Search

Atherosclerotic lesions occur as a result of excess lipid deposition within the vascular tissues. The peroxisome proliferator-activated receptors (PPARs) present in adipose and hepatic tissues have been shown to promote fatty acid oxidation and lipid storage. An immunohistochemical assessment of PPARalpha and PPARgamma revealed both proteins were also present in the medial and intimal layers of human arteries, predominately in regions containing smooth muscle cells. In agreement with this observation, smooth muscle cells isolated from these vessels were found by RT-PCR to express both PPARalpha and PPARgamma1. The functionality of these receptors was tested with selective PPAR agonists. Mitogenic stimulation of smooth muscle cell proliferation was blocked by 15d-PGJ2, a PPARgamma agonist, as well as by WY14643, a PPARalpha agonist. These data indicate PPAR activation by selective agonists could influence lesion progression directly, as well as indirectly through reductions in serum lipoprotein and triglyceride levels.

Background: The internal mammary artery (IMA) has been shown to have a significantly superior long-term patency rate when compared with the saphenous vein (SV) graft. Cultured smooth muscle cells (SMCs) from the IMA are more resistant to the mitogenic effects of platelet-derived growth factor (PDGF), when compared with SMCs that are derived from the SV. The radial artery (RA) is currently being used as an alternative to the SV. However, no long-term patency data are available for the RA, and there is no information on the biological behavior of RA-derived SMCs in culture., Methods: Smooth muscle cell cultures were taken from patients who underwent coronary artery bypass grafting with the IMA, RA, and SV. A quiescent state was induced by serum deprivation for 5 days. Thereafter cells were induced to proliferate by exposure to PDGF-BB. Levels of c-fos expression and 3H-thymidine incorporation were used as markers of cell proliferation., Results: We found that even after serum deprivation, c-fos was still detectable; however, basal levels were higher in cells from the SV than cells from either the RA (p = 0.003) or IMA (p = 0.008). After stimulation with PDGF-BB, c-fos expression was greater in SMCs from the SV relative to the RA (p < 0.001) or the IMA (p = 0.02). Finally, relative to the SV, 3H-thymidine in the RA was 0.76 +/- 0.22 (p < 0.05) and 0.39 +/- 0.24 (p < 0.002) in the IMA, respectively., Conclusions: The data indicate that SMCs from arterial conduits are more resistant to the mitogenic effects of PDGF-BB than those from venous conduits. Our results offer a mechanistic explanation of why arterial conduits might demonstrate patency superior to that of the SV.

The purpose of this study was to examine the impact of concomitant coronary artery bypass grafting (CABG) and valve design on survival following aortic valve replacement (AVR) with stentless and stented bioprostheses. Survival data for 1798 patients undergoing AVR between 1991 and 1997 with either a stentless (Medtronic Freestyle = 700, Toronto SPV = 447; N = 1147) or stented (Hancock II = 224, Carpentier-Edwards SAV = 427; N = 651) valve were analyzed. Bivariable analyses using Kaplan-Meier survival curves and log-rank test were performed to compare survival probabilities by valve type. Multivariable stepwise Cox's proportional hazard models were used to control for potentially confounding variables. Concomitant CABG was performed in 41% of stentless and 46% of stented patients (P =.04). Survival probability at 5 years was 0.84 (95% CI = 0.81, 0.87) for stentless versus 0.79 (95% CI = 0.75, 0.83) for stented patients (P =.004). In the absence of concomitant CABG, survival was superior in stentless (0.84) over stented (0.80) patients, but these differences were not statistically significant (P =.053). In patients that underwent AVR with concomitant CABG, survival was significantly better in stentless patients (0.82) than in stented individuals (0.77, P =.049). The unadjusted hazard ratio for stented versus stentless was 1.44 (95% CI = 1.12, 1.86, P =.005). In the final Cox's proportional hazard model the variables that effected survival were valve type and age in decades. New York Heart Association class at the time of surgery had a marginal effect on survival. The data demonstrate improved midterm survival with stentless versus stented valves. Subgroup analysis suggests survival benefits of stentless valves may be greater in patients who undergo concomitant CABG surgery., (Copyright 2001 by W.B. Saunders Company)

Stentless aortic bioprostheses (SBPs) convey hemodynamic and perhaps survival benefit over stented counterparts. The aim of this study was to determine whether the more taxing operation increases surgical risk. We studied contemporary multicenter (USA) data submitted to the Food and Drug Administration (FDA) for Freestyle stentless (group I, n = 583) and Mosaic stented xenograft approval (group II, n = 1260). The study compared 30-day mortality for the two groups overall, then for isolated aortic valve replacement (AVR) and for AVR and coronary bypass (CABG). Because the USA Freestyle valves were used in selected patients (pts) we included SBP data (group III) from Oxford, where Freestyle valves were used consecutively within the same time frame. We also reviewed hospital mortality in the stentless bioprosthesis literature and compared this with the Society of Thoracic Surgery Database. There were no differences in age, NYHA, or incidence of CABG between the groups. There was no significant difference in operative mortality between stented (group II) and exclusive (group III) SBP patient groups (P =.233 for AVR and P =.478 for AVR + CABG), or between selective (group I) and exclusive (P =.929 for AVR and P =.390 for AVR + CABG) groups, after adjustment for risk factors. However, there was a significantly higher mortality both for isolated AVR (P =.026) and AVR + CABG (P =.001) in the selected stentless group compared with stented. This was partly attributed to greater mortality when the Freestyle was used in elderly patients by the full root replacement method, and to the higher proportion of females, and subjects with intra-aortic balloon pump insertion in this group. A meta-analysis of published stentless valve series, showed mortality rates to be lower than those of the STS National Database average. During the learning curve selective use of SBPs increased hospital mortality for AVR +/- CABG. Consecutive use dispelled the difference and the literature now suggests that SBPs may reduce hospital mortality for high-risk patients., (Copyright 2001 by W.B. Saunders Company)

Background: Serotonin can induce proliferation of vascular smooth muscle cells. We assessed the ability of a specific serotonin receptor antagonist, sarpogrelate, to inhibit proliferation of cultured porcine coronary artery smooth muscle cells., Methods: Cell proliferation and mitotic activity were measured using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide. To determine the effect of sarpogrelate on DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and protein synthesis, radioactive incorporation of 3H-thymidine, 3H-uridine, and 3H-phenylalanine, respectively, was used. Synthesis of DNA was also assessed by flow cytometry with propidium iodide as a fluorochrome., Results: Serotonin, platelet-derived growth factor, endothelin, and angiotensin II all induced proliferation of porcine coronary artery smooth muscle cells. Sarpogrelate specifically inhibited the serotonin-induced cytokine trigger but did not influence platelet-derived growth factor-, endothelin-, or angiotensin II-induced cell proliferation. Sarpogrelate inhibited the serotonin-induced increase in intracellular free ionized calcium concentration, prevented mitogen-activated protein kinase activation, and down-regulated expression of the protooncogenes c-fos and c-jun. Sarpogrelate acted at the G1 phase of the cell cycle., Conclusions: These data suggest that sarpogrelate could be used as a therapeutic agent to inhibit serotonin-induced neointimal hyperplasia and improve patency of coronary artery bypass grafts.

Background: Intimal hyperplasia or restenosis at the site of a coronary artery bypass anastomosis contributes to early graft failure, and growth factor release in response to construction of the anastomotic site strongly influences this process. Due to the difficulties in studying restenosis after coronary artery bypass graft surgery, we have tested whether an organ culture model we have developed can simulate the early events associated with intimal hyperplasia., Methods: End-to-side anastomosis of porcine radial artery to porcine coronary artery were constructed. The vessels were trimmed and incubated under standard tissue culture conditions for 14 days. Appropriate controls were treated similarly. The vessels were frozen, cryosectioned, and immunostained for the expression of the proliferation marker proliferating cell nuclear antigen (PCNA). A proliferative index (PCNA positive nuclei/total nuclei) was calculated for comparative purposes., Results: Limited PCNA staining was observed in noncultured vessel segments (0.046+/-0.045). A slight increase in this index was observed in vessels that had been placed into culture without manipulation (0.230+/-0.141) and in vessels subjected to an arteriotomy (0.462+/-0.249). However, the most significant increase was obtained after construction of an anastomosis (4.98+/-6.66). No change in total cell number was evident over the course of the experiment or in relation to the treatment., Conclusions: Culture conditions and incision slightly stimulate cell proliferation in porcine coronary artery segments when compared with basal conditions of a native artery. In contrast, construction of an anastomosis increases proliferation 108-fold. Therefore, surgical manipulation of arterial conduits during construction of an anastomotic site is the primary trigger for intimal hyperplasia, independent of dissection and incision of the vessel. Furthermore, these data indicate the organ culture model we have developed will be useful for examining the cellular and molecular mechanisms that mediate intimal hyperplasia at the site of a coronary artery bypass graft anastomosis.

The hemodynamic benefits of using stentless valves for replacement of the human aortic valve have become more well known. These devices are associated with significant decrease in left ventricular (LV) mass and LV remodeling in the early postoperative period. However, no large study has examined patient-related and valve-related factors that may contribute to this phenomenon. This study examined 1,103 patients who underwent aortic valve replacement (AVR) with a stentless porcine valve (Freestyle = 840, SPV = 263). In all cases, a subcoronary implant technique was used. Valve performance was assessed by serial echocardiograms. At 3 years' post-AVR, mean gradient was 6.3+/-5.0 mm Hg, and effective orifice area (EOA) was 2.0+/-0.7 cm2. Indexed EOA was 1.2+/-0.4 cm2/m2. There was an association between indexed EOA and the extent of LV mass regression. At 3 years after surgery, LV mass index (LVMI) was reduced to 76.3% to 78.7% of baseline in patients whose indexed EOA was >0.8 cm2/m2. In contrast, for patients with an indexed EOA that was <0.8 cm2/m2, LVMI at 3 years was 95.5% of baseline (P = .0001). Multiple linear regression models were used to identify parameters that predicted the 3-year LVMI. Baseline LVMI (P<.0001), prior myocardial infarction (P = .0009), male gender (P = .0036), and carotid stenosis (P = .022) were independent predictors of LV mass regression. Valve type, valve size, preoperative New York Heart Association class symptoms, coronary disease, prior bypass surgery, chronic obstructive pulmonary disease, or underlying valve pathology had no effect on LV mass regression. Data indicate that baseline LVMI and patient-prosthetic mismatch have major effects on the extent of LV mass regression post-AVR. Long-term hemodynamic benefits of AVR can be optimized by proper selection of the prosthesis so as to avoid mismatch. Furthermore, because the baseline LVMI affects the extent of regression post-AVR, early intervention may result in more complete resolution of LV mass postoperatively, which may have important prognostic implications.

Background: Bypass surgery in the elderly (age >70 years) has increased mortality and morbidity, which may be a consequence of cardiopulmonary bypass. We compare the outcomes of a cohort of elderly off-pump coronary artery bypass (OPCAB) patients with elderly conventional coronary artery bypass grafting (CABG) patients., Methods: Chart and provincial cardiac care registry data were reviewed for 30 consecutive elderly OPCAB patients (age 74.7 +/- 4.2 years) and 60 consecutive CABG patients (age 74.9 +/- 4.1 years, p = 0.82) with similar risk factor profiles: Parsonnet score 17.2 +/- 8.1 (OPCAB) versus 15.6 +/- 6.5 (CABG), p = 0.31; and Ontario provincial acuity index 4.5 +/- 1.9 (OPCAB) versus 4.3 +/- 2.0 (CABG), p = 0.65., Results: Mean hospital stay was 6.3 +/- 1.8 days for OPCAB patients and 7.7 +/- 3.9 days for CABG patients (p < 0.05). Average intensive care unit stay was 24.0 +/- 10.9 h for OPCAB patients versus 36.6 +/- 33.5 h for CABG patients (p < 0.05). Atrial fibrillation occurred in 10.0% of OPCAB patients and 28.3% of CABG patients (p < 0.05). Low output syndrome was observed in 10% of OPCAB patients and 31.7% of CABG patients (p < 0.05). Cost was reduced by $1,082 (Canadian) per patient in the OPCAB group. Postoperative OPCAB graft analysis showed 100% patency., Conclusions: OPCAB is safe in the geriatric population and significantly reduces postoperative morbidity and cost.

A number of recent reports have suggested that valve design has an influence on long-term survival after aortic valve replacement (AVR). The present study examines the clinical results of two large multicenter trials of the Hancock II stented and Medtronic Freestyle stentless bioprosthetic valves. In all cases a subcoronary implant technique was used. All patients were operated on between 1991 and 1994, and all patients were monitored for 5 years. The 5-year actuarial survival rate was 86% for Freestyle and 77% for Hancock patients (P<.05). Late mortality occurred in 40 Freestyle patients (8.8%) compared with 36 Hancock II patients (16.1%, P = .0074). Cox's proportional hazard models were used to identify independent predictors of 5-year survival for the two groups. Hazard ratio (HR) and P value are presented in parentheses. The final analysis included the interactive variable valve*age. The resultant model indicates that the interaction of age and valve type has a significant effect on outcome. In patients < or =60 years of age at the time of operation, AVR with a Hancock II valves was associated with nearly a fivefold risk of death compared with patients of the same age who received a Freestyle valve (HR = 4.97, P = .0004). However, this survival advantage decreased by 50% with each decade thereafter (valve*age interaction HR = 0.50, P = .0027). Our data indicate that AVR with a stentless valve confers a survival advantage to the patient. The probability of dying within 5 years of surgery is 50% greater in patients who received a Hancock II versus a Freestyle valve (HR = 1.50, P = .0442). However, this survival advantage is most prominent in younger patients (<60 years of age) where the probability of death is fivefold greater with Hancock than Freestyle valves. With advancing age the benefits of stentless valves are diminished.

Background: The advances in immunotherapy, along with a liberalization of eligibility criteria have contributed significantly to the ever increasing demand for donor organs. In an attempt to expand the donor pool, transplant programs are now accepting older donors as well as donors from more remote areas. The purpose of this study is to determine the effect of donor age and organ ischemic time on survival following orthotopic heart transplantation (OHT)., Methods: From April 1981 to December 1996 372 adult patients underwent OHT at the University of Western Ontario. Cox proportional hazards models were used to identify predictors of outcome. Variables affecting survival were then entered into a stepwise logistic regression model to develop probability models for 30-day- and 1-year-mortality., Results: The mean age of the recipient population was 45.6 +/- 12.3 years (range 18-64 years: 54 < or = 30; 237 were 31-55; 91 > 56 years). The majority (329 patients, 86.1%) were male and the most common indications for OHT were ischemic (n = 180) and idiopathic (n = 171) cardiomyopathy. Total ischemic time (TIT) was 202.4 +/- 84.5 minutes (range 47-457 minutes). In 86 donors TIT was under 2 hours while it was between 2 and 4 hours in 168, and more than 4 hours in 128 donors. Actuarial survival was 80%, 73%, and 55% at 1, 5, and 10 years respectively. By Cox proportional hazards models, recipient status (Status I-II vs III-IV; risk ratio 1.75; p = 0.003) and donor age, examined as either a continuous or categorical variable ([age < 35 vs > or = 35; risk ratio 1.98; p < 0.001], [age < 50 vs > or = 50; risk ratio 2.20; p < 0.001], [age < 35 vs 35-49 versus > or = 50; risk ratio 1.83; p < 0.001]), were the only predictors of operative mortality. In this analysis, total graft ischemic time had no effect on survival. However, using the Kaplan-Meier method followed by Mantel-Cox logrank analysis, ischemic time did have a significant effect on survival if donor age was > 50 years (p = 0.009). By stepwise logistic regression analysis, a probability model for survival was then developed based on donor age, the interaction between donor age and ischemic time, and patient status., Conclusions: Improvements in myocardial preservation and peri-operative management may allow for the safe utilization of donor organs with prolonged ischemic times. Older donors are associated with decreased peri-operative and long-term survival following. OHT, particularly if graft ischemic time exceeds 240 minutes and if these donor hearts are transplanted into urgent (Status III-IV) recipients.

Background: Myocardial revascularization without cardiopulmonary bypass has been proposed as a potential therapeutic alternative in high-risk patients undergoing coronary artery bypass grafting. To evaluate this possibility we compared 15 high-risk (HR) patients in whom minimally invasive direct coronary artery bypass grafting was used as the method of revascularization with 41 consecutive patients who underwent conventional coronary artery bypass grafting during 1 month., Methods: Patients undergoing myocardial revascularization without cardiopulmonary bypass were significantly older than their low-risk (LR) counterparts (72.2 +/- 11.6 versus 63.3 +/- 9.7 years, p = 0.006). The demographic profile for HR versus LR patients was as follows: female patients, 60.0% versus 26.8%, p = 0.02; diabetes, 20.0% versus 24.4%, p = 0.7; prior stroke, 33.3% versus 7.4%, p = 0.03; chronic obstructive pulmonary disease, 60.0% versus 9.8%, p < 0.0001; peripheral vascular disease, 33.3% versus 12.2%, p = 0.03, congestive heart failure, 26.6% versus 9.8%, p = 0.09; impaired left ventricular (ejection fraction < 0.40), 40.0% versus 17.0%, p = 0.07; urgent operation, 86.6% versus 46.3%, p < 0.0001; and redo operation, 20.0% versus 0%, p = 0.003., Results: There were no deaths in the HR group and one death in the LR group. The average intensive care unit stay was 1.1 +/- 0.5 days in HR patients versus 1.6 +/- 1.6 days in LR individuals (p = 0.2), and the average hospital stay was 6.1 +/- 1.8 versus 7.3 +/- 4.4 days, respectively (p = 0.3). We used an acuity risk score index developed by the Adult Cardiac Care Network of Ontario to predict outcome in the HR group. The expected intensive care unit stay in HR patients was 4.1 +/- 1.2 days (versus the observed stay of 1.1 +/- 0.5 days, p < 0.0001), and the expected hospital stay was 12.5 +/- 1.5 days (versus the observed stay of 6.1 +/- 1.8 days, p < 0.0001). The expected mortality in the HR group was 6.1% versus 0%, p = 0.3. A cost regression model was used to examine predicted versus actual cost (in Canadian dollars) for the HR patient cohort (based on Ontario Ministry of Health funding). The expected cost for the HR cohort would have been $11,997 per patient. In contrast, the average cost for these 15 patients was $5,997 per patient, an estimated cost saving of 50%., Conclusions: Myocardial revascularization without cardiopulmonary bypass appears to be a safe and cost-effective therapeutic modality for HR patients requiring myocardial revascularization.

The excellent hemodynamics of stentless valves have been observed by numerous investigators. With the recent release of the Toronto SPV (stentless porcine valve) and the Medtronic Freestyle stentless valves in North America, it is appropriate to now compare the clinical and hemodynamic performance of these devices. We analyzed the results of 995 patients who underwent aortic valve replacement (AVR) with either of the two valves; in all cases a subcoronary implant technique was used. There were important differences in the preoperative characteristics for the two groups: Medtronic Freestyle patients were notably older than the Toronto SPV patients (70.7+/-8.6 vs 61.8+/-11.1 years, p < 0.001) and were markedly more symptomatic (p < 0.0001). In the Toronto SPV group, most patients had New York Heart Association (NYHA) Class II (41.5%) or Class III (44.7%) symptoms preoperatively, while in the Freestyle group, 61.5% were in Class III and 12.5% were in Class IV. There were no notable differences in mortality or morbidity for the two groups. Both devices demonstrated a meaningful decrease in mean gradient and a corresponding increase in effective orifice area (EOA). Furthermore, the indexed EOA (EOA/body surface area [BSA]) was > 1cm2/m2 for all valves indicating there was no patient-prosthetic mismatch. There was a meaningful decrease in left ventricular (LV) mass as well as LV mass index (LVMI) for both devices up to 3 years postoperatively. Our data indicate that there were no differences in clinical outcome or hemodynamic performance of these two valves. Both devices offer excellent results with normalization of LV function.

To assess the efficacy of arterial revascularization 368 patients were studied who underwent myocardial revascularization with two or more arterial conduits (group M) and compared with 2092 patients in whom a single internal mammary artery +/- veins (group S), and to a third group in which only saphenous vein conduits (group V, n = 602) were used. Group M patients were younger (aged 54.0(9.5) years; 4.1% aged > 70 years) than either group V (67.6(8.9) years, 40.7% > 70 years, P < 0.0001) or group S patients (62.0(8.5) years, 15.7% > 70 years, P < 0.0001). Furthermore, this cohort group had the lowest percentage of females (8.4%), of urgent cases (21.7%), of preoperative myocardial infarction (6.0%), and of redo surgery (0.8%). In contrast, patients who received only saphenous vein conduits had the highest proportion of female patients (29.2%), of urgent cases (47.4%), of preoperative myocardial infarction (16.5%), and of redo surgery (5.5%). By multivariate logistic regression analysis (odds ratio in parentheses), redo surgery (6.06, P = 0.0001), preoperative intra-aortic balloon pump assist (6.11, P = 0.0001), diabetes (1.97, P = 0.03), urgent surgery (1.80, P = 0.05), and advanced age (2.14, P = 0.01) were all predictors of operative mortality. In contrast, while choice of conduit appeared to influence outcome by univariate analysis (4.2% mortality in group V, P < 0.001), it was not found to be a predictor of either mortality or morbidity by regression analysis. The present results indicate that, in carefully selected patients, despite increased technical demands with longer periods of aortic occlusion and longer pump times, multi-arterial grafting (compared with conventional revascularization) is a safe and efficacious procedure. Whether or not this approach to revascularization will increase long-term survival and freedom from reoperation will require further study.

We report on 254 consecutive patients (170 male, 84 female) undergoing aortic valve replacement with the Toronto SPV Stentless Valve (St. Jude Medical, Inc., St. Paul, Minn.). Mean age (+/- standard deviation) was 62.1 +/- 11.6 years. Three patients (1%) received sizes 21 or 22 mm, 24 (9%) received size 23 mm, and 227 patients (89%) received sizes 25, 27, or 29 mm. Serial echocardiography was used to assess valve performance during a 3-year follow-up. Mean gradient decreased by 35.8% (p < 0.0001; 95% confidence interval -39.6%, -31.7%) from postoperative values to the 3- to 6-month follow-up and by 6.1% (p = 0.004; 95% confidence interval -10.1%, -2%) at each subsequent interval; effective orifice area increased by 17.2% (p = 0.0001; 95% confidence interval 12.0%, 22.6%) initially and by 4.4% (p < 0.001; 95% confidence interval 1.8%, 7.0%) thereafter. At 2 years of follow-up, mean gradient was 3.3 +/- 2.1 mm Hg and mean effective orifice area was 2.2 +/- 0.8 cm2. Studies on left ventricular mass were carried out on 84 patients. Left ventricular mass decreased by 14.3% (37.8 +/- 57.9 gm; p < 0.0001; 95% confidence interval -53.7, -21.9 gm) and left ventricular mass index decreased by 15.2% (21.1 +/- 30.5 gm/m2; p < 0.0001; 95% confidence interval -29.5, -12.7 gm/m2) from postoperative values to the 3- to 6-month follow-up interval. The reduction in residual gradient and potential regression in left ventricular hypertrophy may have a beneficial prognostic implication. We believe that the unique stentless design of the Toronto SPV Stentless Valve allows this to occur.

Background: This study is comprised of 3493 consecutive patients who underwent open heart surgery at our institution. Data on all patients were collected prospectively., Methods: In 45 patients (Group P) (1.3%), a permanent pacemaker (PP) was inserted postoperatively. For the purpose of the study, these patients were compared to 3448 patients (Group NP) who did not require insertion of a PP after surgery. Mean follow-up was 33 months (range 1.5 to 66)., Results: We found Group P patients were older (64.8 +/- 11.0 vs 61.0 +/- 11.0 years, p < 0.05), had a higher proportion of elderly (> 70 years) 36% vs 19%, p = 0.01), and of female patients (48.8% vs 22.7%, p < 0.001) compared to Group NP. Group P also had a higher incidence of preoperative rhythm abnormalities (26.6% vs 5.7%, p < 0.0001), redo surgery (13.3% vs 4.6%, p = 0.02), aortic valve surgery (48.8% vs 10.8%, p < 0.001), and tricuspid valve surgery (repair 3, replacement 1) (8.8% vs 0.5%, p < 0.001), in addition to a higher proportion of patients in whom cold (vs warm) blood cardioplegia was used (68.8% vs 52.3%, p = 0.03). Indication for postoperative PP was sick sinus syndrome (SSS) in nine patients; atrial fibrillation in eight patients; atrioventricular block (AVB) in 27 patients; and combined AVB/SSS in 1 patient. There were no operative deaths in Group P. Necessity for PP after heart surgery had a significant impact on resource utilization resulting in prolonged ventilation (3.1 +/- 7.5 vs 1.4 +/- 3.3 days, p < 0.01), intensive care unit (5.1 +/- 10.2 vs 2.5 +/- 4.0 days, p < 0.01), and postoperative hospital stay (18.0 +/- 13.4 vs 8.1 +/- 9.4 days, p < 0.01)., Conclusions: By multivariate logistic regression (odds ratio and p value in parentheses), aortic valve surgery (8.23, p = 0.001), the absence of preoperative sinus rhythm (5.60, p = 0.001), postoperative myocardial infarction (3.46, p = 0.024), and female gender (2.52, p = 0.003), were found to be independent predictors for PP requirement post surgery.

From November 1989 to December 1994, we performed 2264 bypass procedures. Data were collected prospectively. The population was divided into three subgroups: group 1 = single internal mammary artery (IMA) +/- veins (n = 1584); group 2 = veins only (n = 503); and group 3 = two or more arterial conduits +/- veins (n = 177). Patients who received only saphenous vein conduits (group 2) were significantly older (66.7 +/- 8.9 years) than either group 1 (60.3 +/- 8.3 years) or group 3 (51.6 +/- 9.2 years). Furthermore, this cohort group had the highest percentage of females (28.6%), urgent cases (43.5%), preoperative myocardial infarction (MI) (18.5%), and redo surgery (5.4%). In contrast, patients who received two or more arterial conduits were 94.9% male, and had the lowest incidence of urgent cases (18.1%) and redo surgery (0.5%). Mortality was 1.4% in group 1 and 3.2% in group 2; there were no deaths in group 3. Furthermore, group 2 patients had the highest incidence of perioperative MI (6.6%), low output syndrome (22.1%), intra-aortic balloon pump (IABP) assist (6.2%), and stroke (2.7%). By multivariate logistic regression analysis (odds ratio in parentheses), redo surgery (7.92), preoperative IABP (5.53), poor LV function (4.01), renal impairment (3.94), and advanced age (2.12) were all predictors of operative mortality. When mortality and morbidity (death, infarction, low output syndrome, IABP assist) were combined, regression analysis revealed that in addition to the above variables, female gender and cold cardioplegia were also independent predictors of combined mortality and morbidity. Resource utilization was determined for the three patient groups. There was concern that the increased technical demands of multiple arterial grafting along with longer periods of aortic occlusion and pump times may lead to increased complications and prolonged hospital stay. However, we found that group 3 had the lowest ventilation time, intensive care unit stay, and hospital stay. The results no doubt were influenced by case selection. Whether or not this approach to revascularization will increase long-term survival and freedom from reoperation will require further study.

Acute cardiac rupture is a complication of acute myocardial infarction and is often a lethal condition. The successful management of a case of left ventricular rupture by patch repair with concomitant myocardial revascularization is reported. Pre- and postoperative hemodynamic stabilization was achieved with the aid of intra-aortic balloon pump counterpulsation.

There is renewed interest in the use of the radial artery as a conduit for coronary artery bypass. Fifty patients underwent bypass surgery using the radial artery in addition to other conduits between November 24, 1992 and November 8, 1994 at our institution. The mean age was 54.4 +/- 9.1 years (mean +/- SD) and 47 of the patients were male. There were 3.6 +/- 0.9 and stomses per patient, of which 2.2 +/- 0.4 were arterial anastomoses. The most common target vessel for the radial artery has been the obtuse marginal (58.8%), with the aorta as the usual site for proximal anastomosis (80.4%). There have been no ischemic hand complications and no radial nerve deficits. There have been no early or late deaths and no myocardial ischemic complications related to the use of the radial artery. We present the techniques used at our institution for the use of the radial artery as a conduit for coronary artery bypass.

Objective: To evaluate the clinical and hemodynamic performance of a new bioprosthesis for replacement of the aortic valve in humans., Study Design: In a multicentre clinical trial between July 1991 and January 1994, 118 patients underwent aortic valve replacement with the Toronto SPV valve., Results: Valvular pathology was aortic stenosis in 58%, insufficiency in 12% and mixed valvular disease in 30%; congenital bicuspid aortic valve was seen in 42% while heavy calcification was present in 86%. In approximately a third of the patients, concomitant coronary artery bypass surgery was performed. The mean period of aortic occlusion was 89 mins (range 48 to 180). Valve sizes implanted were: 22 mm (1%), 23 mm (7.6%), 25 mm (22.9%), 27 mm (37.3%) or 29 mm (31.4%). There were three deaths in the series: two from subacute bacterial endocarditis and one suicide. Early complications were cardiac arrest (0.8%), thromboembolism (2.5%) and arrhythmia (12.7%), while late complications were cardiac arrest (0.8%), arrhythmia (4.7%), angina (0.8%), thromboembolism (4.4%), endocarditis (1.7%) and other sepsis (0.8%). There were no valve related failures in 119 valve-years (mean follow-up 1.01 valve-year per patient). Follow-up echocardiography demonstrated an average decrease in mean systolic gradient of 36% from early to late postoperative period (P < 0.001) and an average increase in effective orifice area of 35% (P < 0.001) in the same period. No regurgitation was noted in 91% of patients at early, and 89% of patients at late, follow-up., Conclusions: The Toronto SPV valve offers excellent hemodynamics, is relatively easy to insert and has few valve related complications. The observed changes in transvalvular area over time are consistent with a hypothesis that the ventricle undergoes remodelling following aortic valve replacement with this bioprosthesis. Longer follow-up is required to determine durability.

We report herein our experience with the Toronto Stentless Porcine Valve (Toronto SPV, manufactured by St. Jude Medical Inc., Minneapolis, MN, USA) for aortic valve replacement (AVR). To date 146 SPV valves have been implanted, 29 in an initial clinical trial (from October 1987 to April 1987) and 117 in the current FDA trial (September 1991 to January 1994). In the current trial the majority of patients were male (76%), aortic stenosis was the dominant lesion (73%) and 68% of the patients received a valve size 27 mm or greater. The mean age was 61.3 +/- 12.0 years. For the entire group there has been no hospital death and no patient has required a pacemaker. Perioperative complications were myocardial infarction in three patients and suspect subacute bacterial endocarditis (medically treated) in three patients. There have been two late deaths (2%), two patients have had transient ischemic attacks (2%), and one patient suffered stroke with complete neurological recovery (1%). To date there has been no case of primary valve failure. Echocardiographic assessment of the SPV valve has demonstrated excellent effective valve orifice areas with very low transvalvular gradients and 95% of the patients had either 0 or 1+ insufficiency. These results are encouraging and justify the continued use of this valve in clinical trials. Further follow-up is required to determine its durability.

We report our initial experience from April 1992 to November 1993 with a stentless porcine valve (Toronto SPV Valve, St. Jude Medical) for aortic valve replacement (AVR) in 21 consecutive patients and compare this group to a matched cohort that underwent AVR with a Hancock II (Medtronic) bioprosthesis. There were no hospital deaths in either group. Postoperative hospitalization was 5.5 +/- 0.8 versus 7.0 +/- 2.3 days (p = 0.004). Aortic cross-clamp time was 114.5 +/- 15.7 min in the SPV group and 96.0 +/- 25.0 min in the Hancock II group (p = 0.003). Complications in the SPV group were: one patient suffered perioperative infarction, one patient required late reoperation for left main stenosis, and one patient died suddenly following femoral thrombectomy at another center. Complications in the Hancock II group included: one patient with postoperative low output syndrome, and two late deaths (one from an aortic dissection and the other from chronic liver disease secondary to alcohol abuse). Comparison data indicate that the average size valve implanted in the SPV group was higher than in the Hancock II group (26.3 +/- 1.9 vs 24.0 +/- 1.9, p = 0.001). In the SPV group, 16 patients had 0 or trivial regurgitation and 1+ regurgitation was seen in 5 patients; regurgitation did not change over a 12-month follow-up. We observed a decrease in gradients over time (p < 0.01). Our results are compatible with a hypothesis that the ventricle undergoes remodeling over time, once the obstruction is relieved. We think the stentless design is an important feature that allows this to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

During the resection of the intrathoracic trachea by the transsternal approach, the ascending aorta, because of its anatomic position, impedes visualization. Herein, we report a technique that allows excellent exposure of the entire intrathoracic trachea, thereby facilitating this procedure.

DNA synthesis of the early erythropoietic progenitor cell (erythroid burst-forming unit, BFU-E) is inhibited by a growth factor that we have called negative regulatory protein (NRP). This protein appears to act during the S-phase of the cell cycle and to be specific to the BFU-E. It is nontoxic and its action is readily reversible by washing the cells. Erythropoietic burst formation by BFU-E in culture is promoted by interleukin 3 (IL-3). In the present work, using the hydroxyurea suicide assay method, we investigated the effects on DNA synthesis of exposing BFU-E of mouse bone marrow in vitro to NRP, IL-3, and combinations of NRP and IL-3. We found that the action of NRP on BFU-E DNA synthesis was opposed by IL-3 within the 45 min that it took to carry out the cell suicide assay. We also studied transforming growth factor-beta (TGF-beta) and found that its action on DNA synthesis of BFU-E was identical to that of NRP in time scale, reversibility, and opposition by IL-3, although the two have different molecular properties. According to the competence-progression model, regulation of cell proliferation occurs at two sites: 1) the G0 to G1 transition, where competence factors (e.g., platelet-derived growth factor [PDGF] and interleukin 1 [IL-1]) act, and 2) during G1-phase, where progression factors (e.g., interleukin 2 [IL-2] and IL-3) act. Our data indicate that cell proliferation may also be regulated at a third site, during S-phase. Here, the decision as to whether or not DNA synthesis will proceed appears to depend on a balance between positive and negative regulatory signals.

During studies on the influence of Fv-2 on the cycle state of the erythroid burst-forming unit (BFU-E), an activity was found in bone marrow supernatants from C57BL/6 (B6) mice that shut down DNA synthesis of the BFU-E in vitro. It acted within minutes, its action was completely reversed by a single wash, and it appeared specific to the BFU-E. The activity-causing substance, being macromolecular, heat stable, and trypsin-sensitive, was evidently a protein and was named negative regulatory protein. We purified a negative regulatory protein from a bone marrow-derived "B6 Pan" cell line with properties thus far indistinguishable from those of the negative regulatory protein obtained directly from B6 marrow. By gel filtration the protein has a Mr of approximately equal to 79,000, by cation- and anion-exchange chromatography it appears to be a neutral molecule at physiological pH, and the molecule does not bind to Con A. After five sequential chromatographic steps, we obtained a preparation active at a concentration of 25 ng/ml. Our findings are compatible with the hypothesis that quiescence of BFU-E with respect to DNA synthesis in vivo in B6 mice is mediated by negative regulatory protein molecules.

We have investigated the effect of 55Fe on the survival in suspension of erythropoietin (epo)-independent erythroid progenitor cells (CFU-E*) induced by Friend polycythemia virus (FV). Spleen cells from C3Hf/Bi mice previously infected with FV were exposed to carrier-free 55Fe, and the survival of CFU-E* as a function of time in liquid medium was determined from the number of erythroid colonies that developed from these cells seeded in plasma cultures without added epo. The results showed that spleen CFU-E* were highly vulnerable to 55Fe: Do approximately equal to 1 h exposure to 100 microCi/ml. Marrow CFU-E* behaved in a similar manner. The 55Fe responsible for their suicide had been presented to the progenitor cells only during the 4-h period of incubation, after which they were washed and plated in excess nonradioactive iron. We therefore conclude that CFU-E* themselves, and not only their progeny, are capable of actively incorporating iron. Under the same conditions in the absence of added epo, the effect of 55Fe on the survival of normal spleen or marrow CFU-E could not be assessed because two few normal CFU-E survived the incubation period. Normal bone marrow cells incubated in complete medium containing epo retained their capacity for erythrocytic colony formation, and CFU-E could then be shown to be vulnerable to 55Fe. Thus, either the iron-incorporating system of normal CFU-E was inducible by epo, or else epo permitted survival of the CFU-E so that the activity of a constitutive iron-incorporating system could be recognized.