Discrete-choice preference comparison between patients and doctors for the surgical management of oesophagogastric cancer.

BACKGROUND: Establishing preferences for surgery is paramount to preoperative patient counselling. This study aimed to prioritize and compare preferences of patients and doctors towards surgery for oesophagogastric cancer, to aid the counselling process. METHODS: A discrete-choice questionnaire containing hypothetical scenarios was designed to test patient preferences for six treatment attributes: mortality, morbidity, quality of life (QoL), cure rate, hospital type and surgeon's reputation. The survey was mailed to all patients who underwent oesophagogastric cancer resection from 2008 to 2009 at two teaching hospital sites. All doctors at these sites with previous experience in counselling patients for cancer surgery were also identified and presented with the survey. Results were analysed using a random-effects probit regression model. Spearman correlation was used to compare participants' implicit choices from the discrete-choice scenarios (their true preferences) with their explicit choices from the direct ranking of preferences (their perceived preferences). RESULTS: Eighty-one patients and 90 doctors completed the survey. Some 15 per cent of patients and 31 per cent of doctors based their choices solely on QoL. In order of importance, patients based their implicit responses on QoL (ß = 1.19), cure rate (ß = 0.82), morbidity (ß = - 0.70), surgeon's reputation (ß = 0.60), mortality (ß = - 0.57) and hospital type (ß = 0.26). Doctors similarly indicated QoL (ß = 1.14) and hospital type (ß = 0.31) as highest and lowest preferences respectively, but placed far greater emphasis on mortality (ß = - 0.80) than morbidity (ß = - 0.35). Implicit and explicit preferences correlated only for morbidity and surgeon's reputation in the patient cohort. CONCLUSION: Clinicians may better meet patients' expectations and facilitate informed decision-making if QoL, cure rate and morbidity are emphasized foremost. A similar study employing preoperative patients is warranted for further clarification of preferences.

The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype.

Stem cells from bone marrow, skeletal muscle and possibly other tissues can be identified by the 'side-population' (SP) phenotype. Although it has been assumed that expression of ABC transporters is responsible for this phenotype, the specific molecules involved have not been defined. Here we show that expression of the Bcrp1 (also known as Abcg2 murine/ABCG2 human) gene is a conserved feature of stem cells from a wide variety of sources. Bcrp1 mRNA was expressed at high levels in primitive murine hematopoietic stem cells, and was sharply downregulated with differentiation. Enforced expression of the ABCG2 cDNA directly conferred the SP phenotype to bone-marrow cells and caused a reduction in maturing progeny both in vitro and in transplantation-based assays. These results show that expression of the Bcrp1/ABCG2 gene is an important determinant of the SP phenotype, and that it might serve as a marker for stem cells from various sources.

In vitro thyroid hormone rapidly modulates protein phosphorylation in cerebrocortical synaptosomes from adult rat brain.

Thyroid hormones induced rapid changes in phosphorylation in a membrane-containing lysate of synaptosomes purified from adult rat cerebral cortex. The in vitro addition of 3,5,3'-L-triiodothyronine or L-thyroxine strongly influenced incorporation of label from [gamma-32P]-ATP into proteins in a cerebrocortical synaptosomal lysate. Incubation with 3,5,3'-L-triiodothyronine or L-thyroxine had strong biphasic dose-dependent effects on the phosphorylation of 38+/-1, 53+/-1, 62+/-1, and 113+/-1 kDa proteins (which we termed alpha, beta, gamma, and delta, respectively) and several others. Although we observed differing levels of phosphorylation among the four proteins, doses of 3,5,3'-L-triiodothyronine or L-thyroxine ranging from 1 to 30 nM caused significant dose-dependent stimulation of the phosphorylation of all of them, an effect which occurred within three minutes. In each case, the enhancement of phosphorylation diminished with higher concentrations (100 nM-1 microM) of 3,5,3'-L-triiodothyronine. In contrast, incubations with similar doses of 3,3',5'-L-triiodothyronine (reverse L-triiodothyronine) were without significant effect, indicating a specificity for 3,5,3'-L-triiodothyronine and L-thyroxine. Western blots of synaptosomal lysates incubated with 3,5,3'-L-triiodothyronine (1 nM-1 microM) demonstrated phosphorylation at the serine residues of a 112 kDa protein (matching delta) and phosphorylation at tyrosyl residues of a distinct 95 kDa protein. These data support the contention that thyroid hormones have a variety of rapid nongenomic pathways for regulation of protein phosphorylation in mature mammalian brain.

Painless exercise ST deviation on the treadmill: long-term prognosis.

To evaluate the clinical correlates and long-term prognostic significance of silent ischemia during exercise, 1,698 consecutive symptomatic patients with coronary artery disease who had both treadmill testing and cardiac catheterization were studied. These patients were classified into three groups: Group 1 = patients with no exercise ST deviation (n = 856), Group 2 = patients with painless exercise ST deviation (n = 242) and Group 3 = patients with both angina and ST segment deviation during exercise (n = 600). Patients with exercise angina had a history of a longer and more aggressive anginal course (with a greater frequency of angina, with nocturnal episodes and/or progressive symptom pattern) and more severe coronary artery disease (almost two-thirds had three vessel disease). The 5 year survival rate among the patients with painless ST deviation was similar to that of patients without ST deviation (86% and 88%, respectively) and was significantly better than that of patients with both symptoms and ST deviation (5 year survival rate 73% in patients with exercise-limiting angina). Similar trends were obtained in subgroups defined by the amount of coronary artery disease present. In the total study group of 1,698 patients, silent ischemia on the treadmill was not a benign finding (average annual mortality rate 2.8%) but, compared with symptomatic ischemia, did indicate a subgroup of patients with coronary artery disease who had a less aggressive anginal course, less coronary artery disease and a better prognosis. Thus, silent ischemia during exercise testing in patients with symptomatic coronary artery disease represents an intermediate risk response in the spectrum of exercise-induced ischemia.

A new information system for medical practice.

A data bank containing our clinical experience with more than 3,000 patients with suspected and documented ischemic heart disease is being used to expand our ability to care for patients. This report describes how the experience is documented, stored, and retrieved so that it can be used in patient management. Data acquisition is integrated with patient care by means of forms that are part of the patient record. Follow-up information is obtained at six months, one year, and yearly thereafter. All data are stored in a computer information system that allows the doctor to recall the experience of patients like his new patient. Prognostic information is available on each new patient both on-line and in the form of a printed laboratory report. The data bank represents an initial chapter of a computer textbook of medicine.

Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms.

BACKGROUND: Previous studies have demonstrated that myocardial ischemia can be elicited by mental stress in the laboratory and during daily life and that ischemia induced by mental stress is associated with an increased risk for future cardiac events in patients with coronary artery disease. OBJECTIVES: To examine the extent to which ischemia induced by mental stress can be modified by exercise stress management, and to evaluate the impact of these interventions on clinical outcomes. METHODS: One hundred seven patients with coronary artery disease and ischemia documented during mental stress testing or ambulatory electrocardiographic monitoring were randomly assigned to a 4-month program of exercise or stress management training. Patients living at a distance from the facility formed a nonrandom, usual care comparison group. Myocardial ischemia was reassessed following treatment, and patients were contacted annually for as long as 5 years to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. RESULTS: Twenty-two patients (21%) experienced at least 1 cardiac event during a mean (+/- SD) follow-up period of 38 +/- 17 months. Stress management was associated with a relative risk of 0.26 compared with controls. The relative risk for the exercise group also was lower than that of controls, but the effect did not reach statistical significance. Stress management also was associated with reduced ischemia induced by mental stress and ambulatory ischemia. CONCLUSION: These data suggest that behavioral interventions offer additional benefit over and above usual medical care in cardiac patients with evidence of myocardial ischemia.

Predicting outcome in coronary disease. Statistical models versus expert clinicians.

To study the accuracy with which long-term prognosis can be predicted in patients with coronary artery disease, prognostic predictions from a data-based multivariable statistical model were compared with predictions from senior clinical cardiologists. Test samples of 100 patients each were selected from a large series of medically treated patients with significant coronary disease. Using detailed case summaries, five senior cardiologists each predicted one- and three-year survival and infarct-free survival probabilities for 100 patients. Fifty patients appeared in multiple samples for assessing interphysician variability. Cox regression models, developed using patients not in the test samples, predicted corresponding outcome probabilities for each test patient. Overall, model predictions correlated better with actual patient outcomes than did the doctors' predictions. For three-year survival, rank correlations were 0.61 (model) and 0.49 (doctors). For three-year infarct-free survival predictions, correlations with outcome were 0.48 (model) and 0.29 (doctors). Comparisons by individual doctor revealed Cox model three-year survival predictions were better than those of four of five doctors (model predictions added significant [p less than 0.05] prognostic information to the doctor's predictions, whereas the converse was not true). For infarct-free survival, the Cox model was superior to all five doctors. Where predictions were made by multiple doctors, the interphysician variability was substantial. In coronary artery disease, statistical models developed from carefully collected data can provide prognostic predictions that are more accurate than predictions of experienced clinicians made from detailed case summaries.

Non-steroidal antiandrogens. Design of novel compounds based on an infrared study of the dominant conformation and hydrogen-bonding properties of a series of anilide antiandrogens.

Antiandrogenic activity is observed in anilides containing a tertiary hydroxyl group, and these compounds are used to define a pharmacophore in terms of their physicochemical properties. Infrared spectroscopy shows that these anilides exist in a single conformation, which exerts a powerful influence on the hydrogen-bond donor ability of the hydroxyl group in a model system. Arguments are presented which suggest that hydrogen-bonding ability is an important contributor to biological activity. Compounds were synthesized that reproduced these properties in series not containing an amide bond. Such compounds were found to exhibit good antiandrogen activity. We suggest that quantitative information on hydrogen bonding might also be useful in other systems.

Patient-initiated rapid atrial pacing to manage supraventricular tachycardia.

Patient-controlled rapid atrial pacing was used to manage 12 cases of recurrent supraventricular tachycardia refractory to drug therapy. The pacing system consists of an implanted receiver-lead system and an external patient-activated transmitter. In each case, brief periods (5 to 20 seconds) of rapid atrial pacing were effective in terminating the supraventricular tachycardia and resulted in a return to normal sinus rhythm. In three patients, occasional transient episodes of atrial flutter or atrial fibrillation preceded a spontaneous return to normal sinus rhythm. The pacing system was removed in one patient 13 months postoperatively because of persistent pericarditis; one patient died of an unrelated cerebral hemorrhage 13 months postoperatively. Successful management of supraventricular tachycardia has been maintained in the 10 remaining patients for 15 to 36 months (average 26.4). In more than 6,000 patient applications of rapid atrial pacing, there has been only one failure to convert the tachycardia. Successful application of permanent rapid atrial pacing requires (1) prescreening of patients with temporary external rapid atrial pacing to verify susceptibility to conversion of supraventricular tachycardia and absence of anomalous conduction pathways that may permit conduction of rapid pacing rates to the ventricles, and (2) assessment of the patient's ability to use the transmitter properly.

Characteristics of a contemporary population with angina pectoris. TIDES Investigators.

To characterize a contemporary, nonhospitalized population with angina pectoris, data were obtained from a geographically diverse cohort of 5,125 outpatients with chronic stable angina cared for by 1,266 primary care physicians between September and November of 1990. Diagnosis was based on history supported by evidence for coronary artery disease (coronary angiography, old myocardial infarction, or an abnormal stress test, either alone or in combination). The mean age of the patients was 69 years and 53% were women. Seventy percent had > 1 associated illness and 64% took > 1 cardiovascular drug. Median angina frequency was approximately 2 episodes/week and increased angina frequency (p < 0.0001) was associated with decreased overall feeling of well-being. Although effort angina was present in 90% of patients, 47% also had rest angina and 35% had mental stress-evoked angina. Female gender (relative risk [RR] 1.09; 95% confidence interval [CI] 1.02 to 1.16), concomitant illness (RR 1.17; CI 1.09 to 1.25), and pharmacotherapy (RR 1.14; CI 1.07 to 1.22) were associated with excess risk for rest angina. Younger age (RR 1.30; CI 1.20 to 1.41), female gender (RR 1.16; CI 1.07 to 1.26), concomitant illness (RR 1.13; CI 1.03 to 1.24), and pharmacotherapy (RR 1.28; CI 1.15 to 1.93) were associated with excess risk for mental stress angina. These data suggest that contemporary outpatients with angina are frequently women and elderly patients with high rates of associated illness, rest, and mental stress-related angina.

Relative importance of electrode placement over number of channels in transient myocardial ischemia detection by Holter monitoring.

To compare the efficacy of 3-channel ambulatory electrocardiographic monitoring (Holter monitoring) with 2-channel Holter monitoring in the detection of transient myocardial ischemia (TMI), channels CM2, CM5, and modified II were studied. Sixty patients with documented coronary artery disease underwent 48-hour Holter monitoring during their normal daily life, followed by exercise stress testing in the laboratory monitored by means of radionuclide ventriculography and standard 12-lead electrocardiography. Analysis revealed that 3-channel Holter monitoring identified 24 patients with a total of 205 TMI episodes and a total ischemic burden of 371.00 mV-min. By itself, CM2 would have detected only 3 patients (13% of the TMI population), 6 TMI episodes (3% of the total TMI episodes), and a 2.4 mV-min ischemic burden (0.7% of the total ischemic burden). Modified II alone would have identified 17 patients (71% of the TMI population), 160 TMI episodes (78% of the total TMI episodes), and 307.24 mV-min of the ischemic burden (82% of the total ischemic burden). The combination of CM5/modified II identified 23 patients (96% of the TMI population), 201 TMI episodes (98% of the total TMI episodes), and 370.44 mV-min of the ischemic burden (98% of the total ischemic burden). These findings suggest that the electrode placement is more important than the absolute number of channels in the detection of TMI by Holter monitoring.

Accelerated recovery of postischemic stunned myocardium after induced expression of myocardial heat-shock protein (HSP70).

In vitro studies suggest that interventions targeted at myocardial gene regulation of endogenous cytoprotective elements, such as heat-shock protein, may attenuate myocardial ischemic injury. We tested the hypothesis that heat shock-induced expression of myocardial heat-shock protein before ischemia accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Sixteen dogs underwent partial femoral arteriovenous bypass and core temperature was raised to 42 degrees C for 15 minutes in eight dogs (heat-shocked) and maintained at 37 degrees C in eight dogs (nonheat-shocked). After 24 hours dogs were studied to measure myocardial segment length in the circumflex artery region with ultrasonic dimension transducers, left ventricular pressure with a micromanometer, and circumflex coronary flow with an ultrasonic probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals during reperfusion after a 15-minute circumflex artery occlusion followed by 3 hours of reperfusion. Baseline and peak reperfusion hyperemic circumflex flows were 37 +/- 9 ml/min and 154 +/- 33 ml/min, respectively, in heat-shocked dogs (p < 0.001) and 46 +/- 24 ml/min and 171 +/- 57 ml/min, respectively, in nonheat-shocked dogs (p < 0.001), with no differences between groups (p = not significant) at any time during reperfusion. Heart rate and left ventricular peak pressure, end-diastolic pressure, and first derivative of left ventricular pressure were similar (all p = not significant) in heat-shocked and nonheat-shocked dogs during ischemia and reperfusion. Before ischemia, preload recruitable stroke work relationship did not differ (p = not significant) in heat-shocked and nonheat-shocked dogs. Ischemia reduced preload recruitable stroke work relationship to 32% +/- 8% control (p < 0.001) in heat-shocked dogs and to 19% +/- 15% control in nonheat-shocked dogs (p < 0.001) at 15 minutes of reperfusion, indicating a similar (p = not significant) initial degree of injury. During 3 hours of reperfusion, preload recruitable stroke work relationship returned to 80% +/- 38% control in heat-shocked dogs but to only 33% +/- 13% control in nonheat-shocked dogs (p < 0.0001). Myocardial expression of heat-shock protein, quantified by optical densitometry of Western blots using an antibody specific for HSP70, was greater in heat-shocked than in nonheat-shocked dogs (108 +/- 27 versus 71 +/- 14 densitometry units, p < 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Differential ventricular ischemic injury: an experimental model of right ventricular failure with a variable degree of left ventricular dysfunction.

The hemodynamic manifestations of right ventricular dysfunction after ischemic injury depend not only on the severity of injury but also on the degree of coexistent left ventricular dysfunction. A better understanding of right ventricular failure and of optimal therapies has been hindered in part by lack of suitable experimental models of selective and differential ventricular injury. Therefore, we developed a technique of differential ventricular myocardial protection during a period of global cardiac ischemia and examined the effect of such an injury on intrinsic right and left ventricular myocardial function, metabolism, and regional blood flow. Twenty-six dogs were subjected to 30 minutes of ischemia while being supported by cardiopulmonary bypass. During ischemia, right and left ventricular myocardial temperatures were independently varied by selective ventricular endomyocardial thermal regulation. Nine dogs underwent right and left ventricular normothermic ischemia, eight underwent right and left ventricular hypothermic ischemia, and nine underwent right ventricular normothermic and left ventricular hypothermic ischemia. In both ventricles, normothermic ischemia resulted in greater depression of ventricular ability to generate stroke work as a function of end-diastolic dimension (p less than 0.05), greater depletion of myocardial adenine nucleotide content (p less than 0.05), and greater subendocardial reperfusion hyperemia (p less than 0.05). Myocardial temperature of the contralateral ventricle during ischemia had no effect (p = not significant) on intrinsic ventricular functional, metabolic, or regional blood flow response to injury. For a given degree of right ventricular injury assessed by these parameters, the degree of left ventricular injury could be independently varied by as much as 50%. This is a particularly suitable model for the investigation of acute right ventricular failure.

The effects of left heart assist on right ventricular muscle mechanics and ventricular coupling in the injured heart.

So that we could better characterize the effects of left heart assist on right ventricular myocardial muscle mechanics and ventricular mechanical coupling in the injured heart, nine dogs underwent 30 minutes of global cardiac ischemia supported by cardiopulmonary bypass followed by randomly varied levels of left heart assist at 0, 1.0, and 2.0 L/min (0, 37 +/- 4, and 74 +/- 7 ml/kg per minute). A centrifugal pump with left ventricle-to-aorta bypass was used with the intent to cause left ventricular volume unloading but without complete left ventricular pressure unloading. Right ventricular regional free wall and septal-free wall dimensions were measured by a sonomicrometer and right ventricular pressure by a micromanometer. Pressure and dimension data were acquired over a range of preloads produced by transient vena caval occlusion and at steady state at an initial control point and after ischemia at each level of left heart assist. Right ventricular regional early diastolic function was assessed by percent segmental relaxation during the first third of diastole, end-diastolic compliance by the end-diastolic pressure-dimension relationship, systolic contractile performance by the slope (Mw) and dimension axis intercept (Lw) of the linear preload recruitable stroke work relationship, and right ventricular isovolumic relaxation by the pressure decay time constant. Ischemia reduced Mw of both the free wall (38.3 +/- 16.1 to 16.4 +/- 4.2 erg.cm-3 x 10(3), p < 0.01) and septal free wall (30.2 +/- 12.7 to 13.4 +/- 4.9 erg.cm-3 x 10(3), p < 0.01) and shifted Lw rightward (1.3 +/- 0.3 to 1.4 +/- 0.3 mm, p < 0.01, and 2.8 +/- 0.8 to 3.0 +/- 0.9 mm, p < 0.01), which confirmed myocardial ischemic injury. There were no effects of left heart assist on free wall or septal-free wall systolic contractile performance assessed by Mw and Lw or on early diastolic relaxation assessed by percent segmental relaxation during the first third of diastole in either right ventricular region (all p = not significant). There were also no observed characteristic alterations of free wall or septal-free wall end-diastolic pressure-dimension relationships with left heart assist. The pressure decay time constant decreased with increasing levels of left heart assist (51 +/- 14, 49 +/- 16, and 43 +/- 11 msec, p < 0.05), which indicated an improvement in right ventricular isovolumic relaxation attributable to left heart assist. These data demonstrate that mechanical ventricular interactive effects during left heart assist are beneficial, but limited to isovolumic relaxation in the injured heart.(ABSTRACT TRUNCATED AT 400 WORDS)

Dynamic right ventricular dimension. Relation to chamber volume during the cardiac cycle.

Whereas the left ventricle has been analyzed extensively, the apparent complexity of right ventricular geometry and contraction has hindered analysis of right ventricular performance by an assessment of instantaneous ventricular dimensions and volume during the cardiac cycle. To address this issue, we examined the temporal and quantitative relation between dynamic right ventricular free wall dimension, rate of pressure development (dP/dt), and pulmonary artery flow in the open-chest dog. Right ventricular free wall chord dimension was recorded by sonomicrometry, right ventricular pressure by micromanometer-tipped catheter, and pulmonary flow by electromagnetic probe. The point of peak positive right ventricular dP/dt closely correlated with the end of isovolumic contraction and initiation of ejection, occurring within 10 +/- 25 msec of initiation of pulmonary flow. Right ventricular dimension at peak positive dP/dt differed from dimension at initiation of chord shortening by less than 3%. Peak negative dP/dt correlated with end ejection, occurring within 10 +/- 25 msec of cessation of pulmonary flow. Right ventricular dimension at peak negative dP/dt differed from minimal dimension by less than 1%. In all dogs, volume ejected from the right ventricular chamber during each cardiac cycle was directly related to the change in right ventricular dimension during the same period (mean r = 0.969). This relationship between right ventricular stroke volume and dimensional change remained linear and was not changed (p = NS) by increases in right or left ventricular afterload induced by constricting the pulmonary artery or descending aorta. Right ventricular stroke work, calculated as the integral of instantaneous right ventricular pressure and dimension, correlated well (mean r = 0.980) with directly measured global right ventricular stroke work over a wide range; it was also not changed (p = NS) by changes in afterload. Accurate assessments of beat-to-beat right ventricular chamber volume and stroke work can be obtained by analysis of dynamic right ventricular chord dimension.

Outcome of mitral valve repair in patients with preoperative atrial fibrillation. Should the maze procedure be combined with mitral valvuloplasty?

To examine late outcome of mitral valve repair in patients with preoperative atrial fibrillation, we reviewed the cases of 323 consecutive patients who underwent mitral valvuloplasty for mitral regurgitation from 1980 to 1991; average age of 215 men and 108 women was 64 years (range 14 to 88 years), and 224 patients (70%) were in New York Heart Association class III or IV before operation. The main indications for operation were severe mitral regurgitation (76%), coronary artery disease with associated mitral regurgitation (15%), and aortic valve disease (6%). At the time of mitral valve repair, coronary artery bypass grafting was done in 35% of patients, aortic valve replacement was done in 7%, and multiple other procedures were done in 10%. For all patients, the 30-day mortality rate was 2.5% (70% confidence limits 1.6% to 3.4%) and survivorships at 3 and 5 years were 81% and 76%, respectively. Before operation, 216 patients were in sinus rhythm and 97 patients had atrial fibrillation; in the latter group, 11 had recent onset of atrial fibrillation within 3 months preceding mitral valve repair. Comparing patients with preoperative atrial fibrillation to those with sinus rhythm, we found no significant difference in operative mortality (3% versus 1.9%) or 5-year survivorship (74.3% +/- 6.3% versus 76.9% +/- 4.0%). At late follow-up, atrial fibrillation was present in 5% of patients with preoperative sinus rhythm, 80% of patients with preoperative chronic atrial fibrillation, and 0% of patients with preoperative recent onset atrial fibrillation (p < 0.01). The left atrial size by echocardiography was larger in patients with preoperative atrial fibrillation compared with that in those with sinus rhythm (59 +/- 1.4 mm versus 50.9 +/- 0.7 mm; p < 0.05). There was, however, only a weak correlation between preoperative left atrial size and late atrial fibrillation. Further, age, gender, and associated coronary artery disease did not correlate with presence of atrial fibrillation at late follow-up. Prevalence of late thromboembolic events was similar in patients with preoperative sinus rhythm compared with that in those with atrial fibrillation. These data suggest that mitral valve repair should be done before or soon after the onset of atrial fibrillation to maximize the chance of postoperative sinus rhythm and avoid long-term anticoagulation with warfarin. However, the early and late results of mitral valve repair in patients with chronic atrial fibrillation are good, and concomitant operation for supraventricular arrhythmia must have negligible morbidity and no adverse effect on operative mortality.

Bypass conduit vessel wall biology substantially influences downstream myocardial contractile response to injury from ischemia and reperfusion.

Coronary vascular intraluminal release of endogenous endothelium-derived substances, such as prostacyclin, may affect downstream cardiac myocyte contractile function. With a "chronic" canine model of endothelialized and deendothelialized internal thoracic artery coronary grafts, we tested the hypothesis that higher basal release of endothelium-derived prostacyclin in internal thoracic artery bypass conduit effluent accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Eleven dogs underwent left internal thoracic artery-left circumflex artery bypass, and the proximal circumflex artery was then ligated. Internal thoracic artery conduit endothelium was denuded by balloon catheter in five dogs before grafting and left intact in six dogs. After 7 days, awake dogs were studied to measure myocardial segment length in the circumflex region with ultrasonic dimension transducers, left ventricular pressure with micromanometers, and circumflex artery flow with an ultrasonic flow probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals after a 15-minute circumflex graft occlusion followed by 3 hours of reperfusion. Heart rate, left ventricular peak pressure, left ventricular end-diastolic pressure, left ventricular peak first derivative of pressure (dP/dt), and circumflex flow were similar (all p not significant) in endothelialized and nonendothelialized dogs during ischemia and reperfusion. Ischemia reduced the preload recruitable stroke work relationship to 44% +/- 35% of control values (p < 0.01) in endothelialized dogs and to 47% +/- 18% of control values in nonendothelialized dogs (p < 0.01) at 15 minutes of reperfusion, indicating a similar (p not significant) initial degree of injury. During 3 hours of reperfusion, the preload recruitable stroke work relationship returned to 51% +/- 17% of control values in endothelialized dogs but to only 35% +/- 20% of control values in nonendothelialized dogs (p < 0.02). Basal intraluminal release of endogenous prostanoids in excised internal thoracic artery conduits was subsequently quantified by ex vivo bioassay of vasoactive properties of conduit effluent on normal coronary artery smooth muscle. Endothelialized conduits induced greater smooth muscle relaxation than did nonendothelialized conduits (67% vs 23%), and this increased relaxation by endothelialized conduits was eliminated by indomethacin, a blocker of prostanoid synthesis. These data indicate that coronary bypass conduit endothelium-derived substances, such as prostacyclin, significantly influence downstream myocardial contractile response to ischemia and reperfusion, independent of alterations in coronary flow in the intact circulation.

Aortic valve replacement in patients aged eighty years and older: early and long-term results.

UNLABELLED: We have studied 322 patients, 80 years of age or older, who underwent aortic valve replacement between June 1971 and December 1992. Two hundred six patients (64%) have had surgery since the end of 1985. Their mean age was 82.7 years (range 80 to 92 years). One hundred seventy-one (53%) were male and most (86%) were in New York Heart Association class III-IV. Fifty-seven patients (18%) required admission to the coronary care unit before the operation. One hundred seventy-nine patients (56%) underwent an urgent or emergency operation. Known cerebrovascular disease was present in 77 (24% of patients), aortic stenosis in 79%, aortic incompetence in 9%, and combined stenosis and incompetence in 12%. Associated procedures included bypass grafting in 139 (43%), mitral valve replacement/repair in 20 (6%), tricuspid valve repair in 6 (2%), and aortic annular enlargement in 38 (12%). Thirty patients (9.3%) were undergoing reoperation. Hospital mortality was 44 of 322 (13.7%). The median hospital stay was 11 days. On univariate analysis, significant predictors of hospital mortality were female sex, preoperative rest pain, New York Heart Association class III-IV, admission to the coronary care unit, heart failure, mitral valve disease, emergency/urgent operation, chronic obstructive pulmonary disease, bypass grafting, valve size, peripheral vascular disease, and ejection fraction less than 0.35. On multivariate analysis the most important independent predictors of operative mortality were female gender (p = 0.0001), renal impairment (p = 0.001), bypass grafting (p = 0.005), ejection fraction less than 0.35 (p = 0.01), and chronic obstructive pulmonary disease (p = 0.028). Age and year of operation did not influence mortality. Five-year survivals for all patients and for operative survivors were 60.2% +/- 3.2% and 70.3% +/- 3.4%, respectively. On univariate analysis, factors that adversely affected long-term survival were coronary bypass grafting (p = 0.007), more than two comorbidities (p = 0.02), male gender (p = 0.04), and ejection fraction less than 0.35 (p = 0.04). On multivariate analysis, no factor was consistently significant for long-term survival. At most recent clinical follow-up 85% were angina free and 82% were in class I-II. At least 92% of patients, both at 1 year and at most recent clinical follow-up, believed they had significantly benefited from the operation: CONCLUSION: Risk factors for aortic valve replacement in octogenarians include female gender, unstable symptoms, poor ejection fraction, renal impairment, and bypass grafting. However, despite a hospital mortality higher than that reported for younger patients, the outlook for operative survivors is excellent, with good relief of symptoms and an expected survival normal for this particular age group. If possible, aortic valve replacement should be done before development of unstable symptoms.

Outcome of valve repair and the Cox maze procedure for mitral regurgitation and associated atrial fibrillation.

OBJECTIVE: The objective was to determine whether the Cox maze procedure provides adjunctive benefit in patients with atrial fibrillation undergoing mitral valve repair. METHODS: We compared the outcome of 39 patients who had the Cox maze procedure plus mitral valve repair between January 1993 and December 1996 (maze group) with that of 58 patients with preoperative atrial fibrillation who had mitral valve repair during the same interval by the same surgeons (control group). Patients in the 2 cohorts were similar for age, gender, preoperative New York Heart Association class III or IV, and duration of preoperative atrial fibrillation. The control group had a higher incidence of previous heart surgery and coronary artery disease. RESULTS: No operative deaths occurred, and 1 patient in each group required pacemaker implantation after the operation. Duration of cardiopulmonary bypass (122 +/- 40 minutes vs 58 +/- 27 minutes, P <.0001) and hospitalization (12.6 +/- 6.4 vs 9.3 +/- 3.4 days, P <.0025) were prolonged in patients having the Cox maze procedure. Overall, 2-year survival was similar (92% +/- 5% for maze patients and 96% +/- 3% for controls). Freedom from atrial fibrillation in the maze group was 74% +/- 8% 2 years after the operation compared with 27% +/- 7% for the control group (P <.0001). Freedom from stroke or anticoagulant-associated bleeding in the maze group was 100% 2 years after the operation compared with 90% +/- 8% in the control group (P =.04). At most recent follow-up, 82% of maze patients were in normal sinus rhythm (53% in control group). CONCLUSION: The addition of the Cox maze procedure to mitral valve repair is safe and effective for selected patients, and elimination of atrial fibrillation decreased late complications.

Norepinephrine-induced vasoconstriction is increased in intimal hyperplastic arteries of the dog.

Norepinephrine-induced arterial contraction in vitro is known to be increased after endothelial denudation and during the subsequent development of intimal hyperplasia. We now report the response to norepinephrine in intimal-thickened iliac vessels in conscious dogs. Seven dogs underwent balloon catheter deendothelialization of the right iliac artery. Three weeks later, ultrasonic transducers were implanted on both iliac arteries to record dynamic vessel dimension. A catheter was inserted into the terminal abdominal aorta for drug infusion and blood pressure monitoring. The dogs were studied unsedated 2 days after instrumentation. Norepinephrine was infused at doses that did not affect blood pressure (0.01 to 0.05 micrograms/kg/min). Control vessel diameter decreased from 5.2 mm +/- 0.3 to 5.1 mm +/- 0.3 (2.4% +/- 1.0% when standardized to baseline diameter) and intimal hyperplastic vessels from 6.2 mm +/- 0.4 to 5.7 mm +/- 0.4 (7.6% +/- 1.7%). The difference between control and intimal hyperplastic vessel vasoconstriction was significant at p less than 0.0025. The calculated reduction in total vessel cross-section area for control vessels was 4.5% +/- 1.9%. In intimal hyperplastic vessels total cross-sectional area was reduced by 14.5% +/- 3.3% by vasoconstriction and the luminal cross-sectional area was reduced by 17.9% +/- 0.7% by the intimal hyperplasia. These data suggest that luminal compromise due to intimal hyperplasia is compounded by increased sensitivity to norepinephrine. This effect, demonstrated in a large elastic artery shortly after endothelial denudation, may be of even greater significance in a smaller vessel with advanced intimal hyperplasia.