Effect of dobutamine on the arterial ketone body ratio and portal blood flow velocity in cirrhosis

ABSTRACT— We studied the relationship between the portal blood flow velocity and the arterial ketone body ratio in patients with chronic liver disease receiving a dobutamine infusion. We used an ultrasonic Doppler duplex system to evaluate the portal blood flow velocity. Dobutamine was given intravenously at 5 μg/kg/min for 20 min. Dobutamine infusion induced smaller changes in the portal blood flow velocity and ketone body ratio in liver cirrhosis than in chronic hepatitis. The existence of shunts and the poor increase of the cardiac index in response to dobutamine explained the limited improvement of portal blood flow velocity in cirrhosis patients. The ketone body ratio was improved by dobutamine in cirrhosis patients whose portal blood flow velocity was increased by more than 10%, while this ratio decreased when the increase of it was less than 10%. There was no change in portal oxygen extraction in the cirrhosis group, and portal oxygen uptake only increased when the portal blood flow velocity rose by more than 10%. Dobutamine should only be used to treat liver failure if the portal blood flow velocity is increased by more than 10% or the arterial ketone body ratio is improved by a test infusion.     

Effect of the calcium antagonist,diltiazem, on beta-agonist-induced reduction of beta-adrenergic responsiveness in the guinea pig lung

This study was designed to clarify the mechanism of tolerance that occurs during prolonged administration of a beta-agonist in relation to membrane phospholipid degradation and to elucidate the effect of diltiazem, a calcium antagonist. Guinea pigs were divided into 3 groups: (1) control—physiological saline (0.5 ml) was injected once a day for 7 successive days; (2) metaproterenol (Mp)—Mp was injected intraperitoneally (10 mg/kg/day) for 7 successive days; (3) Mp + diltiazem—diltiazem was injected intraperitoneally (20 mg/kg/day) 30 min before Mp injection for 7 successive days. The number of beta-adrenoceptors and the 10⁻⁵ M (−)-isoproterenol-stimulated adenylate cyclase activity were significantly decreased in the metaproterenol group. Diltiazem reduced these decreases. Phospholipase activity was increased and phosphatidylcholine and phosphatidylethanolamine levels were decreased in the metaproterenol group. Diltiazem also reduced these changes. These results suggest that the degradation of membrane phospholipids by phospholipase may be involved in a decrease in beta-adrenergic response caused by successive administration of metaproterenol. Diltiazem protects membrane phospholipids from phospholipase attack, which in turn maintains beta-adrenergic responsiveness. Part of this study was presented at the Annual Meeting of the American Thoracic Society, May 12, 1987, New Orleans, Louisiana     

Chest wall velocity and the second heart sound. An improved sensor of S2 splitting

We report a new method of detection of the timing of the aortic and pulmonary valve closure that depends not on the registration of audible vibrations, but rather, on subtle but distinct movements of the chest wall, which are external manifestations of these events. We studied these phenomena in six open-chest dogs and in 69 human subjects. The dog studies show that the two distinct inward movements detected by a motion sensor applied to the epicardium in the vicinity of the right ventricular outflow tract correlate with the timing of the incisural notches of the pressure signals from the great vessels. In humans, these movements are transmitted to the skin surface and can be detected noninvasively. In 48 of the 69 human subjects (70%), these spikes provided a significantly better indication of the timing of semilunar valve closure than did the conventional phonocardiogram.     

Cathepsins B and L Increased during Response of Periodontal Ligament Cells to Mechanical Stress In Vitro

Cathepsin is a typical and well-characterized lysosomal cysteine protease that, under pathological conditions, is involved in tissue destruction. A recent immunocytochemical study demonstrated that cathepsins B (CAB) and L (CAL) were localized in the periodontal ligament (PDL) of the rat molar, and they were expressed in compressed sites during experimental tooth movement. Further, we demonstrated previously that the levels of CAB and CAL in gingival crevicular fluid increased during orthodontic tooth movement. Therefore, CAB and CAL may play important roles in the process of collagen degradation during orthodontic tooth movement, and our in vitro study examined the secretion of CAB and CAL in PDL cells following mechanical stress. PDL cells were subjected to 0.5, 1.0, 2.0, or 3.0 g/cm² of compression force or an increase in surface area by tension force of 0.28%, 0.95%, 1.72%, or 2.50% for 24 hr. For detection of CAB and CAL in conditioned medium, commercially available ELISA kits were used. We found compression and tension significantly increased the secretions of both CAB and CAL in PDL cells, which were exhibited in a time- and force magnitude-dependent manner. The compression-stimulated secretion of CAB was increased approximately 3-fold and that of CAL 4-fold, as compared with the control. Further, tension-stimulated secretion of CAB was increased by 1.5-fold and that of CAL 2-fold compared with the control. When analyzed using a semiquantitative polymerase chain reaction assay, CAB and CAL mRNA were increased in response to both compression and tension forces. These findings demonstrated that mechanical stress (compression and tension forces) causes an increase in secretion of CAB and CAL in PDL cells in vitro.