Use of the pulmonary autograft for mitral replacement: short- and medium-term experience.

OBJECTIVES: In an effort to find a suitable mitral substitute for our young rheumatic patients who cannot follow a proper anticoagulation regimen for life, we resorted to an old concept reported by one of the authors (D.N.R.) in 1967. This report summarizes our experience with the Ross-mitral operation to date. METHODS: Between 19 June 1997 and 27 June 2000, 43 patients with rheumatic valve disease underwent the Ross-mitral operation. Two patients were excluded because of graft stenosis detected at the end of the procedure for which the autograft had to be sacrificed. Of the remaining 41 patients 29 were female, and the age range was 12--57 years (median 39 years). The autograft was incorporated within a Dacron tubing, with a pericardial collar attached to its proximal end. The conduit was sutured distally to the excised mitral annulus; the pericardium was attached proximally to the atrial wall in 36 patients, and was used simply to cover the Dacron tubing in five patients. The pulmonary artery was replaced with a pulmonary or aortic homograft, or with a pulmonary xenograft. RESULTS: There were two hospital fatalities from a cerebrovascular accident and a lung injury, and two postoperative myocardial infarctions. There were five late deaths, two due to bacterial endocarditis, one due to excessive bleeding at reoperation for a paravalvular leak, and two not related to the procedure. A phenomenon of 'autograft stenosis' occurred intraoperatively in four recent consecutive patients that probably resulted from our use, for the first time, of softer Dacron tubing material. This was repaired in two of the four patients. Echocardiography confirmed excellent functioning of all 34 autografts of surviving patients up to 36 months postoperatively (mean follow-up 18.2 months). Two patients remain in functional Class III status, one due to left heart failure following myocardial infarction, and the other due to recurrent tricuspid insufficiency. CONCLUSIONS: We believe that the mitral pulmonary autograft is a worthwhile alternative to mechanical prostheses in developing countries.

The mitral pulmonary autograft: a follow up cautionary report.

BACKGROUND AND AIM OF THE STUDY: The study aim was to alert surgeons embarking on mitral replacement with the pulmonary autograft to the possibility of graft stenosis resulting from kinking of the Dacron tube support. METHODS AND RESULTS: After having used old-style Dacron tubing for pulmonary autograft support in 32 patients, a change was made to a softer variety. This, together with routine retention of the posterior subvalvular apparatus, resulted in Dacron tube angulation and autograft stenosis detected at intraoperative echocardiography in four consecutive patients, This sequela was corrected in one patient by re-adjusting the pericardial collar, and in another by severing the retained chordae. However, in two patients it was necessary to sacrifice the autograft and replace it with a mechanical prosthesis. When the reason for the complication was identified, and a return to the use of a firmer Dacron material instigated, this phenomenon disappeared and surgery was completed in the final three patients, without mishap. CONCLUSION: The use of a newer soft Dacron tubing to support the pulmonary autograft in mitral replacement might result in autograft stenosis. Thus, a firm-type Dacron should be used for this operation.

Mitral valve replacement with a pulmonary autograft: initial experience.

BACKGROUND AND AIM OF THE STUDY: For long-term substitution of the mitral valve, mechanical prostheses require life-long anticoagulation which is impractical in developing countries, xenografts degenerate early in our young population, and mitral homografts have not yet been established as being suitable. We therefore returned to an original concept first reported by one of the authors (D.N.R.) in 1967. METHODS: Between July 1997 and November 1998, 22 patients (mean age 40.3 years; range: 28 to 57 years) with rheumatic mitral valve disease unsuitable for reconstruction were subjected to excision of their pulmonary valve in the standard fashion of the Ross procedure. The inverted autograft was incorporated in a 2.5 cm-long Dacron conduit, with a pericardial collar attached to its proximal end. The distal end of the autograft-conduit was sutured to the annulus of the excised mitral valve, and the proximal end incorporating the pericardial collar was attached to the adjacent atrial wall. In this way all prosthetic material was covered. The right ventricular outflow was reconstructed with a pulmonary homograft in 17 patients, with an aortic homograft in two, and with a porcine pulmonary xenograft in three. RESULTS: One patient developed a fatal cerebrovascular accident, probably related to an incorrectly placed pericardial collar with rough surface exposed to the blood flow. In a second patient the autograft had to be replaced six weeks after operation due to bacterial endocarditis contracted in the operating room. Echocardiography confirmed excellent function of the remaining autografts up to 16 months postoperatively (mean follow up 8.3 months). CONCLUSIONS: We believe the pulmonary autograft to be a valid option for mitral valve replacement in our patients.

Attenuation of acute lung injury caused by hind-limb ischemia-reperfusion injury by butyrolactone anti-inflammatory agent FL1003.

OBJECTIVE: Activation of systemic inflammation after reperfusion of ischemic tissue results in severe acute lung injury. Neutrophil activation and oxygen radical generation have been implicated in the pathogenesis. This study tested the hypothesis that treatment with FL1003, a butyrolactone with in vitro antioxidant properties, will down-regulate this response and abrogate acute lung injury. METHODS: Male Sprague-Dawley rats (n = 16) were divided into a surgical sham group (n = 4), a group that received 2 hours of ischemia by infrarenal aortic clip followed by 1 hour of reperfusion (n = 7), and an ischemia-reperfusion (I/R) group that received FL1003 100 mg/kg intravenously before ischemia (n = 5). After reperfusion, the heart and lungs were excised en bloc in an isolated lung perfusion apparatus for 1.5 hours of perfusion, while pulmonary artery pressures were held between 5 and 12 mm Hg and venous effluent was collected. Bronchoalveolar lavage fluid and both lungs were harvested at death for determination of tissue water content, pulmonary microvascular permeability, and indicators of neutrophil activation and tissue oxidation. RESULTS: After I/R, there were significant (p < 0.05) increases in intravenous fluid (IVF) requirements (18 +/- 1.2 mL) to maintain hemodynamic stability, wet weight/dry weight ratio of lung tissue, and isolated-lung lavage Ficoll concentrations (0.58 +/- 0.02 microg/mL) compared with sham animals (IVF, 0 mL; Ficoll concentration, 0.08 +/- 0.03 microg/mL). In addition, lung myeloperoxidase activity (0.60 +/- 0.03 vs. 0.12 +/- 0.02 units/g of tissue) and levels of lipid-conjugated dienes (0.042 +/- 0.012 vs. 0.018 +/- 0.006 optical density of 233 nm (OD233)/mL) were significantly higher (p < 0.05) compared with the sham group. In I/R animals treated with FL1003, the IVF requirement (8.5 +/- 1.0 mL), wet weight/dry weight ratio, lung tissue Ficoll concentration (0.21 +/- 0.02 microg/mL), myeloperoxidase concentration (0.217 +/- 0.02 units/g), and lipid-conjugated diene levels (0.012 +/- 0.005 OD233/ mL) were all significantly lower (p < 0.05) than after untreated I/R. CONCLUSION: A pulmonary microvascular permeability defect with pulmonary edema, neutrophil aggregation, and cell membrane damage resulted from ischemia and reperfusion. Treatment of animals with FL1003 significantly attenuated the inflammatory response associated with acute lung injury.

Changes of MPO activity and brain water accumulation in traumatic brain injury experiments.

Comparison of brain tissue water content (BWC) data with myeloperoxidase activity assay (MPO) allows for analysis of the complex pathophysiological mechanisms of cerebral edema following catastrophic brain injuries. The neuroprotective effect of an experimental anti inflammatory drug (FL1003, butyrolactone) was tested in a traumatic brain injury (TBI) model using BWC and MPO analysis. We conducted these studies on a mini-pig model of severe TBI that is well characterized in our laboratory. The animals were divided into three animal groups: no injury, no treatment (control), injured and treated with FL1003, and injured, untreated with FL1003. They were maintained with fluids for 24 hours under general anesthesia. We employed the MPO assay to identify the degree of inflammatory cellular response (polymorphonuclear leukocytes, PMNLs) 24 hours following TBI and calculated brain density from the data of the gravimetric (Percoll) column method for BWC on brain samples. Our results demonstrated increased infiltration of PMNLs and a shift of water into the extravascular space in the injured animals. These changes were significantly (P < 0.05) attenuated in the animal group treated with FL1003.

Mechanisms of cerebrovascular dysfunction.

Cerebrovascular dysfunction characterized by the loss of endothelial integrity has been observed following ischemic and traumatic insults to the brain, resulting in the net movement of fluid and solute out of the intravascular space and into the interstitium. Following traumatic brain injury, the development of intracranial hypertension secondary to cerebral edema plays a major role in the high morbidity and mortality in these patients. Although the precise mechanisms responsible for the disruption of the normally tightly regulated cerebrovascular tissue interface remain unclear, there is increasing evidence implicating inflammatory events in this process through the transient opening of tight junctional complexes. This article will examine the interaction of astrocytes, activated neutrophils, and inflammatory mediators in inducing endothelial contraction, thereby physically opening the permeability barrier and allowing the net movement of fluid out of the intravascular space.

Case management in home total parenteral nutrition: a cost-identification analysis.

BACKGROUND: Home parenteral nutrition (HPN) requires intensive medical case management by practitioners with expertise in the provision of nutrition support. There is expenditure of considerable time and resources for management of these patients not covered by any of the traditional reimbursement mechanisms. The costs associated with this unreimbursed input and follow-up are most often borne by the Nutrition Support Team or individual practitioners. Reimbursement by home care agencies to physicians for management of patients after discharge cannot be done because this may be construed as a "kick-back" for referral of patients to particular home care agencies. METHODS: Time and costs associated with management of HPN patients after discharge from the hospital were assessed using a cost-identification analysis of 24 different factors. Daily activity logs were kept by the Nutrition Support Team members over a 2-week period. Costs of space and furnishings were calculated. RESULTS: On average, a total of 25 h/d was spent by members of the Nutrition Support Team on our HPN patients. Variable activities accounted for 5640.1 hours of time with fixed support at 890.3 hours. This computes to a total annual personnel cost of $168,482 ($1982 per patient). If costs of furnishings and space are also included, the overall cost of all resources was $175,989 per year or $2070 per patient. CONCLUSION: Significant and currently nonreimbursed costs are involved in HPN patient management. These costs are most often absorbed by the Nutrition Support Team and should be considered when evaluating total costs of HPN.

Utility of routine chest radiographs in the surgical intensive care unit. A prospective study.

OBJECTIVES: To correlate patient condition and reasons for obtaining chest radiographs (CXRs) with the utility of CXRs in critical illness and to determine the potential impact of stricter criteria for obtaining a CXR in a surgical intensive care unit (ICU). DESIGN: Inception cohort study of 1003 CXRs examined prospectively. PATIENTS AND SETTING: A total of 157 consecutive patients admitted to the general surgical ICU of a 780-bed, urban, university-affiliated, tertiary care hospital. INTERVENTION: Nothing was done to influence the ordering of CXRs. OUTCOME MEASURES: Influence of CXR findings on clinical management. RESULTS: The likelihood of a clinically important finding was 17% for CXRs obtained for no clear clinical indication (routine), 26% for those obtained to verify the position of a medical device, and 30% for those obtained for suspected clinical conditions. By univariate analysis, suspected pathophysiologic condition, admission APACHE II (Acute Physiology and Chronic Health Evaluation II) score, presence of a central venous or Swan-Ganz catheter, and length of ICU stay were all predictors of a significant finding. By multivariate analysis, the only independent predictor of a finding was a suspected clinical condition, and the only indwelling medical device that was an independent predictor of a finding was a Swan-Ganz catheter. If the criterion that routine CXRs should only be obtained in patients with Swan-Ganz catheters had been used, 200 CXRs would have been avoided during the 3-month study period. The only findings missed by not obtaining those CXRs would have been two malpositioned nasogastric tubes and one malpositioned central venous catheter. CONCLUSIONS: Chest radiographs should only be obtained on surgical ICU patients for specific indications. Routine CXRs for ICU patients are justified only for patients with indwelling Swan-Ganz catheters.

The square-wave approach to impedance measurement of brain tissue water dynamics.

Electrical properties of living soft tissue have been used to analyze their structure and function. Presently, the 'admittance locus' method, with the sine-wave signal of changing frequency, is the most informative continuous method for analyzing extra-and intracellular water content in brain tissue. Using the square-wave signal in lieu of the sine-wave signal, we can avoid cumbersome and costly measurements and facilitate real-time data processing. An isolation-calibration device was developed for the present study in order to condition and stabilize electrical current through the brain cortex. This device was also used for impedance calibration before and after the experiments. We propose a simple algorithm for data analysis on the basis of equivalent circuit approach, which allows to develop a computer program for data processing. Preliminary experiments on rat brains were carried out with a 0.2-0.5 mm stainless-steel tetrapolar electrode system. These studies showed good linearity between stimulating currents (I = 5-30 microA) through the external electrodes in the brain cortex and a drop in voltage which was measured by 2 inner electrodes. The results of the device and the program accuracy tests allow us to choose the optimal range for the working current. We can recommend this method for usage in animal experiments.

Survey of critical care management of comatose, head-injured patients in the United States.

OBJECTIVE: This survey was designed to study current practices in the monitoring and treatment of patients with severe head injury in the United States. DATA SOURCES: The collected data represent answers to telephone interviews of nurse managers, clinical specialists, and staff nurses specializing in neurotrauma care at 277 randomly selected hospitals from a total pool of 624 trauma centers. Overall, 261 (94%) centers participated in the survey. Of the participating centers, 219 (84%) were providers of care for severely head-injured patients. In order to assess reliability and account for differences among respondents, personnel from 40 (15%) centers were resurveyed 6 months later and a different nursing professional was interviewed, although the questions remained the same. DATA EXTRACTION: The largest group of respondents came from level I centers (49%), followed by level II (32%) and level III (2%). Thirty-four percent of the surveyed hospitals had a designated neurologic/neurosurgical intensive care unit, and 24% of all units surveyed were under the direction of either a neurosurgeon or a neurologist. Twenty-eight percent of the centers routinely performed intracranial pressure monitoring, while 7% of the centers reported never using this technique. The use of ventriculostomy catheters for intracranial pressure monitoring was employed in 72% of the centers, but cerebrospinal fluid drainage was utilized by only 44% of the hospitals. The percentage of patients who had their intracranial pressure monitored was significantly higher in level I trauma centers and at hospitals that treated larger numbers of severely head-injured patients (15 to 30 patients per month, which represented 15% of the hospitals surveyed). Hyperventilation and osmotic diuretics were used in 83% of centers to reduce intracranial hypertension. The administration of barbiturates was reported in 33% of the units as a treatment for intracranial hypertension. Corticosteroids were used more than half of the time in 64% of trauma centers. Twenty-nine percent of the centers reported aiming for PaCO2 values of < 25 torr (< 3.3 kPa). CONCLUSIONS: The survey data indicate that there is a considerable variation in the management of patients with severe head injury in the United States. The establishment of guidelines for the management of head injury based on available scientific data and moderated by practical and financial considerations may lead to improvement in the standard of care.

Cerebral edema.

Cerebral edema continues to plague clinicians caring for patients with acute catastrophic neurologic disease. The defect responsible for the accumulation of water in the brain appears to reflect loss of the strict permeability barrier of the cerebral vasculature. A greater understanding of the physiologic mechanisms at work in the blood-brain barrier have helped target therapies at the vascular interface between the circulating blood and the brain. The mounting evidence which implicates inflammatory events as causally related to the loss of cerebrovascular impermeability supports the clinical strategy of suppression of acute inflammation. Clearly, further advances in the management of cerebral edema will be strongly influenced by the development of specific anti-inflammatory pharmaceuticals.

Alterations of pulmonary gas exchange after superimposed carbon monoxide poisoning in acute lung injury.

BACKGROUND: Smoke inhalation injury produces substantial morbidity and mortality caused both by immediate catastrophic pulmonary failure and by the subsequent development of pneumonia. Although carbon monoxide (CO) poisoning is present to a degree in nearly all instances of smoke inhalation, the importance of CO in the pathogenesis of smoke inhalation injury remains controversial because smoke contains numerous other potential pulmonary toxins such as aldehydes, chlorine gas, and hydrochloric acid. This study was performed to determine whether CO poisoning acts as a cofactor in the evolution of inhalation injury. METHODS: Four groups of anesthetized dogs received ventilation with 1% CO in room air alone, intratracheal instillation of 2.0 ml/kg 0.1 N hydrochloric acid (HCl) alone, or acid either immediately or 30 minutes before CO. Ventilation/perfusion relationships were measured for 4 hours thereafter with the multiple inert gas elimination technique. RESULTS: Acid instillation established 30 minutes before CO poisoning resulted in significantly decreased carboxyhemoglobin concentrations after ventilation with 1% CO in air for 10 minutes. However, CO elimination was markedly delayed in both acid-challenged groups ventilated with CO. Moreover, acid instillation immediately before CO poisoning significantly exacerbated the development of ventilation/perfusion inequality caused by the acid, because the development of shunt was accelerated. CONCLUSIONS: CO poisoning is an important cofactor in the development of inhalation injury by acceleration of the development of ventilation/perfusion inequality after inhalation.

A method for monitoring intracranial temperature via tunneled ventricular catheter: technical note.

A simple technique for monitoring intracerebral temperature in humans via a ventricular catheter is described. This differs from a previously described method by enabling such measurements to be accomplished with a commercially available thermistor, a standard ventricular catheter, and common hospital supplies. In contrast to the earlier device, this system allows for the subcutaneous tunneling of the distal ventricular catheter. This is an easily assembled and cost-effective technique with which to conduct investigations on human intracerebral temperature.

Traumatic injury induces interleukin-6 production by human astrocytes.

The brain is being evaluated as a de novo source of cytokines. Because recent evidence indicates that interleukin-6 (IL-6) may influence blood-brain barrier function and vascular permeability, we have sought to determine whether mechanical injury can directly induce in situ cerebral IL-6 production. Adult human astrocyte cultures were subjected to mechanical injury by the in vitro method of fluid percussion barotrauma, developed in our laboratory. Serial supernatant samples were collected for 8 h and evaluated for IL-6 activity using a proliferation assay employing the dependent B cell hybridoma cell line, B9. At optimum injury, the IL-6 level became significantly (P < 0.0001, analysis of variance) elevated from baseline 2 h after trauma and continued to increase over the observation period. Our study shows that following mechanical injury human astrocytes produce IL-6, which may contribute to post-traumatic cerebrovascular dysfunction. Elucidating the precise role of intracerebral cytokines is essential to our understanding of the mechanism responsible for post-traumatic cerebrovascular dysfunction.

A square signal wave method for measurement of brain extra- and intracellular water content.

Brain tissue electrical impedance is a commonly used method to evaluate the dynamics of brain edema. We have found the square wave impedance method simpler and more cost-effective than the currently used sine wave impedance method. This square wave method avoids the necessity for expensive frequency control and amplitude-phase measuring devices as well as simplifying on-line data processing. In our experiments the electrical impulse was generated by a pulse generator of Macintosh data acquisition system. The signal (I = 11 muA, t = 2-20 ms) was delivered every 2-3 s external electrodes of a tetrapolar system through a specially designed isolation-calibration device. This electrode system was inserted into the cerebral cortex of experimental animals (rat). The cerebral cortex was found to have linear electrical properties in the 5-30 muA range. Our impedance measurement system was tested in calibration trials, and showed system reliability and accuracy. The system was also tested in pilot experiments, in vivo, in a rat brain osmotic edema model.

Traumatic brain injury, hemorrhagic shock, and fluid resuscitation: effects on intracranial pressure and brain compliance.

Intracranial hypertension following traumatic brain injury is associated with considerable morbidity and mortality. Hemorrhagic hypovolemia commonly coexists with head injury in this population of patients. Therapy directed at correcting hypovolemic shock includes vigorous volume expansion with crystalloid solutions. It is hypothesized that, following traumatic brain injury, cerebrovascular dysfunction results in rapid loss of brain compliance, resulting in increased sensitivity to cerebrovascular venous pressure. Increased central venous pressure (CVP) occurring with vigorous crystalloid resuscitation may therefore contribute to the loss of brain compliance and the development of intracranial hypertension. The authors tested this hypothesis in miniature swine subjected to traumatic brain injury, hemorrhage, and resuscitation. Elevated CVP following resuscitation from hemorrhage to a high CVP significantly worsened intracranial hypertension in animals with concurrent traumatic brain injury, as compared to animals subjected to traumatic brain injury alone (mean +/- standard error of the mean: 33.0 +/- 2.0 vs. 20.0 +/- 2.0 mm Hg, p < 0.05) or to animals subjected to the combination of traumatic brain injury, hemorrhage, and resuscitation to a low CVP (33.0 +/- 2.0 vs. 24.0 +/- 2.0 mm Hg, p < 0.05). These data support the hypothesis that reduction in brain compliance can occur secondary to elevation of CVP following resuscitation from hemorrhagic shock. This may worsen intracranial hypertension in patients with traumatic brain injury and hemorrhagic shock.

Contribution of increased cerebral blood volume to posttraumatic intracranial hypertension.

Cerebrovascular dysfunction following acute brain injury (BI) may be the critical mediator of excess morbidity and mortality after BI. Despite aggressive therapy, death often is caused by refractory intracranial hypertension (IH). An understanding of the contributions of cerebrospinal fluid (CSF) and vascular factors to IH after BI is essential for management of intracranial pressure (ICP). Marmarou et al. showed that CSF accounted for only one third of the ICP rise after BI. We hypothesized that a vascular mechanism is predominant. Cerebral cortical reflectance photoplethysmography (IP) and radioactively labeled red blood cells were employed to study cerebral blood volume (CBV) changes associated with increased ICP after BI in miniature swine. Immediate posttraumatic IH could be attributed almost entirely to increased CBV. An early elevation in ICP immediately after BI (t = 0) was accompanied by a large increase in CBV compared with pre-BI levels (19.2 +/- 4.9 vs. 8.9 +/- 2.7 mL/100 g tissue, p < 0.05). Decreased CBV corresponded to lower ICP within 1 hour, followed by a slow rise that paralleled the increase in ICP. The CBV (16.1 +/- 3.3 vs. 8.9 +/- 2.7, p < 0.05) and ICP (23 +/- 2.2 vs. 9 +/- 0.6, p < 0.05) were higher at 6 hours than at baseline. Based on compartmental analysis, the data indicate that ICP changes immediately after BI and within 6 hours are predominantly caused by increased CBV.

Human astrocyte production of tumour necrosis factor-alpha, interleukin-1 beta, and interleukin-6 following exposure to lipopolysaccharide endotoxin.

The cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6, have been found in the human central nervous system. Recent studies have demonstrated that murine astrocytes produce these cytokines when induced with lipopolysaccharide endotoxin (LPS). The present study investigates the kinetics of TNF-alpha, IL-1 beta, and IL-6 production by normal adult human astrocytes when exposed to LPS.

Alterations in intracranial pressure and cerebral blood volume in endotoxemia.

Marked deterioration of neurologic function accompanies organ dysfunction in systemic sepsis. Although previous hypotheses have suggested that cerebral hypoperfusion, anoxia or progressive edema of the brain may be causative, the pathogenesis remains unknown. Patients with sepsis with stable or supported hemodynamics and adequate oxygenation may manifest confusion, stupor or coma. Recent evidence has demonstrated that the brain is the source of many classical mediators of inflammation after various forms of injury. These mediators, including the leukotrienes, have pronounced effect on cerebrovascular function. Endotoxin is known to stimulate the release of arachidonate from cell membranes, the rate limiting step in leukotriene synthesis. The current studies were performed to test the hypothesis that neurologic dysfunction associated with endotoxemia is characterized by alterations in cerebrovascular permeability or vasomotor function manifested by intracranial hypertension, or both. We studied the response of miniature swine to experimental endotoxemic shock and compared this response with hemorrhagic hypotension. We observed a dramatic elevation of intracranial pressure in swine subjected to endotoxemic shock, despite arterial hypotension. Moreover, estimation of cerebral blood volume (CBV) by reflectance infrared photoplethysmography demonstrated a dramatic increase in CBV, which corresponded to this elevation in intracranial pressure. However, cerebral cortical oxygen saturation was significantly reduced despite this net increase in CBV, indicative of an increase in the venous volume of the brain, while arterial volume remained the same or decreased from baseline levels. Oxygen extraction across the brain decreased during this same period compared with baseline and control values. These results demonstrate that endotoxemia is associated with the development of intracranial hypertension and an increase in CBV secondary to elevation of cerebrovascular venous volume coupled with reduced oxygen extraction across the brain. This evidence of cerebrovascular dysfunction probably represents blood flow maldistribution, similar to that seen in other organs with sepsis, suggesting a cause for altered neurologic function in systemic sepsis.