Postintubation tracheal stenosis: diagnosis and management.

Postintubation damage is a potential hazard in any patient intubated with an oral or nasal endotracheal tube or with a tracheostomy tube for ventilatory support. Postintubation tracheal stenosis may be fatal unless it is recognized and treated promptly. This paper reviews the important features of diagnosis and treatment of postintubation tracheal stenosis.

Effects of cyclosporine on cerebral blood flow and metabolism in dogs.

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Regulation of pulmonary resistance during cardiopulmonary preservation.

To characterize the neural and vasoactive mediators of pulmonary vasoconstriction and determine whether the beneficial effect of isoproterenol could be mimicked by other agents that increase cyclic adenosine monophosphate, heart and lung organ blocks were harvested from calves and studied in a normothermic autoperfusion circuit. In the experimental protocol, measurements were obtained (A) after sternotomy but before autoperfusion (in vivo); (B) during stimulation of in vivo control with tert-butyl hydroperoxide (t-BuOOH), a lipid peroxide; (C) after cannulation and institution of in situ autoperfusion (innervated preparation); (D) following denervation and explanation (ex vivo); (E) during stimulation of ex vivo preparation with t-BuOOH; and (F,G) after administration of isoproterenol, aminophylline and prostaglandin E1 to the ex vivo preparation with (time G) and without (time F) stimulation using t-BuOOH. Plots of transpulmonary pressure gradient versus cardiac output were generated for each animal, and an index of pulmonary vascular resistance was obtained from the slope of the linear relationship. Blood samples were collected for measurement of thromboxane-B2, 6-keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Pulmonary vasoconstriction occurred during in situ autoperfusion prior to denervation and increased further following denervation and ex vivo autoperfusion; vasoconstriction correlated with increased levels of circulating vasoactive mediators. The pulmonary vasoconstrictor response was greater in the denervated vascular bed compared with the innervated state. All agents reduced postexplant pulmonary vasoconstriction. We conclude that agents that increase cyclic AMP modulate the pulmonary vasoconstrictor response and thus may enhance lung preservation in the autoperfusion model as well as with other current preservation methods.

The role of neural and vasoactive mediators in the regulation of the pulmonary circulation during cardiopulmonary preservation.

The autoperfused working heart-lung preparation has been used for extended cardiopulmonary preservation for transplantation. However, acute lung injury and failure of the preparation can result from pulmonary hypertension, which previous investigators have linked to denervation. We studied the neural and vasoactive mediators of pulmonary vasoconstriction during normothermic autoperfusion of the heart and lungs from 13 calves. Pulmonary vascular resistance was quantitated by multipoint pulmonary artery pressure/flow plots generated by incremental reduction in venous return at three times: A, after sternotomy but before autoperfusion (control); B, during in situ autoperfusion (innervated heart-lung preparation); and C, after explanation (denervated heart-lung preparation). During hemodynamic measurements, left atrial blood samples were obtained for measurement of thromboxane B2, 6-keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Results show that pulmonary hypertension in the autoperfused working heart-lung preparation begins during autoperfusion before denervation and may be related to complement activation and to increased levels of circulating thromboxane B2 and 6-keto-prostaglandin F1 alpha (both the absolute levels and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha). After denervation, both prostaglandin intermediates were markedly increased, but their ratio was not significantly affected. These data suggest that there is an initial stage of pulmonary vasoconstriction at the onset of autoperfusion that is accompanied by increased circulating levels of vasoactive mediators and that denervation further contributes to this response.

Left ventricular function in subacute and chronic mitral regurgitation. Effect on function early postoperatively.

Quantitative analysis of biplane ventriculograms, including calculation of the end-systolic pressure/volume ratio, was used to define left ventricular systolic performance in 10 normal subjects, 10 patients with symptomatic subacute (less than 6 months' duration) mitral regurgitation, and 18 patients with symptomatic chronic mitral regurgitation. Left ventricular volume, mass, and systolic function were similar for patients with subacute and with chronic mitral regurgitation, suggesting that some patients with recent-onset nonischemic mitral regurgitation have partial adaptation to chronic valve insufficiency prior to their symptomatic event. Rate of development of left ventricular wall stress in early systole was increased in subacute mitral regurgitation compared with chronic mitral regurgitation and normal subjects. Duration of symptoms did not correlate with degree of ventricular adaptation to mitral regurgitation, and end-systolic indices of left ventricular performance did not predict early postoperative clinical response to valve replacement or repair.

Thrombotic obstruction of disc valves: clinical recognition and surgical management.

Twenty-seven patients underwent reoperation because of thrombotic obstruction of a disc-type cardiac valve prosthesis. Preoperative clinical features included effort dyspnea in 81%, new-onset angina in 44%, a new murmur in 89%, and an abnormal opening or closing sound associated with the prosthetic valve in 56%. Symptoms were present for 1 week or more before reoperation in 86%, although many patients were referred only after acute exacerbation of heart failure and development of pulmonary edema. Noninvasive studies confirmed prosthetic valve malfunction in only 33%, but cardiac catheterization documented thrombotic obstruction in all 15 patients in whom it was performed. In 14 of the 27 patients, prothrombin time was in the therapeutic range at the time of admission. Prompt reoperation for valve replacement or thrombectomy was performed with an operative mortality of 11%, and long-term outcome was satisfactory in all but 1 hospital survivor. These findings emphasize the importance of considering the diagnosis of thrombosed heart valves in patients with mechanical heart valves who are seen with nonspecific symptoms.

Improved myocardial and pulmonary preservation by metabolic substrate enhancement in the autoperfused working heart-lung preparation.

The autoperfused working heart-lung (AWHL) preparation may provide successful cardiopulmonary preservation for up to 6 hours before transplantation. To determine whether the addition of metabolic substrate could prolong myocardial and pulmonary preservation in the AWHL model, 20 heart-lung blocks were harvested from calves. The brachiocephalic artery and superior vena cava were cannulated with extracorporeal tubing and connected to an elevated reservoir allowing total perfusion through a normothermic autoperfusion circuit. Eight heart-lung blocks were given dextrose and ribose followed by a continuous dextrose-insulin infusion, whereas the remaining 12 specimens received no additional substrates. Myocardial function was assessed by sonomicrometric techniques and pulmonary preservation evaluated by arterial oxygenation on 100% inspired oxygen, static lung compliance, and serial lung biopsies. The addition of substrate prolonged organ survival from 5 +/- 1 to 12 +/- 3 hours (p less than 0.001) and was associated with preservation of myocardial and pulmonary function. Application of substrate addition to the AWHL model will extend the interval of preservation for both heart and heart-lung transplantation.

Donor core-cooling provides improved static preservation for heart-lung transplantation.

Twenty-three dairy calves underwent heart-lung allotransplantation after donor organs were procured using either donor core-cooling through cardiopulmonary bypass (CPB) or pulmonary artery flush (PAF) to assess which method provides optimal graft preservation. In Groups 1 (control) and 2, donors were cooled to 15 degrees C on CPB and organs were either immediately transplanted (Group 1) or stored in saline solution (4 degrees C) for 4 hours (Group 2) prior to transplantation. In Group 3, donors were pretreated with prostaglandin E1 prior to PAF with modified Euro-Collins solution. Organs were stored in saline solution (4 degrees C) for 4 hours and were then transplanted. Acute cardiopulmonary function following transplantation was assessed by the ratio of end-systolic pressure to end-systolic dimension, extravascular lung water (EVLW), lung compliance, arterial oxygenation, and lung biopsy. Cardiac function after the transplantation procedure was similar in all groups, but EVLW values and lung biopsy scores were worse after PAF. Arterial O2 tension appeared lower after PAF, but not significantly so. Core-cooling provides superior static preservation and thus improved graft function in the acute bovine model.

Neurohumoral modulation of the pulmonary vasoconstrictor response in the autoperfused working heart-lung preparation during cardiopulmonary preservation.

Uncontrolled pulmonary hypertension during autoperfusion of the heart and lungs for preservation has been described, and it may result in extensive pulmonary injury and occasional early failure of the preparation. In order to investigate the neurohumoral mediators of the vasoconstrictor response in the pulmonary circulation of the autoperfused working heart-lung preparation, heart-lung organ blocks were harvested from calves, placed in a normothermic autoperfusion circuit, and studied. Effects of beta-adrenergic stimulation with isoproterenol, nonspecific vasodilatation with nitroglycerin, alpha-adrenergic blockade with phentolamine, phospholipase A2 inhibition with methylprednisolone, cyclooxygenase inhibition with indomethacin, and white blood cell depletion were independently evaluated. Untreated animals, pre- and postexplant, served as controls. Multipoint pulmonary vascular pressure-cardiac output plots were constructed for each animal. An index of pulmonary vascular resistance was obtained from the linear relation: mean pulmonary artery pressure minus pulmonary capillary wedge pressure divided by cardiac output. An intense flow-dependent pulmonary vasoconstrictor response was confirmed to exist in the denervated bovine autoperfused working heart-lung preparation. Isoproterenol afforded better protection against this response than the other agents studied. White blood cell depletion reduced postexplant pulmonary vasoconstriction, implying that circulating polymorphonuclear leukocytes mediate the response in the autoperfused working heart-lung preparation. White blood cell depletion and the administration of selected pharmacologic agents provide modalities for regulating the pulmonary vasoconstrictor response, and thus may enhance lung preservation in the autoperfusion model.

A no-flush, core-cooling technique for successful cardiopulmonary preservation in heart-lung transplantation.

In order to determine whether a no-flush, core-cooling technique could provide extended heart-lung preservation, we placed donor calves on cardiopulmonary bypass and instituted rapid cooling to 15 degrees C during the continuous infusion of isoproterenol. The heart and lungs were harvested after the administration of a cardioplegic solution through the aortic root. In the control group (N = 5), heart and lungs were orthotopically allotransplanted immediately. In the preserved group (N = 5), heart and lungs were similarly excised but were stored in a normal saline bath at 4 degrees C for approximately 4 hours and then transplanted. Both groups received isoproterenol during reperfusion and were studied for 6 hours after implantation. A load independent analysis of myocardial function was done by determining with a sonomicrometer the ratio of the end-systolic pressure to the end-systolic dimension. Pulmonary preservation was evaluated by measurement of extravascular lung water with a double-indicator dilution method, arterial oxygenation on 100% inspired oxygen, and serial lung biopsies. Myocardial and pulmonary function after 4 hours of static preservation was found to be similar to controls. No-flush, core-cooling with cardiopulmonary bypass provides adequate cardiorespiratory function after acute bovine heart-lung allotransplantation. With the use of this technique, successful extended cold ischemic cardiopulmonary preservation for heart-lung transplantation may be achieved.

Autoperfused working heart-lung preparation versus hypothermic cardiopulmonary preservation for transplantation.

The effects of preserving the heart and lungs with an autoperfused working heart-lung preparation or simple hypothermia via cardiopulmonary bypass were studied in 18 dairy calves that had combined heart-lung transplantation. Group 1 (n = 6) served as the control group in which animals were cooled with cardiopulmonary bypass and immediately had allotransplantations. In group 2 (n = 6), cardiopulmonary function was maintained in the autoperfusion circuit for 4 hours, followed by transplantation. In group 3 (n = 6), the organs were harvested after cooling by cardiopulmonary bypass, stored in cold (4 degrees C) saline solution for 4 hours, and then transplanted. Cardiopulmonary function was compared between the three groups for 6 hours after implantation. Cardiac function was determined by the ratio of the end-systolic pressure to end-systolic dimension. Pulmonary function was evaluated by the measurement of extravascular lung water, arterial oxygenation on 100% inspired oxygen static lung compliance, and histologic lung injury score. All measurements in groups 2 and 3 were similar to those of the control group at 6 hours after implantation. One may use either the hypothermic cardiopulmonary preservation method after cardiopulmonary bypass or the autoperfused working heart-lung preparation for distant organ procurement and expect adequate cardiopulmonary function after transplantation.

Successful extended cardiopulmonary preservation in the autoperfused working heart-lung preparation.

Myocardial and pulmonary preservation can be prolonged in the autoperfused working heart-lung (AWHL) preparation by metabolic substrate enhancement. However, uncontrolled pulmonary hypertension following denervation may result in extensive lung injury and occasional early failure of the preparation. To determine whether cardiopulmonary preservation could be reliably extended without development of pulmonary hypertension, six heart-lung blocks were harvested from calves, placed in a normothermic AWHL circuit, and studied. Continuous infusions of isoproterenol and dextrose/insulin were administered for the duration of the preparation. Thirteen heart-lung preparations received neither isoproterenol nor metabolic substrate and served as controls. Myocardial function was assessed by sonomicrometric techniques and pulmonary preservation was evaluated by extravascular lung water, arterial oxygenation on 100% inspired oxygen, static lung compliance, and pulmonary vascular resistance. Pulmonary hypertension developed in the control group and these animals did not survive beyond 7.5 hours. The addition of isoproterenol and metabolic substrate increased organ survival from 4.8 +/- 0.4 to 18.0 +/- 1.4 hours (p = 0.0001) and significantly reduced postexplant pulmonary vasoconstriction (p less than 0.05). Addition of isoproterenol and metabolic substrate to the AWHL model prolonged support of cardiorespiratory function and provided a reliable method for distant procurement in heart-lung transplantation.

Successful four-hour heart-lung preservation with core-cooling on cardiopulmonary bypass: a simplified model that assesses preservation.

This study was done to determine whether core-cooling could provide extended cardiopulmonary preservation and if reimplantation could be simulated and evaluated in the ex vivo autoperfused working heart-lung model. Twenty calves were divided into four groups and placed on cardiopulmonary bypass and rapidly cooled to 15 degrees C. Control heart and lungs were harvested after administration of cardioplegia through the aortic root and were subsequently resuscitated in the autoperfused working heart-lung circuit (group 1) or were orthotopically allotransplanted (group 2). Preserved heart and lungs were similarly excised but stored in a normal saline solution bath at 4 degrees C for 4 hours and then were resuscitated in the autoperfusion circuit (group 3) or were orthotopically allotransplanted (group 4). All groups received isoproterenol during explantation and reperfusion and were studied for 4 hours. Myocardial function was assessed by sonomicrometric techniques, and pulmonary preservation was evaluated by measurements of extravascular lung water, arterial oxygen tension on 100% inspired oxygen, and pulmonary vascular resistance. Cardiorespiratory function after 4-hour static preservation was similar in all four groups except that the arterial oxygen tension in group 1 was lower compared with group 3. Core-cooling on cardiopulmonary bypass without pulmonary artery flushing results in cold ischemic heart-lung preservation, comparable to other currently used modalities. In addition, reperfusion in the ex vivo autoperfusion circuit provides a simplified model to assess the adequacy of cardiopulmonary preservation techniques.

Thrombotic occlusion of a prosthetic heart valve: diagnosis and management.

Thromboembolic complications continue to be potential hazards in patients with prosthetic heart valves, and cerebral infarct and transient neurologic deficits as a result of embolism are the most common manifestations. Actual thrombotic obstruction of the valve occurs less frequently but is often fatal unless it is recognized and treated promptly. Tilting disk prostheses, such as the Björk-Shiley valve, seem to be associated with a higher incidence of thrombosis than other prosthetic designs. In this article, we review the important features of diagnosis and treatment of thrombotic occlusion of prosthetic valves.