Depressed Heart Rate Research Articles

Myocyte hypertrophy: the long and winding RhoA'd.

Myocyte hypertrophy: the long and winding RhoA'd.

Resuscitation of the newly born infant: an advisory statement from the Pediatric Working Group of the International Liaison Committee on Resuscitation

The International Liaison Committee on Resuscitation (ILCOR), with representation from North America, Europe, Australia, New Zealand, Africa, and South America, was formed in 1992 to provide a forum for liaison between resuscitation organizations in the developed world. This consensus document on resuscitation extends previously published ILCOR advisory statements on resuscitation to address the unique and changing physiology of the newly born infant within the first few hours following birth and the techniques for providing advanced life support. After careful review of the international resuscitation literature and after discussion of key and controversial issues, consensus was reached on almost all aspects of neonatal resuscitation, and areas of controversy and high priority for additional research were delineated. Consensus on resuscitation for the newly born infant included the following principles. (i) Personnel trained in the basic skills of resuscitation should be in attendance at every delivery. A minority (fewer than 10%) of newly born infants require active resuscitative interventions to establish a vigorous cry and regular respirations, maintain a heart rate greater than 100 beats per minute (bpm), and maintain good color and tone. (ii) When meconium is present in the amniotic fluid, it should be suctioned from the hypopharynx on delivery of the head. If the meconium-stained newly born infant has absent or depressed respirations, heart rate, or muscle tone, residual meconium should be suctioned from the trachea. (ii) Attention to ventilation should be of primary concern. Assisted ventilation with attention to oxygen delivery, inspiratory time, and effectiveness judged by chest rise should be provided if stimulation does not achieve prompt onset of spontaneous respirations and/or the heart rate is less than 100 bpm. (iv) Chest compressions should be provided if the heart rate is absent or remains less than 60 bpm despite adequate assisted ventilation for 30 s. Chest compressions should be coordinated with ventilations at a ratio of 3:1 and a rate of 120 ‘events’ per minute to achieve approximately 90 compressions and 30 rescue breaths per minute. (v) Epinephrine should be administered intravenously or intratracheally if the heart rate remains less than 60 bpm despite 30 s of effective assisted ventilation and chest compression circulation. Common or controversial medications (epinephrine, volume expansion, naloxone, bicarbonate), special resuscitation circumstances affecting care of the newly born, continuing care of the newly born after resuscitation, and ethical considerations for initiation and discontinuation of resuscitation are discussed. There was agreement that insufficient data exist to recommend changes to current guidelines regarding the use of 21% versus 100% oxygen, neuroprotective interventions such as cerebral hypothermia, use of a laryngeal mask versus endotracheal tube, and use of high-dose epinephrine. Areas of controversy are identified, as is the need for additional research to improve the scientific justification of each component of current and future resuscitation guidelines.

Navigation in the mega-trials waters: reflections on the multicenter automatic defibrillator implantation trial and the antiarrhythmics versus implantable defibrillators study

Today, cardiology seems to be driven by mega-trials and meta-analyses. Guidelines published by scientific and professional cardiovascular societies, such as the American Heart Association, the American College of Cardiology, and the European Society of Cardiology, follow the rules of evidence-based medicine. Such evidence is not always sufficiently conclusive to practice clinically helpful medicine. Sometimes, relatively small trials, such as the Multicenter Automatic Defibrillator Implantation Trial and the Antiarrhythmics Versus Implantable Defibrillators study, may be taken as guides for current clinical decisions and as inspiration for future investigations. Large mega-trials with a great lack of homogeneity among the recruited patients are less important for clinically helpful medicine than studies enrolling well-defined, high-risk patients. It is probably important to acknowledge that the best possible treatment for many patients with ventricular tachyarrhythmias remains obscure. Among these situations are the following: (1) sustained ventricular tachycardia (VT) in patients without coronary artery disease; (2) sustained, nonsyncopal VT in patients with coronary artery disease and left ventricular dysfunction; (3) post myocardial infarction survivors with an ejection fraction ≤35%, frequent/complex ventricular arrhythmias, depressed heart rate variability, and inducible sustained ventricular tachyarrhythmias during electrophysiologic study. Many studies are being conducted to add light where uncertainty exists, but probably only a few will contribute to the practice of clinically helpful medicine, although some will be used to produce meta-analysis to sustain evidence-based medicine.

The cardiovascular effects of amperozide: interactions with cocaine.

Amperozide is a 5-HT2A receptor antagonist that significantly reduces the acquisition and expression, by rats, of a cocaine conditioned place preference. In order to rule out the possibility that amperozide affects a cocaine conditioned place preference due to effects on blood pressure or heart rate, the cardiovascular effects of amperozide were investigated. Alternating cumulative doses of amperozide (0.5, 1.0, 1.5 and 2.5 mg kg(-1)) or saline and phenylephrine (8 microg kg(-1)) were administered through the femoral vein of awake freely-moving Sprague-Dawley rats and blood pressure and heart rate were recorded from the femoral artery. A single dose of cocaine (5.0 mg kg(-1)) was administered after all the amperozide or saline doses were given. Amperozide (0.5, 1.0, 1.5 and 2.5 mg kg(-1)) did not have any significant effect on blood pressure compared to the saline control treatment to the same animals. However, 0.5 mg kg(-1) amperozide significantly decreased heart rate at 5 and 10 min. after administration. but higher doses did not further depress heart rate. Amperozide did not affect the increased blood pressure and decreased heart rate caused by phenylephrine. an alpha1-adrenoceptor agonist. In addition, amperozide did not affect the cardiovascular response to an intravenous dose of 5.0 mg kg(-1) cocaine. These results suggest that amperozide does not cause direct cardiovascular effects. The mechanism by which the lowest dose of amperozide caused a decrease in heart rate is unknown. Amperozide affects neither alpha-adrenoceptor mediated vasoconstriction nor the increased sympathetic activity caused by the peripheral and central effects of cocaine. The significance of these results, in terms of locomotor activity and the cocaine conditioned place preference paradigm, is discussed.

Magnetic field exposure and cardiovascular disease mortality among electric utility workers.

Laboratory studies suggest that electric and magnetic field exposure may affect heart rate and heart rate variability. Epidemiologic evidence indicates that depressed heart rate variability is associated with reduced survival from coronary heart disease as well as increased risk of developing coronary heart disease. The authors examined mortality from cardiovascular disease in relation to occupational magnetic field exposure among a cohort of 138,903 male electric utility workers from five US companies over the period 1950-1988. Cardiovascular disease deaths were categorized as arrhythmia related (n = 212), acute myocardial infarction (n = 4,238), atherosclerosis (n = 142), or chronic coronary heart disease (n = 2,210). Exposure was classified by duration of work in jobs with elevated magnetic field exposure and indices of cumulative magnetic field exposure. Adjusting for age, year, race, social class, and active work status, longer duration in jobs with elevated magnetic field exposure was associated with increased risk of death from arrhythmia-related conditions and acute myocardial infarction. Indices of magnetic field exposure were consistently related to mortality from arrhythmia and acute myocardial infarction, with mortality rate ratios of 1.5-3.3 in the uppermost categories. No gradients in risk were found for atherosclerosis or for chronic coronary heart disease. These data suggest a possible association between occupational magnetic fields and arrhythmia-related heart disease.

Physical activity, mental stress, and short-term heart rate variability in patients with ischemic heart disease.

Among the general population, mental stress seems to depress heart rate variability (HRV), and physical activity level seems to be positively associated with HRV. However, the extent to which these relationships exist among patients with ischemic heart disease is not clear. Therefore, this study investigated the association between level of physical activity and HRV among patients with ischemic heart disease during conditions of paced breathing and the Stroop Color-Word Conflict Test (Stroop). Forty-two patients with ischemic heart disease were assigned to groups based on their documented volume of aerobic activity: Low = 1.008-2.646 kJ/wk; Mod = 3.024-3.864 kJ/wk; and High = 4.284-7.560 kJ/wk. These groups did not differ in age, body mass index, or hostility as determined by the Minnesota Multiphasic Personality Inventory. Time and frequency domain measures of HRV were derived from electrocardiograph data obtained during 5 minutes of paced respiratory control and 5 minutes of performing the Stroop Test. There was a main effect of activity level (P < 0.05) on the standard deviation of R-wave to R-wave intervals (SDNN), total spectral power, and high-frequency power such that these dependent variables were greater in the High group than in the Low or Mod group. Furthermore, there was a main effect of the test condition on SDNN and total power, both of which were lower during the Stroop Test as compared to paced respiratory control. The results indicate that, among patients with ischemic heart disease, a high level of physical activity is associated with higher HRV, but is not related to stress reactivity as measured by HRV.

Cost-Effectiveness Analysis of Invasive and Noninvasive Tests in High Risk Patients Treated With Amiodarone After Acute Myocardial Infarction

Objectives. We sought to evaluate 1) the cost-effectiveness of amiodarone therapy in postinfarction patients; and 2) the influence of alternative diagnostic strategies (noninvasive only vs. noninvasive and electrophysiologic testing) on survival benefit and cost-effectiveness ratio of amiodarone therapy.Background. The cost-effectiveness of amiodarone therapy in postinfarction patients is still unknown, and no study has determined which diagnostic strategy should be used to maximize amiodarone survival benefit while improving its cost-effectiveness ratio.Methods. We designed a postinfarction scenario wherein heart rate variability analysis on 24-h Holter monitoring was used as a screening test for 2-year amiodarone therapy in a cohort of survivors (mean age 57 years) of a recent myocardial infarction. Three different therapeutic strategies were compared: 1) no amiodarone; 2) amiodarone in patients with depressed heart rate variability; 3) amiodarone in patients with depressed heart rate variability and a positive programmed ventricular stimulation. Total variable costs and quality-adjusted life expectancy during a 20-year period were predicted with use of a Markov simulation model. Costs and charges were calculated with reference to an Italian and American hospital.Results. Amiodarone therapy in patients with depressed heart rate variability and a positive programmed ventricular stimulation was dominated by a blend of the two alternatives. Compared with the no-treatment strategy, the incremental cost-effectiveness ratio of amiodarone therapy in patients with depressed heart rate variability was $10,633 and $39,422 per gained quality-adjusted life-year using Italian costs and American charges, respectively.Conclusions. Compared with a noninterventional option, amiodarone prescription in all patients with depressed heart rate variability seems to be a more appropriate approach than the alternative based on the combined use of heart rate variability and electrophysiologic study.

Effects of Verapamil on Indexes of Heart Rate Variability After Acute Myocardial Infarction

In patients with previous myocardial infarction (MI), depressed heart rate variability (HRV) may reflect a reduction in vagal activity and lead to cardiac electrical instability. Interventions designed to increase HRV may be of clinical interest. Data on the effects of calcium antagonists on HRV in post-MI patients are very limited. The aim of our study was to assess the effects of verapamil on HRV and on the sympathovagal balance after MI. Fifty consecutive patients with a first MI, stable sinus rhythm, and left ventricular ejection fraction >0.40 were studied. Each patient underwent two 24-hour Holter recordings, 1 at baseline and another after 4 days of treatment with verapamil retard (180 mg 2 times daily). Time and frequency domain parameters of HRV were analyzed. All time domain measurements increased significantly after verapamil: the standard deviation of all NN intervals (SDNN) from 87.1 ± 31.4 to 98.1 ± 30.3 ms (p <0.05) and the log-transformed percentage of pairs of adjacent NN intervals that differ >50 ms (pNN50) from 0.57 ± 0.42 to 0.76 ± 0.45 (p <0.01). The standard deviation of the averages of RR interevals (SDANN) (75.9 ± 30.1 vs 86.3 ± 29.4 ms, p <0.05), root-mean-square of successive differences between RR intervals (rMSSD) (23.0 ± 11.7 and 28.1 ± 13.1 ms, p <0.01), and the triangular HRV index (28.3 ± 9.6 vs 23.4 ± 8.6, p <0.001) also increased. A significant inverse correlation was found between improvement in HRV indexes induced by verapamil and baseline values. Spectral analysis showed a significant increase in high-frequency power of 58.5% without changes in low and very low components. With normalized units, significant reductions in low-frequency power and low- to high-frequency ratio were observed. Diabetic patients did not show any significant changes in HRV on administration of verapamil. These findings indicate that verapamil, administered during the subacute phase of MI, improves both global and short-period indexes of HRV and induces a shift in the sympathetic-parasympathetic interaction toward vagal predominance. This effect may contribute to an explanation of the beneficial effects of verapamil that have been reported in post-MI patients.

Depressed heart rate variability is associated with events in patients with stable coronary artery disease and preserved left ventricular function

Background: Little is known about the value of heart rate variability in patients with symptomatic coronary artery disease with a preserved left ventricular function. We hypothesized that in these patients heart rate variability might be a helpful adjunct to conventional parameters to predict clinical events. Methods: In a prospective 2-year follow-up study ambulatory electrocardiographic recordings were performed in 263 consecutive male patients (mean age 56 ± 8 years) with stable angina pectoris and a mean left ventricular ejection fraction of 71% ± 12%. Clinical events consisted mainly of coronary events such as percutaneous transluminal angioplasty or coronary artery bypass graft operation. Results: Low measures of standard deviation of normal R-R intervals, standard deviation of the mean R-R intervals of 5 minutes, and two spectral components of heart rate variability were found in patients who had had an event compared with patients with no event. Adjusted for severity of angina, the presence of a previous myocardial infarction, and the use of β-blockers in a logistic regression model this relation remained statistically significant for SDNN. Healthy volunteers appeared to have the highest measures of heart rate variability. Conclusion: In patients with ischemic heart disease and normal or near normal ventricular function decreased heart rate variability is associated with adverse clinical events. (Am Heart J 1998;135:571-6.)

Depressed heart rate variability and arterial baroreflex in conscious transgenic mice with overexpression of cardiac Gsalpha.

Recently, we developed a transgenic mouse with cardiac-specific Gsalpha overexpression (TG mouse), which exhibits enhanced postsynaptic beta-adrenergic receptor signaling, ultimately developing a cardiomyopathy. The goal of the present study was to determine whether cardiac Gsalpha overexpression alters autonomic cardiovascular control, which could shed light on the mechanism responsible for the later development of cardiomyopathy. Mean arterial pressure was increased (P<.05) in conscious, chronically instrumented TG mice (123+/-1 mm Hg) compared with age-matched wild-type (WT) control mice (103+/-1 mm Hg). Respiratory frequency was increased (P<.05) in TG mice (269+/-26/min) compared with WT mice (210+/-20/min). By use of telemetric techniques, baseline heart rate (HR) was elevated (P<.05) in conscious, untethered TG mice (696+/-13 bpm) compared with WT mice (568+/-28 bpm). Intrinsic HR, after propranolol and atropine or after ganglionic blockade with hexamethonium, was not different between TG and WT mice. Both the normal minute-to-minute and circadian variations of HR observed in WT mice were markedly blunted in TG mice. HR variability was assessed by the time-domain and frequency-domain methods. At baseline, time-domain analysis indices were reduced (P<.05) in TG mice compared with WT mice. Although the low frequency (LF) component was higher (P<.05) than the high frequency (HF) component in WT mice, the LF component was less (P<.05) than the HF component in TG mice. In addition, arterial baroreflex regulation of HR was markedly blunted in TG mice in response to both nitroglycerin-induced hypotension and phenylephrine-induced hypertension. The reduced LF/HF ratio in TG mice was surprising in view of enhanced beta-adrenergic signaling and may be due to reduced neural tone secondary to the elevated arterial pressure or alterations in arterial baroreflex control. Dobutamine infusion in WT mice also resulted in depressed HR variability. The combination of elevated baseline HR, arterial pressure, and respiratory frequency suggests that enhanced beta-adrenergic signaling in TG mice results in reduced HR variability, in terms of both minute-to-minute variability and the lack of circadian variations in HR. The lack of normal HR variability in general and the failure of HR to decline, even during sleep, may actually be critical mechanisms contributing to the ultimate development of cardiomyopathy in these animals.

Analysis of clinical follow-up databases: risk stratification studies and prospective trial design.

Design of new prospective studies should utilize detailed retrospective evaluations of clinical data. For this purpose, clinical data are needed containing both prospectively recorded values of risk factors and follow-up events. A concept of a new trial can then be modeled within the existing data-set. The development of such a model consists of the following steps: (a) the distribution of values of risk factors has to be investigated in the whole recorded population and the statistical association of the risk factors with follow-up events has to be established; (b) the stratification characteristics (sensitivity, specificity, and predictive accuracies) have to be evaluated for individual risk factors and for their multivariate combinations; (c) the stratification characteristics have to be converted into estimates of mortality reduction expected within the high risk group and used for the optimum trial design in terms of screened and randomized patient numbers. In this review, the strategy of designing a new trial is demonstrated using data of 644 survivors of acute myocardial infarction with available 3-year follow-up during which 74 patients died. A model of a new trial is considered involving reduced left ventricular ejection fraction, increased 24-hour mean heart rate, and depressed 24-hour heart rate variability as risk stratifiers.

Recovery of heart rate variability profile in patients after coronary artery surgery.

We examined the different characteristics of heart rate variability (HRV) to define the time course of HRV profile after coronary artery surgery (CAS). Spectral analysis of HRV was performed on a 512-s segment of R-R intervals of the electrocardiogram on the preoperative day and on Postoperative Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28. Power spectral area was divided into low (0.04-0.15 Hz; LF)- and high (0.15-0.5 Hz; HF)-frequency components. Fractal slope and sympathovagal slope of 1/f characteristics of HRV were determined in two different frequency ranges (from 0.01 to 0.15 Hz and from 0.01 to 0.5 Hz, respectively). Three recovery profiles of HRV were identified. Early HRV recovery profiles (Postoperative Days 1-6) included reduction in LF, HF, and sympathovagal slope, as well as an increase in fractal slope. Subsequent HRV recovery profiles (Postoperative Days 7-21) revealed reductions in LF, HF, and sympathovagal slope. Fractal slope became normal. Later HRV recovery profiles (Postoperative Day 28) demonstrated that all spectral components of HRV remained reduced, but sympathovagal and fractal slopes became normal. These changes in the HRV profile after CAS suggest significant postoperative alterations in cardiovascular homeostasis with significant but incomplete recovery during the first 28 postoperative days. Heart rate variability reflects normal neural regulation of cardiac function. This variability remains depressed as long as 28 days after coronary artery bypass surgery, but can recover as early as 1 wk postoperatively. Despite implied loss of normal neural regulation of cardiac function, a specific correlation between depressed heart rate variability and outcomes was not performed.

Inhibition of Nitric Oxide Synthase byL-NAME Improves Ventricular Performance in Streptozotocin- diabetic Rats

The overall goal of this study was to determine if activation of the nitric oxide synthetic pathway suppressed basal ventricular performance and the responsiveness toβ-adrenergic stimulation characteristic of cardiac function in the 8-week streptozotocin (60 mg/kg, i.v.) diabetic (STZ-Db) rat. Left ventricular performance was measured in isolated working hearts, before and at the peak response to 0.8μm dobutamine, in the absence or presence of NG-nitro-l-arginine methyl ester (l-NAME, 1 mm), a non-selective inhibitor of nitric oxide synthase (NOS). Ventricular performance was suppressed in the STZ-Db heart under basal (decreased heart rate, cardiac output, aortic flow −dP/dt) and dobutamine-stimulated (diminished rise in +dP/dtand maximum systolic pressure) conditions.l-NAME had minimal effects on basal or dobutamine-stimulated ventricular performance in control hearts. In contrast,l-NAME infusion in hearts from STZ-Db returned the depressed heart rate to control values, which was correlated with an increase in aortic flow. In addition, the dobutamine-stimulated rise in maximum systolic pressure and +dP/dtwere similar in the control and STZ-Db rats in the presence ofl-NAME. Western blot analysis detected the presence of inducible nitric oxide synthase (NOS) and a significant (P<0.001) increase in the constitutive NOS in ventricular myocytes from STZ-Db rats. These data suggest that an increased production of nitric oxide by NOS in ventricular myocytes from STZ-Db animals suppressed basal ventricular performance and the responsiveness toβ-adrenergic stimulation in diabetic hearts.

Depressed Heart Rate Variability as an Independent Predictor of Death in Chronic Congestive Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 ± 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 ± 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN <100 ms to be a useful risk factor; 1-year survival in patients with SDNN <100 ms was 78% when compared with 95% in those with SDNN >100 ms (p = 0.008). The coexistence of SDNN <100 ms and a peak oxygen consumption <14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.In 102 consecutive patients with stable chronic congestive heart failure and sinus rhythm, several heart rate variability measures derived from 24-hour electrocardiographic recording were significant prognostic risk markers, independent of clinical variables (New York Heart Association class, peak oxygen consumption, left ventricular ejection fraction). The coexistence of the standard deviation of all normal RR intervals <100 ms and peak oxygen consumption <14 ml/kg/min had the worst prognosis, and it is concluded that heart rate variability analysis is useful for noninvasive heart transplant assessment.

Administration of ATP-MgCl2after Trauma–;Hemorrhage and Resuscitation Restores the Depressed Cardiac Performance

Although adenosine triphosphate (ATP)-MgCl2has been shown to improve cardiac performance under normal and postischemic conditions, it is not known whether this agent has any salutary effects on cardiac performance following trauma–;hemorrhage and crystalloid resuscitation. To determine this, rats underwent laparotomy (i.e., trauma induction) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood using Ringer's lactate over 60 min and received either ATP-MgCl2(50 μmole/kg body wt) in 1 ml volume or an equivalent volume of normal saline intravenously over 95 min. MaximumdP/dtduring contraction as well as relaxation (±dP/dtmax) and ventricular peak systolic pressure (VPSP) were determined 15 min prior to the end of resuscitation and every 30 min thereafter for 4 hr after the completion of resuscitation. The results indicate that both −dP/dtmaxand +dP/dtmaxdecreased significantly beginning at 0 and 2 hr after the completion of resuscitation, respectively, and remained depressed throughout the duration of the study in saline-treated animals. In addition, VPSP was significantly depressed at 2–;4 hr after resuscitation. Treatment with ATP-MgCl2, however, restored these parameters. Moreover, the depressed heart rate was also restored following ATP-MgCl2administration. Since ATP-MgCl2restores various left ventricular performance parameters, this agent appears to be a promising adjunct for improving cardiac function after trauma and hemorrhage, even in the absence of blood resuscitation.

Comparison of verapamil versus felodipine on heart rate variability after acute myocardial infarction

A depressed heart rate variability (HRV) is a powerful predictor of poor outcome in myocardial infarction patients. The beneficial effect of specific interventions on its recovery has been reported, but data concerning calcium antagonists are scarce. We evaluated the effect of a phenylalkylamine derivative, verapamil, and a dihydropyridine derivative, felodipine, on time- and frequency-domain measurements of HRV by 24-hour Holter monitoring in 60 patients with acute myocardial infarction (AMI). After a first Holter recording (65 ± 8 hours from the onset of symptoms), patients were randomly assigned to continue standard treatment or to also receive verapamil retard (120 mg 3 times daily) or felodipine extended-release (10 mg/day). Holter recording was repeated after 7 days. After verapamil, mean RR interval increased from 823 ± 92 to 907 ± 95 ms and the SD of all normal RR (NN) intervals (SDNN) from 99 ± 24 to 120 ± 30 ms (p < 0.01); the root mean square successive difference (r-MSSD) and the percent of differences between adjacent NN intervals >50 ms (pNN50) also increased (p < 0.01). After felodipine, only SDNN increased (p < 0.01). Regarding frequency-domain measurements, after receiving verapamil, very low frequency, low- and high-frequency powers increased (p < 0.01), whereas the low- to high-frequency ratio decreased (p < 0.01). After receiving felodipine, very lowfrequency power increased (p < 0.01), whereas lowand high-frequency powers and the low- to high-frequency ratio remained unchanged. This study demonstrates that verapamil, but not felodipine, improves HRV in the early phase after AMI.

FK453: A Novel Non‐Xanthine Adenosine A1 Receptor Antagonist as Diuretic

Adenosine is a purine nucleotide that is widely distributed throughout the body; it modulates a wide variety of physiological functions via extracellular receptors. Adenosine receptors, located on the cell membranes, are classified into two major subtypes, adenosine A, and A, receptors. This classification was originally based on the effects of a series of adenosine analogs on adenylate cyclase activity; activation of the adenosine A, receptor inhibits, while activation of the adenosine A2 receptor stimulates, adenylate cyclase (26,46). Many adenosine agonists that have a preferential affinity for adenosine A, receptors depress heart rate, myocardial contractility. and impulse conduction velocity (5,10,14). The agonists that have a greater affinity for adenosine A, receptors induce vasodilation ( 1 1.15,17,24,28). A number of workers have found that another adenosine receptor, which has been classified as an adenosine A , receptor, is present in many tissues. This receptor was recently subdivided into adenosine A, and A, receptor subtypes. As knowledge of the different types of adenosine receptors increases, these receptors may prove to be possible targets for novel pharmacologically active drugs. Adenosine itself is used in the acute treatment and diagnosis of supraventricular arrhythmias. To date, however, no selective adenosine receptor agonist or antagonist has been used therapeutically. FK453 is a novel pyrazolopyridine derivative that was synthesized at Fujisawa Pharmaceutical Co., Ltd. (Osaka, Japan). During a search for diuretics, FK453 was found to possess a potent diuretic activity with renal vasodilatory and uricosuric effects (40). In addition. FK453 markedly antagonized the negative inotropic effects of adenosine in isolated guinea pig atria, but was less potent in inhibiting the relaxation induced by adenosine in guinea pig aorta. These results suggested that FK453 is a potent and selective

Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study: X. Copie, K. Hnatkova, A. Staunton, L. Fei, A.J. Camm, M. Malik. Department of Cardiological Sciences, St. George's Hospital, Medical School, London, England. J Am Coll Cardiol 1996;27:270–6

Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study: X. Copie, K. Hnatkova, A. Staunton, L. Fei, A.J. Camm, M. Malik. Department of Cardiological Sciences, St. George's Hospital, Medical School, London, England. J Am Coll Cardiol 1996;27:270–6

Distinction between arrhythmic and nonarrhythmic death after acute myocardial infarction based on heart rate variability, signal-averaged electrocardiogram, ventricular arrhythmias and left ventricular ejection fraction

We investigated whether heart rate variability, the signal-averaged electrocardiogram (ECG), ventricular arrhythmias and left ventricular ejection fraction predict the mechanism of cardiac death after myocardial infarction. Postinfarction risk stratification studies have almost exclusively focused on predicting the risk of arrhythmic death. The factors that identify and distinguish persons at risk for arrhythmic and nonarrhythmic death are poorly known. Heart rate variability, the signal-averaged ECG, ventricular arrhythmias and left ventricular ejection fraction were assessed in 575 survivors of acute myocardial infarction. The patients were followed up for 2 years; arrhythmic and nonarrhythmic cardiac deaths were used as clinical end points. During the follow-up period, 47 cardiac deaths occurred, 29 (62%) arrhythmic and 18 (38%) nonarrhythmic. All risk factors were associated with cardiac mortality in univariate analysis. With the exception of left ventricular ejection fraction, they were also predictors of arrhythmic death. Depressed heart rate variability (p < 0.001), ventricular ectopic beats (p < 0.001) and low ejection fraction (p < 0.001) were related to nonarrhythmic death. In multivariate analysis, depressed heart rate variability (p < 0.001) and runs of ventricular tachycardia (p < 0.05) predicted arrhythmic death. Nonarrhythmic death was associated with depressed heart rate variability (p < 0.001), ventricular ectopic beats (p < 0.001) and low ejection fraction (p < 0.01). By selecting patients with depressed heart rate variability, long filtered QRS duration or ventricular arrhythmias and excluding patients with the lowest ejection fraction, we identified a group in which 75% of deaths were arrhythmic. Similarly, by selecting patients with a low ejection fraction and excluding patients with the lowest heart rate variability, we identified a group in which 75% of deaths were nonarrhythmic. Arrhythmic death was associated predominantly with depressed heart rate variability and ventricular tachycardia runs, and nonarrhythmic death with low ejection fraction, ventricular ectopic beats and depressed heart rate variability. A combination of risk factors identified patient groups in which a majority of deaths were either arrhythmic or nonarrhythmic.

The effects of six pericardial hormones and hypoxia on the semi-isolated heart and sternal arterial valve of the lobster Homarus americanus

Each of three amine and three peptide hormones of the pericardial organs exerts a unique effect on heart rate and ventricular pressure, and on outflow through the sternal arterial valve in Homarus americanus. At the concentrations of 0.1-0.25 μM, all of the six hormones except crustacean cardioactive peptide (CCAP) increased heart rate while only two (proctolin and F2) significantly increased ventricular pressure. Octopamine by itself had almost no effect, but augmented ventricular pressure when combined with proctolin. Whenever a hormone caused an increase in ventricular pressure, there was also an increase in dorsal abdominal artery pressure or flow. All hormones except dopamine caused a reduction in sternal artery flow. Dopamine by relaxing the sternal arterial valve increased the sternal flow, but it had no effect on ventricular pressure or dorsal abdominal artery flow. CCAP and serotonin did not significantly change the magnitudes of ventricular pressure or dorsal abdominal flow, but both reduced flow in the sternal artery. Hypoxia depressed heart rate and to a lesser extent contractility, but did not alter the responsiveness of the heart or sternal arterial valve to hormones.