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Biomedical subjects

E Thaulow

Publications and source records attributed to E Thaulow.

At least 91 records · Page 5Linked to original sources

[Prolonged action nitrates in stable angina pectoris].

A randomized double blind comparison of transdermal nitroglycerin and isosorbide dinitrate tablets was conducted in 100 men with stable angina pectoris. Subjective and objective effects were virtually identical for both regimens (number of angina attacks/nitroglycerin consumption and exercise ECG test variables). The pattern of side effects was also similar for both drugs. A considerable dissociation was observed between subjective effects and effects measured by ergometer test in the individual patient. Lack of both subjective and objective effects--i.e. nitrate tolerance--was observed in approximately one fourth of the patients, and was not prevented by a twelve-hour dosing interval on isosorbide dinitrate nor a six hour transdermal nitroglycerin-free interval. Our data lends credence to the notion that the effects of long-acting nitrates in daily life and the effects measured during stress testing may involve different mechanisms.

Administration, Cutaneous↗

Interventricular redistribution of myocardial blood flow during metabolic vasodilation.

To determine the effect of metabolic vasodilation on the blood flow distribution within the hypoperfused left anterior descending coronary artery (LAD) of the pig (a perfusion bed containing both left and right ventricular myocardium), 28 anesthetized (isoflurane) pigs were studied during intracoronary dobutamine infusion (2.5 +/- 1, SD, micrograms/min) at two levels of reduced, constant coronary inflow. In 8 pigs, coronary inflow was reduced from 59 +/- 9 ml/min to 42 +/- 10 ml/min; coronary perfusion pressure fell to 62 +/- 2 mm Hg (8260 +/- 260 Pa) and then fell further to 54 +/- 6 mm Hg (7190 +/- 800 Pa) during dobutamine infusion. Subendocardial blood flow in the anterior wall of the left ventricle perfused by the LAD decreased from 0.64 +/- 0.12 ml min-1 g-1 with hypoperfusion alone, to 0.40 +/- 0.14 ml min-1 g-1 (P less than 0.002) with the addition of dobutamine. Conversely, blood flow to the right ventricular region supplied by the LAD increased significantly from 0.78 +/- 0.40 ml min-1 g-1 (hypoperfusion alone) to 0.92 +/- 0.50 ml min-1 g-1 (P less than 0.008) with dobutamine. In 10 pigs, a more severe reduction of coronary inflow to 26 +/- 12 ml/min and subsequent dobutamine infusion resulted in a similar redistribution of blood flow from the left to the right ventricular portion of the perfusion bed. Infusion of dobutamine during hypoperfusion, but with a pressure-constant perfusion system, was associated with increases in blood flow to both the right and left ventricular portions of the perfusion territory.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

How important is heart rate?

Mortality rises as resting heart rate increases. Patients who are less able to increase their heart rate while exercising are more likely to die than those whose heart rate does rise. The occurrence of silent ischaemic events shows a circadian distribution, with increased mortality, heart rate and systolic blood pressure early in the morning. Treatment with beta-blockers reduces the number of asymptomatic ischaemic episodes, and lowers heart rate during exercise and at rest. The ischaemic myocardium of the dog loses the ability to undergo wall thickening during exercise. Moreover, blood flow in the ischaemic subendocardium is reduced during exercise. These effects can be overcome using beta-blockers. The effects of beta-blockers in reducing heart rate are less pronounced during mental stress. Furthermore, changes in wall motion abnormalities during mental stress are not improved by beta-blockers. Treatment of patients with beta-blockers after a myocardial infarction reduces the mortality rate. The greater the reduction in heart rate, the greater the reduction in mortality.

Adrenergic beta-Antagonists↗

Blood platelet count and function are related to total and cardiovascular death in apparently healthy men.

BACKGROUND: Experimental animal and clinical studies indicate that blood platelets have an important role in atherosclerosis and formation of thrombi. Prospective studies presenting evidence of an association between blood platelet count and cardiovascular mortality have not been performed. METHODS AND RESULTS: From 1973 to 1975, blood platelets were counted, and their responsiveness to aggregating agents was studied in healthy middle-aged men. The aim was to assess the possible association between these variables and coronary heart disease. At 13.5 years of follow up, a significantly higher coronary heart disease mortality was observed among the 25% of subjects with the highest platelet counts. Platelet aggregation performed in a random subsample (150 of the 487 men), moreover, revealed that the 50% with the most rapid aggregation response after ADP stimulation had significantly increased coronary heart disease mortality compared with the others. These associations could not be explained by differences in age, lipids, blood pressure, or smoking habits. CONCLUSIONS: The present study is the first to present conclusive, prospective evidence of an association between platelet concentration and aggregability and long-term incidence of fatal coronary heart disease in a population of apparently healthy middle-aged men.

Adenosine Diphosphate↗

Alpha-adrenergic regulation of myocardial performance in the exercising dog: evidence for both presynaptic alpha 1- and alpha 2-adrenoceptors.

New evidence supporting both presynaptic alpha 1- and alpha 2-adrenoceptors playing a role in the regulation of myocardial contractile performance in the exercising dog is reviewed. Studies utilized chronically instrumented dogs having sonomicrometers for the measurement of regional wall thickening and transducers for the measurement of left ventricular and systemic hemodynamics. During steady state exercise, either the selective alpha 1-adrenoceptor blocker prazosin (80 micrograms/kg) or the selective alpha 2-adrenoceptor blocker idazoxan (80 micrograms/kg) was infused into the left atrium while exercise continued. Immediately following the administration of either alpha-adrenoceptor blocking agent, there were substantial increases in heart rate, left ventricular dP/dt and regional contractile function as assessed using sonomicrometers, and norepinephrine release by the myocardium increased substantially. beta-adrenergic blockade prevented the heart rate and contractile effects of either alpha 1- or alpha 2-adrenoceptor blocker whereas norepinephrine release was further enhanced. These effects could not be attributed to baroreceptor unloading. In dogs studied under resting conditions with norepinephrine infusion to produce an increase in dP/dt similar to that observed during treadmill exercise, no sympathetic augmentation was observed following either alpha-blocker. Together, these studies provide evidence that both alpha 1- and alpha 2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the canine myocardium.

Adrenergic alpha-Antagonists↗

Myocardial effects of selective alpha-adrenoceptor blockade during exercise in dogs.

To study the effect of selective alpha 1- or alpha 2-adrenergic blockade on the myocardial contractile and chronotropic response to exercise, 29 dogs were chronically instrumented with a sonomicrometer for measuring myocardial wall thickness and a micromanometer for measuring left ventricular pressure. During treadmill exercise, either the selective alpha 1-blocker prazosin (80 micrograms/kg, n = 12) or the alpha 2-blocker idazoxan (80 micrograms/kg, n = 8) was infused into the left atrium beginning 2-3 minutes after the onset of exercise. alpha 1-Adrenoceptor blockade, like alpha 2-adrenoceptor blockade, was found to cause significant increases in systolic wall thickening, thickening velocity, heart rate, and left ventricular contractility, indicating an increase in inotropic state that was comparable to that with alpha 2-adrenoceptor blockade. Preventing the decrease in aortic blood pressure after selective alpha 1-blockade by using either systemic angiotensin II infusion (n = 6) or inflation of an intra-aortic balloon (n = 6) did not prevent the observed increases in wall thickening, heart rate, and left ventricular contractility. In four of the dogs treated with prazosin, the norepinephrine concentration in the coronary sinus was found to more than double after alpha 1-blockade. beta-Adrenergic blockade (propranolol, 1.0 mg/kg) prevented the increased contractile and chronotropic state caused by alpha 1- or alpha 2-blockade. Selective alpha-adrenergic blockade during adrenergic activation by intravenous norepinephrine infusion, in contrast to exercise, had no effect on wall thickening, heart rate, or left ventricular contractility. These data indicate that selective alpha 1-adrenergic blockade, like selective alpha 2-adrenergic blockade, causes a significant augmentation of heart rate and left ventricular contractility in the dog during dynamic exercise. These data are consistent with the hypothesis that this occurs through a presynaptic disinhibition of neural norepinephrine release mediated by a prejunctional alpha 1-adrenoceptor.

Adrenergic alpha-Antagonists↗

Selective thromboxane A2 receptor blockade in experimental exercise-induced myocardial ischaemia in dogs.

Thromboxane A2 receptor stimulation induces blood platelet aggregation and vasoconstriction, both potential causes of impaired perfusion of ischaemic myocardium. To study the potential role of thromboxane A2 receptor blockade in exercise-induced myocardial ischaemia and post-exercise myocardial dysfunction, nine conscious chronically instrumented dogs with single-vessel coronary artery stenosis (ameroid constrictor) were studied before, during and after steady-state treadmill runs which induced regional myocardial ischaemia. Three hours after a control run, the dogs were exercised again after the infusion of a selective thromboxane A2 receptor blocker: BM 13.177 (10 mg kg-1 i.v.). In the control run, systolic wall thickening (WTh, sonomicrometer) in the post-stenotic myocardium decreased from 22.1 +/- 9.1% at rest to 8.8 +/- 5.2% (mean +/- SD). Subendocardial blood flow (microspheres) in the ischaemic area decreased from 0.75 +/- 0.25 to 0.45 +/- 0.27 (ml min-1 g). The WTh in the ischaemic region remained depressed at 20 min after the run. BM 13.177 reduced peak left ventricular (+) dP/dt (micromanometer) and WTh in both control and post-stenotic myocardium at rest, during and after the run. WTh in the ischaemic area was reduced to approximately the same levels during running with BM 13.177 (not significantly different from control exercise) and remained depressed for at least 30 min after the run. Regional myocardial blood flow was not affected by BM 13.177. Thus, selective thromboxane A2 receptor blockade with BM 13.177 had a modest negative inotropic effect and did not improve regional function or blood flow in post-stenotic ischaemic subendocardium.

Animals↗

Characteristics of regional myocardial stunning after exercise in dogs with chronic coronary stenosis.

Persistent impairment of regional contraction of the left ventricle after restoration of blood flow following transient coronary occlusion has been termed "stunning," and reversible regional dysfunction has also been observed during recovery from exercise-induced regional ischemia. To determine whether limitation of subendocardial blood flow after exercise is a determinant of such dysfunction in the presence of chronic coronary stenosis, nine conscious chronically instrumented dogs having an Ameroid constrictor were studied before, during, and after treadmill runs that induced regional ischemia. During exercise, systolic wall thickening (%WTh, sonomicrometers) in the ischemic region decreased from a normal level of 22.1 +/- 9.1% at rest to 8.8 +/- 5.2% (+/- SD, P less than 0.01), whereas subendocardial blood flow (microspheres) in the ischemic region decreased from 0.75 +/- 0.25 to 0.45 +/- 0.27 ml.min-1.g-1 (P less than 0.05). %WTh in the ischemic region gradually improved after exercise but remained depressed (75% of control) at 30 min after the run (P less than 0.05). Postexercise dysfunction was not related to simultaneous regional hypoperfusion, since at 5 and 10 min after running there was a tendency toward subendocardial hyperemia (control 0.75 vs. 1.33 and 1.30 ml.min-1.g-1, NS) with a return to control by 30 min. Thus persistent regional dysfunction after exercise-induced regional ischemia in the conscious dog is not due to sustained subendocardial ischemia in the presence of chronic coronary stenosis and represents an example of myocardial stunning.

Animals↗

Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine.

Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5 +/- 1 microgram/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n = 8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114 +/- 7 mm Hg to 62 +/- 2 mm Hg caused a decrease in percent systolic wall thickening (%WTh) from 34.6 +/- 8.1% to 25.4 +/- 5.8% (p less than 0.005). In the second group of animals (n = 8), CAP was decreased to 46 +/- 5 mm Hg (control: 115 +/- 8 mm Hg) and % WTh decreased from 34.1 +/- 16.4% to 10.4 +/- 6.9% (p less than 0.001). Subendocardial blood flow was reduced from 1.41 +/- 0.38 ml/min/g to 0.65 +/- 0.13 ml/min/g (group 1, p less than 0.001) and from 1.08 +/- 0.22 ml/min/g to 0.24 +/- 0.08 ml/min/g (group 2, p less than 0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by %WTh remained unchanged (26.2 +/- 5.8%, p = NS) in group 1 and decreased significantly to 1.6 +/- 5.1% (p less than 0.041) in group 2. Subendocardial blood flow decreased to 0.44 +/- 0.15 ml/min/g in group 1 (p less than 0.005) and to 0.15 +/- 0.07 ml/min/g in group 2 (p less than 0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work index was developed in which the sum of the instantaneous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p less than 0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.

Animals↗

Role of calcium channel blockers in experimental exercise-induced ischemia.

Calcium channel blockers, which induce vasodilation by relaxing vascular smooth muscle cells, have proven effective in the treatment of angina pectoris. To study mechanisms of calcium blockade in ischemic heart disease, conscious chronically instrumented dogs with a single coronary artery ameroid constrictor were studied during steady-state treadmill runs which induced regional myocardial ischemia. During exercise-induced ischemia, regional systolic wall thickening and subendocardial blood flow were both significantly reduced in the ischemic zone. Calcium channel blockade with verapamil, diltiazem, or nifedipine enhanced regional systolic wall thickening. Regional subendocardial blood flow in the ischemic region, measured during diltiazem and nifedipine experiments, improved during exercise. Reduced coronary artery resistance in the native vessels and/or recruitment of collaterals appears to largely explain the increased total myocardial blood supply in the jeopardized area and the increased function. However, after diltiazem, reduced exercise heart rates as well as reduced left ventricular end-diastolic pressure also contributed to the improvement in the oxygen-supply imbalance in the ischemic myocardium. These data provide a basis for understanding the efficacy of calcium channel blocker treatment in patients with coronary artery disease.

Animals↗

Do data from a previous exercise test influence the prognostic information given by a second routine exercise ECG test? A 13 1/2-year follow-up study in apparently healthy middle aged men.

A positive exercise ECG test in a middle-aged man without confounding disease is a strong indicator of occult coronary heart disease. In the years following a positive test mortality, but CHD events vary considerably compared with subjects having normal exercise tests. If a second exercise test is positive in the same subjects years later, this signifies a disease which is prone to progress in a very severe way in the ensuing years. A first normal test followed by a second pathologic test has an intermediate prognostic significance compared with two normal tests years apart. The clinical course indicates that preventive measures should be taken after observing a positive exercise test, and even more importantly if two positive tests are observed years apart.

Adult↗

Coronary heart disease without angina pectoris: silent ischemia.

Myocardial ischemia without symptoms (= silent ischemia = Sl) has become a well known clinical entity in subjects with heart disease and in apparently healthy subjects. Detection of Sl is easiest and least expensively done with exercise ECG-testing (X-ECG). Data on the significance of Sl in the present report is derived from long-term follow-up of 2014 men aged 40-59 yrs, studied 1972-75, restudied in 1979-81 and 1986-88. The sources of information are: 1) 50 men with Sl detected with X-ECG/coronary angiography in 1972-75; 2) subjects with positive X-ECG in 1979-81 (but not in 1972-75); 3) preliminary data from the last follow-up study; and 4) complete data on cardiovascular mortality by Aug. 1987. The survey data indicate: a) Sl detected with X-ECG, confirmed with angiography is an indicator of later severe CHD-complications over 12-15 yrs; b) positive X-ECGs (not validated invasively) increase the risk of future CHD events and death from CHD 2-4 fold compared with subjects with normal X-ECG of similar age; c) limited isotope studies from the 1986-88 study indicate a very high specificity of a positive X-ECG in CHD, and d) cardiovascular mortality is very accurately predicted by factors known to be associated with the development of CHD. In accordance with the world literature, Sl is frequently observed in apparently healthy middle-aged and old men, and increases the risk of future CHD considerably when encountered.

Adult↗

Rhabdomyoma of the heart with intrapericardial expansion.

A rare case of a rhabdomyoma originating from the surface of the right atrium in a 20-year-old female is reported. The tumor showed electrical activity and caused both outflow obstruction and tamponade symptoms. It was successfully removed by a right-sided thoracotomy. The clinical course, diagnostic investigations, and the therapeutical approach of this rare lesion are discussed.

Adult↗

Failure of combined acetylsalicylic acid and dipyridamole to prevent occlusion of aortocoronary venous bypass graft.

Patients scheduled to receive at least three aortocoronary venous bypass grafts were randomized to active medication or to placebo. The former were given dipyridamole (DP) preoperatively and acetylsalicylic acid (ASA) was added after the operation. For the next 3 months they received DP 75 mg and ASA 325 mg thrice daily. The placebo regimen was identical and the study was conducted with double-blind technique. One patient in each group died. DP-ASA was discontinued in six patients because of gastrointestinal side effects (bleeding peptic ulcer in 2 cases). Angiography after 3 months revealed the patency rate of individual grafts to be 68% in the DP-ASA group and 77% in the placebo group. DP-ASA therefore did not prevent occlusion of aortocoronary venous bypass grafts.

Aspirin↗