Starling Mechanism Research Articles

Central and peripheral limitations to upright exercise in untrained cardiac transplant recipients.

Functional capacity and quality of life are subjectively improved after cardiac transplantation. However, the objective improvement in exercise tolerance after transplantation has been disappointing. The extent to which allograft diastolic dysfunction contributes to this exercise intolerance has not been defined. Thirty cardiac transplant recipients between 3 and 16 months after transplantation and 30 age-matched normal control subjects underwent maximal symptom-limited graded upright bicycle exercise testing with simultaneous radionuclide angiography, invasive hemodynamic monitoring, and breath-by-breath gas analysis. Mean blood pressure was higher in the transplant group at supine rest (112.1 versus 97.7 mm Hg), normalized with upright posture, and became lower than normal at peak exercise (121.1 versus 133.2 mm Hg). Systolic function as measured by ejection fraction was normal in both groups. However, the cardiac transplant recipients had significantly lower exercise tolerance, achieving a mean maximal work rate of 390 kilopond-meters per minute (kpm/min), compared with 825 kpm/min in the normal subjects. Peak oxygen consumption was 12.3 mL.min-1.kg-1 in the transplant group, 46% lower than the normal group's value of 22.9 mL.min-1.kg-1. The transplant patients had a resting tachycardia (94 beats per minute) and a 79% reduction in exercise heart rate reserve compared with normal. Despite this chronotropic incompetence, stroke index response to exercise was consistently lower after transplantation, accounting for a 41% reduction in cardiac index at maximal exercise. The lower stroke index was accompanied by a 32% lower end-diastolic volume index at rest and a 14% lower end-diastolic volume index at peak exercise. Despite the smaller ventricular volumes after transplantation, pulmonary capillary wedge pressure was 35% higher than normal at supine rest and 50% higher at maximal exercise. Right atrial and mean pulmonary arterial pressures were similarly elevated. The ratio of pulmonary capillary wedge pressure to end-diastolic volume index was significantly higher during the postural change and exercise, suggesting allograft diastolic dysfunction. Arteriovenous oxygen difference was similar between groups at rest and with submaximal exercise but was 24% lower at maximal exercise in the transplant group, suggesting an abnormality in peripheral oxygen uptake or utilization. Exercise tolerance is severely limited during the first 16 months after cardiac transplantation despite preservation of allograft left ventricular systolic function. This intolerance is due to an inadequate cardiac index response from a combination of chronotropic incompetence and diastolic dysfunction limiting the appropriate compensatory use of the Starling mechanism. In addition, there is a peripheral abnormality in oxygen transport or utilization that may partially reflect the effects of deconditioning.

Heart size and maximal cardiac output are limited by the pericardium.

We tested the hypothesis that the pericardium, by restricting heart size, limits maximal cardiac output and oxygen consumption. We studied 15 pigs. Five underwent maximal treadmill running before and 14-21 days after thoracotomy and pericardiectomy; these pigs also received sequential volume infusions to determine end-diastolic pressure-dimension relationships. Five underwent maximal treadmill running before and 14-21 days after thoracotomy (pericardium undisturbed) to determine the effect of thoracotomy on exercise performance. Finally, five underwent thoracotomy, instrumentation, loose closure of the pericardium, and sequential volume infusions to determine the effect of thoracotomy without pericardiectomy on end-diastolic pressure-dimension relationships. Pericardiectomy caused similar increases in maximal cardiac output (29% increase; P = 0.007) and maximal oxygen consumption (31% increase; P = 0.02). These results were associated with increased left ventricular end-diastolic dimension (10% increase; P = 0.01) and an estimated 33% increase in end-diastolic volume. In addition, left ventricular mass was increased by pericardiectomy (18% increase; P < 0.04). Thus the pericardium, by limiting utilization of the Starling mechanism, limits maximal cardiac output, and the limit to cardiorespiratory performance lies not in oxygen utilization, but in oxygen delivery. Furthermore, removal of pericardium is associated with myocardial hypertrophy.

Functional significance of the Frank-Starling mechanism under physiological and pathophysiological conditions.

The functional significance of the Frank-Starling mechanism under physiological and pathophysiological conditions is discussed, based mainly on animal experiment results (in the dog, pig and rat). The dependence of individual stroke volume on end-diastolic volume can be described adequately using Frank's diagram. This can be illustrated by varying filling pressure (respiratory cycle, vascular tone in the capacitance system, body position, circulating blood volume) and by alterations in the duration of the filling period (heart rate and rhythm, rate of relaxation) and in ventricular compliance (wall thickness, fibrosis; contracture, rigor). The functional importance of the Frank-Starling mechanism lies mainly in adapting left to right ventricular output. During upright physical exercise an increase in end-diastolic volume due to the action of the peripheral muscle pump and increased venous tone can assist in enhancing stroke volume. Reduced contractility leads to a shift of the operating point to the right in the pressure-volume diagram, thus tending to prevent a decrease in stroke volume. However, the consequences of increased circulating blood volume in chronic heart failure are, as a rule, mainly detrimental (congestive symptoms; myocardial component of coronary resistance; cardiac energetics). Reduced contractility results in a flattening of the relation between stroke volume (or stroke work) and end-diastolic volume. Furthermore, the Starling mechanism is prevented from becoming effective if the sarcomere-length reserve is exhausted, or in the presence of inadequate sarcomere extension due to impaired relaxation or reduced distensibility of the ventricular wall. The latter is illustrated using the example of a dilated fibrotic left ventricle from a rat with experimental supravalvular aortic stenosis.

Abdominal aortic aneurysm repair in a patient with a cardiac transplant

We describe successful elective abdominal aneurysm repair in a patient with a cardiac transplant. In light of the unique physiology and pharmacology of the denervated heart, this presented an unusual combination of complex problems. Whereas the normally innervated heart increases cardiac output via neural stimuli, the denervated heart relies primarily on the Frank Starling mechanism which is dependent on preload and myocardial contractility. Thus, rapidly changing haemodynamic variables associated with aortic cross-clamping require scrupulous attention to the maintenance of adequate preload as well as myocardial function which can only be manipulated by direct-acting agents. We conclude that the denervated heart will readily compensate for the haemodynamic changes brought about by infrarenal aortic crossclamping if a high-normal preload is maintained and if the transplanted donor heart is free of pathology with good inherent myocardial contractility.

Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure-dimension relation

To analyze left atrial (LA) pump function in normal subjects, in patients with essential hypertension and in patients with a healed myocardial infarction, LA dimension (aortic-root echogram) and pressure (catheter-tip manometer) were simultaneously recorded in 25 patients (8 normal subjects, 7 with hypertension and 10 with myocardial infarction). The pressure-dimension relation of the left atrium was composed of 2 loops: the A loop (expressing the pump function of the left atrium) and the V loop. LA dimension at the beginning of active LA shortening was significantly greater in hypertensive subjects (33 ± 3 mm) and in those with myocardial infarction (32 ± 4 mm) than in normal subjects (28 ± 3 mm) (p < 0.01, p < 0.05, respectively). The area of the A loop significantly increased in subjects with hypertension (48 ± 3 mm Hg · mm, p < 0.01) and in subjects with myocardial infarction (29 ± 10 mm Hg · mm, p < 0.05), compared with normal subjects (20 ± 8 mm Hg · mm). The mean fractional shortening velocity of the left atrium significantly increased in subjects with hypertension, compared with normal subjects and those with myocardial infarction (p < 0.05 for both). LA peak wall tension during the LA active contraction period significantly increased with hypertension and with myocardial infarction, compared with normal subjects (p < 0.01, p < 0.05, respectively). The area of the A loop was directly proportional to the LA dimension at the beginning of active LA shortening (r = 0.53), p < 0.01). The mean fractional shortening velocity of the left atrium was inversely correlated with the LA peak wall tension during the LA active contraction period (r = −0.44, p < 0.05). With hypertension, the relation between the mean shortening velocity and the peak wall tension of the left atrium shifted up and rightward. It is concluded that the augmented pump function of the left atrium in patients with a healed myocardial infarction is attributed to Starling's mechanism, whereas with hypertension the increased pump function of the left atrium may be attributed not only to Starling's effect, but also to the enhanced inotropic state of the left atrium.

Local and Global Function of the Right Ventricle in a Canine Model of Pulmonary Microembolism and Oleic Acid Edema

Right ventricular (RV) dysfunction may occur due to increased RV afterload and, hence, might also contribute to the decrease in cardiac output following institution of PEEP in patients with adult respiratory distress syndrome (ARDS). To test this hypothesis, the authors examined the influence of PEEP on local and global RV function in 12 anesthetized dogs with experimental ARDS (eARDS) induced by pulmonary microembolization with glass beads and oleic acid. Local RV function was analyzed in the RV inflow tract (RVIT) and RV outflow tract (RVOT) by assessing both diastolic segment length, systolic segment shortening, and segment work (sonomicrometry). Global RV contractility was quantified by measuring maximum rate of pressure rise (dRVP/dtmax) and maximum velocity of contractile element shortening (Vmax). In eARDS, despite a fivefold increase in pulmonary vascular resistance, there was no change in cardiac index (CI), global RV contractility, RVIT and RVOT work, and RVIT shortening, whereas RVOT shortening decreased from 12.4 to 7.4% (P less than 0.01). Diastolic segment length increased in RVIT (P less than 0.05) but not in RVOT. PEEP of 10 cmH2O did not alter global RV contractility, RVIT and RVOT shortening, and RVIT work but reduced RVOT work (-35%; P less than 0.01) and CI (-11%; P less than 0.001). Cardiac index further decreased during PEEP of 20 cmH2O (-38%; P less than 0.001), while global RV contractility remained intact despite decreased RVIT and RVOT shortening (-32% and -69%; P less than 0.05) and work (-26% and -59%; P less than 0.01) in the presence of reduced fiber preload in both regions. From these findings, it was concluded that 1) the decreased CI during mechanical ventilation with PEEP at constant right ventricular end-diastolic pressure (RVEDP) is not caused by depressed global RV contractility in dogs with eARDS and a normal myocardium prior to insult. Decreased diastolic segment length and segment shortening during PEEP suggest that 2) PEEP reduces stroke volume by the Starling mechanism rather than by ischemia of the RV free wall. Finally, regionally incongruent changes of fiber preload indicate that 3) local differences in RV wall compliance are likely to occur subsequent to eARDS and PEEP.

The effects of increasing mean arterial pressure on left ventricular output in newborn lambs.

We developed a preparation in which the mean arterial pressure of the newborn lamb is varied with little change in left ventricular preload. Seven lambs underwent balloon atrial septostomy and were instrumented with vascular catheters, an electromagnetic flow transducer on the aorta, and a balloon occluder on the aorta. Four different preload conditions were established by volume infusion or withdrawal. Aortic flow was measured continuously during gradual occlusion of the aorta. Curves relating mean left atrial pressure to stroke volume before balloon inflation showed a plateau, with little increase in stroke volume with increases in atrial pressure above 7 mm Hg. With balloon inflation, stroke volume decreased linearly with increases in mean arterial pressure. Curves relating left atrial pressure to stroke volume constructed at constant mean atrial pressure showed no plateau but showed continued increases in stroke volume as left atrial pressure was increased to 10 mmHg. When mean arterial pressure is constant, the Starling mechanism is operative in newborn left ventricles. The plateau in newborn lamb function curves is due to increases in mean arterial pressure that accompany volume infusion.

Ventricular energetics

Ventricular energetics

The regulation of the ratio of the cardiopulmonary blood volume to stroke volume in sheep

Volume expansion with dextran was used in unanaesthetised sheep to investigate the mechanisms which are responsible for keeping the ratio of the cardiopulmonary blood volume to stroke volume (CPFI) constant under physiological conditions. For animals with heart rates lower than 80, active pulmonary vasoconstriction was mainly responsible for the regulation obtained with volume expansion, while the Starling mechanism was responsible for keeping the ratio constant for animals with heart rates above 79. The involvement of a regulatory mechanism was shown by the absence of large changes in the CPFI after inducing mechanical stress on the cardiopulmonary system as a result of experimental hypertension. Results obtained with receptor blockade showed that active pulmonary vasoconstriction may be the result of a reflex mechanism with parasympathetic efferents. It is suggested that the receptors for this reflex are situated in the pulmonary arteries and are activated by the pressure changes as a result of heart contractions.

Ventricular interaction in a canine model of acute pulmonary hypertension and its modulation by vasoactive drugs

To determine the effect of a pulmonary glass bead embolism (GBE) upon left ventricular filling, we studied 13 dogs (seven with pericardium open, six with pericardium closed) before and after embolizing the pulmonary artery with sufficient glass beads to triple the pulmonary artery pressure. Furthermore, we examined the nature of the ventricular interaction and the effect upon hemodynamics created by intravenous nitroglycerin, dobutamine and hydralazine. Each dog was implanted with segment length crystals directed in the septal free wall plane of both ventricles, Millar catheters (Millar, Houston) placed in the right ventricle, left ventricle, and pulmonary artery (PA), and a thermodilution catheter placed in the PA. GBE reduced left ventricular end diastolic length (LVEDL) and stroke work, and shifted the left ventricular diastolic pressure-segment relationship (LVDPSR) upwards. The presence of a pericardium had little effect on the biventricular response to any of the test interventions. Nitroglycerin reduced right ventricular end diastolic length (RVEDL) and shifted the LVDPSR downwards. It did not increase LVEDL. Dobutamine increased left ventricular stroke work (LVSW) without altering LVEDL or the LVDPSR. Hydralazine did not change LVEDL, LVSW or shift LVDPSR. We conclude that GBE depresses left ventricular function by the Frank Starling mechanism and shifts the LVDPSR upwards. Because pericardiectomy die not prevent the decrease in LVEDL mediated by GBE, and nitroglycerin did not increase LVEDL despite decreasing RVEDL, a series interaction must dominate.

Pulmonary injury depresses cardiac systolic function through Starling mechanism.

To determine whether pulmonary microvascular injury or lung hyperinflation changes left ventricular (LV) performance and whether ventricular interaction plays a role in mediating such changes, we studied seven open-chest, closed-pericardium, anesthetized dogs before and after right ventricular (RV) injections of 150- to 200-micron glass beads. Because people with pulmonary disease are often treated with positive end-expiratory pressure, we also hyperinflated the lungs before and after creating the pulmonary microvascular injury. Measurements of LV and RV pressures and dimensions were taken at end expiration during the basal state, during lung hyperinflation, and after microvascular injury at RV end-diastolic pressures of 5, 10, and 15 mmHg produced by volume loading. Acute volume loading produced upward shifts in the LV diastolic pressure-size curve both before and after microvascular injury. Neither microvascular injury nor lung hyperinflation substantially affected the LV diastolic pressure-size relationship. LV end-diastolic size determined LV stroke work with no consistent independent influence of microvascular injury or lung hyperinflation. Neither microvascular injury nor lung hyperinflation depressed systolic performance beyond that associated with changes in end-diastolic heart size.

The effect of controlled changes in volume on the active state of the rabbit isolated left ventricle.

The contractile properties of isovolumically contracting isolated rabbit left ventricles are studied under the influence of controlled rapid volume changes during systole and diastole. The time integral of the pressure curve (TTI), representing the active state, is used to quantify the energy consumption of the ventricle. Steady state conditions resulting from an introduced volume change show a TTI/EDV relation which represents the Starling curve. However, immediately after a quick volume increase (decrease) introduced in diastole, the TTI/EDV ratio has a higher (lower) value than indicated by the Starling relation. This shows a volume dependent activation (deactivation), related to changes in the inotropic state of the heart muscle cells within the ventricular wall. A volume increase at a later moment (in systole) always produces a lower rate of activation. Indeed, if the rapid volume change is introduced at moments later than 70% of time to peak pressure, TTI is less than observed from the Starling mechanism, indicating a deactivation. When comparing the decreasing effect on the active state introduced by volume decrease during systole, it is shown that this effect is not only a function of the amplitude of the decrease itself but is highly dependent upon the way EDV is reached.

Immediate effects of diastolic loading variations on the left ventricular inotropic state in open chest dogs.

The influence of left ventricular filling and variations in end diastolic volume on cardiac performance was studied in the intact dog heart. Left ventricular filling volumes and stroke volumes were calculated on a beat to beat basis from measurements of natural mitral inflow and aortic outflow obtained by electromagnetic flow sensors. Instantaneous controlled modifications of end diastolic volume were performed through a cannula situated in the left ventricle and connected to a pump system outside the dog. This system enabled controlled increases or decreases of the end diastolic volume at any prechosen moment during the diastolic pause. Absolute volume variations in end diastolic volume and end systolic volumes could be calculated by combining the integrated flow signals from different consecutive beats. Left ventricular performance was evaluated in terms of end systolic volume and end systolic pressure variations. When the diastolic volume was abruptly increased by the pump system, natural mitral inflow decreased but end diastolic volume increased. The effect on diastolic pressure was dependent on the variation in filling rate, the amplitude of the infusion, the moment at which the infusion was started, and the diastolic pressure at the start of the infusion. Also stroke volume, maximal systolic pressure (Pmax), end systolic pressure, and end diastolic volume increased. The increased systolic performance was attributed to the increased end diastolic volume as expected according to Starling's law. When end diastolic volume was rapidly decreased during diastole by the pump, natural filling volumes increased to compensate for the volume loss by the pump. End diastolic volume was, however, smaller indicating that full compensation was not achieved. Evaluation of ventricular performance in terms of end systolic pressure and end systolic volume showed a decreased end systolic pressure and increased end systolic volume compared with the control values. The effect of a pump withdrawal was 1.62(0.38) times larger than could be explained on the basis of Starling's law. After the infusion of adrenaline the intrinsic depression disappeared and the influence of the volume withdrawal on cardiac performance was as expected from the Starling mechanism.

Integrative Nature and Time Course of Cardiovascular Alterations in the Diabetic Rat

Time-dependent alterations in integrated cardiovascular function were assessed in the streptozotocin-diabetic rat. Hemodynamic measurements in the intact, anesthetized animal revealed significant and progressive reduction in heart rate after 2, 4, and 8 weeks of diabetes. Myocardial contractility (+ dP/dt) and rate of relaxation (-dP/dt) were preserved at 2 weeks, but progressively declined thereafter. Integrative mechanisms maintained mean arterial blood pressure within normal limits at all time points. Pressure was regulated by minimizing cardiac output reduction via slight increases in stroke volume (Starling mechanism) and concomitant small increases in total peripheral resistance. In response to graded isoproterenol infusion and brief, total aortic occlusion, percent increase of heart rate and + dP/dt was maintained despite decrements in absolute values. Reduced peripheral vasodilation resulted in elevated sensitivity of the heart rate-blood pressure relationship during isoproterenol challenge. The -dP/dt was uniformly impaired in diabetic rats during isoproterenol infusion. When given a rapid saline infusion, diabetic hearts appropriately augmented volume output via the Starling mechanism. Initial hemodynamic abnormalities observed in the intact, diabetic rat are consistent with known defects in cardiac adrenergic receptor density, contractile protein ATPase activity, and sarcoplasmic reticulum calcium uptake. However, many cellular and subcellular defects are compensated by integrative hemodynamic mechanisms while latent alterations are observed only in the intact cardiovascular system.

Regulation of stroke volume during submaximal and maximal upright exercise in normal man.

To characterize the hemodynamic factors that regulate stroke volume during upright exercise in normal man, 24 asymptomatic male volunteers were evaluated by simultaneous right heart catheterization, radionuclide angiography, and expired gas analysis during staged upright bicycle exercise to exhaustion. From rest to peak exercise, oxygen consumption increased from 0.33 to 2.55 liters/min (7.7-fold), cardiac index increased from 3.0 to 9.7 liters/min per m2 (3.2-fold), and arteriovenous oxygen difference increased from 5.8 to 14.1 vol% (2.5-fold). The increase in cardiac index resulted from an increase in heart rate from 73 to 167 beats/min (2.5-fold), and an increase in left ventricular stroke volume index from 41 to 58 ml/m2 (1.4-fold). During low levels of exercise, there was a linear increase in cardiac index due to an increase in both heart rate and stroke volume index; stroke volume index increased as a result of an increase in left ventricular filling pressure and end-diastolic volume index and, to a much smaller extent, a decrease in end-systolic volume index. During high levels of exercise, further increases in cardiac index resulted entirely from an increase in heart rate, since stroke volume index increased no further. Left ventricular end-diastolic volume index decreased despite a linear increase in pulmonary artery wedge pressure; stroke volume index was maintained by a further decrease in end-systolic volume index. The degree to which stroke volume index increased during exercise in individuals correlated with the change in end-diastolic volume index (r = 0.66) but not with the change in end-systolic volume index (r = 0.07). Thus, the mechanism by which left ventricular stroke volume increases during upright exercise in man is dependent upon the changing relationship between heart rate, left ventricular filling, and left ventricular contractility. At low levels of exertion, an increase in left ventricular filling pressure and end-diastolic volume are important determinants of the stroke volume response through the Starling mechanism. At high levels of exertion, the exercise tachycardia is accompanied by a decrease in end-diastolic volume despite a progressive increase in filling pressure, so that stroke volume must be maintained by a decrease in end-systolic volume.

Alternating contractility in pulsus alternans studied in the isolated canine heart.

We examined pulsus alternans in seven isolated, perfused canine left ventricles ejecting into a simulated arterial impedance. Left ventricular pressure-volume loops were measured during pulsus alternans while filing-source pressure was lowered. In all cases two distinct linear end-systolic pressure-volume relationships (ESPVRs) were noted for the strong and weak beats. The slopes of the ESPVRs of the strong beats were significantly greater than those of the weak beats (mean difference 0.9 +/- 0.6 mm Hg/ml, p less than .01), while the intercepts were not significantly different (mean difference 0.06 +/- 0.5 ml). Diastolic pressure-volume relationships for the strong and weak beats were not significantly different, excluding incomplete relaxation as a cause of pulsus alternans. Although the weak beats had both a smaller preceding end-diastolic volume and a larger end-systolic volume, the presence of two distinct ESPVRS for the strong and weak beats shows there is alternating ventricular chamber contractility in pulsus alternans that is not solely due to the Starling mechanism. The magnitude of alternation in pump function parameters such as pressure and stroke volume during pulsus alternans reflects the complex interactions of alternating contractile state with alternations in preload and afterload.

Radionuclide ventriculographic responses to graded supine and upright exercise: Critical role of the Frank-starling mechanism at submaximal exercise

To assess the influence of work load and posture on the response to exercise, 25 patients with coronary artery disease (CAD) and 17 normal subjects underwent graded supine and upright exercise radionuclide ventriculography. In both groups, end-diastolic counts increased with supine exercise (p < 0.001). The ejection fraction and peak systolic pressure-end-systolic volume relation increased in normal subjects (p < 0.02), but not in patients with CAD. At upright rest, end-diastolic counts decreased in both groups (p < 0.001) and then increased with exercise ( p < 0.001). The increase in end-diastolic counts was most pronounced on the transition from upright rest to the 150-kpm work load and resulted in a significant increase in stroke counts (p < 0.05) for both patients with CAD and normal subjects, without a measurable change in the ejection fraction or the peak systolic pressure-end-systolic volume relation. Later in exercise, end-diastolic counts plateaued, and the ejection fraction and the peak systolic pressure, end-systolic volume relation increased only among normal subjects. Thus, lowlevel upright exercise is highly dependent on the Starling mechanism in both normal subjects and patients with CAD, with enhanced contractility apparent only during more vigorous exercise in normal subjects.

Blood flow measurements in the fetal descending aorta: technique and clinics.

A combination of two-dimensional and realtime pulsed-Doppler ultrasound provides a noninvasive method of measuring human fetal blood flow without side effects. By not altering the physiological conditions of the fetus, it minimizes external stimuli that might affect blood flow. However, due to the inaccessibility of the vessels under investigation, errors from the ultrasound technique arise and these are still being assessed. Studies of fetal blood flow suggest that the fetal circulation has a low peripheral resistance and that the increase in blood flow found with increasing gestational age is due predominantly to the increase in the actual dimensions of the fetal vasculature. Investigations in abnormal pregnancies, such as small-for-dates and those with cardiac arrhythmias have shown that the fetal cardiovascular system is capable of compensating efficiently to maintain normal physiological conditions, but only within the limits defined by the Frank Starling mechanism.

Left ventricular function at rest and during exercise in congenital complete heart block: A radionuclide angiographic evaluation

This study evaluates intrinsic cardiac performance during upright exercise in patients with congenital complete heart block. Left ventricular ejection fraction and volume were measured at rest and peak upright exercise with radionuclide angiography in 5 patients aged 11 to 39 years with congenital complete heart block: 4 were in New York Heart Association class I and 1 was in class II. The resting cardiac output was maintained at a normal level by an increase in end-diastolic volume rather than by a decrease in end-systolic volume. The left ventricular ejection fraction was normal at rest in all patients, but an abnormal response to exercise was noted in 3 patients. There was no appreciable change in the end-diastolic volume during exercise. Thus, patients with congenital complete heart block utilize the Starling mechanism to maintain normal resting cardiac output, but the response to exercise is usually abnormal even in the absence of symptoms.

Diastolic properties of the hypertrophied left ventricle in spontaneously hypertensive rats.

The influence of myocardial hypertrophy on left ventricular volume compliance was studied in vitro in isolated hearts of 4 and 19 month old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). In both SHR groups diastolic volume compliance was similar to that in the controls, despite the presence of left ventricular hypertrophy. This seems to be mainly due to an altered geometric situation, since with increased wall thickness to internal radius ratio (w/ri), which was at hand, the less are outer myocardial layers stretched at a given increase in ventricular volume. This may imply that these layers will only little interfere with luminal distension (and thereby with diastolic volume compliance) in SHR. It was also observed that the progressive increase of ventricular hypertrophy from 4 to 19 months of age did not further increase w/ri in SHR, indicating an increase in overall ventricular size with age. Left ventricular end diastolic pressure (LVEDP) was also measured in conscious 5 week and 4 month old SHR compared with matched controls. LVEDP increased with the development of hypertension and was significantly elevated in 4 month old SHR. This will increase also the average diastolic pre-stretch of the SHR left ventricle and mobilize the "Starling mechanism" to maintain a normal stroke volume against the increased afterload for the heart in established hypertension. This seems particularly important since the hypertrophic w/ri increase (about 20%) is smaller than the great elevation of mean arterial pressure (40-50%) in SHR.