Calcitonin gene-related peptide enhances the recovery of contractile function in stunned myocardium.

INTRODUCTION: Calcitonin gene-related peptide, a potent vasodilating inotropic agent, increases coronary artery perfusion when administered exogenously and reduces ischemic injury in nonmyocardial tissue. However, it is unclear whether this agent improves recovery of myocardial performance after reversible myocardial ischemia. METHODS: Nine dogs underwent complete occlusion of the left anterior descending coronary artery for 15 minutes and were monitored during 24 hours of reperfusion. Calcitonin gene-related peptide (0.07 microgram. kg(-1). min(-1)), nitroglycerin (65 microgram. kg(-1). min(-1)), or saline solution placebo was infused intravenously during initial reperfusion. Ischemia/reperfusion was repeated in concurrent 24-hour periods until all animals received infusions in random order. Micromanometry and sonomicrometry determined left ventricular pressure and myocardial segment length. Myocardial performance, based on the linear relationship between stroke work and end-diastolic segment length, was estimated with the preload recruitable work area. Results were analyzed as percent control and compared statistically with the use of repeated measures analysis of variance. RESULTS: Recovery of myocardial performance was augmented during reperfusion with calcitonin gene-related peptide infusion relative to placebo

Severe stenosis of the left main coronary artery with endarterectomy and graft: 33-year follow-up.

In 1964, a patient with symptomatic, severe left main coronary artery stenosis underwent operative treatment. Endarterectomy and pericardial patch grafting were performed successfully. The original operation is described, and the 33-year follow-up is provided.

Myocardial beta-adrenergic receptor function and high-energy phosphates in brain death--related cardiac dysfunction.

BACKGROUND: Cardiac failure remains an important problem after heart transplantation and may be associated with events that occur during brain death (BD) before transplantation. In this study, cardiac function is studied after BD, and biochemical evaluation of myocardial high-energy phosphates and the beta-adrenergic receptor system is presented. METHODS AND RESULTS: The hearts of 17 mongrel dogs (23 to 31 kg) were instrumented with flow probes, micromanometers, and ultrasonic dimension transducers to measure ventricular pressure and volume relationships. In a validated canine BD model, systolic right and left ventricular (RV/LV) function was analyzed by load-insensitive measurements during caval occlusion (preload-recruitable stroke work, PRSW). The beta-adrenergic receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and creatine phosphate (CP) were measured before and 6 to 7 hours after BD. Results are expressed as mean +/- SEM (*P < .05 versus baseline, paired two-tailed Student's t test). Myocardial function deteriorated significantly from baseline PRSW (RV, 22 +/- 1 erg x 10(3); LV, 75 +/- 4 erg x 10(3)) by 37 +/- 10% for the RV (P < .001) and 22 +/- 7% for the LV (P < .001). BAR density increased from 282 +/- 42 to 568 +/- 173 fmol/mg for the RV and from 291 +/- 64 to 353 +/- 56 fmol/mg for the LV. Isoproterenol-stimulated AC activity was also significantly enhanced after BD. ATP and CP, however, remained unchanged after BD compared with baseline values before BD. CONCLUSIONS: BD causes significant systolic biventricular dysfunction. The loss of ventricular function after BD was more prominent in the right ventricle and may contribute to early postoperative RV failure in the recipient. These injuries occurred despite BAR system upregulation after BD. Global myocardial ischemia is unlikely, since ATP and CP remained normal before and after BD.

Desensitization of myocardial beta-adrenergic receptors and deterioration of left ventricular function after brain death.

Brain death often results in a series of hemodynamic alterations that complicate the treatment of potential organ donors before transplantation. The deterioration of myocardial performance after brain death has been described; however, the pathophysiologic process of the myocardial dysfunction that occurs after brain death has not been elucidated. This study was designed to analyze the function of the myocardial beta-adrenergic receptor and the development of left ventricular dysfunction in a porcine model of experimental brain death. Analysis of the beta-receptor included determination of receptor density and adenylate cyclase activity after stimulation independently at the receptor protein, the G protein, and the adenylate cyclase moiety. Myocardial beta-receptor density did not change after the induction of brain death. A decrease in stimulated adenylate cyclase activity was observed within the first hour after brain death at the level of the beta-receptor, the G protein, and the adenylate cyclase moiety, which suggests the occurrence of rapid desensitization of beta-receptor function. Significant deterioration of myocardial performance also occurred within the first hour after brain death, represented by a decrease in preload-recruitable stroke work compared with the baseline value. The deterioration of myocardial performance after brain death correlates temporally with desensitization of the myocardial beta-receptor signal transduction system. The mechanism of impairment appears to be localized to the adenylate cyclase moiety itself.

Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths in women and men in the United States, with more than 157,000 estimated deaths in 1995. Surgical resection remains the mainstay of therapy in Stage I and II disease. However, local and distant recurrence account for the disappointing survival rates after resection. Appropriate selection of surgical procedures and effective use of adjuvant therapies will depend upon the elucidation of prognostic factors that predict for recurrence. METHODS: A detailed analysis was undertaken to evaluate surgical therapy and to define risk factors associated with recurrence and cancer death in 289 consecutive patients with NSCLC who were diagnosed, resected and followed at the Duke University Medical Center from January 1, 1980, until December 31, 1988. These patients had no evidence of metastases on head and chest/abdominal computed tomograms and radionuclide bone scans before resection. Resected specimens from these patients pathologic verification of Stage I disease. Follow-up was complete in all cases through 8/1/94 (median, 61 months). Variables analyzed included age, sex, smoking history, presenting signs and symptoms, operative procedure, histopathology, hospital course including complications, and the time and location of any recurrence or cancer death. RESULTS: The 30-day mortality rate was 5 of 289 (1.7%), with minor and major morbidity rates of 17% and 9%, respectively. Statistical comparison of lobectomy (193) wedge resection (75) and pneumonectomy (21) revealed significantly (P < 0.04) smaller tumors (T1), more comorbidity, and fewer complications for wedge resection patients. A trend (P < 0.09) toward an increased rate of local/regional recurrence and no difference in survival was also observed for wedge resection. One hundred five patients died of cancer (13-month median time to recurrence) for an actual 5-year survival of 63%. Significant univariate predictors of early recurrence and decreased survival (P < 0.01) were: male sex, the presence of symptoms, hemoptysis, chest pain, type of cough, tumor size in cm and by T-classification, visceral pleural invasion, high mitotic index, and vascular invasion. Significant (P < 0.05) multivariate independent variables for early recurrence and cancer death were the presence of symptoms, vascular invasion, pleural invasion, high mitotic index, and tumor size greater than 3 cm. CONCLUSION: Current surgical therapy for stage I NSCLC has an acceptable morbidity and mortality rate. The current data also stratify patients with Stage I NSCLC into high and low risk populations that can be used in future randomized trials of adjuvant therapy.

Load-independent analysis of a pulsatile right ventricular assist device.

BACKGROUND: Right ventricular assist devices are becoming increasingly used as both a bridge to heart transplantation and as a means of temporary support after cardiopulmonary bypass. There has also been a resurgence of interest in pulsatile devices fueled by anecdotal, clinical reports. However, a load-independent analysis of biventricular function after right ventricular assistance comparing a pulsatile versus a continuous-flow right ventricular assist device has not been performed, and we hypothesize that a pulsatile device is less detrimental to cardiac function than a conventional, nonpulsatile pump. METHODS: Sixteen dogs (20 to 25 kg) were instrumented through a median sternotomy for placement of left ventricular and right ventricular epicardial dimension transducers in the major, minor, and septal-free wall axes. Intracavitary micromanometers were placed in both ventricles as well. Baseline pressure-dimension data were collected, and the right atrium and pulmonary artery were cannulated. Right ventricular bypass with the use of a pneumatically driven pulsatile right ventricular assist device (SV = 60 ml; n = 7) or a conventional continuous-flow centrifugal right ventricular assist device (n = 9) was instituted for a 4-hour duration. Animals were then weaned from right ventricular support and decannulated. After bypass, biventricular function data were then collected. The load-insensitive stroke work-end diastolic volume relationship known as preload recruitable stroke work was derived and expressed as a fraction of baseline function along with conventional hemodynamic indexes, cardiac output, and pulmonary vascular resistance. RESULTS: Results of this analysis show no significant benefit to either right ventricular or left ventricular function (right ventricular preload recruitable stroke work index: 0.863 +/- 0.3 [pulsatile] versus 0.849 +/- 0.2 [continuous], left ventricular preload recruitable stroke work index: 0.880 +/- 0.4 [pulsatile] versus 0.821 +/- 0.3 [continuous] after pulsatile right ventricular support. Likewise, cardiac output (1.4 +/- 0.1 [pulsatile] versus 1.5 +/- 0.2 [continuous] L/min) and pulmonary vascular resistance (4.8 +/- 1.0 [pulsatile] versus 3.2 +/- 1.1 [continuous] Wood Units) were not significantly different in either study group. CONCLUSIONS: We conclude from these data that pneumatically driven pulsatile right ventricular assist devices provide no additional benefit to myocardial performance beyond that of conventional, nonpulsatile pumps. Further studies investigating a speculative benefit from pulsatile circulatory support are necessary to further define a potential role for these novel devices.

Preoperative determinants of postoperative costs associated with coronary artery bypass graft surgery.

BACKGROUND: Procedure-related costs are of increasing concern in selecting the appropriate procedure for the treatment of coronary artery disease (CAD). METHODS AND RESULTS: To determine what preoperative factors influence total postoperative hospital costs, data on 604 coronary artery bypass graft surgery (CABG) patients from 1990 to 1991 were analyzed. Professional fees were excluded. Hospital costs were computed by multiplying patient charges by the Medicare cost-to-charge ratio used in determining federal reimbursement. Median postoperative cost was $12,912 (range $7100 to $259,546). Data were analyzed with a semiparametric regression model. Patients dying in the hospital were censored at time of death. There were significant differences among surgeons in costs but no significant differences in operative mortality. Significant risk factors for increased cost after adjusting for surgeon were: older age (P < .0001), lower left ventricular ejection fraction (P < .0001), prior CABG (P < .0001), female sex (P < .0049), no prior percutaneous transluminal coronary angioplasty (P < .0091), increased degree of CAD (P < .0102), black race (P < .0190), and diabetes (P < .032). CONCLUSIONS: These results suggest that preoperative characteristics have important economic and medical implications. Surgeons should compare their management strategies on the basis of data analysis to determine the most effective practice with regard to mortality and cost.

Thoracic intrathymic thyroid.

OBJECTIVE: The authors introduce thoracic intrathymic thyroid as a clinical entity. SUMMARY BACKGROUND DATA: Although accessory aberrant thyroid has not been found in other tissues in the mediastinum, a thoracic intrathymic location has not been described previously. It is believed that mediastinal thyroid tissue represents accessory ectopic tissue from the median thyroid anlage. Moreover, the close association of the thymus and thyroid supports the theory that mediastinal ectopic thyroid tissue develops from abnormal descent of these structures during embryogenesis. METHODS: Benign thoracic intrathymic thyroid lesions are described in patients with mediastinal masses. CONCLUSION: Thoracic intrathymic thyroid is a distinct entity. Its occurrence is supported both clinically and embryologically.

Comparison of balloon valvuloplasty with operative treatment for mitral stenosis.

To determine the optimal role for percutaneous balloon mitral valvuloplasty or open mitral commissurotomy, the outcome of 164 consecutive patients undergoing either percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, or mitral valve replacement for mitral stenosis was reviewed. No preoperative differences existed between percutaneous balloon mitral valvuloplasty and open mitral commissurotomy in age, symptoms, or mitral valve characteristics. Symptoms improved similarly in all groups, and median hospital stays after procedures were 2, 9, and 10 days for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.005). Actuarial survivals at 36 months did not differ significantly (83% +/- 6%, 94% +/- 4%, and 90% +/- 4%). Actuarial freedoms from subsequent mitral valve procedures at 36 months were 66% +/- 7%, 87% +/- 6%, and 100% +/- 13% (p < 0.005), with the linearized rate of subsequent mitral valve procedures being 12% +/- 3%, 4% +/- 2%, and 1.2% +/- 0.8%/patient-year for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.01). Prior mitral commissurotomy increased the likelihood of subsequent mitral procedures after percutaneous balloon mitral valvuloplasty from 10% +/- 3% to 20% +/- 7%/patient-year.

Regional geometry and function during myocardial ischemia and recovery.

To define the effects of altered left ventricular (LV) geometry on regional myocardial function during ischemia and recovery, regional and global LV geometry and transmural pressure (P) were measured in seven conscious dogs with sonomicrometry and micromanometry. Data were obtained at steady state and during rapid vena caval occlusion (VCO) under control conditions, after 15 min of left anterior descending occlusion, and after 1, 4, and 24 hr of reperfusion. Regional midwall minor axis (MA) Lagrangian strain (epsilon) and stress (sigma) were calculated from measured MA segment length (L), MA midwall radius, and wall thickness. Unstressed regional geometry was quantified using L0, the value of L at P = 0 during maximal VCO. Conventional (SWL) and normalized (SW sigma epsilon) regional MA stroke work were calculated for each cardiac cycle as the area of P vs L and sigma vs epsilon relationships, respectively. Regional Frank-Starling mechanisms corrected for changes in unstressed LV geometry were quantified as the slope (M sigma epsilon) of the linear end diastolic epsilon vs SW sigma epsilon relationship for data obtained during VCO (mean r = 0.98). M sigma epsilon returned to baseline levels within 1 h of reperfusion (P = 0.314 vs control). In contrast, 15 min of ischemia increased L0 by 15.2 +/- 2.5% (P < 0.05), which remained increased 5.7 +/- 1.7% above control values after 1 hr of reperfusion (P < 0.05). Both steady-state SWL and SW sigma epsilon decreased with ischemia and slowly returned towards baseline, remaining 28.7 +/- 7.5% and 26.4 +/- 6.3% below control values after 1 hr of reperfusion (both P < 0.05). Therefore, late functional recovery from reversible ischemic injury is primarily correlated with reversal of changes in regional geometry, specifically the reversal of diastolic creep. As a result, adequate quantification of postischemic regional myocardial performance requires characterization of changes in regional geometry as well as indicators of Frank-Starling mechanisms.

Recovery of myocardial function after repetitive episodes of reversible ischemia.

The question of whether recovery of regional myocardial function after repetitive, reversible ischemia differs from recovery after a single episode of myocardial ischemia remains controversial. Therefore, eight conscious dogs were instrumented with ultrasonic dimension transducers and left ventricular micromanometers. Each animal underwent (in random sequence, 72 h apart) a single 15-min left anterior descending coronary arterial (LAD) occlusion and two 15-min LAD occlusions separated by 1 h of reperfusion. The preload recruitable work area (PRWA; the area beneath the regional stroke work vs. end-diastolic length relationship) quantified regional myocardial performance. Repetitive ischemia significantly delayed recovery of PRWA over the first 24 h (P < 0.05). Although postischemic myocardial creep resolved rapidly after single occlusion, double occlusion prevented recovery of creep during the first 4 h of reperfusion. The recovery time course of PRWA paralleled the resolution of myocardial creep, suggesting that creep contributed significantly to delayed functional recovery and that myocardial "stunning" after repetitive ischemia may result in part from interaction between postischemic diastolic properties and systolic dysfunction.

The efficiency of pulmonary blood transport following single lung transplantation.

Perioperative right ventricular (RV) dysfunction remains a significant problem following single lung transplantation (SLT), especially in patients with pulmonary hypertension. Total RV power (Wt), a determinant of RV function, is the sum of the mean component (Wm) which contributes to actual blood flow and the oscillatory component (Wo) which is the energy expended on arterial pulsation. Calculation of Wo is possible only through harmonic analysis of pulmonary arterial (PA) pressure and flow waveforms, and as much as 33% of RV power is attributed to it. The purpose of this study was to precisely quantify changes in RV power output using Fourier analysis of PA pressure and flow waveforms after SLT. Fourteen dogs (donors) were instrumented with a PA ultrasonic flow probe, PA and left atrial (LA) micromanometers, and LA epicardial pacing leads. Control (Pre-Tx) pressure-flow data were acquired during transient occlusion of the right PA at a heart rate of 140. The PA was cannulated, the lungs were flushed with 1 liter of modified Euro-Collins solution at 4 degrees C, and the left lung was harvested and transplanted to 14 recipient dogs in a standard manner. After 1 hr of reperfusion, PA (Post-Tx) pressure-flow data were acquired as above. All recipient animals survived SLT with a mean ischemic time of 183 +/- 3 min. Following SLT, both the mean, Wm, (69 +/- 9 to 161 +/- 23 mW) and oscillatory, Wo, (23 +/- 3 to 46 +/- 10 mW) components of RV power output increased significantly after SLT (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of local ventricular pacing on recovery from regional myocardial ischemia.

After surgical revascularization of ischemic myocardium, temporary ventricular pacing is often used, yet no data exist to indicate whether pacing ischemic versus nonischemic myocardium affects myocardial recovery. Therefore, chronically instrumented conscious dogs were studied with segment length transducers in the left anterior descending (LAD) distribution, left ventricular and pericardial micromanometers, pneumatic occluders on the LAD and venae cavae, and bipolar ventricular pacing wires, one pair in the LAD zone and one pair in the nonischemic (LCX) zone. Six dogs underwent a total of twelve 15-min LAD occlusions, each followed by 48 hr of reperfusion. Just after reperfusion, either the LAD or LCX zone was paced at 150 bpm for 45 min. LAD versus LCX pacing decreased regional stroke work (6 +/- 5 versus 19 +/- 5 kerg.cm-2) and produced contractile asynchrony. Myocardial contractile function was assessed using preload recruitable work area (PRWA), the area under the regional stroke work versus end-diastolic length relationship. Relative to LCX pacing, LAD pacing significantly delayed the recovery of PRWA after 4 hr of reperfusion (54 +/- 9 versus 83 +/- 9% control PRWA, P < 0.05). Perhaps by increased contractile asynchrony despite the decreased regional stroke work, ventricular pacing of ischemically injured myocardium delays functional recovery and should be avoided in clinical settings where the ventricular pacing site may be chosen.

The Duke University Medical Center.

The events leading up to the creation of Duke University, the Duke University School of Medicine, and Duke Hospital are reviewed. The efforts of many individuals during more than 80 years were rewarded by an endowment and then a bequest by James B. Duke that converted Trinity College into Duke University and made possible the origination of its Medical Center. The first neurosurgical operation at the new hospital was performed on July 24, 1930, the fourth day it was open.

Effects of triiodothyronine and vasopressin on cardiac function and myocardial blood flow after brain death.

Previous studies have documented decreases in serum-free triiodothyronine (T3) after brain death and improved hemodynamics with its replacement, suggesting its controversial, but promising, clinical utility for managing potential organ donors. Vasopressin is also commonly used clinically as a pressor agent after brain death. A load-independent analysis of cardiac function and an assessment of myocardial blood flow (MBF) with these agents have not been reported, however. Eighteen pigs were instrumented with left ventricular epicardial dimension transducers and a left ventricular micromanometer. MBF was assessed by standard microsphere techniques. Baseline left ventricular pressure-dimension data were collected, and brain death was induced by ligating the innominate and left subclavian arteries. Left ventricular function data were collected every 30 minutes after brain death to 6 hours or until the animal died. Microsphere injections were performed before brain death and hourly thereafter to 4 hours. At 90 minutes after brain death, animals were assigned to a vasopressin (2 units/hr, intravenously, n = 6), T3 (0.05 microgram/kg/hr, intravenously, n = 6), or control (n = 6) treatment group. Preload recruitable stroke work (PRSW), a load-independent index of left ventricular function, was derived from the pressure-dimension data. MBF was calculated by conventional methods. At 4 hours after brain death, PRSW and MBF decreased significantly in the control, vasopressin, and T3 groups relative to the baseline, pre-brain dead state (PRSW: -36% +/- 12%, -48 +/- 7%, -52% +/- 5%; MBF: -27% +/- 15%, -38% +/- 5%, -78% +/- 2%, respectively). Neither vasopressin nor T3, however, showed any advantage over the control group in terms of preserving left ventricular function or prolonging survival. Furthermore, these data show a marked decrease in MBF in the T3 group (p < 0.01 versus control and vasopressin groups) without a significant change in cardiac function. Analysis of endocardial to epicardial flow ratios disclosed no significant differences between groups at any time. In summary, animals treated with T3 had a greater decline in MBF than the control group at 4 hours, without any benefit to cardiac function. Further studies examining the mechanism responsible for the deterioration of MBF and cardiac dysfunction will be necessary to optimally manage the brain dead patient before organ harvest, especially regarding the precise role of T3.

Performance status and outcome after coronary artery bypass grafting in persons aged 80 to 93 years.

Although coronary artery bypass grafting (CABG) effectively eliminates or diminishes symptoms of myocardial ischemia, the overall performance status and functional outcome in elderly patients undergoing CABG is poorly documented. Therefore, 86 consecutive patients aged 80 to 93 years undergoing isolated CABG were reviewed. Preoperative, intraoperative, and postoperative characteristics and pre- and postoperative performance status (Karnofsky score) were examined. Forty patients (47%) were women, and most patients had highly symptomatic coronary artery disease with class III or IV angina in 94% and unstable angina in 90%. Significant co-morbid disease was present in 49% of patients, and cardiac catheterization revealed left main or 3-vessel disease in 74% of patients. The rate of significant in-hospital complications was 29%, with infection in 14%, stroke in 9%, and respiratory failure in 8% being most frequent. Median performance status (Karnofsky score) improved from 20 to 70% (p = 0.0001) with 89% of hospital survivors being discharged home. Factors associated with failure to achieve a successful functional outcome at discharge were presence of 1 or more preoperative co-morbid conditions (p = 0.048), preoperative myocardial infarction within 7 days of operation (p less than 0.01), and postoperative low cardiac output (p less than 0.01). Survival at 30 days, 6 months, and 3 years were 90, 78, and 64%, respectively. These data demonstrate that CABG can be offered to selected elderly patients with acceptable morbidity and mortality, marked improvement in performance status, and an acceptable quality of life.