograft was tested and the regurgitant flow was compared with that of the original tricuspid allograft. The transvalvular systolic pressure gradient was measured with the bicuspid allograft placed in a pulsatile extracorporeal perfusion circuit at a flow rate of 1 L/min and a mean pressure of 20.5 +/- 2.6 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

West syndrome following deep hypothermic infant cardiac surgery.

Postoperative seizures are among the more common complications of cardiac surgery in children. These seizures have traditionally been considered benign, transient phenomena with little, if any, prognostic significance. We report 4 infants with early postoperative seizures following cardiac surgery who later developed the previously unreported complication of West syndrome, with infantile spasms, hypsarrhythmia, and developmental delay. This group constitutes 6% of 67 infant spasms evaluated over a 5-year period at Boston Children's Hospital. The postoperative seizures in these 4 patients were more difficult than usual to control with antiepileptic therapy; otherwise no intra- or perioperative features distinguished these infants who later developed West syndrome from infants with apparently benign "postpump seizures."

Adrenocorticotropic Hormone↗