[Use of analyses in acute myocardial infarction evaluated by quality assurance methods].
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Biomedical subjects
Publications and source records attributed to M Tangø.
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Twelve patients in severe congestive heart failure were given placebo, 100 mg xamoterol (Corwin) twice daily and 200 mg xamoterol twice daily, respectively, in 3 two-week periods in a double-blind randomised study. At the end of each treatment period the patients were evaluated. No differences were found between placebo and xamoterol in the following parameters: New York Heart Association function group index, heart volume, body weight, exercise duration on bicycle and treadmill, heart rate and systolic and diastolic blood pressure at rest. However, during exercise we found significantly lower heart rate and rate-pressure product during xamoterol treatment. This reduction is probably indicating occupation of beta-adrenoreceptors with concomitant reduced oxygen consumption during exercise.
In Denmark, 6,000-10,000 persons die annually from sudden cardiac death. The majority of these die on account of ventricular fibrillation. A patient is presented here who suffered from recurrent lipothymic seizures which were primarily diagnosed as epilepsy. On account of absence of paraclinical documentation and because of suspected depression, treatment with a cyclic antidepressive agent was commenced, which further increases the tendency to sudden cardiac death. The patient was then brought to hospital with Lidocaine-resistant ventricular fibrillation which responded partly to Ajmalin and partly to Disopyramide. The lipothymic seizures were then interpreted as being precipitated by intermittent malignant episodes of cardiac arrhythmia. During the subsequent six months, the patient has felt well and has been free from lipothymic seizures while receiving 200 mg Mexiletin thrice daily. Attention is drawn to the value of Holter monitoring in the investigation of lipothymic seizures. Lidocaine (despite the existence of resistant cases) must still be considered to be the preparation of first choice on account of extensive knowledge about and confidence in the preparation.
The purpose of the study described here was to investigate the reliability of impedance cardiography (IC) in measuring cardiac output (CO) and central blood volume. Absolute values and changes in these variables obtained by impedance cardiography and by isotope- or thermodilution techniques were compared. The reproducibility of IC within the same day was compared with that of isotope dilution and the reproducibility in IC from day to day was derived. Finally, the effects of the readings of impedance tracings by different observers were quantified. The results are based on 270 measurements in 37 healthy subjects and in 25 unmedicated patients with ischaemic heart disease. We obtained significant correlations between absolute values (y = 0.68x + 1.48) and changes (y = 1.00x + 0.0003) in CO measured by IC and isotope- or thermodilution. IC significantly overestimated absolute values of CO (P less than 0.001). We found a qualitative but no quantitative correlation between thoracic fluid volume measured by IC and central blood volume measured by isotope dilution. IC was highly reproducible both when studies were repeated within the same day (SD on differences in CO = 0.36 1 min-1 for IC; SD on differences in CO = 0.30 1 min-1 for isotope dilution) and on different days (SD on differences in CO = 0.45 1 min-1). A low intra-observer variability was found (SD on differences in CO = 0.12 1 min-1). We conclude that impedance cardiography is reliable in measuring changes in cardiac output and thus suitable for repeated measurements in studies on the haemodynamic effects of physiological or pharmacological intervention. Impedance cardiography is sufficiently reliable for comparison of absolute values of CO between different groups of patients. We cannot recommend impedance cardiography for quantitative studies of central blood volume.
The purpose of this study was to compare the systolic time intervals (STI) obtained by impedance cardiography and by the conventional carotid technique. This comparison was done with respect to: 1) correlations between variables obtained by the two methods, 2) ability to reflect drug-induced changes, 3) reliability in terms of reproducibility and 4) heart rate dependency of the variables measured. The study included 25 unmedicated patients with ischaemic heart disease and 36 healthy subjects. We obtained significant correlations between STI-variables measured by the two methods (p less than 0.001) and found that left ventricular ejection times were longer when determined by the carotid technique (p less than 0.01). We found a significant correlation between drug-induced changes in STI-variables measured by the two methods (p less than 0.001). Both methods had a high degree of reproducibility and this parameter was significantly better within the same day, when impedance cardiography was used (p less than 0.01). The error due to the reading of STI-tracings obtained by impedance cardiography was very small when performed by the same observer. We found the pre-ejection period to be independent upon heart rate, while the left ventricular ejection time depended upon this parameter. We conclude that impedance cardiography and carotid technique differ with respect to the measurement of left ventricular ejection times, but not with respect to the measurement of other STI-variables. We furthermore conclude that both methods are reliable, but we recommend the use of impedance cardiography because it is easier to apply, it may be more precise and it can be used for simultaneous measurements of other haemodynamic variables.
The immediate haemodynamic effects of prenalterol and nitroglycerine were examined in 15 patients, with severe chronic heart failure. Prenalterol was given intravenously in increasing doses of 2, 4, and 8 mg. Cardiac index increased significantly by 16%, 24%, and 32%, respectively. Heart rate increased by 16%, 19%, and 24%. Stroke volume index, systemic artery pressure, pulmonary artery pressure, and right atrial pressure did not change. Prenalterol reduced systemic vascular resistance by 15%, 17%, and 24%, respectively. Forearm blood flow and forearm vascular resistance was unchanged. Cardiac index and heart rate were not changed by 0.5 mg nitroglycerine, administered sublingually. Systolic and diastolic blood pressure were on average reduced by 14% and 12%, respectively. Systolic and diastolic pulmonary artery pressure and right atrial pressure were similarly reduced by 17%, 31%, and 39%, respectively. Nitroglycerine lowered calculated systemic vascular resistance by 11%, whereas forearm blood flow and forearm vascular resistance was unchanged. The conclusion is that prenalterol acutely increased cardiac index and improved haemodynamics in 14 out of 15 patients, mainly due to an increased heart rate. Nitroglycerine did not change cardiac index in the same group of patients.
Nine patients with severe congestive heart failure were treated with a partial beta-1-agonist prenalterol for 9.6 months on average. Five of the nine patients improved with an increase in NYHA-functional capacity of one class. In four of these patients, the improvement was maintained for 12 months. Upon discontinuation, deterioration occurred only in one case; in the latter, improvement reoccurred on reinstitution of prenalterol treatment. Significant improvement on exercise testing, however, occurred only in two patients. Prediction as to which patients would benefit from oral prenalterol was not possible from the pretreatment haemodynamic variables; similarly, the effect of oral prenalterol treatment could not be predicted from the response to prenalterol given intravenously. A critical review of the methods for evaluation of therapeutic intervention in congestive heart failure concludes the article.
In a double blind, cross over study the haemodynamic effects of an i.v. infusion of adrenaline during concomitant administration of atenolol, pindolol, propranolol or placebo were examined in 7 healthy volunteers. During coadministration with placebo, adrenaline caused an increase in systolic blood pressure (SBP) of 26 mm Hg and a decrease in diastolic blood pressure (DBP) of 20 mm Hg. Heart rate (HR) and stroke volume (SV) were increased by about 20-30%. Total peripheral resistance (TPR) fell significantly. When the subjects were pretreated with atenolol, the adrenaline increased SBP by 16 mm Hg, the DBP did not change, HR and SV increased by 19 and 30%, and TPR fell. During concomitant administration of the non-selective betablocker pindolol, which has strong intrinsic sympathomimetic activity (ISA), adrenaline increased SBP by 11 mm Hg and DBP by 17 mm Hg. This pure pressor response led to a significant reduction in HR and SV and an increase in TPR, probably mediated through the baroreceptors. The haemodynamic response to adrenaline during coadministration of propranolol was very similar to that seen after pindolol. It is concluded that a beta1-selective blocker interferes very little with the haemodynamic response to adrenaline, whereas it is changed to a pure pressor response during coadministration of a non-selective betablockers. ISA did not significantly modify the pressor response.
Dose-response curves for heart rate, arterial blood pressure, cardiac output, total peripheral resistance, systolic time intervals, forearm blood flow and forearm vascular resistance were obtained after i.v. administration of seven logarithmically increasing doses of xamoterol to 8 healthy volunteers. The total cumulative dose was 0.2 mg/kg b.w. At rest after the seventh dose of xamoterol heart rate, systolic blood, pressure, cardiac output and forearm blood flow were increased by 10%, 20%, 23% and 41%, respectively. Diastolic blood pressure was unchanged. Forearm vascular resistance was reduced by 21% and total peripheral resistance by 10%. Systolic time intervals were reduced: total electromechanical systole index (QS2I), left ventricular ejection time index (LVETI), pre ejection period index (PEPI) and PEP/LVET ratio by 4%, 2%, 12% and 14%, respectively. No side-effects were observed. During upright exercise after the seventh dose of xamoterol heart rate was reduced by 11% and systolic BP by 6%. Diastolic blood pressure was unchanged. Thus xamoterol increased the contractility of the heart with only a small increase in heart rate, increased systolic blood pressure and caused vasodilatation in resting skeletal muscle. During exercise the reduction in heart rate and blood pressure suggests beta-adrenoceptor blocking activity of the drug.
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Renal function and structure were studied in 57 patients on long-term lithium treatment. Nine per cent had a moderate decrease in glomerular filtration rate (GFR), 75% had decreased concentrating ability. No correlation between GFR and the duration of the lithium treatment was found. Twenty-four renal biopsy specimens were studied by light microscopy and compared with kidney biopsies from an age-matched control group of patients without arterial hypertension and who had never been treated with lithium or neuroleptics, but who suffered from acute oliguria or slight proteinuria. The number of sclerotic glomeruli and the focal distribution of intestitial fibrosis was significantly increased in the group of patients treated with lithium. No difference in the total amount of fibrous tissue or the number of atrophic tubules was demonstrated. There was no correlation between the duration of lithium treatment and the structural changes. The biopsy material originated from patients treated with a single and reduced dose regimen only. This regimen might explain the few and slight structural changes found, in contrast to other investigations in which patients were treated with lithium in divided doses.
In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I-II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p less than 0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p less than 0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the change in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p less than 0.05); four patients complained of oedema.(ABSTRACT TRUNCATED AT 250 WORDS)
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1 Steady state concentrations and clearance of lignocaine were determine in eight healthy volunteers during 360 min continuous lignocaine infusion (2 mg/min). Before the infusion propranolol (0.18 mg/kg i.v.), pindolol (0.023 mg/kg i.v.) or placebo were administered in a random double-blind, cross over design. 2 During the infusion of lignocaine heart rate, cardiac output and arterial blood pressure were measured every 60 min. 3 Propranolol decreased heart rate and cardiac output significantly by 10--20%, while pindolol or lignocaine did not change cardiac output or heart rate significantly. None of the drugs changed the arterial blood pressure. 4 Propranolol pretreatment decreased lignocaine significantly by 14.7% and the steady state concentration was increased by 22.5%. Pindolol produced no significant change in steady state concentration or clearance of lignocaine.
1 A random double-blind study was performed in healthy volunteers. The immediate effects of three different beta-adrenoceptor blocking agents, metoprolol, pindolol and propranolol, on the plasma concentrations of adrenaline and noradrenaline were compared in a situation of pleasant psychic stimulation during a television-game of tennis. The immediate effects of labetalol in a group of patients with arterial hypertension were studied in a similar experimental situation. 2 During psychic stress the plasma concentration of noradrenaline rose significantly by 85% after placebo, by 95% after labetalol, by 63% after metoprolol and by 55% after propranolol. After pindolol the noradrenaline concentration remained unchanged. 3 During psychic stress the plasma concentration of adrenaline rose significantly by 135% after labetalol, by 110% after metoprolol and by 83% after propranolol. After pindolol and placebo the adrenaline concentration remained unchanged. 4 The present results are taken to indicate that the intrinsic sympathomimetic activity possessed by pindolol prevents the rise in plasma noradrenaline normally seen during psychic stress. It is suggested that beta-adrenoceptor blockers with strong intrinsic sympathomimetic effect reduce the release of catecholamines during psychic stress.
The purpose of this study was to evaluate the immediate central and peripheral haemodynamic effects of a new vasodilating agent P 1134, in hypertensive man. After oral administration of 25 mg P 1134, the maximal haemodynamic changes were (mean +/- 1 SEM): mean blood pressure fell from 121.8 +/- 6.5 to 80.5 +/- 7.8 mmHg, heart rate increased 24.2 +/- 4.5 beats/min, cardiac output rose 2.9 +/- 0.3 1/min and forearm blood flow increased 1.0 +/- 0.1 ml/100 ml tissue/min. Stroke volume increased 17.0 +/- 2.1 ml and the inotropic state of the heart as judged from systolic time intervals increased. Total peripheral resistance and forearm vascular resistance were both reduced by approx. 50%. Linear correlations were found between the serum concentration of P 1134 and the change in mean blood pressure and total peripheral resistance. Changes in the other parameters mentioned above occurred progressively with changes in mean blood pressure and total peripheral resistance. It can be concluded that P 1134 is a very potent hypotensive agent with a haemodynamic profile identical to that seen with vasodilators with preferably act on precapillary resistance vessels. Potency and maximal efficacy exceeds that of hydralazine and seems like that of minoxidil. P 1134 is remarkably free from side-effects apart from causing water retention as all other vasodilators. It can be administered orally as well as intravenously. This makes P 1134 a very interesting compound in the treatment of moderate to severe hypertension, and further studies are well-founded.