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Background: Pharmacologically potentiated electrical stimulation of the right vagus nerve achieves controlled intermittent asystole cardiac therapy. The present study examined pathophysiologic consequences of repetitive intermittent asystoles on contractile function, myocardial blood flow, and vagus nerve function and morphology., Methods: Open-chest anesthetized canines, with either normal left anterior descending (LAD) coronary arteries (n = 8) or severely stenotic LADs (n = 8), received pharmacologic pretreatment with pyridostigmine (0.5 mg/kg), propranolol (80 microg/kg), and verapamil (50 microg/kg) before vagus nerve stimulation. Time-matched control animals with normal (n = 4) or severely stenotic LADs (n = 6) received drugs but no vagus nerve stimulation. The vagus nerve was stimulated for 12 seconds ("on") and rested for 15 seconds ("off"). This algorithm was repeated for 15 on-off cycles, simulating using controlled intermittent asystole during the placement of 15 sutures in a distal coronary anastomosis. This 15-cycle sequence was repeated twice more, simulating a three-vessel bypass., Results: Normal coronary arteries: Ninety minutes after three sets of controlled intermittent asystole, LAD blood flow was unchanged from base line (36.6 +/- 4.5 versus 33.0 +/- 4.2 mL/min, p = 0.4), and global left ventricular performance (impedance catheter, end-systolic pressure-volume relations) was similar to baseline (7.4 +/- 1.2 versus 7.2 +/- 1.0 mm Hg/mL, p = 0.1). Left anterior descending coronary artery stenosis model: Ninety minutes after CIA, there were no significant differences versus control animals in regional LAD blood flow (27 +/- 4 versus 29 +/- 5 mL/min, p = 0.4) or fractional shortening of LAD myocardium (sonomicrometry; 6.2% +/- 1.8% versus 5.4% +/- 1.2%, p = 0.1). Vagus nerve conduction and morphology were unchanged from baseline., Conclusions: Repetitive controlled intermittent asystole does not impair poststimulation coronary blood flow, cardiac contractile function, or vagus nerve function. Controlled intermittent asystole may be useful to facilitate off-pump or endoscopic coronary artery bypass grafting.

In 1967, Christian Barnard performed the first successful human-to-human heart transplant. Following this triumph, the ensuing decade saw a waning interest in heart transplantation given the complications related to rejection and immunosuppression. With the introduction of cyclosporine immunotherapy in the early 1980s, however, success was more the rule than the exception, and cardiac transplantation became an acceptable therapy. Currently, heart transplantation is considered the gold standard therapy for end-stage heart failure refractory to medical treatment. One-year survival is now approximately 85%, and 10-year survival approaches 60%. While the main obstacles in the early years of heart transplantation were immunosuppression, the current issue at hand is organ availability. Approximately 2500 heart transplants are done yearly, but the list of candidates exceeds 50,000. What is perhaps even more alarming is the fact that while the number of heart transplants performed in the United States has dropped every year since 1994, the prevalence of heart failure increases every year and is predicted to do so into the year 2030. Nevertheless, the last 20 years has seen dramatic improvements in the ways we diagnose rejection, the fine-tuning of immunosuppressive regimens, and the advent of better preservation techniques. We have a better understanding of the causes of acute and chronic rejection and ways to treat these problems. Undoubtedly, we will continue to fine-tune the therapy in the years to come. This article is a review of the current indications, techniques, and medical therapies involved with cardiac transplantation.

The optimal management of endoleaks after endovascular repair of abdominal aortic aneurysms remains to be established. In this report, we describe a persistent side-branch, or type II, endoleak 1 year after endograft implantation treated with catheter-directed embolization of the aneurysm sac and the inferior mesenteric artery via the superior mesenteric artery, with embolization agents including thrombin, lipiodol, and gelfoam powder. Shortly after the embolization procedure, colonic necrosis developed in the patient, manifested by peritonitis, which necessitated a partial colectomy. This case underscores the devastating complication of colonic ischemia as a result of catheter-directed embolization of the inferior mesenteric artery in the management of an endoleak.

Background: NO has been advocated as an adjunct to cardioplegia solutions. However, NO undergoes a rapid biradical reaction with superoxide anions to produce peroxynitrite (ONOO(-)). ONOO(-) in crystalloid cardioplegia solution induces injury to coronary endothelium and to systolic function after cardioplegia and reperfusion. However, ONOO(-) may be degraded to less lethal or cardioprotective intermediates with glutathione (GSH) in reactions separate from its well known antioxidant effects. We hypothesized that GSH detoxifies ONOO(-) and reverses defects in endothelial function and systolic function when present in crystalloid cardioplegia., Methods and Results: In anesthetized dogs on cardiopulmonary bypass, a 45-minute period of global normothermic ischemia was followed by 60 minutes of intermittent cold crystalloid cardioplegia (Plegisol) and 2 hours of reperfusion. The cardioplegia solution contained 5 micromol/L authentic ONOO(-); catalase was included to attenuate the potential antioxidant effects of GSH and to unmask the effects on ONOO(-). In 1 group (CP+GSH, n=5), the cardioplegia contained 500 micromol/L GSH, whereas 1 group received crystalloid cardioplegia without GSH (CCP, n=6). There were no group differences in postcardioplegia left ventricular systolic function (end-systolic pressure-volume relation, impedance catheter: CCP 10.0+/-2.4 versus CP+GSH 10.6+/-1.3 mm Hg/mL) or diastolic chamber stiffness (ss-coefficient: CCP 0.35+/-0.2 versus CP+GSH 0.31+/-0.18). Myocardial neutrophil accumulation (myeloperoxidase activity) was attenuated in CP+GSH versus CCP (2.2+/-0.7 versus 5.4+/-1.2, P:<0.05). In postexperimental coronary arteries, maximal endothelium-dependent relaxation was greater in CP+GSH than in CCP (118+/-6% versus 92+/-5%, P:<0.05), with a smaller EC(50) value (-7. 10+/-0.05 versus -6.98+/-0.03, respectively, P:<0.05). Smooth muscle relaxation was complete in both groups. The adherence of neutrophils to postexperimental coronary arteries as a measure of endothelial function was less in CP+GSH than in CCP (98+/-18 versus 234+/-36 neutrophils/mm(2), P:<0.05). Nitrosoglutathione, a byproduct of the reaction between ONOO(-) and GSH, was greater in CP+GSH than in CCP (4.1+/-2.3 versus 0.4+/-0.2 microg/mL, P:<0.05)., Conclusions: GSH in crystalloid cardioplegia detoxifies ONOO(-) and forms cardioprotective nitrosoglutathione, resulting in attenuated neutrophil adherence and selective endothelial protection through the inhibition of neutrophil-mediated damage.

Heparin reduces ischemia-reperfusion injury to myocardium. This effect has been attributed to complement inhibition, but heparin also has other activities that might diminish ischemia-reperfusion. To further probe these mechanisms, we compared heparin or an o-desulfated nonanticoagulant heparin with greatly reduced anticomplement activity. When given at the time of coronary artery reperfusion in a canine model of myocardial infarction, heparin or o-desulfated heparin equally reduced neutrophil adherence to ischemic-reperfused coronary artery endothelium, influx of neutrophils into ischemic-reperfused myocardium, myocardial necrosis, and release of creatine kinase into plasma. Heparin or o-desulfated heparin also prevented dysfunction of endothelial-dependent coronary relaxation following ischemic injury. In addition, heparin and o-desulfated heparin inhibited translocation of the transcription nuclear factor-kappaB (NF-kappaB) from the cytoplasm to the nucleus in human endothelial cells and decreased NF-kappaB DNA binding in human endothelium and ischemic-reperfused rat myocardium. Thus heparin and nonanticoagulant heparin decrease ischemia-reperfusion injury by disrupting multiple levels of the inflammatory cascade, including the novel observation that heparins inhibit activation of the proinflammatory transcription factor NF-kappaB.

Objective: The purpose of the present study was to investigate whether apoptosis is triggered during ischemia (I) and reperfusion (R) and whether I/R-induced apoptosis is correlated with changes in expression of Bcl-2 and Bax., Methods: Anesthetized open-chest dogs were divided into two groups. Group I: 7 h of permanent I without R (PI, n = 7); Group II: 60 min I followed by 6 h R (I/R, n = 8). Apoptosis was identified as "DNA ladder" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end labeling (TUNEL) assay., Results: Collateral myocardial coronary blood flow during I, confirmed by colored microspheres was comparable in both groups. Although PI caused 72 +/- 5% infarct size, very few TUNEL-positive cells were detected in the necrotic area (0.2 +/- 0.1% of total normal nuclei), consistent with an absence of DNA laddering. In contrast, the appearance of TUNEL-positive cells was significantly displayed after 6 h R in the necrotic area in I/R group (26 +/- 4%, P < 0.001 vs. PI group), and DNA ladder occurred in all experimental animals, suggesting that myocardial apoptosis is primarily elicited by R. Densitometrically, Western blot analysis showed significant reduction in expression of Bcl-2 (16 +/- 1%) and increase in Bax (29 +/- 8%) after 6 h R in the necrotic area compared with normal tissue while expression of these two proteins was not changed in the PI group. Polymorphonuclear neutrophil (PMN) accumulation in the necrotic area determined either by immunohistochemistry with anti-CD18 antibody or by myeloperoxidase activity was significantly increased in the I/R group compared to the PI group (358 +/- 24 vs. 24 +/- 2, mm2 myocardium, P < 0.01) and (2.9 +/- 0.3 vs. 0.4 +/- 0.1, U/100 mg tissue, P < 0.01). There was a significant linear relationship between CD18-positive PMNs and TUNEL-positive cells (P < 0.05) in the I/R group., Conclusions: These results indicate that (1) PI without R did not induce apoptotic cell death, while two types of cell death, necrosis and apoptosis were found after I/R, (2) the Bcl-2 family may participate in early R-induced myocardial apoptosis, (3) PMN accumulation may play a role in the development of apoptosis.

This article discusses general mediastinal embryology, and provides anatomy and algorithms for the investigation of mediastinal masses. The superior, anterior, middle, and posterior mediastina also are detailed.

Background: Peroxynitrite (ONOO(-)) has been implicated as a primary mediator in the deleterious effects of nitric oxide (NO) in crystalloid solutions, possibly due to a lack of detoxification mechanisms, leading to the formation of.OH. In contrast, ONOO(-) may exert cardioprotective effects in blood environments secondary to detoxification and the subsequent formation of NO-donating nitrosothiols. This dichotomy in physiological effects of ONOO(-) may exist between crystalloid and blood cardioplegia (BCP) environments. In the present study, we tested the hypothesis that ONOO(-) is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts., Methods and Results: In anesthetized dogs on cardiopulmonary bypass, global 37 degrees C ischemia was imposed for 30 minutes, followed by 60 minutes of intermittent 4 degrees C hyperkalemic crystalloid (Plegisol) or BCP with (+) or without (-) 5 micromol/L authentic ONOO(-). After 2 hours of reperfusion, left ventricular (LV) function (end-systolic pressure-volume relations, in percent of baseline) was 56+/-3% in Plegisol-, which was further reduced in Plegisol+ to 40+/-4%.* In contrast, postischemic systolic function was better in BCP+ groups than in BCP- groups (96+/-2%* versus 82+/-2%, respectively). Differences in functional recovery could not be attributed to differences in hemodynamics. LV end-diastolic stiffness was significantly increased with the addition of ONOO(-) in both Plegisol (298+/-26% versus 466+/-30%*) and BCP (201+/-22% versus 267+/-13%*) groups. Consistent with increased LV chamber stiffness, myocardial edema was increased in BCP+ compared with BCP- (78.9+/-0.3% versus 76.4+/-0.3%*) and in Plegisol+ compared with Plegisol- (81.1+/-0.3% versus 79.6+/-0.4%*). Creatine kinase activity was significantly increased in Plegisol+ (48+/-6) compared with that in Plegisol- (31+/-6) but was unchanged in BCP- (14+/-2) relative to BCP+ (18+/-1). Nitrotyrosine (ng/mg protein) accumulation in LV myocardial biopsy samples confirmed myocardial exposure to ONOO(-) or its metabolites (Plegisol- 1.2+/-0.1, Plegisol+ 3.31+/-0.3*, BCP- 1.4+/-0.2, BCP+ 2.9+/-0.2*)., Conclusions: We conclude that (1) the postcardioplegic cardiodynamic effects of ONOO(-) depend on its environment and (2) ONOO(-) in crystalloid solution impairs postcardioplegia systolic and diastolic functional recovery, whereas (3) ONOO(-) in BCP increases functional recovery. This environment-dependent dichotomy in the effect of ONOO(-) may affect the benefits of NO-related adjuncts to crystalloid or BCP solutions (*P<0.05 versus group without ONOO(-)). :II-384-II-391.)

Background: Various studies have reported that the administration of adenosine (ADO) in cardioplegia reduces myocardial ischemic injury, but this timing may not utilize ADO's potential against myocardial reperfusion injury. This study tested the hypothesis that ADO-supplemented blood cardioplegia (BCP) or ADO administered during reperfusion reduces postischemic dysfunction after severe regional ischemia., Methods and Results: After 75 minutes of left anterior descending coronary artery occlusion, total cardiopulmonary bypass was initiated; cold (4 degrees C) antegrade BCP (8:1 blood:crystalloid) was delivered every 20 minutes for the first 3 doses, and 27 degrees C BCP was delivered for the terminal infusion. Dogs (n=6 per group) received unsupplemented BCP, ADO (100 micromol/L/L) supplemented in all infusions of BCP (ADO-CP), or ADO (100 micromol x L(-1) x L(-1)) supplemented only in the terminal infusion of BCP followed by intravenous ADO (140 microg x kg(-1) x min(-1)) infusion for the first 30 minutes of reperfusion (ADO-R). Postischemic regional systolic shortening was significantly greater in the ADO-R group (5+/-2.0%) than in the BCP group (-3+/-1.0%), but not in the ADO-CP group (2+/-0.2%). Postischemic regional diastolic stiffness in the area at risk during end reperfusion was lower with ADO-R (1.8+/-0.3%) than with ADO-CP (2.7+/-0.3%) or BCP (4.4+/-0.5%). Infarct size was reduced in the ADO-CP (29+/-2%) and ADO-R (21+/-2%) groups compared with the BCP group (42+/-4%). Edema in the myocardial area at risk was decreased in the ADO-CP (82+/-0.2%) and ADO-R (80+/-0.4%) groups compared with the BCP group (86+/-0.7%). Adherence of fluorescently labeled neutrophils (PMNs) to postischemic coronary artery endothelium was attenuated by ADO-R (55+/-2 PMNs/mm(2)), but not by ADO-CP (114+/-5 PMNs/mm(2)), compared with BCP (118+/-3 PMNs/mm(2))., Conclusions: The results show that BCP supplemented with ADO reduces infarct size, preserves postischemic systolic and diastolic regional function but does not attenuate coronary artery endothelial dysfunction unless administered during reperfusion.

Ischemia-reperfusion results in contractile dysfunction, necrosis, and vascular injury. This postischemic injury is mediated in part by superoxide radical production, neutrophils, dysfunction to ionic pumps, and edema formation. Adenosine is an autacoid released tonically by myocytes, endothelium, and neutrophils; the release of adenosine from the myocyte compartment into the interstitium is increased during ischemia. The major effects of adenosine are mediated by specific receptors identified as A1, A2a, A2b, and A3. Each receptor subtype contributes to physiological responses that influence ischemia-reperfusion injury. Adenosine has potent cardioprotective properties exerted during three major windows of opportunity: pretreatment, ischemia, and reperfusion. The cardioprotective effects exerted during pretreatment and ischemia may involve metabolic changes and hyperpolarization via K(ATP)-channel activation, mediated through A1 receptor mechanisms. The cardioprotective mechanisms exerted during reperfusion involve inhibition of neutrophils directly (superoxide anion generation, expression of adhesion molecules), and by inhibiting activation of the endothelium through A2 receptor-mediated mechanisms, thereby preventing neutrophil-endothelial cell interactions, which initiate the inflammatory-like component of reperfusion injury. Activation of the newly identified A3 receptor has been shown to be cardioprotective partially by inhibition of neutrophil adherence to endothelium and by neutrophil-independent mechanisms. These mechanisms of cardioprotection have been suggested to play major roles in the reduction of infarction and apoptosis after myocardial ischemia, cardioplegic arrest, and subsequent reperfusion. Adenosine has been used as an adjunct to both crystalloid and blood cardioplegia, but its potential as a cardioprotective agent has not been fully explored.

Nitric oxide is an endogenous autacoid produced primarily by the vascular endothelium. Under basal conditions, nitric oxide undergoes a rapid biradical reaction with superoxide anions to form peroxynitrite. This reaction, and hence the formation of peroxynitrite is augmented in inflammatory-like conditions such as ischemia-reperfusion injury when both substrates are present in high concentrations. Peroxynitrite has been implicated as a physiologically active toxic metabolite of nitric oxide leading to vascular and myocardial dysfunction. Recent evidence, however, has suggested that peroxynitrite may actually have beneficial properties under in vivo biological conditions when thiol-containing agents (glutathione, albumin, cysteine) agents are available to convert the peroxynitrite anion to nitrosothiols and related products demonstrating antineutrophil and cardioprotective properties. The dichotomy of physiologically relevant properties of peroxynitrite has important clinical applications with respect to nitric oxide therapy for cardiac, vascular, cerebral and pulmonary disease states. This review summarizes the biological properties of peroxynitrite relevant to the cardiovascular system.

We tested the hypothesis that selective adenosine A(3)-receptor stimulation reduces postischemic contractile dysfunction through activation of ATP-sensitive potassium (K(ATP)) channels. Isolated, buffer-perfused rat hearts (n = 8/group) were not drug pretreated (control) or were pretreated with adenosine (20 microM), 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA; A(3) agonist, 100 nM), Cl-IB-MECA + 8-(3-noradamantyl)-1,3-dipropylxanthine (KW-3902; A(1) antagonist, 5 microM), Cl-IB-MECA + glibenclamide (Glib; K(ATP)-channel blocker, 0. 3 microM), or Glib alone for 12 min before 30 min of global normothermic ischemia followed by 2 h of reperfusion. After 2 h of reperfusion, left ventricular developed pressure (LVDP, %baseline) in control hearts was depressed to 34 +/- 2%. In hearts pretreated with Cl-IB-MECA, there was a statistically significant increase in LVDP (50 +/- 6%), which was reversed with coadministration of Glib (37 +/- 1%). Control hearts also showed similar decreases in left ventricular peak positive rate of change in pressure (dP/dt). Therefore, the A(3) agonist significantly attenuated postischemic cardiodynamic injury compared with the control, which was reversed by Glib. Cumulative creatine kinase (CK in U/min) activity was most pronounced in the control group (10.4 +/- 0.6) and was significantly decreased by Cl-IB-MECA (7.5 +/- 0.4), which was reversed by coadministration of Glib (9.4 +/- 0.2). Coronary flow was increased during adenosine infusion (160% of baseline) but not during Cl-IB-MECA infusion. Effects of Cl-IB-MECA were not reversed by the specific A(1) antagonist KW-3902. We conclude that cardioprotection afforded by A(3)-receptor stimulation may be mediated in part by K(ATP) channels. Cl-IB-MECA may be an effective pretreatment agent that attenuates postischemic cardiodynamic dysfunction and CK release without the vasodilator liability of other adenosine agonists.

The normal coronary vascular endothelium (VE) tonically releases nitric oxide (NO) by converting L-arginine to citrulline by a constitutive NO synthase. Reperfusion after myocardial ischemia reduces basal and stimulated release of NO. This "vascular reperfusion injury" is mediated largely by neutrophils (PMN) through specific interactions between adhesion molecules on the endothelium and the PMN, an interaction that precedes myocyte injury. NO inhibits the PMN-mediated reperfusion injury by direct effects on both the PMN and the vascular endothelium. Cardioprotective strategies include augmentation of endogenous NO by the precursor L-arginine and the administration of exogenous NO donors at the time of perfusion, which (1) attenuates PMN adherence to the coronary artery and venous endothelium, (2) reduces PMN-mediated endothelial dysfunction, (3) reduces PMN accumulation in the area at risk, and (4) reduces infarct size. Hence, NO represents a powerful therapeutic tool with which to attenuate the consequences of ischemia-reperfusion injury on vascular injury and infarction.

Background: The cardioprotective effects of the adenosine A3 receptor in a cardioplegia model have not been described. We tested the hypothesis that infusion of the A3 receptor agonist, Cl-IB-MECA (100 nM), as a pretreatment (PTx) and/or as a cardioplegic (CP) additive reduces postischemic myocardial injury., Methods: Isolated perfused rat hearts underwent 30 minutes of normothermic ischemia, 60 minutes of intermittent hypothermic cardioplegia (10 degrees C), followed by 2 hours of reperfusion. Hearts were divided into four groups: (1) no pretreatment (PTx) and unsupplemented cardioplegia (CP) (control), (2) Cl-IB-MECA PTx and unsupplemented CP (A3-PTx), (3) no PTx and Cl-IB-MECA CP (A3-CP), or (4) Cl-IB-MECA PTx and Cl-IB-MECA CP (A3-[PTx+CP])., Results: Coronary flow was not increased after A3 pretreatment when compared to baseline values. After 2 hours of reperfusion, left ventricular developed pressure in control and A3-CP groups was depressed to 43% +/- 3% and 47% +/- 2% of baseline; while A3-PTx and A3-[PTx+CP] significantly increased left ventricular developed pressure (65% +/- 3% and 61% +/- 5%) from baseline relative to control and A3-CP. Effluent creatine kinase activity was significantly decreased by A3-PTx (1520 +/- 32 IU/L), A3-[PTx+CP] (1481 +/- 41 IU/L) from control (1734 +/- 54 IU/L) and A3-CP (1750 +/- 43 IU/L). Myocardial edema (% tissue water) was significantly less in A3-PTx (78 +/- 0.6%) and A3-[PTx+CP] (76% +/- 2%) compared with control (85% +/- 0.4%) and A3-CP (83% +/- 2%)., Conclusions: Adenosine A3 receptor stimulation as a pretreatment attenuates postischemic cardiodynamic dysfunction and creatine kinase release but has no cardioprotection as an adjunct to cold cardioplegia.

Background: This study compared clinical outcomes, length of stay, and hospital costs in patients having off-pump coronary bypass (OPCAB) versus conventional bypass surgery (CABG)., Methods: From November 1996 through April 9, 1999, OPCAB was performed for 125 consecutive patients and compared with a contemporaneous, matched control group of 625 CABG patients. Patients were matched according to age, gender, incidence of renal failure, diabetes, pulmonary disease, stroke (CVA), hypertension, peripheral vascular disease, and previous myocardial infarction. Follow-up in the OPCAB patients was 100% and averaged 15 months., Results: An average of 2.0 grafts per patient were performed in the OPCAB group (range 1-5). Ninety-four OPCAB patients (75.2%) had a total of 179 grafts assessed angiographically prior to hospital discharge. All but 4/179 grafts (2.2%) were patent, including 94 of 94 IMA grafts (100%). There were no in-hospital deaths in the OPCAB group compared to a mortality rate of 1.4% in the CABG group. OPCAB reduced postoperative hospital stay from 5.5 days in the traditional CABG group to 3.3 days (p=.002), with a decrease in hospital cost of 24% (p = .01). In addition, there was a significant reduction in the rate of transfusion in the OPCAB group (29.6%) compared to the CABG group (56.5%, p = .0001). Two OPCAB patients required postoperative intervention to improve graft patency during the follow-up period. No internal mammary grafts required revision. There was one perioperative CVA and one myocardial infarction in the OPCAB group., Conclusions: OPCAB surgery reduces hospital cost, postoperative length of stay, and transfusion rate compared to CABG. OPCAB is safe, cost effective, and associated with excellent graft patency and clinical outcomes.

Thoracoscopy has been a valuable modality for the diagnosis and treatment of pleural-based disease for almost 100 years. With the development of video technology and improved instrumentation, video-assisted thoracoscopy is the procedure of choice for effusions of unknown origin, pleural mass biopsy, and free-flowing empyema drainage when conventional techniques fail. Reported success rates have been very good for diagnosis and treatment of both benign and malignant disease, and the morbidity is low.

Background: Cardiopulmonary bypass contributes to platelet loss and dysfunction by exposure to shear stresses, foreign surfaces, and hypothermia. This study tested the hypothesis that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) accelerates recovery of the platelet population after hypothermic extracorporeal circulation (HEC)., Methods: In a blinded study, subcutaneous injections of drug or placebo were given to dogs daily for 3 days preoperatively (day 0, 1, and 2) with no drug on day 3. On day 4, the animal was prepared for arteriovenous HEC. After heparinization, HEC was initiated at 30 to 40 mL x kg(-1) x min(-1). Hypothermic extracorporeal circulation (25 degrees C) was continued for 90 minutes., Results: Preoperative platelet count (x10(3) platelets/microL) did not differ from predrug count in placebo (256+/-27 versus 255+/-20) or PEG-rHuMGDF (271+/-30 versus 291+/-38). During 60 minutes of HEC, the platelet count decreased to approximately 10% of baseline in placebo (29+/-5) and PEG-rHuMGDF (46+/-8), and recovered to approximately 70% of baseline after rewarming (90 minutes of HEC: placebo, 185+/-17, versus PEG-rHuMGDF, 169+/-22). After HEC, platelet count was greater in PEG-rHuMGDF-treated animals (p < 0.05) without altering function (aggregation responses). Within the first 6 hours after HEC, platelet count in PEG-rHuMGDF-treated animals was rising and increased to 260+/-29 (p < 0.01), but was unchanged in placebo animals (186+/-21). Thereafter, platelet count in placebo animals declined to a nadir of 124+/-15 (72 hours after HEC), whereas platelet count in PEG-rHuMGDF animals approximated the preoperative value (>200) at all times., Conclusions: Appropriately timed presurgical administration of PEG-rHuMGDF counteracts post-HEC relative thrombocytopenia without increasing platelet population and enhancing aggregation preoperatively or during extracorporeal circulation.

Background: In an attempt to avoid the deleterious effects of cardiopulmonary bypass, off-pump coronary artery bypass grafting has been rediscovered and refined. The purpose of this study was to compare clinical outcomes, length of stay, and hospital costs with coronary artery bypass grafting on cardiopulmonary bypass., Methods: Coronary artery bypass was performed on 51 patients without cardiopulmonary bypass. Patients were selected on the basis of coronary anatomy, with significant stenoses in the left anterior descending, ramus intermedius, diagonal, right coronary, acute marginal, or posterior descending territories. Outcomes were compared with those of a computer-generated matched control group having coronary artery bypass grafting on cardiopulmonary bypass (n = 248) during the same time period., Results: No preoperative differences were noted between groups. There were no deaths in the off-pump group and a mortality rate of 1.6% (4/248) in the control group. There was no incidence of stroke, myocardial infarction, or reentry for bleeding among patients in the off-pump group. There was a reduction in length of stay by 3 days (p = 0.01), blood transfusions by 50% (p = 0.0001), and hospital charges by one third (p = 0.05) in the off-pump group. Twenty-six patients had repeat coronary angiography before discharge; 41/43 grafts were widely patent, 1/43 was totally occluded, and 1/43 was narrowed by more than 50%. All internal mammary artery grafts were widely patent., Conclusions: Off-pump multivessel cardiopulmonary bypass grafting is a safe and effective means of revascularization for patients with coronary stenoses in the anterior or inferior regions, with excellent short-term patency rates and minimal morbidity.