Management of adults with congenital bidirectional cardiac shunts,cyanosis, and pulmonary vascular obstruction: Successful operative repair in 3 patients

Patients with congenital cardiac shunts in whom marked functional disability, cyanosis and pulmonary arterial hypertension develop have been considered inoperable or at exceedingly high risk. Three adult patients, 2 with atrial septal defect (ASD) and 1 with patent ductus arteriosus (PDA), presented with New York Heart Association class IV symptoms, bidirectional shunting with cyanosis, polycythemia, severe pulmonary hypertension, and increased pulmonary vascular resistance. Pulmonary arterial pressure did not decrease in response to administration of 100% oxygen in any patient, and 2 had lung biopsy results showing advanced pulmonary vascular obstruction. While a right-to-left shunt caused cyanosis in all patients, the net shunt was left to right ($\text{Q}{}_{\mathrm{p}}\text{Q}{}_{\mathrm{s}}\text{> 1}$) and the resistance ratio $\text{(}\text{R}{}_{\mathrm{p}}\text{R}{}_{\mathrm{s}}\text{) <0.5}$. All 3 patients survived operation, became acyanotic with normal hematocrit, and are in functional class I or II a mean of 36 months post-operatively. At repeat cardiac catheterization, pulmonary arterial pressure and resistance had decreased substantially.This high-risk group of patients with bidirectional shunts, in whom cyanosis due to pulmonary vascular obstruction and polycythemia develop and who appear to be at very high operative risk, should still be considered for surgical correction if the usual criteria for operability exist: net left-to-right $\text{Q}{}_{\mathrm{p}}\text{Q}{}_{\mathrm{s}}$ and $\text{R}{}_{\mathrm{p}}\text{R}{}_{\mathrm{s}}\text{<0.50}$.     

Hemodynamics in endomyocardial fibrosis

Nine patients with endomyocardial fibrosis have been studied. The clinical diagnosis was confirmed by right ventricular angiography in all of them. They were submitted to right and left ventricular catheterization and had the cardiac pressures, the pulmonary arteriolar resistance, and the cardiac index measured. The ratio between the end-diastolic and systolic ventricular pressures has been taken as an index of the degree of impairment to ventricular filling, and, based on this, patients were classified into two groups: I, predominant or isolated right ventricular disease (seven patients); and II, predominant left ventricular disease (two patients).Group I patients were characterized by a right ventricular $\text{D}{}_2\text{S}$ ratio above 60 per cent, severe tricuspid regurgitation, a diastolic pulmonary artery pressure slightly lower than the right ventricular plateau and end-diastolic pressures, and a reversal of the gradient between the left ventricular end-diastolic pressure and the right atrial mean pressure; these two latter findings strongly suggesting a diastolic blood flow between the right atrium and the left ventricle.The two patients in Group II did not show evidences suggestive of tricuspid regurgitation or of an early opening of the pulmonic valve. Even presenting high values for the left ventricular $\text{D}{}_2\text{S}$ ratio, the pulmonary arteriolar resistance was normal in one patient and mildly elevated in the other patient.     

In vitro calibration of a video-based method for measuring blood velocity in kidney medulla and other tissues subject to respiratory motion

Three problems must be solved to apply the dual-slit method for measuring mean erythrocyte velocity ($\text{V}{}_{\mathrm{<mtext>R</mtext>}}$) to the study of blood flow regulation in the kidney medulla: (1) An estimator is needed to calculate blood velocity ($\text{V}{}_{\mathrm{<mtext>B</mtext>}}$) from $\text{V}{}_{\mathrm{<mtext>R</mtext>}}$. This estimator must relate erythrocyte diameter to blood vessel diameter, and since fluids of the medulla are hypertonic, erythrocyte diameter may not be the same as in systemic blood. (2) In the usual experimental arrangement, respiratory movement is transmitted to the kidney, so that the image of the blood vessels moves with respect to fixed photodetectors. We have used a video adaptation of the dual-slit method to deal with this problem, but (3) this limits the estimates of erythrocyte transit time between the two slits to integer multiples of the video framing interval, if standard cross-correlation methods are used. We have therefore analyzed the time series in the frequency domain to provide continuous estimates of transit time. Glass tubes ranging in diameter from 16 to 28 μm were connected to a pump and perfused with blood at rates comparable to vasa recta flow rates. There was a dependence of $\text{V}{}_{\mathrm{<mtext>R</mtext>}}\text{V}{}_{\mathrm{<mtext>B</mtext>}}$ on tube diameter, as expected, but little effect of osmolality, hematocrit, or velocity. Simulated respiratory noise was effectively eliminated, and an estimator that relates $\text{V}{}_{\mathrm{<mtext>B</mtext>}}$ to $\text{V}{}_{\mathrm{<mtext>R</mtext>}}$ was provided.     

Effect of fluocarbon exchange transfusion on myocardial infarction size in dogs

Fluosol DA (20% ), a perfluocarbon with high oxygen solubility, was administered by concurrent exchange transfusion (30 ml/kg) to anesthetized open-chested adult greyhounds (n = 9) 1 hour after left anterior descending coronary ligation. Mechanical ventilation using 100% oxygen was used throughout the experiment. A second similar group (n = 9) received 0.9% normal saline solution (30 ml/kg), and a third group (n = 9) received no further intervention. Systemic, right atrial, and left atrial pressures were not altered by the exchange transfusion. Monastryl blue dye was injected through the left atrial line at 6 hours after ligation to define the area of myocardium at risk (A_R); the animals were then killed and the heart was excised. The left ventricle was sliced at 5 mm intervals and stained using triphenyltetrazolium chloride, defining areas of necrosis (a_n). The ratio of $\text{A}{}_{\mathrm{N}}\text{A}{}_{\mathrm{R}}$ and total left ventricular mass were then compared with the use of planimetry.The results were as follows: the $\text{A}{}_{\mathrm{N}}\text{A}{}_{\mathrm{R}}$ ratio in the 9 control animals was 90 ± 2 (mean ± standard error of the mean); in the 9 animals who received saline solution it was 88 ± 2; and in the animals who received Fluosol it was 67 ± 4 (p < 0.01 compared with control; p < 0.001 compared with the saline group).Fluocarbon exchange transfusion may reduce infarct size when administered after coronary occlusion.     

Noninvasive measurement of ventricular pressure throughout systole.

A simple method is proposed for measuring right or left ventricular systolic pressure based on analysis of the right or left ventricular time-activity curve, obtained with a scintillation camera or cardiac probe after intravenous injection of technetium-99m albumin or red blood cells. The method is based on three principles: (1) intraventricular pressure equals force per area of the aortic opening; (2) force equals mass (of blood) times its acceleration; and (3) acceleration can be derived from the ventricular volume curve. The following differential equation was derived $\text{(}\text{?}\text{P}\text{?}\text{t}\text{)}{}_{\mathrm{<mtext>x</mtext>}}\text{=}\text{?}\text{A}{}^2\text{α}{}^2\text{da}\text{dt}\text{d}{}^2\text{a}\text{dt}{}^2$ where ($\text{?}\text{P}\text{?}\text{t}\text{)}{}_{\mathrm{<mtext>x</mtext>}}$ is the first derivative of left ventricular pressure; ? is the density of blood; A is the area of the aortic opening¹; α is the ratio of blood volume to radioactivity (a) measured within the ventricle, $\text{da}\text{dt}$ is the first derivative (velocity) of the activity (a) within the véntricle and $\text{d}{}^2\text{a}\text{dt}{}^2$ is the second derivative (acceleration). The integration of this equation is readily accomplished, and the integrated curve reflects the pressure changes. Absolute calibration in millimeters of mercury requires knowledge of the end-diastolic volume and the area of the aortic opening. It is assumed that the area of aortic opening is relatively constant, that blood flow is laminar and that the pressure pulse travels with the velocity of blood through the aortic opening. In validation studies in dogs, calculated and observed ventricular pressure curves were nearly identical in shape and absolute value. In patients, although an absolute pressure measurement still awaits an accurate method for calculation of left ventricular enddiastolic volume, differences in the shape and amplitude of the curves were found. The procedure can be performed easily, and the calculation can be made within minutes. With further validation, the method may provide noninvasively a pressure and volume relation that is valuable in characterizing the function of the heart as a pump, both at rest and during graded exercise.     

Right ventricular infarction

The cases of 27 consecutive patients aged 40 to 78 years with ventricular septal rupture during acute myocardial infarction were reviewed. Myocardial infarction was inferior in 16 patients and anterior in 11. The time from myocardial infarction to rupture was less than 24 hours in 9 patients, 24 to 48 hours in 6 patients, 2 to 7 days in 11 patients, and 14 days in 1 patient. In 23 patients pressures (in mm Hg) were pulmonary arterial systolic 28 to 70 (mean 52), diastolic 9 to 34 (mean 23) and left ventricular end-diastolic 15 to 35 (mean 24). Cardiac index was 1.1 to 2.5 (mean 2.0) liters/min per m² and the ratio of pulmonary to systemic flow ($\text{Q}{}_{\mathrm{<mtext>p</mtext>}}\text{Q}{}_{\mathrm{<mtext>s</mtext>}}$) 1.5 to 4.8 (mean 3.4). The number of coronary vessels with more than 50 percent obstruction was one in 8 patients, two in 11 patients and three or more in 8 patients. Of the eight patients with single vessel disease three had right, one had left circumflex, and four had left anterior descending coronary artery disease.All seven patients treated without surgery died 1 to 13 days after ventricular septal rupture; all seven had inferior myocardial infarction, and none had previous transmural myocardial infarction. Of these seven patients, two were considered inoperable, one died during study, and four died abruptly while awaiting study. Eleven of 20 patients (55 percent) survived operation. The survival rate in seven patients operated on less than 2 days after ventricular septal rupture was 72 percent. Of 11 patients operated on 2 to 28 days after ventricular septal rupture 4 survived, whereas the 2 patients operated on later than 4 weeks after rupture survived. It is concluded that (1) early surgery in ventricular septal rupture has relatively low mortality; (2) delay of study and surgery is done at the expense of unacceptable and unpredictable mortality; and (3) ventricular septal rupture can occur with single vessel coronary artery disease.     

Rest and exercise hemodynamics in children before and after aortic valvotomy

The rest and exercise hemodynamics in children with congenital valvar aortic stenosis were studied before and after aortic valvotomy. Eighteen patients were studied at rest; ten of the 18 patients were also studied during supine leg exercise using a bicycle ergometer.Aortic valvotomy resulted in a significant reduction in the mean left ventricular-aortic pressure gradient and in peak left ventricular systolic pressure with an increase in aortic valve area in most patients. There was an associated increase in the subendocardial blood flow assessed indirectly by the $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio. There was a minor increase in the degree of aortic insufficiency in most patients.Although, in general, there was significant hemodynamic improvement, three of the 18 patients still had significant residual stenosis after surgery and another four patients had a major increase in aortic insufficiency. The three patients with residual obstruction and one of the four patients with moderate to severe aortic insufficiency still had a $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio of less than 10, suggesting possible residual subendocardial ischemia. Also, the increased left ventricular end-diastolic pressures (LVEDP) present in nearly 50% of the patients before surgery did not change significantly after surgery. Three patients showed an actual increase in LVEDP after surgery.Before surgery, the left ventricular systolic pressure and mean gradient increased on exercise, but this increase was proportionately less than the increase in cardiac output, so that calculated aortic valve area increased on exercise. The $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio decreased significantly on exercise, suggesting an increase in myocardial ischemia. Successful surgery resulted in a reduction in left ventricular systolic pressure and mean left ventricular-aortic gradient on exercise, and in improvement in the subendocardial blood flow as assessed by the $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio.In general, children with severe aortic stenosis have relatively normal cardiac function on exercise. Some children did show a reduction of stroke index on exercise in spite of rising LVEDP. However, stroke work index increased in all of our children. Adult studies have shown many patients with decrease in stroke work index relative to LVEDP on exercise.The results of pre- and postoperative rest and exercise hemodynamics may be useful in evaluating results of surgery; the postoperative hemodynamic evaluation including the use of $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio provides additional useful information which can be used in making decisions concerning exercise activity after surgery.     

Role of prostaglandin E1 infusion in the management of transposition of the great arteries.

That prostaglandin E₁ can produce an increase in systemic oxygen saturation in patients with cyanotic heart disease and ductus dependent pulmonary blood flow has been well documented. However, its use in complete transposition to increase systemic oxygen saturation by increasing mixing has not been well investigated. Ten newborn infants with angiographic diagnosis of d-transposition of the great arteries and patent ductus arteriosus were studied; 6 had an intact ventricular septum. Prostaglandin E₁ infusion (0.1 μg/kg per min) was started after balloon atrial septostomy because of a persistently low systemic oxygen saturation of 26 ± 12 percent (mean ± standard deviation) and oxygen tension of 17 ± 5 torr. The infusion resulted in an increase in systemic oxygen saturation to 53 ± 19 percent (P < 0.01) and oxygen tension to 30 ± 9 torr (P < 0.001). In 2 of 10 patients, there was no increase in systemic oxygen saturation with the infusion (1 had the infusion before the septostomy and both had the infusion for less than 10 minutes). In 8 of 10 patients, the infusion was continued from 4 to 312 hours (average 98 hours) until a Blalock-Hanlon procedure was performed. Two babies became septic, and one of them died. A third had a transient fever. All children whose prostaglandin E₁ infusion was discontinued before atrial septectomy had a reduction in systemic oxygen saturation to unacceptable levels. Two patients who required infusion (for 5 days) after septectomy were successfully weaned from the drug.It is concluded that dilation of the ductus by prostaglandin E₁ infusion increases pulmonary blood flow (left to right shunt) which in turn favorably influences atrial mixing (left to right shunt) and increases systemic oxygen saturation. Pulmonary blood flow may be further increased by a decrease in pulmonary vascular resistance induced by prostaglandin E₁.     

Computer analysis of oximetry data in cardiac catheterization

An on-line computer technique is described for the detection and quantitation of left-to-right shunts. The computer used Student's t test to evaluate the probability that variations in right heart oxygen saturations were due to left-to-right shunts. The computer method was found to compare favorably to the present step-up method of detecting left-to-right shunts. The computer also calculated pulmonary blood flow, systemic blood flow, their ratio, and shunt blood flow as accurately as standard methods, as evidenced by correlation coefficients of 0.98, 0.94, 0.95, and 0.71 between the computer and hand calculations.     

Computer analysis of oximetry data in cardiac catheterization.

An on-line computer technique is described for the detection and quantitation of left-to-right shunts. The computer used Student's t test to evaluate the probability that variations in right heart oxygen saturations were due to left-to-right shunts. The computer method was found to compare favorably to the present step-up method of detecting left-to-right shunts. The computer also calculated pulmonary blood flow, systemic blood flow, their ratio, and shunt blood flow as accurately as standard methods, as evidenced by correlation coefficients of 0.98, 0.94, 0.95, and 0.71 between the computer and hand calculations.     

Factors affecting unstimulated flux through the hexose monophosphate shunt during incubations of human red blood cells

Factors affecting the flux of glucose through the hexose monophosphate shunt in unstimulated human red blood cells were studied in vitro. Reduction of oxyhemoglobin or free O₂ each accounted for about one-third of the total flux of reducing equivalents through the shunt. Approximately one third of total flux remained after removal of oxyheme activity and free O₂. Both deoxyhemoglobin and methemoglobin stimulated flux in the absence of free O₂ suggesting that the small amount of deoxyheme and metheme (1%), in equilibrium with the large pool of oxyheme (99%), may contribute to the total oxidizing effect of the heme group. The flux of reducing equivalents through the hexose monophosphate shunt in unstimulated red cells primarily involved oxidation and reduction of oxyhemoglobin or free O₂. In low phosphate buffer (1.2 mM), glutathione served as the source of reducing equivalents for the remaining “electron sinks” (after removal of oxyheme activity and free O₂) during the 1st hr of incubation so that glutathione stimulated flux through the hexose monophosphate shunt; during the 2nd hr of incubation, glutathione acted as a reservoir of reducing equivalents maintaining NADPH and inhibiting flux through the hexose monophosphate shunt. When red cells were incubated in high phosphate buffer (17.4 mM), glutathione behaved as an inhibitor of flux in the 1st hr of incubation in red cells lacking oxyheme activity and free O₂. The $\text{H}{}_2\text{PO}{}_4{}^{\mathrm{?}}\text{HPO}{}_4{}^{\mathrm{2?}}$ anion couple appears to alter the pattern of NADPH oxidation in red cells lacking oxyheme activity and free O₂. Flux was inhibited by incubation of red cells in a medium containing lactate (4 mM). Inhibition of flux by lactate was not dependent on heme, free O₂ or glutathione but all these factors had complex influences on lactate-mediated inhibition. The inhibitory effect of lactate on flux is complementary to the well-characterized stimulatory effect of pyruvate. The lactate/pyruvate couple may act by directly filling or creating electron sinks, by interacting with the $\text{NADPH}\text{NADP}{}^{\mathrm{+}}$ couple through lactic dehydrogenase or through transhydrogenation between the $\text{NADH}\text{NAD}{}^{\mathrm{+}}$ and $\text{NADPH}\text{NADP}{}^{\mathrm{+}}$ couples.     

Experimental myocardial infarction with left ventricular failure in the isolated perfused rat heart. Effects of isoproterenol and pacing.

Within one minute of acute coronary artery occlusion in the isolated rat heart performing external mechanical work, cardiac output and left ventricular peak systolic pressure fell by one-third to onequarter and there were decreases in the contents of ATP and phosphocreatine (CP) in the ischaemic tissue. Left ventricular and diastolic pressure rose, and $\text{d}\text{p}\text{d}\text{t}{}_{\mathrm{<mtext>max</mtext>}}$ fell. Cardiac output was steady for 60 min post-ligation. The size of infarction was quantified by the use of radioactive microspheres; over one-half of the left ventricle was rendered ischaemic. There was a biphasic response to dl-isoprenaline HCl (10^?6m) added to the perfusate. A temporary increase in cardiac output was followed by a rapid decrease as the heart rate exceeded about 350/min, although $\text{d}\text{p}\text{d}\text{t}{}_{\mathrm{<mtext>max</mtext>}}$ increased throughout. When the heart rate was fixed by pacing, isoproterenol was able to double stroke volume and $\text{d}\text{p}\text{d}\text{t}{}_{\mathrm{<mtext>max</mtext>}}$, coronary flow rose by about one-third. Thus in this model the positive inotropic effect of isoproterenol on the ischaemic myocardium became masked as a negative contribution associated with a concomitant chronotropic effect developed. There was also a negative effect of pacing on the cardiac output of non-ligated hearts, but the magnitude was less. It is proposed that a fixed coronary flow rate limited the oxygen delivery to the myocardium as the heart rate rose.     

Margination of leukocytes in blood flow through small tubes

Leukocyte margination in the vessels of the microcirculation has been attributed to a flow-dependent interaction with red cells. To determine the extent of this effect, experiments with human blood were done in 100- to 180-μm tubes to detect changes in cell distribution as a function of hematocrit and flow rate. Using a flow visualization technique, the leukocyte concentration distribution was determined in 45% ghost cell suspensions. Migration of cells toward the wall was observed at centerline velocities > 1 mm sec^?1 and increased with increasing flow rate. The effect was probably due to a more rapid inward migration of ghosts than leukocytes because of fluid inertia and cell density differences. Experiments were therefore carried out in whole blood at hematocrits from 20 to 60%, measuring the number concentration of leukocytes and erythrocytes within the tube, n_t, and comparing it to that in the infusing reservoir, n₀, (Fahraeus effect). At mean tube shear rates $\text{G}\text{< 100}\text{sec}{}^{\mathrm{?1}}\text{,}\text{n}{}_{\mathrm{<mtext>t</mtext>}}\text{n}{}_0\text{< 1}$ for both leukocytes and erythrocytes showing net migration of cells away from the wall, although at nearly all hematocrits there was an enrichment of leukocytes relative to erythrocytes in the tubes. At $\text{G}\text{< 50}\text{sec}{}^{\mathrm{?1}}\text{,}\text{n}{}_{\mathrm{<mtext>t</mtext>}}\text{n}{}_0$ remained < 1 for erythrocytes but increased to > 1 for leukocytes showing migration toward the wall, the increase being greatest at 20% hematocrit in the 100-μm tubes. The nature of the effect was revealed by cine films which showed that, as the flow rate decreased, erythrocytes formed rouleaux which migrated inward creating a core and displacing leukocytes to the periphery. In control experiments using washed blood cells in phosphate buffer-albumin, $\text{n}{}_{\mathrm{<mtext>t</mtext>}}\text{n}{}_0\text{< 1}$ for both leukocytes and erythrocytes at all $\text{G}$ and hematocrits, and leukocytes were now depleted relative to erythrocytes in the tubes, i.e., the leukocytes were more axially distributed. Cine films of washed blood confirmed that, in the absence of rouleaux, no significant inward migration of erythrocytes occurred.     

In vivo cellular and plasma velocities in microvessels of the cat mesentery.

The simultaneous determination of RBC and plasma velocities in microvessels (<11.6 μm lumen diameter) of the cat mesentery has yielded information on the dependence of their ratio on other flow parameters. The $\text{V}{}_{\mathrm{<mtext>RBC</mtext>}}\text{V}{}_{\mathrm{<mtext>plasma</mtext>}}$ ratio is found to increase with increasing V_RBC, and to be more sensitive to vessel diameter changes at higher values of V_RBC. Vessel diameter itself has been found to be an unreliable indicator of blood volume flow rate in this size range of microvessels.     

Systemic artery—pulmonary vein fistulas Congenital and acquired left to left shunt

Fistulas from systemic arteries to the pulmonary vein may be congenital or acquired. Hemodynamically significant left to left shunts are associated with a continuous murmur, bounding peripheral pulses and left ventricular enlargement. Clinically they may be indistinguishable from left to right shunts into the pulmonary artery. Atypical location of the continuous murmur, lack of evidence of increased pulmonary flow and evidence of localized lesions in pulmonary parenchyma should lead to a suspicion that a left to left shunt is present. At cardiac catheterization left to left shunts are not associated with increased oxygen saturation in the pulmonary artery and may be clearly outlined with the use of arteriography. Two cases are presented, 1 representing a congenital and the other an acquired left to left shunt.     

Hypoxia in skeletal muscle at rest and during the transition to steady work.

This paper reviews O₂ transport to skeletal muscle at rest and during the transition to steady work. In animals whose surface area is large relative to volume, mean intracellular PO₂ is about 5 mm Hg, and $\text{V}\text{?}\text{O}{}_2$ increases if flow increases. However, coupled $\text{V}\text{?}\text{O}{}_2$ of mitochondria in vitro and in vivo is maximal when intracellular PO₂ exceeds about 0.1 mm Hg. The 50-fold difference between the critical PO₂ for $\text{V}\text{?}\text{O}{}_2$ of mitochondria and $\text{V}\text{?}\text{O}{}_2$ of whole muscle is accounted for, at least in part, by nonuniformities in the muscle microcirculation. These nonuniformities cause focal anoxia, even though mean intracellular PO₂ greatly exceeds critical mitochondrial PO₂. It remains to be determined whether biochemical pathways to O₂ parallel and/or, alternative to the classical respiratory chain, contribute to the flow dependence of muscle $\text{V}\text{?}\text{O}{}_2$. Most of the O₂ debt in phasic contraction is acquired during the first 30–60 sec. while blood flow is increasing rapidly. This initial phase of vasodilation is entirely due to short neurones intrinsic to skeletal muscle arterioles. A minor component of the O₂ debt is acquired after maximum flow is attained. This may be accounted for by slow recruitment of capillaries, which are under metabolic rather than neural control.     

A network model of glomerular function

A model has been developed to establish the determinants of glomerular function by means of a network analysis. The topological and dimensional parameters of the capillary network were obtained by reconstructing the lobular structures of two Wistar rat glomeruli. Calculation of the hydrostatic pressure drop from the afferent to the efferent extremity of the network () was based on the concept of the additional pressure drop per red cell in single-file flow, or, in multiple-layer flow, on in vitro experimental data relating apparent viscosity of blood to dynamic hematocrit and capillary radius. Partition of red cells at bifurcations was calculated as a function of the velocity ratio within the branches. The micropuncture data obtained in Munich-Wistar rats at distal pressure disequilibrium (net ultrafiltration pressure greater than 0) were used to establish the validity of the model. ε was found to be 3.1%. The efferent ultrafiltration pressure was close to the value predicted from the micropuncture data. At distal pressure disequilibrium, 100% of the glomerular surface area was utilized for filtration. In this case, the mean integrated ultrafiltration pressure and the filtration coefficient were close to the values reported by R. C. Blantz, F. C. Rector, Jr., and D. W. Seldin ((1974) Kidney Int.6, 209–225) using the single-tube model of W. M. Deen, C. R. Robertson, and B. M. Brenner ((1972) Amer. J. Physiol.223, 1178–1183). The hydraulic conductance was estimated between 0.046 and 0.09 μl sec^?1 mm Hg^?1 cm^?2S.A. but was dependent on the value chosen for the glomerular surface area.     

Volume of capillary exchange vessels measured with a gravimetric method in rat hindquarters.

To measure the volume of the true exchange vessels, i.e., that of the “functional” capillaries, in rat skeletal muscle, two parallel-coupled hindquarter vascular beds were perfused at a constant flow with oxygenated plasma substitute. Continuous recordings were performed of changes in the total weight of the two preparations, caused by sudden arterial occlusion in one, thus doubling the flow to the other while venous drainage was left open in both. Venous outflow pressure was kept constant, usually at a level where the veins remained well distended. After a rapid and small change in total weight, reflecting the balance between vascular distension and recoil in the two circuits, the subsequent weight change showed a continuous increase, but after a distinct delay. From this delay, caused by transient absorption into the semistagnant capillary contents of the arterially occluded vascular bed, the absorbed fluid amount, Q, was calculated. Functional capillary volume, V_c, was then calculated from the following equation (see text for derivation):

$\text{V}{}_{\mathrm{c}}\text{=}\text{Q}\text{ln}\text{[}\text{π}{}_{\mathrm{c}}\text{π}{}_{\mathrm{c}}\text{−P}{}_{\mathrm{c}}\text{+P}{}_{\mathrm{v}}\text{]}$

where π_c, P_c, and P_v represent effective plasma colloid osmotic pressure, equivalent capillary pressure, and venous outflow pressure during isogravimetric conditions. This functional capillary volume, which thus includes permeable venular sections, amounted to 0.55–0.60% of the tissue weight, varying slightly with the prevailing P_c, and corresponding to 10–15% of the total volume of the regional vascular bed. Capillary density in skeletal muscle was also deduced from these data and from known microvascular diameters, giving a value of 450–500/mm², which is in fair agreement with morphological data. The physiological significance of measuring the functional capillary volume by this method is discussed.     

Different intracellular cation-content present in right and left ventricle dependent on varying extracellular Ca2+-concentrations.

The different intracellular cation-contents present in the right and left ventricle depend on varying Ca²⁺-concentrations. The effect of extracellular Ca²⁺-concentrations varied within the physiological range has been studied on an isolated guinea pig heart preparation, showing excellent stable experimental conditions. By increasing the extracellular Ca²⁺-concentration from 0.45 mm to 3.6 mm the tissue contents of calcium and potassium were increased dependent on [Ca]_e whereas that of Na was reduced. This was due to a change in the composition of the intracellular cations as the extracellular space (inulin) and water-content of the heart muscle tissue were not influenced by increasing the extra-cellular Ca²⁺-concentration. At any given [Ca]_e the Ca- and Na-content of the right ventricular myocardium was higher than that in the left. The ratio $\text{Ca}{}_{\mathrm{right}}\text{Ca}{}_{\mathrm{left}}$ varied from 2.0 at 0.45 mm to 1.6 at 3.6 mm [Ca]_e. The left ventricular contractile force showed a log linear relationship to Ca_net as well as [Na]_i.     

The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 micron).

Measurements of the Fahraeus effect were performed in glass capillaries (i.d. 3.3 to 11.0 μm) during perfusion with suspensions of human red blood cells in Ringer's solution at reservoir hematocrits (H_F) varying between 0.1 and 0.6. The flow velocity of the red cells (v_c) and that of the suspending fluid (v_p) were determined by dual slit photometry. The tube hematocrit (H_T) was obtained from microphotographs and/or by analysis of photoelectric signal recordings; the discharge hematocrit (H_D) was calculated from these measurements. The ratio of cellular and suspending medium flow velocity ($\text{v}{}_{\mathrm{<mtext>c</mtext>}}\text{v}{}_{\mathrm{<mtext>p</mtext>}}$) was seen to vary between 1.65 in the 11.0-μm capillary and 1.09 in the 3.3-μm capillary at H_F = 0.35. The Fahraeus effect was observed to decrease with capillary diameter: the ratio $\text{H}{}_{\mathrm{<mtext>T</mtext>}}\text{H}{}_{\mathrm{<mtext>D</mtext>}}$ increased from 0.67 in the 11.0-μm to 0.94 in the 3.3-μm capillary at H_F = 0.35. Furthermore the Fahraeus effect increased with decreasing hematocrit in the two larger capillaries used (i.d. 9.5 and 11.0 μm) whereas it was independent of hematocrit in the smaller capillary tubes. Likewise, calculations of the thickness of the cell-free marginal zone demonstrated an increase with decreasing hematocrit in the larger tubes, but no hematocrit dependence in capillaries < 6.3 μm. Significant effects of variation in flow rate on the Fahraeus effect were not detected although shear-dependent shape changes of the flowing red blood cells were observed.