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Biomedical subjects

M O Halinen

Publications and source records attributed to M O Halinen.

17 recordsLinked to original sources
PubMed1989

Effect of early metoprolol injection followed by oral dosage on CK-MB release, and myocardial function in suspected acute myocardial infarction. A double-blind controlled study.

The effect of metoprolol on indices of infarct size and left ventricular function was compared with that of placebo in a double-blind randomized trial in patients with definite or suspected acute myocardial infarction. Intravenous metoprolol (15 mg) or placebo was given within 24 h of the onset of symptoms, and oral treatment (200 mg daily) was continued for 15 days. Thirty-five patients received metoprolol and 34 patients placebo. The mean (+/- SD) of maximal creatinine phosphokinase (CK)-MB activities was 142 +/- 110 IU/l in the placebo group and 74 +/- 72 IU/l in the metoprolol group (p less than 0.001). The ECG QRS score at discharge from hospital was 5.22 +/- 4.47 and 4.61 +/- 3.06 (NS), respectively. Global left ventricular ejection fraction at rest was 44 +/- 14 and 51 +/- 15% (p = 0.054), respectively, and no change occurred in either group from rest to peak exercise. Ventricular fibrillation occurred in 1 placebo patient during the first day in hospital and in 1 metoprolol patient on the 14th day. Holter monitoring revealed no significant difference in the occurrence of ventricular arrhythmias during the first 24 h. Smaller enzyme release and higher ejection fraction suggest myocardial protection by early metoprolol treatment in acute myocardial infarction.

Clinical Trials as Topic↗
PubMed1989

Morphometric study of human myocardium in acquired valvular diseases.

To study the effect of various valvular heart diseases on the quantitative histology of myocardium, 38 human hearts with valvular lesions were examined (11 aortic stenoses, nine mitral stenoses, nine mitral incompetence and nine combined aortic and mitral valve lesions). The control group consisted of ten hearts without any valvular lesions. With morphometrical methods the volume fractions of myocardial components (myocardial fibres, interstitial space and diffuse connective tissue), the numerical density of arterioles and the mean fibre diameter were estimated. Myocardial fibrosis was more severe in hearts with valvular lesions than in the controls (5.4% vs 3.3%, P less than 0.01), but did not correlate with the anatomical severity of the valvular lesions. The most severe myocardial fibrosis was found in hearts with mitral incompetence (6.7%). Fibre hypertrophy was most severe in hearts with aortic stenosis and in hearts with mitral incompetence (22 microns and 23 microns, respectively). In hearts with severe valvular lesions the mean fibre diameter was 23 microns and in hearts with mild to moderate lesions 19 microns (P less than 0.01). Good correlation was observed between the mean fibre diameter and the weight of the left ventricle (r = 0.81, P less than 0.01). The volume fractions of connective tissue and interstitial space were significantly higher and the volume fraction of myocardial fibres was correspondingly lower in the subendocardium than in the subepicardium in hearts with either pressure overload (aortic stenosis) or volume overload (mitral incompetence). In conclusion, myocardial fibrosis occurs in patients with various valvular lesions, but the severity of the fibrosis does not correlate with the anatomical severity of valvular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cirrhosis of the liver markedly impairs the elimination of mexiletine.

To study the effects of cirrhosis of the liver on the pharmacokinetics of mexiletine a single i.v. dose of 200 mg was administered to six cirrhotic patients and to six healthy controls. The distribution of mexiletine in both study groups was similar, as indicated by similar values of V1 and Vss, but it tended to occur more slowly in the cirrhotics. The plasma protein binding of mexiletine was unchanged in the patients with cirrhosis. The elimination of mexiletine was markedly retarded in the cirrhotics, as indicated by its lower total clearance (2.31 vs. 8.27 ml/kg/h,) lower total elimination rate constant (0.059 vs 0.353 h-1), and longer elimination half-life (28.7 vs 9.9 h). The antipyrine half-life was 38.3 h in the patients and 14.7 h in the controls. One healthy volunteer had a Morgagni-Stokes-Adams type of syncopal attack 5 min after administration of mexiletine due to disturbance of AV conduction induced by the drug. Thus, on a pharmacokinetic basis the loading dose of mexiletine need not be modified in cirrhotic patients, whereas the maintenance dosage should be reduced to one fourth - one third of the usual dose.

Adult↗
PubMed1986

Changes occurring in the postinfarction ECG in relation to age, sex, and previous myocardial infarction.

Minnesota codes (MC), expressing Q-QS, ST segment, and T wave abnormalities in ECGs taken during the acute event and at a 1-year follow-up were studied in 256 survivors of myocardial infarction (MI). On the 1-year ECGs large Q waves (MC 1.1) were more common in patients with a history of previous MI than in those with a first MI. Regression of Q-QS, ST segment, and T wave changes occurred more extensively in first MIs, whereas progression of MC Q-QS and ST segment signs tended to be common in those with recurrent MI. On the acute ECGs large Q waves were more frequent in men (52%) than in women (36%), but ST segment depression of 1 mm or more (MC 4.1) was predominant in women in both the acute and 1-year ECGs. This ECG sign was related to the advanced age of the patients. There was no significant sex difference in the regression of the Q-QS signs, but the disappearance of ST and T wave changes occurred more extensively in men. The ECG returned to normal in 12% of men with a first MI but only infrequently in women and men with recurrent MI.

Adult↗
PubMed1986

Enalapril in chronic heart failure, a double-blind placebo-controlled study.

The efficacy of enalapril, a new angiotensin-converting enzyme inhibitor, was investigated in a double-blind placebo-controlled study in 24 patients with chronic heart failure. The patients belonging to NYHA functional class II-IV and treated with digoxin and diuretics were randomized to enalapril (12 patients) or placebo (12 patients) treatment for a 12-week period. Assessments were carried out at baseline and at 4 and 12 weeks during the treatment period. Complete data could be obtained on 10 patients receiving enalapril and on 11 patients receiving placebo. NYHA functional class improved by at least one class in 6 of 10 patients in the enalapril group, but only in 1 of 11 patients in the placebo group (chi 2 = 6.54; p less than 0.05). Duration of bicycle ergometer exercise increased significantly in the enalapril group from 8.8 +/- 3.4 to 11.3 +/- 4.2 (4 weeks) and to 11.2 +/- 3.6 min (12 weeks; p less than 0.05 for both), whereas it remained unchanged in the placebo group. Left ventricular ejection fraction by radionuclide ventriculography in the enalapril group increased significantly (baseline: 33.5 +/- 19.9%, 4 weeks: 40.0 +/- 20.0% (p less than 0.001), 12 weeks: 39.6 +/- 20.1% (p less than 0.01], whereas in the placebo group it did not change significantly from the baseline of 48.8 +/- 16.7%. The results indicate that enalapril induces a sustained relief of symptoms and improves exercise capacity in patients with heart failure. This subjective improvement appears to be accompanied by an increase in ejection fraction.

Adult↗
PubMed1984

Antiarrhythmic efficacy of combined intravenous and oral mexiletine in acute myocardial infarction. A double blind placebo-controlled study.

The antiarrhythmic efficacy of mexiletine in acute myocardial infarction (AMI) was studied in 99 patients randomized to mexiletine or placebo treatment. The loading dose was 250 mg i.v. and 400 mg orally followed by 200 mg orally 2 h later, and thereafter 200 mg t.i.d. up to 42 h. Arrhythmias occurring during 48 h were analysed from continuous electrocardiographic recordings. AMI was verified in 35 of 50 mexiletine patients and in 38 of 49 placebo patients. No deaths or instances of ventricular fibrillation occurred in the AMI patients. The number of patients who had any event of accelerated idioventricular rhythm (AIVR; P less than 0.05) runs of ventricular premature beats (VPBs; P less than 0.01), ventricular tachycardia (P less than 0.01) and Ron T beats (P less than 0.05) was smaller in the mexiletine group than in the placebo group. The number of all VPBs (P less than 0.05), hours with occurrence of AIVR (P less than 0.05), runs (P less than 0.01) and Ron T beats (P less than 0.05) was smaller in the mexiletine than in the placebo group. Serum levels of mexiletine tended to be low throughout the study. The half-life of the elimination was 13.7 +/- 7.2 h (means +/- S.D.). Adverse effects were infrequent, and the treatment was well-tolerated. Combined iv. and oral mexiletine prophylaxis significantly suppressed repetitive ventricular tachyarrhythmias and Ron T beats. However, no clinical benefit from mexiletine treatment could be shown in a coronary care unit with a low frequency of primary ventricular fibrillation.

Adult↗
PubMed1983

Pharmacokinetics of oral mexiletine in patients with acute myocardial infarction.

To study the effects of acute myocardial infarction on its pharmacokinetics a single oral dose of 400 mg mexiletine HCl was administered to seven patients. The study was performed within 24 h of the onset of pain (Study I) and was repeated 10-14 days later, during the recovery phase (Study II). Mexiletine in plasma and urine was quantified by a GLC method. The peak plasma concentrations of mexiletine were 0.65 +/- 0.05 (SEM) microgram ml and 1.08 +/- 0.11 micrograms/ml (p less than 0.05) in Studies I and II, respectively. The corresponding peak times were 4.68 +/- 2.04 h and 1.46 +/- 0.17 h (N.S.). The lag time averaged 0.48 +/- 0.08 h in Study I and 0.39 +/- 0.05 h in Study II (N.S.). The area under the plasma concentration-time curve remained unchanged. The elimination half-life was 15.03 +/- 0.61 h and 11.75 +/- 0.80 h (p less than 0.01) in Studies I and II, respectively. The recovery of unchanged mexiletine in urine and its renal clearance was also the same in both studies. The plasma protein binding of mexiletine was similar in Studies I and II (61 +/- 2% and 63 +/- 3%; N.S.). Thus, the rate of gastrointestinal absorption of mexiletine was definitely slowed in the acute phase of myocardial infarction, whereas the extent of absorption was not altered. The prolongation of the elimination half-life of mexiletine in the acute phase of myocardial infarction is probably related to an increase in its volume of distribution.

Absorption↗
PubMed1978

Suppresion of autonomic postganglionic discharges by pentobarbital in dogs, with or without endotoxemia.

Initial effects of pentobarbital (8 mg/kg) on autonomic efferent and afferent discharge rates were studied in 26 dogs under morphine-chloralose anesthesia. Half of the dogs were given endotoxin E. coli (1 mg/kg) before pentobarbital. The postganglionic cervical vagal efferentation of all the dogs decreased as did the postganglionic cardiac sympathetic efferentation. The heart rate of the dogs given endotoxin decreased, while an increase in heart rate with abolition of respiratory arrhythmia, was observed in dogs without endotoxin. The aortic pressure of the former dogs dropped while it fell only slightly in the latter ones. The aortic arch baroreceptor activity decreased while the changes of left atrial B-type receptor activity were not significant. The changes of the left atrial and central venous pressures were slight but those of the pulmonary arterial pressure generally paralleled the changes in the aortic pressure. Pentobarbital, accordingly, seems to exert both sympatholytic and vagolytic effects. These explain the heart rate changes, as well as the impaired cardiac contractility it evokes. The obvious impairment of cardiovascular control mechanisms by pentobarbital should be seriously considered in investigations into the cardiovascular control.

Action Potentials↗
PubMed1977

Circulatory reflex responses during the initial stage of feline endotoxin shock.

Cardiovascular and autonomic nervous responses to an injection of E. coli endotoxin were followed for up to 15 min. in cats anesthetized with chloralose and given artificial respiration. Within 60 seconds, endotoxin induced a drop of aortic pressure, with simultaneous cardiac acceleration and slight central venous hypertension. There was an associated, almost complete cessation of the aortic arch baroreceptor afferentation. The cardiac sympathetic efferentation increased up to 1.4 times the control level at its maximum. The splenic sympathetic efferentation increased up to 10.6 times the control level at the end of the 15 min period, when the other parameters studied showed a trend to control level. The sympathetic autonomic system seems to be activated through cardiovascular receptors sensing hemodynamic changes touched off by endotoxin-induced release of vasoactive substances.

Animals↗
PubMedDate not supplied

Pharmacokinetics of intravenous mexiletine in patients with acute myocardial infarction.

Acute myocardial infarction (AMI) is known to alter the pharmacokinetics of several antiarrhythmic agents. To study the effects of AMI on the kinetics of mexiletine (MEX), a single intravenous dose of 200 mg MEX HCl was infused over 30 min in 11 patients with AMI. The study was performed within 24 h of the onset of pain (study I) and repeated about 2 weeks later in seven patients at discharge (study II). MEX was quantitated in plasma and urine samples by a gas-liquid chromatographic method. The decline of MEX in plasma was three-exponential, with a terminal half-life of 14.7 +/- 3.4 (mean +/- SE) h in study I and 11.3 +/- 2.4 h (p less than 0.05) in study II, in the seven patients studied in both phases. The steady-state volume of distribution averaged 578 +/- 97 L in study I and 415 +/- 33 L in study II (p less than 0.05). The total plasma clearance, renal clearance, and recovery of MEX in urine were similar in the two studies, as was the plasma protein binding of MEX (64 +/- 2 vs. 57 +/- 3%, NS). Thus, an increase in the volume of distribution with consequent prolongation of the elimination half-life of MEX occurs in the acute phase of AMI, whereas the rate of elimination remains unchanged.

Adult↗