Daniel David

Intramyocardial conduction: a major determinant of R-wave amplitude during acute myocardial ischemia.

The relationship of changes in ventricular activation patterns and variations in R-wave amplitude on the surface ECG during the hyperacute phase of myocardial ischemia were studied in nine open-chest dogs. The sum of R-wave amplitude (2RWA) changes in surface ECG leads L2, V5 and Frank orthogonal leads X, Y and Z were correlated with changes in the conduction time along the specialized conduction.system and in intramyocardial conduction times, as well as with hemodynamic and echocardiographically determined left ventricular dimensional changes. The hyperacute phase of myocardial ischemia induced by a one-stage occlusion of the left circumflex coronary artery was marked by a progressive increase in left ventricular enddiastolic diameter and left ventricular end-diastolic pressure as well as a progressive decrease in cardiac output. At the same time, ZRWA and intramyocardial conduction time followed a synchronous biphasic pattern. In the first 30 seconds after coronary artery ligation, intramyocardial conduction time in the ischemic zone accelerated to a peak of 11.3% above control (p < 0.001). This acceleration of conduction was followed closely by a decrease in ZRWA to 16.8% below control (p < 0.001). A second phase ensued, characterized by a gradual slowing of intramyocardial conduction time in the ischemic zone to 135.1% above control (p < 0.001) and a synchronous increase in 2RWA to 53.1% above control (p < 0.001). Conduction time along the specialized conduction system did not change significantly. Thus, the asynchrony of ischemic 2RWA alterations with hemodynamic and left ventricular dimensional changes and the similarity of the biphasic responses of 2RWA to the changes in intramyocardial conduction time in the ischemic area suggest that ventricular activation patterns rather than hemodynamic and intracardiac dimensional changes may play the major role in determining R-wave amplitude responses to acute myocardial ischemia.

Verapamil improves exercise capacity in chronic atrial fibrillation: Double-blind crossover study

Oral verapamil has previously been shown to reduce heart rate at rest and during mild exercise in chronic atrial fibrillation. Its efficacy in improving cardiovascular performance at higher levels of exercise and its safety were investigated in a prospective, randomized, placebo controlled double-blind study preceded by an open label titration phase in 20 digitalized patients with chronic atrial fibrillation. Maximal exercise capacity was improved (from 522 +/- 257 to 806 +/- 348 work units, p less than 0.0005) when tested by a standardized multistage ergometry exercise test. Heart rate was also reduced at rest, at the end of 3 minutes of 300 KPM exercise, and at the point of maximal exercise. Blood pressure and double product were also reduced. Its efficacy and safety may make verapamil the treatment of choice in chronic atrial fibrillation.

The acute hemodynamic effects of intravenous verapamil in coronary artery disease. Assessment by equilibrium-gated radionuclide ventriculography.

The acute hemodynamic effects of an i.v. bolus of verapamil, 0.1 mg/kg or 0.06–0.075 mg/kg, were examined by serial radionuclide studies in 46 patients with coronary artery disease. In 20 patients with ejection fractions (EFs) > 35% (group 1A), verapamil, 0.1 mg/kg given over 1–1½ minutes, had a biphasic effect: first, a transient decrease in EF accompanied by increased left ventricular (LV) volumes and cardiac output equivalents; then, an overshoot of EF to values above control, accompanied by a decrease in peripheral vascular resistance and a drastic decrease in LV volumes, while cardiac output equivalent remained slightly elevated. In eight patients with EFs < 35% (group 1B), only the first effect on EF was noted. In 10 patients with EFs > 35% (group 2), verapamil, 0.06–0.075 mg/kg, exerted qualitatively similar but milder effects on hemodynamic function. Finally, verapamil, 0.1 mg/kg given more slowly, over 2–2½ minutes, produced no significant changes in EF or LV volumes in another eight patients (group 3). The acute effects of verapamil are thus both time-related and dose-dependent. They are also related to the baseline functional reserve of the left ventricle. This study documents that verapamil exerts a depressant effect on LV function. However, the transient nature of this depression and the quick recovery to normal or above-normal values indicate that verapamil, in the doses used in this study, is safe to use intravenously in patients with coronary artery disease.

R-wave amplitude variations during acute experimental myocardial ischemia: an inadequate index for changes in intracardiac volume.

The role of intracardiac volume in controlling electrocardiographic R-wave amplitude changes during acute myocardial ischemia was studied in 24 open-chest dogs. The R-wave amplitude in surface ECG leads 2, V. and Frank X, Y and Z leads were correlated with hemodynamic, echocardiographic and angiographic changes in a 5-minute circumflex coronary artery ligation and reperfusion model. After coronary ligation, left ventricular end-diastolic diameter and volume increased progressively above control, reached a peak and plateau at 120–130 seconds after ligation and did not return to control levels until more than 5 minutes after release of the occlusion. In contrast, the R-wave amplitude showed a biphasic response to acute ischemia, reaching a nadir (Σ = 18.2% below control) at 30 seconds after coronary ligation and only subsequently increased to reach a peak (ΣR 52% above control) at 150 seconds after ligation. In addition, R-wave amplitude returned immediately to control levels within 10 seconds after reperfusion. In six other dogs, both venae cavae were occluded for a 30-second period, beginning 180 seconds after coronary ligation. Although intracardiac volume decreased markedly, R-wave amplitudes increased even more. Thus, the demonstration of discordance between alterations in intracardiac volume and R-wave amplitude in these studies suggests that factors other than intracardiac volume determine R-wave amplitude changes in the course of acute myocardial ischemia.

Serum Leptin Levels Increase following Acute Myocardial Infarction

Leptin is secreted into the circulation and communicates the peripheral nutritional status to specific hypothalamic centers. Recent studies suggest that leptin may be involved in the acute response to stress, and that its interaction with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system may be of clinical importance. Since these systems are activated during acute myocardial infarction (AMI), we studied leptin and cortisol levels during hospitalization in 30 consecutive patients admitted for AMI. The results show that leptin reached its peak on the second day of hospitalization, with a 2-fold increase from its baseline level on admission (p < 0.02). On day 3, leptin levels declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5, respectively. The mean cortisol level was elevated on day 1 and decreased toward normal levels thereafter (p < 0.001). The cortisol level did not correlate with leptin concentration throughout the study. These findings suggest that leptin may have a role in the metabolic changes taking place during the first days after an AMI.

Diastolic "locking" of the mitral valve: the importance of atrial systole and intraventricular volume.

Diastolic mitral valve “locking,” defined as sustained diastolic closure of the mitral valve after atrial systole, was investigated by simultaneous hemodynamic and echocardiographic recordings during a protocol of programmed pacing in six dogs with surgically induced atrioventricular block. Atrial extrasystoles were introduced at progressively increasing coupling intervals during programmed prolonged pauses in ventricular pacing. As the coupling interval of the atrial extrasystole was increased, both the mitral reopening time (MRT) and the calculated left ventricular volume (LVV) at the end of the MRT increased proportionally. These interrelations could be best expressed by a general logarithmic function of the form y = a + b In (x), where x = the coupling interval of the atrial extrasystole and y = the MRTor the LVV. Correlations between the measured data and the predicted data were excellent (r &phis; 0.95). In each dog, a specific LVV had to be attained to allow a diastolic “locking” of the mitral valve. Atrial standstill and atrial fibrillation were also induced in each dog to study the relative role of atrial systole in locking of the mitral valve. During either atrial standstill or atrial fibrillation, the mitral valve closed transiently, but did not lock, despite the accumulation of a LVV larger than the LVV necessary to lock the valve during sinus rhythm. Thus, diastolic locking of the mitral valve has several determinants, including the presence of active atrial systole and the accumulation of a sufficient intraventricular volume.

Myocardial regional blood flow: Quantitative measurement by computer analysis of contrast enhanced echocardiographic images

Quantitation of regional myocardial blood flow constitutes the missing link between the anatomy of coronary obstruction and its physiological effect on regional oxygen supply. Microscopic air bubbles, introduced into the coronary circulation, were shown to produce a transitory enhancement of the myocardial tissue contrast, easily detectable with standard ultrasonic imaging equipment. This study presents a new approach linking the tissue blood flow with the time-dependent changes in the intensity of the ultrasonic reflections produced by the microbubbles. The tissue blood flow is evaluated using the well-known indicator dilution relation, according to which flow equals the ratio between the intravascular fraction of the tissue sample volume and the mean transit time of the contrast agent. We derive these two parameters from the time curves representing the contrast induced variations in the mean videointensity measured in two regions of interest, a reference region in the left ventricular cavity and the region of interest within the myocardial tissue. The intravascular volume fraction is computed as the ratio of the total power of the above two intensity curves, as each of these is assumed to be proportional to the total amount of tracer traversing the corresponding region of interest. The mean transit time is computed using combined time- and frequency-domain processing, involving Fourier deconvolution of the response function of the myocardial tissue sample. This approach was validated in an in vivo model in a series of animal experiments involving left atrial injection of albumin coated air microbubbles (Albunex). Videointensity curves obtained during contrast enhancement of the myocardium were analyzed to provide values of regional myocardial blood flow (in mL/min/100 g) in 45 myocardial regions of interest defined in 7 experiments performed on 4 animals. The values obtained with our approach correlated well (r = 0.77, p < 0.001) with standard reference measurements based on radiolabeled microspheres. The intertechnique variability was found to be smaller than the intersegment variability characterizing our technique. The difference between the mean flow values obtained with microspheres for segments of the entire heart and the mean flow obtained with our technique for all regions of interest ranged between 1 to 19% in the 7 experiments. In its present form, based on left atrial or left ventricular injection of contrast solution, this method may allow, for the first time, quantitative evaluation of myocardial regional blood supply in the cardiac catheterization laboratory or the operation theater.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of doppler indexes of left ventricular diastolic function with simultaneous high fidelity left atrial and ventricular pressures in idiopathic dilated cardiomyopathy

Doppler echocardiographic indexes of ventricular inflow have been used clinically to characterize left ventricular (LV) diastolic function. The reliability of these indexes as markers for intrinsic myocardial diastolic properties has been questioned. Micro-manometer left atrial (LA) and LV pressures as well as transmitral Doppler flow velocity signals and M-mode and 2-dimensional echocardiograms were simultaneously recorded. These unique measurements were acquired in patients with dilated cardiomyopathy under baseline conditions and during infusion of high dose amrinone. The response to amrinone was chosen as a hemodynamic model because this drug has previously been described as having beneficial effects on overall LV systolic and diastolic performance. At peak amrinone effect, LV contractility increased (as assessed using load independent end-systolic indexes) and early diastolic relaxation improved whereas passive chamber stiffness, heart rate and stroke volume were unchanged. There was a significant decrease in LV end-diastolic pressure as well as a parallel downward shift of the entire LV diastolic pressure-dimension relation. These findings, which indicated an improvement in overall LV diastolic properties, probably represent the combination of more rapid early diastolic relaxation in conjunction with a reduction in venous return, the relief of pericardial restraint or the reduction in right ventricular-LV interaction. In contrast, the ratios of Doppler-determined peak transmitral early-to-late flow velocities and early-to-late diastolic flow velocity integrals decreased with amrinone infusion, thereby suggesting a drug-induced decrease in LV diastolic compliance. Thus, in patients with idiopathic dilated cardiomyopathy, administration of amrinone has a complex effect on LV diastolic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial transit time of the echocardiographic contrast media

The mean transit time of a tracer through a sample of tissue is a quantitative marker most closely related to regional tissue blood flow. Therefore, an accurate estimation of the mean time of transit of an ultrasonic tracer through a sample of myocardial tissue, obtained by contrast echocardiography, may provide a quantitative noninvasive estimate of myocardial perfusion. We hereby present an algorithm for the determination of the mean transit time by computerized analysis of a series of contrast-enhanced echocardiographic images. The algorithm comprises the evaluation of the echocardiographic impulse response function of a selected region of interest, using a deconvolution technique based on a fast Fourier transform and a frequency domain division of the videointensities measured in the sample, by that measured in a predetermined reference region. An extensive computer simulation study was designed to facilitate the optimization of the steps of analysis. We present the results of the evaluation study performed in order to assess the accuracy of the procedure in computer-simulated echocardiographic images. Within a wide range of parameters chosen to define these functions, the analysis is shown to be essentially independent of the rise and decay times of the impulse response function of the tissue sample as well as of the simulated intensities. The effects of random noise introduced into the simulated intensity curves and of their variable width were investigated. The mean transit time was found to be accurately evaluated within about 10% of error for the variety of widths and noise levels permitted. The reconvolution error did not correlate with the accuracy of the evaluation of the mean transit time, indicating that the reconvolution error cannot be used as an estimate of the accuracy of the procedure. The numerical methods and the results of the computer study are discussed in detail. The approach is proposed to be used as part of a more general technique for the quantitative measurement of regional myocardial tissue blood flow.

Peripheral Monocytosis following Acute Myocardial Infarction: Incidence and Its Possible Role as a Bedside Marker of the Extent of Cardiac Injury

Infiltration by mononuclear cells, mostly monocytes, into necrotic myocardial tissue can be detected beyond the 3rd day after the onset of infarction. These monocytes, mobilized by an unknown mechanism, initiate phagocytosis of necrotic tissue. We observed in patients having sustained an acute myocardial infarction (AMI) a significant increase in monocyte count 2–3 days following presentation, possibly representing peripheral recruitment of monocytes to the injured myocardium. To establish this observation, we prospectively documented monocyte and neutrophil counts throughout hospitalization in 186 consecutive patients (118 patients having sustained an AMI, 34 patients with angina, and 34 patients admitted for nonischemic reasons). Average monocyte count, which rose on the 2nd day and reached a peak on day 3, was significantly elevated in these patients compared with control subjects (p < 0.001). Neutrophil count exhibited a similar phase-shifted response. Peak monocyte count exceeded 800/mm3 (upper limit of normal range) in 69 (58%) of AMI patients but in only 3 of the 68 (4%) non-AMI patients, yielding a sensitivity and specificity of 58 and 95%, respectively, for the diagnosis of AMI by this criterion. A significant correlation between maximal creatine kinase (CK) representing the extent of myocardial necrosis and peak monocyte count was shown (r = 0.51, p < 0.0001). A correlation between CK and monocyte count sum of days 1–3 (r = 0.51, p < 0.001) was found in a substudy of 25 patients with AMI. Similarly, a correlation was shown with cardiac function score as evaluated by 2-dimensional echocardiography (p < 0.001 and p < 0.008 for difference between CK sum and monocyte count sum of high and low echo score groups, respectively). Hence, the peak monocyte count recorded during the immediate postinfarction period provides a bedside marker of the extent of myocardial damage that is the preponderant prognostic determinant. If validated in future studies this phenomenon may have diagnostic and prognostic implications.