Comparison of the isotopical tracer and the Triton WR 1339 methods for triglyceride kinetics in carbohydrate-fed rats

Radiolabeled tracer [3H] very low density lipoprotein (VLDL)-triglyceride (TG) and non-tracer (Triton WR 1339) methods were used to determine VLDL-TG kinetics in normal rats and in rats given either a 10% glucose or a 10% fructose drinking solution for 16 h ad libitum. The carbohydrate-fed rats were hypertriglyceridemic compared to control animals. VLDL-TG was endogenously prelabeled with [3H] glycerol in control, glucose- and fructose-fed rats, and injected into identically treated recipients. Triton WR 1339, a potent inhibitor of VLDL-TG catabolism, was injected into the same animal 30 min after the end of the tracer method to measure TG secretion rate (TGSR). The tracer and non-tracer methods showed that fructose-fed rats had a significantly lower fractional catabolic rate (FCR) than either control or glucose-fed rats. In contrast, glucose-fed rats had a TGSR greater than control without a reduction in FCR. For all treatments, TG concentration correlated with FCR for the tracer method and with TGSR for the non-tracer method. There was good correlation of TGSR determined by the tracer and non-tracer method for control rats despite the substantial difference in the absolute values. No such relationship was observed in carbohydrate-fed rats. Control rats were made hypertriglyceridemic by Intralipid infusion. A lower FCR was observed when determined by the tracer method, but this was not observed by the triton method. These results suggest that TG kinetics determined by the tracer and the triton methods cannot be readily correlated, especially in hypertriglyceridemic state. However, the two kinetic studies both suggested that overproduction of VLDL-TG in glucose-fed rats and impaired VLDL-TG catabolism in fructose-fed rats were the primary cause for their hypertriglyceridemia, respectively.     

Correlation of insulin deficiency and hypertriglyceridemia in diabetic rats

The relationship between plasma insulin (IRI) and lipid concentration, or triglyceride (TG) kinetics was studied in streptozotocin-induced diabetic rats (DM) to examine how insulin deficiency is associated with the mechanism of hypertriglyceridemia (HTG) in diabetes. Plasma glucose and ketones were significantly elevated and IRI reduced in DM. Plasma glucagon concentration in DM was similar to controls. The plasma concentration of TG, total cholesterol phospholipid and apoprotein B was 3-4-fold higher in DM compared to control rats. The HTG in DM was mainly attributable to an increase in the concentration of TG-rich lipoprotein (TRL). Multiple linear regression analysis showed a positive relationship between the concentration of non-esterified fatty acid and plasma lipids, but the decrease in IRI best correlated with increased concentrations of lipids and apoprotein B in plasma and TRL. Neither glucose nor glucagon correlated significantly with lipids or apoprotein B concentration in plasma or TRL. The rate of entry of TG into blood was similar between DM and controls, and in DM this significantly correlated with IRI. Clearance of radiolabeled TRL-TG in DM was significantly decreased and correlated with IRI. Conversely, the removal of radiolabeled Intralipid-TG was similar for DM and controls. The data suggest that insulin critically regulates TRL-TG metabolism in DM and that a catabolic defect of TRL-TG due to insulin deficiency is a main reason for the HTG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurogenic influence on local cerebral blood flow. Effect of catecholamines or sympathetic stimulation as correlated with the sympathetic innervation.

Local cerebral flow was measured continuously in conscious rabbits (thermoclearance technique), and PaO2 and PaCO2 were recorded by mass spectrometry. Though inhalation of CO2 increased flow in caudate nucleus and lateral geniculate body, catecholamines only had effect on caudate nucleus where isoproterenol enhanced and epinephrine and norepinephrine reduced flow. Reduction by electrical stimulation of the neck sympathetic trunk was particularly evident in the caudate. Blood flow increased markedly in both regions after preganglionic conduction blockade. The effects were correlated with a significantly lower degree of sympathetic arteriolar innervation (fluorescence histochemistry) in the lateral geniculate body compared with the caudate nucleus.     

Cholesterol esters regulate apoB48 secretion in CaCo2 cells

In this study, we investigated the effect of atorvastatin, an HMG-CoA reductase inhibitor and CL277082, an ACAT inhibitor, on apolipoprotein B48 synthesis, degradation and secretion in transformed human intestinal enterocytes (CaCo2 cells). Cells were incubated with atorvastatin or CL277082 in the absence or presence of sterol containing media and pulsed with [S35]-methionine and chased with unlabelled methionine. Concomitantly, the effect of atorvastatin and CL277082 on the relative amount of apoB48 protein in cells and media was also quantified by western blotting using an apoB antibody and enhanced chemiluminescence. Suppression of cholesterol synthesis with atorvastatin did not attenuate the production or secretion of apoB48 from CaCo2 cells under basal conditions. On the other hand, suppression of cholesterol biosynthesis with atorvastatin under stimulatory conditions accelerated the degradation of apoB48 in cells without affecting its synthesis or secretion. There was no effect of exogenous sterols on apoB48 secretion. Taken together, neither endogenous nor exogenous cholesterol appears to acutely modulate apoB48 secretion from intestinal cells. In contrast, inhibition of cholesterol esterification with ACAT inhibitor significantly attenuated apoB48 secretion under basal and stimulatory conditions by a mechanism which enhanced apoB48 degradation. Collectively, our results suggest that in CaCo2 cells, newly synthesized cholesterol ester may be an immediate regulator apoB48 secretion.     

Beating-heart coronary artery bypass graft surgery at San Raffaele Hospital: four years of experience

OBJECTIVE: To review the database of 1,902 consecutive patients who underwent coronary artery bypass graft (CABG) surgery in the period 1998 through 2001 at this institution, and to compare the preoperative status, anesthetic management, and postoperative outcome of 364 patients with the beating-heart technique with 1,538 patients who underwent the operation on cardiopulmonary bypass. DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Consecutive patients (n = 1,902) who underwent CABG surgery in the period 1998 through 2001. MEASUREMENTS AND MAIN RESULTS: Comparison (chi-square test) of the preoperative status shows that surgeons' choice for the beating-heart technique was based on the presence of severe preoperative comorbidities: renal impairment (p < 0.0001), chronic obstructive pulmonary disease (p < 0.04), and low ejection fraction (p < 0.0001). On a multivariate analysis, the beating-heart technique was associated with reduced transfusion needs and duration of mechanical ventilation. CONCLUSION: Beating-heart surgery is gaining popularity as a safe method for myocardial revascularization. Excellent results have been achieved with this technique in this center.