Oxygen radical system in chronic infarcted rat heart: the effect of combined beta blockade and ACE inhibition.

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myocardial oxidative stress. To test this hypothesis in an in vivo model, the beta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (1 mg) were given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP), contractile function of papillary muscles, enzymatic antioxidative defense (indicated by the activities of the superoxide dismutase isoenzymes and glutathione peroxidase), and the extent of lipid peroxidation were studied. Placebo-treated rats showed cardiac hypertrophy, increased LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid peroxide levels, when compared with sham-operated animals. Combined beta blockade and ACE inhibition improved the antioxidative defense, reduced hypertrophy and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockade and ACE inhibition after infarction may decrease myocardial oxidative stress and thereby could be beneficial in heart failure.

Combined treatment with ramipril and metoprolol prevents changes in the creatine kinase isoenzyme system and improves hemodynamic function in rat hearts after myocardial infarction.

Beneficial effects of monotherapy with ACE inhibitors or beta-blockers on hemodynamic function after myocardial infarction are well known. Until now, the effects of combined treatment on cardiac function and energy metabolism have been poorly described. This study examines the effects of combined ramipril and metoprolol treatment on the creatine kinase (CK) system and hemodynamic function in rats after infarction. Wistar rats with experimental infarction were randomized for treatment with ramipril (R), metoprolol (M), combined treatment (MR), or placebo (P). Sham-operated (SO) animals served as controls. After 6 weeks, we assayed for CK isoenzymes and performed hemodynamic measurements. In P versus SO, left ventricular systolic pressures (dp/dt(max) and dp/dt(min)) diminished, whereas left ventricular end-diastolic pressure (LVEDP) increased. Decreased total CK activity and mitochondrial CK isoenzyme, increased CK-MB, and increased CK-BB isoenzymes were measured in P versus SO. With infarct size < or =45%, mitochondrial CK increased in M and R versus P. Combined treatment had an additional enhancing effect on mitochondrial CK isoenzyme level versus M and R, decreased LVEDP versus P, as well as increased dp/dt(max) and dp/dt(min) versus R. These results provide evidence of an interaction between normalization of energy metabolism and improvement in cardiac function due to a combination of ACE inhibition and beta blockade after myocardial infarction.

Autonomic effects of dipyridamole stress testing on frequency distribution of RR and QT interval variability.

Transient myocardial ischemia and associated changes in the autonomic nervous system may influence heart rate and ventricular repolarization to variable degrees. This study evaluated the effect of dipyridamole (DIP) induced ischemia on the autonomic balance by spectral analysis of RR and QT intervals variability. Patients with coronary artery disease undergoing DIP stress echocardiography were studied. From high resolution ECG recordings, RR and QT interval measurements were performed by a dynamic template-matching algorithm. A time-variant analysis was used to estimate power in the LF (0.05-0.15 Hz) and in the HF (0.15-0.4 Hz) band of RR and QT interval spectra. Patients were grouped in ischemic and nonischemic subgroups based on the echocardiographic detection of wall-motion abnormalities. In patients without ischemia (n = 28), DIP caused a decrease in LF power and an increase in HF power of the RR and QT interval variability, indicating concordant changes of both intervals. In contrast, patients with inducible ischemia (n = 11) showed a decrease in HF power of the RR interval spectra and an increase of HF power of QT interval spectra. Furthermore, LF power was increased for RR but decreased for QT interval spectra. Our study suggests that DIP induced ischemia causes a loss of autonomic coupling between heart rate and ventricular repolarization for sympathetic and parasympathetic activities. This lability in ventricular repolarization may constitute an arrhythmogenic substrate during acute ischemia in patients with coronary artery disease.

Differences in the effect of acute ischemia on late potentials in susceptible and resistant dogs for sudden cardiac death.

The low predictive value of the signal averaged ECG (SAECG) at rest may be due to the absence of any physiological perturbation. This study assessed changes of late potentials (LP) in the SAECG due to acute ischemia in five susceptible (S) and five resistant (R) dogs for sudden cardiac death. SAECGs were measured at rest prior to and during the last 3 min of 4 min transient occlusion of the left circumflex artery (CAO). At rest no significant differences were seen in the QRS duration (QRSD), the low amplitude signal duration (LAS40) and the root mean square voltage (RMS20) between S and R dogs. However, acute ischemia caused significant increases in QRSD and LAS40, but only in the S dogs. These results indicate differences in the ischemic modulation of the arrhythmogenic substrate in S and R group. Analysis of LP during acute ischemia may provide an important increase in the positive predictive value of the SAECG.

Analysis of alternans in late potentials. Correlations between epicardial and body surface recordings.

The methodical performance of the signal-averaged electrocardiogram is strongly influenced by the beat-to-beat reproducibility of late potentials (LPs). Especially at higher heart rates, epicardial recordings from infarct regions show progressive beat-to-beat prolongations with alternating conduction block. To analyze the influence of beat-to-beat-alternans of LPs on the signal-averaging process, epicardial and body surface recordings were studied at different heart rates and extrastimulation. Epicardial and body surface recordings were obtained from dogs with 4-day postligation of the left anterior descending coronary artery (Harris model). Body surface potentials were averaged in different modes to a final noise level of 0.3 microV (rms) and digitally bandpass filtered (40-250 Hz). Modulation of the heart rate was performed by atrial or His-bundle pacing and by atrial premature extrastimulation. Pacing up to heart rates close to 180 beats/min produced no significant changes in the duration of LPs in epicardial and averaged body surface recordings; however, at higher pacing rates, considerable prolongation of LPs with different patterns in the epicardial leads was observed. In these cases, averaging of all beats revealed only a slight prolongation of LPs, as seen from the body surface. Selective averaging of beats with prolonged epicardial LPs showed the prolongation or absence of LPs, as seen in the epicardial recordings. Similar observations were made using an atrial extrastimulation technique, whereby the average of the premature beats was compared to the average of all normal sinus beats. Selective beat averaging of body surface potentials can unmask the prolongation of LPs due to atrial pacing or extrastimulation, as seen in recordings from the infarcted epicardium. The evidence of this modulation of LPs may improve the positive predictive value of the signal-averaged electrocardiogram.

The association of carious dentin microflora with tissue changes in human pulpitis.

Correlations were sought between the number and type of microorganisms recovered from sampled carious dentin and the cellular responses observed in dental pulpal tissues from a sample of 65 vital, carious teeth extracted from adult humans who had declined the option of tooth restoration. Standardized homogenates of carious dentin were plated using selective and nonselective media under anaerobic and microaerophilic conditions. Pulpal responses were characterized histopathologically on the basis of the nature of the cellular infiltrate and the extent of degenerative changes. A significant association between the number of Prevotella intermedia and Prevotella melaninogenica in carious dentin and extensive, principally mononuclear, inflammatory infiltration was evident despite a high degree of complexity and intersubject variability in the microbial flora. There was no apparent association between other microorganisms or total microbial load and the histopathological category.