Performance of the isolated and perfused working heart of the teleostConger conger: study of the inotropic effect of prostacyclin

Summary An in vitro preparation of the heart of the teleostConger conger, isolated without the pericardium, was set up. The procedure allowed subambient pressures to develop in the perfusion chamber during contraction, mimicking the in vivo situation with the pericardium intact. The ventricle produced a cardiac output of about 15 ml·min^-1·kg wet body weight^-1 at subambient input pressure, and was able to double the stroke work with an increase of preload up to about 0.2 kPa. Using this preparation it was found that prostacyclin has a positive inotropic effect on the atrium and ventricle, but it does not affect the heart rate. Semilogarithmic doseresponse curves of prostacyclin on the atrium are reported, showing a threshold concentration of about 10^-9 M. The isolated and perfusedConger conger heart provides a useful model for a detailed analysis of the action of prostacyclin on myocardial contractility.     

The pericardium facilitates pressure work in the eel heart

An in siru perfused eel (Anguilla dieffenbachü) Gray 1842) heart was used to investigate the role of the pericardium in cardiac function. Hearts with intact pericardia were compared with hearts in which the pericardia were either punctured or opened completely. Cardiac function was assessed at low and high adrenaline levels by determining: maximum cardiac output; maximum sustainable output pressure; power output under maximal filling and output pressures; and maximum power output. Puncturing a small hole in the pericardium equalizing ambient and intrapericardial pressures had little effect on cardiac function and performance. Opening the pericardium, thereby fully exposing the chambers of the heart, severely limited the heart's ability to do pressure work. This effect was reversed at high adrenaline concentrations. Flow related work, and maximum power output levels were maintained after opening the pericardium.     

Role of creatine phosphokinase in the energy supply of the pumping function of the heart]

The cardiac output of isolated working rat heart and left ventricular pressure were estimated in either almost complete inhibition of creatine kinase by iodoacetamide or predominant fall in adenine nucleotides (AdN) content induced by 2-deoxyglucose treatment. In the former case, a profound cardiac pump failure was observed despite almost normal levels of myocardial AdN and phosphocreatine. Those hearts could not maintain the aortic output at standard load due to lower LV systolic pressure, that was accompanied by increased minimal and maximal diastolic pressures by 5-7 mm Hg as well as by LV diastolic stiffness. As LV systolic pressure in those hearts was unchanged in retrogradely perfused and unloaded hearts it might be suggested that the cardiac pump failure was caused by the decreased LV distensibility. On the contrary, deoxyglucose treatment that resulted in 70% fall in the AdN content was accompanied by only moderate reduction of the cardiac output and insignificant changes in LV diastolic pressure and stiffness. The results suggested that creatine kinase plays a crucial role in the maintenance of normal myofibrillar compliance, which is necessary for cardiac filling and pump function.     

Mechanisms responsible for the enhanced pumping capacity of the in situ winter flounder heart (Pseudopleuronectes americanus)

In situ Starling and power output curves and in vitro pressure-volume curves were determined for winter flounder hearts, as well as the hearts of two other teleosts (Atlantic salmon and cod). In situ maximum cardiac output was not different between the three species (approximately 62 ml.min(-1).kg(-1)). However, because of the small size of the flounder heart, maximum stroke volume per milliliter per gram ventricle was significantly greater (2.3) compared with cod (1.7) and salmon (1.4) and is the highest reported for teleosts. The maximum power output of the flounder heart (7.6 mW/g) was significantly lower than that measured in the salmon (9.7) and similar to the cod (7.8) but was achieved at a much lower output pressure (4.9 vs. 8.0 and 6.2 kPa, respectively). Although the flounder heart could not perform resting levels of cardiac function at subambient pressures, it was much more sensitive to filling pressure, a finding supported by pressure-volume curves, which showed that the flounder's heart chambers were more compliant. Finally, we report that the flounder's bulbus:ventricle mass ratio (0.59) was significantly higher than in the cod (0.37) and salmon (0.22). These data, which support previous studies suggesting that the flatfish cardiovascular system is a high-volume, low-pressure design, show that vis-à-fronte filling is not important in flatfish, and that some fish can achieve high levels of cardiac output by vis-à-tergo filling alone; and suggest that a large compliant bulbus assists the flounder heart in delivering extremely large stroke volumes at pressures that do not become limiting.     

Acidaemia reduces cardiac output and left ventricular contractility in conscious lambs

We studied the effects of HCI-induced metabolic acidaemia on cardiac output, contractile function, myocardial blood flow, and myocardial oxygen consumption in nine unanaesthetized newborn lambs. Through a left thoracotomy, catheters were placed in the aorta, left atrium and coronary sinus. A pressure transducer was placed in the left ventricle. Three to four days after surgery, we measured cardiac output, dP/dt, left ventricular end diastolic and aortic mean blood pressures, heart rate, aortic and coronary sinus blood oxygen contents, and left ventricular myocardial blood flow during a control period, during metabolic acidaemia, and after the aortic pH was restored to normal. We calculated systemic vascular resistance, myocardial oxygen consumption and left ventricular work. Acidaemia was associated with reduction in cardiac output, maximal dP/dt, and aortic mean blood pressure. Left ventricular end diastolic pressure and systemic vascular resistance increased, and heart rate did not change significantly. The reduction in myocardial blood flow and oxygen consumption was accompanied by fall in cardiac work. Cardiac output returned to control levels after the pH had been normalized but maximal dP/dt was incompletely restored. Myocardial blood flow and oxygen consumption increased beyond control levels. This study demonstrates that HCI-induced metabolic acidaemia in conscious newborn lambs is associated with a reduction in cardiac output which could have been mediated by the reduction in contractile function and/or the increase in systemic vascular resistance. The decreases in myocardial blood flow and oxygen consumption appear to reflect diminished cardiac work. The restoration of a normal cardiac output after normalization of the pH appears to have resulted from the increases in heart rate and left ventricular filling pressures in conjunction with an incomplete restoration of contractile function.     

Hemodynamic effects of anti-G suit inflation in a 1-G environment

This study evaluated effects of various anti-G inflation pressures on cardiac volumes and the relationship of these volume changes to mean arterial pressure changes. Ventricular volumes were calculated using two-dimensional echocardiography. An anti-G suit was inflated to 2, 4, and 6 psi in the standing and supine positions for 10 male subjects. In the supine position, mean arterial pressure increased from base line for all three inflation pressures (P = 0.05). The end-diastolic volume increased after 2-psi inflation (P = 0.03). Cardiac output or stroke volume did not change. After standing, mean arterial pressure (P = 0.002), end-diastolic volume (P = 0.002), and stroke volume (P = 0.05) fell after suit deflation. Peripheral vascular resistance fell in the 2- and 4-psi inflation profiles. In the standing protocol, mean arterial pressure, end-diastolic volume, stroke volume, and cardiac output rose with all three inflation pressures (P less than 0.05). After reclining, heart rate increased (P = 0.02) and mean arterial pressure fell (P less than 0.05) in the 4- and 6-psi inflation profiles after suit deflation. Increases in mean arterial pressure are caused by increases in cardiac preload and cardiac output after inflation of the anti-G suit while subjects were standing. Increased cardiac preload was not consistently seen after inflation while subjects were supine. Changes in end-diastolic volume and mean arterial pressure were dependent on the pressure used to inflate the anti-G suit.     

Haemodynamic effects of beta-adrenergic blockade in hyperthyroid patients with and without heart failure.

Haemodynamic studies were performed in 10 patients with uncomplicated thyrotoxicosis and seven with thyrotoxic cardiac failure. The cardiac output of those with uncomplicated hyperthyroidism was higher than normal at rest. After 2 mg of intravenous propranolol there was a 13% fall but the level was still higher than normal. In patients with thyrotoxic cardiac failure the resting cardiac output was normal, but it fell after propranolol by 30% to subnormal levels. In both groups there was an increase in right heart pressures and fall in the rate of increase in arterial pressure, which indicated a decrease in myocardial contractility. These results indicate that increased autonomic activity is a compensatory phenomenon in hyperthyroid heart failure and that its abolition by beta-blocking drugs has a deleterious effect on cardiac function. They are therefore contraindicated in patients with thyrotoxic heart failure.     

Cardiac performance of an isolated eel heart: effects of hypoxia and responses to coronary artery perfusion.

The pericardial sac containing the heart was removed from large (2.7-6.3 kg) long-finned eels (Anguilla dieffenbachii). Coronary arteries were cannulated in preparation for perfusion with eel Ringer or red cell suspensions. The hearts were maintained by Ringer perfusion while the performance of the heart was assessed. Responses of the hearts to increases in filling pressure and output pressure were recorded. Maximum cardiac output was 22.3 +/- 1.4 ml/min/kg body mass (mean +/- 1 SEM; N = 9). The highest cardiac power output was measured at maximum cardiac output and was 3.39 +/- 0.32 mW/g ventricle mass (mean +/- 1 SEM; N = 9). Eel hearts could sustain output pressures near 80 cm H2O, but cardiac output was reduced and cardiac power output was 1.89 +/- 0.24 mW/g ventricular mass (mean +/- 1 SEM; N = 9). Maximum cardiac output decreased by 14% when hearts pumped hypoxic Ringer with a PO2 of 11.5 torr. At high input pressures concomitant with high output pressures (80 cm H2O), cardiac power output decreased by 38% upon exposure to hypoxic Ringer. Coronary perfusion of hypoxic hearts with red cell suspensions (mean hematocrit 10.4%) at a rate of 2% of control cardiac output (0.20 ml/min/kg body mass) had no effect on maximum cardiac output. However, coronary perfusion enabled hypoxic hearts to maintain cardiac output when output pressure was raised to 80 cm H2O. Under conditions of high input pressure and high output pressure, power output increased by 20% compared to hypoxic hearts without coronary perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transcapillary fluid shifts in tissues of the head and neck during and after simulated microgravity.

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head-down for 8 h, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.7 +/- 1.5 mmHg (mean +/- SE) pre-HDT to 33.9 +/- 1.7 mmHg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, whereas interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressure dropped significantly by 4 h of HDT (21.5 +/- 1.5 mmHg pre-HDT to 18.2 +/- 1.9 mmHg), suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 h of seated recovery from HDT, microvascular pressures in the lip (capillary and venule pressures) remained significantly elevated by 5-8 mmHg above baseline values. During HDT, urine output was 126.5 ml/h compared with 46.7 ml/h during the control baseline period. These results suggest that facial edema resulting from HDT is caused primarily by elevated capillary pressures and decreased plasma colloid osmotic pressures. The negativity of interstitial fluid pressures above heart level also has implications for maintenance of tissue fluid balance in upright posture.     

The pericardium and cardiac transmural filling pressure in the fetal sheep

Fetal pericardial physiology may be important for understanding normal and abnormal circulatory states. Right atrial, pericardial, thoracic, and amniotic fluid pressures were measured simultaneously in chronically-instrumented, near-term fetal sheep. Fourteen experiments were performed in 8 fetuses 4-21 days after surgery. The pressure gradient from the right atrium to the amniotic fluid and its components (transatrial, transpericardial and transthoracic pressures) were measured during control and with rapid infusion and withdrawal of blood. Under control conditions, right atrial minus amniotic pressure was 3.2 +/- 1.8 (SD) torr, right atrial minus pericardial pressure 2.5 +/- 1.7, pericardial minus thoracic pressure 0.6 +/- 0.7, and thoracic minus amniotic pressure 0.1 +/- 1.4. At right atrial pressures above control, pericardial minus thoracic pressure rose linearly with right atrial minus thoracic pressure. The average regression coefficient was 0.50 with an intercept of -1.5 torr. Administration of dextran-saline solution (121% of estimated blood volume) over 2-4 hs in 10 experiments did not reduce the pericardial minus thoracic to right atrial minus thoracic pressure relationship. Fluid added to the pericardium of three lambs progressively shifted the pericardial minus thoracic to right atrial minus thoracic pressure relationship up and to the left. The pericardial minus thoracic to right atrial minus thoracic pressure relationship was unaffected by fetal growth. Thus, the fetal pericardium affects cardiac filling pressures. The affect of the pericardium is increased markedly by pericardial liquid but is unchanged during growth.     

Determinants of intrapericardial pressure in dogs

This study investigates factors that influence the pressure measured in the intrapericardial (IP) space. Seven dogs were studied after they were anesthetized with pentobarbital sodium. With the chest closed, intravascular volume expansion by dextran infusion from a mean left atrial (LA) transmural pressure of 8.4 +/- 1.2 (SD) to 15.5 +/- 1.6 Torr caused an increase in mean IP of from 2.6 +/- 1.2 to 3.9 +/- 1.7 Torr (P less than 0.01). This reflected a predominant increase in the influence of the cardiac fossa (CF), which accounted for 56% of the IP pressure after volume expansion. In the open-chest state an increase in mean LA transmural pressure from 9.5 +/- 2.5 to 16.4 +/- 0.6 Torr caused IP pressure to increase from 1.1 +/- 0.9 to 3.0 +/- 1.6 (P less than 0.005), representing the influence of the elastic pericardium alone. The use of positive end-expiratory pressure (PEEP) significantly increased the influence of the CF. Of note, the relation of LA to right atrial (RA) pressure was significantly different with and without the influence of the CF; the RA-to-LA ratio was higher with the chest open under each set of volume conditions with and without PEEP. In four dogs, acute transection of the pericardiodiaphragmatic ligaments led to a small (1-2 Torr) but distinct drop in IP pressure. Thus, IP pressure is affected by the intracardiac volume, the elastic pericardium, the CF, and the pericardiodiaphragmatic attachments, all of which must be considered in an analysis of diastolic properties of the heart in situ.     

Cardiovascular and neuroendocrine responses to left lateral position in non-obese young males

Previous results from our laboratory indicate that the heart is distended by the left lateral position (LAT) compared to horizontal supine (SUP). We therefore tested the hypothesis that cardiac output is increased by LAT and that mean arterial pressure is maintained unchanged or even decreased through peripheral vasodilatation induced by cardiopulmonary low-pressure receptor stimulation. Twelve non-obese young males were investigated. The location of the mid-aorta between the aortic valves was used as the hydrostatic reference point for the arterial pressure measurements. It was determined by magnetic resonance (n=6) to be 7.0 +/- 0.2 cm below the sternum in SUP (1/3 of anteroposterior chest diameter below the sternum) and 2.5 +/- 0.2 cm below the midsternal level in LAT. Brachial mean (auscultation) and finger mean arterial pressures (infrared photoplethysmography), cardiac output (foreign gas rebreathing), heart rate, and plasma concentrations (n=6) of vasoactive hormones were unchanged by LAT. In conclusion, cardiac output, mean arterial pressures, and vasoactive hormone releases were unaffected by 30 min of LAT. Furthermore, the hydrostatic reference points for arterial pressure measurements is located one third of the antero-posterior chest diameter below the sternum in SUP and 2.5 cm below the midsternal level in LAT in non-obese young males.     

A 2D FE model of the heart demonstrates the role of the pericardium in ventricular deformation

During pulmonary artery constriction (PAC), an experimental model of acute right ventricular (RV) pressure overload, the interventricular septum flattens and inverts. Finite element (FE) analysis has shown that the septum is subject to axial compression and bending when so deformed. This study examines the effects of acute PAC on the left ventricular (LV) free wall and the role the pericardium may play in these effects. In eight open-chest anesthetized dogs, LV, RV, aortic, and pericardial pressures were recorded under control conditions and with PAC. Model dimensions were derived from two-dimensional echocardiography minor-axis images of the heart. At control (pericardium closed), FE analysis showed that the septum was concave to the LV; stresses in the LV, RV, and septum were low; and the pericardium was subject to circumferential tension. With PAC, RV end-diastolic pressure exceeded LV pressure and the septum inverted. Compressive stresses developed circumferentially in the septum out to the RV insertion points, forming an arch-like pattern. Sharp bending occurred near the insertion points, accompanied by flattening of the LV free wall. With the pericardium open, the deformations and stresses were different. The RV became much larger, especially with PAC. With PAC, the arch-like circumferential stresses still developed in the septum, but their magnitudes were reduced, compared with the pericardium-closed case. There was no free wall inversion and flattening was less. From these FE results, the pericardium has a significant influence on the structural behavior of the septum and the LV and RV free walls. Furthermore, the deformation of the heart is dependent on whether the pericardium is open or closed.     

Role of beta-adrenergic agonists in the control of vascular capacitance

The role of beta-adrenergic agonists, such as isoproterenol, on vascular capacitance is unclear. Some investigators have suggested that isoproterenol causes a net transfer of blood to the chest from the splanchnic bed. We tested this hypothesis in dogs by measuring liver thickness, cardiac output, cardiopulmonary blood volume, mean circulatory filling pressure, portal venous, central venous, pulmonary arterial, and systemic arterial pressures while infusing norepinephrine (2.6 micrograms.min-1.kg-1), or isoproterenol (2.0 micrograms.min-1.kg-1), or histamine (4 micrograms.min-1.kg-1), or a combination of histamine and isoproterenol. Norepinephrine (an alpha- and beta 1-adrenergic agonist) decreased hepatic thickness and increased mean circulatory filling pressure, cardiac output, cardiopulmonary blood volume, total peripheral resistance, and systemic arterial and portal pressures. Isoproterenol increased cardiac output and decreased total peripheral resistance, but it had little effect on liver thickness or mean circulatory filling pressure and did not increase the cardiopulmonary blood volume or central venous pressure. Histamine caused a marked increase in portal pressure and liver thickness and decreased cardiac output, but it had little effect on the estimated mean circulatory filling pressure. Isoproterenol during histamine infusions reduced histamine-induced portal hypertension, reduced liver size, and increased cardiac output. We conclude that the beta-adrenergic agonist, isoproterenol, has little influence on vascular capacitance or liver volume of dogs, unless the hepatic outflow resistance is elevated by agents such as histamine.     

Right ventricular function in acute myocardial ischaemia

A haemodynamic examination of 10 dogs was carried out at rest, during volume loading and after ligation of the right coronary artery in the presence of a closed pericardium. Ligation of the right coronary artery led to haemodynamic signs of depression of right ventricular function--a drop in systolic pressure and an increase in end diastolic pressure, together with a shift of the functional curve to the right and downwards. Overall performance of the heart (cardiac output and the mean systemic pressure, also fell. Our results show that the depression of the systolic function of the myocardium in the presence of right ventricular infarction can be an important factor in the genesis of low cardiac output syndrome observed in clinical situations. Its pathophysiological mechanisms and some of the clinical consequences are discussed.     

Pericardium modulates left and right ventricular stroke volumes to compensate for sudden changes in atrial volume

The pericardium may modulate acute compensatory changes in stroke volumes seen with sudden changes in cardiac volume, but such a mechanism has never been clearly demonstrated. In eight open-chest dogs, we measured left and right ventricular pressures, diameters, stroke volumes, and pericardial pressures during rapid (approximately 300 ms) systolic infusions or withdrawals of approximately 25 ml blood into and out of the left atrium and right atrium. Control beats, the infusion/withdrawal beat, and 4-10 subsequent beats were studied. With infusions, ipsilateral ventricular end-diastolic transmural pressure, diameter, and stroke volume increased. With the pericardium closed, there was a compensatory decrease in contralateral transmural pressure, diameter, and stroke volume, mediated by opposite changes in transmural end-diastolic pressures. The sum of the ipsilateral increase and contralateral decrease in stroke volume approximated the infused volume. Corresponding changes were seen with blood withdrawals. This direct ventricular interaction was diminished when pericardial pressure was <5 mmHg and absent when the pericardium was opened. Pericardial constraint appears essential for immediate biventricular compensatory responses to acute atrial volume changes.     

A method for calculation of human systolic and diastolic blood pressures using an elastic reservoir theory of the systemic arterial system,and some clinical and physiological applications

Two equations have been developed that describe the interrelationship of the clinically measurable variables of the human systemic arterial system. An approximation method is given for their simultaneous solution for systolic and diastolic pressures in terms of heart rate, cardiac output, total peripheral resistance, and aortic distensibility. In this way, blood pressures were calculated for various clinically important and didactically useful situations. The effects on systolic and diastolic pressures due to changing either cardiac output or peripheral resistance or heart rate or aortic distensibility alone are shown. The effects on pulse pressure of varying cardiac output and peripheral resistance while holding mean arterial pressure constant are demonstrated. Compensatory mechanisms in hypertension and exercise are explored. Opinions and conclusions contained in this report are those of the author. They are not to be construed as necessarily reflecting the views or the endorsement of the Navy Department.     

Effects of positive end-expiratory pressure on the right ventricle

Transmural cardiac pressures, stroke volume, right ventricular volume, and lung water content were measured in normal dogs and in dogs with oleic acid-induced pulmonary edema (PE) maintained on positive-pressure ventilation. Measurements were performed prior to and following application of 20 cmH2O positive end-expiratory pressure (PEEP). Colloid fluid was given during PEEP for ventricular volume expansion before and after the oleic acid administration. PEEP significantly increased pleural pressure and pulmonary vascular resistance but decreased right ventricular volume, stroke volume, and mean arterial pressure in both normal and PE dogs. Although the fluid infusion during PEEP raised right ventricular diastolic volumes to the pre-PEEP level, the stroke volumes did not significantly increase in either normal dogs or the PE dogs. The fluid infusion, however, significantly increased the lung water content in the PE dogs. Following discontinuation of PEEP, mean arterial pressure, cardiac output, and stroke volume significantly increased, and heart rate did not change. The failure of the stroke volume to increase despite significant right ventricular volume augmentation during PEEP indicates that positive-pressure ventilation with 20 cmH2O PEEP decreases right ventricular function.     

Cardiac function of the leopard shark,Triakis semifasciata

Summary The pressure difference between the cardinal sinus and the pericardium, and the transmural ventricular diastolic pressure at rest and during swimming in the leopard shark, Triakis semifasciata, was measured to characterize the mechanism of cardiac filling in chronically-instrumented fish and to evaluate cardiac responses to swimming. Echo-Doppler and radiographic imaging were also used to fully describe the cardiac cycle. Swimming induces an increase in preload as manifested by a large increment of cardinal sinus pressure (0.26/0.20 [systolic/diastolic] to 0.49/0.32 kPa) which always exceeds pericardial pressure. Increases in both mean ventricular diastolic transmural pressure (0.30–0.77 kPa) and cardinal sinus pressure during swimming suggest increased cardiac filling by vis a tergo as the mechanism for augmenting cardiac output. In contrast to mammals, the fluid-filled pericardial space of elasmobranchs is considerably larger and the pericardium itself does not move in concert with the heart throughout the cardiac cycle. Also, modest increases in heart rate drastically curtail the duration of diastole, which becomes much less than that of systole, a phenomenon not found in mammals. In the absence of tachycardia (<40 bpm), ventricular filling is characterized by a period of early rapid filling, and a late period of filling owing to atrial systole, separated by a period of diastasis. Ventricular filling in elasmobranchs is thus biphasic and is not solely dependent on atrial systole. Atrial diastole is characterized by three filling periods associated with atrial relaxation, ventricular ejection, and sinus venosus contraction. The estimated ventricular ejection fraction of Triakis (80%) exceeds that of the mammalian left ventricle.     

Effect of exercise on blood flow through the aortic valve: a combined clinical and numerical study

The aim of this study was to measure the cardiac output and stroke volume for a healthy subject by coupling an echocardiogram Doppler (echo-Doppler) method with a fluid–structure interaction (FSI) simulation at rest and during exercise. Blood flow through aortic valve was measured by Doppler flow echocardiography. Aortic valve geometry was calculated by echocardiographic imaging. An FSI simulation was performed, using an arbitrary Lagrangian–Eulerian mesh. Boundary conditions were defined by pressure loads on ventricular and aortic sides. Pressure loads applied brachial pressures with (stage 1) and without (stage 2) differences between brachial, central and left ventricular pressures. FSI results for cardiac output were 15.4% lower than Doppler results for stage 1 (r = 0.999). This difference increased to 22.3% for stage 2. FSI results for stroke volume were undervalued by 15.3% when compared to Doppler results at stage 1 and 26.2% at stage 2 (r = 0.94). The predicted mean backflow of blood was 4.6%. Our results show that numerical methods can be combined with clinical measurements to provide good estimates of patient-specific cardiac output and stroke volume at different heart rates.