[Dependence of the arterial blood pressure on cardiac filling in severe orthostatic hypotension]. / Det arterielle blodtryks afhaengighed af hjertets fyldning ved svaer ortostatisk hypotension.

The present study aimed at an investigation of the relation between arterial blood pressure and cardiac filling in patients with severe postural hypotension. Seven patients aged 49 to 84 years were studied during head-up tilt at three different tilt angles (median values: 0, 25, and 45 degrees) using intraarterial blood pressure recordings and estimates of left ventricular volumes by radioisotope ventriculography. Mean arterial blood pressure was reduced from 105 mmHg (79-129) in the horizontal position to 97 mmHg (61-112) and 83 mmHg (36-93; p < 0.0001), respectively, in parallel with a reduction in left ventricular end-diastolic volume index from 59 ml m-2 (30-65) to 36 ml m-2 (23-44) and 22 ml m-2 (16-38; p < 0.001). Left ventricular contractility was high, and the postural reductions in cardiac output were unopposed by vasoconstriction. The study has demonstrated that blood pressure is strongly dependent upon cardiac filling in severe postural hypotension, and has underlined the importance of intravascular volume expansion as a measure against postural hypotension.

[The effect of thrombolytic therapy on the outcome of early exercise test in patients with acute myocardial infarction]. / Effekt af trombolytisk behandling på udfaldet af tidlig arbejdstest hos patienter med akut myokardieinfarkt.

UNLABELLED: Exercise test variables, such as an impaired heart rate response, 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 infarct patients following either intravenous thrombolysis or placebo. Symptom-limited bicycle ergometer tests, carried out one to two weeks from the infarction, were performed in 85 patients randomized to intravenous streptokinase (n = 41) or placebo (n = 44) given within 12 hours from onset of symptoms. Resting heart rate, systolic blood pressure and rate-pressure product were similar in the two groups. At maximum workload the streptokinase treated patients had a significantly higher median maximal heart rate than controls (136 vs. 126 min-1; p < 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 x min-1; p < 0.01). A significantly smaller number of patients in the streptokinase group had exercise capacity below 50 W (0% vs. 15.9%; p < 0.01). IN CONCLUSION: patients treated with intravenous streptokinase for acute myocardial infarction reach both higher heart rates and rate-pressure products at maximum workload than their controls thus indicating that the beneficial effects of thrombolysis after acute myocardial infarction are reflected in an improved heart rate response during exercise.

Dependency of blood pressure upon cardiac filling in patients with severe postural hypotension.

Autonomic denervation of the vascular bed results theoretically in a stronger dependency of blood pressure upon intravascular volume, and the study described aimed at an investigation of the relation between cardiac filling and arterial blood pressure in patients with severe postural hypotension. Seven patients were studied during head-up tilt at three different tilt angles using intra-arterial blood pressure recordings and estimates of left ventricular volumes by radioisotope ventriculography. Blood pressure fell dramatically during head-up tilt due to reductions in cardiac output unopposed by vasoconstriction. The reduction in cardiac output resulted from reductions in left ventricular end-diastolic volumes with unchanged left ventricular ejection fractions and only moderate increments in heart rate. The study was demonstrated that blood pressure is strongly dependent upon cardiac filling in severe autonomic dysfunction, and that volume expansion is an important measure against postural hypotension.

The effect of erythropoietin on platelet function and fibrinolysis in chronic renal failure.

The influence of erythropoietin therapy on platelet function and fibrinolysis was evaluated in 12 anemic hemodialysis patients. Six months of therapy with human erythropoietin (50 to 80 IU/kg initially) raised the hemoglobin level to 10.8 g/dl but did not increase platelet activity in vivo as measured by beta-thromboglobulin or platelet factor 4. There was no change in the platelet aggregation thresholds in vitro for ADP, adrenaline, thrombin or collagen during treatment. Platelet number and volume were also unaffected. Fibrinolytic activity intensified as erythropoietin treatment proceeded, with a fall of euglobulin clot lysis time and rise in the activity of t-PA. PAI-1 levels also showed a downward trend, without reaching significance. Thus erythropoietin treatment in modest doses does not seem to adversely influence the hemostatic system in patients on hemodialysis.

Erythropoietin treatment does not compromise cardiovascular function in chronic renal failure.

The anemia in patients with chronic renal failure can be corrected through treatment with recombinant human erythropoietin treatment. This correction is associated with changes in the rheologic variables, which could explain the changes in hemodynamics found by many investigators. The authors have followed up 11 patients with chronic renal failure on hemodialysis before and during six months of therapy with erythropoietin. The measurements were made before treatment, after four months of therapy, and after six months of therapy. The measurements included hematocrit, osmotic resistance of the red blood cells, red blood cell volume, plasma volume, heart rate, arterial blood pressure, and cardiac output measured by the indicator dilution method. They found a significant increase in hematocrit hemoglobin, and red blood cell volume and a decrease in osmotic resistance while the hemodynamic variables were unchanged. The conclude that, in spite of changes in rheologic variables, increasing viscosity of the blood and thus possibly increasing the peripheral resistance, these had no effect on the cardiovascular state. Erythropoietin treatment improves the subjective well-being in patients on chronic hemodialysis without compromising their cardiovascular function.

The left ventricular end-systolic pressure and pressure-volume index. Comparison between invasive and auscultatory arm pressure measurements.

The slope of the left ventricular (LV) end-systolic pressure-volume relation (ESPVR) has been established as a valuable clinical method to assess LV contractile function independent of LV loading factors. The purpose of the present study was to evaluate whether the ESPVR could be reliably determined from auscultatory blood pressure (BP) measurements and from LV volume measurement by contrast ventriculography (CVG). Twenty-four patients with suspected or known ischemic heart disease were studied by cardiac catheterization with simultaneous, blinded, intravascular and auscultatory pressure measurements. LV volume was determined by CVG. The auscultatory mean arterial blood pressure (MAP) derived from: [formula: see text] was found to be a useful measure of the LV end-systolic pressure in this connection. The correlation between invasively measured LV end-systolic pressure (ESP) and MAP was highly significant (r = 0.82; SEE = 6.9 mmHg; p = 0.001). The correlation between invasively and semi-invasively measured ESPVR fell close to the line of identity (r = 0.99; SEE = 0.23 mmHg.mL-1; p < 0.001). The replacement of ESP by MAP induced only a minimal error in the assessment of the ESPVR. A complete noninvasive determination of the ESPVR and LV contractility therefore seems possible by using the MAP and by measuring the end-systolic volume by radionuclide ventriculography or by echocardiography.

Hormonal and hemodynamic changes following single-dose felodipine treatment during mental stress.

Mental stress induces changes in hemodynamic variables and in the plasma level of many hormones and plasma peptides. These changes can be modulated by various drugs, eg, beta-blockers. In a double-blind, placebo-controlled crossover study, the authors evaluated the hormonal and hemodynamic changes during psychological stress and the effect of felodipine 10 mg (plain tablet). Eight male volunteers participated. Heart rate, blood pressures, and stroke volume were measured by ECG, mercury sphygmomanometer, and impedance cardiography. Catecholamines and atrial natriuretic factor in plasma were measured by electrochemical and radioimmunoassay techniques. A single dose of felodipine, 10 mg, exaggerates the heart rate decreases the left ventricular ejection time and augments the plasma level increment of noradrenaline. The stress-induced changes in other variables were not influenced by felodipine treatment. In conclusion, acute felodipine treatment influences the reflex activation of the sympathetic nervous system during psychological stress. In the treatment of patients, especially patients with heart disease, these findings could be important but further investigations in patients need to be done.

Platelet activation in mental stress.

Platelets are known to become activated in vivo by different stressful stimuli such as surgery and dynamic exercise. Mental stress has been shown to increase platelet aggregability. Platelet activation is thought to be of major importance in atherogenesis and cardiac fatalities. In order to clarify further stress-induced platelet activation with special reference to the period after the stress, we studied eight young, healthy volunteers during and for 1 h after a mental stress test (Stroops Colour Word Conflict Test). Using highly standardized techniques, we have measured platelet aggregability ex vivo and the platelet release products beta-thromboglobulin, platelet factor 4 and serotonin in plasma. As markers of the stress response we measured cyclic-AMP in plasma, heart rate, cardiac output and blood pressure. The stress test induced a significant cardiovascular response with increases in heart rate, blood pressure, and cardiac output and as a measure of adrenergic activity an increase in cyclic AMP in plasma during the test. Platelet aggregability was unaffected during the test but decreased following the stress. During the first hour following the test and release products beta-thromboglobulin and serotonin increased significantly in plasma. We conclude that platelets are activated during mental stress and that this activation involves a post-stress release of vasoactive compounds from platelets.

[Systolic blood pressure at rest and during submaximal and maximal exercise on ergometer bicycle. The value of automatic and auscultatory determination]. / Systolisk blodtryk i hvile og under submaksimal og maksimal arbejdsbelastning på ergometercykel. Voerdien af automatisk og auskultatorisk bestemmelse.

Fifteen normal subjects participated in this comparison of systolic blood pressure measurement determined both automatically (AU) with the Kivex Ergometrics 900 and by the standard auscultatorically method (AM). Maximal exercise, was achieved by work performed on an electronically braked ergometer bicycle. In the first part of this study, simultaneous measurements of systolic blood pressure were made by the Kivex device and by the standard method at rest, every minute during exercise, and one minute after stopping exercise. The differences (two standard deviations) between AU and AM (n = 229) were +/- 19 mmHg at rest, +/- 15 mmHg at submaximal level, and +/- 49 mmHg at maximal exercise level. The acceptable difference was determined to +/- 15 mmHg by Bland and Altman. In the second part of this study, the differences between simultaneously measured auscultatoric systolic blood pressure by two observers (n = 205) was +/- 10 mmHg at rest, +/- 9 mmHg at submaximal level, and +/- 10 mmHg at the maximal exercise level. It can therefore be concluded that Kivex automatic blood pressure device, Ergometrics 900, is unable to measure accurately systolic blood pressure with sufficient agreement in normal subjects at the maximal stress level or at rest. However, at the submaximal exercise level, the Kivex device was able to measure systolic blood pressure with an acceptable agreement with the standard method. Therefore, the blood pressure results obtained by the Kivex device are highly influenced by the exercise level. The agreement between two observers using standard auscultatory method for systolic blood pressure measurement was found to be acceptable at all levels of exercise.

Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension.

The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients with mild essential hypertension were entered into a double-blind crossover study. Examinations were carried out after 2 weeks of placebo run-in, and after 6 and 12 months of active treatment. Mean resting blood pressure was reduced from 115 +/- 12 mm Hg to 106 +/- 12 mm Hg with atenolol, and to 107 +/- 8 mm Hg with isradipine. The increase in the product of heart rate times blood pressure was significantly greater during isradipine treatment, as was the maximum exercise capacity. Left ventricular mass was increased from 228 +/- 36 g to 305 +/- 68 g with atenolol whereas it remained unchanged with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may prevent the development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility.

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.

Central haemodynamics in patients with severe postural hypotension.

Central haemodynamics in the supine and head-up tilted positions were studied in 24 patients with severe postural hypotension with and without supine hypertension. Results were compared with those obtained in eight normotensive and eight untreated hypertensive controls. In the supine position the patients had higher vascular resistances, lower stroke volumes and longer left ventricular ejection time indexes compared to controls, whereas left ventricular ejection fractions did not differ significantly. The patients with supine hypertension had significantly higher vascular resistance compared to those with supine normotension. The highest supine blood pressure levels were found in patients with multiple system atrophy. During tilt, vascular resistance and heart rates were increased and stroke volumes and left ventricular ejection time indexes were decreased in the controls. The patients were unable to increase their vascular resistance, but increased their heart rate and decreased their left ventricular ejection time indexes to a degree similar to the controls. The reductions in stroke volume were smaller in the patients compared to the controls. Changes in haemodynamics in response to head-up tilting did not differ significantly between patients with supine hypertension and supine normotension. It is concluded that patients with postural hypotension have higher supine vascular resistance and are unable to contract peripheral arteries and arterioles during head-up tilting. Contractility of the left ventricle is preserved and the baroreceptors are partially intact. Postural hypotensive patients with supine hypertension differ from those with supine normotension only with respect to supine vascular resistances.

Silent ischemia and severity of pain in acute myocardial infarction.

An overall low tendency to complain of pain, due to a low perception of pain, has been suggested in the pathogenesis of silent ischemia, independent of the extent of the diseased coronaries and a history of previous acute myocardial infarction. This hypothesis has been tested indirectly in this retrospective study by comparison of the use of analgesics during admission for a first acute myocardial infarction with the occurrence of silent ischemia at exertion tests four weeks after discharge from hospital. The study did not show a lower use of analgesics in patients with silent ischemia, but this may be due to methodologic problems. Suggestions are given for another study design to overcome these problems.

[Cardiovascular manifestations of hypothyroidism]. / Kardiovaskulaere manifestationer af hypotyreoidisme.

On the basis of a case history, the clinical and paraclinical manifestations of hypothyroidism are reviewed. Exertion dyspnoea without signs of cardiac insufficiency occurs frequently. The minute and stroke volume and heart rate are reduced. The blood pressure may rise (reversible) and hypertension may occur. The function of the left ventricle is reversibly reduced. A tendency to formation of exudates has been observed. X-ray of the thorax may revial massive relatively asymptomatic pleural exudates and cardiomegaly. Pericardial exudate occurs frequently and is demonstrated best by echocardiography. Inter- and intracellular deposits, infiltrations and fibroses have been demonstrated in the myocardium and these probably contribute to some of the non-specific, reversible ECG changes (low voltage, flattening/inversion of T waves, sinus bradycardia). The plasma concentrations of several different enzymes (including creatine kinase (CK), CK-MB and LDH) may be raised in myxoedema. The reason for this is perhaps compromized membrane function in the skeletal muscle cells. The diagnosis of myocardial infarction in myoedema requires that CK-MB constitutes at least 6% of the total CK and that the increase is transient. In patients with coronary sclerosis, substitution treatment should be initiated carefully because the risk of ischaemic symptoms is otherwise considerably increased. It is not elucidated whether the hypothyroidism per se can increase atheroma formation.

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)

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)

Pericardial haematopoiesis with tamponade in myelofibrosis.

A 52-year-old male with idiopathic myelofibrosis of 8 years' duration developed pericardial tamponade during recovery from acute tubular interstitial nephropathia following septicaemia. Splenectomy had been performed 7 yr previously. The tamponade was relieved by pericardiocentesis and its recurrence was prevented by a minor pericardiectomy. Pathological examination, including staining for factor VIII-positive cells, demonstrated extramedullary haematopoiesis in the pericardium. In patients with myelofibrosis and increased silhouette on X-ray film, with or without clinical heart failure, echocardiographic examination is recommended in order to identify a possible pericardial effusion.