PubMed Health⌕ Search

Biomedical subjects

J H Svendsen

Publications and source records attributed to J H Svendsen.

At least 37 records · Page 2Linked to original sources

Effect of 5-aminosalicylic acid on myocardial capillary permeability following ischaemia and reperfusion.

OBJECTIVE: The aim was to evaluate the effect of 5-aminosalicylic acid on myocardial capillary permeability for small hydrophilic molecules after ischaemia and reperfusion. METHODS: Open chest anaesthetised dogs were subjected to a 20 min occlusion of the left anterior descending coronary artery followed by 1 h reperfusion. 5-Aminosalicylic acid (bolus injection 12 mg.kg-1, followed by 105 micrograms.kg-1.min-1) (n = 10) or saline (control, n = 12) was given intravenously for 1 h, starting 20 min before ischaemia. The myocardial plasma flow rate, myocardial capillary extraction fraction, and myocardial capillary permeability-surface area (PS) product for 99mTc-DTPA were determined before ischaemia, and 5 and 60 min after the start of reperfusion by employing the single injection residue detection method. Immediately after reperfusion, the reactive hyperaemic plasma flow was measured by the 133Xe washout method. RESULTS: Four dogs (two untreated and two treated with 5-aminosalicylic acid) were eliminated due to ventricular fibrillation at the time of reperfusion. In the remaining animals (10 controls and eight treated) the plasma flow rate, capillary extraction fraction and PS were similar before myocardial ischaemia. After 5 min reperfusion, the plasma flow rate and PS were significantly increased in control animals (p < 0.02 and p < 0.008, respectively), but were unchanged in dogs treated with 5-aminosalicylic acid. In addition, after 5 min reperfusion, PS was significantly higher in the control group than in treated animals (p < 0.005). Microcirculatory variables returned to preocclusive values in both groups by 60 min after reperfusion. 5-Aminosalicylic acid had no significant effect on haemodynamics or on reactive hyperaemic plasma flow. CONCLUSIONS: The results suggest that 5-aminosalicylic acid can attenuate the microvascular changes after reversible myocardial ischaemia. The effect is potentially beneficial, and may be mediated by well recognised anti-inflammatory actions of 5-aminosalicylic acid (ie, scavenging of oxygen free radicals and neutrophil inhibition).

Aminosalicylic Acids↗

Effect of thrombolytic therapy on exercise response during early recovery from acute myocardial infarction: a placebo controlled study.

Several studies have shown that infarct size is reduced following thrombolytic treatment in patients with acute myocardial infarction. Exercise test variables, such as an impaired heart rate response during exercise, are known to be related to left ventricular function and patient prognosis following acute myocardial infarction. The present study was performed to compare exercise test variables in acute myocardial infarction patients following either intravenous thrombolysis or placebo. Symptom-limited bicycle ergometer tests, carried out 1-2 weeks from the infarction, were performed in 85 patients randomized to intravenous streptokinase (N = 41) or placebo (N = 44) given within 12 h from onset of symptoms. At rest heart rate, systolic blood pressure and rate-pressure product were similar in the two groups. At maximum workload the streptokinase treated patients had a higher median maximal heart rate than controls (136 vs. 126 b.min-1, P less than 0.01) but only a trend towards higher systolic blood pressure was seen (175 vs. 163 mmHg, P = 0.09). Rate-pressure product at maximal exercise was 23,620 vs. 20,100 mmHg.b.min-1 respectively, (P less than 0.01). Total exercise time, ST-segment deviation, occurrence of angina pectoris and left ventricular ejection fraction were similar in the two groups. The trend towards an increased heart rate at maximum workload in streptokinase-treated patients was seen at all levels of left ventricular ejection fraction, and at all levels of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Evaluation of left-to-right shunts in adults with atrial septal defect using first-pass radionuclide cardiography.

Non-invasive determination of left-to-right shunts at the atrial level was performed by a new procedure using first-pass radionuclide measurement of cardiac output of the right and left ventricle. In 23 patients with coronary artery disease without shunt the mean difference between the cardiac outputs of the right and left ventricle was 0.04 l.min-1, the limits of agreement -0.80 to 0.88 l.min-1 and the 95% confidence interval for the bias -0.14 to 0.22 l.min-1. Right-sided cardiac catheterization was performed to assess the severity of the arterio-venous shunt by oximetry in 18 adult patients with atrial septal defects. The range of pulmonary-to-systemic flow ratios was 1.4 to 5.0 (mean 2.7) by oximetry and 1.3 to 4.4 (mean 2.5) by the radionuclide technique. The mean difference between flow ratios measured by the two methods was 0.25, the limits of agreement, -0.85 to 1.35 and the 95% confidence intervals for the bias -0.02 to 0.52. In two patients the difference in flow ratios was more than 1. In one of these the oximetric value was more than 2, and the radionuclide value less than 2. The limits of agreement between flow ratios determined by repeated measurements were -1.05 to 0.97, and by two independent observers -0.75 to 0.77. The present findings suggest that first-pass radionuclide determination of left-to-right shunts through atrial septal defects is both reproducible and accurate when compared to the oximetric technique.

Aged↗

Miniature silicon diode matrix-detector for in vivo measurement of 133xenon disappearance in the canine myocardium following local tissue injection.

After local tissue depositioning of 133Xenon (133Xe) the regional washout is usually registered by a NaI(Tl) detector. The residual radioactivity of 133Xe is usually measured at its 81 keV photopeak. However, using small Silicon (Si) photodiodes it is feasible to measure only the low-energy activity in the X-ray energy range. In the myocardium of open chest dogs 133Xe washout measurements by a matrix of Si diodes composed in a 4 x 4 array and a conventional NaI(Tl) detector were carried out simultaneously. Fourteen separate pairs of measurements were performed in 3 dogs. When the Si-diodes in the matrix were selected individually in accordance to the position with reference to the diode with maximum count rate or pooled, comparisons could be made between the corresponding washout rate constants measured by the reference detector. In the correlation between the rate constants the intercepts with the y axis were not significantly different from zero allowing the correlation lines to be fitted through (0.0). The slope of the correlation line was close to unity. The registration of the low-X-ray energy of 133Xe by the Si-detectors is an alternative to the conventional high energy activity recording appearing from the gamma-energy of the photopeak. The detector matrix concept allows elimination of motion artefacts and indicator distribution in the myocardial tissue. Due to the uniformity and low cost of Si-diodes the perspective may be the introduction as a disposable transducer useful during cardiac surgery for example.

Animals↗

Capillary permeability of 99mTc-DTPA and blood flow rate in the human myocardium determined by intracoronary bolus injection and residue detection.

The aims of the present study were to quantitate blood flow rate and capillary permeability of 99mTc-DTPA in the human myocardium and to assess whether capillary permeability is influenced by the presence of small degree atherosclerotic lesions. Myocardial blood flow rate and capillary permeability of 99mTc-DTPA were quantitated during coronary angiography by the single injection, residue detection method. Eighteen patients undergoing a diagnostic coronary angiography because of uncharacteristic chest pain were studied. In 12 patients with angiographically normal epicardial coronary arteries, a mean value of the capillary permeability-surface area (PS) product of 54.0 ml.(100 g.min)-1 (SD 13.0) was determined from a capillary extraction of 55.0% (SD 9.4%) and a regional myocardial plasma flow rate of 74.6 ml.(100 g.min)-1 (SD 6.3) equivalent with a regional myocardial blood flow rate of 121.7 ml.(100 g.min)-1 (SD 13.0). Similar values of blood flow rate, capillary extraction fraction and the PS product were determined in 6 patients with localized coronary atheroma without hemodynamically significant coronary artery stenosis (25-50% luminal narrowing). The values for the regional myocardial blood flow rate in the human heart are in accordance with values obtained by other methods, and the PS product of 99mTc-DTPA is similar to results obtained in canine hearts. Localized coronary atheroma leading to insignificant coronary artery stenosis does not produce any measurable dysfunction of the coronary microcirculation, in terms of capillary permeability and blood flow rate, during resting conditions.

Adult↗

Heart rate index: an indicator of left ventricular ejection fraction. Comparison of left ventricular ejection fraction and variables assessed by exercise test in patients studied early after acute myocardial infarction.

The present study compares the variables assessed by standard exercise test with the left ventricular ejection fraction (LVEF) measured by multigated radionuclide angiocardiography (MUGA) in 77 patients early after myocardial infarction. The exercise test and MUGA were performed within two weeks after the myocardial infarction. A significant correlation (Spearman's correlation coefficient rs, p less than 0.05) was found between LVEF at rest and the following variables assessed at exercise test: 1) the heart rate at rest, 2) rise in heart rate, 3) ratio between maximal heart rate and heart rate at rest, 4) rise in systolic blood pressure, 5) rate pressure product at rest, 6) rise in rate pressure product, 7) ratio (rHR) between maximal rate pressure product and rate pressure product at rest, 8) total exercise time. The heart rate was corrected for effects caused by age (heart index (HR%)) and a significant correlation was found between 1) the HR% at rest, 2) the rise in HR% and the LVEF. A simple method to identify patients with an abnormal LVEF is described.

Adult↗

[Reperfusion injury in the myocardium--significance of the oxygen-derived free radicals].

Convincing proof is now available that reperfusion of the ischaemic myocardium results in release of oxygen-derived free radicals (ODFR). Experimental data support the hypothesis that ODFR play a pathological physiological role in the development of post-ischaemic systolic dysfunction (stunning), microcirculatory disturbances and reperfusion arrhythmias. In addition, the free radicals appear to modify the energy metabolic conditions after reperfusion. The results from investigations of the effects of ODFR on the extent of myocardial infarction are difficult to interpret as, in various experimental series in which formation of ODFR is reduced to a minimum, the infarct reducing effect has not been found to be in agreement with similar durations of ischaemia. The varying results concerning the extent of the infarcts suggests that other factors e.g. collateral circulation and balance between oxygen supply and oxygen requirements play a dominating role in these problems. It has not yet been elucidated whether ODFR are of significance in man in connection with reperfusion of the ischaemic myocardium.

Animals↗

Tissue to plasma capillary permeability of 131I-albumin in the perfused rabbit ear.

The tissue to plasma transfer of 131I-albumin was recorded in perfused rabbit ears (n = 6) following equilibration for 24 hr. 125I-fibrinogen served as the plasma marker, and was introduced intravenously 15 min before clamping. The ears were rollerpump perfused with isotonic diluted plasma at a constant rate of (mean +/- SD) 5.1 +/- 1.5 ml (min.100 g)-1. The mean extravascular albumin distribution volume was 12.4 +/- 1.1 ml.100 g-1, and the fibrinogen volume (plasma volume in tissue) was 3.1 +/- 0.4 ml.100 g-1 as determined from biopsies of the contralateral ear. The initial transfer of albumin was marked, and occurred at rates corresponding to a unidirectional clearance (Cl(0)) of 0.068 +/- 0.012 ml (min.100 g)-1. However, with a reduction of mean interstitial albumin tracer content of no more than 4%, net transport decreased to reach slowly declining levels 5 to 10 times lower within 10 min of continued perfusion. The decrease was considered due to rapid exhaustion of a small interstitial pool of tracer immediately adjacent to the exchange vessel membrane, followed by an increasingly retarded outwash from more distant areas. The results suggest a bimodal structural resistance to albumin movement: a relatively low resistance in the capillary membrane, and a considerable restriction to albumin transport located within the interstitial space.

Animals↗

Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium.

Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion. In anesthetized cats the hearts were excised. Apparent diffusion coefficients in cat myocardium at 37 degrees C (D'37) for 14C-verapamil (protein bound), 3H-metoprolol (lipophilic), 3H-atenolol (hydrophilic), and 3H-propranolol (lipophilic and protein bound) were determined by means of a "true transient diffusion" method and compared with the free diffusion coefficients in water (D37). D'37 of 14C-verapamil, 3H-metoprolol, 3H-atenolol, and 3H-propranolol (in cm2 s-1 10(5)) were (mean +/- SEM) 0.025 +/- 0.002, 0.055 +/- 0.003, 0.041 +/- 0.007, and 0.025 +/- 0.002, respectively. The mean diffusive progression of the concentration profile of 3H-metoprolol and 3H-atenolol into the tissue during 20 min was calculated to be 0.36 and 0.31 mm, respectively. The protein binding of 14C-verapamil and 3H-propranolol caused a significant fall in the progression to 0.24 mm for both drugs. These results indicate that, by diffusion, these drugs traverse the tissue too slowly to reach a significant amount of myocardium before myocyte necrosis occurs during conditions of noflow. Cardioprotective drugs are probably most effective, provided sufficient amounts are present in the tissue prior to the ischemic episode or sufficient supply via collateral blood flow is achieved.

Adrenergic beta-Antagonists↗

Incidence of spontaneous bacterial peritonitis in patients with ascites. Diagnostic value of white blood cell count and pH measurement in ascitic fluid.

During a 21-month period, 65 consecutive patients admitted with ascites were included in a prospective study of the incidence of spontaneous bacterial peritonitis, and paracentesis was performed on admission. The ascitic fluid was cultured, ascitic leucocytes were counted and pH was measured. Bacterial growth was found in five patients with chronic liver disease, who were diagnosed as having spontaneous bacterial peritonitis (SBP), since no intra-abdominal focus could be demonstrated. Thus, the incidence of SBP in this material was 7.7% (95% confidence limits: 2.5-17%). SBP was caused by Escherichia coli (n = 3), coagulase negative staphylococcus (n = 1), and Bacteroides species (n = 1). Abdominal tenderness, abnormal intestinal sounds, fever and hepatic encephalopathy were equally frequent in the group with SBP and in patients with sterile ascites. Infection was not anticipated in any of the patients with SBP. In contrast to several previous studies, neither ascites pH nor ascites leucocyte counts were any help in obtaining a rapid diagnosis. Survival time of patients with SBP was significantly shorter than of patients without SBP.

Ascites↗

Myocardial capillary permeability after regional ischemia and reperfusion in the in vivo canine heart. Effect of superoxide dismutase.

This study assesses the effect of the superoxide anion scavenger superoxide dismutase on myocardial capillary permeability-surface area (PS) products for small hydrophilic molecules after ischemia and reperfusion. Open-chest dogs underwent a 20-minute occlusion of the left anterior descending coronary artery followed by 1 hour of reperfusion. Myocardial plasma flow rate and capillary extraction of chromium 51-labeled EDTA or technetium 99m-labeled diethylenetriaminepentaacetic acid were measured by the single-injection, residue-detection method before ischemia and 5 and 60 minutes after the start of reperfusion. In 13 dogs, no scavenger treatment was given (nonprotected control group), whereas eight dogs were treated systemically with 15,000 units/kg superoxide dismutase during 1 hour, starting 20 minutes before ischemia. In the control group, three dogs developed reperfusion ventricular fibrillation in contrast to none in the superoxide dismutase group. Before ischemia, plasma flow rate, myocardial capillary extraction fraction, and PS values were similar in the two groups. Five minutes after the start of reperfusion, plasma flow rate increased significantly (p less than 0.01) in both groups. In the control group, capillary extraction fraction increased by 12% (p = NS) in spite of the higher plasma flow; these increases in capillary extraction fraction and plasma flow induced a 69% increase in PS (p less than 0.01). In the superoxide dismutase-treated group, capillary extraction fraction decreased by 32% (p less than 0.05) in accordance with the increased plasma flow rate, resulting in an unchanged PS (p = NS). Sixty minutes after reperfusion, plasma flow rate, capillary extraction fraction, and PS returned to preocclusion values in both groups (p = NS). The increased capillary extraction fraction and PS values seen in the control group suggest an increased capillary permeability after ischemia and reperfusion. Superoxide anions seem to participate, directly or indirectly, in this response.

Animals↗

Myocardial capillary permeability for small hydrophilic indicators during normal physiological conditions and after ischemia and reperfusion.

Myocardial capillary permeability for small hydrophilic solutes (51Cr-EDTA or 99mTc-DTPA) has been measured using intracoronary indicator bolus injection and external radioactivity registration (the single injection, residue detection method). The method is based on kinetic separation of the injected indicator molecules in an extracted and a transmitted fraction of molecules. In open chest dog hearts measurements performed during normal physiological conditions gave mean capillary extraction values of 43.5-47.5% and the corresponding calculated PdS values were 47.1 - 57.5 ml.(100g.min)-1. From these PdS values Pd values between 1.57.10(-5) and 1.92.10(-5) cm.s-1 were calculated, in accordance with values obtained by other methods. Similar data have been obtained in myocardium of patients undergoing coronary angiography. Oxygen derived free radicals seems to participate in reperfusion injury including microvascular alterations. In open chest dogs transitory increases in capillary extraction fraction and PdS for small hydrophilic solutes were seen following 20 minutes of regional myocardial ischemia and reperfusion. This response could be inhibited by treatment directed against superoxide radicals.

Animals↗

Measurement of capillary permeability in canine heart determined by the tissue injection, residue detection method.

In previous studies the tissue injection, residue detection method failed to provide results of diffusional capillary permeability comparable to those of other methods. For this reason we reconsidered the kinetic theory and found that it is necessary to take into account the apparent (restricted) diffusion coefficient of the indicator within the tissue, D', in order to determine the permeability-surface area product, PdS = Vev.D.D'-1.tev-1 = Vev'.klo where D is the diffusion coefficient in free aqueous solution, Vev is the physical interstitial water volume of distribution, Vev' is the virtual (apparent) interstitial volume of distribution, tev is the mean transit time of the indicator, and klo is the recorded fractional initial washout rate constant. In experiments on open chest dog hearts we examined capillary permeability for 51Cr-EDTA and 99mTc-DTPA with the tissue injection, residue detection method and the single injection, residue detection method. Blood flow was measured independently with local 133Xenon washout. D and D' were measured by a true transient diffusion method. We found that the tissue injection, residue detection method gave results for capillary extraction and PdS-product similar to those obtained with a number of other methods based on indicator diffusion, so the tissue injection, residue detection method in its new kinetically correct formulation could prove useful in clinical studies of capillary permeability since it is applicable to determination of relative changes of permeability during interventional procedures.

Animals↗

ECG and enzymatic indicators of therapeutic success after intravenous streptokinase for acute myocardial infarction.

Thrombolytic therapy has been documented to result in reperfusion of jeopardized myocardium and reduction in the size of the acute myocardial infarction (AMI). The effect of intravenous streptokinase on a creatine kinase-MB (CK-MB) reperfusion index and an ECG estimate of myocardial salvage was therefore studied in 65 patients with a first AMI, randomized to treatment with streptokinase (n = 33) or placebo (control group, n = 32). Reperfusion was defined as a CK-MB appearance rate constant (k1) greater than 0.185. The final AMI size was first predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. The final AMI size was estimated from the QRS score on the predischarge ECG. Myocardial salvage was defined as a greater than or equal to 20% decrease from predicted to final AMI size. The k1 value in the control group was significantly lower than that in the streptokinase group (median 0.157 versus 0.328; p = 0.0001). Accordingly the reperfusion rate was higher in the streptokinase group than in the control group (88% versus 34%; p = 0.0002). The difference in AMI size (final-predicted) was significantly greater in the streptokinase group than in the control group (median -7% versus +1%; p = 0.0001). Myocardial salvage occurred in 60% and 19%, respectively (p = 0.004). A significant correlation was found between CK-MB reperfusion and ECG salvage: 19 of 20 streptokinase-treated patients with salvage also had reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine Kinase↗

Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts.

Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

Effects of neuropeptide Y on regulation of blood flow rate in canine myocardium.

The effect of neuropeptide Y (NPY) on tension development was examined in isolated canine coronary arteries, and the effects on local myocardial blood flow rate were studied in open-chest anesthetized dogs by the local 133Xe washout technique. By immunohistochemistry, numerous NPY-like immunoreactive nerve fibers were identified in the adventitia of canine coronary arteries. NPY (10(-9)-10(-6) M) supplied to isolated epicardial segments of the left anterior descending coronary artery induced a modest vasoconstriction, with a maximum tension of 0.95 mN, that was only 6.9% of the response to K+. In contrast, intracoronary NPY (0.01-10 micrograms) induced a considerable degree of vasoconstriction; the reduction of blood flow rate was dose related, with a maximum reduction to 52% of control values. The effect of intracoronary NPY (1 microgram) on maximally relaxed arterioles elicited by 30 s of ischemia was studied in separate experiments during reactive hyperemia. NPY induced a decrease in maximum blood flow during reactive hyperemia (166.6 vs. 214.6% of preocclusive blood flow rate, mean values; P = 0.05), an increase in the cumulative excess blood flow (61.0 vs. 35.3 ml/100 g; P = 0.02), and an increase in the duration of reactive hyperemia compared with control values (66 vs. 41 s; P = 0.02). Thus we conclude that in the heart NPY is a potent vasoconstrictor that seems to act preferentially on smaller intramyocardial arterioles. Furthermore, NPY inhibits vascular relaxation of myocardial resistance vessels after ischemia, suggesting that this peptide may participate in the regulation of myocardial blood flow not only during physiological conditions but also after ischemia.

Animals↗