Factors contributing to blood pressure elevation during norepinephrine and phenylephrine infusions in dogs

To examine the factors contributing to the rise in systemic blood pressure during α- and β- adrenergic stimulation, phenylephrine, an α-adrenergic agonist, and norepinephrine, an α- and β-adrenergic agonist, were infused intravenously to anesthetized dogs until mean aortic blood pressure was raised equally by 40–60 mmHg. Changes in preload were estimated by changes in left ventricular end-diastolic pressure or segment length recorded by an ultrasonic technique. By obstructing the inferior vena cava (IVC), the increase in preload could be reduced to control level during phenylephrine and norepinephrine infusions without altering peripheral resistance (mean aortic blood pressure/cardiac output). Normalization of preload reduced the pressure response by 2/3 during phenylephrine infusion and by 1/4 during norepinephrine infusion. However, after β-adrenergic blockade by propranolol, normalization of preload reduced the pressure response by 2/3 during both phenylephrine and norepinephrine infusions. Thus, during α-adrenergic stimulation, the increase in preload is a more important factor than the increase in peripheral resistance. Norepinephrine raised stroke volume by 24±5%. When the increase in stroke volume was prevented by IVC obstruction, the pressure response to norepinephrine was halved. Thus, during norepinephrine infusion the rise in stroke volume caused by β-adrenergic stimulation is as important as α-adrenergic stimulation for the pressure response.     

Mechanism of blood pressure elevation during angiotensin infusion

The mechanism of increased preload and its contribution to the rise in blood pressure during intravenous angiotensin infusion were studied in anesthetized dogs. In open-chest dogs angiotensin increased mean aortic blood pressure by 58±12 mmHg. Left ventricular end-diastolic dimension, measured as myocardial chord length (MCL) by ultrasonic technique, increased by 7±1 %. By inflating a balloon in the inferior vena cava, end-diastolic MCL was reduced to control value and the rise in mean aortic blood pressure was almost halved to 32±10 mmHg above control value. A similar preload effect was recorded in closed-chest dogs using end-diastolic left ventricular pressure as an estimate of left ventricular volume. During angiotensin infusion to the upper body only, end-diastolic MCL did not increase. When redistribution of the splanchnic blood volume was prevented, the effect of angiotensin on end-diastolic MCL was reduced to 1/3. Angiotensin reduced liver but not splenic dimension measured by ultrasonic technique. We conclude that about half of the rise in blood pressure during angiotensin infusion is due to increased end-diastolic volume caused by blood redistribution. About 2/3 of this increase in preload is due to redistribution from the splanchnic bed, mainly from the liver.     

Determinants of pulmonary blood volume. Effects of acute changes in pulmonary vascular pressures and flow

To examine the effects of pulmonary vascular pressures and flow on pulmonary blood volume (PBV), experiments were performed at constant heart rate and zone 3 conditions (mean left atrial pressure (LAP) above airway pressure) in six anesthetized, open-chest dogs. PBV was calculated as the product of electromagnetic aortic flow and pulmonary mean transit time for ascorbate, obtained without blood withdrawal by polarographic recording of aortic ascorbate changes. In three series of experiments LAP was raised similarly in three steps, from 4.5 to 14.8 mmHg: by mitral constriction which reduced pulmonary blood flow, by blood volume expansion which more than doubled pulmonary blood flow, or by a combination of the two procedures which kept pulmonary blood flow constant. In all three series, LAP and mean pulmonary arterial pressure (PAP) rose in proportion, but PBV was better correlated to PAP (r=0.87±0.02) than to LAP (r=0.66±0.09). These experiments suggest that PAP is the most important factor in determining PBV under zone 3 conditions, whether PAP is raised by increasing pulmonary blood flow or by mitral constriction.     

Molecular characterization of CTX‐M‐15‐producing clinical isolates of Escherichia coli reveals the spread of multidrug‐resistant ST131 (O25:H4) and ST964 (O102:H6) strains in Norway

Nationwide, CTX‐M‐producing clinical Escherichia coli isolates from the Norwegian ESBL study in 2003 (n=45) were characterized on strain and plasmid levels. Bla_CTX‐M allele typing, characterization of the genetic environment, phylogenetic groups, pulsed field gel electrophoresis (PFGE), serotyping and multilocus sequence typing were performed. Plasmid analysis included S1‐nuclease‐PFGE, polymerase chain reaction‐based replicon typing, plasmid transfer and multidrug resistance profiling. Bla_CTX‐M‐15 (n=23; 51%) and bla_CTX‐M‐14 (n=11; 24%) were the major alleles of which 18 (78%) and 6 (55%), respectively, were linked to ISEcp1. Thirty‐two isolates were of phylogenetic groups B2 and D. Isolates were of 29 different XbaI‐PFGE‐types including six regional clusters. Twenty‐three different O:H serotypes were found, dominated by O25:H4 (n=9, 20%) and O102:H6 (n=9, 20%). Nineteen different STs were identified, where ST131 (n=9, 20%) and ST964 (n=7, 16%) were dominant. Bla_CTX‐M was found on ≥100 kb plasmids (39/45) of 10 different replicons dominated by IncFII (n=39, 87%), FIB (n=20, 44%) and FIA (n=19, 42%). Thirty‐nine isolates (87%) displayed co‐resistance to other classes of antibiotics. A transferable CTX‐M phenotype was observed in 9/14 isolates. This study reveals that the majority of CTX‐M‐15‐expressing strains in Norway are part of the global spread of multidrug‐resistant ST131 and ST‐complex 405, associated with ISEcp1 on transferrable IncFII plasmids.     

Contributions of blood drainage from the liver,spleen and intestines to cardiac effects of aortic occlusion in the dog

By occluding the descending thoracic aorta, blood transferred from the lower to the upper part of the body increases left ventricular end-diastolic volume and maintains stroke volume despite a rise in systolic left ventricular pressure (LVP) of about 60 mmHg. Seventy percent of the blood drained stems from the splanchnic circulation. To examine which splanchnic organs contribute to the cardiac effects, selective occlusions were performed during ultrasonic measurements of spleen and liver dimensions and left ventricular myocardial chord length (MCL) in atropinized, open-chest dogs. Drainage of 15±2 ml from the spleen accounted for 18±4% of the increase in end-diastolic MCL, whereas liver dimensions remained unaltered. Similar results were obtained during aortic occlusion at high inotropy (isoproterenol infusion). it was ascertained by occlusion of the coeliac and mesenteric arteries that about 50% of the cardiac response to aortic occlusion was due to drainage from the intestines and the aorta. Liver blood volume could be reduced by combined occlusion of the aorta and portal vein or coeliac and mesentenc arteries and was sensitive to changes in pressure in the inferior vena cava, but did not contribute to the cardiac response to aortic occlusion.     

Cardiac effects of splanchnic and non-splanchnic blood volume redistribution during aortic occlusions in dogs

Translocation of blood from the lower body dilates the left ventricle during occlusion of the descending thoracic aorta and by increased activation of the Frank-Starling mechanism, stroke volume is maintained despite raised aortic blood pressure. The contributions from the splanchnic and non-splanchnic blood volumes to the left ventricular dilation were examined by ultrasonic measurements of myocardial chord length (MCL) in atropinized open-chest dogs. End-diastolic MCL rose by 2.5±0.9% during abdominal suprarenal aortic occlusion, draining blood from the non-splanchnic region, and by 7.4±1.7% during thoracic aortic occlusion draining blood from both splanchnic and non-splanchnic regions. Systolic left ventricular pressure rose by 16±3 mmHg and 76±12 mmHg, respectively. End-diastolic MCL rose by 6.0±1.2% during combined thoracic aortic and abdominal infrahepatic vena cava occlusion draining blood solely from the splanchnic region and further by 2.5±0.8% by blood drained from the non-splanchnic region after release of the vena cava occlusion. Similar results were obtained using a shunt permitting selective drainage first from the non-splanchnic region during thoracic aortic occlusion. Blood translocation from the non-splanchnic region maintains cardiac output during abdominal aortic occlusion. During occlusion of the thoracic aorta, drainage from the splanchnic region accounts for about 70% of the increase in end-diastolic MCL.     

A model for quantitative sampling of myocardial venous blood in the pig

A lack of good models for studies of myocardial metabolism prompted us to develop a model which allows the continuous measurement of myocardial blood flow and sampling of adequate amounts of coronary sinus (c. s.) blood without admixture of blood from the right atrium, with the working heart in situ. In the pig the left azygos vein drains into the c. s.and can easily be cannulated after thoracotomy. Thus, a shunt to the right atrium can be established by closing the entrance of the c. s.into the right atrium by a stitch ligature. More than 90% of shunt flow originates from the left ventricular myocardium. It is presently shown that establishing the shunt does not compromise myocardial flow, and there are no observable changes in left ventricular pressure, flow or dimensions. Myocardial flow in the drained and adjacent regions, as determined by injections of microspheres, and flow determined by electromagnetic flowmetry on the shunt are all identical. The model is stable during aortic constriction and isoproterenol infusion which induce expected changes in myocardial flow-and oxygen consumption. Thus, the model described is suitable for hemodynamic and metabolic studies of the left ventricular myocardium with the working heart in situ.     

Gastric Ulcer and Risk of Cancer

Abstract In 1976, 121 patients with benign gastric ulcer and 13 with gastric carcinoma were diagnosed in our department by endoscopy, cytology and directed biopsies. At a 5-year follow-up, 78 of these patients were re-examined with endoscopy and biopsies. None had developed gastric cancer during the observation time. Of the 78 patients who underwent endoscopy, 16 had gastric ulcer, 2 duodenal ulcer and 27 atrophic gastritis, including 3 with moderate dysplasia of the gastric mucosa. The patients with ulcer had remarkably few symptoms. Only few data are available concerning the postulated link between gastric ulcer disease and gastric malignancy. The cancer-ex-ulcere hypothesis seems to be a medical dogma. However, well planned prospective studies with endoscopic follow-up of gastric ulcers are needed to elucidate the question properly     

Prospective evaluation of an EDB-based diagnostic program to be used in patients admitted to hospital with acute chest pain

A recently designed computer based decision support system (DSP),almost exclusively based on case history data, was developedto facilitate immediate differentiation between patients withand without urgent need for coronary care unit (CCU) transferralfrom the emergency room, and additionally to distinguish betweenpatients with and without acute myocardial infarction (MI). One-year's prospective testing in a consecutive series of 1252patients with acute chest pain revealed that the DSP, used inaddition to ECG and clinical examination, demonstrated a sensitivityof 96% in the detection of patients in need of CCU observation(MI-sensitivity of 98%), and a specificity of 56% in excludingpatients who were not in need of CCU observation. The proportionof referrals to the CCU judged to be unnecessary was only 17%of the total number of patients seen in the emergency room.