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Biomedical subjects

O A Smiseth

Publications and source records attributed to O A Smiseth.

At least 91 records · Page 5Linked to original sources
PubMed1986

Reversible and irreversible changes in the dog heart during acute left ventricular failure due to experimental multifocal ischaemia.

Acute left ventricular (LV) failure was induced in closed-chest pentobarbital anaesthetized dogs (n = 15), by injection of 50 micron plastic microspheres into the main left coronary artery. There were marked reductions of cardiac output and peak LV dp/dt after the embolization, while LV end-diastolic pressure (LVEDP) increased markedly. Biopsies were taken 1, 2, 3, 4, 6, 8, 10, 36, 48 hours, 7 and 14 days after injection of microspheres. Histological examination of the left ventricle revealed multiple ischaemic lesions distributed throughout the are supplied by the left main coronary artery. Oilred O staining revealed deposition of fine lipid droplets in the ischaemic cardiac muscle cells bordering on the necrotic areas. Ultrastructurally the lipid-containing cells showed numerous vacuoles localized in association with the mitochondria. The vacuoles could be observed already 1 hour after embolization and increased in number up to 48 hours. At the end of the observation period at two weeks, the number of lipid droplets was markedly reduced and the heart regained its functional activity. It is concluded that the myocardial lesions induced by coronary embolization of plastic microspheres were associated with acute left ventricular pump failure and consist of multiple foci of damaged myocardium with a central core of necrotic tissue. In the periphery of these lesions there were myocytes with lipids and other signs of light and moderate ischaemic injury. Our suggestion is that these cells represent a region of intermediate injury of "border zone" cells that are a potentially salvageable myocardium.

Animals↗
PubMed1986

The relationship between pericardial pressure and right atrial pressure: an intraoperative study.

The objective of this study was to determine the constraining effect of the normal human pericardium. Accordingly, immediately after thoracotomy in nine patients undergoing elective cardiac surgery, we measured mean pericardial surface pressure over the lateral free wall of the left ventricle with a flat balloon as well as mean right atrial pressure while incrementally infusing up to 2.1 liters of Ringer's solution to increase right atrial pressure. In each case, the slope of the relationship between right atrial (range -4 to 20 mm Hg, overall) and pericardial pressures was near unity (1.16 +/- 0.20 mean +/- SD) and the intercept was approximately zero (0.71 +/- 2.48 mm Hg). Correlation coefficients ranged from .86 to .97. These observations suggest that right atrial pressure can be used as an estimate of pericardial surface pressure. If this is the case, true left ventricular preload (i.e., effective distending pressure or transmural diastolic pressure) might be estimated from the difference between left ventricular filling pressure and right atrial pressure, both conveniently measurable clinically by means of a triple-lumen, flow-directed catheter.

Aged↗
PubMed1985

The pericardial hypothesis: a mechanism of acute shifts of the left ventricular diastolic pressure-volume relation.

Changes in LV diastolic P-V relations may be caused by changes in myocardial distensibility and by changes in extraventricular constraint. Experimental studies suggest that the upward shift of the LV diastolic P-V relation associated with pacing tachycardia, in patients with angina pectoris, is due to decreased myocardial distensibility which possibly represents incomplete relaxation. However, shifts in the LV diastolic P-V relation with vasodilator and vasoconstrictor agents seem to be caused by changes in extraventricular constraint. Experimental and clinical data show that such interventions do not significantly change the LV transmural P-V relation. This supports the hypothesis that these shifts are due to changes in pericardial pressure. Our data suggest that such vasoactive agents act by shifting blood between the (splanchnic) venous compartment and the heart, thereby changing heart size and in turn pericardial pressure. These concepts have significantly improved our understanding of the mechanisms of action of vasoactive agents. It seemed a paradox that vasodilators (e.g., nitroglycerine) could substantially lower filling pressure of the failing left ventricle without reducing cardiac output. Because of the downward-shift in the P-V relation with nitroglycerine, preload is virtually unchanged and therefore stroke volume is maintained. Appreciation of these phenomena has considerable impact on how haemodynamic measurements are interpreted. It is obvious that the use of LV end-diastolic pressure as an index of end-diastolic volume may lead to serious misinterpretations of ventricular function. Our demonstration that right atrial pressure might be used to assess pericardial pressure provides a potentially useful way to estimate LV transmural pressure, and therefore an accurate measure of preload.

Animals↗
PubMed1985

Assessment of pericardial constraint in dogs.

To determine the better method of measuring pericardial constraint, pericardial pressure was recorded by a liquid-filled open-ended catheter and a liquid-containing flat balloon in six open-chest anesthetized dogs. Left ventricular pressure was measured by a micromanometer-tipped catheter and left ventricular anteroposterior diameter was measured by sonomicrometry. Left ventricular end-diastolic pressure was raised to 20 +/- 1.7 (mean +/- SD) mm Hg by intravenous saline. Left ventricular diastolic pressure-diameter loops were constructed (1) with incremental amounts of saline (0 to 50 ml) in the resealed pericardium, (2) with several small holes in the pericardium, and (3) with the pericardium widely open. Measured pericardial pressures were compared with what was assumed to be the correct pericardial pressure, i.e., the calculated difference between left ventricular diastolic pressure (at a given left ventricular diameter) before and after opening the pericardium. Pressure recorded by the flat balloon was similar to the calculated pericardial pressure at all pericardial liquid volumes. Pressure recorded by the open-ended catheter, however, was significantly lower (p less than .05) than the calculated pressure unless there was at least 30 ml of liquid in the pericardium. After several holes had been made in the pericardium it still exerted a constraining effect, as shown by a marked rightward or downward shift of the left ventricular diastolic pressure-diameter relationships after completely opening the pericardium. After holes were made in the pericardium pressure recorded by the flat balloon was still similar to the calculated pericardial pressure. However, pressure recorded by the open-ended catheter was significantly (p less than .02) lower than the calculated pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Haemodynamic and metabolic consequences of elevated plasma free fatty acids during acute ischaemic left ventricular failure in dogs.

Haemodynamic and metabolic effects of elevated plasma concentrations of free fatty acids (FFA) were studied during acute ischaemic left ventricular failure in closed-chest anaesthetized dogs. Embolization of the left main coronary artery with 50 micron plastic microspheres induced severe depression of left ventricular performance as indicated by a marked increase in left ventricular end-diastolic pressure (LVEDP), and marked reductions in LVdP/dtmax, cardiac output and myocardial oxygen consumption (MVO2). When stable conditions were reached, eight dogs received a triglyceride emulsion and heparin to raise plasma FFA. This was associated with increased MVO2 and further elevation of LVEDP. In two dogs receiving the triglyceride emulsion but no heparin, plasma FFA was not elevated, and MVO2 and LVEDP were unchanged. In conclusion, elevation of plasma FFA was associated with increased myocardial oxygen requirement and further depression of LV function in dogs with acute ischaemic LV failure.

Animals↗
PubMed1984

Mechanism of action of nitrates. Role of changes in venous capacitance and in the left ventricular diastolic pressure-volume relation.

Nitroglycerin, when administered to patients with heart failure, causes a marked reduction in left ventricular filling pressure but often an increase in stroke volume and stroke work; based on the Frank-Starling principle, such a reduction in "preload" would be expected to result in a decrease in left ventricular end-diastolic volume and, therefore, a decline in stroke volume. Assessment of pressure-volume coordinates, however, has revealed that nitroglycerin produces a downward shift in the pressure-volume relationship. This apparent improvement in left ventricular compliance cannot be attributed to alterations in the elastic properties of the myocardium but rather appear to reflect a reduction in left ventricular external constraint. Recent animal and clinical investigations in our laboratory suggest that nitroglycerin causes venous dilatation (particularly in the mesenteric bed), thereby decreasing venous pressure at any given vascular volume. This decrease in cardiac filling pressure results in a decrease in heart size and, therefore, a reduction in pericardial pressure. Left ventricular transmural (intracavitary minus pericardial) pressure is little changed, however, so that end-diastolic volume and stroke volume are maintained.

Animals↗
PubMed1984

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs.

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

Animals↗
PubMed1983

Effects of the beta-adrenergic receptor agonist pirbuterol on cardiac performance during acute ischaemic left ventricular failure in dogs.

The effects of the beta-adrenergic receptor agonist pirbuterol on left ventricular (LV) performance were examined during acute ischaemic LV failure in anaesthetized dogs. Plastic microspheres (50 microns) were injected into the left main coronary artery, and the dogs developed severe LV failure. The stability of the heart failure model was demonstrated in a group of untreated control dogs (n = 5). Administration of pirbuterol 7 micrograms X kg-1 i.v. during failure caused an increase in cardiac output from 1.52 +/- 0.14 (mean +/- S.E.M., n = 7) to 2.56 +/- 0.32 1 X min-1 (P less than 0.01) at 30 min after drug administration. The LV end-diastolic pressure (LVEDP) decreased from 24.6 +/- 1.1 to 21.0 +/- 1.9 mmHg (P less than 0.05), and maximum LV dP/dt was increased from 2012 +/- 124 to 2602 +/- 119 mmHg X s-1 (P less than 0.01). The LVEDP-stroke work relation (n = 2) shifted markedly upward. Heart rate was not significantly changed by pirbuterol. Mean aortic blood pressure and total peripheral resistance decreased from 103 +/- 3 to 85 +/- 5 mmHg (P less than 0.05) and from 68 +/- 6 to 34 +/- 4 mmHg X 1(-1) X min (P less than 0.01), respectively. Pirbuterol increased plasma free fatty acid concentrations from 264 +/- 45 (n = 4) to a maximum value of 956 +/- 169 mumol X 1(-1). In conclusion, by a combination of inotropic stimulation and systemic vasodilation, pirbuterol markedly improved cardiac performance in dogs with acute ischaemic LV failure.

Adrenergic beta-Agonists↗
PubMed1983

Inosine infusion in dogs with acute ischaemic left ventricular failure: favourable effects on myocardial performance and metabolism.

Haemodynamic and metabolic effects of inosine were examined during acute left ventricular (LV) failure in closed-chest anaesthetised dogs. Embolisation of the left main coronary artery with 50 microm plastic microspheres induced severe depression of LV function, and the dogs remained in stable failure throughout the experimental period as shown in the untreated control dogs (n = 4). Intravenous infusion of inosine 3.8 to 7.5 mg . min-1 . kg-1 caused an increase in maximum LVdP/dt from 290 +/- 32 (mean +/- SEM, n = 8) to 376 +/- 39 kPa . s-1 and a decrease in LV end-diastolic pressure from 3.6 +/- 0.2 to 2.5 +/- 0.1 kPa. Total peripheral resistance decreased from 10.2 +/- 1.0 to 7.4 +/- 0.7 kPa . litre-1 min, and cardiac output increased from 1.64 +/- 0.17 to 2.27 +/- 0.23 litre . min-1 during inosine infusion. Myocardial blood flow increased from 65 +/- 10 to 94 +/- 16 cm3 . min-1 . 100 g-1 with no change in myocardial oxygen consumption. Inosine markedly decreased arterial concentrations and myocardial uptake of FFA. Arterial concentrations of glucose were moderately decreased while myocardial uptake of glucose showed a non-significant increase. Inosine markedly increased myocardial uptake of lactate. These metabolic changes were associated with increased plasma concentrations of insulin. In conclusion, inosine improved myocardial performance and increased myocardial uptake of carbohydrates relative to FFA during acute ischaemic LV failure in dogs.

Animals↗
PubMed1983

Progression of myocardial damage following coronary microembolization in dogs.

The aim of the present study was to determine whether induction of ischaemic heart failure by micro-embolization leads to only a single episode of myocardial injury or whether it sets up a vicious cycle of progressive myocardial damage. Acute left ventricular (LV) failure was produced in 15 closed-chest anaesthetized dogs by injection of 50 microns plastic microspheres into the left main coronary artery. The dogs showed signs of severely depressed LV function; there was a marked increase in LV end-diastolic pressure and a marked decrease in stroke volume. Myocardial lactate uptake decreased or reversed to production. Six dogs with very high LV end-diastolic pressure died during the subsequent 3 days and autopsy revealed pulmonary edema. The LV function was re-examined in four dogs at 2 and 4 weeks after embolization. Except for a modest elevation of LV end-diastolic pressure there were no haemodynamic or metabolic signs of myocardial dysfunction. Gross and light microscopic examination of the heart in dogs 8 hours to 6 weeks following microsphere injections revealed numerous small infarcts or focal areas of granulation or scar tissue throughout the entire left ventricle. At 1 to 6 weeks close to the infarcts there were scattered myocytes with strong eosinophilia and pyknosis or loss of nuclei, interpreted as myocytolysis. In two dogs killed at six weeks after the embolization there were areas of granulation tissue, similar to a recent infarction about 1 week old. Thus, in spite of apparent functional restoration there were morphological signs of repeated and progressive myocardial injury several weeks after coronary embolization.

Animals↗
PubMed1983

Regional blood flow during acute heart failure in dogs. Role of adipose tissue perfusion in regulating plasma-free fatty acids.

The effect of acute ischaemic left ventricular failure on regional blood flow and the possible role of adipose tissue perfusion in the regulation of plasma FFA during failure were examined. Left ventricular failure was induced in closed-chest anaesthetized dogs by injection of 50 micrometer plastic microspheres into the left main coronary artery. Regional blood flow, measured with tracer microspheres, showed a redistribution of cardiac output after the induction of failure. Adipose cardiac output (P less than 0.05), while skeletal muscle and pancreatic blood flow decreased about in proportion to the decrease in cardiac output. There was only a moderate decrease in renal blood flow and in left ventricular myocardial blood flow. In the free wall of the right ventricle blood flow was unchanged. There was a marked decrease in plasma FFA during failure (P less than 0.05), which could not be attributed to enhanced FFA turnover rate nor to inhibition of adipose tissue lipolysis, as plasma glycerol tended to increase. The marked decrease in adipose tissue blood flow during failure suggests that plasma FFA decreased due to trapping of FFA in adipose tissue.

Adipose Tissue↗
PubMed1982

Effect of hyaluronidase on substrate exchange and blood flow in the ischaemic myocardium of the dog.

The mechanism for reduced myocardial ischaemic injury by hyaluronidase was studied in open chest anaesthetized dogs. Repeated coronary artery occlusions were performed and the effect of hyaluronidase (225 NF units per kg) was studied during infusion of noradrenaline 0.125 mg/kg . min. Ischaemic injury was measured as the sum of ST-segment elevations (sigma ST) at 10-15 sites. Regional myocardial blood flow was determined by tracer microspheres. Blood for metabolic studies was sampled from a local coronary vein draining ischaemic tissue and from the coronary sinus draining predominantly non-ischaemic tissue. Hyaluronidase reduced sigma ST and increased subepicardial and transmural blood flow in ischaemic myocardium, but flow was not significantly changed in the ischaemic subendocardium or in non-ischaemic myocardium. Hyaluronidase had no significant effect on arterio-local venous differences of oxygen, glucose, lactate or free fatty acids across the ischaemic myocardium. In conclusion, reduction of myocardial ischaemic injury by hyaluronidase can be explained by increased collateral blood flow and not by an effect on fluxes of substrates across the ischaemic myocardium.

Animals↗
PubMed1982

A reproducible and stable model of acute ischaemic left ventricular failure in dogs.

A model of acute ischaemic left ventricular (LV) failure is presented. In closed-chest anaesthetized dogs 50 micrometer plastic microspheres were injected repeatedly into the left main coronary artery over a period of about 40 min. The injections effected stepwise elevations of LV end-diastolic pressure (LVEDP). Thus, LVEDP could be increased to a desired level, about 20 mmHg, in a very controlled manner. All dogs developed signs of markedly depressed LV performance. Haemodynamic conditions stabilized about 60 min after embolization. The maximum LVDP/dt decreased from 2696 +/- 169 to 1823 +/- 98 mmHg . x-1, cardiac output decreased from 2.81 +/- 0.20 to 1.98 +/- 0.14 l . min-1 and mean aortic blood pressure decreased from 144 +/- 4 to 127 +/- 3 mmHg, while total peripheral resistance increased from 56 +/- 3 to 69 +/- 3 mmHg . l-1 . min. Myocardial blood flow decreased from 103 +/- 7 to 79 +/- 6 ml . min-1 . 100 g-1 and myocardial oxygen consumption decreased from 12.5 +/- 0.9 to 8.3 +/- 0.8 ml . min-1. 100 g-5. Myocardial uptake of lactate and free fatty acids decreased markedly. Electrocardiography showed signs of acute ischaemia. There were no deaths due to ventricular fibrillation. Morphological studies showed multiple small infarcts throughout the entire LV. In conclusion, repeated coronary embolization with 50 micrometers plastic microspheres, guided by the rise of LVEDP represents a simple and reproducible method for induction of uniform and stable acute LV failure.

Animals↗
PubMed1981

Haemodynamic and metabolic effects of the antiarrhythmic drug melperone during acute left ventricular failure in dogs.

Haemodynamic and metabolic effects of the new antiarrhythmic drug melperone were studied during acute ischaemic left ventricular failure in closed-chest anaesthetized dogs. Embolisation of the left main coronary artery with 50 micrometer plastic microspheres induced severe depression of left ventricular performance as evidenced by a marked increase in left ventricular end-diastolic pressure and a marked reduction in the maximum rate of left ventricular pressure rise (LVdP/dtmax), cardiac output, and stroke volume. Six dogs received intravenous melperone 1.0 and 2.5 mg . kg-1 (cumulative dose) 90 and 115 min after the embolisation, respectively. Six other dogs received no treatment and served as controls. Melperone effected a marked reduction in left ventricular end-diastolic pressure, a slight but transient increase in LVdP/dtmax, a moderate reduction in heart rate, a moderate reduction in mean aortic blood pressure and total peripheral resistance and a moderate increase in stroke volume. Melperone moderately decreased myocardial O2-consumption, while myocardial lactate uptake remained unchanged. In conclusion, in contrast to commonly used antiarrhythmic drugs which may all induce cardiodepression, melperone improved left ventricular function in dogs with acute ischaemic left ventricular failure.

Acute Disease↗
PubMedDate not supplied

Intraventricular early diastolic velocity profile during acute myocardial ischemia: a color M-mode Doppler echocardiographic study.

The aim of the study was to investigate the effect of acute myocardial ischemia on the early diastolic mitral-to-apical velocity profile. Intraventricular filling velocities were measured by color M-mode Doppler echocardiography, which allows simultaneous measurements of velocities at multiple sites. Twenty patients were examined during angioplasty and eight dogs during transient coronary artery occlusion. Velocities at each 0.46 cm level from the mitral tip toward the apex were determined at the time of peak early transmitral velocity. Before angioplasty, early diastolic flow velocities decreased progressively from the mitral tip toward the apex. During angioplasty, intraventricular velocities showed a more abrupt decrease from the middle region toward the apex (p < 0.05). A similar change in the mitral-to-apical profile was found during myocardial ischemia in dogs (p < 0.05). Also, there was a decrease in peak early transmitral velocity (p < 0.01) and peak early transmitral pressure gradient (p = 0.06). Volume loading and constriction of the caval veins performed in the nonischemic ventricle did not appear to change the mitral-to-apical velocity profile. Regional myocardial ischemia was associated with a change in the mitral-to-apical velocity profile as measured by color M-mode Doppler echocardiography. The altered filling pattern could not be explained by changes in loading conditions and may reflect impaired relaxation of the ischemic ventricle.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

Vasodilator and inotropic effects of the antiarrhythmic drug melperone.

We investigated the hemodynamic and inotropic effects of the new class III antiarrhythmic drug melperone. In eight pentobarbital-anesthetized dogs, the effects of intravenous melperone 0.5, 2.5, and 12.5 mg/kg-1 were tested. During atrial pacing we measured cardiac output (CO), mean aortic blood pressure (MAP), right (RV) and left (LV) ventricular pressures, and LV dP/dt. In six RV papillary muscles isolated from cats and suspended in a muscle bath containing Krebs-Henseleit solution, we studied the direct effects of melperone 10(8)-5 X 10(-5) M. Administration of melperone decreased total peripheral resistance, MAP, RV and LV systolic and end-diastolic pressures, while CO remained unchanged. Melperone increased LV dP/dtmax. The contractile force (F) and dF/dtmax of the isolated ventricular muscle preparations increased slightly with increasing concentrations of melperone, up to 10(-5) M. In conclusion, melperone has vasodilator and slight positive inotropic effects in addition to its class III antiarrhythmic effect.

Animals↗