Cardiovascular responses to graded reductions in leg perfusion in exercising humans.

Our objective was to determine whether the chemoreflex from human muscle is elicited by small graded reductions in muscle blood flow (MBF) during mild exercise or whether this reflex has an obvious threshold associated with large changes in femoral venous lactate and H+ levels (i.e., as in dogs with high muscle oxidative capacity). Seven subjects exercised supine at 40, 87, and 142 W; lower body positive pressure (LBPP) was applied in 3-min steps at 25, 35, 45, and 50-60 mmHg with the lower body and the cycle ergometer in a sealed box. Estimated MBF (Fick) fell by 5.3 +/- 4.3 to 19.9 +/- 3.8% at four levels of LBPP over three work rates. Mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) concentration rose with increasing LBPP. MAP was significantly correlated with femoral venous pH, lactate, O2 tension, and O2 content during moderate and heavy exercise, without an apparent threshold. Percentage decreases in muscle vascular conductance exceeded the decreases in MBF twofold, indicating significant opposition to reduction in MBF by the chemoreflex. Approximately 50% of the correction of MBF back toward control (i.e., at 0 LBPP) could be explained by increased cardiac output, calculated from the rise in HR; the remaining correction could be attributed to both sympathetic vasoconstriction (indicated by high NE levels) and to mechanical effects of partial occlusion. Results suggest that in humans stepwise reductions in MBF gradually elicit muscle chemoreflexes with no apparent threshold at these levels of exercise.

Hypotension induced by central hypovolaemia and hypoxaemia.

Our question was whether the reduced orthostatic tolerance that accompanies hypoxaemia in some (not all) subjects might be associated with an abnormally large release of adrenaline. Eight normal young men were exposed to lower body negative pressure (LBNP) at -30 to -40 mmHg while breathing air or 10% O2 in N2. Four subjects developed hypotension and bradycardia whenever LBNP was applied during hypoxaemia; four showed a rise in heart rate and stable blood pressure. During normoxia plasma adrenaline concentration did not rise during LBNP in any subject, nor during hypoxaemia plus LBNP in the subjects who remained normotensive. In the four men whose heart rates and blood pressures fell during LBNP with hypoxaemia, adrenaline rose markedly, reaching 200-1600 pg ml-1. All subjects showed similar elevations in noradrenaline concentration during LBNP in both normoxia and hypoxaemia. The results suggest that reduced tolerance to central hypovolaemia during hypoxaemia could stem from known vasomotor and cardiac effects attending high plasma concentrations of adrenaline.

Venomotor responses during central and local hypoxia.

Venomotor responses, measured as the pressure rise in occluded forearm veins, were used in a two-part experiment to test presence or absence of sympathetic neuroeffector mechanisms in 10 men made moderately to severely hypoxemic. In part I, forearm venoconstriction was induced by ice water on the contralateral forearm (a spinal reflex) in eight supine, resting men who breathed air, 10.3% oxygen or 7.7% oxygen. Large reflex venoconstrictions persisted during hypoxia. In part II (seven men), venoconstriction was centrally induced by exercise while subjects were 1) normoxic; 2) arm hypoxic, body normoxic; 3) arm hyperoxic (or normoxic), body hypoxic; or 4) both arm and body hypoxic. Arm vs. body oxygen tensions were separated by occluding the arm as one gas mixture was breathed, then switching the subject to another mixture as the arm remained occluded. Strong venoconstrictor responses to moderate exercise (100-150 W) persisted during both local and central hypoxemia. We conclude that moderate to severe hypoxemia does not block, pre- or postjunctionally, sympathetic venoconstriction that originates from spinal reflexes (cold). Venoconstriction in exercise (presumably originating in higher centers) was not blocked by moderate hypoxemia; severe hypoxemia was not studied.

Human cardiovascular adjustments to acute hypoxaemia.

Traditionally, cardiovascular adjustments to hypoxaemia are viewed as resultants of competing local vasodilation and vasoconstriction via arterial chemoreflexes with net effects of increased cerebral and coronary blood flows (local) and reduced flow to visceral organs and muscle (reflex). Although true in asphyxia, breathing activates lung mechanoreceptors which reduce vagal outflow and apparently, in humans, abolishes sympathetic vasomotor activity (SNA). During rest, moderate to severe hypoxaemia (PaO2 = 35 to 27 mmHg) caused no splanchnic, cutaneous or muscle vasoconstriction. Local vasodilator effects of hypoxaemia were not sufficient to overwhelm vasoconstriction; splanchnic arterioles responded normally to infused noradrenalin (NA) during hypoxaemia. Possibly, central effects of hypoxaemia blunt SNA or peripheral, prejunctional effects impair neuronal release of NA. Persistent orthostatic tolerance with normal skeletal muscle vasoconstriction and retained spinal venomotor reflexes during hypoxaemia argue against prejunctional inhibition of NA release. Results so far suggest that beyond a certain threshold, hypoxaemia centrally inhibits SNA. In contrast to rest, even moderate hypoxaemia during exercise markedly increases plasma NA concentration (and SNA), but the usual relationship among splanchnic blood flow, plasma NA and heart rate was not observed--NA and heart rate rose together, whereas the predicted splanchnic vasoconstriction was not observed. In moderate hypoxaemia, muscle blood flow and cardiac output are greater than in normoxia at a given submaximal oxygen uptake; but at maximal oxygen uptake, blood pressure, total vascular conductance and maximal cardiac output are unaffected. Given the fixed upper limit to cardiac output and the greater capacity of active muscle to vasodilate and exceed cardiac pumping capacity during hypoxaemia, we conclude that blood pressure is maintained by baroreflex- (not chemoreflex-) mediated vasoconstriction in the active muscle which must be the primary target of increased SNA and the source of NA.

Hepatic splanchnic function in acutely hypoxemic humans at rest.

Splanchnic metabolism of O2, glucose, and lactate was studied in five normal men during rest while breathing air, 10.4% O2 [arterial O2 partial pressure (PaO2) = 34.8 Torr], and in four men breathing 7.6% O2 (PaO2 = 27.0 Torr). Despite reduction in arterial O2 content to 10.7 ml/100 ml, splanchnic O2 uptake (VO2) and arteriovenous O2 difference remained constant through a fall in hepatic venous O2 content to 7.3 ml/100 ml. Hepatic release of glucose and uptake of lactate were unaffected by either moderate or severe hypoxemia. In five other men hepatic extraction efficiency, removal rate, and clearance of norepinephrine (NE) and epinephrine (E) (radioenzymatic assay) were determined, while air and 10.27% O2 were breathed, and while NE was infused over widely ranging rates (constant in a given subject). Over arterial concentrations of 1.8-17 ng/ml for NE and 0.03-0.3 ng/ml for E, splanchnic removal was closely related to arterial concentration and was unaffected by hypoxemia. NE extraction efficiency rose from 60 (control) to 94% (during infusion in normoxia and hypoxemia); E extraction efficiency remained constant at 85% under all conditions. Hepatic clearances of both NE (556-824 ml/min) and E (630-804 ml/min) were unaffected by hypoxemia. The only observed deficiency in hepatic function was a significant decrease in extraction of indocyanine green in all 10 subjects at both levels of hypoxemia.

Lack of sympathetic vasoconstriction in hypoxemic humans at rest.

A three-part experiment was designed to show whether hypoxemia alters splanchnic vasomotor responses to other stresses by vasodilating splanchnic organs, preventing norepinephrine (NE)-induced vasoconstriction, or altering total sympathetic nervous activity (SNA) assessed by plasma levels of NE and epinephrine (Epi). Splanchnic blood flow (SBF) was measured by plasma clearance and hepatic extraction of indocyanine green (constant infusion). Part I: two degrees of hypoxemia [fractional concn of inspired O2 (FIO2) = 10.4 and 7.6%, arterial PO2 (PaO2) = 34.8 and 27 Torr] caused a small splanchnic vasodilation; resistance fell 16 and 26%, respectively, in five men; and SBF rose from 1.78 to 2.04 (10.4% O2) and to 2.02 1 X min-1 (7.6% O2). Plasma NE was unaffected by hypoxemia and by a fall in mean arterial pressure from 82 to 63 Torr at FIO2 = 7.6%. Part II: NE infused intravenously to raise pressure by 20 Torr in five subjects breathing air and 10.3% O2 caused splanchnic vasoconstriction irrespective of PaO2. Part III: in six subjects, two levels of hypoxemia (FIO2 = 10.4 and 7.7%) did not increase NE levels in five men, and Epi increased in two men only at FIO2 = 7.7%. We conclude that hypoxemia caused only a small splanchnic vasodilation not mediated by Epi, did not prevent transient NE-induced vasoconstriction, and either did not significantly increase SNA or prejunctionally inhibited NE release. Severe hypoxemia abolished the rise in NE and heart rate in response to falling pressure.

Splanchnic vasomotor and metabolic adjustments to hypoxia and exercise in humans.

To determine whether hypoxia increases splanchnic vasoconstriction and impedes splanchnic metabolism during exercise, 11 subjects were exercised for 72 min at O2 uptake (VO2) of 1.8 1/min; 11% O2 was breathed during 30-50 min. Splanchnic blood flow (SBF), arterial and hepatic venous concentrations of indocyanine green (ICG), O2, CO2, metabolites, and catecholamines were determined in seven subjects; complete sets of all measurements were obtained from four. Arterial O2 content and tension fell from normal values to 12.3 ml/100 and to 32.2 Torr, respectively, during hypoxia; heart rate rose to 159 from 117 beats/min, arterial blood pressure was unchanged, and plasma norepinephrine (NE) and epinephrine (E) concentrations rose from 0.79 (NE) and 0.2 (E) ng/ml (normoxia) to 2.7 and 0.72, respectively, during hypoxia. SBF rose insignificantly from 1.14 (normoxia) to 1.35 l/min during hypoxia and fell significantly to 1.01 1/min after return to normoxia. Splanchnic VO2 was maintained at normal levels by increased extraction as hepatic venous O2 fell to 1.7 ml/100 ml and hepatic venous O2 tension to 7.5 Torr. Hepatic glucose release rose from 642 (normoxia) to 1,164 mg/min (hypoxia); lactate uptake increased from 0.26 to 2.1 mM/min; NE uptake rose from 417 to 1,508 ng/min, but hypoxia reduced ICG extraction by 28%. Thus hypoxia did not cause splanchnic vasoconstriction normally accompanying increases in HR and NE concentration or reductions in maximum VO2. SBF was maintained at a level sufficient to maintain all metabolic functions except ICG extraction.

Sensitivity for Telemed diagnosis of myocardial infarction by use of 12-lead electrocardiogram derived from Frank XYZ leads.

Another comparison of sensitivity for diagnosis of myocardial infarction in conventional and derived 12-lead ECGs processed by the computer diagnostic program of the Telemed Cardio-Pulmonary System is reasonably consistent with the original trial of these two methods of recording ECG signals reported earlier by Dower and Machado. Other similarities and disparities are cited, together with brief comments about the theoretical and clinical implications of those findings and the relationship to a more rigorous analysis from this laboratory.

Human cardiovascular and respiratory responses to graded muscle ischemia.

Responses of heart rate (HR), mean arterial blood pressure (MAP) ventilation (VE), and forearm blood flow (FBF) to different degrees of leg muscle ischemia were measured in eight subjects in a four-part experiment. Part I. Total circulatory occlusion (OCCL) of resting legs for 15 min had little or no effect on HR, MAP, VE, or FBF. Part II. OCCL of the legs for 3 min immediately after exercise at 50-250 W did not affect HR or end-tidal CO2; it lowered VO2 and VE and prevented recovery of MAP. Part III. OCCL beginning at end and 10, 20, 30 s before end of 7-min exercise (100-150 W) and continuing 3 min into recovery period produced sustained and graded increments (5-10 mmHg) in MAP, only small changes in HR, and accelerated recovery of VE while end-tidal CO2 remained constant. Part IV. OCCL at end and 30 s before end of exercise increased FBF 2.5-3.5 times; both skin and muscle vasodilated. Thus muscle ischemia preceded by exercise can raise MAP without affecting VE, whereas baroreflexes may lower HR and raise FBF. The results suggest the presence of muscle chemoreceptors whose major effect is on MAP.