The antiproliferative activity of DMDC is modulated by inhibition of cytidine deaminase.

We showed that the efficacy of the new 2'-deoxycytidine (2'-dCyd) analogue antimetabolite 2'-deoxy-2'-methylidenecytidine (DMDC) correlates well with tumor levels of cytidine (Cyd) deaminase in human cancer xenograft models. DMDC was highly effective in tumors with higher levels of Cyd deaminase, whereas lower levels yielded only slight activity. In contrast, gemcitabine (2',2'-difluorodeoxycytidine), which has action mechanisms similar to those of DMDC, is only slightly active in tumors with higher levels of the enzyme. In the present study, we investigated the roles of Cyd deaminase in the antitumor activity of the two 2'-dCyd antimetabolites in 13 human cancer cell lines. Tetrahydrouridine, an inhibitor of Cyd deaminase, reduced the antiproliferative activity of DMDC (P = 0.0015). Furthermore, tumor cells transfected with the gene of human Cyd deaminase become more susceptible to DMDC both in vitro and in vivo. These results indicate that Cyd deaminase is indeed essential for the activity of DMDC. In contrast, the antiproliferative activity of gemcitabine was increased to some extent by tetrahydrouridine (P = 0.0277), particularly in tumor cell lines with higher levels of Cyd deaminase. This suggests that higher levels of Cyd deaminase may inactivate gemcitabine. Among nucleosides and deoxynucleosides tested, only dCyd, a natural substrate of both Cyd deaminase and dCyd kinase, suppressed the antiproliferative activity of DMDC by up to 150-fold. Because the Vmax/Km of DMDC for dCyd kinase was 8-fold lower than that for dCyd, the activation of DMDC to DMDC monophosphate (DMDCMP) by dCyd kinase might be competitively inhibited by dCyd. In addition, the dCyd concentrations in human cancer xenografts were inversely correlated with levels of Cyd deaminase activity. It is therefore suggested that higher levels of Cyd deaminase reduce the intrinsic cellular concentrations of dCyd in tumors, resulting in efficient activation of DMDC to DMDCMP by dCyd kinase. These results indicate that the efficacy of DMDC may be predicted by measuring the activity of Cyd deaminase in tumor tissues before treatment starts and that DMDC may be exploited in a new treatment modality: tumor enzyme-driven cancer chemotherapy.

Analysis by early angiography of right internal thoracic artery grafting via the transverse sinus : predictors of graft failure.

BACKGROUND: There has been debate regarding whether technically demanding right internal thoracic artery (RITA) grafting via the transverse sinus can be extensively applied to patients in high-risk groups, such as patients with a small body size, elderly patients, and woman with relatively smaller coronary artery and internal thoracic artery (ITA) diameters. METHODS AND RESULTS: Of the 1456 patients who underwent isolated coronary artery bypass grafting between January 1989 and December 1998 at Kumamoto Central Hospital, 393 patients (mean age, 62.4+/-9.0 years) with the RITA anastomosed to the major branches of the circumflex artery were studied. Left ITA grafting was performed in 384 patients, and in 369, the in situ left ITA was anastomosed to the left anterior descending coronary artery using standard methods. Early postoperative angiography was performed in 381 patients. The RITA was occluded in 4 patients, and string-like artery and significant stenosis were present in 11 and 7 patients, respectively; RITA graft patency was thus 94.1%. Of the preoperative variables and angiographic data, simple and multiple logistic regression analyses identified decreased severity of native stenosis, diffuse sclerosis of native vessels, and residual side branches of the ITA as independent predictors of nonfunctional grafts. The method of ITA grafting did not influence the patency of the graft. CONCLUSIONS: The excellent patency rate demonstrated by this study, the largest angiographic study to date of RITA grafting via the transverse sinus, indicates that this technique can provide reliable revascularization of the left ventricle and that it has the potential to be applied to a wide variety of patients with diseased circumflex arteries.

Ultrasonographic demonstration of manipulation-related aortic injuries after cardiac surgery.

OBJECTIVES: This study was performed to evaluate the frequency and risk factors associated with new aortal lesions induced by surgical manipulation and their correlation with postoperative stroke. BACKGROUND: Little is known about the causative mechanism of intraoperative atheroembolism after cardiac surgery. METHODS: Epiaortic echocardiography was performed before cannulation and after decannulation in 472 patients undergoing cardiac surgery with extracorporeal circulation. RESULTS: A new lesion in the ascending aortal intima was identified in 16 patients (3.4%) after decannulation. New lesions were severe, with mobile lesions or disruption of the intima in 10 patients. Six of the severe lesions were related to aortic damping and the other four to aortic cannulation. Three patients in this group had postoperative stroke. Univariate analysis identified only the maximal thickness of the atheroma near the aorta manipulation site as a predictor of new lesions. The incidence of new lesions was 11.8% if the atheroma was approximately 3 to 4 mm thick and as high as 33.3% if the atheroma was >4 mm, but only 0.8% when it was <3 mm. Total 10 patients (2.1%) sustained neurological complications. Arteriosclerosis obliterans, atherosclerosis of the aorta and new mobile lesions were identified as predictors of strokes. CONCLUSIONS: This study demonstrated an association between new lesions created by surgical maneuvers and postoperative stroke. Embolic strokes were more likely to occur if new lesions were complicated with intimal disruption, especially of the mobile type. Modifications in surgical procedures will be needed if thick plaque (especially >4 mm) is noted near the manipulation site.

High susceptibility of human cancer xenografts with higher levels of cytidine deaminase to a 2'-deoxycytidine antimetabolite, 2'-deoxy-2'-methylidenecytidine.

2'-Deoxy-2'-methylidenecytidine (DMDC) is a new 2'-deoxycytidine (dCyd) antimetabolite. The present study compared its antitumor activities with those of 2',2'-difluorodeoxy-cytidine (gemcitabine) in 15 human cancer xenograft models. DMDC was highly resistant to cytidine (Cyd) deaminase, which deaminates the dCyd analogues to inactive molecules, whereas gemcitabine was susceptible to the enzyme. Given p.o., high antitumor activity with therapeutic index of more than 10 was found with DMDC in 7 of 15 xenograft lines. In contrast, gemcitabine given i.v. or p.o. was highly effective in 4 of 15 human cancer xenograft lines. The antitumor spectrum of these compounds was quite different, although their molecular targets are reported to be similar. DMDC was highly effective in tumors with higher levels of Cyd deaminase activity, whereas it showed only slight activity in those with lower levels of Cyd deaminase. In contrast, gemcitabine appeared to be less effective in tumors with high levels of Cyd deaminase. We also investigated the correlation with the susceptibility to the two dCyd antimetabolites and dCyd kinase activity in tumors, but none was observed. Cyd deaminase activity was found to be high in tumor tissues from various types of human cancers thus far tested, such as colorectal cancer and non-small cell lung cancer. Such cancer types or individual patients who have tumors with high activity of the enzyme may be targets for DMDC therapy.

Requirement of the two-headed structure for the phosphorylation dependent regulation of smooth muscle myosin.

It is known for smooth muscle myosin that while acto-HMM ATPase activity is regulated by phosphorylation, acto-S-1 ATPase activity is not regulated. To clarify the heavy chain structure required for the regulation, smooth muscle myosin containing 7 different lengths of the S-2 portion were expressed in Sf9 insect cells using Baculovirus expression system. Myosin containing longer than 991 residues of heavy chain formed a stable two-headed structure while myosin with shorter than 944 residues of heavy chain formed a single-headed structure, indicating that the residues Gln945-Asp991 are critical for the formation of the two-headed structure. The actin activated ATPase activity of myosin mutants having a two-headed structure was activated by phosphorylation while that of myosin mutants that failed to form the two-headed structure was completely independent of phosphorylation. These results suggest that the two-headed structure is critical for the phosphorylation-dependent regulation.

Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue.

Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel oral fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FU) selectively in tumours through a cascade of three enzymes. The present study investigated tissue localisation of the three enzymes in humans, which was helpful for us to design the compound. Carboxylesterase was almost exclusively located in the liver and hepatoma, but not in other tumours and normal tissue adjacent to the tumours. Cytidine (Cyd) deaminase was located in high concentrations in the liver and various types of solid tumours. Finally, thymidine phosphorylase (dThdPase) was also more concentrated in various types of tumour tissues than in normal tissues. These unique tissue localisation patterns enabled us to design capecitabine. Oral capecitabine would pass intact through the intestinal tract, but would be converted first by carboxylesterase to 5'-deoxy-5-fluorocytidine (5'-dFCyd) in the liver, then by Cyd deaminase to 5'-deoxy-5-fluorouridine (5'-dFUrd) in the liver and tumour tissues and finally by dThdPase to 5-FU in tumours. In cultures of human cancer cell lines, the highest level of cytotoxicity was shown by 5-FU itself, followed by 5'-dFUrd. Capecitabine and 5'-dFCyd had weak cytotoxic activity only at high concentrations. The cytotoxicity of the intermediate metabolites 5'-dFCyd and 5'-dFCyd was suppressed by inhibitors of Cyd deaminase and dThdPase, respectively, indicating that these metabolites become effective only after their conversion to 5-FU. Capecitabine, which is finally converted to 5-FU by dThdPase in tumours, should be much safer and more effective than 5-FU, and this was indeed the case in the HCT116 human colon cancer and the MX-1 breast cancer xenograft models.

Effect of centrifugal force and catecholamines on glycosaminoglycans synthesis of vascular smooth muscle cells in culture.

To evaluate the effect of hypertension on glycosaminoglycan (GAG) synthesis, cultured vascular smooth muscle cells (CVSMCs) from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were exposed to centrifugal forces and catecholamines. GAG synthesis of CVSMCs was measured by the incorporation of [3H]glucosamine into GAGs which were secreted into the culture medium for 24 h. Basal level of GAG synthesis was much higher in SHR than in WKY, when expressed in terms of DNA contents. When exposed to centrifugal force, CVSMCs from rats of both strains synthesized more GAGs. GAG synthesis was enhanced by both noradrenaline (NA) and adrenaline (Ad) in WKY. The enhanced GAG synthesis in WKY by NA or Ad was prevented by pretreatment with propranolol, but not prazosin. In SHR, NA and Ad did not enhance GAG synthesis at this concentration of catecholamines. However, the effects of propranolol or prazosin on GAG synthesis in SHR, when incubated with either NA or Ad, were compatible with the phenomena observed in WKY. Adding dibutyryl cyclic AMP to the culture medium enhanced GAG synthesis in rats of both strains. These data suggest that not only the mechanical stress of high intra-arterial pressure but also beta receptor stimulation, via increasing cyclic AMP, enhance GAG synthesis of vascular smooth muscle cells in hypertension.

Enhanced DNA synthesis of cultured vascular smooth muscle cells from spontaneously hypertensive rats. Difference of response to growth factor, intracellular free calcium concentration and DNA synthesizing cell cycle.

It is widely reported that cultured vascular smooth muscle cells (CVSMCs) from spontaneously hypertensive rats (SHR) show enhanced proliferation compared with cells from Wistar-Kyoto rats (WKY). The present studies were designed to find out whether this exaggerated proliferation in SHR is determined genetically and, if so, to evaluate the mechanism on the cell cycle. (1) Incorporation of [3H]thymidine into DNA was enhanced in CVSMCs from 3- and 12-week-old SHR compared with WKY but not in CVSMCs from DOCA-salt hypertensive rats compared with the cells from sham-operated rats. (2) DNA synthesis in SHR cells was enhanced further by addition of insulin (which is considered to be a progression factor) but not by arginine-vasopressin (AVP; considered to be a competence factor) or by angiotensin II (AII). On the other hand, insulin, AVP and AII significantly augmented DNA synthesis in WKY cells. (3) Intracellular free calcium concentration was slightly, but significantly, higher in SHR cells. (4) An increase in the population of DNA-synthesizing S-phase cells and decrease in (G2 + M)-phase cells in SHR were observed by flowcytometry. These data suggest (1) that enhanced DNA synthesis in CVSMCs from SHR is determined genetically, (2) that enhanced DNA synthesis in CVSMCs from SHR is largely dependent on an increased proportion of S-phase cells and (3) that this increase in S-phase cells in CVSMCs from SHR could be due to enhanced competence gene expression in SHR cells. (4) The increased intracellular free calcium concentration is compatible with an activation of the inositol-trisphosphate pathway.

In situ right internal thoracic artery graft via transverse sinus for revascularization of posterolateral wall: early results in 116 cases.

The in situ right internal thoracic artery graft brought through the transverse sinus was used to revascularize the posterolateral wall in 116 patients. Its advantages were assessed retrospectively. The graft was anastomosed to the circumflex marginal branch in 70 patients (60%) or to the posterolateral branch in 41 patients (35%). One patient died (mortality rate 0.9%). Perioperative myocardial infarction occurred outside the territory of the right internal thoracic artery graft in 10 patients, four of whom required mechanical support for hemodynamic deterioration. Postoperative early angiography in 114 patients found the graft to be patent in 97.4%. The ratio of the diameter of the right internal thoracic artery to that of the recipient marginal branch was 0.94 +/- 0.18 (n = 69), and that to the posterolateral branch was 0.88 +/- 0.18 (n = 37) (not significantly different). Results of a postoperative stress test were abnormal in one patient (1/96 tested patients). This retrospective study suggests that the right internal thoracic artery brought through the transverse sinus to revascularize the posterolateral wall provided excellent early patency and good clinical results, even to the most distally located branches. This continues to be our procedure of choice for patients with multivessel coronary disease.

Contribution of calmodulin and protein kinase C to renin release in spontaneously hypertensive rats.

This study was designed to evaluate the contribution of calmodulin and protein kinase C to renin release from isolated glomeruli of spontaneously hypertensive rats (SHR, Okamoto and Aoki). Male 7-week-old SHR and age-matched control Wistar-Kyoto rats (WKY) were used in this study. Isolated glomeruli were sealed in the superfusion chamber and perfused with Krebs-Ringer solution at a constant flow of 0.3 mL/min. Renin release was increased by calmodulin inhibitor, W-7, and protein kinase C inhibitor, H-7, in both SHR and WKY. SHR showed higher maximal levels of renin release by W-7 and lower maximal levels by H-7 compared to WKY. These results indicate that calmodulin and protein kinase C play inhibitory roles in renin release from juxtaglomerular cells. The calmodulin-mediated suppression mechanism in renin release appears to be augmented in the SHR, whereas the protein kinase C-mediated system is attenuated.

Responses of cytosolic free calcium to ADP in platelets of spontaneously hypertensive rats.

Abnormalities of Ca2+ handling have been reported in patients with essential hypertension and in spontaneously hypertensive rats (SHR). In this study, responses of cytosolic Ca2+ to ADP in platelets of SHR were examined. Four- and seven-week-old male SHR and age- and sex-matched Wistar-Kyoto rats (WKY) were used. Basal levels of the intracellular Ca2+ concentration in platelets and responses to ADP were estimated using fluorescent indicator fura-2 in the medium containing 1 mmol/L CaCl2 and Ca2(+)-free buffer with 1 mmol/L EGTA. Basal levels of platelet cytosolic Ca2+ of SHR were significantly higher than those of WKY at 4 and 7 weeks of age in the presence of external Ca2+. However, no significant difference was observed in basal levels of platelet cytosolic Ca2+ in the Ca2(+)-free EGTA-containing buffer between SHR and WKY. The peak cytosolic Ca2+ concentration evoked by ADP was significantly diminished in SHR compared with WKY in the absence of external Ca2+, whereas the responses of platelet cytosolic Ca2+ to ADP were similar in SHR and WKY in the presence of external Ca2+. These results suggest that release from intracellular Ca2+ store is reduced in SHR and that the regulation of cytosolic Ca2+ in SHR is more dependent on extracellular Ca2+ compared with WKY.

Bilateral internal thoracic artery use for dialysis patients: does it increase operative risk?

BACKGROUND: The efficacy and risk of using the bilateral internal thoracic artery (BITA) for coronary artery bypass grafting in dialysis patients is virtually unknown. METHODS: Twenty-five patients on dialysis who underwent coronary artery bypass grafting using the BITA were retrospectively studied (BITA group). For comparison purposes, 52 patients on dialysis who underwent coronary artery bypass grafting using the left ITA were selected (LITA group). RESULTS: No wound healing problems occurred in the BITA group. Mean postoperative bleeding volume was 1,427 +/- 808 mL and 800 +/- 508 mL in the BITA and LITA groups, respectively (p = 0.00009). Blood transfusions for the BITA and LITA groups required an average of 6.8 and 6.2 units of packed red blood cells, respectively, with no significant difference. Five patients in the BITA group (20%) showed severe atherosclerotic deterioration of the ascending aorta, precluding clamping. Hospital mortality was 4% (1 of 25 patients) in the BITA group and 7.7% (4 of 52 patients) in the LITA group, with no significant difference (p = 0.49). CONCLUSIONS: In patients on dialysis, especially those with severe atherosclerotic or calcified deterioration of the ascending aorta, coronary artery bypass grafting using BITA grafting (arterial in situ conduits) may offer the easiest and most suitable solution without increased operative risk.

Growth potential of left internal thoracic artery grafts: analysis of angiographic findings.

BACKGROUND: The growth potential of the internal thoracic artery (ITA) is still undetermined, and little is known about the long-term effects of anastomosing it to the coronary artery. METHODS: Fifty-three patients whose left ITA (LITA) had been anastomosed to the left anterior descending (LAD) coronary artery underwent coronary angiography within 1 month of operation and in late follow-up (mean interval: 4.5 +/- 1.5 years). The diameter ratios of LITA to LAD were designated as the matching ratio. RESULTS: In follow-up, the diameter of the LITA increased from 1.83 +/- 0.40 to 2.46 +/- 0.53 mm in the 29 patients with progressive proximal native coronary stenosis. However, late results indicate that the matching ratio did not vary according to the location of the LITA anastomosis on the LAD (proximal portion: 1.13 +/- 0.16, distal portion 1.19 +/- 0.13), and reached an upper limit of about 1.4. CONCLUSIONS: Growth potential of the LITA is limited by the diameter of the coronary artery onto which it is anastomosed. The most effective procedure for enhancing the growth potential of the LITA is to anastomose as proximally as possible onto the LAD.

Bileaflet mechanical valve (St. Jude Medical valve) replacement in long-term dialysis patients.

BACKGROUND: Few reports exist on the results of bileaflet mechanical valve (St. Jude Medical prosthesis; St. Jude Medical, Inc, St. Paul, MN) replacement in long-term dialysis patients. METHODS AND RESULTS: We retrospectively reviewed 12 patients, ranging in age from 50 to 86, undergoing long-term renal dialysis who had also undergone mechanical valve replacement at our institution. Operative procedures included aortic valve replacement, aortic and mitral valve replacement, aortic valve replacement and mitral annuloplasty, mitral valve replacement, and modified Bentall's operation. There was 1 hospital death (8.3%). During the mean follow-up period of 37.1 months (range: 5-87 months), there were 2 noncardiac late deaths. Bleeding from the esophageal varix and from a duodenal ulcer occurred in 1 patient with end-stage liver cirrhosis. There were no other major cases of bleeding or cerebrovascular accidents. There were no valve-related complications. All the survivors demonstrated excellent clinical improvement under the NYHA functional classification. CONCLUSIONS: Our study demonstrated good early and long-term results of mechanical valve replacement in patients undergoing long-term dialysis. These favorable results support the continued use of mechanical valves in dialysis patients.

Long-term results of bilateral internal thoracic artery grafting.

BACKGROUND: Little is known about the long-term results of the uniform group of patients who had bilateral internal thoracic artery (ITA) grafting with the method of left ITA-to-left anterior descending coronary artery and right ITA-to-circumflex artery. METHODS: Late follow-up study was performed in the first consecutive 203 patients (mean age, 62.6 +/- 9.1 years) who underwent isolated coronary artery bypass grafting with the left ITA anastomosed to the left anterior descending coronary artery and the right ITA to major branches of the circumflex artery. The patients were grouped according to the patency of ITA grafts demonstrated by early postoperative angiography (Both patent (BP) group, 168 patients: both ITAs showed complete patency; Not patent (NP) group, 23 patients: at least one ITA was dysfunctional). RESULTS: Actuarial 7-year survival in all patients was 89.3% +/- 3.1%. The cumulative probability of event-free survival for cardiac death, myocardial infarction, intervention, and angina at 7 years was 96.6% +/- 1.8%, 98.0% +/- 1.5%, 86.7% +/- 3.2%, and 90.7% +/- 2.9%, respectively. NP group had more myocardial infarction and angina than the BP group, but was not statistically significant. Because of failed grafts at the early angiography, intervention was performed more frequently in NP group (p < 0.01). CONCLUSIONS: Our results of actuarial 7-year survival and the cumulative probability of event-free survival were at least comparable to the results of other similar studies using bilateral ITA. The freedom from angina appeared to be better than in the previous study. Overall our study supports the continued use of this method of ITA grafting.

Coronary artery bypass grafting in dialysis patients.

BACKGROUND: To analyze the characteristic problems of coronary artery bypass grafting in patients with chronic renal failure. METHODS: Fifty-one consecutive dialysis patients who required isolated coronary bypass grafting over a 9-year period were studied retrospectively. RESULTS: Nine patients (18%) had emergent operation, 4 of whom had intraaortic balloon counterpulsation instituted preoperatively. A mean of 3.3 +/- 1.0 bypasses per patient were grafted; 14 patients (27%) had bypass with two arterial grafts, 13 (25%) of which used left internal mammary artery and gastroepiploic artery and one of which used bilateral internal mammary artery grafts. A mean of 4.2 +/- 2.6 coronary artery segments were calcific according to American Heart Association classification. Eight patients (16%) required operative modifications to avoid manipulating calcific plaques on the ascending aorta. Four patients (7.8%) died, and 15 had nonlethal complications. The actuarial survival rates in 47 hospital survivors at 1, 3, and 5 years were overall 89%, 84%, and 71%, respectively, and estimates for cardiac deaths 93%, 93%, and 82%, respectively. Cardiac event-free rates after coronary artery bypass grafting were 83% and 65% for 3- and 5-year periods, respectively. CONCLUSIONS: Calcification of coronary arteries and the ascending aorta is a serious problem in long-term dialysis patients. However using arterial grafts, preferentially, in situ, seems to provide a practical alternative to minimize manipulating the ascending aorta during coronary artery bypass grafting, with acceptable perioperative morbidity and mortality rates and long-term survival.

Extracorporeal circulation before and after ultrasonographic evaluation of the ascending aorta.

BACKGROUND: To further gain insight into atheroembolization mechanisms epiaortic two-dimensional echocardiographic evaluation before extracorporeal circulation and after decannulation may be helpful. METHODS: Epiaortic two-dimensional echocardiography was performed before cannulation and after decannulation in 188 (124 men) patients (mean age, 67.7 years; range, 43 to 86 years) undergoing operation with extracorporeal circulation for ischemic heart disease during 1996. RESULTS: After decannulation, a new intimal lesion was recognized in 10 of 188 patients (5.3%): mobile type in 5 patients (3 ending with a stroke [60%], 2 having brain computed tomographic scans compatible with embolism), intimal tear in 2, and intimal irregularity in 3 patients. Stroke occurred in a significantly smaller number of patients (2 of 178 [1.1%]; p < 0.001) without new lesions. CONCLUSIONS: Clamp- or cannula-induced new lesions, especially of mobile type, are often complicated by postoperative stroke. Aggressive surgical technique modifications may need to be considered to avoid creating new lesions, particularly of the mobile type.

The impact of chronic renal failure on atherosclerosis of the internal thoracic arteries.

BACKGROUND: Little is known about the impact of renal failure on atherosclerotic changes in the internal thoracic artery (ITA). METHODS: A total of 20 consecutive patients on chronic dialysis who underwent coronary artery bypass grafting (CABG) during April 1998 through September 1999 were investigated. The 20 control patients were selected from the same interval to rigorously match risk factors. Atherosclerosis of the ITA collected from each patient was analyzed using the subjective evaluation proposed by Kay and colleagues. RESULTS: There were no cases of greater than 25% atherosclerotic luminal narrowing among a total of 35 ITA specimens from dialysis patients. The degree of atherosclerosis was not significantly different from that of the specimens from matched patients (p = 0.18). No calcification was found in ITA grafts either microscopically or macroscopically. The number of elastic lamellae, an index of the elasticity of the ITA graft, was not significantly different from those obtained from the matched patients. Analysis of preoperative coronary angiography revealed that coronary calcification was significantly more frequent in dialysis patients (15 patients, 75%) than in matched patients (p < 0.05). By analysis of postoperative angiography in dialysis patients, no evidence of atherosclerotic changes was found in 28 opacified ITAs. In addition, despite the presence of calcification in the native coronary, no calcification was evident along the entire length of the ITAs. CONCLUSIONS: This study revealed the minimal impact of chronic renal failure on atherosclerotic changes in the ITA. The results of this study support the continued use of ITA grafting in dialysis patients.

Technical aspects and outcome of in situ right internal thoracic artery grafting to the major branches of the circumflex artery via the transverse sinus.

BACKGROUND: Little is known about the anatomic limitations of in situ right internal thoracic artery (RITA) grafting to the circumflex artery. METHODS: To evaluate the technical aspects and outcome of revascularization of the proximal and distal major branches of the circumflex artery (obtuse marginal [OM] branch and posterolateral [PL] branch), a total of 145 patients who possessed a graftable branch of the circumflex artery were enrolled into the prospective project. There were 73 patients who had the PL branch as a primary target and 72 patients with OM branches, which were allocated by a blinded observer who reviewed the preoperative angiography. RESULTS: Changes of primary target vessels were required in 9 patients (6.2%), yielding an overall success rate of RITA grafting of 93.8%. The success rates of RITA grafting to the OM branch and the PL branch were 95.8% (69/72; CI 88.3% to 99.1%) and 91.7% (67/73; CI 83.0% to 96.9%), respectively. The univariate analysis identified grafting under hypothermic ventricular fibrillation as predictors of inability to use in situ RITA grafting for revascularization of the circumflex artery. RITA grafting to the PL branch is not identified as a predictor. Postoperative angiography in 136 patients revealed only one occlusion (0.75%) of the RITA graft anastomosed to the marginal artery. There were no significant differences in patency rates between left and right ITA grafts. CONCLUSIONS: This prospective study showed that in situ RITA was, in most cases, able to reach most branches of the major circumflex artery and demonstrated an excellent patency rate.

Craniocervical and aortic atherosclerosis as neurologic risk factors in coronary surgery.

BACKGROUND: Advanced age is associated with increased systemic atherosclerosis and is a consistent neurologic risk factor after coronary artery bypass grafting (CABG). METHODS: We studied prospectively whether varying degrees of a total atherosclerotic score derived from the brain, carotid arteries, and ascending aorta predicted postoperative neuropsychologic (NP) dysfunction and stroke in 177 elderly patients (> or = 60 years) undergoing CABG. RESULTS: Group L (low total atherosclerotic score) had rates of NP dysfunction of 25% and 4%, group I (intermediate) had rates of 33% and 22%, and group H (high) had rates of 79% and 43% on postoperative days 1 and 7, respectively (p < 0.001). The incidence of stroke was higher in group H (14.3%) than in groups I and L (7.8% and 0.9%; p = 0.013). Stepwise logistic regression analysis demonstrated the significant predictors of NP dysfunction on postoperative day 7 to be total atherosclerotic score, peripheral vascular disease, and diabetes mellitus, and those of stroke to be total atherosclerotic score, peripheral vascular disease, and hyperlipidemia. CONCLUSIONS: Perioperative evaluation of craniocervical and aortic atherosclerosis is useful to identify a high-risk patient at postoperative NP dysfunction and stroke after CABG.