Search

In man ketanserin tartrate reduces plasma LDL cholesterol. To clarify the mechanism of this effect the effect of ketanserin on 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and LDL receptor activity in cultured human skin fibroblasts has been examined. After incubation with ketanserin for 14 h HMG CoA reductase activity was decreased in a dose-dependent manner up to 300 ng/ml (550 nM) without changing the free cholesterol content in the cells. Ketanserin increased specific binding and specific internalization of 125I-LDL dose-dependently. There was a significant inverse relationship between the percentage changes in HMG CoA reductase and LDL receptor activity. It appears that ketanserin induces up-regulation of LDL receptor activity by direct suppression of HMG CoA reductase, and this may be one mechanism by which plasma LDL-cholesterol is reduced by ketanserin.

Nine patients with CNS damage who had been transferred to our critical care unit were treated with a commercially available kit for percutaneous dilational tracheostomy (PDT). The mean procedure time was about 11 minutes, and the perioperative complication rate was 22% (2/9). Only one complication, wound infection, occurred, and the patient was cured with conventional therapy. On the other hand, premature extubation of the translaryngeal tube occurred in one case. Long-term complications like tracheal stenosis and tracheal malacia were not experienced in two patients. They were discharged from the hospital after decannulation. In conclusion, the advantages of PDT include a short procedure time, the ability to perform the procedure at the bedside, and reduced stimulation of the trachea. Because of the safety and simplicity of the procedure, we recommend PDT for patients with CNS damage.

The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein (LDL) oxidation was examined in 20 treated hypertensive subjects. The randomized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil. Fish oil significantly (-24%, P0.01) reduced plasma triglyceride, and increased LDL-cholesterol (+6%, P0.01 compared to corn oil). LDL particles were larger (P0.01) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride (P0.001) both before and after fish oil supplementation, and positively correlated with high density lipoprotein cholesterol (P0.01). Fish oil reduced lag time before onset of copper-induced LDL oxidation (-25%, P0.001) and significantly increased production of thiobarbituric acid-reactive substances (TBARS) during oxidation, compared with corn oil. Corn oil had no significant effect on lag time and oxidation rate. Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL. Corn oil was without effect. Additionally, macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly (P0.001) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids. We conclude that from the standpoint of atherosclerosis, fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable.

The relationship between atherosclerosis and fat soluble vitamin, especially vitamin E is reviewed on the basis of oxidised modification of low density lipoprotein (LDL). Data now support the notion that the oxidised LDL is present in the blood and arterial wall and antioxidant drugs such as probucol and vitamin E, beta-carotene, may prevent the progression of atherosclerosis. LDL alpha-tocopherol levels are generally correlated to the plasma concentrations and supplementation with alpha-tocopherol increases its content in LDL. There is a significant correlation between the LDL alpha-tocopherol level and the resistance to oxidative modification. Epidemiological data also shows the relation between low levels of plasma vitamin E and the increased incidence of coronary heart disease. Clinical application of vitamin E should be clarified in detail to inhibit the progression of atherosclerosis.

Atrial natriuretic peptide (ANP) was administered intravenously to three goats at a dose of 0.1 micrograms/kg/min for 40 min both before total artificial heart (TAH) placement and at 1, 7, and 14 postoperative weeks to determine whether exogenous ANP exhibits the same effect on animals with TAHs as it does on normal animals. No significant changes in the increases in plasma levels of ANP and cyclic guanosine monophosphate (c-GMP) were observed during ANP administration after TAH insertion. In preoperative animals, urine volume and urinary sodium excretion increased greatly during ANP administration, but this natriuretic effect was strongly suppressed in TAH animals. The changes in the decreases in arterial pressure and in central venous pressure (CVP) or right atrial pressure that occurred during the administration of ANP were not significant either pre- or post-operatively. Thus, only the natriuretic effect of ANP on the kidney was significantly suppressed in TAH animals, which might be due to some down-regulation of ANP receptors in the kidney, the production of some antagonists of ANP, sympathetic hypertonicity, or the elevation of CVP.

The blood compatibility of the jellyfish valve was studied. Artificial heart (AH) blood pumps incorporating jellyfish valves were connected to 18 goats as total artificial hearts (TAHs) and pumped for 1 to 125 days without anticoagulant or antiplatelet drugs. No thrombus was formed on the valve membrane or around the valve seat. Scanning electron microscopy showed almost no platelet deposition or microfibrin clot formation on the valve membrane, including its central region; the spokes of the valve seat were also free from platelet and microfibrin clots. No calcification was observed during these tests, and plasma free hemoglobin was between 2 and 7 mg/dl. The jellyfish valve revealed good blood compatibility, even without anticoagulant use.

By fixing the function of one ventricle, a total right heart bypass model can clarify the function and regulatory mechanism of the natural heart, and the etiology of abnormal hemodynamics in TAH animals such as increased CVP blood pressure and hepatic congestion. The pulmonary artery of a right heart bypass in a goat was clamped proximally; the pulmonary circulation was thus supplied entirely by the artificial heart and the systemic circulation by the natural heart. This model enabled studies of long-term effects of an artificial right heart on systemic circulation at a right heart output of 80-100 ml/kg/min; the response of the natural left heart to changes in output of the right heart; and the response of the natural left heart and artificial right heart to treadmill exercise. It was found that only slight increase in CVP or no increase in blood pressure was observed during the experiment (112 days); a rapid increase in output of the RAH resulted in an increase in left atrial pressure, stroke volume and output of the left ventricle, and a decrease in its heart rate at rest; and significant increase in both artificial right heart and natural left heart output and heart rates were observed during treadmill exercise, despite the marked decrease in left atrial pressure. The above results suggest that the increase in CVP and blood pressure in total artificial heart animals are not due to factors involving the artificial right heart, and that although left ventricular function acts in accordance with Starling's law at rest, this is no longer true during treadmill exercise.

This study was designed to determine if spinally administered epinephrine is capable of suppressing noxiously evoked activity of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord. Extracellular activity was recorded from single WDR neurons in the dorsal horn of decerebrate, spinal cord-transected (T-12) cats. Activity was evoked by the presentation of a noxious radiant heat stimulus (51 degrees C) to the cells' receptive fields on the hind paws. Evoked activity was monitored both before and after the spinal administration of either 50 micrograms (n = 6) or 100 micrograms (n = 6) epinephrine. Both doses of epinephrine produced a significant suppression of noxiously evoked activity, which was dose-dependent. In addition, the 100-microgram dose produced a suppression that was of longer duration than that seen following the 50-microgram dose. Recovery from suppression was recorded following both the 50- and 100-microgram dose. These results indicate that spinally administered epinephrine is capable of suppressing noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord. Since WDR neurons have been identified as cells of origin for the spinothalamic tract, such an action may block the central transmission of afferent pain information. This may be a mechanism by which spinally administered epinephrine enhances the duration or intensity of spinal anesthesia produced by local anesthetics and may also explain spinal analgesia resulting from the spinal administration of adrenergic agonists. Interactions between spinally administered epinephrine and spinally administered opioids also were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

A practical model (Model-1) of a jellyfish valve was developed, which was composed of a valve seat and a flexible membrane. The valve seat has 12 spokes to hold the membrane, and is made of solution-cast polyurethane coated with segmented polyurethane or Cardiothane. The flexible membrane is 200 microns thick, and made of segmented polyurethane or Cardiothane by a casting method. The valves were built into a sac type blood pump. In mock circulation tests, this jellyfish valve revealed performance superior to Bjork-Shiley (B-S) valves. No stagnation point was observed in the flow visualization study, and durability testing is ongoing beyond 7.5 months. The valves were used in animal artificial heart experiments for up to 112 days with good performance. No thrombi were formed on the valve membrane or around the spokes. Although a ring thrombus was observed behind the valve, it would be prevented by perfect adhesion of the valve seat to the blood pump. The plasma free hemoglobin level was less than 2 mg/dl during these experiments. These results suggest that a jellyfish valve (Model-1) is useful in ventricular assist devices, and in short-term bridge use of a total artificial heart.

Short-latency somatosensory evoked potential (SEP) was serially monitored in head-injured patients and its clinical significance was evaluated in relation to auditory brain stem response (ABR), prognosis and other parameters such as intracranial pressure (ICP). SEP, ABR, and ICP were monitored serially and automatically in 16 patients with acute head injury. Glasgow Coma Scale (GCS) score was equal to or less than 8 in 14 cases. High dose barbiturate therapy was performed in 7 cases and intracranial hematoma was removed operatively in 14 cases. SEP was recorded from C3'or C4'-Fz leads on the lesion side following stimulation of the contralateral median nerve, and the difference between the two potentials (N20, N13) defined as central conduction time (CCT) was followed at a basic time interval of 10-20 min. The patients were divided into 3 groups according to N20 finding and the prognosis of each group was analyzed. The final outcome (assessed 6 months after injury) was graded according to Glasgow Outcome Scale as follows: good (good recovery, moderate disability), poor (severe disability, persistent vegetative state), death (death). Three patients with no CCT change showed good recovery (table, 11). Out of 7 patients with no N20 on admission, 5 died due to severely increased ICP and the prognosis for the other 2 cases was poor. The last group consisted of 6 patients in whom CCT varied during hospitalization. In 3 out of these 6 cases N20 finally disappeared due to increased ICP and they died in the acute stage.(ABSTRACT TRUNCATED AT 250 WORDS)