Hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate in acute myocardial infarction.

Acute hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate (FDP), an agent that is supposed to restore anaerobic glycolytic flux in the ischemic myocardium, were studied in 40 patients with acute myocardial infarction who were grouped into 4 subsets: subset 1, normal (15 mm Hg or less) pulmonary artery (PA) wedge pressure and normal (35 g-m/m2 or greater) left ventricular (LV) stroke work index; subset 2, elevated (more than 15 mm Hg) PA wedge pressure and normal LV stroke work index; subset 3, normal PA wedge pressure and reduced (less than 35 g-m/m2) LV stroke work index; subset 4, elevated PA wedge pressure and LV stroke work index moderately reduced to a range between 16 and 34 g-m/m2. Patients were randomized into an FDP (250 mg/kg body weight in isotonic saline solution intravenously in 20 minutes) and into a placebo group. Each subset contained 5 FDP- and 5 placebo-treated patients. After basal measurements, hemodynamic measurements were reassessed at 60, 90 and 120 minutes from the infusions, while a standard 12-lead electrocardiogram was recorded in the basal state and 120 minutes after infusion. Nonsignificant hemodynamic change was observed in the placebo subsets, and FDP failed to exert any effect in subsets 1, 2 and 3. A 24% (p less than 0.02) increase in cardiac index occurred 60 minutes after FDP in subset 4. LV stroke work index also increased, while PA wedge pressure remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Features of excessive alcohol drinking in older adults distinctively captured by behavioral and biological screening instruments. An epidemiological study.

The entire > or =65-year-old population living in a small Italian town, where alcohol use is almost ubiquitous, was assessed with a frequency-quantity questionnaire for alcohol intake and with two screening instruments for alcohol problems, the CAGE questionnaire and the MCV-gammaGT test. Aim of the study was to assess whether these instruments identify different subsets of subjects with alcohol problems. Of the 649 participants, 19.1% were at-risk drinkers (average intake > 40 g/day in men and > 20 g/day in women). Both the screening instruments were positive in only a minority of participants. Of the 377 drinkers, 53 gave > or =1 affirmative response to the CAGE questionnaire, whereas 24 had a positive MCV-gammaGT test. The concordance between positive CAGE questionnaire and MCV-gammaGT test was limited to seven subjects (kappa = 0.10), and these tests identified subjects who differed for several health and psychosocial characteristics. Participants aged > or =75 years drank less, but had similar prevalence of CAGE and MCV-gammaGT positive markers as compared to younger participants. In conclusion, excessive drinking is common in the elderly. Screening tests based on behavioral and biological markers identify two different sets of subjects with possible alcohol problems. This might indicate the opportunity to use these instruments in conjunction.

Disease severity and health-related quality of life across different chronic conditions.

OBJECTIVES: Measurements of health-related quality of life (HRQL) are an essential component in overall assessment of health status, particularly in older patients. Nevertheless, how measures of HRQL relate to measures of disease severity is largely unexplored. This study was carried out to explore the relationship between a measure of HRQL and measures of severity of ischemic stroke, Parkinson's diseases (PD), or chronic coronary heart disease (CHD). DESIGN AND SETTING: Cross-sectional analysis of three groups (54 subjects each) of patients aged > or = 65 years consecutively referred to outpatient clinics for stroke, PD, or CHD, excluding those with cognitive impairment and severe comorbidity. MEASUREMENTS: Severity of stroke, PD, and CHD assessed by Fugl-Meyer Scale (FMS), Webster Rating Scale (WBRS), and total work capacity (TWC, from graded exercise test), respectively. HRQL was determined by the Sickness Impact Profile (SIP). RESULTS: In PD, WBRS correlated linearly with SIP global score, whereas a significant linear relationship between measures of disease severity and SIP score was limited to the least severely diseased stroke (FMS score>160) and the most severely diseased CHD (TWC <700 Kg x m) patients. CONCLUSIONS: In some disease, the relationship between clinical measures of disease severity and HRQL is nonlinear. Thus, depending on initial severity, similar changes in disease severity may have different impacts on HRQL. These findings may help in identifying patients most likely to improve their SIP score substantially, after even small changes in disease severity. However, studies examining the metric properties of SIP across the whole score range are needed to verify whether such improvement really translates into a better HRQL.

Heart failure in community-dwelling older persons: aims, design and adherence rate of the ICARe Dicomano project: an epidemiologic study. Insufficienza Cardiaca negli Anziani Residenti a Dicomano.

BACKGROUND: The prevalence of heart failure (HF) increases with age, and HF is a major cause of disability and mortality in older persons. Detection of HF in epidemiological studies has relied on criteria validated only in young and middle-age adults, and, therefore, may prove inadequate in older subjects, because they do not take into account the pathophysiologic and clinical peculiarities of HF in old age. Thus, the true prevalence of HF in the older general population remains uncertain and has probably been underestimated in previous studies. Moreover, the mechanism and the extent by which HF hinders physical functioning in older people has not been fully elucidated. OBJECTIVES: This paper describes the design of the ICARe study, carried out in an older home-dwelling population to collect data about: (1) the sensitivity and specificity of diagnostic criteria used previously in epidemiological studies of HF; (2) the prevalence of the different pathophysiologic forms of HF; and (3) the impact of HF on overall health status, and on physical functioning, in the absence or presence of chronic comorbidity. DESIGN AND SETTING: This was a cross-sectional survey. Eligible were all community-dwelling persons aged 65 years or older recorded in the Registry Office of Dicomano, a small town nearby Florence (Italy). All the domains of multidimensional geriatric assessment were explored through different phases of the study (home interview, laboratory testing, geriatric visit) that comprised an extensive cardiopulmonary instrumental assessment including: color Doppler echocardiography, echotomography of the carotid arteries used in an original method to determine arterial compliance, and bell spirometry. Presence of major chronic conditions was ascertained by predefined, standard algorithms that were based largely on clinical examination. RESULTS: There were 864 older persons eligible for the ICARe study. Even with a substantial decline from home interview (91.2%) to the cardiopulmonary study (71.1%), the adherence rate remained high throughout the study, and the population examined was fairly representative of the original eligible population. Thus, we believe that the data collected in this study offer a unique opportunity to assess the validity of the diagnostic clinical criteria for HF in the general older population, to identify the pathophysiology underlying the syndrome, and to investigate the relationship between HF, comorbidity, and disability.

Effects of antiplatelet and calcium antagonist drugs on infarct size in rats.

The authors performed the experimental model of infarct-like myocardial lesions in rats treated with large doses of ISP. Myocardial necrosis was assessed on the basis of serum enzyme changes as well as of gross and microscopic findings. The infarct size was measured by a direct enzymatic method assaying creatine kinase (CK) depletion in infarcted myocardium. Pretreatment of the infarcted rats with antiplatelet (Lysin Acetyl Salicylate) or calcium antagonist drugs (Verapamil or Nifedipine) allowed the reduction of the necrotic area. Since a smaller size of infarct was achieved through different types of interventions it should be suggested that ISP-myocardial damage is due to several effects of the drug involving metabolic, vascular and/or coagulative patterns.

[Cerebral infarction: lacunae]. / Degli infarti cerebrali: le lacune.

Lacunae are small deep cerebral infarcts which are believed to occur in hypertensive patients, producing characteristic clinical syndromes. Previous reports suggested to differentiate this type of stroke from other cerebrovascular diseases, but failed to provide any evidence that this classification is useful in clinical practice. We reviewed the present literature concerning pathogenesis, clinical features, diagnostic, and therapeutic aspects of lacunae and we established that current concepts in lacunar stroke are inadequately supported. Although lacunar syndromes are reported to be correlated with lacunar infarcts, these syndromes are also described in patients with different pathological findings. The assumption that lacunae always result from a distinct and specific small-vessel arteriopathy is not confirmed; in fact, an atheroma may occlude a single perforating artery at the base of the brain as well as larger arteries. Lipohyalinosis, initially referred to as the underlying pathologic vascular lesion specific for lacunae, is found most commonly in a subset of patients with severe hypertension associated with multilacunar dementia. Large infarcts and hemorrhages are reported to coexist with lacunae in autoptic and neuroradiological studies; intracranial atherosclerosis is associated with lacunae as well as with large superficial infarcts. The percentage of patients with hypertension is approximately the same regardless of type of the infarct, lacunar or cortical. Diagnostic criteria are not clear-cut: clinical onset, neurological examination, and assessment of risk factors are unable to take lacunae apart from other infarcts; the size of the lesion, but not the site or the pathogenesis, determines clinical course, degree of motor deficit, and prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative assessment of infarct size in isoproterenol-infarcted rats.

The authors performed a number of experiments aiming at quantifying the infarct size in Sprague-Dawley male rats. The experimental model employed was isoproterenol (ISP) induced, infarctlike myocardial lesions. In quantifying the extent of the infarct area they compared the cross reliability of enzymatic and histological methods. ISP was administered in two subcutaneous injections (50 mg/100 Gm body weight) at a 24 hour interval. At the peak of the necrotic process (48 hrs after the first injection), the heart was subjected to enzymatic or histological studies. Thus, a group of infarcted animals (n = 25) and their controls (n = 15) underwent the assessment of creatine kinase (CK) content in the homogenate of the myocardium. Another group of animals (n = 15) was used for histological observations, including measurement of infarct size by planimetry from histological sections. A good relationship was observed between the percentage of necrotic tissue calculated on the basis of CK values (69.11 +/- 2.39%) and the infarction area assessed by planimetry (72.37 +/- 2.69%) (mean +/- standard error of the mean [SEM]). Thus, the present study confirms that ISP-induced myocardial lesions are a simple and reliable model for experimental infarct. Moreover, the assessment of the CK content in the heart is correlated with histological studies by planimetry, and is suggested as a direct enzymatic method to quantify the extent of myocardial necrosis.

Adrenergic activity as a modulating factor in the genesis of myocardial hypertrophy in the rat.

Sprague Dawley male rats (200-220 g) were subjected to a long-term treatment with low doses of catecholamines in an attempt to assess the effect of the adrenergic stimulation on ventricular weights, hemodynamics, and hydroxyproline content in the myocardium. Data are presented indicating that both exogenous catecholamines (i.e., isoproterenol) and endogenous catecholamines (released from tyramine) are able to bring about a degree of myocardial hypertrophy associated with a significant increase in the ventricular concentrations of hydroxyproline, without affecting hemodynamic parameters (blood pressures and heart rate). Thus the modulation of sympathetic tone in the genesis of cardiac hypertrophy is demonstrated, and a direct effect of the catecholamines on cardiac cells is postulated which is independent of hemodynamic changes.

Inhibition of hypoxia-induced cardiac hypertrophy by verapamil in rats.

Male Sprague-Dawley rats (200-220 g) were employed to study the effect of a calcium antagonistic drug on hypoxia-induced myocardial hypertrophy. The hypoxic condition was obtained by exposure of animals to reduced barometric pressure in a hypobaric chamber. The rats, divided in groups, were exposed to acute or chronic intermittent hypoxia (0.42 atmospheres of air for 24 hrs or 0.42 atm for 12 hrs per day for 10 days, respectively). Verapamil (VRP) was given subcutaneously in a total dose of 200 mg/kg/b.w./rat. In hypoxic rats, the drug significantly reduced the values of dry heart weight calculated on the basis of its relationship to total body weight. This phenomenon is probably due to: (1) reduced activation of the contractile system and a thereby resulting decrease in ATP breakdown as a result of blocking of Ca++ inflow into myocardial cells; (2) the effect of Verapamil on hypoxia-induced pulmonary hypertension and/or (3) a direct effect of the drug on the myocardial cell.

Effect of experimental infarct on the mortality rate in alloxan-diabetic rats.

The authors report the wide mortality observed in alloxan diabetic rats infarcted with large doses of isoproterenol. The experimental data are in line with the results of clinical studies testifying that the diabetic disease involves the cardiovascular system and affects the prognosis of myocardial infarct. These experiences do not permit to define the direct mechanism(s) responsible for the high mortality in diabetic infarcted rats over controls (diabetic not infarcted); however these results give rise to a discussion on the following topics: 1. The damage of intramural coronary vessels as a cause of depressed cardiac contractility in diabetic rats. 2. The role of reduced plasmatic levels of insulin in depressing myocardial performance in alloxan diabetic rats. 3. The hyperglycaemia-provoking effect of isoproterenol as a contributing factor in the death of diabetic rats. 4. The possible direct action of diabetogenic doses of alloxan on the myocardium.

Development of cardiac hypertrophy in rats exposed to acute hypobaric hypoxia. - Studies with protein synthesis inhibitors.

The study is based on the experimental model of myocardial hypertrophy in rats. Male Sprague-Dawley adult rats were exposed to acute hypoxia in a hypobaric chamber (0.40 atmospheres of air for 24 hours). Myocardial hypertrophy was detected by wet and dry heart weight values when calculated on the basis of total body weight; i.e., ratio heart weight in mg to body weight in 100 g. The behaviour of myocardial hypertrophy was assessed after treatment of intact animals with Puromycin (10 mg/rat i.p.) or Actinomycin-D (100 micrograms/rat i.p.). The experimental results showed the following dry heart weight values (mean +/- SEM): room pressure 60.5 +/- 1.5; hypoxia 69.2 +/- 0.9; Actinomycin-D + hypoxia 63.5 +/- 0.6; Puromycin + hypoxia 62.4 +/- 1.5, (P less than 0.001). From the comparison of data reveals that inhibitors of protein synthesis completely inhibit the myocardial hypertrophy due to hypoxia. Thus it is documented that acute hypobaric hypoxia is able to induce in the rat an actual myocardial hypertrophy condition as expressed of the enhanced protein synthesis.

[A case of postinfarction spontaneous angina: physiopathological study of the therapeutic effectiveness of intra-aortic balloon pumping]. / Un caso di angina spontanea post-infartuale: inquadramento fisiopatologico dell'efficacia terapeutica della contropulsazione intra-aortica.

A 46-year-old patient showed spontaneous angina with anterior S-T segment depression 30 hours after an inferior acute myocardial infarction. Myocardial ischemia, which was resistant to drug therapy and induced acute left ventricular failure, was promptly reversed by intra-aortic balloon pumping (IABP). Coronary angiography demonstrated diffuse, severe atherosclerotic disease. Efficacy of IABP in this case of spontaneous angina might be ascribed to an increase of the coronary cross-sectional area in response to the increased intraluminal pressure ("passive vasomotion").

Intra-aortic balloon pumping in the elderly: percutaneous versus surgical catheter insertion.

The feasibility and safety of percutaneous versus intra-aortic balloon pumping (IABP) in the elderly were evaluated in 45 patients who were over 65 years of age (range 65-79). All the patients required counterpulsation for complicated acute myocardial infarction. IABP insertion was attempted by the surgical technique in 22 patients, while the percutaneous approach was performed in 23. A consistent improvement in the incidence rate of successful insertion was attained with the use of the percutaneous technique as compared with the surgical one (91.3% v 59.1%, P is less than 0.05). Furthermore, no major complication was observed with the percutaneous catheter, while a 9.1% (2/22) incidence rate of serious complications was reported with the surgical technique. Thus, percutaneous IABP substantially decreased the unsuccessful insertions and the risk of severe complications in old patients, despite presumably severe aorto-iliac disease. No specifically age-related technical problem seems, therefore, to limit the applicability of intra-aortic counterpulsation to elderly patients, when percutaneous IABP is employed.

Hemodynamic effects of digoxin in acute myocardial infarction in man: a randomized controlled trial.

Hemodynamic effects of digoxin in acute myocardial infarction (AMI) have been acknowledged to depend on the basal cardiocirculatory state. In the present study, the effects of digoxin in patients with AMI were evaluated in four hemodynamic subsets, based on the relationship between mean pulmonary capillary wedge pressure (PCWP, in mm Hg) and left ventricular stroke work index (LVSWI, in g-m/m2): subset 1: normal (less than or equal to 15 mm Hg) PCWP and normal (greater than or equal to 35 g-m/m2) LVSWI; subset 2: elevated (greater than 15 mm Hg) PCWP and normal LVSWI; subset 3: reduced (less than 35 g-m/m2) LVSWI and normal PCWP; and subset 4: elevated PCWP and LVSWI moderately reduced to a range between 16 and 34 g-m/m2. Forty patients were admitted to the study and were randomly assigned to one of two groups in each subset: control group (19 patients) and treated group (21 patients). Five patients were randomized into each of the subsets 2, 3, and 4 in both the control and treated groups, while in subset 1 there were four control and six digoxin-treated patients. Control patients were administered a placebo saline solution and digoxin-treated patients received 0.50 mg of the drug intravenously in 20 minutes. The effects of the placebo and of the drug were evaluated at 30, 60, and 90 minutes from the end of the infusion. Hemodynamic data did not vary in the control group, and digoxin did not exert any relevant effect in subsets 1 and 2. After drug infusion, cardiac index (Cl, in L/min/m2) significantly increased in subset 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)