Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting.

OBJECTIVE: Retrospective comparisons of selected patients undergoing off-pump versus conventional on-pump coronary artery bypass grafting have yielded inconsistent results and raised concerns about completeness of revascularization in off-pump coronary artery bypass grafting. METHODS: Two hundred unselected patients referred for elective primary coronary artery bypass grafting were randomly assigned to undergo off-pump coronary artery bypass grafting with an Octopus tissue stabilizer (Medtronic, Inc, Minneapolis, Minn) or conventional coronary artery bypass grafting with cardiopulmonary bypass by a single surgeon. Revascularization intent determined before random assignment was compared with the revascularization performed. All management followed strict, unbiased, criteria-driven protocols. Patients and nonoperative care providers were blinded to surgical group. RESULTS: Baseline characteristics were similar. The number of grafts performed per patient (mean +/- SD 3.39 +/- 1.04 for off-pump coronary artery bypass grafting, 3.40 +/- 1.08 for conventional coronary artery bypass grafting) and the index of completeness of revascularization (number of grafts performed/number of grafts intended, 1.00 +/- 0.18 for off-pump coronary artery bypass grafting, 1.01 +/- 0.09 for conventional coronary artery bypass grafting) were similar. Likewise, the index of completeness of revascularization was similar between groups for the lateral wall. Combined hospital and 30-day mortalities and stroke rates were similar. Postoperative myocardial serum enzyme measures were significantly lower after off-pump coronary artery bypass grafting, suggesting less myocardial injury. Adjusted postoperative thromboelastogram indices, fibrinogen, international normalized ratio, and platelet levels all showed significantly less coagulopathy after off-pump coronary artery bypass grafting. Patients undergoing off-pump coronary artery bypass grafting received fewer units of blood, were more likely to avoid transfusion altogether, and had a higher hematocrit at discharge. Cardiopulmonary bypass was an independent predictor of transfusion (odds ratio 2.42, P =.0073) by multivariate analysis. More patients undergoing off-pump coronary artery bypass grafting were extubated in the operating room and within 4 hours. Postoperative length of stay (in days) was shorter for off-pump coronary artery bypass grafting (5.1 +/- 6.5 for off-pump coronary artery bypass grafting, 6.1 +/- 8.2 for conventional coronary artery bypass grafting, P =.005 by Wilcoxon test). One patient (in the conventional coronary artery bypass grafting group) required angioplasty for graft closure within 30 days. CONCLUSIONS: When compared with conventional coronary artery bypass grafting with cardiopulmonary bypass, off-pump coronary artery bypass grafting achieved similar completeness of revascularization, similar in-hospital and 30-day outcomes, shorter length of stay, reduced transfusion requirement, and less myocardial injury.

Clinical outcomes, angiographic patency, and resource utilization in 200 consecutive off-pump coronary bypass patients.

BACKGROUND: This retrospective study compared clinical outcomes and resource utilization in patients having off-pump coronary artery bypass grafting (OPCAB) versus conventional coronary artery bypass grafting (CABG). Angiographic patency was documented in the OPCAB group. METHODS: From April 1997 through November 1999, OPCAB was performed in 200 consecutive patients, and the results were compared with those in a contemporaneous matched control group of 1,000 patients undergoing CABG. Patients were matched according to age, sex, preexisting disease (renal failure, diabetes, pulmonary disease, stroke, hypertension, peripheral vascular disease, previous myocardial infarction, and primary or redo status. Follow-up in the OPCAB patients was 93% and averaged 13.4 months. RESULTS: Hospital death (1.0%), postoperative stroke (1.5%), myocardial infarction (1.0%), and re-entry for bleeding (1.5%) occurred infrequently in the OPCAB group. There were reductions in the rates of transfusion (33.0% versus 70.0%; p < 0.001) and deep sternal wound infection (0% versus 2.2%; p = 0.067) in the OPCAB group compared with the CABG group. Angiographic assessment of 421 grafted arteries was performed in 167 OPCAB patients (83.5%) prior to hospital discharge. All but five were patent (98.8%) (93.3% FitzGibbon A, 5.5% FitzGibbon B, 1.2% FitzGibbon O). All 163 internal mammary artery grafts were patent. Off-pump coronary artery bypass grafting reduced postoperative hospital stay from 5.7 +/- 5.3 days in the CABG group to 3.9 +/- 2.6 days (p < 0.001), with a decrease in hospital cost of 15.0% (p < 0.001). CONCLUSIONS: Off-pump coronary artery bypass grafting reduces hospital cost, postoperative length of stay, and morbidity compared with CABG on cardiopulmonary bypass. Off-pump coronary bypass grafting is safe, cost effective, and associated with excellent graft patency and clinical outcomes.

The use of intrastent peripheral stent in large coronary arteries: report of three cases.

We report three cases of coronary angioplasty using the IntraTherapeutics Intrastent biliary stent. We describe a technique utilizing routine coronary angioplasty equipment including 8 Fr guiding catheters and 0.014" guidewires. This technique can be easily performed in large-diameter coronary arteries.

Coronary sinus compression as a sign of cardiac tamponade.

Coronary perforation and resultant cardiac tamponade are well-known but rare complications of percutaneous coronary interventions. We present a case that demonstrates coronary sinus compression caused by increasing pericardial pressure as a new sign of impending cardiac tamponade. This previously unreported angiographic sign preceded hemodynamic, symptomatic, and echocardiographic evidence of tamponade.

Differential cell replication within the periosteum of the pig mandibular ramus.

The periosteum is anatomically and functionally divided into two layers. The inner osteoblastic layer contributes to local appositional bone growth. The outer fibroblastic layer receives the attachments of muscles and responds to bone growth by a more global enlargement. Coordinated growth of the layers could theoretically be produced by parallel replication rates in the layers followed by migration of fibroblastic layer cells. Alternatively, replication rates in the layers could differ, those in the osteoblastic layer reflecting local apposition and those in the fibroblastic layer responding to total bone growth. To test these alternatives, we compared two regions of the pig mandible, one appositional and one resorptive, equidistant from the major growth sites of the bone. Four 2-week-old pigs were injected i.p. with 5-bromo-2'-deoxyuridine (BrdU) to label replicating cells. Three hours subsequent to BrdU injection, animals were sacrificed. The mandibles were sectioned and processed immunocytochemically for BrdU. Periosteal cell mitotic activity was analyzed selectively at the level of the mandibular foramen on the medial and lateral ramal surfaces. The proportion of labeled cells was determined by grid-point analysis. Individual differences were minor but regional differences were striking. As expected, the osteoblastic layer of the lateral surface exhibited a greater proportion of mitotic cells than did the medial surface (p = 0.037). However, no such difference was seen in the fibroblastic layer, where medial and lateral sides exhibited identical replication activity. These results strongly support the second alternative, that cell division is differentially controlled in the two periosteal layers.

Subclavian artery dissection during diagnostic cardiac catheterization: the role of conservative management.

Dissection of the subclavian artery during routine cardiac catheterization while obtaining cannulation to the left internal mammary artery is an unusual complication and to our knowledge has never been reported. Conservative management of this vascular injury can avoid the sequelae of high-risk surgical repairs made difficult by a complex operative exposure. We describe a case in which dissection of the left subclavian artery was treated conservatively with an excellent outcome.

Subclavian balloon angioplasty in the management of the coronary-subclavian steal syndrome.

The syndrome of coronary-subclavian steal presenting with angina pectoris after coronary revascularization with the mammary arteries is not common. This disorder should be suspected in post LIMA patients with blood pressure differences between the arms and confirmed by angiography. PTA of the subclavian artery via the brachial approach, in appropriately selected patients, offers potential advantages over carotid subclavian bypass including an apparent lower complication rate with equally good results. Recurrences, which are apt to be more common after PTA versus carotid subclavian bypass, are easily managed with repeat dilatation. This course of management in our patient resulted in an excellent clinical outcome without complication. This report emphasizes the importance of considering subclavian stenosis in patients with prior LIMA bypass grafting, particularly when the ipsilateral arm blood pressure is reduced. In such cases, subclavian PTA offers a reasonable nonsurgical approach for correction.

Assembly of double-shelled, viruslike particles of bluetongue virus by the simultaneous expression of four structural proteins.

Bluetongue is a disease of ruminants. The etiologic agent is bluetongue virus (BTV), a gnat-transmitted member of the Orbivirus genus of the Reoviridae. The virus has a genome of 10 double-stranded RNA species L1 to L3, M4 to M6, S7 to S10). The L2 and M5 genes of BTV which encode the outer capsid proteins VP2 and VP5, respectively, were inserted into a recombinant baculovirus downstream of duplicated copies of the baculovirus polyhedrin promoter. Insect cells coinfected with this virus plus a recombinant baculovirus expressing the two major core proteins VP3 and VP7 of BTV (T.J. French and P. Roy, J. Virol. 64:1530-1536, 1990) synthesized noninfectious, double-shelled, viruslike particles. When purified, these particles were found to have the same size and appearance as authentic BTV virions and exhibited high levels of hemagglutination activity. Antibodies raised to the expressed particles contained high titers of neutralizing activity against the homologous BTV serotype. The assembly of these bluetongue viruslike particles after the simultaneous expression of four separate proteins is indicative of the potential of this technology for the production of a new generation of viral vaccines and for the study of complex, multiprotein structures.

Endothelium-derived relaxing factors. A perspective from in vivo data.

We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions.

Biophysical studies on the morphology of baculovirus-expressed bluetongue virus tubules.

Bluetongue virus tubules were purified from Spodoptera frugiperda cells infected with a recombinant baculovirus containing the NS1 gene from bluetongue virus serotype 10, and expressed under control of the Autographa californica nuclear polyhedrosis virus polyhedrin promoter. These tubules were subjected to a variety of chemical and physical treatments and the resulting effects on tubule morphology were examined by electron microscopy. A number of morphological similarities were noted between bluetongue virus tubules and cellular microtubules despite a lack of homology between the component proteins at the primary sequence level. A possible multistranded helical configuration is proposed for the tubule structure.

High level expression of the two outer capsid proteins of bluetongue virus serotype 10: their relationship with the neutralization of virus infection.

DNA representing RNA segments 2 and 5 of bluetongue virus (BTV) serotype 10, corresponding to the genes that code for the outer capsid proteins VP2 and VP5, have been inserted into a baculovirus transfer vector in lieu of the coding region of the polyhedrin gene of Autographa californica nuclear polyhedrosis virus (AcNPV). After co-transfection of Spodoptera frugiperda cells with wild-type AcNPV DNA in the presence of the recombinant transfer vector DNAs polyhedrin-negative recombinant baculoviruses were recovered. When S. frugiperda cells were infected with these recombinant viruses proteins of similar size and antigenic properties to BTV VP2 and VP5 were synthesised. The recombinant VP2, but not the recombinant VP5, was shown to be capable of inducing antibodies that neutralized the infectivity of BTV-10 in vitro.

Similar responsiveness of smooth muscle of the canine basilar artery to EDRF and nitric oxide.

Experiments were designed to compare the reactivity of canine basilar arteries to endothelium-derived relaxing factor (EDRF) and nitric oxide. Preparations with endothelium activated by bradykinin were used to study relaxations induced with EDRF, whereas the inhibitory effect of nitric oxide was studied in preparations without endothelium. All experiments were performed in the presence of indomethacin. EDRF- and nitric oxide-induced relaxations were significantly augmented in the presence of superoxide dismutase plus catalase but were reduced in the presence of methylene blue, LY 83583, and hemoglobin. M & B 22984 did not affect relaxations to either EDRF or nitric oxide. These results indicate that in the canine basilar artery EDRF is not an oxygen-derived free radical. The similar responsiveness of the basilar artery to EDRF and nitric oxide is consistent with the proposal that in the canine basilar artery nitric oxide is the factor.

Direct vasoconstriction and endothelium-dependent vasodilation. Mechanisms of acetylcholine effects on coronary flow and arterial diameter in patients with nonstenotic coronary arteries.

An endothelium-dependent vasodilator response to acetylcholine has been described recently in patients with coronary artery disease. Those studies determined responses only of large epicardial arteries. Our study was designed to determine the integrated effects of acetylcholine on epicardial diameter, coronary flow, and vascular resistance. Patients (n = 64) with nonstenotic epicardial coronaries underwent coronary angiography with simultaneous recording of coronary flow velocity using a 3F subselective Doppler catheter. Measurements of epicardial arterial cross-sectional area (ECA), velocity, estimated flow (velocity times area), and vascular resistance were made before and after bolus administration of acetylcholine (100 micrograms i.c.). Similar measurements were made after papaverine (12-15 mg i.c.), a nonendothelium-dependent vasodilator. Acetylcholine resulted in a reduction of ECA of 19 +/- 3%, whereas papaverine increased ECA by 9 +/- 2%. Estimated flow increased 69 +/- 12% after acetylcholine and 147 +/- 12% after papaverine. Resistance fell after both agents (acetylcholine, -17 +/- 13%; papaverine, -61 +/- 2%). Transvascular resistance fell after acetylcholine in all but five patients. These patients had dramatic epicardial artery constriction (40 +/- 8% decrease in ECA). The effect of acetylcholine on both ECA and resistance was blocked by atropine (1 mg i.c.). Nitroglycerin (300 micrograms i.c.) resulted in epicardial dilatation (7.5 +/- 2.8%) in the same patients in whom acetylcholine caused constriction (-11.2 +/- 3.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo bioassay of endothelium-derived relaxing factor.

We devised a technique for the in vivo assay of endothelium-derived relaxing factor (EDRF) from cerebral microvessels. We used anesthetized cats equipped with two cranial windows. One window (assay window) was subjected to muscarinic blockade with atropine to inhibit the direct effects of acetylcholine. EDRF production was induced in the donor window by superfusion with acetylcholine. The superfusate was then directed through the assay window with a delay of 6 s where it caused vasodilation equal to that seen in the donor window. The dilation was eliminated by lengthening the transit time from the donor to the assay window to greater than 2 min or by muscarinic blockade with atropine in the donor window but not by indomethacin in the donor window. It was also inhibited by hemoglobin and methylene blue or by selective damage to the endothelium of the vessels in the donor window with topical application of arachidonate or hydrogen peroxide. We conclude that the vasoactivity of the superfusate is due to EDRF released by acetylcholine from cerebral microvessels.

Independent blockade of cerebral vasodilation from acetylcholine and nitric oxide.

We investigated the mechanisms of cerebral arteriolar dilation from topical acetylcholine and the nitrovasodilators, sodium nitroprusside, nitroglycerin, and nitric oxide, in anesthetized cats equipped with cranial windows for the observation of the cerebral microcirculation. Acetylcholine-mediated dilation was eliminated by topical methylene blue. This blockade was reversed by either topical superoxide dismutase, catalase, or deferoxamine. Nitroprusside- and nitric oxide-induced dilation were not affected by methylene blue. Vasodilation from the nitrovasodilators was significantly diminished by topical nitro blue tetrazolium, but acetylcholine-mediated dilation was unaffected by nitro blue tetrazolium. Neither methylene blue nor nitro blue tetrazolium affected dilation from topical 8-bromoguanosine 3',5'-cyclic monophosphate. These data show that methylene blue selectively blocks acetylcholine-mediated endothelium-dependent dilation by generating oxygen radicals. The mechanism involved is hydroxyl radical-mediated oxidation of endothelium-derived relaxing factor. Nitro blue tetrazolium selectively blocks dilation from the endothelium-independent nitrovasodilators. The endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is not nitric oxide.

Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer.

A comparative study of reduced glutathione (GSH) concentrations and activities of GSH related-enzymes in urinary bladder transitional epithelium (UBTE), urinary bladder nontransitional tissue (UBNT), and liver of the rabbit, was carried out to investigate the reasons for the susceptibility of UBTE towards peroxidase-mediated chemical carcinogenesis. Cooxidative activation of chemical carcinogens by prostaglandin H synthase occurs at high levels in UBTE and minimally in UBNT. Other peroxidases are also likely to activate carcinogenic xenobiotics in the urinary bladder. GSH concentrations in UBTE and UBNT were low compared to that in the liver. gamma-Glutamyl transpeptidase activities were much lower in UBTE and in UBNT than those in the liver. Activities of selenium-dependent and selenium-independent glutathione peroxidases were very low in UBTE and UBNT. Cytosolic glutathione S-transferase activity towards 1,2-epoxy-(4-nitrophenoxy)propane was very low in UBTE. Microsomal glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene was much lower in UBTE than in the liver. We propose that the low GSH concentration and diminished activities of glutathione peroxidases, gamma-glutamyl transpeptidase, and certain isozymes of glutathione S-transferase could be responsible for the vulnerability of UBTE towards chemical carcinogenesis.

Differential distribution of glutathione and glutathione-related enzymes in rabbit kidney. Possible implications in analgesic nephropathy.

Whole tissue reduced glutathione (GSH) concentration was found to be lowest in rabbit renal inner medulla and progressively higher in outer medulla and cortex. Activities of cytosolic glutathione reductase in inner medulla and outer medulla were similar, and each was only approximately 50% of that of cortex. Whole tissue and microsomal gamma-glutamyl transpeptidase activities were high in cortex and outer medulla but were low in inner medulla. Cytosolic activity of selenium-dependent glutathione peroxidase ( GPx -I) was similar in both outer medulla and inner medulla but was only 50% of that of cortex. Activity of cytosolic selenium-independent glutathione peroxidase ( GPx -II) was highest in cortex and lowest in inner medulla (approximately 15% of cortex and approximately 50% of outer medulla). Cytosolic glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene as substrate was high in all three regions of kidney. With 1,2-dichloro-4-nitrobenzene and 1,2-epoxy-(4-nitrophenoxy)propane as substrates, cytosolic glutathione S-transferase activities were very low in cortex, outer medulla, and inner medulla. Microsomal activities of glutathione reductase, GPx -I, GPx -II and glutathione S-transferases were much lower than activities of corresponding cytosolic enzymes. Activities of the glutathione peroxidases in renal inner medulla would hence be expected to cause little interference to prostaglandin endoperoxide synthetase mediated cooxidative activation of paracetamol. It has been demonstrated that the paracetamol metabolite can react rapidly with GSH, forming not only glutathione conjugate but also paracetamol itself and oxidized glutathione. Low GSH concentrations, as well as low activities of glutathione reductase, GPx -I, GPx -II, and gamma-glutamyl transpeptidase, may therefore render the inner medullary region of kidney particularly vulnerable to paracetamol-related analgesic nephropathy.

The growth of nerves in relation to the formation of premuscle cell masses in the developing chick forelimb.

A description is given of the growth of segmental nerves 13 to 16 (SN13 to SN16) from the brachial myotomes into the ventral and dorsal premuscle cell masses of the chick forelimb. At stage 25 (Hamburger and Hamilton, '51), segmental nerves have converged to form two nerve trunks which enter the ventral and dorsal premuscle cell masses. These nerves grow into the limb, parallel to its proximodistal axis. The nerve trunk in the ventral compartment, the brachialis longus inferior (bli n), grows on the brachial artery as far as the metacarpals. The nerve trunk in the dorsal compartment, the brachialis longus superior (bls n), grows on the precartilage adjacent to a dorsal premuscle density as far as the metacarpals. The brachialis longus inferior and superior nerve trunks give rise to a number of nerves during their growth to the metacarpals. Each of these nerves appears at the time of formation of a new premuscle cell density. At late stage 25, a posterior and ventral premuscle density forms in the middle of the stylopodium; posterior fascicles of the bli n diverge at this level and grow toward this new density to form the ulnar nerve. By stage 26 a posterior and ventral premuscle density is prominent over the bli n, at the junction of the stylopodium and the zeugopodium; ventral fascicles of the bli n grow into this density to form the flexor digitorum profundus nerve. At this stage a posterior and dorsal premuscle density forms just beyond the junction of the stylopodium and zeugopodium. Posterior fascicles of the bls n diverge at this level and grow toward this density to form a nerve from which the extensor metacarpi ulnaris, extensor digitorum communis, and radialis laterialis nerves are destined to form. At stage 29 the premuscle cell masses of the autopodium have formed. The remaining nerve fascicles comprising the bls n (the radialis profundus nerve) grow into the autopodium and branch to innervate each of the dorsal premuscles. The remaining nerve fascicles comprising the bli n (the middle nerve) grow into the autopodium and branch to innervate each of the ventral premuscles.

Purification and characterization of a pig intestinal alpha-limit dextrinase.

Mucosa from the duodenal and jejunal regions of pig small intestine was repeatedly freeze-thaw treated to solubilize an enzyme preparation, enriched in maltase, glucoamylase and alpha-limit dextrinase activities; isomaltase and sucrase remained essentially insoluble during the treatment. Chromatographic procedures, including ion-exchange, gel filtration and hydroxylapatite chromatography of the solubilized preparation, brought to homogeneity an alpha-glucosidase active towards maltose, alpha-limit dextrins and starch in decreasing order, with only a very weak capacity to hydrolyse alpha-1,6-linkages. Michaelis constants and maximal velocities, as well as relative rates of hydrolysis of several substrates, including maltodextrins and alpha-limit dextrins, were determined and served to characterize what seems to be a rather specific alpha-1,4-glucosidase. The participation of this enzyme in the hydrolysis of alpha-limit dextrins and more generally in pathways for starch breakdown in the pig digestive tract is examined and discussed.