Postexercise ischemia is associated with increased neuropeptide Y in patients with coronary artery disease.

BACKGROUND: Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. METHODS AND RESULTS: Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE. CONCLUSIONS: The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Correlation of coronary arteriography after acute myocardial infarction with predischarge limited exercise test response.

This study of post-acute myocardial infarction (AMI) patients compared the extent and distribution of coronary narrowings and left ventricular dysfunction in 45 patients who had greater than or equal to 1 mm ST-segment depression on a predischarge low-level exercise test (positive-result group) with those found in 78 patients who had less than 1 mm ST depression (negative-result group). Cardiac catheterization was done 50 +/- 20 days (mean + standard deviation) after AMI. Patients with positive responses more often had multivessel coronary artery disease (80 vs 47%, p = 0.001) and a greater than or equal to 75% narrowing in the left anterior descending (LAD) (87 vs 62%, p = 0.003) and left circumflex (71 vs 37%, p = 0.001) arteries, as well as in the proximal LAD segment before the first septal branch (58 vs 29%, p = 0.002). Among patients with positive responses 93% had normal or hypokinetic wall motion in the vascular territory of a severely diseased coronary artery (viable but potentially ischemic myocardium) while 63% of the negative-result group had these findings (p = 0.001). No difference in ejection fraction could be identified between the 2 groups (54 +/- 15% vs 54 +/- 16%). Prior studies of AMI patients have shown that ST-segment depression on a predischarge low-level exercise test will identify patients at higher risk of subsequent cardiac death. Our observations have identified differences in cardiac angiographic findings between patients with positive and negative responses to this test that may explain this difference in outcome.

Fat cell number, resting metabolic rate, mean heart rate, and insulin elevation while seeing and smelling food as predictors of slimming.

The explanatory value of total fat cell number, resting metabolic rate, mean heart rate during sleep, and peripheral insulin while seeing and smelling food were examined in relation to weight reduction in 19 obese women on a 1100-kcal/day diet. The insulin response while seeing and smelling food was expressed as the insulin area (mU x min x 1(-1)) over the baseline level. Food was presented in front of the patient for 5 min. Insulin was determined in short intervals 20 min before and 20 min after start of food presentation. Fat cell number, resting metabolic rate, and mean heart rate during sleep were determined with standard techniques. All patients went through a period of weight loss, a plateau phase, and a period of weight regain. Body weight, fat cell number, resting metabolic rate, and/or heart rate correlated significantly with degree and rate of weight loss, duration of plateau phase, and rate of regain. In multiple regression analysis fat cell number and resting metabolic rate explained 81% of the variance for weight loss, 66% for rate of regain, and 29% for duration. For duration, only fat cell number contributed significantly. The variance of rate of weight loss was explained up to 49% by metabolic rate and insulin response while seeing and smelling food. The possibility of predicting weight reduction to a certain target weight is of great practical importance since the patients can obtain a realistic goal for their efforts to reduce body weight. Hopefully systematic investigations of factors associated with the inability of obese subjects to maintain weight reduction will improve treatment in the future.

The importance of nose-breathing for the systolic blood pressure rise during exercise.

The effect of nose breathing on the systolic blood pressure was examined in ten healthy men. Nose breathing was increased above normal by exercise and tested by maximum bicycle ergometry. When the anterior part of the nose was dilated with Nozovent the nasal airflow increased by on average 29%. In this condition, all ten men could cycle at maximum load without mouth breathing and there was a significantly lower increase (13 mmHg) in the systolic blood pressure than when the nasal dilator was not used. The reason for this lower blood pressure increase is unknown. The hypothesis is put forward, however, that facilitated nose breathing decreases the respiratory work, which in turn lowers the systolic blood pressure during exercise.

Excretion of thromboxane A2 and prostacyclin metabolites before and after exercise testing in patients with and without signs of ischemic heart disease.

We addressed the hypothesis that platelets are not activated in association with effort-induced myocardial ischemia in stable coronary disease. Seventy-two patients undergoing a diagnostic bicycle exercise test were stratified according to the development of chest pain (yes/no, 33/39) and of exercise-induced ST-segment depression of at least 200 microV in the electrocardiogram (yes/no, 12/60). Noninvasive indexes of platelet activation and of platelet/vessel wall interaction (urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 [Tx-M] and prostacyclin [PGI-M], respectively) were analyzed in samples collected in the basal state and after the test. Basal Tx-M and PGI-M did not differ in patients with (236 +/- 35 and 131 +/- 22 pg/mg creatinine, respectively) and without (185 +/- 16 and 101 +/- 13 pg/mg creatinine, respectively) chest pain, or in those with (178 +/- 45 and 162 +/- 41 pg/mg, respectively) and without (216 +/- 22 and 104 +/- 11 pg/mg, respectively) ST-segment depression during the test. Patients without chest pain or without ST-segment depression moderately increased (p less than 0.05) their urinary Tx-M (by 21% and 13%, respectively) and PGI-M (by 28% and 23%, respectively) after exercise. No significant increases were observed in those developing chest pain or ST depression during exercise. These data indicate that effort-induced myocardial ischemia is not associated with an increase in platelet activation or platelet/vessel wall interaction in patients with stable coronary disease.

Pafenolol, a new beta 1-selective blocking agent, in mild hypertension. Result of an inpatient study and a subsequent outpatient follow-up.

Pafenolol, a new selective adrenergic beta 1-blocking agent, has been tested for the first time in 6 hypertensive patients. After single oral doses of pafenolol 25 to 100 mg, there was a marked reduction in heart rate and systolic blood pressure during exercise tests. These effects were dose dependent. A significant positive correlation was found between the reduction in heart rate during exercise and the plasma level of pafenolol 5 hours after drug intake (correlation coefficient r = 0.94). Side effects were mild and seemed to be dose dependent. It is concluded that this new beta 1-blocking agent was effective in reducing blood pressure and was well tolerated.

A program for processing of multiple-lead exercise ECGs in real time.

A computer program for continuous recording and real-time processing of 8-channel exercise ECGs is presented. Current average ECG complexes and trends of various morphological and rhythmic parameters can be displayed on a TV monitor during the stress test. Average complexes computed every 10 s, the time of occurrence and 6 morphological coefficients of all detected tentative QRS complexes, and data manually entered by the operator are stored in a file on disk. The operational procedures and the principal signal processing are briefly presented. The main attention is given to a description of the software structure, explaining the subdivision of the program into dedicated autonomous sections and the system for the coordination of simultaneous activities of different priority.

Real-time processing of multiple-lead exercise electrocardiograms.

A system for continuous recording and real-time processing of eight-channel exercise ECGs is presented with emphasis on the algorithms performing the principal signal processing. The hardware and the operational procedures are briefly described. New methods have been developed for the detection, alignment, and selection of complexes to be used in the creation of eight-dimensional average ECG complexes every 10 s. These algorithms are based on digital filter functions approximating low-order Legendre polynomials in order to be robust in the presence of noise.

Relation between ST-depression and chest pain in patients with coronary heart disease receiving no treatment and after beta-blockade and combined alpha-beta-blockade.

The bicycle exercise tolerance was studied in ten patients with angina pectoris after one week's treatment with an alpha-beta-blocker (labetalol 300 mg b.d.), alpha-beta-blocker (propranolol 80 mg b.d.) and placebo. The ST-segment of the ECG was continuously evaluated by on-line computerized averaging of complexes which greatly reduces noise and eliminate artefacts caused by varying baseline. Blood pressure was lowest with labetalol and heart rate lowest with labetalol and of heart rate during exercise was equally well depressed by both drugs. They also attenuated ST-depression at a given load but enhanced ST-depression for a given heart rate. At heart rate 100/min ST-depression was significantly greater with propranolol than with labetalol. It is concluded that provided ST-depression during treatment with B-blockers is correlated to myocardial ischemia in the same way as without such treatments used, other factors, e.g. an increase in cardiac size, will contribute more to the ischemia. labetalol may cause less increase in cardiac size than propranolol.

Effects of cold on ST amplitudes and blood pressure during exercise in angina pectoris.

To investigate the mechanisms of cold susceptibility in angina pectoris nine male angina patients were studied. All were cold susceptible by history and had developed ischaemic ST changes during a previous exercise test. The patients underwent two additional bicycle exercise tests, one in a cold chamber with an average temperature of -8 degrees C, and the other at room temperature. The ECG was computer analysed and the intra-arterial blood pressure was measured. No significant decrease in work capacity was found during exercise in the cold chamber. In the cold, systolic blood pressure was consistently higher throughout the test and in seven of nine subjects ST depression was more pronounced at corresponding workloads. ST depression was also analysed versus heart work which was assessed as rate pressure product. In the cold, 1 mm ST depression appeared at a somewhat higher rate pressure product when compared to room temperature. It was concluded, therefore, that an augmented heart work, secondary to substantial increases in blood pressure, appears to account for the cold-induced increase in ST depression found in the angina patients in this study.