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Biomedical subjects

O A Smiseth

Publications and source records attributed to O A Smiseth.

At least 55 records · Page 3Linked to original sources

[Lipid-lowering medication--indications and possible hazards. Report from a hearing].

Drug treatment of hyperlipidaemia should be founded on scientific evidence. A hearing was arranged to arrive at practical measures based on reported clinical trials. Several studies during recent years have shown regression of coronary atheromatosis, and some people would say the effect is striking. Studies using clinical endpoints, like morbidity and mortality, have not yielded equally convincing results, but it should be noted that the results of studies with more than 10% reduction in total serum cholesterol levels are not yet available. So far, the trials have been too small to judge effects on total mortality. It is uncertain whether the treatment actually has untoward effects on the incidence of violent deaths and neoplasms. An upper limit for drug treatment of about 8 mmol/l was proposed during the hearing. The limit can be lowered to 7 if established coronary disease is present. For women without coronary disease the limit should be higher than that for men. All in all, this implies an increase in the total number of individuals treated compared with present practice. It was agreed that at present, high risk individuals are undertreated. The new levels have been set partly on the basis of economic considerations.

Arteriosclerosis↗

Changes in pulmonary vein flow pattern during volume loading.

OBJECTIVE: The aim was to investigate the effect of increased left ventricular filling pressure on the pulmonary vein flow (PVQ) pattern. METHODS: Pulmonary vein flow was recorded using an ultrasonic transit time flow meter in six anaesthetised dogs. Mean left atrial pressure was increased by stepwise volume loading from 7.8(SEM 1.3) to 18.9(1.9) mm Hg (p < 0.01). RESULTS: With loading the PVQ signal developed several characteristic positive and negative waves which corresponded to directionally opposite pressure waves in the left atrium. There was a marked increase in the amplitude of the PVQ signal: peak flow increased from 165(50) to 310(38) ml.min-1 (p < 0.01), while minimum flow decreased from 49(37) to -61(23) ml.min-1 (p < 0.01). The minimum value of PVQ occurred during early ventricular systole, corresponding to the left atrial C wave. With progressive loading there was an increasing deceleration of flow during atrial contraction. To quantify the effect of atrial contraction and the C wave on the flow pattern a ratio was calculated between the integrated flow from the start of atrial contraction to the nadir of the x descent and the integrated flow during the rest of the cardiac cycle. This ratio decreased from 0.40(0.06) to 0.11(0.07) with loading (p < 0.01). In each experiment this flow ratio varied inversely with mean left atrial pressure (regression coefficients between 0.66 and 0.97). CONCLUSIONS: Volume loading caused marked changes in the pulmonary vein flow pattern. The PVQ waves reflected the pressure waves in the left atrium. The relative flow during atrial contraction varied inversely with mean left atrial pressure. Further studies should be done to determine whether this index reflects left ventricular filling pressure under different conditions.

Animals↗

Effect of nifedipine on splanchnic and pulmonary vascular capacitance.

This study examines the hypothesis that nifedipine may increase splanchnic vascular capacitance and thus change the distribution of blood between the splanchnic and pulmonary circulation in heart failure patients. Relative regional blood volumes were determined by equilibrium blood pool scintigraphy during a 10 min baseline period and for 30 min after nifedipine 20 mg sublingually, with simultaneous recordings of systemic and pulmonary arterial pressures, hepatic venous wedge pressure, and cardiac output. Eight patients with ischaemic heart failure received nifedipine. Four patients served as controls. Nifedipine reduced mean arterial pressure and systemic vascular resistance in every patient. There were no significant changes in the relative blood volumes of the intestinal, hepatic, or splenic regions or in hepatic venous wedge pressure (reflecting portal venous pressure), suggesting unchanged splanchnic vascular pressure-volume relationship. Nifedipine caused a 6.3 +/- 1.0% increase in relative pulmonary blood volume and a slight increase in pulmonary vascular distending pressure from 16.1 +/- 2.9 mmHg to 17.5 +/- 2.8 mmHg (P < 0.05), suggesting that the increase in pulmonary blood volume was passively mediated. In conclusion, nifedipine did not change splanchnic vascular capacitance, but caused a small increase in pulmonary blood volume, which probably was a passive response to increased distending pressure.

Adult↗

Intraventricular early diastolic filling during acute myocardial ischemia, assessment by multigated color m-mode Doppler echocardiography.

BACKGROUND: Color M-mode Doppler echocardiography has been suggested as a new noninvasive technique for assessing left ventricular diastolic function. The present study investigated intraventricular filling pattern by color M-mode Doppler in patients during percutaneous transluminal coronary angioplasty (PTCA). In a dog model of myocardial ischemia, the color M-mode flow pattern was related to indices of global and regional myocardial function. METHODS AND RESULTS: From color M-mode images, the time difference (TD) between occurrence of peak velocity in the apical region and at the mitral tip was determined in 20 patients and eight anesthetized dogs during coronary occlusions. During PTCA, the timing of peak velocity was progressively delayed from mitral valve to apex. Consistent with this, the dog model showed delayed apical filling during coronary occlusion; TD increased from 18 +/- 4 to 71 +/- 9 milliseconds (P < .01). In the ischemic region, systolic shortening (sonomicrometry) decreased from 20 +/- 3% to -5 +/- 2% (p < .01). The one-third filling fraction decreased from 59 +/- 5% to 31 +/- 6% (P < .01) and correlated with TD (r = .85, P < .01). The time constant of isovolumic relaxation (tau) increased slightly and correlated with TD (r = .81, P < .01). Pacing tachycardia, caval constriction, and volume loading were performed to mimic the ischemia-induced changes in heart rate, stroke volume, and intracavitary filling pressure, respectively. There were no significant changes in TD or tau during these interventions. CONCLUSIONS: Color M-mode Doppler echocardiography showed a marked delay of apical peak filling velocity during PTCA. The experimental data suggest that this reflects retarded filling of the ischemic ventricle. Thus, color M-mode Doppler may provide a useful method for assessing diastolic dysfunction.

Adult↗

Haemodynamic effects of selective positive end-expiratory pressure after unilateral pulmonary hydrochloric acid-aspiration in dogs.

We investigated 1) the effects of HCl-mediated acute left lung injury on regional juxtacardiac pressures and 2) the haemodynamic effects of different modes of ventilation before and after induction of left lung injury. The study was done in 7 mechanically ventilated, anaesthetized dogs. Juxtacardiac pressures and haemodynamic variables were recorded during 1) differential ventilation (DV) with zero positive end-expiratory pressure (PEEP = 0) and 2) DV with general (G) PEEP and selective right (R) and left (L) lung PEEP. Left lung injury increased left, but not right pleural pressure of pericardial pressure. Pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) were increased moderately. Cardiac output (CO) did not change. GPEEP reduced LV filling and cardiac output markedly and by approximately the same degree before and after lung injury. The haemodynamic effects of LPEEP were minor before as well as after the induction of lung injury. RPEEP, which had only moderate haemodynamic effects during control, caused a marked reduction in cardiac function after the induction of left lung injury. The transmission of airway pressure to the pleura was reduced in the diseased lung. These results suggest that serious haemodynamic side effects may be avoided by applying PEEP selectively to the diseased lung.

Animals↗

Effect of the pericardium on atrial systolic function.

The effect of pericardial constraint on atrial systolic function was investigated in nine acutely instrumented anesthetized dogs. Left and right atrial pressures were recorded by high-fidelity catheters; auricular diameters and free wall segment lengths were measured by sonomicrometry. Atrial function curves were constructed by relating atrial systolic dimensional shortening to atrial end-diastolic pressure during progressive volume loading. With the pericardium closed, the function curves were shifted markedly downward and rightward, such that atrial systolic shortening was reduced at any given pressure. There was a concomitant leftward and upward shift of the atrial end-diastolic pressure-dimension relationship. The relationship between atrial systolic shortening and atrial end-diastolic dimension was not shifted. These results suggest that the apparent depression of atrial systolic function with the pericardium closed is due to a restrictive effect of the pericardium on atrial filling. In conclusion, in the acutely dilated heart, the pericardium restricts atrial filling and thus causes a reduction in atrial systolic contribution to ventricular filling.

Animals↗

Selective positive end-expiratory pressure and intracardiac dimensions in dogs.

Effects of differential ventilation with general vs. selective right (R) and left (L) positive end-expiratory pressure (PEEP) on left (LV) and right ventricular (RV) end-diastolic dimensions were compared in seven pentobarbital-anesthetized dogs. All three modes of PEEP reduced LV cross-sectional area: general PEEP more than RPEEP and RPEEP more than LPEEP. General PEEP and, to a lesser degree, RPEEP decreased both the LV anteroposterior diameter and LV septum-free wall diameter, whereas LPEEP reduced the LV septum-free wall diameter only. Cardiac output was unaffected by LPEEP, whereas general PEEP (20 cmH2O) reduced cardiac output by 48%, and RPEEP (20 cmH2O) reduced it by 23%. RV septum-free wall diameter was not changed by any mode of PEEP. In conclusion, cardiac output was better maintained with selective PEEP than with general PEEP because LV filling was less impeded with selective PEEP. During LPEEP LV assumed a different configuration than during RPEEP and general PEEP, probably reflecting a different pattern of heart-lung interaction.

Animals↗

Nitroprusside and regional vascular capacitance in patients with severe congestive heart failure.

BACKGROUND: This study investigates the effects of sodium nitroprusside on regional vascular capacitance in eight patients with severe congestive heart failure (New York Heart Association class IV) and pulmonary hypertension. METHODS AND RESULTS: Regional relative blood volumes in the splanchnic and pulmonary region were determined by equilibrium blood pool scintigraphy. Hepatic venous wedge pressure and the mean of pulmonary artery and pulmonary capillary wedge pressure were used to represent the distending pressures of the splanchnic and pulmonary capacitance vessels, respectively. The dose of sodium nitroprusside was increased stepwise until systolic pulmonary artery pressure decreased below 50 mm Hg. This caused reductions in mean aortic pressure from 89 +/- 5 to 66 +/- 3 mm Hg (p less than 0.005), in pulmonary capillary wedge pressure from 31 +/- 1 to 16 +/- 2 mm Hg (p less than 0.001), and in hepatic venous wedge pressure from 10.0 +/- 1.0 to 5.9 +/- 0.6 mm Hg (p less than 0.005). Intestinal blood volume increased by 26 +/- 7% (p less than 0.005), whereas hepatic blood volume decreased by 9 +/- 3% (p less than 0.02). Pulmonary blood volume was unchanged. Analysis of intestinal and pulmonary vascular pressure-volume relations showed larger or equal blood volumes contained at lower distending pressures, indicating that sodium nitroprusside reduced smooth muscle tone of the capacitance vessels in these regions. The reduction of hepatic blood volume was compatible with passive expulsion of blood subsequent to reduced venous pressure. There was no change in the count rate from the spleen. CONCLUSIONS: Nitroprusside reduced venous pressure in patients with congestive heart failure by active relaxation of intestinal and pulmonary capacitance vessels. Hepatic vascular volume was probably reduced by a passive mechanism.

Gated Blood-Pool Imaging↗

The effect of nitroglycerin on pulmonary vascular capacitance in dogs.

In this study we investigated the hypothesis that the decrease in pulmonary vascular pressures observed after administration of nitroglycerin is in part due to a shift in the pulmonary vascular pressure-volume relationship. The experiments were done in six closed-chest dogs anesthetized with pentobarbital, in which pulmonary, cardiac, and intestinal relative blood volumes were determined by equilibrium blood pool scintigraphy. Nitroglycerin (30 micrograms/kg/min) caused 7% (p less than 0.02) and 12% (p less than 0.02) reductions in pulmonary and total cardiac blood volume, respectively, and a 7% (p less than 0.01) increase in intestinal blood volume. This shift of blood from the heart and the pulmonary circulation to the systemic (intestinal) circulation was accompanied by reductions in mean pulmonary artery pressure from 16 +/- 2 mm Hg to 12 +/- 1 mm Hg (p less than 0.01), in mean pulmonary capillary wedge pressure from 11 +/- 2 mm Hg to 6 +/- 1 mm Hg (p less than 0.01), and in mean portal pressure from 9 +/- 1 mm Hg to 8 +/- 1 mm Hg (p less than 0.01). The position of the pulmonary vascular pressure-blood volume relationship was unaffected by nitroglycerin, whereas the portal pressure-intestinal blood volume relationship was shifted to the left and upward. These changes suggest that pulmonary vascular tone remained unchanged, whereas intestinal vascular tone decreased during administration of nitroglycerin. In conclusion, nitroglycerin decreased pulmonary vascular pressures through a passive emptying of the pulmonary circulation as a result of increased systemic (intestinal) vascular capacitance.

Animals↗

Endocrine responses to positive end-expiratory pressure ventilation in patients who have recently undergone heart surgery.

The effect of positive end-expiratory pressure ventilation (PEEP) on angiotensin II and atrial natriuretic factor (ANF) was studied postoperatively following heart surgery. In nine patients pressures were recorded in the radial artery, pulmonary artery and the right atrium. PEEP of 5 cmH2O (0.5 kPa) and 10 cmH2O (1 kPa) increased angiotensin II from 38.8 +/- 20.3 (mean +/- s.e.mean) to 56.7 +/- 29.6 (n.s.) and 66.7 +/- 28.7 (P less than 0.05) pmol/l, respectively. Plasma-ANF showed no significant changes during PEEP. Pulmonary artery wedge pressure increased from 12.9 +/- 2.0 to 14.1 +/- 2.0 (n.s.) and 18.5 +/- 2.1 (P less than 0.01) mmHg, and right atrial pressure from 8.3 +/- 1.7 to 9.8 +/- 1.7 (n.s.) and 12.9 +/- 1.7 (P less than 0.01) mmHg with 5 and 10 cmH2O (0.5 and 1.0 kPa) of PEEP, respectively. Systemic blood pressure tended to decrease (n.s.) with PEEP. In conclusion, PEEP markedly increased angiotensin II. This may represent an important compensatory mechanism, helping to prevent reduction in aortic pressure during PEEP. ANF, however, did not change with PEEP of 5 or 10 cmH2O (0.5 and 1.0 kPa).

Anesthesia, General↗

The effect of positive end-expiratory pressure ventilation on atrial filling.

As a measure of atrial filling, left and right auricular diameter and free wall segment length were recorded by sonomicrometry during incremental positive end-expiratory pressure (PEEP) in eight acutely instrumented closed chest dogs. The effect of PEEP was assessed with the pericardium open (n = 6) and closed (n = 8). On both occasions, PEEP decreased left auricular diameter (P less than 0.05). PEEP also caused a reduction in right auricular diameter with the pericardium open (P less than 0.05), while the variable was unchanged with the pericardium closed. PEEP did not cause any changes in either left or right free wall segment lengths. Both left and right auricular pressure-diameter relationships were progressively shifted leftwards with incremental PEEP. These observations suggest that PEEP may reduce left ventricular output not only by interfering with passive ventricular filling, but also by reducing atrial dimensions.

Anesthesia, Inhalation↗

The relationship between atrial pressure, atrial dimensions and atrial natriuretic factor during pacing tachycardia in dogs.

Acute supraventricular tachycardia is known to increase the plasma level of atrial natriuretic factor (ANF). The purpose of these experiments was to investigate if such an increase in plasma-ANF could be ascribed to changes in atrial pressure and atrial dimensions. Eight anaesthetized dogs were instrumented with atrial pressure catheters and sonomicrometers to measure left and right auricular and atrial free wall dimensions. An acute increase in atrial rate from 150 to 200 min-1 for 10 min did not change plasma-ANF or atrial haemodynamic variables. A further increase in atrial rate to 250 or 300 min-1 increased right and left atrial intracavitary pressures (P less than 0.01), both auricular diameters and right atrial free wall segment length (P less than 0.05). Left atrial free wall segment length remained unchanged. Plasma-ANF increased in all dogs (P less than 0.01). The change in plasma-ANF correlated well with changes in atrial pressures as well as with changes in atrial dimensions. These results support the hypothesis that release of ANF during acute atrial tachycardia may in part be attributed to atrial dilatation.

Animals↗

Left and right ventricular diastolic function during acute pericardial tamponade.

The aim of the study was to determine the effect of acute pericardial tamponade on left (LV) and right ventricular (RV) intracavitary and transmural pressure-volume (P-V) relations and to assess the effect of changing blood volume during tamponade on LV and RV volumes. The experiments were done in 11 acutely instrumented anaesthetized dogs in which LV and RV volumes were determined by computed tomography (CT) (n = 5) and LV and RV diameters by sonomicrometry (n = 6). Pressures were measured in the pericardium (balloon transducer), in the aorta and in the ventricles. Incremental pericardial infusion (up to 180 ml) caused a progressive left and upward shift of the LV and the RV intracavitary P-V relationship. This shift was entirely due to increased pericardial pressure (PP). The induction of tamponade caused no change in the LV and RV transmural P-V relationship. During tamponade with ventricular filling pressures above 10-15 mmHg, blood volume expansion caused only minimal increase in LV and RV volumes. In conclusion, pericardial tamponade shifted the LV and the RV intracavitary diastolic P-V relation by increasing PP. However, there was no change in the transmural P-V relationship, indicating unchanged myocardial compliance. Volume loading caused only minimal increase in LV and RV volumes during tamponade.

Animals↗

Rate-induced increase in plasma atrial natriuretic factor can occur independently of changes in atrial wall stretch.

Tachycardia is known to increase the plasma level of atrial natriuretic factor (ANF). The aim of the study was to determine whether such release of ANF can occur independently of increased atrial wall stretch. Seven anesthetized dogs were instrumented with pressure catheters and sonomicrometer crystals to measure left and right auricular and atrial free wall dimensions. During atrial pacing, the measured atrial dimensions were kept constant by adjusting vascular constrictors placed around the great vessel trunks. When atrial rate was increased progressively by pacing at 150, 200, and 250 min-1, plasma ANF increased from 40.8 +/- 5.4 to 43.0 +/- 6.0 (P = NS) and 103.1 +/- 17.6 (SE) pmol/l (P less than 0.05), respectively. Repeating the pacing sequence at two different levels of elevated left atrial pressure caused at each level a similar increase in plasma ANF at 250 min-1. The relationship between plasma ANF and atrial dimensions was shifted upward by pacing, such that ANF was higher for any given atrial dimension. In conclusion, pacing tachycardia elevates plasma ANF in the presence of constant atrial dimensions. These results support the hypothesis that chronotropic stimulation can cause release of ANF by a mechanism that is independent of atrial stretch.

Animals↗

Blood volume changes in liver and spleen during cardiogenic shock in dogs.

Changes in vascular capacitance of the liver and spleen were studied in seven anesthetized dogs during cardiogenic shock induced by coronary microembolization. Left ventricular end-diastolic pressure increased from 2 +/- 2 to 28 +/- 4 mmHg (P less than 0.001), and mean aortic pressure decreased from 111 +/- 7 to 56 +/- 9 mmHg (P less than 0.001). Hepatic venous pressure increased from 1.8 +/- 0.6 to 5.0 +/- 1.0 mmHg (P less than 0.05). Portal venous pressure did not change. Blood volume changes were assessed from sonomicrometric measurements of organ diameters. Hepatic diameter increased after embolization, corresponding to an estimated 54 +/- 14 ml increase of hepatic blood volume (P less than 0.01). Splenic diameter gradually decreased during shock until an estimated 33 +/- 12 ml of blood had been released (P less than 0.05). Occlusion of hepatic venous outflow by a balloon catheter was used to cause ramp changes in hepatic volume and hepatic venous pressure so that a pressure-volume curve could be estimated. Analysis of the hepatic curves showed an increase in unstressed volume with no change in vascular compliance during shock. The blood volume increase could in part be attributed to increased outflow pressure, but active dilation of hepatic capacitance vessels probably contributed. Splenic curves were shifted downward, suggesting expulsion of blood by active contraction.

Animals↗

Splanchnic vascular capacitance and positive end-expiratory pressure in dogs.

We have investigated the effect of positive end-expiratory pressure ventilation (PEEP) on regional splanchnic vascular capacitance. In 12 anesthetized dogs hepatic and splenic blood volumes were assessed by sonomicrometry. Vascular pressure-diameter curves were defined by obstructing hepatic outflow. With 10 and 15 cmH2O PEEP portal venous pressure increased 3.1 +/- 0.3 and 5.1 +/- 0.4 mmHg (P less than 0.001) while hepatic venous pressure increased 4.9 +/- 0.4 and 7.3 +/- 0.4 mmHg (P less than 0.001), respectively. Hepatic blood volume increased (P less than 0.01) 3.8 +/- 0.9 and 6.3 +/- 1.4 ml/kg body wt while splenic volume decreased (P less than 0.01) 0.8 +/- 0.2 and 1.3 +/- 0.2 ml/kg body wt. The changes were similar with closed abdomen. The slope of the hepatic vascular pressure-diameter curves decreased with PEEP (P less than 0.01), possibly reflecting reduced vascular compliance. There was an increase (P less than 0.01) in unstressed hepatic vascular volume. The slope of the splenic pressure-diameter curves was unchanged, but there was a significant (P less than 0.05) decrease in unstressed diameter during PEEP. In conclusion, hepatic blood volume increased during PEEP. This was mainly a reflection of passive distension due to elevated venous pressures. The spleen expelled blood and thus prevented a further reduction in central blood volume.

Animals↗

[Drug therapy of acute coronary syndrome. Summary of a hearing arranged by the Norwegian Cardiologic Society and the Institute of pharmacotherapy].

Acute coronary syndrome is defined as unstable angina or acute myocardial infarction. A discussion on drug treatment of these conditions was arranged by the Norwegian Society of Cardiology and the Department of Pharmacotherapeutics, University of Oslo, soon after preliminary results of the GISSI II study were available. Relatively simple rules were agreed for the use of analgetics, nitrates and fibrinolytic agents. The last are used only after established myocardial injury. Consensus was also reached on the restricted use of calcium antagonists, inotropic agents and diuretics. There was disagreement concerning the dosage of heparin and the exact use of betablockers, aspirin, warfarin, ACE-inhibitors, magnesium and antiarrhythmics.

Adrenergic beta-Antagonists↗

Selective positive end-expiratory pressure and cardiac function in dogs.

Effects of general (G) versus selective (S) right (R) and left (L) positive end-expiratory pressure (PEEP) were compared during differential lung ventilation in 11 anaesthetized dogs in the supine position. GPEEP 20 cmH2O decreased cardiac output (1 min-1) from 2.9 +/- 0.2 (mean +/- SE) to 1.7 +/- 0.5 (p less than 0.05), RPEEP from 2.8 +/- 0.2 to 2.2 +/- 0.2 (p less than 0.05) while LPEEP caused no significant change in cardiac output. GPEEP increased pleural pressure more than SPEEP. Pleural pressure was asymmetric during SPEEP. Both SPEEP and GPEEP increased pericardial pressure uniformly, but the increase was less marked with SPEEP. During GPEEP 20 cmH2O transmural left ventricular end-diastolic pressure (LVEDP) decreased markedly. SPEEP caused less marked reductions in transmural LVEDP. Qualitatively similar, but less marked changes were observed with PEEP 10 cmH2O. In conclusion, cardiac output decreased less with selective PEEP than with general PEEP. This was explained by less increase in pleural and pericardial pressure, and accordingly less decrease in LV transmural filling pressure.

Animals↗