bluuebunny/crossref_metadata_2025_split huggingface dataset:
ELECTROPHYSIOLOGICAL AND BIOCHEMICAL DERANGEMENTS IN ISCHEMIC MYOCARDIUM: INTERACTIONS INVOLVING THE CELL MEMBRANE
Authors: Corr Peter B. , Lee Benjamin I. , Sobel Burton E. 
Published: August 2010

ABSTRACTSeveral lines of evidence indicate that metabolites accumulating in ischemic tissue may have a profound influence on membrane function and may thereby mediate many of the electrophysiological derangements characteristic of ischemic tissue in vivo. Recently, we have detected the accumulation of lysophosphoglycerides (LPG), intermediate metabolites of membrane phospholipids, in ischemic tissue in vivo, in effluents from ischemic isolated hearts and in venular effluents from ischemic regions in vivo. Furthermore, LPG, at comparable concentrations, induces reversible electrophysiological alterations in normoxic Purkinje fibers and ventricular muscle in vitro closely analogous to those changes characteristic of ischemic tissue in vivo. Concentration‐dependent changes seen include a reduction in resting potential, Vmax of phase 0, action potential duration and amplitude, with profound decreases in conduction velocity, heterogenous phase 0 depolarization, enhanced automaticity at reduced membrane potentials, and post‐repolarization refractoriness. Experiments utilizing 14C‐lysophosphatidyl choline (14C‐LPG) indicated that incorporation by LPC to a level of less than 1% of total cellular phospholipid is sufficient to induce electrophysiological derangements in isolated ventricular muscle. Based on the observations that venular effluents from ischemic regions in vivo exert deleterious electrophysiological effects in vitro, we have recently demonstrated a two‐fold increase in LPC in venular effluents from ischemic regions in vitro. at Although this two‐fold increase did not produce significant electrophysiological effects in vitro at normal pH, concomitant acidosis (pH = 6.7) comparable to that seen during ischemia in vivo, resulted in dramatic electrophysiological derangements after exposure to LPC. Subsequent experiments indicated that acidosis alone had modest electrophysiological effects but decreased the LPC concentrations three‐fold required to induce membrane effects but did not enhance the incorporation of 14C‐LPC into the cellular phospholipid fraction. Since long‐chain acyl carnitine also accumulate in ischemic myocardium and are also amphiphilic metabolites with many structural similarities to LPC, the effects of these compounds were also assessed in vitro. Palmitoyl carnitine at concentrations identical to LPC, induced electrophysiological derangements similar to LPC. In addition, the effects of the two compounds were additive and as with LPC, acidosis (pH = 6.7) decreased three‐fold the concentration of palmitoyl carnitine required to induce membrane derangements. The additive nature of the effects of these two different amphiphiles suggests that
THE IMMEDIATE ANTECEDENTS OF SUDDEN DEATH
Authors: Hinkle Lawrence E. 
Published: August 2010

ABSTRACTA 5 yr prospective survey of 1839 coronary heart disease (CHD) deaths, in 260.000 employed men aged 20–65 – and a detailed study of 142 deaths of all causes in 1020 men aged 40–65 who were observed for 5 yrs with repeated examinations and 24 hr ECG recordings shows the following:60.4% of CHD deaths were «sudden» (SD) in <1 hr; 42.5% of SDs were in men not previously known to have heart disease. The cardiac phenomena of all deaths could be classified as «arrhythmic» (ARD) or «circulatory failture» (CFD). 91% of SDs in <1 hr and 85% of SDs in <24 hrs were ARDs. ARDs and CFDs occurred under different conditions with different precipitating causes and different predictive «risk factors».At time of death 85% of ARDs were asleep, 88% awake and 42% active. 92.5% had myocardial disease: occlusions of major coronary vessels, scarring or fibrosis; recent acute MI or CO; hypertrophy 400 gms 80%; congestive heart failure 45%; cardiac dilatation 23%. 25% had severe anemia or anoxemia. 85% had major chronic disorders of rhythm or conduction (VPCs 10/1000 36%; pairs of PVC 15%; EC VPCs 23%; QRS . 11 sec 28 %).At time of death 100% of CFDs were comatose and not arousable. 48% had no clinical evidence of heart disease. 57% had myocardial disease: definite CHD 26%; hypertrophy 400 gms 47%; chronic CHF 29%; cardiac dilatation 13%. 27% had major disorders of rhythm or conduction (VPC 10/1000 20%; pairs of PVC 10%; EC VPCs none; QRS. 11 sec 10%).ARDs were precipitated by activities known to be associated with vagal effects on heart in 17.1% of the men; by activities known to be associated with sympathetic effects of heart in 34.1%, episodes of acute myocardial ischemia in 14.6%; or occurred during no apparent precipitating event in 34.1%. CFDs were precipitated by hemorrhage, trauma, infection, stroke, or other cause of peripheral vascular failure (87%), and by myocardial failure (13%).Risk factors at age 55 for ARD in 5 years are confounded and interact. Men with combinations have higher risk. A risk factor for CFD is the presence of potentially fatal non‐cardiac disease likely to cause coma or peripheral vascular collapse.
EFFECT OF TIMOLOL ON LATE VENTRICULAR ARRHYTHMIAS AFTER ACUTE MYOCARDIAL INFARCTION
Authors: von der Lippe G. , Lund‐Johansen P. , Kjekshus J. 
Published: August 2010

SUMMARYThis is a subproject of the Norwegian timolol myocardial infarction study carried out at one of the clinical centers. High risk patients surviving either a reinfarction or large initial infarction were randomized to placebo (44 pts) or timolol (37 pts). A 24 hour ECG was obtained the day before randomization (at baseline, 7–28 days after the acute attack) then 3 days, 1 month and 6 months after start of therapy. During this period the number of patients with one or more of ventricular couplets, bigemini, ventricular tachycardia or early cycle premature ventricular contractions (PVC) (i.e. complex ventricular arrhythmias) and the average number of PVC per hour increased significantly in the placebo group but not in the timolol group.The results indicate that there is an increased severity and incidence of ventricular arrhythmias in the first 6 months after myocardial infarction. Timolol effectively inhibited this trend. The importance of timolol as an antiarrhythmic agent may therefore be to prevent subclinical infarct extension and secondary ventricular arrhythmias related to the size of the myocardial damage.
Use of Hypnosis in Studies of the Effect of Stress on Cardiovascular Function and Hormones
Authors: Adlercreutz Herman , Kuoppasalmi Kimmo , Närvänen Sakari , Kosunen Kari , Heikkinen Risto 
Published: August 2010

ABSTRACT. In an attempt to separate the somatic and mental components of stress, groups of young male volunteers underwent running exercises and sauna baths, and roughly one year later had the same experiences recalled under hypnosis. In addition, experiments involving mental stress in the form of mental arithmetic were performed. A variety of physiological and biochemical parameters was measured on each occasion.Results for cardiovascular responses, reninangiotensin–aldosterone, Cortisol, testosterone, androstenedione, prolactin and growth hormone are reported. It is concluded that the mental component of combined mental and somatic stress may be separated from the somatic component by hypnotic suggestion. The response during hypnotic suggestion of the stress is usually of less but sometimes of the same magnitude as that obtained during the actual stress. Occasionally the response goes in the opposite direction during hypnotic suggestion as compared to the real situation. The individual responses vary considerably between individuals. The hormones most sensitive to mental stress are growth hormone, androstenedione, Cortisol, renin and angiotensin II. In the present study, mental stress had a depressing effect, if any, on plasma prolactin. Hypnosis in itself has no effect on plasma hormones in unstressed subjects compared to the normal diurnal variations.
Effect of Diazepam on Endothelial Permeability, Plasma Lipids and Lipoproteins in Cholesterol Fed Rabbits
Authors: Mänttäri M. , Mälkönen M. , Manninen V. 
Published: August 2010

ABSTRACT. In order to investigate the effect of diazepam in reducing the incidence and severity of cholesterol induced atherosclerosis in rabbits, 3 treatment groups were compared. The control Group I received the laboratory diet alone. Group II received cholesterol (1 gm daily, given by syringe). Animals in Group III additionally received diazepam (3 mg/kg/day) orally, again by syringe.After 21 days, animals were injected with Evans blue and 3 hours later their aortas were removed and examined for permeability changes. Serum was assayed for various lipid and lipoprotein components.Cholesterol feeding produced a 10–fold increase in serum cholesterol values in Groups II and III compared to the control Group I. The aortic uptake of Evans blue was significantly increased in animals treated with cholesterol but not in those which simultaneously received diazepam. Thus, diazepam prevented the increased endothelial permeability produced by hypercholesterolaemia, but it is not yet clear whether this effect involves the central nervous system or is a consequence of some more local membrane stabilizing action.
Effects of labetalol and propranolol on the peripheral circulation in hypertensive patients
Authors: Nyberg Gunnar , Berglund Goran 
Published: August 2010

ABSTRACT. Eleven patients with essential hypertension participated in a double–blind cross–over comparison of labetalol (L) and propranolol (P). Each drug was given for 5–8 weeks. The dose reducing the supine diastolic blood pressure when given b.d. to or below 90 mm Hg was titrated out. At the end of each period, isometric exercise (sustained handgrip) and calf plethysmography were performed.L (mean daily dose 636 mg) was slightly more effective in lowering supine and standing blood pressure than P (mean dose 276 mg). There was no significant difference between the drugs in their effect on the blood–pressure response to handgrip. However, compared with no treatment, L attenuated the blood–pressure rise at near–maximal handgrip; this has not been reported with other β–blockers. Resting vascular resistance and basal vascular tone were significantly lower (20%, p < 0.05) during treatment with labetalol than when the patients were taking propranolol. – The differences may be explained by the α–receptorblocking action of labetalol.
Labetalol in resistant hypertension
Authors: Hedstrand Hans 
Published: August 2010

ABSTRACT. In 12 patients with resistant hypertension labetalol was added to existing therapy. The average dose was 1333 mg (range 400–3600). The subjects were followed up for three and a half years. Mean supine blood pressure (BP) was reduced from 202/123 to 163/103 mm Hg and mean standing BP from 193/127 to 144/100 mm Hg. Mean BP after exercise was 134/93 mm Hg. The main side–effect was postural hypotension during exercise, causing withdrawal of labetalol in two subjects.In patients with severe hypertension, resistant to several combinations of antihypertensive drugs, the addition of labetalol may lead to satisfactory BP reduction, especially when combined with a potent diuretic.
Labetalol, a combined α– and β–blocker, in hypertension of pregnancy
Authors: Lunell Nils–Olov , Fredholm Bertil , Hjemdahl Paul , Lewander Rolf , Nisell Henry , Nylund Lars , Persson Bengt , Sarby Bert , Wager Jan 
Published: August 2010

ABSTRACT. Labetalol was given to women with hypertension of pregnancy in their last trimester to study its acute effect on circulation and metabolism. Seven women were given 50 mg labetalol i v. There was a significant decrease of blood pressure from a mean of 143/101± 4/2 (SEM) to 127/88 ± 5/2 mm Hg. Maternal heart rate fell significantly from 77 ± 5 to 68 ± 3 beats per min. These changes persisted during a three–hour observation period. The hypotensive response was accompanied by a significant increase in plasma noradrenaline from 1.54 ± 0.16 to 2.37 ± 0.41 nmol/l, suggesting sympathetic activation. Plasma cyclic AMP, which is increased by β2–adrenoceptor stimulation, was significantly elevated after labetalol. This supports the hypothesis of partial β–agonist activity of labetalol. Lipid metabolism, as judged from measurements of plasma FFA, glycerol and 3–hydroxybuturic acid, showed little change.The acute effect of labetalol on uteroplacental blood flow was determined in eight women with pregnancy hypertension using a gammacamera on line with a computer. 0.5 mCi indium–113m was given i v before and 30 min after labetalol was administered i v in a dose of 1 mg per kg body weight. After the injections of indium–113m, serial scintigrams were recorded during 10 s periods for 240 s. By computerized summation of the scintigrams, an image was obtained in which the placenta could be outlined for time–activity analysis of the isotope accumulation curve. From this curve a uteroplacental blood flow index could be calculated. Labetalol induced a significant drop of mean arterial blood pressure from114 ± 2 mm Hg to 100 ± 3 mm Hg after 30 min in this group of women. However, the uteroplacental blood flow index did not change. As we have earlier shown with this technique that uteroplacental blood flow can be severely impaired in hypertension of pregnancy, the Finding of substained uteroplacental blood flow simultaneously with a decrease in blood pressure should be of clinical importance.Taken together with other studies of clinical effects, these results indicate that labetalol is useful in the treatment of hypertension of pregnancy
Basic pharmacological properties of prenalterol
Authors: Mattsson H. , Hedberg A. , Carlsson E. 
Published: August 2010

ABSTRACTThe cardiac selectivity of prenalterol as an agonist was demonstrated in the anaesthetised cat, in which the heart rate was dose dependently increased without any effect on peripheral vascular resistance. When doses of prenalterol, isoprenaline (non–selective) and terbutallne (β2–selective) were adjusted to give the same increase in heart rate, prenalterol displayed a significantly higher inotropic effect than the other two agonists.It is generally accepted that cAMP acts as a second messenger in β–mediated responses. Prenalterol induced an inotropic effect in the cat heart, which at its maximum was 80% of that of isoprenaline without, however, any significant increase in cAMP content. In tissue homogenate from cat left ventricle, prenalterol caused only a minor activation of the adenylate cyclase activity. These results may indicate that only a small increase of the adenylate cyclase activity and cAMP level is sufficient for a maximal inotropic response or that production of cAMP is not essential for the positive inotropism produced by prenalterol.In isolated electrically driven rabbit papillary muscle prenalterol induced a positive inotropic response, which was inhibited by the β1–antagonist metoprolol but not by the α–blocker phentolamine or the β2–blocker IPS 339. This indicates that the contractile effect of prenalterol in the heart is mediated via β1–adrenoceptors and that α– or β2–adrenoceptors are not involved. An interindividual variation in intrinsic activity of prenalterol in rabbit papillary muscle was found to be correlated to the sensitivity to isoprenaline.Binding experiments have shown that prenalterol binds with equal affinity to both β1– and β2–adrenoceptors. Prenalterol did not affect subtetanlc contractions in soleus muscle, which indicates a lack of β2–agonistic activity of prenalterol in the skeletal muscle. When the cardiostimulatory effect of prenalterol was compared with the β2–blocking effect in the anaesthetised dog, the results revealed that the β2–blocking effect of prenalterol is produced at doses higher than those inducing cardiac stimulation.
Clinical experiences with prenalterol as an antidote to β–adrenoceptor blockade
Authors: Kulling P. 
Published: August 2010

ABSTRACTThe cases presented in this paper suggest that prenalterol is useful in the treatment of myocardial depression due to β–blockade. According to its pharmacological properties, prenalterol might even be the drug of choice in these situations. It is wellknown that massive β–blocker overdosage may be difficult to manage and as the therapeutic guidelines in these cases have not yet been definitely stated, it is obvious that prenalterol In this context will be of utmost Importance. What remains to be solved is the dosage level. So far, experience has shown that high doses, widely exceeding the recommended initial dose of 50–100 μg/kg, are necessary to restore normal circulation in massive β–blocker overdosage.Prenalterol has been introduced as an antidote to counteract unwanted cardiac effects of β–blockade [l, 2]. In this paper examples will be given where prenalterol has been successfully used to reverse unwanted cardiac effects (like hypotension and/or cardiac failure) in chronic therapeutic β–blockade (Figures 1–2), in acute therapeutic β–blockade (Figure 3) and in intentional overdosage with β–blockers (Figures 4–6).
Haemodynamic effects of intravenously administered prenalterol in patients with severe heart failure
Authors: Waagstein F. , Estrada–Yamamoto M. , Reiz S. , Reyesl C. , Hjalmarson Å. 
Published: August 2010

ABSTRACTThe acute haemodynamic effects of prenalterol 75–225 μg/kg i.v. were studied at rest and during exercise in the supine position in 12 patients with chronic congestive heart failure secondary to myocardial infarction (6 pts), chronic valvular disease with valvular replacement (4 pts), ischaemic cardiomyopathy (1 pt) and post myocarditis (1 pt). In 5 of the b AMI patients the effect of prenalterol on myocardial oxygen consumption at rest was measured. Pulmonary artery end–diastolic pressure decreased significantly from 17 to 10 mm Hg at rest and from 31 to 21 mm Hg during exercise. Resting heart rate increased from 78 to 90 at rest but was unchanged during exercise. MVO2 in the 5 patients was unchanged or lower in 4 patients and increased in one in whom angina developed after prenalterol. In general, dyspnoea and angina during exercise were less pronounced after prenalterol. The calculated triple product was lower after prenalterol, especially during exercise, indicating lower myocardial oxygen consumption and probably less myocardial lschaemia.It can be concluded that prenalterol may be of value for treatment of chronic congestive heart failure in addition to digitalis and diuretics even in the presence of ischaemic heart disease and effort angina.
Effects of i.v. prenalterol in patients with severe cardiac failure at rest and during exercise
Authors: Doering W. , Wauer B. , Isbary J. 
Published: August 2010

ABSTRACTPrenalterol administration (150 μg/kg i.v.) exerted beneficial effects on resting and/or exercise cardiac performance in patients with congestive cardiomyopathy (n=12) and 1 patient with hypertensive heart disease (=group I, n = 13), while the haemodynamic response in patients with severe coronary heart disease (n = 3) or cor pulmonale (n = l) was non–uniform. At rest mean right and left ventricular filling pressures decreased by 26 and 19% (p < 0.02 and p < 0.02), respectively, while stroke volume increased by 8% (p < 0.05), cardiac index by 25% (p < 0.01) and heart rate by 15% (p < 0.005) 5 min after prenalterol administration in group I. During exercise there was no further Increase in heart rate, while filling pressures decreased and cardiac index increased significantly compared to control exercise. This typical inotropic response to prenalterol was observed in fully digitalised patients. Maximal effects occurred about 15 min after i.v. administration.
The Influence of Calcium Antagonists on Plasma Digoxin Concentration
Authors: Pedersen Knud Erik 
Published: August 2010

SummarySeveral investigators have independently discovered that the calcium antagonist, verapamil, causes a 60–80% increase in plasma digoxin. Pharmacokinetic studies indicate, that the elevated plasma digoxin level is due to verapamil‐induced inhibition of both renal and extrarenal digoxin clearance. No significant changes in single‐dose digoxin pharmacokinetics were observed during nifedipine coadministration.To elucidate the clinical relevance of this interaction, we investigated the influence of verapamil on digoxin‐induced inotropism as assessed from systolic time intervals. In single‐dose trials, the verapamil‐induced elevation of plasma digoxin was associated with a more sustained reduction in left ventricular ejection time as compared to control. Correspondingly, the concentration‐response relationship of digoxin inotropism was unaffected by verapamil.In‐vitro studies showed that verapamil had no influence on the number of digitalis receptors on human lymphocytes. In accordance, verapamil enhanced the digoxin‐induced elevation of intracellular sodium concentration possibly reflecting an increased receptor effect.The plasma digoxin elevation resulting from verapamil coadministration seems cardioactive with regard to both inotropism and toxic effects.
Plasma HDL Cholesterol and Blood Glucose in Non‐insulin‐dependent Diabetics Related to Liver Lipids and Microsomal Enzyme Activity
Authors: LUOMA P. V. , SAVOLAINEN M. J. , SOTANIEMI E. A. , ARRANTO A. J. , PELKONEN R. O. 
Published: August 2010

ABSTRACT.Luoma PV, Savolainen MJ, Sotaniemi EA, Arranto AJ, Pelkonen RO. (Clinical Research Unit, Department of Medicine, and Departments of Medical Biochemistry, Pathology and Pharmacology, University of Oulu, Oulu, Finland.) Plasma HDL cholesterol and blood glucose in non‐insulin‐dependent diabetics related to liver lipids and microsomal enzyme activity.The major lipid predictors of coronary events, plasma high density lipoprotein cholesterol (HDL‐C) and the HDL‐C/total cholesterol (T‐C) ratio, and blood glucose (BG) in 12 subjects with non‐insulin‐dependent diabetes mellitus were related to hepatic lipids, proteins and microsomal enzyme activity assessed by liver cytochrome P‐450 (P‐450). Non‐insulin‐dependent diabetics had low HDL‐C/T‐C ratio, liver phospholipid (PL) and P‐450 and high serum and liver triglyceride (TG) concentrations. Plasma HDL‐C was decreased, and BG high, especially in subjects with reduced PL and P‐450. The HDL‐C/T‐C ratio was directly proportional to liver PL and P‐450 and unrelated to hepatic TG. Increases in liver PL and microsomal enzyme activity may be favorably reflected both in cholesterol distribution and diabetic control.
Haemostatic Parameters in Cushing's Syndrome
Authors: IKKALA E. , MYLLYLÄ G. , PELKONEN R. , RASI V. , VIINIKKA L. , YLIKORKALA O. 
Published: August 2010

ABSTRACT.Ikkala E, MyllylÄ G, Pelkonen R, Rasi V, Viinikka L, Ylikorkala O. (Finnish Red Cross Blood Transfusion Service and Helsinki University Central Hospital, Helsinki, Finland.) Haemostatic parameters in Cushing's syndrome.We have studied haemostatic parameters in 12 patients with Cushing's syndrome. Three patients had prolonged bleeding times, and in all seven patients whose bleeding times were measured 3–6 months after surgical treatment the postoperative bleeding times were shorter (mean 7.5 min) than the pretreatment times (mean 12.3 min). In ADP‐ or adrenaline‐induced aggregation the second wave was lacking in six and the degree of aggregation was borderline or subnormal in five patients. One patient had, in addition, a severe defect in collagen‐induced aggregation. However, thromboxane B2production of the platelets from both endogenous and exogenous arachidonic acid was unaffected. Factor VIII:C, RAg and Rcof activities were all elevated, and in patients with severe disease F VIIIR:Ag and F VIII:Rcof activities were markedly more elevated than F VIII:C activity. The changes in both primary haemostasis and in factor VIII activities correlated clearly with the clinical severity of the disease.