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.     

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.     

Left ventricular A wave amplitude in patients after myocardial infarction

The relations between left ventricular (LV) A wave amplitude and left ventricular dimensions, compliance, systolic function, and the size of abnormally contracting segments (ACS) of the left ventricle were examined in 42 patients studied within 1 year after acute myocardial infarction. Left ventricular A wave amplitude was measured from left ventricular pressure tracings both from zero (A₀) and from pre-A wave pressures (A_PAP). Left ventricular compliance was calculated from left ventricular volumes obtained from biplane angiograms and the left ventricular pressure recorded immediately before angiograms. Left ventricular compliance was evaluated by three formulas: $\text{ΔV}\text{ΔP}$ (angiographic stroke volume/left ventricular end-diastolic pressure (LVEDP) minus lowest early diastolic pressure); $\text{ΔV}\text{LV}$ end-systolic $\text{volume}\text{ΔP}$; and $\text{dV}\text{dP}{}_{\mathrm{ED}}\text{× 1/EDV/m}{}^2$. Percent ACS was measured as the akinetic or dyskinetic length along the end-diastolic perimeter on biplane left ventricular angiograms expressed as a percentage of the total left ventricular diastolic perimeter.A_O had a direct quadratic relation with A_PAP (r² = 0.72), and A₀ had high inverse quadratic correlations with $\text{ΔV}\text{ΔP}$ (r² = 0.59), $\text{δV}\text{ESV}$/δP (r² = 0.63), and dV/dPED × 1/EDV/m² (r² = 0.72). A₀ correlated directly with LVEDP (r² = 0.76), end-diastolic volume (r² = 0.32), LV mass (r² = 0.22) and percent ACS (r² = 0.36), and inversely with ejection fraction (r² = 0.43).Seven of the 42 patients were studied by dextran infusion. Diastolic volume change (ΔV_Ind.-Dil.) calculated from indicator-dilution cardiac output values, left ventricular diastolic pressure change (ΔP), and A₀ were obtained before infusion and after each 200 ml infusion. Values for diastolic pressure-volume slope ($\text{ΔP}\text{ΔV}{}_{\mathrm{Ind.-Dil.}}$ ) and A₀ increased with dextran infusion in all seven patients. The $\text{ΔP}\text{ΔV}{}_{\mathrm{Ind.-Dil.}}$ slopes had a significant direct linear relation with corresponding left ventricular A wave amplitudes. Thus, the slope of the diastolic pressure-volume curve for any ventricle, as reflected by the compliance values, is a major determinant of the increase in left ventricular A wave amplitude for a particular volume of dextran infused.In summary, increased left ventricular A wave amplitudes in patients after myocardial infarction signify a decrease in both left ventricular diastolic compliance and systolic function.     

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.     

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.     

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.     

Early sequential changes in left ventricular dimensions and filling pressure in patients after myocardial infarction

Early consecutive changes in pulmonary arterial end-diastolic pressure (PAEDP) and echocardlographic left ventricular dimensions were measured in 14 patients within the first 8 days after acute myocardial infarction. Left ventricular volumes were estimated from echocardiographic left ventricular dimensions. Left ventricular compliance was assessed by three formulas, $\text{ΔV}\text{ΔP}$, ΔV/ESV/ΔP and $\text{LVID}{}_{\mathrm{d}}\text{PAEDP}$, where AV = echocardiographic stroke volume, ΔP = a derived left ventricular diastolic pressure change from the lowest level of early diastolic to the end-diastolic pressure, ESV = left ventricular end-systolic volume, and LVID_d = echocardiographic left ventricular end-diastolic dimension. To compare pressure, dimension and compliance values, linear relations were assumed between values for left ventricular end-diastolic volume, end-systolic volume, pulmonary arterial end-diastolic pressure and the day after infarction. The estimated third day values for the variables obtained from these linear relations were used so that each patient's values would contribute equal weight to the statistical analysis.The estimated third day compliance values from each formula correlated highly with one another (r = 0.69 ? 0.82). Neither $\text{ΔV}\text{ΔP}$ nor ΔV/ESV/ΔP had a significant correlation with LVID_d. Echocardiographic end-diastolic volume correlated with both end-systolic volume (r = 0.89) and echocardiographic stroke volume (r = 0.62) but not with pulmonary arterial end-diastolic pressure. When the first and last measurements for each patient are used, large changes in pulmonary arterial end-diastolic pressure associated with no or small alterations in echocardiographic left ventricular end-diastolic dimension in 12 patients imply acute changes in ventricular compliance. Sequential compliance values ($\text{ΔV}\text{ΔP}$) increased in seven survivors and decreased in one. $\text{ΔV}\text{ΔP}$ decreased in the five patients who died or had electrocardiographic evidence of extension of infarction. Early sequential changes in filling pressure, echocardiographic dimensions, and left ventricular compliance had a close correlation with the clinical course of the patients in our series and these data may assist in the management of patients with hemodynamic instability after acute myocardial infarction.     

Platelet aggregation in Poiseuille flow: II. Effect of shear rate

Using a double infusion technique described in the previous paper, the effect of shear rate, G, on platelet aggregation was studied in citrated platelet-rich plasma in Poiseuille flow over a range of mean linear flow rates, $\text{u}{}_3$ from 50 to 1500 μm sec^?1 corresponding to $\text{G}$ from 2 to 54 sec^?1. At 1 μm ADP, aggregates were formed at all $\text{u}{}_3$ and, except at the lowest flow rate, both the degree of aggregation (net fraction of cells in aggregates, A′) and size of the aggregates increased with distance down the tube. The degree of aggregation was both time and shear rate-dependent. Over the first 10 sec, A′ appeared to be independent of the mean transit time indicating that the collision capture efficiency decreased with increasing G. Thereafter, A′ increased with increasing shear rate leading to the formation of an appreciable number of aggregates >10 cells at $\text{G}\text{> 24}\text{sec}{}^{\mathrm{?1}}$. Small aggregates initially formed near the tube wall and, as they grew in size, migrated toward the axis as their rotation was physically impeded by the wall. In addition, the values of A′ in cPRP from five female donors were significantly greater than those from five male donors.     

Increased immunoglobulin-secreting cells in the blood of patients with active systemic lupus erythematosus

Peripheral blood lymphoid cells actively secreting immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) were quantitated in 24 patients with systemic lupus erythematosus (SLE) and compared with the frequency of such immunoglobulin secreting cells (IgSC) in normal controls utilizing a reverse hemolytic plaque assay. The geometric mean frequency of IgG-secreting cells in the patients with SLE was $\text{489}\text{10}{}_6$ peripheral blood mononuclear cells which was significantly higher (p < 0.005) than the mean control value of 137. The mean frequency of IgA-secreting cells in the patients with SLE was $\text{293}\text{10}{}_6$ cells which was also significantly higher (p < 0.01) than the mean of 96 in the control group. IgM-secreting cells were present in normal frequency in the patients with SLE (53 versus $\text{66}\text{10}{}^6$ in controls). The 24 patients were ranked in order of disease activity, and correlation coefficients were calculated comparing disease activity with laboratory findings including white blood cell count, erythrocyte sedimentation rate, third component of complement (C3) levels, immunoglobulin levels, anti-DNA antibody concentrations and the frequency of IgSC. Disease activity had a significant positive correlation with the serum levels of IgG (p < 0.001) and IgM (< 0.01), and the erythrocyte sedimentation rate (< 0.01), and had a significant negative correlation with serum C3 levels (p < 0.01). There was a highly significant correlation between disease activity and the level of anti-DNA antibody (r = 0.711, p < 10^?5) but the highest correlation with disease activity found was the frequency of IgG-secreting cells in the blood of the patient with SLE (r = 0.777, p < 10^?6). These data demonstrate that SLE is associated with increased numbers of IgG- and IgA-secreting cells in the peripheral blood and that increases in these parameters are closely associated with active clinical disease.     

QTQS2 ratio as an index of autonomic tone changes

The effects of changes in sympathetic tone on $\text{QT}\text{QS}{}_2$ ratio were studied in 10 healthy subjects aged 21 to 24 years. The subjects underwent a bicycle ergometer exercise, a tilt test, a decrease in carotid transmural pressure induced by means of pneumatic neck chamber, an i.v. injection of phenylephrine. A phonocardiogram and ECG were simultaneously recorded at a paper speed of 100 mm/s to evaluate QT and QS₂ intervals in each test. In basal conditions, the $\text{QT}\text{QS}{}_2$ ratio was less than 1, whereas it increased progressively during the physical exercise and became greater than 1 at peak exercise. Both the upright position and the increase in neck-tissue pressure induced a significant increase in the $\text{QT}\text{QS}{}_2$ ratio as compared with the basal values, whereas i.v. administration of phenylephrine reduced significantly the $\text{QT}\text{QS}{}_2$ ratio. These results demonstrate that those stimuli which induce a rise in adrenergic activity may increase the $\text{QT}\text{QS}{}_2$ ratio. In contrast, the reflex inhibition of the adrenergic activity induced by phenylephrine is accompanied by a reduction in $\text{QT}\text{QS}{}_2$ ratio. Therefore, the $\text{QT}\text{QS}{}_2$ ratio might represent a reliable index of sympathetic cardiac tone.     

Gold-195m,a new generator-produced short-lived radionuclide for sequential assessment of ventricular performance by first pass radionuclide angiocardiography

The feasibility of performing rapid sequential first pass radionuclide angiocardiography using a new short-lived radiotracer, gold-195m (^195mAu) half-life 30.5 seconds) was evaluated. This radionuclide emits a 262 keV gamma ray and is the daughter of mercury-195 (^195mHg) (half-life 41.6 hours). The prototype tabletop ${}^{\mathrm{<mtext>195</mtext><mtext>m</mtext>}}\text{Hg}{}^{\mathrm{<mtext>195</mtext><mtext>m</mtext>}}\text{Au}$ generator produced 20 to 25 mCi of ^195mAu in 2 ml of eluate (yield of 40 percent). The breakthrough of ^195mHg in the eluate was 0.02 percent of the amount of ^195mHg in the generator. The eluate contained 20 μCi of ^195mHg per study, resulting in an estimated human radiation dose of 0.007 rad/study to the whole body and 0.34 rad/study to the kidney.Four dogs each had 15 to 20 sequential first pass studies performed with ^195mHg at 3 to 10 minute intervals using a computerized multicrystal gamma camera. During the left ventricular phase, 160,000 to 190,000 counts/s were acquired. The end-diastolic left ventricular region of interest contained 3,000 to 6,000 counts (background- and decay-corrected). Multiple reproducible values for left ventricular ejection fraction were obtained during stable conditions. The mean (± standard deviation) interstudy variability was 4 ±2 percent. During infusion of isoproterenol, rapid increase of left ventricular ejection fraction was demonstrated. Excellent agreement was observed between studies performed with technetium-99m diethylenetriaminepentaacetic acid (^99mTc-DTPA) and ^195mAu. The mean jnterstudy difference was 4 ±3 percent. Thus, sufficiently high yield and dose are obtained from the ${}^{\mathrm{<mtext>195</mtext><mtext>m</mtext>}}\text{Hg}{}^{\mathrm{<mtext>195</mtext><mtext>m</mtext>}}\text{Au}$ generator for reliable high count rate first pass determination of left ventricular ejection fraction. This new short-lived radiotracer makes possible rapid sequential assessments of ventricular function at greatly reduced patient exposure to radiation.     

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 $\text{R}{}_{\mathrm{p}}\text{R}{}_{\mathrm{s}}\text{<0.50}$.     

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.     

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.     

Effect of increased aortic perfusion pressure on fluorescent emission of the isolated rat heart

When the isolated rat heart was perfused at a range of aortic pressures, left ventricular peak systolic pressure varied from 40 to 140 mmHg. The fluorescent emission at 481 nm decreased, which was interpreted as an increased myocardial tissue $\text{NAD}{}^{\mathrm{+}}\text{NADH}$ ratio at higher pressures. Because the perfusion conditions (fasted rats, β-hydroxybutyrate 5 mm substrate) were such as to minimize glycolytic flux and because the cytoplasmic NAD pool did not change as assessed by perfusate and tissue lactate/pyruvate ratios, it was probable that the mitochondrial NAD pool had changed towards NAD⁺. The effect of increased perfusion pressure on the fluorescent emission was dependent on the substrate of the heart.     

Ventricular function and coronary hemodynamics after intravenous nitroglycerin in coronary artery disease.

Left ventricular dynamics as well as systemic and coronary hemodynamics were determined in 14 patients with coronary artery disease (1) under control conditions, (2) under intravenous infusion of nitroglycerin, (3) under continued infusion of nitroglycerin with restored arterial and pulmonary artery pressures induced by the parallel infusion of dextran. Heart rate was kept constant by atrial pacing.Intravenous nitroglycerin infusion resulted in a significant reduction in left ventricular systolic (20 per cent) and end-diastolic pressure (43 per cent), peak $\text{dp}\text{dt}$ (13 per cent), cardiac index (16 per cent), stroke volume index (15 per cent), and stroke work index (30 per cent). Peak (dp/dt/total pressure) increased (15 per cent). Pulmonary vascular resistance markedly decreased (29 per cent), whereas total peripheral resistance did not change significantly (?3 per cent). Both coronary blood flow of the left ventricle (13 per cent) and myocardial oxygen consumption (15 per cent) decreased parallel to the reduction in preload and afterload. The action of nitroglycerin at restored left ventricular and pulmonary artery pressures was characterized by increase in peak $\text{dp}\text{dt}$ (12 per cent), peak ($\text{dp}\text{dt}$ total pressure) (18 per cent), cardiac index (13 per cent), stroke volume index (14 per cent), and stroke work index (10 per cent). Both coronary blood flow (28 per cent) and myocardial oxygen consumption (21 per cent) increased parallel to the enhancement of ventricular performance.The results demonstrate that intravenous nitroglycerin produces effective diastolic and systolic unloading of the heart associated with reduction in myocardial oxygen consumption and in coronary blood flow. There was marked vascular pooling which quantitatively averaged 437 ± 128 ml. This occurred concomitant with a 43 per cent decrease in left ventricular end-diastolic pressure or a 20 per cent decrease in peak systolic pressure. Significant coronary dilating properties of nitroglycerin could not be detected in these coronary patients. The increase in left ventricular contractility indices at restored pressure suggests a moderate but significant positive inotropic effect of nitroglycerin.     

Dog lymph flow in increased capillary permeability states

The lung lymph flow rate ($\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$) is increased in edema caused by an increase in lung microvascular permeability. This increase in $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ could be caused by either a decrease in the effective resistance of the lymph vessels (R_L), or by an increase in the effective lymph driving pressure (P_L), or by a change in both R_L and P_L. We estimated P_L and R_L from the linear relationship between $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ and the pressure at the outflow end (P_O) of five cannulated dog lung lymph vessels ($\text{R}{}_{\mathrm{<mtext>L</mtext>}}\text{=}\text{?ΔP}{}_{\mathrm{<mtext>O</mtext>}}\text{Δ}\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ and P_L = the P_O at which $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}\text{= 0}$). We increased lung microvascular permeability by giving the dogs 100 mg/kg of alloxan and found that $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ increased from 24.5 ± 8.9 μl/min to 112 ± 41 μl/min (mean ± SD). R_L decreased from 0.35 ± 0.12 to 0.11 ± 0.04 cm H₂O min/μl and P_L increased from 8.5 ± 1.5 to 15.9 ± 2.7 cm H₂O. We then increased the capillary pressures from 18.3 ± 3.8 to 41.3 ± 7.3 cm H₂O and $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ increased to 169.9 ± 47.8 μl/min. P_L increased by an additional 6.3 cm H₂O but R_L decreased by only an additional 0.02 cm H₂O min/μl. These results show that the $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ vs P_O relationship is changed in edema secondary to an increase in microvascular permeability, and that this change can be represented as changes in R_L and P_L. In terms of these parameters, $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ increased in edema as a result of a decrease in R_L and an increase in P_L.     

Estimation of pulmonary/systemic resistance ratios from echocardiographic systolic time intervals in young patients with congenital or acquired heart disease

Previous work has shown the positive correlation of echocardiographic right ventricular preejection period/right ventricular ejection time ratio ($\text{RPEP}\text{RVET}$) with pulmonary vascular resistance and pulmonary arterial diastolic pressure obtained at cardiac catheterization. However, the correlation was insufficient to predict pulmonary arterial diastolic pressure or vascular resistance from a given $\text{RPEP}\text{RVET}$ ratio. In this study the $\text{RPEP}\text{RVET}$ ratio was compared with left ventricular preejection period/ejection time ratio ($\text{LVEP}\text{LVET}$) in 25 patients undergoing cardiac catheterization, and a strong correlation was found between the ratio $\text{(}\text{RPEP}\text{RVET}\text{)}\text{(}\text{LPEP}\text{LVET}\text{)}\text{=}\text{R}\text{L}$ and the ratio of pulmonary arteriolar resistance/systemic arteriolar resistance ($\text{PAR}\text{RS}$), especially when $\text{R}\text{L}$ was correlated with $\text{log}{}_{10}\text{PAR}\text{RS}$ (r = 0.902). A very high correlation (r = 0.960) was found between $\text{R}\text{L}$ and $\text{log}{}_{10}\text{PAR}\text{RS}$ when the group was restricted to patients with a ventricular septal defect or a complete endocardial cushion defect. Regression equations for prediction of $\text{PAR}\text{RS}$ have been derived for the various groups.     

Catheter evaluation of left ventricular shape and function 1 or more years after anatomic correction of transposition of the great arteries

Twenty-eight children were reinvestigated by cardiac catheterization and angiography > 1 year after anatomic correction of transposition of the great arteries (TGA). Seventeen patients with simple TGA underwent banding of the pulmonary trunk plus or minus systemic to pulmonary artery shunt to prepare the left ventricle for anatomic correction. In addition to TGA, 10 of the remaining 11 patients had a large ventricular septal defect and 1 had an aorticopulmonary window. They required no preparation of the left ventricle. Age at repair ranged from 2 to 120 months (mean 26).Catheterization 12 to 48 months after anatomic repair revealed a left ventricular end-diastolic pressure of 4 to 14 mm Hg (mean 9.5 ± 2.5 [± standard deviation]). Ejection fraction ranged from 52 to 75% (mean 66 ± 8). Frame-by-frame computer-assisted analysis of left ventricular (LV) contraction and relaxation was performed in 14 patients and compared with normal left ventriculograms. Shape index, derived as $\text{4π ×}\text{cavity area}\text{perimeter}{}^2\text{× 100}$, was measured in 24 patients and showed a mean index of 89 ± 3% at end-diastole and 79 ± 8% at end-systole. A control group had a mean diastolic index of 86 ± 6% and mean systolic index of 73 ± 8%.It is concluded that LV shape after anatomic correction tends to be more globular than normal and changes little during systole. LV ejection fraction and end-diastolic pressure are normal.     

Ventricular performance in patients based upon rate of change of power during isovolumic contraction

Energy is expended by the ventricle during isovolumic contraction as the blood within the ventricle is compressed. This isovolumic energy of compression, as well as the isovolumic rate of energy transfer (power) and acceleration of energy transfer (rate of change of power), was calculated in 17 patients with angina pectoris who underwent diagnostic cardiac catheterization. The peak isovolumic rate of change of power in patients with normal left ventricular performance (based upon the ejection fraction, mean velocity of circumferential fiber shortening and end-diastolic volume index) was 31,000 ± 3,000 dynes cm sec^?2 (mean ± standard error), whereas in those with poor ventricular performance it was 18,000 ± 2,000 dynes cm sec^?2 (P < 0.01). None of the patients with poor ventricular performance had a peak isovolumic rate of change of power that exceeded 25,000 dynes cm sec^?2. Overlap between patients with normal performance and those with reduced performance was less with the peak rate of change of power than with peak power, peak rate of change of intraventricular pressure ($\text{dp}\text{dt}$), maximal (dp/dt)/p or Vmax. The derivation of these isovolumic energy transfer rates requires no assumptions related to ventricular geometry or characteristics of muscle fibers. Peak isovolumic rate of change of power may be a useful and sensitive indicator of ventricular performance in patients with coronary artery disease.