Donald H. Schmidt

Comparative analysis of physiologic responses to three different maximal graded exercise test protocols in healthy women

The purpose of this study was to compare the three most commonly used maximal graded exercise test (GXT) protocols in healthy women. Submaximal and maximal metabolic and hemodynamic responses were determined from two treadmill protocols, Bruce and Balke, and a bicycle protocol, in 49 women. Maximum oxygen uptake (VO2 max) was significantly different among protocols (Bruce=40.3, Balke=38.4, and Bike=36.6 ml/kg . min -1). Maximum heart rate (HR max) was significantly lower during Bike (178 beats/min) than during Bruce (182) and Balke (183) protocols. No differences in rate of increase in HR or systolic blood pressure (BP) per increase in multiples of the rest metabolic (METs) were found between Bruce and Balke protocols. The rate of recovery of HR and systolic BP was not different among tests. Comparisons of active and sedentary groups showed differences in VO2 max and submaximal HR and recovery HR at common minutes; however, the rate of increase in HR and systolic BP during exercise and the rate of decrease during recovery were not significantly different. Prediction of VO2 max with Bruce and Balke protocols from treadmill time was r=0.91 (SEE +/- 2.7 ml/kg . min -1) and r=0.94 (SEE 2.2 ml/kg . min -1), respectively. These data suggest a difference between men and women in increased HR and systolic BP per METs increase in exertion.

Generalized equations for predicting functional capacity from treadmill performance

Abstract The evaluation of functional capacity is an important aspect of the graded exercise test. It provides data which may be of diagnostic and prognostic significance 1–3 as well as of importance for exercise prescription. 4 Functional capacity is a general term most closely associated with the maximal oxygen uptake (VO 2 max), which represents the integrated product of maximal cardiac output and maximal arteriovenous oxygen difference. 5,6 Because of the technical requirements of measuring VO 2 max, and because of concern over difficulties with patient communication, many laboratories do not directly measure VO 2 max during exercise testing. Typically, VO 2 max is estimated through linear regression equations relating treadmill performance to oxygen uptake. 6–8 These prediction equations, however, tend to be population specific and valid only through a limited range. Bruce et al., 6 who developed the most widely cited prediction equations, have developed three separate linear regression equations, which take into account treadmill performance, health status (known cardiovascular disease/healthy), and physical activity habits (sedentary/active). Examination of the slope of Bruces equations, however, suggests that the overall relationship between treadmill performance and VO 2 max may be nonlinear. Taken together with the problems inherent in evaluating health status (Bruce includes asymptomatic hypertensive patients as well as patients with exertional angina or prior myocardial infarction) and activity habits, this apparent nonlinearity suggests that using a family of population-specific linear regression equations may not be the optimal method of approaching the estimation of VO 2 max. The problems of predicting VO 2 max enumerated previously are analogous to the problems of estimating body composition from anthropometric measurements. We have dealt with these problems and have developed generalized equations for predicting body composition employing a nonlinear regression model that estimates body density from the quadratic sum of skinfold measurements adjusted for sex and age. 9,10 It seems possible that a similar approach might prove to be a useful way of combining the several, partially overlapping linear equations for predicting VO 2 max. It may also, by virtue of a heterogeneous sample, increase the applicability of the regression approach. Since the direct measurement of VO 2 max during exercise testing is unlikely to become universally employed in clinical laboratories, the development of a single, easy to use regression equation with wide applicability would be a valuable tool for the clinician. Accordingly, the purpose of the present investigation was to develop a multifactorial regression equation for predicting VO 2 max from treadmill performance and clinical characteristics and to determine if such an equation could simplify the prediction of VO 2 max without sacrificing accuracy. This investigation is limited to evaluating responses to the Bruce treadmill protocol, since this protocol is the most widely employed clinically 11 and has already been the subject of considerable study relative to predicting oxygen uptake. 6–8

On the Possible Role of Reactive Oxygen Species in Angiogenesis

Human microvascular endothelial cells grown on a 3-D reconstituted extracellular matrix (Matrigel) spontaneously and rapidly form a capillary network of tubular structures, thus modeling part of the angiogenic cascade. Exposure of the cells at the time of plating onto Matrigel to a brief episode of hypoxia (40-60) min and subsequent reoxygenation, significantly accelerated (up to 3-fold) the rate of tubular morphogenesis, as determined by computer-aided morphometry. This effect was not dependent on activation of PKC or upregulation/release of angiogenic growth factors. Rather, hypoxia/reoxygenation (H/R), but not hypoxia alone, caused the formation of reactive oxygen species (ROS) and the activation of the nuclear transcription factor NF kappa B, both of which were inhibited by ROS-scavengers, such as pyrollidine dithiocarbamate. Tube formation was inhibited, also under normoxic conditions, by diverse ROS antagonists in a dose-dependent fashion. Our results indicate that angiogenesis is accompanied by and/or requires generation of ROS. We hypothesize that in the clinical setting of hypoxia/reoxygenation during ischemic pre-conditioning, enhanced activation of ROS-dependent intracellular signaling may accelerate the rate of neovascularization also in vivo, thus contributing to the alleviation of certain ischemic lesions.

Measurement of regional myocardial blood flow in man: Description and critique of the method using xenon-133 and a scintillation camera

A method has been devised to measure regional myocardial blood flow in man. The approach consists of selective injection of xenon-133 into a coronary artery and the external monitoring of radioisotope washout curves from multiple areas of the myocardium with a multiple crystal scintillation camera. Rate constants of isotope washout are calculated using a monoexponential model, and the capillary blood flow rates in multiple regions of the heart are calculated by the Kety formula. The pattern of perfusion rates is related to the coronary arteriogram obtained in the same study. Myocardial perfusion patterns obtained in patients with and without coronary artery disease and during atrial pacing are given, as well as examples of results obtained in myocardial aneurysms, in regions of ischemic myocardium supplied by collateral vessels and after tracer injection into an aortocoronary bypass graft. Advantages of the method are discussed along with limitations related to the tracer, the scintillation camera, the form of mathematical analysis and the three dimensional nature of the heart.

Peak exercise and immediate postexercise imaging for the detection of left ventricular functional abnormalities in coronary artery disease

Eleven patients without significant coronary artery disease (CAD) (group A), 22 patients with significant CAD and no prior myocardial infarction (MI) (group B), and 10 patients with CAD and a previous MI (group C) were imaged at rest, at peak exercise and immediately after exercise by first-pass radionuclide angiography. At peak exercise, mean left ventricular (LV) ejection fraction (EF) did not change significantly in group A or C and decreased significantly in group B. However, in all groups mean LVEF increased significantly immediately after exercise. Examination of potential criteria for an abnormal LVEF response showed that changes from rest to peak exercise were sensitive for detection of CAD but were not specific. Postexercise criteria were more specific but relatively insensitive: 15 of 32 patients (47%) with CAD showed a normal (greater than 5% increase over rest) response after exercise. Similarly, a regional abnormality at peak exercise was 100% sensitive, compared with a sensitivity of 78% after exercise for the whole group, and only 68% in patients without prior MI. Seven patients would have been misclassified as normal if postexercise imaging alone had been performed. The likelihood of an abnormal postexercise EF response was related to the extent of CAD: No patient with 1-vessel, 8 of 17 with 2-vessel and 9 of 12 with 3-vessel CAD showed such a response. Peak exercise imaging is necessary to achieve maximal sensitivity for the detection of CAD, and a high false-negative rate will be obtained if postexercise imaging only is used. The combination of peak exercise and postexercise imaging may be of value in assessing the severity of CAD.

Pentobarbital-induced changes in vagal tone and reflex vagal activity in rabbits

The effects of pentobarbital on heart rate, reflexly mediated vagal activity and the automaticity (intrinsic rate) of the sinoatrial (SA) node were investigated in rabbits. When administered in three cumulative doses (10 mg/kg i.v. each) at 15 min intervals, each dose produced transient hypotension which was not modified by prior muscarinic receptor blockade (MRB), beta-receptor blockade (BRB), or combined MRB and BRB. Subanesthetic doses (10 mg/kg) of pentobarbital produced tachycardia in normal rabbits, as well as in rabbits with prior BRB. After pentobarbital, MRB failed to increase the heart rate, indicating total loss of resting vagal tone. Failure to induce tachycardia in rabbits with prior MRB indicated the absence of sympathetic stimulation in pentobarbital-induced tachycardia. In rabbits with prior BRB, pentobarbital enhanced the hypotensive effects of acetylcholine and nitroglycerin and abolished nitroglycerin-induced tachycardia without significant effects on the magnitude of reflex bradycardia produced by norepinephrine. Pentobarbital had minimal, transient depressant effects on the intrinsic rate of the SA node. These results indicate that pentobarbital produces total loss of resting vagal tone without major impairment of reflex vagal activation.

Time Course of Recovery During Cardiac Rehabilitation

PURPOSE Exercise-based rehabilitation programs improve effort tolerance in patients with cardiovascular disease. Little is known regarding the time course of recovery of objective and subjective indices of exercise tolerance. METHODS Twenty-six patients were studied at 0, 4, 8, and 12 weeks following early entry into rehabilitation following acute myocardial infarction (AMI), coronary artery bypass graft surgery (CABGS), or valve surgery. Exercise tolerance was assessed objectively by percent predicted cycle power output (%PO), and subjectively by a self-efficacy questionnaire for ambulatory (ASE) and muscular (MSE) items and by a disease-specific, health-related, quality-of-life questionnaire (HRQL). RESULTS With the exception of percent predicted cycle power output, all exercise tolerance measures improved throughout the rehabilitation program. Extrapolation of recovery curves suggest that recovery to 85% predicted can be achieved in 10, 11, 18, and 21 weeks for a disease-specific, health-related, quality-of-life questionnaire, self-efficacy questionnaire for ambulatory items, muscular items, and power output, respectively. CONCLUSIONS The data demonstrate that evaluation of both objective and subjective indices of exercise tolerance may be important in documenting outcomes of participation in structured rehabilitation programs. The time course of recovery of objective and subjective indices of exercise tolerance may not be highly correlated.

Assessment of single vessel coronary artery disease: Results of exercise electrocardiography, thallium-201 myocardial perfusion imaging and radionuclide angiography

The sensitivity of the commonly used stress tests for the diagnosis of coronary artery disease was analyzed in 46 patients with significant occlusion (greater than or equal to 70% luminal diameter obstruction) of only one major coronary artery and no prior myocardial infarction. In all patients, thallium-201 perfusion imaging (both planar and seven-pinhole tomographic) and 12 lead electrocardiography were performed during the same graded treadmill exercise test and radionuclide angiography was performed during upright bicycle exercise. Exercise rate-pressure (double) product was 22,307 +/- 6,750 on the treadmill compared with 22,995 +/- 5,622 on the bicycle (p = NS). Exercise electrocardiograms were unequivocally abnormal in 24 patients (52%). Qualitative planar thallium images were abnormal in 42 patients (91%). Quantitative analysis of the tomographic thallium images were abnormal in 41 patients (89%). An exercise ejection fraction of less than 0.56 or a new wall motion abnormality was seen in 30 patients (65%). Results were similar for the right (n = 11) and left anterior descending (n = 28) coronary arteries while all tests but the planar thallium imaging showed a lower sensitivity for isolated circumflex artery disease (n = 7). The specificity of the tests was 72, 83, 89 and 72% for electrocardiography, planar thallium imaging, tomographic thallium imaging and radionuclide angiography, respectively. The results suggest that exercise thallium-201 perfusion imaging is the most sensitive noninvasive stress test for the diagnosis of single vessel coronary artery disease.

Evaluation of Functional Capacity during Exercise Radionuclide Angiography

This study compared functional capacity during treadmill exercise testing and during bicycle exercise radionuclide angiography. 262 patients performed maximal upright bicycle exercise and also perform

Effects of intraaortic balloon counterpulsation on myocardial blood flow in patients with severe coronary artery disease

The purpose of this study was to test the hypothesis that myocardial blood flow distal to a critical stenosis would increase during intraaortic balloon counterpulsation. Accordingly, 13 patients with severe coronary artery disease were studied at the time of elective preoperative insertion of an intraaortic balloon catheter. Hemodynamic measurements and measurements of myocardial blood flow were made before and during counterpulsation. Myocardial blood flow was measured with a xenon-133 washout technique. Compared with control measurements, the heart rate decreased from 87.8 +/- 18.8 to 82.8 +/- 13.4 beats/min (p = 0.02) and systolic arterial pressure decreased from 112.1 +/- 17.9 to 97.8 +/- 14.8 mm Hg (p = 0.004) during counterpulsation. Diastolic arterial pressure increased from 72.2 +/- 10.1 to 120.2 +/- 21.4 mm Hg (p = 0.00002) during counterpulsation. Myocardial blood flow for the entire group decreased from 48.8 +/- 14.1 to 42.6 +/- 11.0 ml/100 g per min (p = 0.008). Regional flows in the left anterior descending and circumflex distributions also decreased. Left anterior descending artery blood flow decreased insignificantly from 51.5 +/- 14.4 to 47.4 +/- 11.7 ml/100 g per min (p = not significant), while circumflex flow decreased from 50.7 +/- 12.2 to 41.1 +/- 8.9 ml/100 g per min (p = 0.008). When normalized for the rate-pressure product, myocardial blood flow was 53 +/- 16 X 10(-4) at rest and 55 +/- 12 X 10(-4) (p = not significant) during counterpulsation.(ABSTRACT TRUNCATED AT 250 WORDS)