The effect of regular physical activity on the left ventricle systolic function in patients with chronic coronary artery disease.

The purpose of this study was to assess the influence of aerobic training on the left ventricular (LV) systolic function. Thirty patients with stable coronary artery disease, who had participated in the conducted 3-month physical training, were retrospectively divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted program. Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. The peak systolic velocities of mitral annulus (Sa) were assessed by tissue Doppler imaging for individual LV walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob). According to the blood supply, left ventricular walls were divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis ≤50 %; C- walls supplied by coronary artery with stenosis 51-70 %; D- walls with stenosis of supplying artery 71-99 %; and E- walls with totally occluded supplying artery. In global systolic function, the follow-up values of Sa glob in cohort I were improved by 0.23±0.36 as compared with baseline values at rest, and by 1.26±0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53±0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively. Concerning the resting regional function, the only significant difference between cohorts in follow-up changes was found in walls E: 0.37±0.60 versus -1.76±0.40 cm/s (p<0.05). At the maximal load, the significant difference was found only in walls A (0.16±0.84 versus -2.67±0.87 cm/s; p<0.05). Patients with regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.

AMBULATORY BLOOD PRESSURE MONITORING: THE NEED OF 7-DAY RECORD.

The need for systematic around-the-clock self-measurements of blood pressure (BP) and heart rate (HR), or preferably for automatic monitoring as the need arises and can be met by inexpensive tools, is illustrated in two case reports. Miniaturized unobtrusive, as yet unavailable instrumentation for the automatic measurement of BP and HR should be a high priority for both government and industry. Automatic ambulatorily functioning monitors already represent great progress, enabling us to introduce the concept of eventually continuous or, as yet, intermittent home ABPM. On BP and HR records, gliding spectra aligned with global spectra visualize the changing dynamics involved in health and disease, and can be part of an eventually automated system of therapy adjusted to the ever-present variability of BP. In the interim, with tools already available, chronomics on self- or automatic measurements can be considered, with analyses provided by the Halberg Chronobiology Center, as an alternative to "flying blind", as an editor put it. Chronomics assessing variability has to be considered.

Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart.

INTRODUCTION: Melatonin (MEL), a pineal hormone, is well known as a potent antioxidant in a variety of ischemia-reperfusion models. Recent studies have assumed a pivotal role of reactive oxygen species (ROS) in the development of apoptosis. There are few pieces of information concerning a possible protective role of MEL against apoptosis in ischemia-reperfusion injury of myocardium. METHODS: We conducted an in vitro experiment: (1) to study the effect of MEL in the model of isolated and perfused working rat heart; (2) to evaluate the antioxidant capacity of MEL by a simple fluorescence test; and (3) to analyze the extent of apoptosis inhibition by MEL. Four groups of male Wistar rat were used: (a) group 'MEL 50 muM' (n=8); (b) group 'ischemia 30 min' (n=8); (c) group 'controls' (n=8); and (d) group 'controls+MEL 50 muM' (n=8). The perfusion medium was an oxygenated Krebs-Henseleit buffer (KHB). Hearts in groups (a) and (b) underwent 30 min of global normothermic ischemia and 45 min of reperfusion; 3 min before ischemia the hearts of group (a) received KHB with MEL 50 muM (and MEL 50 muM was also present in KHB solution during reperfusion). Hearts of group (c) were only perfused by KHB, and hearts of group (d) perfused by KHB+MEL 50 muM throughout the experiment. Registered were basic hemodynamic parameters: coronary, aortic, cardiac output and heart rate. At the end of each experiment, a left ventricle samples were taken for in situ detection of apoptosis using a TUNEL in-situ detection kit (POD) and quantitative analysis was performed. Malonedialdehyde concentrations were evaluated from heart homogenate to determine the severity of oxidative damage. To study the antioxidant capacity of MEL, a fluorescence test with allophycocyanin as an indicator was performed. A peroxyl radical generator, 2,2'-azobis(2-amidinopropan)-4-hydrochloride (AAPH) was used, and the antioxidant effect of MEL was expressed in oxygen-radical absorbing capacity (ORAC) units. RESULTS: Treatment by MEL resulted in a significant improvement of hemodynamic parameters and reduction of postischemic arrhythmias during reperfusion. All hearts in group 'ischemia 30 min' developed fatal ventricular fibrillations. MEL significantly reduced the incidence of apoptotic cells (14+/-4.3%; **P<0.01) vs. group 'ischemia 30 min' (58+/-2.1%). No apoptotic cells were detected in both control groups (c) and (d). In the fluorescence test, MEL exhibited a significant dose-dependent protective effect against peroxyl radical; MEL also reduced significantly the level of lipoperoxidation (MDA; *P<0.05). Analysis of hemodynamic parameters in both control groups (c) and (d) did not show any significant differences; the presence of MEL 50 muM in KHB solution did not have any important influence on cardiac performance in this type of experiment. CONCLUSION: We confirmed the previously reported beneficial effects of MEL against ischemia-reperfusion injury, presumably via its antioxidant properties. A significant suppression of apoptosis and the peroxyl radical scavenging properties of MEL in our study could contribute to the hypothesis of a close link between oxidative stress and apoptosis promotion.

[Combined training in patients with systolic left ventricular dysfunction]. / Kombinovaný trénink u nemocných se systolickou dysfunkcí levé komory srdecní.

The objective of the work was to evaluate the effect of eight-week combined training on the performance, aerobic capacity and basic haemodynamic parameters in patients with systolic dysfunction of the left ventricle and to assess its safety. The investigation comprised 26 patients, men mean age (x +/- SD) 61.8 +/- 11.1 years with coronarographically verified chronic ischaemic heart disease and with a left ventricular ejection fraction lower than 40% (EF 35 +/- 4%). Before the beginning and after completion of the rehabilitation programme (eight weeks) a spiroergometric examination was made, up to the symptom-limited maximum. Fitness elements were included after 2 weeks of aerobic training. The lesson lasted 60 mins. and included warming up (10 mins.), aerobic load on an ergometer with an intensity of the load at the level of the anaerobic threshold (20 mins.), the stage of fitness training on a combined training machine (20 mins) and the relaxation stage (10 mins). In the fitness stage the patients started to exercise at the 30% level, after two weeks at the 60% level 1-RM (one repetition maximum) The results showed after eight-week combined training a significant (p < 0.05) increase of the maximum achieved performance (from 104 +/- 27 to 132 +/- 32 W) in patients with systolic left ventricular dysfunction. There was a significant increase in the capacity of the transport system expressed by the value of the maximum oxygen uptake (from 1545 +/- 312 to 1740 +/- 359 ml.min-1) and MET (from 5.3 +/- 1.3 to 6.0 +/- 1.4). There was a significant decrease of the blood pressure at rest, systolic and diastolic, and of the baseline value of the heart rate at rest and of the "product rate, pressure"--RPP. Changes in the EF were not significant.

[The effect of walking exercise on aerobic capacity and serum lipids in type 2 diabetics]. / Vliv tréninku chuzí na aerobní kapacitu a krevní lipidy u diabetiku 2. typu.

Regular physical activity can have a favourable impact on other risk factors of ischaemic heart disease (IHD) and associated diabetes (DM), such as obesity, hypertension, dyslipidaemia, insulin resistance and others. This important part of treatment of diabetes is frequently difficult to implement because of the lack of willingness ("adherence") of type 2 diabetics to practice regular exercise, and unequivocal data are lacking on the intensity of exercise which will influence effectively these risk factors and be at the same time safe, readily available and psychologically acceptable. The objective of the work was to find out whether walking, i.e. locomotor activity with a low to medium intensity can effectively influence parameters of aerobic capacity and blood lipids. The authors submit the results of two groups of type 2 diabetics. The experimental group B (n = 10, age 57 +/- 7 years, BMI 31 +/- 3, duration of DM 8 +/- 5 years) participated in a 12-week training programme of walking; at the beginning and at the end of this period indicators of aerobic capacity at the level of the anaerobic threshold (VO2ANP) were evaluated as well as at the level of the symptom limited maximum (VO2SL, TepO2SL), and the blood lipid levels. In the control group A (n = 6, age 58 +/- 7 years, BMI 32 +/- 4) indicators of aerobic capacity and blood lipids were assessed after a 12-week period of the usual habitual physical activity. In group B the 12-week walking training led to significant improvement of parameters of aerobic capacity at the level of the anaerobic threshold (ANP), oxygen pulse at the level of the symptom limits maximum (SL) and a significant reduction of total and LDL cholesterol. In the control group no significant changes occurred in aerobic capacity nor blood lipid values. The training programme where walking was selected as physical activity with a low to medium intensity can be considered suitable for everyday life of motivated patients with type 2 diabetics, preferably in the form of a domestic training programme. The prerequisite of success is its regular and frequent evaluation by health professionals.

Microvessels of bulbar conjunctiva in UPTAH goats.

Aiming to observe directly the microcirculation after total artificial heart (TAH) implantation, we performed a long-term follow-up in 2 goats using conjunctival angioscopy. A short segment of parallel arteriole and venule was photographed and analyzed on computer picture program (magnification 40x). Three main parameters were measured: arteriole diameter, venule diameter, and arteriovenous ratio (A/V ratio). The intrathoracically implanted TAH was the undulation pump total artificial heart (UPTAH) with cardiac output of 100 ml/kg/min. To stabilize the peripheral hemodynamics a 1/R biofeedback control system was used. Our results provided only elementary data about morphology of bulbar microvessels. The main finding was the tendency to general vasoconstriction, more intensive on the venous side (*P < 0.05 in one goat). We did not observe any pathological shapes (e.g., tortuosities, varicosities, or sludge); this result could be attributed to the high effectivity of 1/R control method. These preliminary results should be considered only as an attempt to apply the widely used clinical method of conjunctival angioscopy to the conditions of TAH.

[Effect of physical training on the magnitude of left ventricular ischaemic dysfunction in patients with chronic ischaemic heart disease]. / Vliv telesného tréninku na velikost ischemické dysfunkce levé komory u nemocných s chronickou ischemickou chorobou srdecní.

Twenty-two patients with chronic ischaemic heart disease (IHD) and reversible myocardial ischaemia after a load as recorded by single photon emission computed tomography (SPECT) participated in an eight-week rehabilitation programme. Before exercise their efficiency was tested by spiroergometric examinatin and the patients were randomized into two groups. Group A (10 patients) took exercise at the level of the anaerobic threshold (high intensity training), group B (12 patients) trained at the level of the 60 % anaerobic threshold (low intensity training). The exercise unit including the warming up and relaxation stage lasted 50 minutes and was repeated three times per week. Before and after the rehabilitation programme in all patients spiroergometry was performed as well as exercise pulsed tissue Doppler echocardiography to evaluate regional systolic and diastolic left ventricular function in the ischaemic area, localized beforehand by the SPECT. The following parameters were evaluated by echocardiograpphy: the peak velocity of motion in the ischaemic area in systole (Si), the peak velocity of motion in the ischaemic area in early diastole (Ei) ad in atrial contraction (Ai), and the ratio Ei/Ai was calculated. With the exception of the decline of the value at rest Ai from 8.4 +/- 1.3 cm/sec to 7.3 +/- 1.3 cm/s (p < 005) in the exercising group A none of the parameters of left ventricular regional function changed significantly after an eight-week rehabilitation programme. The maximal performance achieved in spiroergometry increased however after rehabilitation in group A (from 145 +/- 36 W to 162 +/- 39 W, p < 0.01) as well as in group B (from 112 +/- 36W to 122 +/- 36W, p < 0.05). I It may be concluded that a rehabilitation programme of high and low intensity improved the load tolerance during spiroergometry but did not lead to significant improvement of regional systolic and diastolc left ventricular function in the area of reversible ischaemia.

[Involvement of the cardiac muscle in anemia]. / Postizení srdecního svalu pri anémii.

Anemia is probably the most widespread syndrome associated with a very wide spectrum of pathological conditions with a different genesis. In malignities and their treatment it is one of the very serious complications the impact of which is manifested in particular in the state of the circulation. Thus anemia can cause deterioration of primary cardiac and cardiovascular complications which develop either as a result of the malignant disease or as a result of its treatment by cardiotoxic drugs. Thus risk conditions with the functional consequence of cardiovascular impairement are potentiated. This can complicate the disease or limit therapeutic possibilities. In the submitted work the authors tried to analyze the importance of anemia from the aspect of cardiovascular pathophysiology and outline results of their own observation supported by data from the literature concerned with this problem. From the observations ensues that in the group of patients studied by the authors who had careful substitution treatment with erythrocyte concentrates there were no serious drops of Hb which could be of fundamental importance from the aspect of cardiovascular damage. For this reason the cardiovascular status can be evaluated only from the aspect of primary toxicity of oncological treatment (if we omit direct damage by the disease) and it is not necessary to consider the consequences of hematological complications which must be taken into account when HB levels are lower than 70 g/l.

[Changes in left ventricular function during chemotherapy with doxorubicin]. / Zmeny funkce levé komory srdecní v prubehu chemoterapie doxorubicinem.

The authors investigated by echocardiography changes of left ventricular function in 79 patients with non-Hodgkin lymphoma or Hodgkin's disease who were treated by chemotherapy containing doxorubicin. In 22% patients they diagnosed during treatment a significant gradual decline of the left ventricular ejection fraction (change > 10% or a drop of EF below 50%) after a cumulative dose of 185 +/- 52 mg/m2 doxorubicin (median 200 mg/m2). Changes of the ejection fraction were at the expense of an increasing endsystolic left ventricular volume. These changes correlated closely with the increase of endsystolic stress of the left ventricular wall (r = -0.87). After administration of a cumulative doxorubicin dose of 100 mg/m2 a significant deterioration of indicators of diastolic filling of the left ventricle occurred--of the isovolumic relaxation period (IRP) and deceleration time (DT). The contribution of these early changes of diastolic function of the left ventricle for assessment of the risk of development of systolic dysfunction is not unequivocal. Prolongation of IRP > 12% as compared with the baseline value and at the same time above 95 ms had a 50% sensitivity, 50% specificity, a 26% positive prediction value a 74% negative prediction value and 50% diagnostic accuracy, change of DT > 13%, and at the same time prolongation above 200 ms had a 47% sensitivity 55% specificity, a 22% positive prediction value, a 78% negative prediction value and a 53% diagnostic accuracy. The authors found a significant relationship between the assessed changes of left ventricular function and clinical and haemodynamic indicators. Only the patients' age correlated significantly with IRP and DT values. Changes of the left ventricular ejection fraction were not associated with clinical signs of cardiac failure, they did not call for cardiological intervention and did not affect the course of chemotherapy. Contrary to some statements in the literature, the authors did not consider the described functional changes as sufficient to justify interference with chemotherapy. On the other hand, their importance for the development of late sequelae of chemotherapy with anthracyclines in adult patients must be based on long-term prospective follow-up.

Monitoring blood levels of selected drugs. Remember to factor in the many confounding variables.

Appropriate use of various pharmacologic agents involves not only awareness of therapeutic indications and side effects but also familiarity with clinical use and timing of blood level monitoring. The effective as well as the toxic level of antiepileptic drugs varies widely among patients, so the patient's response is more important than the serum drug level. These agents may interact with other disease states, other drugs, and even other antiepileptic agents. Because of digoxin's long half-life and the effect of physical exercise on serum concentration, the timing of serum collection is important. The usefulness of measuring amiodarone serum concentrations is controversial, but findings may help identify patients at risk for side effects related to the drug. Procainamide has a very short half-life and concentrations change over a short period, so blood levels of this agent should be measured before administration of a dose. The dose of levothyroxine required to restore a normal thyroid hormone level varies with age, coexistent conditions, and use of other medications. After the appropriate dose is determined, follow-up monitoring yearly is necessary (more often in the elderly). Efficacy and toxicity of theophylline are directly related to serum concentrations, and a reduced target level of 5 to 15 micrograms/mL has recently been suggested. Proper monitoring is important, because metabolic changes and drug interactions can cause either subtherapeutic or toxic levels.

Current patterns of prescribing and administering morphine in trauma patients.

We attempted to characterize the current prescribing practices and administration patterns for intravenous intermittent morphine in trauma patients in a multicenter, open prospective, observational study. The subjects were 141 patients admitted to the surgical intensive care units (ICU) of five United States trauma centers within 12 hours of injury who received intermittent intravenous morphine for pain relief. The study was conducted from April 15, 1992, to February 15, 1993. Data obtained during the first 32 hours of the ICU stay included morphine regimen, doses administered, and time between doses. One hundred sixty-one orders were prescribed by surgeons. The most frequently ordered dose was 2-4 mg and the most frequently ordered interval was every hour as necessary. There was no relationship between the severity of injury and the minimum dose ordered. During the 492 nursing shifts studied, 1257 doses were administered. Of these, 44% were at or below the minimum amount prescribed by the surgeons. Thirty-three percent of the patients received a dose at an interval of more than 3 hours. We concluded that small amounts of narcotic analgesics are given to severely injured patients, and amount ordered is not affected by the severity of injury.

Comparison of sprinkle versus syrup formulations of valproate for bioavailability, tolerance, and preference.

We compared a new coated-particle formulation of valproate (Depakote Sprinkle) capsules with valproic acid (Depakene) syrup for bioavailability, side effects, and patient and parent preference. Twelve children with epilepsy, aged 5 to 16 years, participated in this randomized, two-period, crossover study. They were assigned to a 7-day regimen with one formulation and then crossed over to the other; the drug was given every 12 hours. On day 7, blood samples collected during a 12-hour period were analyzed for the presence of valproate. At the study's end, parents and children were asked structured questions regarding formulation preference and adverse events. The extent of absorption from sprinkle equaled that from syrup (relative bioavailability = 1.02), but absorption was slower (time to maximum concentration = 4.2 vs 0.9 hour; p less than 0.01). Fluctuations in serum concentrations were less with sprinkle (34.8% vs 62.3%; p less than 0.01). Sprinkle was preferred by 9 of the 12 parents because of east of administration, and by nine of the children because of improved palatability. We conclude that sprinkle may be substituted for syrup without changing the daily dose. Furthermore, sprinkle, because of its prolonged absorption, may be given every 12 hours to children receiving monotherapy. Compliance may be enhanced because of the more convenient dosing schedules and the high degree of patient and parent acceptance.