Biomarkers and longitudinal changes in lumbar spine degeneration and low back pain: the Johnston County Osteoarthritis Project.

OBJECTIVE: To determine if baseline biomarkers are associated with longitudinal changes in the worsening of disc space narrowing (DSN), vertebral osteophytes (OST), and low back pain (LBP). DESIGN: Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for severity of DSN and OST. LBP severity was self-reported. Concentrations of analytes (cytokines, proteoglycans, and neuropeptides) were quantified by immunoassay. Pressure-pain threshold (PPT), a marker of sensitivity to pressure pain, was measured with a standard dolorimeter. Binary logistic regression models were used to estimate odd ratios (OR) and 95% confidence intervals (CI) of biomarker levels with DSN, OST, or LBP. Interactions were tested between biomarker levels and the number of affected lumbar spine levels or LBP. RESULTS: We included participants (n = 723) with biospecimens, PPT, and paired lumbar spine radiographic data. Baseline Lumican, a proteoglycan reflective of extracellular matrix changes, was associated with longitudinal changes in DSN worsening (OR = 3.19 [95% CI 1.22, 8.01]). Baseline brain-derived neuropathic factor, a neuropeptide, (OR = 1.80 [95% CI 1.03, 3.16]) was associated with longitudinal changes in OST worsening, which may reflect osteoclast genesis. Baseline hyaluronic acid (OR = 1.31 [95% CI 1.01, 1.71]), indicative of systemic inflammation, and PPT (OR = 1.56 [95% CI 1.02, 2.31]) were associated with longitudinal increases in LBP severity. CONCLUSION: These findings suggest that baseline biomarkers are associated with longitudinal changes occurring in structures of the lumbar spine (DSN vs OST). Markers of inflammation and perceived pressure pain sensitivity were associated with longitudinal worsening of LBP.

Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative.

OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7. RESULTS: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. CONCLUSION: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.

Hip symptoms are associated with premature mortality: the Johnston County Osteoarthritis Project.

OBJECTIVE: To investigate the impact of hip osteoarthritis (OA) and/or hip symptoms on excess mortality. DESIGN: We analyzed data from 3,919 individuals in a community-based prospective cohort of African Americans and Caucasians age ≥45 years. Women ≥50 years of age and all men underwent supine anteroposterior pelvic radiography at baseline, with the participant's feet in 15 degrees of internal rotation. Hip radiographic (rOA) was defined as a Kellgren-Lawrence grade of ≥2 in at least one hip. Participants completed questionnaires at baseline to determine presence of hip symptoms and covariate status. Participants with symptomatic hip rOA (SxOA) are a subset of individuals with hip rOA and symptoms in the same hip. Multiple imputation was used to impute missing values of covariates. Mortality was determined through 2015 and follow-up time was calculated from baseline assessment until death or censoring which took place when a participant was lost to follow-up or reached the end of study period. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We carried out additional analyses stratified by sex, race, age and obesity. RESULTS: Mean follow-up time was 14.2 years during which 1762 deaths occurred. There were 29.9% participants in our population with hip rOA at baseline. Compared to those with neither hip rOA nor hip symptoms, we observed an increased risk of all-cause mortality in participants with hip symptoms alone (HR = 1.28, 95% CI = 1.13-1.46), but no association for hip rOA either with or without symptoms. In stratified analyses we observed increased associations for hip symptoms alone and hip sxOA in those <65 years (43% and 39% increase, respectively) and in Caucasians (34% and 21% increase, respectively). CONCLUSIONS: Individuals who had hip symptoms without hip rOA had an increased risk of mortality. These effects were particularly strong for those who were <65 years of age and Caucasians. Effective interventions to identify those with hip pain in order to lessen it could reduce premature mortality.

The association between walking speed from short- and standard-distance tests with the risk of all-cause mortality among adults with radiographic knee osteoarthritis: data from three large United States cohort studies.

OBJECTIVE: Adults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA. METHODS: Participants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over 9 years, hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders. A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality. RESULTS: Deaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI + MOST. Walking 0.2 m/s slower during short- and standard-distance walk tests was associated with 23% (aHR [95%CI]; 1.23 [1.10, 1.39]) and 25% (1.25 [1.09, 1.43]) higher mortality risk, respectively. Walking <0.5 m/s on short-distance and <1.2 m/s standard-distance walk tests, best discriminated those with and without mortality risk. CONCLUSION: Slower walking speed measured via short- and standard-distance walk tests was associated with increased mortality risk in adults with rKOA.

The impact of painful knee osteoarthritis on mortality: a community-based cohort study with over 24 years of follow-up.

OBJECTIVE: To investigate the impact of knee osteoarthritis (OA) and/or knee pain on excess mortality. METHOD: We analyzed data from 4,182 participants in a community-based prospective cohort study of African American and Caucasian men and women aged ≥45 years. Participants completed knee radiographs and questionnaires at baseline and at up to three follow-ups to determine knee OA (rOA), knee pain and covariate status. Mortality was determined through 2015. We used Cox proportional hazards regression with time-varying covariates (TVC) to estimate hazard ratios (HR) and 95% confidence intervals (CI). Additional analyses stratified by sex, race and age were carried out. RESULTS: Median follow-up time was 14.6 years during which 1822 deaths occurred. Baseline knee radiographic osteoarthritis (rOA) was 27.7%, 38.8% at first follow-up, 52.6% at second follow-up and 61.9% at the third follow-up. Knee rOA with pain and knee pain alone were both associated with a >15% increase in premature all-cause mortality. In analyses stratified by sex, race and age, associations between knee pain, with or without knee rOA, and all-cause death were found among women, Caucasians, those ≤65 years of age, and those with a body mass index (BMI)≥30, with observed increased risks of death between 21% and 65%. We observed similar, somewhat attenuated, results for cardiovascular disease (CVD) deaths. CONCLUSION: In models taking into account variables that change over time, individuals who had knee pain, alone or with knee rOA, had increased mortality. These effects were particularly strong among those obese. Effective interventions to reduce knee pain, particularly those including weight management and prevention of comorbidities, could reduce mortality.

A machine learning approach to knee osteoarthritis phenotyping: data from the FNIH Biomarkers Consortium.

OBJECTIVE: Knee osteoarthritis (KOA) is a heterogeneous condition representing a variety of potentially distinct phenotypes. The purpose of this study was to apply innovative machine learning approaches to KOA phenotyping in order to define progression phenotypes that are potentially more responsive to interventions. DESIGN: We used publicly available data from the Foundation for the National Institutes of Health (FNIH) osteoarthritis (OA) Biomarkers Consortium, where radiographic (medial joint space narrowing of ≥0.7 mm), and pain progression (increase of ≥9 Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] points) were defined at 48 months, as four mutually exclusive outcome groups (none, both, pain only, radiographic only), along with an extensive set of covariates. We applied distance weighted discrimination (DWD), direction-projection-permutation (DiProPerm) testing, and clustering methods to focus on the contrast (z-scores) between those progressing by both criteria ("progressors") and those progressing by neither ("non-progressors"). RESULTS: Using all observations (597 individuals, 59% women, mean age 62 years and BMI 31 kg/m2) and all 73 baseline variables available in the dataset, there was a clear separation among progressors and non-progressors (z = 10.1). Higher z-scores were seen for the magnetic resonance imaging (MRI)-based variables than for demographic/clinical variables or biochemical markers. Baseline variables with the greatest contribution to non-progression at 48 months included WOMAC pain, lateral meniscal extrusion, and serum N-terminal pro-peptide of collagen IIA (PIIANP), while those contributing to progression included bone marrow lesions, osteophytes, medial meniscal extrusion, and urine C-terminal crosslinked telopeptide type II collagen (CTX-II). CONCLUSIONS: Using methods that provide a way to assess numerous variables of different types and scalings simultaneously in relation to an outcome of interest enabled a data-driven approach that identified key variables associated with a progression phenotype.

Evaluation of the self-directed format of Walk With Ease in patients with systemic lupus erythematosus: the Walk-SLE Pilot Study.

OBJECTIVE: To conduct a proof-of-concept pilot evaluation of the self-directed format of Walk With Ease (WWE), a 6-week walking program developed for adults with arthritis, in patients with systemic lupus erythematosus (SLE). METHODS: This was a single arm, 6-week pre- and post-evaluation of the self-directed WWE program to assess feasibility, tolerability, safety, acceptability, and effectiveness. Adult patients with physician-diagnosed SLE were recruited to participate during regularly scheduled visits to an academic rheumatology clinic. Self-reported outcomes of pain, stiffness, and fatigue were assessed by visual analog scales (VAS) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) scale at baseline and at completion of the 6-week program. Patients also completed a satisfaction survey at the end of the program. Multivariate linear regression models were used to calculate mean changes between baseline and 6-week follow-up scores, adjusting for covariates. Mean change scores were used to estimate effect sizes (ES). RESULTS: At 6 weeks, 48 of the 75 recruited participants completed the WWE program. Participants experienced modest improvements in stiffness and fatigue (ES = 0.12 and ES = 0.23, respectively, for VAS scores; ES = 0.16 for FACIT-fatigue score) following the intervention. The majority of participants reported satisfaction with the program (98%) and benefitted from the workbook (96%). CONCLUSIONS: The self-directed format of WWE appears to reduce stiffness and fatigue in patients with SLE. It also seems to be a feasible and acceptable exercise program to patients with SLE. Larger studies are needed to confirm these findings.

Osteoarthritis induced by destabilization of the medial meniscus is reduced in germ-free mice.

OBJECTIVE: To determine the contribution of the gut microbiota to the development of injury-induced osteoarthritis (OA). DESIGN: OA was induced using the destabilized medial meniscus (DMM) model in 20 germ-free (GF) C57BL/6J male mice housed in a gnotobiotic facility and 23 strain-matched specific pathogen free (SPF) mice in 2 age groups -13.5 weeks avg age at DMM (17 SPF and 15 GF) and 43 weeks avg age at DMM (6 SPF and 5 GF). OA severity was measured using scores for articular cartilage structure (ACS), loss of safranin O (SafO) staining, osteophyte size, and synovial hyperplasia. Microbiome analysis by 16S rRNA amplicon sequencing was performed on stool samples and LPS and LPS binding protein (LBP) were measured in plasma. RESULTS: Compared to the SPF DMM mice, the maximum (MAX) ACS score per joint was 28% lower (p = 0.036) in GF DMM mice while the SafO sum score of all sections evaluated per joint was decreased by 31% (p = 0.009). The differences between SPF and GF mice in these scores were greater when only the younger mice were included in the analysis. The younger GF DMM mice also had significant reductions in osteophyte size (36%, P = 0.0119) and LBP (27%, P = 0.007) but not synovial scores or LPS. Differences in relative abundance of a number of Operational Taxonomic Units (OTUs) were noted between SPF mice with high vs low maximum ACS scores. CONCLUSIONS: These results suggest factors related to the gut microbiota promote the development of OA after joint injury.

Digital subtraction angiography in patients with transposition of the great arteries after surgical repair.

Digital subtraction angiography was used for postoperative evaluation of seven patients who underwent the Senning procedure for repair of d-transposition of the great arteries. Their ages ranged from 2.5 to 3 years. The patients were premedicated with methohexital (25 mg/kg rectally), and 0.3 to 0.4 ml/kg of diatrizoate was injected into a peripheral vein through a plastic needle. Images were obtained on a Technicare DR-960 or Diasonics DA 100 digital angiographic unit at four frames per second using 256 X 256 matrix and a 6 inch (15.24 cm) field size. In all patients, the venous systems, cardiac chambers and great arteries were well visualized. Two patients had obstruction of the superior vena cava with a dilated azygos vein draining into the inferior vena cava. One patient had severe obstruction of the left pulmonary artery. Digital subtraction angiography is safe and easy to perform and appears to be a valuable alternative method for evaluating patients after surgical repair of transposition of the great arteries. The small amount of contrast material required and the low radiation dose make it attractive for use in children.

Combined discrete subaortic stenosis and ventricular septal defect in infants and children.

Eight patients, aged 1 to 8 years, with discrete subaortic stenosis (DSS) and ventricular septal defect (VSD) were studied by 2-dimensional (2-D) and M-mode echocardiography. Initial cardiac catheterization and angiocardiography showed VSD and other associated cardiac lesions, including coarctation of the aorta and patent ductus arteriosus. None had evidence of DSS. Six patients underwent surgical repair of the associated lesions, but none required closure of the VSD. Ultimately, 6 patients had spontaneous closure of VSD, and 2 had a residual small VSD. Subsequent serial echocardiography showed evidence of subaortic membrane, prompting repeat cardiac catheterization, which confirmed moderate to severe peak systolic pressure gradients between the left ventricle and ascending aorta. Surgical resection of the membrane was performed in 5 patients. Thus, in patients with small or spontaneously closed VSDs, DSS may develop. Evaluation of the left ventricular outflow tract area is recommended in patients with small or closed VSD in whom a significant heart murmur or electrocardiographic abnormality remains.

In vitro analysis of mechanisms of balloon valvuloplasty of stenotic mitral valves.

Preliminary reports indicate that percutaneous balloon valvuloplasty is efficacious for treatment of mitral stenosis. The present study was designed to evaluate whether anatomic features of stenotic mitral valves in older adults affect the efficacy of balloon valvuloplasty and to determine the mechanism by which increased orifice area is accomplished. Fifteen mitral valves excised intact at the time of mitral valve replacement from patients with no more than 2+/4+ mitral a regurgitation were selected for study. Balloon valvuloplasty was performed using a sequence of dilation catheters with balloons 18 to 25 mm in inflated diameter. Mitral valve area, measured with a conical valve sizer, increased from 0.71 +/- 0.06 cm2 (mean +/- standard error of the mean) to 1.77 +/- 0.19 cm2 (p less than 0.0001) after valvuloplasty, resulting in an increase in calculated orifice area of 185 +/- 27% (range 34 to 407%). The increase in calculated orifice area correlated inversely with orifice area before valvuloplasty (r = -0.57; p = 0.026), but was unrelated to extent of calcific deposits on the prevalvuloplasty x-ray of the excised mitral valve. Gross examination together with x-ray analysis after valvuloplasty revealed that the mechanism of balloon valvuloplasty in each case involved commissural splitting, including splits through heavily calcified commissures, without grossly apparent detachment of tissue fragments. These findings suggest that balloon valvuloplasty augments the functional mitral valve orifice area in a manner analogous to standard surgical commissurotomy, and balloon valvuloplasty is likely to be efficacious for a wide spectrum of adult mitral valvular stenosis, including severe stenosis with extensive calcific deposits.

Laser myoplasty for hypertrophic cardiomyopathy. In vitro experience in human postmortem hearts and in vivo experience in a canine model (transarterial) and human patient (intraoperative).

The feasibility of performing a myotomy/myectomy for hypertrophic cardiomyopathy (HC) by means of laser phototherapy was evaluated experimentally in vitro and in vivo, and the procedure then applied to a patient intraoperatively. In vitro experience revealed that the beam of an argon laser, delivered directly or via an optical fiber, could both cut and vaporize myocardium, producing a myotomy/myectomy morphologically similar to that produced by the conventional blade technique. In vivo experiments, in which the beam of an argon laser was delivered via an optical fiber to the ventricular septum of a canine heart, confirmed that a laser myoplasty could be achieved in 4 of 5 dogs by a transarterial approach. Finally, laser myoplasty was performed intraoperatively in a patient with HC, using a 200-mu fiber interfaced with an argon laser. Measured laser power was 1.5 W; cumulative exposure was less than 4 minutes; the myoplasty was 4 X 1 X 0.5 cm. These investigations establish the feasibility of using laser therapy to create a myoplasty trough that is similar in appearance to that typically achieved by the conventional blade technique. Illumination of the intraventricular operative field and precise modeling of the myoplasty trough constitute the principal advantages of laser myoplasty for HC.

Left ventricular inotropic effect of atrial pacing after coronary artery bypass grafting.

The effect of atrial pacing on left ventricular (LV) performance was studied in 19 patients, 24 hours after coronary artery bypass grafting (CABG). LV volumes were calculated from simultaneous radionuclide-thermodilution measurements at rest (heart rate 82 +/- 12 beats/min), 10 minutes after the start of atrial pacing (100 beats/min), and with atrial pacing plus volume loading to return preload toward baseline. Atrial pacing reduced preload as reflected by LV end-diastolic volume index (69 +/- 14 vs 60 +/- 14 ml/m2, mean +/- standard deviation) (p less than 0.0001), but returned to baseline with volume loading. Afterload, as reflected by arterial end-systolic pressure, did not change with atrial pacing (63 +/- 9 at baseline vs 64 +/- 8 mm Hg with pacing, difference not significant). Afterload increased with volume loading (68 +/- 10 mm Hg, p less than 0.025 vs baseline and pacing). LV stroke volume decreased with atrial pacing due to reduced preload, but returned to baseline with volume loading. Cardiac index increased with atrial pacing and increased further with volume loading. Compared with baseline, LV end-systolic volume index was reduced during atrial pacing both before and after volume loading, despite unchanged or augmented afterload. The combination of atrial pacing and volume loading resulted in augmentation of LV stroke work, despite no increase in preload compared with baseline. Thus, after CABG, increased (paced) heart rate augments inotropic state, as indicated by reduced LV end-systolic volume under conditions of unchanged or increased afterload, and elevated LV stroke work without an increase in preload or a decrease in afterload.

Clinical and hemodynamic performance of the Ionescu-Shiley valve in the small aortic root. Results in 117 patients with 17 and 19 mm valves.

The Ionescu-Shiley pericardial valve was our bioprosthetic valve of choice between 1981 and 1985 for patients in whom the aortic anulus could not accept a valve larger than 19 mm in outer diameter or in whom the avoidance of warfarin sodium (Coumadin) was important. A series of 117 consecutive patients who received 17 or 19 mm valves for isolated aortic valve replacement or aortic valve replacement combined with coronary artery bypass grafting or other valvular procedures was analyzed. Overall, 74% of the patients were female, with a mean age of 70.9 years and a body surface area of 1.67 +/- 0.19 m2; 92.3% were in New York Heart Association class III-IV, and the operation was urgent or emergent in 46%. The operative mortality rate was 7.7%, with no deaths in patients undergoing isolated elective first-time aortic valve replacement. Mean follow-up for survivors was 2.5 years (10 to 62 months). There were 20 late deaths, of which three were valve related, three were due to sudden death or arrhythmias, and two were due to persistent heart failure. The actuarial survival rate at 5 years was 68%. Clinical follow-up revealed a low incidence of valve-related complications, and 96.4% of survivors were in class I-II. Postoperative echocardiography before hospital discharge revealed a maximum instantaneous gradient of 18.4 +/- 3.0 mm Hg in five patients having a 17 mm valve and 31.3 +/- 12.7 mm Hg in 20 patients having a 19 mm valve. Doppler echocardiography was performed in 22 patients at a mean follow-up of 39.3 +/- 11.7 months. The maximum instantaneous gradient was 25 +/- 17.2 mm Hg for 17 mm and 17.41 +/- 5.4 mm Hg for 19 mm valves at late follow-up. The effective orifice area was 0.85 +/- 0.1 cm2 for 17 mm and 1.21 +/- 0.21 cm2 for 19 mm valves. This study defines the normal range of Doppler echocardiographic transprosthetic gradients for the Ionescu-Shiley valve and confirms that low operative mortality and excellent clinical improvement can result from the use of small Ionescu-Shiley valves in elderly patients despite moderate postoperative transvalvular gradients.

The third manpower study of thoracic surgery: 1980 report of the Ad Hoc Committee on Manpower of The American Association for Thoracic Surgery and The Society of Thoracic Surgeons.

An ad hoc committee was appointed by The Society of Thoracic Surgeons (STS) in 1977 in order to determine the available manpower and workload of thoracic surgeons in 1976. This committee conducted a survey of the professional activities and geographic location of all known surgeons certified by the American Board of Thoracic Surgery (ABTS) at that time. A summary of this study indicated the available and projected thoracic surgery manpower. The report also determined the present and projected health care needs of the population of the United States through 1993. Because thoracic surgery needs to continue to meet the health care needs of the United States in an appropriate yet economical fashion, the STS and The American Association for Thoracic Surgery (AATS) undertook a joint review to determine again the available manpower and its workload in calendar year 1980. In addition, this study compared its findings with the 1976 report in order to detect changes in the workload and need for thoracic surgical services. A questionnaire was mailed to 3,584 certified thoracic surgeons. There were 2,675 responses. The material was sent to the Academic Computer Services at George Washington University Medical Center for tabulation and data processing. This report summarizes the results of this survey. It also compares these data with those obtained in the 1976 study and, based on this information, attempts to project the thoracic surgery manpower needs in the next decade by using several hypothetical models.

Extended ex vivo preservation of the heart and lungs. Effects of acellular oxygen-carrying perfusates and indomethacin on the autoperfused working heart-lung preparation.

The autoperfused working heart-lung preparation has been proposed as a method for long-term heart-lung preservation. We investigated the effects of acellular oxygen-carrying perfusates (study 1) and the effect of donor pretreatment with indomethacin (study 2) on the working ex vivo heart-lung block. In study 1 perfusion with stroma-fee hemoglobin resulted in significantly reduced survival (118 +/- 46 minutes) compared with autologous blood (561 +/- 125 minutes, p less than 0.05) or perfluorocarbon (438 +/- 114 minutes, p less than 0.05). Decrease in survival with stroma-free hemoglobin perfusate is associated with a marked decrease in left ventricular performance and a significant increase in pulmonary vascular resistance. Perfusion with autologous blood is associated with a significant increase in pulmonary vascular resistance after 240 minutes of explantation, which is significantly delayed by perfusion with perfluorocarbon. Perfusion for 6 hours with blood pretreated with indomethacin (study 2) resulted in a decrease in the concentration of prostacyclin and thromboxane A2 metabolites but an increase in the prostaglandin/thromboxane A2 metabolite ratio. This is associated with abrogation of the increase in pulmonary vascular resistance (12,787 +/- 1682 dynes/sec/cm-5, T = 0; 13,134 +/- 2654 dynes/sec/cm-5, T = 360 minutes) observed in preparations perfused with autologous blood (13,194 +/- 1942 dynes/sec/cm-5, T = 0; 24,768 +/- 3325 dynes/sec/cm-5, T = 360 minutes, p less than 0.05). We conclude that alteration of the cellular and humoral components of autologous blood may prove advantageous for increasing the utility of the autoperfused working heart-lung preparation as a preservation technique.

Control of acute aortic dissection.

An experimental model of acute aortic dissection has been designed in an effort to examine myocardial contractility and systolic arterial pressure as factors influencing the progression of dissection. Thirty mongrel dogs divided into three experimental groups underwent left thoracotomy and construction of a standard intimal tear in the proximal descending aorta. Nine of ten animals in the control group showed progression of the aortic dissection a mean of 81.5 percent of the distance from the aortotomy to the celiac axis. Group II consisted of ten dogs pretreated with propranolol. The myocardial contractility (dp/dt) was significantly depressed in this group without change in systolic pressure. However, progression of dissection occurred in nine of ten animals as in the control group. In Group III, ten dogs were pretreated with trimethaphan lowering the systolic blood pressure to 90 mm. Hg and depressing the dp/dt to levels equal to those of Group II. There was no progression of aortic dissection in any of the animals in this group. The results indicate that, under these experimental conditions, depression of myocardial contractility alone has no inhibitory effect on the progression of dissection. When controlled hypotension is added to myocardial depression, aortic dissection is inhibited completely.

Cefamandole pharmacokinetics during standard and pulsatile cardiopulmonary bypass.

The pharmacokinetics of cefamandole during standard or pulsatile cardiopulmonary bypass were studied in 13 adult cardiac surgery patients. All patients received 20 mg/kg of cefamandole intravenously at midnight before surgery, 6 AM on the morning of surgery and just prior to the initiation of cardiopulmonary bypass (CPB) surgery. Serum, skeletal muscle, and fat samples were taken at the beginning of CPB and at 30-minute intervals thereafter and assayed for cefamandole concentration. The average elimination rate constant and elimination half-life for cefamandole in patients undergoing standard CPB were 0.73 +/- 0.09 hour-1 and 0.94 +/- 0.11 hour, respectively. In contrast patients undergoing pulsatile CPB had significantly slower elimination rate constants (0.50 +/- 0.1 hour-1 and 1.4 +/- 0.28 hours, respectively; P less than or equal to .05). Area under the curve (AUC) values for cefamandole in fat and muscle tissue were higher in patients undergoing pulsatile CPB, but the differences were not statistically significant. Prolonged elimination from the serum, skeletal muscle, and adipose tissue, as compared with normal subjects, is seen with both pulsatile and standard CPB but is greater for the pulsatile method. Intraoperative dosing of cefamandole is required to maintain adequate serum and tissue levels for operations lasting longer than 4 or 6 hours in which standard or pulsatile CPB, respectively, are used.

Atrial pacing during intraaortic balloon pumping.

Intraaortic balloon pumping and atrial pacing are both useful in treating postoperative low output syndrome. However, the electrocardiographic atrial pacing spike can interfere with the electrocardiogram tracking mechanism of many balloon consoles. Bipolar epicardial pacing can avoid this problem and allow simultaneous atrial pacing and intraaortic balloon pumping.

Patch aortotomy for aortic valve replacement after previous coronary artery bypass grafting.

Exposure for aortic valve operations after previous coronary artery bypass grafting may be technically difficult owing to the presence of patent vein grafts on the proximal aorta. A patch or "island" aortotomy technique that allows excellent exposure of the aortic valve is presented here. In select patients this approach may facilitate cardioplegia administration.