Early outcomes of coronary artery bypass with and without cardiopulmonary bypass in octogenarians.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery has been successfully used in diverse patient populations and has been postulated to be safer than conventional coronary artery bypass (CCAB) surgery in some high-risk patients, including the elderly. OBJECTIVE: To compare the safety of OPCAB surgery versus CCAB surgery in the octogenarian population of two large southwestern Ontario cardiac surgical units. RESULTS: Two hundred thirty-six consecutive octogenarians underwent primary isolated coronary artery bypass surgery from November 2000 to March 2005. Patients undergoing OPCAB surgery tended to have higher Parsonnet scores, while patients undergoing CCAB surgery had a greater number of emergent operations. The Canadian Cardiovascular Network predicted that mortality risk was similar in both groups. In-hospital mortality was similar between groups, as was postoperative myocardial infarction and new onset of renal dysfunction. However, in the OPCAB group, there was a decreased incidence of postoperative neurological dysfunction (2.3% in the OPCAB group versus 10.5% in the CCAB group, P=0.01), in particular cerebrovascular accidents (1.5% in the OPCAB group versus 7.6% in the CCAB group, P=0.05), and a decreased incidence of prolonged intubation (5.3% in the OPCAB group versus 13.3% in the CCAB group, P=0.04). Multivariable analysis found that cardiopulmonary bypass had no significant impact on mortality or length of stay. CONCLUSIONS: In octogenarian patients, OPCAB surgery is as safe as CCAB surgery in terms of mortality and major morbidity. Furthermore, a significant reduction in neurological dysfunction and prolonged intubation was seen in the OPCAB group compared with the CCAB group.

Predictors of general surgical complications after heart transplantation.

BACKGROUND: Several studies have reported the incidence, morbidity, and mortality of general surgical conditions (GSCs) in orthotopic heart transplant (OHT) patients. The following is the largest reported series of such patients and the first study with sufficient patient numbers to formally evaluate peritransplant variables as risk factors for GSC development. STUDY DESIGN: A GSC was defined as a condition for which a general surgeon had been consulted or as a general surgical condition recognized at the time of autopsy. The records of 453 consecutive patients who underwent OHT between 1981 and 1999 were reviewed to identify patients who developed a GSC. Kaplan-Meier actuarial analysis on this cohort, and univariate and multivariate logistic regression models applied to a subpopulation of 324 consecutive OHT patients between 1987 and 1997 were used to determine factors associated with and predictive of GSC after OHT. RESULTS: Of 453 OHT patients, 371 (81.9%) were men, and the average age was 44.5 +/- 15 (standard deviation) years. Median followup was 2,086 days (range 1 to 6,642 days). Ninety-three patients (20.5%) developed 111 GSCs. Of these, 78 were men, and the average age was 49.9+/-10.2 years. There were 83 general surgical interventions. Actuarial analyses revealed that age greater than 50 years, pretransplant diagnosis of ischemic (PTDxI) versus nonischemic heart disease, and previous general surgical history were factors associated (p < 0.05) with a higher GSC incidence. Gender, more urgent transplant priority status, cardiopulmonary bypass time, total graft ischemic time, and intensive care unit length of stay were not associated with GSC. Factors associated with GSC on univariate analysis, with odds ratios (ORs) and 95% confidence intervals (CIs) included: age analyzed as a continuous variable (OR 1.04 per year; CI 1.01, 1.06 per year; p = 0.0021), PTDxI (OR 2.40; CI 1.39, 4.15; p = 0.0016), and pretransplant general surgical history (OR 3.35; CI 1.65, 6.82; p = 0.0008). Multivariate analysis revealed that only pretransplant general surgical history (OR 3.27; CI 1.58, 6.76; p = 0.0004) and PTDxI (OR 2.37; CI 1.35, 4.16; p = 0.0023) were associated with subsequent development of GSC. CONCLUSIONS: A pretransplant diagnosis of ischemic heart disease and previous history of a general surgical procedure are two independent risk factors that predispose OHT patients to development of GSC. Because GSC may arise insidiously in immunosuppressed patients, identification of OHT patients at higher risk for GSC will permit timely intervention decisions, decreasing morbidity and mortality in this challenging group of patients.

Does human leukocyte antigen matching influence the outcome of lung transplantation? An analysis of 3,549 lung transplantations.

BACKGROUND AND OBJECTIVE: Human leukocyte antigen (HLA) compatibility has been shown to improve the outcome of renal and cardiac transplantation. However, its impact on outcome following lung transplantation is not clear, with several single-center studies reporting inconsistent results. We studied the influence of HLA matching on survival and the development of rejection and obliterative bronchiolitis after lung transplantation, using data from the United Network for Organ Sharing/International Society for Heart and Lung Transplantation registry. METHODS: The study population included adult patients who received cadaveric lung transplants between October 1987 and June 1997 for whom HLA data were available. Two cohorts were examined, depending on the era of transplantation: (1) October 1987 to June 1997 (n = 3,549): Differences in actuarial survival as stratified by either the total number of HLA mismatches or the number of mismatches at each HLA locus were determined using a log-rank test. Multivariate logistic regression models were developed to determine independent predictors of survival at 1, 3, and 5 years following lung transplantation. (2) April 1994 to June 1997 (n = 1,796): The association of HLA mismatching with acute rejection and obliterative bronchiolitis was determined using a chi-squared analysis. RESULTS: Only 164 patients (4.6%) received lung grafts with 2 or fewer HLA mismatches. Univariate analyses demonstrated a significant difference in post-transplant survival by mismatch level, with the total number of HLA mismatches (p = 0.0008) and mismatching at the HLA-A locus (p = 0.002) associated with worse survival. Multivariate logistic regression demonstrated that the number of mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality (incremental odds ratios 1.18, p = 0.01, and 1.15, p = 0. 03, respectively). The total number of HLA mismatches predicted 3- and 5-year mortality (incremental odds ratios 1.13 at 3 years, p = 0. 0004, and 1.14 at 5 years, p = 0.0002). However, other covariates such as repeat transplantation, transplantation for congenital heart disease, advanced recipient age, and an early era of transplantation were stronger predictors of mortality. We found no significant association between HLA mismatching and the development of obliterative bronchiolitis, although there was an association between mismatching at the HLA-A locus and acute rejection episodes requiring hospital admission (p = 0.008). We also found no association between mismatching at the HLA-B locus and rejection episodes requiring either hospitalization or the alteration of anti-rejection medications (p = 0.034). CONCLUSION: Although the number of HLA mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality and the total number of mismatches predicted 3- and 5-year mortality following lung transplantation, the effect of each covariate was small in this multicenter study of 3,549 patients. Further close follow-up of registry patients is necessary to determine the effect of HLA matching on long-term survival and freedom from obliterative bronchiolitis and rejection following lung transplantation. A prospective study of HLA matching for lung transplantation should not yet be considered in view of the small number of grafts with 2 or fewer mismatches and the modest effect of HLA matching on outcome.

Late presentation of an intra-abdominal foreign body.

Bowel obstruction by a foreign body is rare. The authors describe the case of a 77-year-old woman who had small-bowel obstruction due to a foreign body 40 years after a transabdominal hysterectomy. A loop of small bowel had herniated through a metal ring and had become necrotic. The ring and involved bowel were excised and the patient's clinical course was uncomplicated. The original purpose of the ring remains a mystery. The time frame between the introduction of a foreign body and the occurrence of symptoms in this case appears to be the longest ever reported.

The enigma of myocardial preconditioning models.

Myocardial preconditioning has been reported in the hearts of many species of animals, including dogs, pigs, rabbits, rats, and anecdotally in humans. However, most studies were carried out in the regional ischemic model, although protection against global ischemic injury had been observed in rat models. Besides biochemical endpoints, the criterion of protection in regional ischemia was usually reduction in infarct size, while in global ischemia, recovery of contractile force and time-to-onset of ischemic contracture were used. We attempted to reproduce preconditioning of myocardium against global ischemic injury using an isolated perfused rabbit heart model with the rationale that global ischemia is more relevant to cardiac surgery, the rabbit model is logistically convenient, and it can be used for future comparison with the responses in immature hearts. The preconditioning was induced with 5 minutes of normothermic global ischemia followed by 10 minutes of reperfusion. The principal ischemic injury lasted 35 minutes, followed by 60 minutes of reperfusion. The control group underwent similar principal ischemic injury and reperfusion but no prior preconditioning ischemia. Results showed that there was no difference between the two groups in left ventricular resting tension, recovery in left ventricular developed pressure, contractility (dP/dt), and rate of relaxation (-dP/dt), nor were there any differences in heart rate and coronary flow rate. The reason for our negative findings is not clear, but if the results are confirmed, it will suggest that extrapolation of observations obtained from one experimental model to another should be made with caution.

Sarcoplasmic reticulum in globally stunned adult and newborn myocardium.

Dysfunctional sarcoplasmic reticulum (SR) is thought to be involved in the phenomenon of myocardial stunning. Adult (3 to 4 kg) and neonatal (5 to 7 day old) rabbit hearts were examined for structural SR alterations following ischemic damage and myocardial stunning induced by incubation in Ringer's lactate at 39 degrees C. SR protein yield in neonate hearts (but not adult hearts) significantly decreased (p = 0.01) following 30 minutes of ischemia. In addition, calcium ATPase activity was reduced in both adult p = 0.006) and neonatal (p = 0.02) ischemic hearts. Examination of SR proteins by gel electrophoresis indicated that the levels of several proteins were altered by ischemia. In adult hearts, decreased levels of proteins of 22.5, 31.5, 33, and 83 kilodaltons (kd) were observed. In newborn ischemic hearts, decreases in 29, 37.5, 82, and 83 kd proteins were detected. The quantitative changes in calcium ATPase levels and SR protein content may adversely affect myocardial excitation-contraction coupling and relaxation, contributing to dysfunction in myocardial stunning.

Unique responses of immature hearts to ischemia. Functional recovery versus initiation of contracture.

The characterization of unique responses of immature hearts to ischemic injury is important in devising better methods of myocardial protection for neonatal cardiac operations. Two end-points used to assess the vulnerability of immature myocardium to ischemic injury, namely, the time between onset of ischemia to the beginning of contracture and the functional recovery after reperfusion, had yielded results that appeared to be contradictory. In this study both the immature and adult rabbit hearts were used to study these two end-points in the same model, to assess their relationships and physiologic implications. Our data confirmed that, although immature hearts have greater capacity than adult hearts for functional recovery after identical periods of ischemic insult, their times to ischemic contracture are not prolonged, as could have been expected. A negative correlation between the rise in resting myocardial tension (i.e., contracture) and the recovery of ventricular function after reperfusion was noted both in the neonatal and in the adult hearts. However, reperfusion undertaken after "the onset of contracture" showed that the ventricle could still regain a measure of its function, which indicates that the "irreversibility" in global ventricular function is a gradual and progressive phenomenon. Biochemical studies of sarcoplasmic reticular calcium-adenosinetriphosphatase activity indicated that the immature myocardium has a significantly lower activity of this enzyme. Further depression of this enzyme activity after ischemia is seen in the immature hearts and may in part explain the earlier onset of contracture reported. A unifying concept to explain these unique responses of neonatal hearts to ischemia is proposed, based on the immaturities of certain key enzymes. The implications of these findings in the development of better protective techniques are also discussed.

Adverse effect of prearrest hypothermia in immature hearts: rate versus duration of cooling.

It has been suggested that rapid cooling before the induction of arrest may be harmful to the newborn myocardium. The objective of this study was twofold: (1) to evaluate whether prearrest rapid cooling is indeed detrimental to myocardial recovery and (2) if so, to evaluate whether the adverse effect of prearrest hypothermia is dependent on the rate of cooling or the total duration of cold perfusion. After an initial stabilization period isolated Langendorff hearts (n = 5 per group) from neonatal piglets (5 to 7 days old) were randomized to four groups: group 1, 5 minutes of rapid cooling to 15 degrees C; group 2, 20 minutes of slow cooling to 15 degrees C; group 3 and group 4, rapid and slow cooling, respectively, with the addition of St. Thomas cardioplegic solution. All groups were then subjected to 2 hours of ischemia at 15 degrees C followed by 30 minutes of reperfusion at 38.5 degrees C. Post-ischemic recovery of left ventricular developed pressure was significantly greater in group 1 versus group 2 (80% +/- 3% versus 61% +/- 2%; p less than 0.05) and in the presence of cardioplegia, group 3 versus group 4 (72% +/- 3% versus 57% +/- 3%; p less than 0.05). The increase in left ventricular end-diastolic pressure was significantly less in group 1 versus group 2 (8% +/- 5% versus 33% +/- 7%; p less than 0.01). Myocardial adenosine triphosphate content recovery correlated with ventricular recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute lymphocytosis after trauma--early recognition of the high-risk patient?

An absolute lymphocyte count is included in the routine results provided by most automated blood cell counters, providing a prompt indication of peripheral blood lymphocytosis. Transient lymphocytosis is seen in many acutely ill patients, including those with multiple injuries. We have observed a significantly higher death rate among trauma patients with lymphocytosis at presentation; patients with lymphocytosis, on subsequent assessment of injury, proved to have higher Injury Severity Scores than those without lymphocytosis. Investigation of lymphocyte subsets in nine patients with lymphocytosis showed an increase in T cells, reversal of the CD4:CD8 ratio, and, in seven patients, an increase in "natural killer" cells. The presence of lymphocytosis and its early detection as part of a routine blood count may supply a readily available means of identifying a high-risk trauma patient.

Pharmacological response of quinidine induced early afterdepolarisations in canine cardiac Purkinje fibres: insights into underlying ionic mechanisms.

The purpose of these experiments was to study the pharmacological response of quinidine induced early afterdepolarisations to gain insights into underlying ionic mechanisms. Quinidine (8.5 microM) induced stable early afterdepolarisations at low activation frequencies in 80% of canine cardiac Purkinje fibres superfused with a modified Tyrode's solution. Early afterdepolarisations arose from a secondary plateau in the voltage range of -30 to -60 mV. Calcium channel blockers (verapamil, 1 microM, in 3/6 preparations; verapamil, 10 microM in 6/6 preparations; nifedipine, 0.1 microM in 5/5 preparations) completely eliminated early afterdepolarisations, despite continued quinidine superfusion, without altering the underlying action potential. Isoprenaline (0.2-1 microM) restored them in 75% of these preparations during continued calcium blocker superfusion. Tetrodotoxin (5/5 preparations) eliminated early afterdepolarisations by abbreviating action potentials and reducing or eliminating the quinidine induced secondary plateau. While low concentrations of isoprenaline favoured the occurrence of early afterdepolarisations, larger concentrations eliminated them by enhancing spontaneous automaticity. These experiments suggest that voltage dependent and/or receptor regulated slow inward current plays an important role in quinidine induced early afterdepolarisations. Beta receptor stimulation can enhance or suppress early afterdepolarisations, depending on whether effects on slow inward current (tending to favour them) or on automaticity (suppressing them) predominate.

The antiarrhythmic efficacy of amiodarone and desethylamiodarone, alone and in combination, in dogs with acute myocardial infarction.

Antiarrhythmic activity of amiodarone's desethyl metabolite, which accumulates during oral amiodarone therapy, has been postulated to explain the delayed onset of antiarrhythmic effects during long-term amiodarone therapy. To determine their relative antiarrhythmic efficacy, amiodarone and its desethyl metabolite, desethylamiodarone, were administered to mongrel dogs with ventricular tachycardia 24 hr after ligation of the left anterior descending coronary artery. Cumulative doses of amiodarone, desethylamiodarone, a combination of amiodarone and desethylamiodarone, or the vehicle for drug administration were given at 1 hr intervals. Both amiodarone and desethylamiodarone suppressed ventricular arrhythmias in a dose-dependent fashion. The metabolite, however, was more potent with a 50% effective concentration for suppression of premature ventricular complexes of 1.4 mg/liter compared with 4.6 mg/liter for the parent compound. Plasma and myocardial drug concentrations were similar to those measured during long-term amiodarone therapy in man, with desethylamiodarone producing greater myocardial concentrations than amiodarone for a given plasma concentration. Coadministration of the metabolite along with the parent drug resulted in suppression of arrhythmias at lower doses of amiodarone than when the latter was administered alone, and concentration-response analysis indicated an additive antiarrhythmic effect. These experiments suggest that the accumulation of desethylamiodarone that occurs with long-term oral amiodarone therapy contributes importantly to the antiarrhythmic effects of the drug, and may account for the gradual increase in antiarrhythmic action during the course of amiodarone therapy.

Frequency-dependent effects of amiodarone on atrioventricular nodal function and slow-channel action potentials: evidence for calcium channel-blocking activity.

The purpose of these experiments was to determine the frequency dependence of the effects of amiodarone and its active desethyl metabolite on slow-channel tissues. Intravenous amiodarone and desethylamiodarone (10 or 25 mg/kg) increased atrioventricular conduction time (AVCT) and refractory period (AVERP) in open-chest, chloralose-anesthetized dogs. Drug effects on AVCT and AVERP were greatly augmented by increasing atrial stimulation frequency. The frequency dependence of drug effects was quantified by studying the response of atrioventricular (AV) conduction to changes in coupling interval. Under control conditions, premature atrial stimulation increased AVCT with a time constant of 70 msec. In the presence of amiodarone and desethylamiodarone, a biexponential relationship between AVCT and coupling interval was observed. One component had a time constant similar to control, and a slower component with a time constant of about 1 sec appeared. Slow-channel action potentials produced in canine cardiac false tendons by elevated potassium (25 mM) and isoproterenol in vitro showed interval-dependent changes in Vmax with a time constant averaging 74 msec in the absence of amiodarone. In the presence of amiodarone, a slower recovery phase of Vmax with a time constant averaging 0.94 sec was observed. These results indicate that amiodarone and its metabolite produce heart rate-dependent changes in AV nodal function in vivo and suggest use-dependent calcium-channel blockade as a mechanism of this action. Amiodarone's rate-related effects on slow-channel properties should produce selective depression of supraventricular tachyarrhythmias involving rapid activation of the AV node.

Lymphocyte surface marker studies in the diagnosis of unexplained lymphocytosis.

Fifty-six patients with unexplained lymphocytosis were investigated with a panel of antibodies to lymphocyte surface antigens. In 23 the distribution of cell surface markers suggested reactive lymphocytosis. The remaining 33 patients showed a distribution of cell surface markers that indicated or suggested a diagnosis of B-cell lymphoproliferative disease. Two illustrative case reports show how such studies performed early in the investigation of unexplained lymphocytosis may permit earlier diagnosis of the underlying mechanism.

Rat liver and intestinal mucosa differ in the developmental pattern and hormonal regulation of carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase gene expression.

cDNA probes were employed to measure levels of carbamoyl-phosphate synthetase I (CPS) and ornithine carbamoyltransferase (OCT) mRNAs in fetal and neonatal livers and intestines. In the fetal liver, significant levels of OCT mRNA were present at 15-days gestation while CPS mRNA could not be detected until day 17 of fetal development. Apart from a small decline just after birth, amounts of both mRNAs increased steadily to reach adult levels in postnatal life. In contrast to the situation in liver, CPS and OCT mRNA levels in the fetal intestine rose rapidly to peak at day 21 of gestation and then declined steadily in the first seven days after birth. Using the methyl-sensitive restriction isoschizomeric pair, MspI/HpaII, the 5' ends of both the CPS and OCT genes were shown to undergo demethylation during development. In the case of the OCT gene, however, the hypomethylation characteristic of the adult liver and intestinal mucosa was not observed in the 15-day-old fetal liver, where significant levels of gene expression had already been established. Levels of CPS and OCT mRNA in livers of adults responded to glucagon in normal animals (1.5-fold and 2.2-fold increases, respectively) and to dexamethasone in experimentally induced diabetic animals (3-fold increase in CPS mRNA with no change in OCT mRNA). These treatments were all without effect on the levels of CPS and OCT mRNA in intestinal mucosa.

Sensitivity of routine blood bank methods for the detection of anti-D as determined during proficiency testing.

A proficiency testing program in immunohematology, involving over 240 laboratories, was used to assess the detection of anti-D in six concentrations ranging from 11 to 8,500 ng/mL. Using the indirect antiglobulin test, more than 98% of laboratories reporting detected anti-D at all concentrations. Enzyme and albumin antiglobulin methods as routinely practiced did not clearly increase sensitivity, and the direct agglutination methods used were much less sensitive than indirect antiglobulin methods. If proficiency testing truly reflects performance in practice in Ontario, Canada, the sensitivity of manual indirect antiglobulin methods in routine use for the detection of anti-D appears to meet reasonable expectations of these technics.

Proficiency testing in immunohaematology in Ontario, Canada, 1977-1979.

An analysis of the results of a compulsory proficiency testing programme in immunohaematology is presented. Error rates have been calculated for the determination of ABO and Rh(D) groups, the direct antiglobulin test and antibody detection according to defined criteria. The introduction of proficiency testing has been associated with alterations in error rates for some determinations. An educational programme introduced for laboratories with poor performance has proved effective in improving their results in the proficiency testing programme.

Proficiency testing in immunohematology in Ontario, Canada, 1975-1977.

Since April 1975 the proficiency of laboratories in Ontario that perform immunohematology tests has been assessed. While the majority of test samples have required only ABO and Rh(D) typing, others have posed problems. The error rate in uncomplicated ABO typing was 1.3/1,000 in 17,479 tests and that in straightforward Rh(D) grouping, 6.6/1,000 in 17,757 tests. False-negative (36/1,000) and false-positive (1.4/1,000) direct antiglobulin tests occurred. Errors in detection of strong alloantibodies (e.g., anti-D) were 19.7, 10.2 and 5.1/1,000 in three test samples. A2B or A2 cells with anti-A1 in serum were sent out in two surveys; error rates in ABO interpretation were 189 and 52/1,000, respectively. Laboratories also experienced difficulty in interpreting the Rh(D) type of cells with positive antiglobulin tests. These surveys have had several effects: (1) laboratories with poor performance have been identified, (2) patterns of practice have been influenced, (3) areas of ignorance have been identified, and (4) a stimulus has been provided for continuing education in immunohematology.