Increase In Cardiac Stroke Volume Research Articles

The Cardiovascular Effects of a Meal: J-Tpeak and Tpeak -Tend Assessment and Further Insights Into the Physiological Effects.

Meal intake leads to a significant and prolonged increase in cardiac output to supply the splanchnic vasculature. A meal is associated with sympathetic activation of the cardiovascular system, and food ingestion is correlated with an increase in heart rate, an increase in cardiac stroke volume, and QTc interval shortening for up to 7 hours. Given the complexity of the system, one or several of many mechanisms could explain this observation. The shortening of the QTc interval was correlated with a rise of C‐peptide following food ingestion, but the mechanisms by which C‐peptide may be involved in the modulation of cardiac repolarization are still unknown. This shortening of the myocardial action potential caused by the ingestion of food was further investigated in the present study by measuring the QRS, J‐Tpeak, and Tpeak‐Tend intervals in search of further clues to better understand the underlying mechanisms. A retrospective analysis was conducted based on data collected in a formal thorough QT/QTc study in which 32 subjects received a carbohydrate‐rich “continental” breakfast, moxifloxacin without food, and moxifloxacin with food. We assessed the effect of food on T‐wave morphology using validated algorithms for measurement of J‐Tpeak and Tpeak‐Tend intervals. Our findings demonstrate that a standardized meal significantly shortened J‐Tpeak for 4 hours after a meal and to a much lesser extent and shorter duration (up to 1 hour) prolonged the Tpeak‐Tend and QRS intervals. This suggests that the QTc shortening occurs mainly during phase 2 of the cardiac action potential. As there was no corresponding effect on Tpeak‐Tend beyond the first hour, we conclude that a meal does not interfere with the outward correcting potassium channels but possibly with Ca2+ currents. An effect on mainly Ca2+ aligns well with our understanding of physiology whereby an increase in stroke volume, as observed after a meal, is associated with changes in Ca2+ cycling in and out of the sarcoplasmic reticulum during cardiac myocyte contraction.

Do Bar-Headed Geese Train for High Altitude Flights?

Exercise at high altitude is extremely challenging, largely due to hypobaric hypoxia (low oxygen levels brought about by low air pressure). In humans, the maximal rate of oxygen consumption decreases with increasing altitude, supporting progressively poorer performance. Bar-headed geese (Anser indicus) are renowned high altitude migrants and, although they appear to minimize altitude during migration where possible, they must fly over the Tibetan Plateau (mean altitude 4800 m) for much of their annual migration. This requires considerable cardiovascular effort, but no study has assessed the extent to which bar-headed geese may train prior to migration for long distances, or for high altitudes. Using implanted loggers that recorded heart rate, acceleration, pressure, and temperature, we found no evidence of training for migration in bar-headed geese. Geese showed no significant change in summed activity per day or maximal activity per day. There was also no significant change in maximum heart rate per day or minimum resting heart rate, which may be evidence of an increase in cardiac stroke volume if all other variables were to remain the same. We discuss the strategies used by bar-headed geese in the context of training undertaken by human mountaineers when preparing for high altitude, noting the differences between their respective cardiovascular physiology.

Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long duration spaceflight.

Weightlessness in space induces initially an increase in stroke volume and cardiac output, accompanied by unchanged or slightly reduced blood pressure.It is unclear whether these changes persist throughout months of flight.Here, we show that cardiac output and stroke volume increase by 35–41% between 3 and 6 months on the International Space Station, which is more than during shorter flights.Twenty-four hour ambulatory brachial blood pressure is reduced by 8–10 mmHg by a decrease in systemic vascular resistance of 39%, which is not a result of the suppression of sympathetic nervous activity, and the nightly dip is maintained in space.It remains a challenge to explore what causes the systemic vasodilatation leading to a reduction in blood pressure in space, and whether the unexpectedly high stroke volume and cardiac output can explain some vision acuity problems encountered by astronauts on the International Space Station. Acute weightlessness in space induces a fluid shift leading to central volume expansion. Simultaneously, blood pressure is either unchanged or decreased slightly. Whether these effects persist for months in space is unclear. Twenty-four hour ambulatory brachial arterial pressures were automatically recorded at 1–2 h intervals with portable equipment in eight male astronauts: once before launch, once between 85 and 192 days in space on the International Space Station and, finally, once at least 2 months after flight. During the same 24 h, cardiac output (rebreathing method) was measured two to five times (on the ground seated), and venous blood was sampled once (also seated on the ground) for determination of plasma catecholamine concentrations. The 24 h average systolic, diastolic and mean arterial pressures (mean ± se) in space were reduced by 8 ± 2 mmHg (P = 0.01; ANOVA), 9 ± 2 mmHg (P < 0.001) and 10 ± 3 mmHg (P = 0.006), respectively. The nightly blood pressure dip of 8 ± 3 mmHg (P = 0.015) was maintained. Cardiac stroke volume and output increased by 35 ± 10% and 41 ± 9% (P < 0.001); heart rate and catecholamine concentrations were unchanged; and systemic vascular resistance was reduced by 39 ± 4% (P < 0.001). The increase in cardiac stroke volume and output is more than previously observed during short duration flights and might be a precipitator for some of the vision problems encountered by the astronauts. The spaceflight vasodilatation mechanism needs to be explored further.

Acute Changes in Systemic Hemodynamics and Serum Vasopressin After Complete Cervical Spinal Cord Injury in Piglets

Spinal cord injury (SCI) produces acute hemodynamic alterations through disruption of sympathetic output of the autonomic nervous system and places individuals with SCI at high risk of secondary ischemic insult to the spinal cord as well as to other organs. The purpose of this study was to examine hemodynamics and serum vasopressin concentration in the acute period following complete cervical SCI in piglets. We developed a new model of traumatic complete cervical SCI in piglets and measured acute hemodynamic variables and serum arginine vasopressin (AVP) concentrations at baseline and for 4 h after SCI under fentanyl anesthesia. Complete cervical SCI caused an immediate tachycardia which lasted for approximately 1 h, immediate hypotension which was sustained for the 4-h duration of the study, decreases in both systemic and pulmonary vascular resistance, and a compensatory increase in cardiac output, which resulted initially from an increase in heart rate (HR) but was later sustained after resolution of tachycardia by an increase in cardiac stroke volume. Serum AVP concentration increased significantly after SCI and did not change in the control group. Neurogenic shock did not occur due to the robust increase in cardiac output and cardiac stroke volume. Complete cervical SCI produces hemodynamic alterations consistent with the withdrawal of sympathetic tone. Although mean arterial pressure (MAP) decreased significantly after SCI, the increase in serum vasopressin may have played a role in maintaining blood pressure and preventing circulatory collapse, a complication which is encountered frequently in patients with cervical and upper thoracic SCI.

Tribute to P. L. Lutz: a message from the heart – why hypoxic bradycardia in fishes?

The sensing and processing of hypoxic signals, the responses to these signals and the modulation of these responses by other physical and physiological factors are an immense topic filled with numerous novel and exciting discoveries. Nestled among these discoveries, and in contrast to mammals, is the unusual cardiac response of many fish to environmental hypoxia - a reflex slowing of heart rate. The afferent and efferent arms of this reflex have been characterised, but the benefits of the hypoxic bradycardia remain enigmatic since equivocal results have emerged from experiments examining the benefit to oxygen transfer across the gills. The main thesis developed here is that hypoxic bradycardia could afford a number of direct benefits to the fish heart, largely because the oxygen supply to the spongy myocardium is precarious (i.e. it is determined primarily by the partial pressure of oxygen in venous blood, Pv(O(2))) and, secondarily, because the fish heart has an unusual ability to produce large increases in cardiac stroke volume (V(SH)) that allow cardiac output to be maintained during hypoxic bradycardia. Among the putative benefits of hypoxic bradycardia is an increase in the diastolic residence time of blood in the lumen of the heart, which offers an advantage of increased time for diffusion, and improved cardiac contractility through the negative force-frequency effect. The increase in V(SH) will stretch the cardiac chambers, potentially reducing the diffusion distance for oxygen. Hypoxic bradycardia could also reduce cardiac oxygen demand by reducing cardiac dP/dt and cardiac power output, something that could be masked at cold temperature because of a reduced myocardial work load. While the presence of a coronary circulation in certain fishes decreases the reliance of the heart on Pv(O(2)), hypoxic bradycardia could still benefit oxygen delivery via an extended diastolic period during which peak coronary blood flow occurs. The notable absence of hypoxic bradycardia among fishes that breathe air during aquatic hypoxia and thereby raise their Pv(O(2)), opens the possibility that that the evolutionary loss of hypoxic bradycardia may have coincided with some forms of air breathing in fishes. Experiments are needed to test some of these possibilities. Ultimately, any potential benefit of hypoxic bradycardia must be placed in the proper context of myocardial oxygen supply and demand, and must consider the ability of the fish heart to support its routine cardiac power output through glycolysis.

A Cardiovascular Drug Rescues Mice from Lethal Sepsis by Selectively Attenuating a Late-Acting Proinflammatory Mediator, High Mobility Group Box 1

The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., TNF, IL-1, and IFN-gamma) and late (e.g., high mobility group box 1 (HMGB1) protein) proinflammatory cytokines. The recent discovery of HMGB1 as a late mediator of lethal sepsis has prompted investigation for development of new experimental therapeutics. We found that many steroidal drugs (such as dexamethasone and cortisone) and nonsteroidal anti-inflammatory drugs (such as aspirin, ibuprofen, and indomethacin) failed to influence endotoxin-induced HMGB1 release even at superpharmacological concentrations (up to 10-25 microM). However, several steroid-like pigments (tanshinone I, tanshinone IIA, and cryptotanshinone) of a popular Chinese herb, Danshen (Salvia miltiorrhiza), dose dependently attenuated endotoxin-induced HMGB1 release in macrophage/monocyte cultures. A water-soluble tanshinone IIA sodium sulfonate derivative (TSNIIA-SS), which has been widely used as a Chinese medicine for patients with cardiovascular disorders, selectively abrogated endotoxin-induced HMGB1 cytoplasmic translocation and release in a glucocorticoid receptor-independent manner. Administration of TSNIIA-SS significantly protected mice against lethal endotoxemia and rescued mice from lethal sepsis even when the first dose was given 24 h after the onset of sepsis. The therapeutic effects were partly attributable to attenuation of systemic accumulation of HMGB1 (but not TNF and NO) and improvement of cardiovascular physiologic parameters (e.g., decrease in total peripheral vascular resistance and increase in cardiac stroke volume) in septic animals. Taken together, these data re-enforce the pathogenic role of HMGB1 in lethal sepsis, and support a therapeutic potential for TSNIIA-SS in the treatment of human sepsis.

WISE‐2005: Exercise countermeasure protects against changes in cardiovascular response to sublingual nitroglycerin after 56‐d bed rest

Cardiovascular responses to 0.3mg sublingual nitroglycerin spray (NG) were assessed before and after 56 days head-down tilt bed rest (HDT) with (EX) and without (No-EX) treadmill in LBNP and resistive exercise countermeasure. Heart rate (HR), mean arterial pressure (MAP, finger photoplethysmography), and aortic blood velocity (pulse Doppler ultrasound) were recorded before and after administration of NG. In response to NG stimulation pre HDT, MAP decreased by 5.5±3.3mmHg (mean±SD), and HR increased by 12±4bpm. The increase in HR, combined with a small increase in cardiac stroke volume (SV), resulted in cardiac output (CO) increasing by 0.97±0.55L/min. Post HDT, a trend was observed to higher resting HR and lower MAP in No-EX. Responses to NG were similar to the pre HDT condition, however, No-EX showed an augmented HR increase (11±8bpm) when compared to EX (7±4bpm, p=0.035). As SV did not change from the pre HDT condition, the increased HR response resulted in increased CO. MAP responses were similar in both groups post HDT; therefore, it would appear that No-EX had a greater reliance on the heart rate component of blood pressure regulation. This is likely the result of increased vasodilation and or lack of compensatory sympathetic vasoconstriction in the peripheral vasculature. The results of this study suggest that exercise protects against cardiovascular changes during HDT that would alter responses to NG stimulation. Supported by Canadian Space Agency, NASA, ESA, CNES

Factorial Aerobic Scope Is Independent of Temperature and Primarily Modulated by Heart Rate in Exercising Murray Cod (Maccullochella peelii peelii)

Several previous reports, often from studies utilising heavily instrumented animals, have indicated that for teleosts, the increase in cardiac output (Vb) during exercise is mainly the result of an increase in cardiac stroke volume (V(S)) rather than in heart rate (fH). More recently, this contention has been questioned following studies on animals carrying less instrumentation, though the debate continues. In an attempt to shed more light on the situation, we examined the heart rates and oxygen consumption rates (Mo2; normalised to a mass of 1 kg, given as Mo2kg) of six Murray cod (Maccullochella peelii peelii; mean mass+/-SE = 1.81+/-0.14 kg) equipped with implanted fH and body temperature data loggers. Data were determined during exposure to varying temperatures and swimming speeds to encompass the majority of the biological scope of this species. An increase in body temperature (Tb) from 14 degrees C to 29 degrees C resulted in linear increases in Mo2kg (26.67-41.78 micromol min(-1) kg(-1)) and fH (22.3-60.8 beats min(-1)) during routine exercise but a decrease in the oxygen pulse (the amount of oxygen extracted per heartbeat; 1.28-0.74 micromol beat(-1) kg(-1)). During maximum exercise, the factorial increase in Mo2kg was calculated to be 3.7 at all temperatures and was the result of temperature-independent 2.2- and 1.7-fold increases in fH and oxygen pulse, respectively. The constant factorial increases in fH and oxygen pulse suggest that the cardiovascular variables of the Murray cod have temperature-independent maximum gains that contribute to maximal oxygen transport during exercise. At the expense of a larger factorial aerobic scope at an optimal temperature, as has been reported for species of salmon and trout, it is possible that the Murray cod has evolved a lower, but temperature-independent, factorial aerobic scope as an adaptation to the largely fluctuating and unpredictable thermal climate of southeastern Australia.

Cardiorespiratory responses to hypercarbia in tambaquiColossoma macropomum: chemoreceptor orientation and specificity

Experiments were carried out to test the hypothesis that ventilatory and cardiovascular responses to hypercarbia (elevated water P(CO2)) in the tambaqui Colossoma macropomum are stimulated by externally oriented receptors that are sensitive to water CO(2) tension as opposed to water pH. Cardiorespiratory responses to acute hypercarbia were evaluated in both the absence and presence of internal hypercarbia (elevated blood P(CO2)), achieved by treating fish with the carbonic anhydrase inhibitor acetazolamide. Exposure to acute hypercarbia (15 min at each level, final water CO(2) tensions of 7.2, 15.5 and 26.3 mmHg) elicited significant increases in ventilation frequency (at 26.3 mmHg, a 42% increase over the normocarbic value) and amplitude (128%), together with a fall in heart rate (35%) and an increase in cardiac stroke volume (62%). Rapid washout of CO(2) from the water reversed these effects, and the timing of the changes in cardiorespiratory variables corresponded more closely to the fall in water P(CO2) (Pw(CO2)) than to that in blood P(CO2) (Pa(CO2)). Similar responses to acute hypercarbia (15 min, final Pw(CO2) of 13.6 mmHg) were observed in acetazolamide-treated (30 mg kg(-1)) tambaqui. Acetazolamide treatment itself, however, increased Pa(CO2) (from 4.81+/-0.58 to 13.83+/-0.91 mmHg, mean +/-S.E.M.; N=8) in the absence of significant change in ventilation, heart rate or cardiac stroke volume. The lack of response to changes in blood P(CO2) and/or pH were confirmed by comparing responses to the bolus injection of hypercarbic saline (5% or 10% CO(2); 2 ml kg(-1)) into the caudal vein with those to the injection of CO(2)-enriched water (1%, 3%, 5% or 10% CO(2); 50 ml kg(-1)) into the buccal cavity. Whereas injections of hypercarbic saline were ineffective in eliciting cardiorespiratory responses, changes in ventilation and cardiovascular parameters accompanied injection of CO(2)-laden water into the mouth. Similar injections of CO(2)-free water acidified to the corresponding pH of the hypercarbic water (pH 6.3, 5.6, 5.3 or 4.9, respectively) generally did not stimulate cardiorespiratory responses. These results are in agreement with the hypothesis that in tambaqui, externally oriented chemoreceptors that are predominantly activated by increases in water P(CO2), rather than by accompanying decreases in water pH, are linked to the initiation of cardiorespiratory responses to hypercarbia.

Respiratory muscle training increases cycling endurance without affecting cardiovascular responses to exercise.

We tested whether the increased cycling endurance observed after respiratory muscle training (RMT) in healthy sedentary humans was associated with a training-induced increase in cardiac stroke volume (SV) during exercise, similar to the known effect of endurance training. Thirteen subjects underwent RMT by normocapnic hyperpnea, nine underwent aerobic endurance training (cycling and/or running) and fifteen served as non-training controls. Training comprised 40 sessions performed within 15 weeks, where each session lasted 30 min. RMT increased cycling endurance at 70% maximal aerobic power (Wmax) by 24% [mean (SD) 35.6 (11.9) min vs 44.2 (17.6) min, P < 0.05], but SV at 60% Wmax was unchanged [94 (21) ml vs 93 (20) ml]. Aerobic endurance training increased both SV [89 (24) ml vs 104 (32) ml, P < 0.01] and cycling endurance [37.4 (12.8) min vs 52.6 (16.9) min, P < 0.01]. In the control group, no changes were observed in any of these variables. It is concluded that the increased cycling endurance that is observed after RMT is not due to cardiovascular adaptations, and that the results provide evidence for the role of the respiratory system as an exercise-limiting factor.

Feedback control of mean aortic pressure in a dynamic model of the cardiovascular system.

Orbital measurements of the cardiac function of Space Shuttle crew members have shown an initial increase in cardiac stroke volume upon entry into weightlessness, followed by a gradual reduction in stroke volume to a level approximately 15% less than preflight values. In an effort to explain this response, it was hypothesized that gravity plays a role in cardiac filling. A mock circulatory system was designed to investigate this effect. Preliminary studies carried out with this system on the NASA KC-135 aircraft, which provides brief periods of weightlessness, showed a strong correlation between cardiac filling, stroke volume, and the presence or absence of gravity. The need for extended periods of high quality zero gravity was identified to verify this observation. To accomplish this, the aircraft version of the experiment was reduced in size and fully automated for eventual integration into a Get Away Special canister to conduct an orbital version of the experiment. This article describes the automated system, as well as the development and implementation of a control algorithm for the servoregulation of the mean aortic pressure in the orbital experiment. Three nonlinearities that influence the ability of the apparatus to regulate to a mean aortic pressure of 95 mm Hg were identified and minimized. In preparation for a Space Shuttle flight, the successful function of the servoregulatory scheme was demonstrated during ground tests and additional test flights aboard the KC-135. The control algorithm was successful in carrying out the experimental protocol, including regulation of mean aortic pressure. The algorithm could also be used for the automated operation of long-term tests of circulatory support systems, which may require a scheduled cycling of the pumping conditions on a daily basis.

Cardio-vascular and ventilatory effects of prostaglandin E 2 in the European eel Anguilla anguilla

Prostaglandin E2 (PGE2) injection caused an initial decrease in heart rate (HR) (55%), cardiac output (QC) (55%), ventral (VAP, 40%) and dorsal (DAP, 60%) aortic pressures, associated with a marked gill vasoconstriction (100%) and a systemic vasodilation (30%) while cardiac stroke volume (CSV) remained unchanged. It was followed by a progressive recovery of HR, DAP, and vascular resistances to control values while VAP, QC, and CSV significantly increased (20%, 40%, and 40%, respectively). Bradycardia was abolished either by atropine treatment or bilateral section of the cardiac vagus, suggesting that bradycardia could be the consequence of a vagal mechanism triggered by a central action of PGE2. The increase in QC is due to the increase in CSV, which suggests a positive inotropic action of PGE2. Infusion with PGE2 (10−9 to 10−5 mol · l−1) did not cause any significant effect on the branchial vasculature in vitro, but when the preparation was pre-treated with adrenaline (10−8 mol · l−4), a dose-related vasoconstrictory response to PGE2 (10−9 to 10−5 mol · l−1) occurred. A significant rise (25%) in gill vascular resistance was observed in vivo after treatment with the β-blocker propranolol (2.0 mg · kg−1), suggesting the existence of a vasodilatory β-adrenergic control of the branchial vasculature. PGE2 caused an apnea followed by a simultaneous tachypnea (50%) and decrease in ventilatory amplitude (40%). The resulting decrease in ventilatory water flow (Qw) was accompanied by a fall in arterial O2 tension (Pa O2). Under steady Qw in curarized eels, an initial fall in Pa O2 was still observed during the PGE2-induced gill vasoconstriction. It is concluded that PGE2 could play a role in the regulation of gas exchanges and blood circulation in particular environmental conditions which require an impairment of gill respiration and a redistribution of blood to the benefit of the systemic vascular bed.

Peptidergic modulation of cardiovascular dynamics in the Dungeness crab, Cancer magister

Decapod crustacean pericardial organs contain extensive neurohormonal reserves which can be released directly into the haemolymph to act as physiological modulators. The present paper concerns the in vivo effects of two pericardial peptides, proctolin and crustacean cardioactive peptide, on cardiovascular dynamics in the crab Cancer magister. Infusion of proctolin into the pericardial sinus caused a slight decrease in heart rate concurrent with a large increase in cardiac stroke volume. It decreased haemolymph flow anteriorly through the paired anterolateral arteries and increased flow posteriorly and ventrally through the posterior aorta and sternal artery, respectively. The threshold for responses occurred at circulating concentrations of 10-9 mol·l-1, and haemolymph flows remained elevated for up to 30 min after peptide infusion. The effects of crustacean cardioactive peptide were less dramatic. Heart rate was not affected but a significant increase in stroke volume was observed. Crustacean cardioactive peptide increased haemolymph flow through the anterolateral arteries and increased scaphognathite rate. The threshold for crustacean cardioactive peptide activity was higher than for proctolin (10-7 mol·l-1 and 10-6 mol·l-1) but the responses to crustacean cardioactive peptide were of longer duration. The effects of proctolin on regional haemeolymph distribution in Cancer magister closely resemble the cardiovascular responses of this species when exposed to hypoxic conditions. These peptides may be implicated as cardiovascular regulators during environmental perturbations.

Effectiveness of training programmes for prepubescent children.

Early investigators suggested that endurance training had little influence upon the aerobic function of the prepubescent child. It is shown that the twin explanations of this supposed phenomenon (a high intrinsic level of physical activity and an immaturity of biochemical systems) have little foundation. Moreover, critical examination of the original experiments shows a number of problems of experimental design, often including an inadequate sample size, a lack of control group, an inappropriate pattern of training relative to the initial fitness of the child, and too short a period of observation. Recent, well-designed studies all show a response in prepubescent children. Comparison with adults is hampered by difficulties in matching training intensity, but there is no immediate evidence that the training response of the prepubescent child is less than in an older person. The main basis for the increase of oxygen transport seems an increase of cardiac stroke volume. Plainly, the development of athletic performance and the attack upon cardiac risk factors can be begun before puberty, although in the average prepubescent it may be more important for the school programmes to develop positive, lifelong attitudes, than to maximise aerobic function.

Elevated Pericardial Pressure And Cardiac Output in the Leopard Shark Triakis Semifasciata During Exercise: The Role Of The Pericardioperitoneal Canal

ABSTRACT Changes in pericardial pressure, pericardial fluid volume, cardiac stroke volume and heart rate induced by swimming were monitored for Triakis semifasciata (Girard). Maximum pericardial pressure (Pmax, 0.07±0.03kPa) in resting sharks was typically above ambient, whereas minimum pressure (Pmin, –0.08±0.03 kPa) was slightly subambient. During swimming, both Pmax (0.23±0.03 kPa) and Pmin (–0.02±0.03kPa) became elevated, as did heart rate (51±2 to 55±2 beats min−1) and fractional cardiac stroke volume (0.49±0.03 to 0.65±0.04ml). After swimming, all variables fell, except fractional cardiac stroke volume. Estimates of total cardiac output from fractional cardiac stroke volume data during rest, exercise and recovery were 33.1, 56.2 and 60.4 ml kg−1 min−1, respectively. The occurrence of both elevated pericardial pressure and cardiac output during swimming argues against a primary role for pericardial-induced vis a fronte filling as the principal mechanism responsible for increasing cardiac output with exercise. Pericardial fluid loss via the pericardioperitoneal canal (PPC) occurs during swimming as a result of steady-state elevation of pericardial pressure, a series of transient high pericardial pressures, or both. Good general agreement seen for net pericardial fluid loss (0.6 ml kg−1) and the net increase in cardiac stroke volume (0.45 ml kg−1) during swimming establishes fluid displacement as a mechanism for increasing cardiac stroke volume and suggests that this is the primary function of the PPC.

Hemodynamic assessment of nicardipine alone and with atenolol in coronary artery disease using a modified echo-doppler device

We have used a modified noninvasive echo-Doppler cardiac output device, based on the principle of attenuated compensation volume flow, to assess the cardiovascular effects of the slow-calcium antagonist nicardipine in coronary disease. The dose-response effects of 2.5, 5.0 and 10.0 mg intravenous nicardipine were determined in 8 patients with angina. Dose-related decreases were seen in systemic mean arterial pressure (p <0.01) after administration of nicardipine. Cardiac pumping indexes were improved, as evident from linear increases in cardiac stroke volume (p <0.01), stroke length (p <0.01) and time-averaged mean velocity (p <0.01). The echo-Doppler device was also used to assess β-blocking/nicardipine combination therapy in patients with angina. When nicardipine was given after the cardioselective β blocker atenolol the reduction in heart rate and cardiac output after atenolol was reversed compared with a group that received atenolol followed by placebo. Cardiac performance improved and the 35% reduction in systemic vascular resistance was associated with markedly increased cardiac index (p <0.01), augmentation of time-averaged mean velocity (p <0.01) and cardiac stroke length (p <0.05). These data are consistent with previous invasive studies of nicardipine, either alone or when combined with β blockade in coronary disease. The data also suggest that nicardipine/β-blocking combination is safe in patients with coronary heart disease and that the echo-Doppler method of cardiovascular monitoring will prove useful in human pharmacodynamic studies.

The Effect of Progressive Hypoxia on Heart Rate, Ventilation, Respiratory Gas Exchange and Acid-Base Status in the Crayfish Austropotamobius Pallipes

ABSTRACT Male and female crayfish, Austropotamobius pallipes (Lereboullet) maintained a constant rate of O2 uptake during a progressive reduction in ambient O2 tension down to a critical tension (Pc) of 40 mmHg at 15 °c. Heart rate (fH) slowed progressively during hypoxia but blood flow was maintained by an increase in cardiac stroke volume. At a , of 50 mmHg the rate of ventilation had increased to 2·8 times the normoxic value. This was effected by a doubling in respiratory frequency (fR) accompanied by increases in both the mean amplitude of the pressure pulse and the mean hydrostatic pressure recorded in the branchial chambers. The effectiveness of removal of O2 from the water ventilating the gills was maintained (Ew), and there is evidence that the ability of the respiratory surface to transfer O2 improved during hypoxia. The hyperventilation enhanced CO2 elimination so that CO2 tensions were halved and respiratory alkalosis occurred in the haemolymph. This alkalosis had the effect of increasing the affinity of the blood pigment for O2, reducing the half saturation pressure (P50) from 8 to 4·5 mmHg. Thus despite reductions in pre- and postbranchial O2 tensions by 50% the arteriovenous O2 content difference was maintained and the effectiveness of removal of O2 into the blood (Eb) remained high in moderately hypoxic water ( 63 ± 1 mmHg). At , levels below 40 mmHg, when crayfish were denied access to air, they were unable to sustain the hyperventilation. Haemolymph O2 content and the a – v O2 content difference decreased, and as the haemolymph was no longer saturated with O2 on its passage through the gills, Eb was reduced. As a consequence of these changes fell. Under these conditions a partial switch to anaerobic metabolism occurred, with lactic acid accumulating in the haemolymph. The resultant metabolic acidosis partially offset the respiratory alkalosis.

The reflex control of heart rate and cardiac output in the rainbow trout: interactive influences of hypoxia, haemorrhage, and systemic vasomotor tone.

In cannulated trout there was no cholinergic vagal tone as revealed by atropine blockade during normal heart rates. Reductions in heart rate occasionally occurred under normoxia without apparent external stimuli ('spontaneous' bradycardia) and always occurred under environmental hypoxia (hypoxic bradycardia) due to the imposition of significant vagal tone. Direct measurements of cardiac output (Q) during these bradycardias showed that increases in cardiac stroke volume compensated for the falls in heart rate so that total Q remained unchanged or increased slightly. Sudden experimental reductions in arterial blood pressure via blockade of systemic vasomotor tone with yohimbine or via haemorrhage had no effect on heart rate during normal rates, but caused cardioacceleration during both types of bradycardia. These increases in heart rate never exceeded the point of zero vagal tone (normal heart rate) and were largely or wholly due to reductions in endogenous vagal tone. These cardioaccelerations were temporary; spontaneous bradycardia could re-occur at any time, while hypoxic bradycardia always re-occurred if the hypoxic stimulus were maintained. The results are interpreted in terms of a central interaction between the baroreceptor and chemoreceptor reflexes.

The effectiveness of oxygen transfer during normoxia and hypoxia in the dogfish (Scyliorhinus canicula L.) before and after cardiac vagotomy

1. The effectiveness of oxygen transfer across the gills of dogfish was measured during normoxia and hypoxia, both before and after transection of the cardiac vagus nerves. Direct measurement of ventilation volume (\(\dot Vw\)) agreed with values calculated by the Fick technique. 2. Hypoxia caused a significant reduction in blood oxygen tension and content and in rate of oxygen consumption (\(\dot M_{O_2 }\)). There was a marked bradycardia accompanied by a compensatory increase in cardiac stroke volume (Table 1). The ventilation/perfusion ratio (\(\dot Vw/\dot Vb\)) increased due to an increase in respiratory stroke volume. % Extraction (% Ext) and effectiveness of transfer (Ew) of oxygen from water were maintained during hypoxia, possibly due to an increase in the transfer factor (\(T_{O_2 }\)). 3. Cardiac vagotomised fish showed an increase in normoxic heart rate accompanied by a decrease in cardiac stroke volume. There was no bradycardia during hypoxia. The absence of the bradycardia had no observable effect on the efficacy of oxygen transfer during hypoxia (Table 3). 4. Following cardiac vagotomy, the oxygen tension in the venous blood (\(P\bar v_{O_2 }\)) was reduced both during normoxia and hypoxia, and\(\dot Vw\) did not increase during hypoxia (Table 3). These differences were, however, apparent in sham-operated fish (Table 2). 5. The measured variables and derived values for effectiveness of oxygen transfer are compared with those described for other fish.

The effect of a decrease in salinity on respiration, Osmoregulation and activity in the shore crab,Carcinus maenas (L.) at different acclimation temperatures

1. The rates of oxygen consumption (\(\dot V_{{\text{O}}_2 } \)) of individual crabs varied with their live mass. Mean\(\dot V_{{\text{O}}_2 } \) increased with acclimation temperature in 100% seawater (Q10 2.36) but not in 50% seawater. 2. Exposure to 50% seawater caused a significant increase in\(\dot V_{{\text{O}}_2 } \) to twice the rate in 100% seawater at 10°C. There was no significant increase in\(\dot V_{{\text{O}}_2 } \) on dilution at 18°C (Fig. 5). 3. Heart rate, ventilation volume (\(\dot V\)) and a-VO2 content difference were unaffected by dilution. The rise in\(\dot V_{{\text{O}}_2 } \), following dilution at 10°C may, as far as the cardiovascular system is concerned, arise from an increase in cardiac stroke volume. 4. Crabs were isosmotic with 100% seawater at 10°C, 14°C and 18°C. In 50% seawater all crabs showed a significant reduction in blood osmolarity, though they maintained the ΔF.p. and Na+ concentration significantly above that of the medium. Crabs acclimated to 10°C maintained a significantly higher blood ΔF.p. and Na+ concentration in 50% seawater than crabs at 18°C (Fig. 6). 5. Crabs acclimated to 10°C were significantly more active after exposure to 50% seawater. There was no significant change in activity, following dilution, in crabs at 18°C (Fig. 7). 6. The variations in\(\dot V_{{\text{O}}_2 } \) with temperature and salinity seem to relate to the measured changes in patterns of osmoregulation and activity. At 10°CCarcinus osmoregulates more effectively than at 18°C and is hyperactive in low salinities, which may represent an avoidance reaction. At 18°C, the summer temperature, the crab tolerates internal dilution and is relatively quiescent.