Characterization of human coronary sinus valves by direct visualization during biventricular pacemaker implantation.

BACKGROUND: The precise reasons for failure to cannulate the coronary sinus during biventricular device implantation are unknown. Visualization of the coronary sinus ostium during electrophysiology procedures may enhance understanding of how unusual anatomy can affect successful cannulation of the coronary sinus. OBJECTIVES: The aim of this study was to describe the morphology of valves at the coronary sinus ostium (CSO) visualized directly with an illuminated fiberoptic endoscope during implantation of biventricular devices. METHODS: The coronary sinus anatomy of one hundred consecutive patients undergoing implantation of biventricular devices was investigated using a fiberoptic endocardial visualization catheter (EVC). RESULTS: The CSO was clearly visualized in 98 patients using the EVC. A Thebesian valve was seen in 54% of these. Almost all Thebesian valves were positioned at the inferior (61%) or posterior (33%) aspect of the CSO. Only six patients had Thebesian valves that covered more than 70% of the CSO, but all were successfully implanted with a transvenous left ventricular pacing lead after cannulating the coronary sinus under direct visualization. CONCLUSIONS: Over half of patients undergoing biventricular device implantation have identifiable Thebesian valves. Even valves covering the majority of the ostial area may be traversed using direct visualization and modern catheterization techniques.

Early human experience with use of a deflectable fiberoptic endocardial visualization catheter to facilitate coronary sinus cannulation.

BACKGROUND: Despite improvements in cardiac resynchronization therapy (CRT) implantation techniques, a significant minority of CRT attempts are unsuccessful. Inability to cannulate the coronary sinus (CS) because of difficult anatomy is a major reason for unsuccessful CRT implantation. Direct visualization of intracardiac structures during the implant may facilitate access into the CS. The present study describes CRT implantation with the aid of an endocardial visualization catheter (EVC). METHODS: Fifty-eight consecutive patients (mean age 72 +/- 12 years; ejection fraction 26.2% +/- 7.0%; New York Heart Association [NYHA] class 2.9) underwent CRT implantation using a steerable fiberoptic EVC (Acumen Medical, Inc., Sunnyvale, CA). RESULTS: The EVC was able to visualize the CS ostium in all cases. The CS was successfully cannulated in 57 (98.3%) of 58 patients. The time from vascular access to CS visualization was 6 +/- 5 minutes, and the total time to CS access was 8 +/- 6 minutes. Successful left ventricle (LV) lead implantation was accomplished in 55 (94.8%) of 58 patients. Three patients who had a previous history of failed LV lead implantation were successfully implanted using the EVC. CONCLUSION: Fiberoptic imaging of intracardiac structures during CRT implantation may be performed rapidly in a wide range of patients with an EVC. The ability to visualize right atrial anatomy may aid CS access and LV lead implantation.

Quantitation of soluble and skeletal alkaline phosphatase, and insoluble alkaline phosphatase anchor-hydrolase activities in human serum.

BACKGROUND: The current studies were intended to compare the circulating levels of total and anchorless (soluble) skeletal and hepatic ALP isoenzyme activities, and insoluble ALP anchor-hydrolase activity in serum of postmenopausal women. METHODS: Preliminary studies of the insoluble ALP anchor-hydrolase activity in serum revealed a pH optimum of pH 5-6.5, a sensitivity to inactivation by heat at temperatures >45 degrees C (t(1/2)=8-9 min at 60 degrees C), and an apparent K(M) (at pH 7.5) of 40-45 mU/ml of insoluble skeletal ALP activity. RESULTS: Serum analyses showed that 94.5+/-0.5% (mean+/-SEM) of the ALP activity in serum was in the anchorless, soluble form. The data were also consistent with the notion that the amount of insoluble ALP anchor-hydrolase activity in serum, 52.8+/-0.8 U/l (mean+/-SEM), was sufficient for the conversion of anchor-intact (insoluble) ALP into the anchorless, soluble form, assuming activation by serum lipids and/or bile salts. Distributions of results for total, skeletal, hepatic, and insoluble ALP anchor-hydrolase activity were skewed toward the higher range and leptokurtotic (p<0.01 for each). Total ALP activity ranged from 42% to 208% of the group mean value; skeletal, hepatic, and insoluble ALP anchor-hydrolase activities ranged from 5% to 306%, 33% to 277%, and 2% to 325%, respectively. In contrast, the soluble ALP fraction only ranged from 71% to 106% of the group mean value. CONCLUSIONS: The correlations between the total and both skeletal (r=0.711, p<0.001) and hepatic (r=0.782, p<0.001) ALP isoform activities were predictive. Although correlations were also observed between insoluble ALP anchor-hydrolase activity and total (r=0.197, p<0.001), hepatic (r=0.184, p<0.001) and skeletal ALP activities (r=0.118, p<0.05), those relationships were not predictive (r(2)<0.04).

Skeletal alkaline phosphatase activity is primarily released from human osteoblasts in an insoluble form, and the net release is inhibited by calcium and skeletal growth factors.

Skeletal alkaline phosphatase (ALP) is anchored to membrane inositol-phosphate on the outer surface of osteoblasts. Although skeletal ALP activity in serum is, essentially, all in an anchorless (soluble) form, in vitro studies indicate that ALP can be released in either an anchorless, soluble form (e.g., by a phospholipase) or an anchor-intact, insoluble form (e.g., by vesicle exocytosis). The current studies were intended to define the contributions of each of these putative processes of ALP release and to assess the significance of regulation by calcium (Ca) and skeletal effectors. ALP activity was measured in serum-free medium from replicate cultures of human osteosarcoma (SaOS-2) cells and normal human bone cells. Temperature-sensitive phase distribution (in Triton X-114) allowed separation of soluble from insoluble ALP activity. Our studies revealed that most of the ALP activity released from SaOS-2 cells was in an insoluble form (78% +/- 8%), a percentage that was constant between 2 and 96 hours. A similar result was seen for normal human bone cells. Calcium had a negative, biphasic dose-dependent effect on net release of ALP activity: r = -0.85, P < 0.001 at 24 hours, with KIapparent values for biphasic inhibition of 20 and 300 mumol/l Ca. Of the skeletal effectors tested, insulin-like growth factor-II (IGF-II) had the greatest effect, decreasing the net release of ALP activity in a dose-dependent manner (r = -0.82, P < 0.005). Neither Ca nor IGF-II affected the distribution of soluble/insoluble ALP activity by more than 9%. IGF-II had no effect on extracellular ALP stability, but the addition of Ca to Ca-free cultures resulted in parallel losses of extracellular ALP activity and ALP immunoreactive protein (P < 0.001 for each). A similar effect was seen when Ca was added to Ca-free, cell-free, conditioned medium, but not when Ca was added to purified ALP, which is consistent with the general hypothesis that a Ca-dependent protease might be present in the cell-conditioned medium. Together, these data suggest that most of the ALP activity released from osteoblasts is insoluble (and, presumably, anchorless), net release of ALP activity is negatively regulated by Ca and skeletal growth factors, the effect of Ca may reflect Ca-dependent protease activity, and an exogenous (e.g., serum) phospholipase may be responsible for releasing ALP from its insoluble anchor.