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Biomedical subjects

D Kling

Publications and source records attributed to D Kling.

At least 109 records · Page 6Linked to original sources

[Plasma level of lidocaine following intraoperative bolus injection and infusion in heart failure].

In two groups of ten patients each (group I: myocardial insufficiency, group II: no myocardial insufficiency) during anaesthesia arterial plasma levels of lidocaine were studied, following iv bolus administration (1 mg./kg. bw) and subsequent lidocaine infusion (2 mg./min.) for 15 minutes. With this dosage, recommended for antiarrhythmic therapy, plasma levels exceeded the therapeutic range in group I and in some patients reached almost toxic levels (10 micrograms./ml.). In group II lidocaine plasma levels were within the therapeutic range (1,5-4 micrograms./ml.). In patients with myocardial insufficiency and/or reduced hepatic metabolism antiarrhythmic therapy with lidocaine has to be performed with significantly reduced dosages; drug monitoring is recommended.

Arrhythmias, Cardiac↗

[Effect of postoperative parenteral feeding on protein metabolism in heart surgery patients. A comparative study].

To investigate the importance of amino acid infusions in immediate postoperative parenteral nutrition, cardiac patients were randomly allocated into two groups. Applicating identical carbohydrate calories (2000 kcal/day) group 1 received only essential amino acids while in group 2 a combined pattern of essential and non essential amino acids was infused. In addition to routine laboratory data several parameters of protein metabolism including nitrogen balance were evaluated. Although nitrogen balance was positive only in group 2 the differences between the two groups concerning other parameters measured were minimal. The different infusion regimes are discussed revealing the significance of additional parenteral nutrition in these patients.

Amino Acids↗

[Sequential pacing following cardiopulmonary bypass].

Twenty patients with combined mitral valve disease were studied to evaluate whether the mode of cardiac pacing can influence myocardial performance after cardiopulmonary bypass. All patients underwent the same surgical procedure (mitral-valve-replacement) under standardized anaesthetic procedure. After weaning from extracorporeal circulation the following haemodynamic measurements were performed either under ventricular pacing or under sequential ("physiological") pacing: blood-pressure (radial artery), central venous pressure (CVP, jugular vein), cardiac output (as cardiac index, C. I.), pulmonary artery pressure (PAP) using Swan-Ganz-thermodilution catheter (jugular vein) and left atrial pressure (LAP). All patients were investigated as well under ventricular pacing as under sequential pacing (heart rate: 90 X min-1; AV-delay: 200 msec; stimulation with a pacemaker Medtronics 5330). Compared with the situation under ventricular pacing the haemodynamic parameters changed, when sequential pacing was applied: arterial pressure and cardiac output increased, whereas CVP as well as PAP and LAP decreased. The data indicate that there is some influence on cardiac work by the mode of pacing. Physiological pacing compared to ventricular pacing seems to lead to a marked improvement in cardiac performance. Particularly patients with severe dysrhythmia following cardiopulmonary bypass should be treated by physiological (sequential) pacing.

Blood Pressure↗

[Alfentanil, a new, short-acting opioid. Hemodynamic and respiratory aspects].

The haemodynamic and respiratory-depressive effects of 20 micrograms/kg and 40 micrograms/kg of alfentanil in 54 patients with coronary bypass operation were compared with a control group (n = 36). The measurements were carried out at 3 different times, each lasting over a 10 min period: 1. Before induction of anaesthesia but after premedication with flunitrazepam. 2. During anaesthesia and 3. during extracorporeal circulation (standardized conditions).--The preoperative as well as the intraoperative investigations showed a reduction in pulse rate, mean arterial pressure, left ventricular pressure and arterial perfusion pressure during extracorporeal circulation. As cardiac output remained constant in the awake patient, peripheral vasodilatation was predominant. Aside from this during anaesthesia reduction in cardiac output may have been responsible for the decrease in pressure although the cause of this could be the nitrous oxide as well. During the preoperative period a clear increase in wedge pressure, mean pulmonary artery pressure, right atrial pressure and pulmonary vascular resistance occurred from the 3rd minute after the injection. The cause is a vasoconstriction during apnoea. In the intraoperative period this did not occur. The respiratory depression(paO2: -34%, paCO2: +29%) resembles that after fentanyl, except that it starts earlier and lasts for a shorter time. In summary, it can be stated that all effects after alfentanil are similar to those of fentanyl.

Adult↗

[Effect of aspartate compounds on the biochemical characteristics of myocardial energy metabolism in man].

Twenty-five patients undergoing aortic valve replacement were administered two different electrolyte solutions pre- and intraoperatively: patients in group A (n = 9) received a balanced solution of electrolytes and trace metals with aspartate as anion (Inzolen), patients in group B (n = 16) received Ringer's solution with potassium chloride referenced to frequently-measured serum potassium levels. From the left ventricular apex region, needle biopsies were obtained at three points in time: 1. beginning of CPB, 2. end of ischemia, 3. after ten minutes of reperfusion. The tissue samples were enzymatically analyzed for the content of ATP, CP, ADP and lactate. In group A (patients with aspartate) ATP (moderately) and CP (markedly) decreased after ischemia with a marked increase after reperfusion. ADP and lactate in this group (A) increased at the end of ischemia and decreased after reperfusion. ATP and CP in group B (KCl) showed a similar course during the investigation. Lactate (markedly) and ADP (moderately) increased after ischemia without changing after reperfusion. Mean values of ATP and CP in group A were significantly higher than those of group B at all times. Mean values of ADP and lactate, however, in group A were below those of group B. The data indicate an improvement in energetic metabolism of myocardium in man. The results point out the possible importance of aspartates in compound with electrolytes and trace metals in preservation of biochemical energy.

Adenosine Diphosphate↗

[Hemodynamic changes following the injection of lormetazepam under premedication and anesthesia conditions in coronary surgery patients].

Lormetazepam, a new short-acting benzodiazepine, was studied in 30 patients undergoing coronary artery bypass grafting (10 patients before induction of anaesthesia, 8 patients before extracorporeal circulation, 12 patients during extracorporeal circulation). Before induction of anaesthesia lormetazepam caused only a small reduction in CI, heart rate and a moderate hypoventilation. During anaesthesia (fentanyl, pancuronium bromide, ventilation with N2O/O2 1: 1) there was a decrease in CI (26%), SI (18%), HR (5,7%), dp/dt (15%) and an increase in TSR (25%) and TPR (32%); Part, PAP, PCWP and PRA remained unchanged. There was a small decrease in myocardial oxygen consumption. During ECC lormetazepam increased the arterial perfusion pressure (20%); the priming volume of the oxygenator decreased by 48% at the same time, indicating venous pooling.

Anesthesia, General↗

[Haemodynamic effects and characteristics of midazolam during induction of anesthesia (author's transl)].

Our investigations have shown the following: 1. 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) produces no adverse haemodynamic changes in healthy subjects. 2. The reduction in peripheral resistance becomes apparent mainly in the case of raised baseline values, as, for example, in hypertensive subjects, but it can also be of significance prior to anaesthesia, when there may be raised systemic vascular resistance due to stress. 3. Venous pooling, which leads to a decrease in pre-load and subsequent lowering of the cardiac index, can have a compensatory effect in cardiac insufficiency. Under certain conditions, as for example, in the case of imminent volume deficit, a marked fall in pressure is to be expected. 4. The haemodynamic effects of midazolam are thus limited to vascular reactions. Under certain circumstances volume therapy may be necessary before the drug is used.

Adult↗

Polychlorinated biphenyls: in vivo and in vitro modifications of phospholipid and glyceride biosynthesis.

In vivo administration of Aroclor 1254 (PCB) alters the biosynthesis of glycerides and phospholipids. Different percentages of total radioactivity distribution patterns were observed in microsome, mitochondria, and homogenate preparations from rat liver. (14C)palmitate and (U-14C)sn-glycerol-3-phosphate were differently incorporated when assayed in the same preparation, suggesting compartmentation of the substrates. Acyl CoA sn-glycerol-3-phosphate acyl transferase was inhibited by PCB in vitro. Inhibition was noncompetitive. After 30 days of dietary pretreatment with PCB, acyl CoA sn-glycerol-3-phosphate acyl transferase activity was increased in the liver. In vitro, the total radioactivity incorporated into phospholipids and glycerides was decreased in the presence of PCB. There was, however, no significant change in the percent of total distribution of radioactivity when either (U-14C)sn-glycerol-3-phosphate or (1-14C)palmitate was the substrate. PCB had no significant effect on glycerol kinase activity. PCB initially did not inhibit phosphatidate, but after prolonged incubation there was a small increase or decrease under in vitro and in vivo conditions respectively. Phosphorylase b, but not phosphorylase a, was inhibited by PCB. 2,4,5,2'4',5'-hexachlorobiphenyl inhibited sn-glycerol-3-phosphate acyl transferase, phospholipid biosynthesis, and glyceride biosynthesis. The results indicate that PCB alters biosynthesis of phospholipids and glycerides in vitro and in vivo. Apparent differences between the results obtained under the two conditions are probably due to qualitative and/or quantitative variations in metabolic products formed from PCB in vivo.

Animals↗

Polychlorinated biphenyls: in vivo and in vitro modifications of cholesterol and fatty acid biosynthesis.

Aroclor 1254 (0.1 percent w/w) administered in the diet caused moderate to severe vacuolar degeneration of periportal hepatocytes, heptocyte enlargement, lipid accumulation, and necrosis of the liver. The incorporation of [2-14C]mevalonate into nonsaponifiable lipids was inhibited 18 percent and 26 percent after 14 days and 30 days, respectively. Biosynthesis of cholesterol from [2-14C]acetate and [2-14C]mevalonate was decreased by 51 percent and 31 percent respectively after 30 days, but no significant inhibition was observed after 14 days of feeding Aroclor 1254. [2-14C]Acetate incorporation into non-saponifiable lipids was 1.66 times greater in homogenates from Aroclor-treated rats than in those from control rats. Similar results were obtained when 3H2O, Mevalonate-14C, and acetate-2-14C were incubated in vivo. The conversion of [2-14C-A1acetate to fatty acids was decreased 43 percent by Aroclor 1254 (0.1 percent w/w, dietary) and 73 percent by Aroclor 1254, 500 ppm, in vitro. The in vitro incorporation of each [2-14C]acetate, [2-14C]mevalonate and [1-14C]isopentenyl pyrophosphate into cholesterol was inhibited by Aroclor 1254. There was no inhibition of the conversion of [1-14C]mevalonate to CO2, indicating that there was no inhibition of mevalonate-5-pyrophosphate anhydrodecarboxylase. Fatty acid synthase was not inhibited by PCB. Citrate cleavage enzyme was inhibited by Aroclor 1254. When ATP and citrate concentrations were varied, the Ki's were 5.3 X 10(-5)M and 11.5 X 13(-5)M, respectively. Acetyl CoA carboxylase activity was not inhibited by 1000 ppm Aroclor 1254 in vitro. Inhibition of citrate cleavage enzyme is a possible explanation for the observed decrease in fatty acid synthesis. There was an apparent diversion of acetate from fatty acid synthesis into the formation of non-saponifiable lipids, accompanied by an inhibition of the biosynthesis of cholesterol per se.

Acetyl-CoA Carboxylase↗

Enhanced endothelial permeability and invasion of leukocytes into the artery wall as initial events in experimental arteriosclerosis.

The temporal sequence of the very early events in arteriosclerosis, as induced by electrical stimulation in carotid arteries of rabbits, was examined by combined light microscopy and transmission electron microscopy. After one session (30 min) of DC impulses, the endothelial permeability to horse-radish peroxidase was increased mainly beneath the anode, judging from the massive accumulation of reaction products of peroxidase in the subendothelium. After a further stimulation period, some of the endothelial cells displayed alterations in pattern and size and heavy cytoplasmic deposition of silver salt. However, the endothelium was maintained as a continuous lining. During this initial phase, a considerable number of granulocytes and monocytes was found adhering to the endothelium of the stimulated region and also within the subendothelial space. The invasion of the leukocytes preceded the migration of smooth muscle cells from the media into the intima, a process which began after two days of the electrical stimulation schedule. These initial phases of plaque development may represent a special form of an inflammatory response.

Animals↗

Increased contractile responses of isolated arteriosclerotic rabbit carotid arteries to various vasoactive stimuli.

Clinical observations indicate that atherosclerotic vessels are prone to develop vasospasm. It was assumed that this property is related to hypercholesterolemia, but the basic mechanisms are still unknown. To investigate further mechanical stimulation experiments were performed with segments of rabbit carotid arteries. Arteriosclerotic lesions were induced in vivo in these arteries by application of DC impulses either in hyper- or normo- cholesterolemic animals. Contractions were evoked by noradrenaline, KCl or hydrogen peroxide. The results show that all the arteriosclerotic segments were hypersensitive to noradrenaline and hydrogen peroxide, compared with the corresponding controls. An increase in contraction force was also found upon application of KCl to lipid-containing plaques. However, in arteriosclerotic segments obtained from normally fed animals, the contraction response to KCl was lower than in controls. This indicates that complex alterations in the contractile properties occur in smooth muscle during atherogenesis which cannot be explained solely on the basis of the influence of cholesterol on the arterial cells.

Animals↗