Aerobically generated CO(2) stored during early exercise.

Previous studies have shown that a metabolic alkalosis develops in the muscle during early exercise. This has been linked to phosphocreatine hydrolysis. Over a similar time frame, the femoral vein blood pH and plasma K(+) and HCO(-)(3) concentrations increase without an increase in PCO(2). Thus CO(2) from aerobic metabolism is converted to HCO(-)(3) rather than being eliminated by the lungs. The purpose of this study was to quantify the increase in early CO(2) stores and the component due to the exercise-induced metabolic alkalosis (E-I Alk). To avoid masking the increase in CO(2) stores by CO(2) released as HCO(-)(3) buffers lactic acid, the transient increase in CO(2) stores was measured only for work rates (WRs) below the lactic acidosis threshold (LAT). The increase in CO(2) stores was evident at the airway starting at approximately 15 s; the increase reached a peak at approximately 60 s and was complete by approximately 3 min of exercise. The increase in CO(2) stores was greater, but the kinetics were unaffected at the higher WR. Three components of the change in aerobically generated CO(2) stores were considered relevant: the carbamate component of the Haldane effect, the increase in CO(2) stores due to increase in tissue PCO(2), and the E-I Alk. The Haldane effect was calculated to be approximately 5%. Physically dissolved CO(2) in the tissues was approximately 30% of the store increase. The remaining E-I Alk CO(2) stores averaged 61 and 68% for 60 and 80% LAT WRs, respectively. The kinetics of O(2) uptake correlated with the time course of the increase in CO(2) stores; the size of the O(2) deficit correlated with the size of the E-I Alk component of the CO(2) stores. We conclude that a major component of the aerobically generated increase in CO(2) stores is the new HCO(-)(3) generated as phosphocreatine is converted to creatine.

Factors affecting the components of the alveolar CO2 output-O2 uptake relationship during incremental exercise in man.

The VCO2-VO2 (alveolar CO2 output-alveolar O2 uptake) relationship (V-slope) during increasing work rate (ramp) cycle ergometer exercise has two approximately linear components: a lower component slope (S1) with a value of about 0.95 and a steeper, upper component (S2). We examined the effect of muscle glycogen depletion (protocol 1) and the rate of increase in work rate (ramp rate) without muscle glycogen depletion (protocol 2) on S1 and S2. In protocol 1, ten healthy men with a mean age of 31.4 years (S.D. 6.2) were studied on each of 3 days (days 1 and 3 were control days). They performed a ramp exercise test to maximum tolerance and steady-state tests at rest, during unloaded pedalling and at two constant work rates below their anaerobic threshold (AT). To deplete muscle glycogen before the test on day 2, the subjects performed 2 h of very heavy cycle exercise on the preceding day and fasted overnight. S1 was reduced on day 2 (0.79 compared with 0.95, P less than 0.001), as was the VCO2-VO2 slope derived from steady-state measurements (0.81 compared with 0.99, P less than 0.001), but AT and the slope difference (S2 - S1) were unchanged. In protocol 2, seven healthy men with a mean age of 20.6 years (S.D. 2.4) performed ramp tests at three different rates of increasing work rate (15, 30 and 60 W min-1), each ramp rate being performed twice in random sequence. The ramp rate did not affect S1 but S2 was steeper with the faster rates of work rate increase (1.27, 1.43 and 1.63, respectively, P less than 0.01). Our findings support the concept that the lower component of the V-slope plot (below AT) represents muscle substrate respiratory quotient (RQ) while the difference between S1 and S2 reflects 'excess CO2' derived from bicarbonate buffering of lactic acid.

Contralateral femoral neuropathy: an unusual complication of anticoagulation following PTCA.

This case report describes the occurrence of femoral neuropathy secondary to a hematoma of the iliacus muscle. This unusual complication was a result of heparin therapy following Percutaneous Transluminal Coronary Angioplasty (PTCA). We have reviewed the anatomic correlates, mechanism, and treatment options of this condition.

Evidence supporting the existence of an exercise anaerobic threshold.

In this paper, we provided evidence to support the concept that work above the anaerobic threshold, measured by the V-slope method, is, in fact, performed partially anaerobically. In contrast, work performed below the anaerobic threshold is totally aerobic (Figure 2, 4 and 5). The VO2 at the transition from aerobic to partial anaerobic metabolism must depend on cardiovascular performance since it regulates the capillary PO2 level needed for O2 diffusion transport into the mitochondria (Figure 1). At high work rates, the capillary PO2 needed for the oxygen requirement might not be met by the cardiovascular oxygen supply. This would result in the oxygen consumed being less than the oxygen required by the working tissue (Figure 2), with the oxygen equivalent difference necessarily coming from anaerobic metabolism. The consequences are increased lactate formation and metabolic acidosis, and the physiological and biochemical disturbances which result from the latter.

Gas exchange theory and the lactic acidosis (anaerobic) threshold.

The physiological requirements of performing exercise above the anaerobic threshold are considerably more demanding than for lower work rates. Lactic acidosis develops at a metabolic rate that is specific to the individual and the task being performed. Although numerous pyruvate-dependent mechanisms can lead to an elevated blood lactate, the increase in lactate during muscular exercise is accompanied by an increase in lactate/pyruvate ratio (i.e., increased NADH/NAD ratio). This is typically caused by an inadequate O2 supply to the mitochondria. Thus, the anaerobic threshold can be considered to be an important assessment of the ability of the cardiovascular system to supply O2 at a rate adequate to prevent muscle anaerobiosis during exercise testing. In this paper, we demonstrate, with statistical justification, that the pattern of arterial lactate and lactate/pyruvate ratio increase during exercise evidences threshold dynamics rather than the continuous exponential increase proposed by some investigators. The pattern of change in arterial bicarbonate (HCO3-) and pulmonary gas exchange supports this threshold concept. To estimate the anaerobic threshold by gas exchange methods, we measure CO2 output (VCO2) as a continuous function of O2 uptake (VO2) (V-slope analysis) as work rate is increased. The break-point in this plot reflects the obligate buffering of increasing lactic acid production by HCO3-. The anaerobic threshold measured by the V-slope analysis appears to be a sensitive index of the development of metabolic acidosis even in subjects in whom other gas exchange indexes are insensitive, owing to irregular breathing, reduced chemoreceptor sensitivity, impaired respiratory mechanics, or all of these occurrences.

Esophageal-atrial fistula.

We report an unusual case of an esophageal-atrial fistula in a patient with CREST (calcinosis, Raynaud's phenomenon, esophagitis, sclerodactyly, telangiectasia) variant of scleroderma. An ulcer in Barrett's esophagus perforated into the left atrium and led to systemic embolization and cerebral abscess. A review of similar reports of esophageal-atrial fistula reveals a symptom complex that includes chronic esophageal pathology, gastrointestinal bleeding, and neurological signs. An antemortem diagnosis has never been made.

A new method for detecting anaerobic threshold by gas exchange.

Excess CO2 is generated when lactate is increased during exercise because its [H+] is buffered primarily by HCO-3 (22 ml for each meq of lactic acid). We developed a method to detect the anaerobic threshold (AT), using computerized regression analysis of the slopes of the CO2 uptake (VCO2) vs. O2 uptake (VO2) plot, which detects the beginning of the excess CO2 output generated from the buffering of [H+], termed the V-slope method. From incremental exercise tests on 10 subjects, the point of excess CO2 output (AT) predicted closely the lactate and HCO-3 thresholds. The mean gas exchange AT was found to correspond to a small increment of lactate above the mathematically defined lactate threshold [0.50 +/- 0.34 (SD) meq/l] and not to differ significantly from the estimated HCO-3 threshold. The mean VO2 at AT computed by the V-slope analysis did not differ significantly from the mean value determined by a panel of six experienced reviewers using traditional visual methods, but the AT could be more reliably determined by the V-slope method. The respiratory compensation point, detected separately by examining the minute ventilation vs. VCO2 plot, was consistently higher than the AT (2.51 +/- 0.42 vs. 1.83 +/- 0.30 l/min of VO2). This method for determining the AT has significant advantages over others that depend on regular breathing pattern and respiratory chemosensitivity.

Mechanisms and patterns of blood lactate increase during exercise in man.

The close balance between the O2 requirement to perform exercise and the O2 supply was analyzed. A non-uniform capillary PO2 can result in anaerobic metabolism in some muscle fibers despite an apparently adequate mean capillary PO2. The pattern of lactate increase for constant work rates and incremental exercise is described. Lactate increases without an increase in pyruvate at a threshold work rate above which the lactate/pyruvate ratio increases. The latter decreases immediately at the start to recovery. From simultaneous measurements of arterial lactate and pyruvate during exercise and recovery, we conclude that the lactate increase at the lactate threshold is consequent to a change in redox state rather than a mass action effect.

Bicarbonate buffering of lactic acid generated during exercise.

The pattern of decrease in arterial bicarbonate concentration ([HCO3-]) during progressive incremental exercise was compared with that of the rise in arterial lactate ([La-]) to determine the degree of buffering of lactic acid by bicarbonate. A mathematical model was derived for the change in [HCO3-] beyond the lactate threshold. This was based on a log-log transformation of the data, a model previously found to provide a very good fit to the [La-]-O2 consumption (VO2) relationship. The results of the analysis of incremental exercise data from 10 subjects show that the decrease in [HCO3-] very nearly matches the increase in [La-]. However, it was found by comparing regression models that the correspondence between [HCO3-] and [La-] could be improved by assuming that the [HCO3-] decrease was delayed until the arterial lactate level had increased by approximately 0.4 meq/l. This result is compatible with the existence of buffering mechanisms in the cell which buffer the initial increase of lactic acid. Beyond this initial buffering, lactic acid appears to be buffered almost entirely by the bicarbonate buffer system.

Improved detection of lactate threshold during exercise using a log-log transformation.

The pattern of arterial lactate concentration ([La-]) increase during incremental exercise was studied using a transformation defined by plotting log([La-]) vs. log(VO2), where VO2 is O2 uptake. A plot of this function exhibits a phase of very slow increase followed by a phase of rapid increase, defining a transition in the underlying relationship between [La-] and VO2. These phases were found to be linear on the log-log plot; linear regression analysis may therefore be used to locate the transition between them (lactate threshold). A transition point was found at a lower VO2 on the semilog plot of log([La-]) vs. VO2. Consideration of the data from all studies led to the conclusion that a more accurate result is provided by the log-log transformation. This analysis shows lactate to have a small, but significant, increase before the transition and to increase beyond it with a power law having an exponent of about 2.9. This result shows that, during incrementally increasing work rate tests, arterial lactate exhibits a threshold behavior, i.e., an abrupt transition from a phase of slow increase to a phase of rapidly accelerating increase.

Lactate, pyruvate, and lactate-to-pyruvate ratio during exercise and recovery.

The pattern of lactate increase and its relation to pyruvate and lactate-to-pyruvate (L/P) ratio were studied during exercise and early recovery in 10 normal subjects for incremental exercise on a cycle ergometer. Gas exchange was measured breath by breath. Lactate and pyruvate were measured by enzymatic techniques. Lactate and log lactate changed only slightly at low levels of O2 uptake (VO2) but both began to abruptly increase at approximately 40-55% of the maximal VO2. However, the point of abrupt increase in pyruvate occurred at higher work rates and the rate of increase was not as great as that for lactate. Thus L/P ratio increased at the same VO2 as the log lactate increase. Following the exercise, pyruvate continued to increase steeply for at least the first 5 recovery min, whereas at 2 min lactate increased only slightly or decreased. Thus arterial L/P ratio reversed its direction of change and decreased toward the resting value by 2 min of recovery. Lactate, as well as L/P ratios, decreased in all subjects by 5 min. This study demonstrates that lactate and pyruvate concentrations increase slightly at low levels of exercise without a change in L/P ratio until a threshold work rate at which lactate abruptly increases without pyruvate. The resulting increase in L/P ratio is progressive as work rate is incremented and abruptly reverses when exercise stops.

Anomalous right coronary artery arising from left mainstem.

Various coronary artery anomalies occur in both symptomatic and asymptomatic individuals. We have described a unique case of an aberrant right coronary artery arising from the left mainstem, resulting in clinical myocardial infarction in the absence of coronary atherosclerosis. Though different anomalies of the right coronary artery have been described, we feel this case is unique in that the right coronary artery arises from the left mainstem, truly forming a single coronary artery.

Breath-by-breath measurement of true alveolar gas exchange.

A method has been developed for on-line breath-by-breath calculation of alveolar gas exchange by correcting the gas exchange measured at the mouth for changes in lung gas stores. The corrections are applied to the total lung gas exchange, which is found by directly subtracting expired from inspired volume of each gas. Corrections are made for both breath-to-breath changes in lung volumes and changes in alveolar gas concentrations. The lung volume correction term has the effect of reducing the large error sensitivity of O2 exchange that has, in the past, resulted from direct determination by total lung gas exchange. Error each gas. Corrections are made for both breath-to-breath changes in lung volumes and changes in alveolar gas concentrations. The lung volume correction term has the effect of reducing the large error sensitivity of O2 exchange that has, in the past, resulted from direct determination by total lung gas exchange. Error each gas. Corrections are made for both breath-to-breath changes in lung volumes and changes in alveolar gas concentrations. The lung volume correction term has the effect of reducing the large error sensitivity of O2 exchange that has, in the past, resulted from direct determination by total lung gas exchange. Error sensitivity analysis shows that the effect of inaccuracies due to errors in measuring gas flow or gas concentrations are similar in magnitude to those in the open-circuit method that has traditionally been used. The algorithm for alveolar gas exchange has been implemented in a computer program for on-line respiratory analysis alongside the open-circuit calculation of gas exchange at the mouth that has been used in out laboratory. By use of several experimental studies, it is shown that there are very apparent breath-to-breath differences between the gas exchange measured by the two methods. During metabolic and respiratory transients, these differences often have significant influence on interpretation of the underlying physiology.

In vitro quantitation of canine left ventricular volume by phased-array sector scan.

Ultrasonic sector-scan images can delineate the entire circumference of the canine left ventricle in vitro. This study was undertaken to (1) assess the accuracy of sector scanning for estimating canine left ventricular volume in vitro compared to volume estimates by M-mode echo in the same hearts and (2) determine the optimal techniques for estimating left ventricular volume with sector scanning. 16 volumes (1 volume from 8 hearts and 2 volumes from 4 hearts) were estimated by obtaining sector-scan images from orthogonal long-axis, short-axis and apical views. The sector-scan volumes were calculated by single and biplane area-length methods, as well as biplane Simpson's rule methods, and compared to measured left ventricular volumes. M-mode echo volumes were calculated by cubing the mid-ventricular minor-axis diameter. Sector-scan views containing a long-axis dimension plus the short-axis dimension of the left ventricle had a high correlation with true left ventricular volume while sector-scan views not containing a long-axis view showed only a fair correlation with volume. M-mode echo produced a poor estimate of the true left ventricular volume. It is concluded that (1) sector scanning can provide highly accurate in vitro volume estimates of canine left ventricles which is superior to estimates derived by M-mode echocardiographic methods and (2) the optimal sector-scan views for estimating left ventricular volume are those that make the fewest assumptions about left ventricular geometry and have the greatest amount of dimensional information.

Alteration by hyperoxia of ventilatory dynamics during sinusoidal work.

The effects of hyperoxia on ventilatory and gas exchange dynamics were studied utilizing sinusoidal work rate forcings. Five subjects exercised on 14 occasions on a cycle ergometer for 30 min with a sinusoidally varying work load. Tests were performed at seven frequencies of work load during air or 100% O2 inspiration. From the breath-by-breath responses to these tests, dynamic characteristics were analyzed by extracting the mean level, amplitude of oscillation, and phase lag for each six variables with digital computer techniques. Calculation of the time constant (tau) of the ventilatory responses demonstrated that ventilatory kinetics were slower during hyperoxia than during normoxia (P less than 0.025; avg 1.56 and 1.13 min, respectively). Further, for identical work rate fluctuations, end-tidal CO2 tension fluctuations were increased by hyperpoxia. Ventilation during hyperoxia is slower to respond to variations in the level of metabolically produced CO2, presumably because hyperoxia attenuates carotid body output; the arterial CO2 tension is consequently less tightly regulated.