Circulatory responses to a meal in patients with a newly transplanted heart.

It is well established that consumption of a meal releases a gradually developing and quite marked increase in blood flow to the gastrointestinal organs and a similar and simultaneous increase in cardiac output (CO). It is not known through which mechanism the pumping of the heart adjusts so accurately to the gastrointestinal flow increase. We have approached this problem by serving a standardized, mixed meal to five patients with recently transplanted and thus denervated hearts and to five sex- and age-matched controls. Pre- and postprandial levels of CO and blood flow in the superior mesenteric artery (SMA) were recorded with Doppler ultrasound technique. The patients with transplanted hearts had significantly higher preprandial levels of heart rate (HR) and CO than the controls. With a timing similar to that seen in the controls did all five patients develop considerable and synchronous postprandial increases in superior mesenteric arterial flow and in CO. Increases in superior mesenteric arterial flow were significantly greater than the controls. Also, COs, high even before meals were given, increased further and to the same relative extent as in the control persons. The marked postprandial increase in CO, probably secondary to the increase in intestinal blood flow, could hardly come about through any sort of nervous reflex to the recently transplanted and denervated hearts. It appears more likely that a humoral connection of some sort exists between the two circulatory events.

[Distribution of left ventricular output]. / Fordelingen av blodstrømmen fra venstre hjertekammer.

BACKGROUND: This survey focuses on distribution of cardiac output to various organs and on some dynamic changes occurring in cardiac output and its distribution. MATERIALS AND METHODS: Data presented are largely related to work carried out in our research group, where Doppler ultrasonography is widely used for measurement of cardiac output and arterial blood flow. Additional data are drawn from relevant literature, in part compiled through search in the PubMed database. DATA AND INTERPRETATIONS: The difference in blood flow to various organs is emphasised, with e.g. brain and endocrine organs receiving large and stable blood supplies, whereas inactive muscles are sparsely perfused. Attention is drawn to distribution patterns in situations where cardiac output is markedly increased. Such situations are muscular exercise, with a dramatic increase in muscle blood flow, the occurrence of bodily heat surplus, with increased skin blood flow, and the postprandial situation, with augmented blood flow to the gastrointestinal tract. Of particular interest are situations where two or more demands for increased blood supply occur simultaneously, such as muscular exercise in the period just after a meal. Physically trained persons are apparently better than others at maintaining gastrointestinal blood supply during exercise.

Involvement of the human splanchnic circulation in pressor response induced by handgrip contraction.

We have analysed the adjustment of blood flow and vascular conductance in the abundantly supplied splanchnic circulation to a generally released pressor reaction. Pressor responses were induced by 2-min periods of standardized, sustained handgrip in seven healthy students. The effects of handgrip tests were followed both in the fasting state and after the consumption of a substantial, mixed meal. In the first of the two sessions, changes in superior mesenteric artery blood flow were recorded and concomitant changes in local vascular conductance derived. In the other session, pressor released cardiac output changes were recorded and changes in total peripheral vascular conductance derived. Both types of flow changes were recorded using ultrasound Doppler technique. Typically, blood flow in the superior mesenteric artery increased two- to threefold after a meal. Handgrip contractions induced an initial rapid increase in heart rate, cardiac output and total peripheral conductance, followed by a gradual decline in total peripheral conductance and stroke volume and a gradual increase in heart rate and mean arterial pressure for the rest of the period. At the end of 2-min pressor periods, total peripheral conductance was only about 10% below the pre-handgrip level, whereas vascular conductance locally in the area of the superior mesenteric artery decreased by some 30%. Thus, it appears that the splanchnic vascular bed contributes markedly to the compound pressor response. Handgrips caused significantly less reduction in local vascular conductance in the post-prandial than in the pre-prandial state, indicating that blood flow to the digesting gastrointestinal tract retains a relatively high priority also in a pressor situation.

[Digestive system's large and changing needs of blood supply]. / Fordøyelseskanalens store og vekslende behov for blodtilførsel.

Doppler utrasonography has made it possible to record blood flow to the digestive tract (the superior mesenteric artery) directly and continuously in unanaesthetized, healthy humans. Several research groups have demonstrated how blood flow to the tract increases gradually and markedly after a meal, and more so after a big meal than after a small one. The increase in blood flow reaches its maximum after 20-40 minutes and lasts for 1.5-2 hours. In the postprandial period there is a parallel and similar increase in cardiac output; the meal thus imposes an increased work load on the heart. Carbohydrate meals, as well as meals of protein or fat all release increases in local blood flow as well as in cardiac output. Surprisingly, during physical exercise of relatively high intensity, there is no reduction in blood flow to the digestive tract in humans. This is in contrast to the exercise-caused flow reduction observed in several animal species. In the postprandial state the large increase in cardiac output caused by muscular exercise is actually added to the increase already established by the meal. This course of events helps to explain why patients with angina pectoris are more prone to chest pains after a meal.

Priority of blood flow to splanchnic organs in humans during pre- and post-meal exercise.

Cardiac output and superior mesenteric arterial flow in five healthy young men were followed using Doppler ultrasound techniques at rest and during 4 min bouts of bicycle exercise in both a pre- and a post-meal situation. The meal given was mixed and heavy, with an energy content (related to body size) of about 1400-1600 kcal (5.9-6.9 MJ). Two levels of exercise, 50-65 W and 150-200 W (about 75% of VO2max), were tested, with the subjects cycling in a reclining position. Superior mesenteric arterial flow increased threefold, to about 1.1 l min-1, after the meal. During exercise in the fasting situation there were only modest changes in splanchnic vascular conductance, and moderate increases in superior mesenteric arterial flow were actually recorded. Exercise in the post-prandial state caused appreciable reductions in splanchnic vascular conductance, and a 38% reduction was observed during the most heavy exercise. However, not even such a decrease in conductance resulted in any definite reduction in superior mesenteric arterial blood flow, which was maintained at the pre-exercise level. Cardiac output increased by about 1.3 l min-1 after the meal. The exercise-induced increases in cardiac output were of the same order in the fasting and in the post-prandial state. Variance analyses showed the high cardiac output levels reached during post-prandial exercise to be no different from levels that would be reached by pure summation of the changes caused by eating alone and by exercise alone. It is concluded that blood flow to the splanchnic organs in reclining man retains its high pre- and post-prandial priority during short exercise bouts of up to 75% of VO2max.

Post-prandial cardiovascular responses in man after ingestion of carbohydrate, protein or fat.

Changes in cardiac output and in superior mesenteric arterial flow were followed with Doppler ultrasound techniques in five young, healthy persons for 2 h after ingestion of medium-sized (4 MJ), fluid meals containing either carbohydrate, protein, fat or water only. Measurements were carried out before meals and at regular post-meal intervals, during which mean arterial blood pressure was also followed. All energy-containing meals caused marked and gradually developing post-prandial increases in cardiac output as well as in superior mesenteric arterial flow. The maximum flow levels were reached in the course of 30-60 min and maintained until the observations ended after 2 h. The intake of water caused no such flow increases. There were considerable interpersonal variations in the size and in the speed of development of the flow increases after the three types of energy-containing meals. The flow-increasing effects of the three meal types were not significantly different, even if the most marked increases (median values about 11 min-1 for both cardiac output and superior mesenteric arterial flow) occurred after carbohydrate meals. The marked effects on circulation of the three food components were also revealed in the calculated, integrated amounts of 'extra' cardiac output and superior mesenteric arterial flow observed in the course of the 2 h following the meal. Values of more than 100 1 for such 'extra' flows were seen after carbohydrate meals. The marked ingestion-released increase in blood flow to the splanchnic organs is apparently partly met by an increase in cardiac output, and partly by some redistribution of flow, which benefits the digestive system.

The effect of meal size on postprandial increase in cardiac output.

Heart rate, stroke volume, cardiac output and mean arterial blood pressure were followed from the resting pre-meal situation and for 2 hours after intake of standardized meals in four healthy individuals. Continuous records of stroke volume and cardiac output were achieved with an improved method of Doppler ultrasonography. A smallish meal and one 2 1/2 times larger were both given twice and in random order to each of the four test persons. The consumption of a meal invariably resulted in a cardiac output increase, which developed gradually to reach a maximum level 30 to 60 min after end of the meal. The postprandial cardiac output increase resulted from significant increases in both heart rate and stroke volume. There were distinct and significant differences between the circulatory responses to small and large meals. The increase in cardiac output after a large meal was considerably larger and lasted for longer than the increase after a small meal. Two hours after a small meal cardiac output was nearly or fully back to pre-meal values, while cardiac output was still markedly elevated 2 hours after a large meal. Consequently, the total 'extra' amount of blood delivered by the heart over 2 post-meal hours was significantly--about 100%--larger after the large meal than after the small one. Mean arterial blood pressure either fell or remained almost unchanged in the hour after a meal, so that total peripheral resistance was consistently and significantly reduced in the postprandial period--and considerably more so after a large meal than after a small one.

The effect of a meal on cardiac output in man at rest and during moderate exercise.

Cardiac output at rest increased by 11-63% in a group of healthy individuals after the consumption of a medium-sized, mixed meal. The maximum post-prandial levels of cardiac output were reached from 10 to 30 min after termination of the meal. Cardiac output values at rest fluctuate around a mean level, and this fluctuation was considerably more marked after a meal, when changes in cardiac output from one 15-s period to another could be of the order of 1-1.5 l min-1. Recording of flow in the superior mesenteric artery before and also after a meal was successful in two subjects in whom anatomical conditions were favourable. Flow in the artery was approximately doubled from the fasting to the post-prandial situation, an augmentation that accounted for about 50% of the concomitant increase in cardiac output. The increases in cardiac output caused by 2-min bouts of standardized, moderate and rhythmic exercise were consistently larger in the post-prandial than in the fasting situation. It thus appears that any tendency for redistribution of blood flow, for example from the gastrointestinal tract to the working muscles, during moderately intense exercise is less marked after a meal than before.

Dynamics and dimensions of cardiac output changes in humans at the onset and at the end of moderate rhythmic exercise.

1. An improved Doppler ultrasound technique was used to measure stroke volume (SV) and cardiac output (CO) on a beat-to-beat basis in a group of supine humans before, during and after periods of standardized, rhythmic exercise, involving the quadriceps muscle groups on both sides. The development of CO on such bouts of exercise was compared to Doppler ultrasound records of the simultaneous femoral arterial flow (FF) response. 2. Records of CO at rest revealed spontaneous fluctuations around a mean level, with differences between the minimal and maximal values of the order of 1 l min-1. The mean CO level at rest again varied considerably from one day to another and from test run to test run. 3. Upon start of exercise an immediate and rapid increase in heart rate (HR) and CO took place. The entire increase, the size of which varied appreciably from test run to test run, was completed within 10-15 s. No or only minor changes were seen in the mean SV level during the exercise periods. 4. The time course of the increase in FF was indistinguishable from that of the increase in CO, which occurred without any detectable delay relative to the changes in FF. These closely parallel developments indicate a tight regulatory coupling between the two types of flow changes. 5. In the majority of tests the total and two-sided increase in FF seen in the steady-state situation in the last part of an exercise period was significantly larger than the recorded increase in CO. This discrepancy implies that some redistribution of flow from tissues other than the working muscles might take place, even at this moderate level of work. 6. Upon the end of exercise a striking but transient increase in CO occurred, resulting from an increase in SV concomitant with a maintained HR. In the course of five to eight post-exercise cardiac cycles about 100 extra milliliters of blood were expelled from the heart. This cardiac outflow overshoot was found to occur during a post-exercise fall in mean arterial blood pressure (MAP).

On the existence of stretchable pores in the exchange vessels of the isolated rabbit lung preparation.

In the present work our aim has been to seek evidence for or against the existence of stretchable pores in the exchange vessels of the lungs. In isolated rabbit lungs ventilated by positive pressure and perfused with homologous blood we performed repeated tests with fluid filtration from the exchange vessels. In these tests the outflow pressure was elevated to specific values for periods of 6 min. The rate of weight gain of the preparation during the last 2 min of each test period was taken as the rate of fluid filtration from the exchange vessels. We found a linear relationship between rate of filtration and outflow pressure in the range from 5 to 20 mm Hg. This indicates that the hydraulic conductivity of the exchange vessels did not change with outflow pressure and thus that no pore stretching occurred within this pressure range. An abrupt increase in filtration rate took place when the outflow pressure was set at 25 or 30 mm Hg. The hydraulic conductivity of the exchange vessels was therefore probably increased at these high pressures. Since in 3 lungs this increase in filtration rate was fully reversible we suggest that a stretching of pores in the exchange vessels of the lungs contributed to the increase in hydraulic conductivity. This stretching of pores occurred only when vascular pressures were at or above the upper level of the physiological pressure range for the lungs.

Rabbit lung plasma and erythrocyte volumes. Lung hematocrit in relation to total body hematocrit.

The total body hematocrit has been reported to be 85--90% of packed cell volume (PCV) in several species. We have found similar values in rabbits. An "extra" plasma volume must exist somewhere in the vascular bed to explain this observation. We have looked for such an extra plasma volume in the pulmonary vasculature. The dynamic hematocrit was estimated in isolated, perfused rabbit lungs from distribution volumes for plasma and erythrocyte tracers. Estimation was also obtained from indicator-dilution curves using bolus-injections of such tracers avoiding their recirculation. It was thus possible to calculate mean transit times for the tracers from their dilution curves directly or applying monoexponential extrapolation from the first part of the downslope of the curves. The dynamic hematocrit of the lung vessels was about 94% of perfusate PCV and there was no difference between the results obtained by the different methods. We concluded that in the rabbit only a very small part of the extra plasma volume is located in the lung vessels. The lung plasma volume is not underestimated by the indicator-dilution technique.

Aggregation fo blood platelets and increased hydraulic conductivity of pulmonary exchange vessels.

Pulmonary microembolization secondary to platelet aggregation has been suggested to be a pathogenetic component of the shock lung syndrome. In vitro experiments have also shown that platelets can release factors with a permeability-enhancing activity. We studied the effect of collagen-induced platelet aggregation on the hydraulic conductivity of thexchange vessels in isolated, blood-perfused rabbit lungs. The net rate of fluid filtration in each pair of lungs was determined during standardized elevations of left atrial pressure before and after platelet aggregation induced by intraarterial collagen infusions. Such infusions were followed by a significant, but transient increase in the net rate of fluid filtration. These lungs were papaverinized so that collagen infusions caused only minor increases in inflow pressure. Separate experiments indicated that the observed increase in pulmonary arterial pressure could not explain the increase in net filtration rate after collagen infusion. When platelet-poor plasma was used as a perfusate no change in the net rate of fluid filtration was observed after collagen infusion. The conclusion from these experiments is then that intravascular platelet aggregation induced by collagen infusion caused a transient increase in the permeability of the pulmonary exchange vessels.

Interstitial fluid and transcapillary fluid balance in the lung.

Alterations in extravascular lung water content when capillary pressure or plasma colloid osmotic pressure is increased have been evaluated in isolated, continuously weighed, plasma-perfused pairs of rabbit lungs. After modest increases in left atrial pressure, most preparations rapidly reached a new stable weight, and thus a new transcapillary fluid balance, but no significant increase in extravascular lung water content could be detected. In preparations where there was still a steady, slow gain in weight and thus still some transvascular filtration of fluid 15 min after the increase in pressure, a moderate but significant increase in extravascular water could be detected. It is concluded that only very small transvascular shifts of fluid occur in the lungs when capillary pressure changes, as long as this change is kept below the level that causes oedema. This limitation of pressure-induced transvascular shifts of fluid in the lung could be explained by the existence, close to the capillaries, of a small interstitial space containing fluid with a high protein concentration. Alterations in the colloid osmotic pressure exerted by this fluid would then contribute markedly towards continuous readjustment of the transcapillary fluid balance in the lung. Experiments by other workers indicate that alveolar pressure can markedly affect the transcapillary fluid balance of the isolated perfused lung.

Pulmonary vasomotor nerve responses in isolated perfused lungs of Macaca mulatta and Papio species.

1. Lung lobes of Macaca mulatta and Papio species were isolated from the body and perfused by a pump delivering a constant volume inflow. The left atrial pressure was kept constant and therefore any recorded change in pulmonary arterial pressure reflected a change in pulmonary vascular resistance. 2. In five Macaca mulatta preparations stimulation of the upper thoracic sympathetic chain, the stellate ganglion, the middle cervical ganglion and the thoracic vagosympathetic nerve caused a small increase in calculated pulmonary vascular resistance usually followed by a larger decrease. Evidence is produced which suggests that the depressor response is mediated by adrenergic beta-receptors. In three preparations no change in pulmonary vascular resistance occurred. 3. In four Papio preparations stimulation of similar nerves invariably caused an increase in calculated pulmonary vascular resistance. In one animal no change in vascular resistance occurred. 4. A regression analysis of the results showed an inverse relationship between the magnitude of the pulmonary vascular response to nerve stimulation and the degree of excitement of the animals during capture, restraint and anaesthesia (P less than 0.01).

Interrelations between pulmonary liquid volumes and lung compliance.

We have investigated the relative effects of lung edema and of increases in pulmonary blood volume (PBV) on lung compliance (CL), and also the effects of selective elevations of pulmonary arterial (Ppa) and left atrial (Pla) pressures on PBV and on CL, using an isolated, perfused, and ventilated rabbit lung preparation. Lung weight was continuously recorded. A step rise in Pla at constant flow caused a rapid rise in PBV accompanied by an immediate fall in CL. With maintained high vascular pressures interstitial edema accumulated with no further fall in CL. Not until 3 times the normal amount of extra-vascular fluid had accumulated did a further, secondary reduction in CL occur. When Ppa was elevated to the same level by 1) a rise in flow and 2) a rise in Pla, the latter type of experiment gave 3-5 times larger increases in PBV. Pla elevations with or without rise in Ppa (flow adjusted) gave almost the same rises in PBV. The fall in CL was related to rises in PBV regardless of how such rises were obtained. Our conclusion is that increases in PBV, but not accumulation of interstitial edema, reduced CL in this preparation.