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.     

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.     

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.     

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.     

Synthesis of glucose in human thrombocytes

Net synthesis of carbohydrates could be demonstrated at a rate of $\text{12 μ}\text{mole/hr}\text{10}{}^{11}$ cells by incubating human thrombocytes in a buffered solution in the presence of 20 mM pyruvate and 2.5 mM ATP. Moreover, incorporation of isotopic carbon from pyruvate-2-¹⁴C into carbohydrates was measured to occur at a rate of $\text{0.7 μ}\text{mole/hr}\text{10}{}^{11}$ cells in the absence of added ATP and of $\text{2.2 μ}\text{mole/hr}\text{10}{}^{11}$ cells in the presence of 7.5 mM ATP. The addition of 20 mM pyruvate and of increasing amounts of ATP (up to 7.5 mM) were shown to have a sparing effect on carbohydrate utilization. On the other hand, increasing the cell concentration from 3.3 × 10⁸ to 16.5 × 10⁸ cells/ml in the incubation medium resulted in an increase of glucose uptake from the medium. It is concluded that thrombocytes are capable of synthesizing carbohydrates from pyruvate.     

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.     

Influence of nifedipine on left ventricular systolic and diastolic function: Relationships to manifestations of ischemia and congestive failure

In addition to the favorable effects of calcium antagonists on symptoms related to coronary spasm, we recently documented preclusion of ergonovine-induced coronary spasm angiographically in four patients with proved Prinzmetal's angina.To determine whether nifedipine has similar “relaxing” or negative inotropic actions on left ventricular myocardial function, we studied 19 patients with various degrees of left ventricular dysfunction before and after nifedipine (20 mg sublingually) during cardiac catheterization. Left ventricular afterload was reduced, with a significant (13 percent) decline in arterial pressure; left ventricular diastolic pressures were unchanged. Left ventricular ejection function was augmented, with significant increases in ejection fraction (14 percent), mean velocity of circumferential fiber shortening (41 percent), systolic ejection rate (25 percent), and end-systolic $\text{pressure}\text{volume}$ ratio (19 percent). Cardiac index increased significantly by 16 percent. Early diastolic relaxation, diastolic pressure-volume relations and end diastolic stiffness remained unchanged after nifedipine. When patients were categorized (Group I: left ventricular end-diastolic volume ≤ 90 ml/m², end-diastolic pressure ≤ 20 mm Hg; Group II: end-diastolic volume > 90 ml/m², end-diastolic pressure > 20 mm Hg), highly pertinent differences were apparent. Nifedipine significantly reduced left ventricular preload and end-diastolic pressures in Group II but not in Group I patients. Enhancement of left ventricular ejection function in Group II patients was significantly more prominent than that in patients with normal baseline function. Although diastolic properties were insignificantly changed overall, the left ventricular diastolic pressure-volume relation was displaced downward by nifedipine in Group II, but not in Group I patients. Both systemic and pulmonary vascular resistance declined significantly more in Group II patients, whereas cardiac index was increased 25 percent compared with a negligible change in group I patients. These results indicate beneficial effects of nifedipine on myocardial oxygen requirements, particularly in patients with impaired left ventricular function in whom left ventricular preload and afterload were both significantly reduced, cardiac index augmented and the pressure-volume relation shifted downward.To confirm predicted symptomatic benefits in 13 other patients with fixed coronary, disease, incremental atrial pacing to anginal threshold was performed before and 30 minutes after nifedipine (20 mg sublingually). Mean paced heart rate at onset of angina increased 19.3 percent after nifedipine. Concomitantly, aortic pressure decreased significantly by 22.1 percent at the onset of angina; double product was unchanged at the anginal threshold. Thus, although left ventricular afterload was reduced by nifedipine, the anginal threshold was unchanged in terms of myocardial oxygen requirements.In concert, these results indicate that therapeutically effective influences of nifedipine in patients with fixed coronary disease are attributable basically to hemodynamic alterations consequent upon left ventricular afterload reduction. Nevertheless, such effects imply therapeutic benefit, the reduced afterload concomitantly permitting greater exercise-induced tachycardia before the anginal threshold is reached.     

Progressive transmural electrographic,myocardial potassium ion/sodium ion ratio and ultrastructural changes as a function of time after acute coronary occlusion

The progressive transmural electrographic, biochemical and ultrastructural changes as a function of time after acute coronary occlusion were systematically assessed in eight dogs. Transmural plunge electrodes with poles 1 mm apart were placed in the ischemic and nonischemic zones, and coronary occlusion was maintained for 4 hours. Transmural full thickness biopsy specimens were obtained from each zone for electron microscopy before, and 1 and 4 hours after occlusion. Endocardial and epicardial layers were also obtained for assessment of myocardial potassium ion (K⁺) and sodium ion (Na⁺) concentrations. Before coronary occlusion, local Q waves were recorded an average depth of 1.0 ± 0.34 mm from the endocardial surface. After 1 hour of occlusion, Q waves appeared at an average depth of 3.8 ± 0.67 mm and progressed to a depth of 5.2 ± 0.7 mm at 2 hours, 6.2 ± 0.5 mm at 3 hours and 7.0 ± 0.5 mm at 4 hours. After 1 hour, ultrastructural changes of early ischemia, including a decrease in glycogen and mild mitochondrial swelling, were seen in the endocardial layer; the epicardial layer showed normal morphologic features. After 4 hours, the endocardial layer showed well developed ischemic changes marked by the loss of mitochondrial cristae, vacuolization, the appearance of amorphous mitochondrial densities, an increase in interfibrillary space and the appearance of I bands. In contrast, the epicardial layer at this time showed only early ischemic changes. At the end of 4 hours, the endocardial layer showed a marked decrease in myocardial K⁺ concentration and an increase in Na⁺ concentration leading to complete reversal of the $\text{K}{}^{\mathrm{+}}\text{Na}{}^{\mathrm{+}}$ ratio (0.7 ± 1.0; P < 0.001). In the epicardial layer, a smaller decrease in K⁺ concentration and an increase in Na⁺ concentration occurred, resulting in a diminution but not a reversal of the $\text{K}{}^{\mathrm{+}}\text{Na}{}^{\mathrm{+}}$ ratio (1.4 ± 0.2; P < 0.005).Thus, the dynamic evolution of an acute myocardal infarction involves a sequential progression from endocardium to epicardium as a function of time, resulting in an epicardial “border zone” in the early stages after acute coronary occlusion.     

Blood oxygen measurements in the assessment of intracardiac left to right shunts: A critical appraisal of methodology

The proper use of sequential diagnostic blood oxygen determinations for assessing left to right shunts requires a thorough understanding of the normal variability of blood oxygen measurements among the various right heart chambers and the influence of alterations in circulating hemoglobin levels and systemic blood flow. Oximetric measurements were obtained in 23 patients without a left to right shunt and compared with measurements obtained in 42 patients with a proved left to right shunt to examine the normal range of oxygen variability in blood samples from right heart chambers. The effect of fluctuations in hemoglobin levels was evaluated by comparing increases in percent oxygen saturation and oxygen content. Differences in percent saturation were found to be more useful than differences in oxygen content for detection of cardiac shunts. A mean difference of at least 7 percent oxygen saturation was found to be required for a firm diagnosis of a shunt at the atrial level, and 5 percent oxygen saturation for a shunt at the ventricular or great vessel level.The curvilinear relation between systemic blood flow and oxygen step-up in determining the pulmonary to systemic flow ($\text{Q}{}_{\mathrm{P}}\text{Q}{}_{\mathrm{S}}$) ratio was expressed in a series of equations and depicted by a three dimensional surface. Interventions such as exercise augment both systemic blood flow and oxygen step-up, resulting in a shift to a more steeply rising portion of the surface and a dramatic increase in shunt flow. The minimal left to right shunt detectable with oxlmetry is largely dependent on the level of systemic blood flow.     

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.     

Variability in sequential measures of left ventricular performance assessed with radionuclide angiocardiography

The variability of left ventricular ejection fraction, normalized mean ejection rate and regional wall motion was evaluated from first pass quantitative radionuclide angiocardiograms obtained with a computerized multicrystal scintillation camera. Three radionuclide studies separated by an average of 4.3 days were obtained in each of 20 patients. Ejection fraction and ejection rate obtained on the first, second and third studies did not differ significantly. The mean (± standard deviation) variability of sequential ejection fraction measurement was 4.4 ± 3.6 percent, and of sequential ejection rate was 0.56 ± 0.47 sec^?1. Variations in measurements were not related to fluctuations in heart rate or blood pressure. Variability in ejection rate was significantly greater in patients with normal function than in those with abnormal function. Regional wall motion analysis was constant in 19 of 20 patients. Thus, sequential quantitative radionuclide angiocardiography allows reproducible serial assessment of left ventricular performance that can be performed with a low level of intrinsic variability.     

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.     

Left ventricular function in systole and diastole in constrictive pericarditis

Left ventricular function was studied in systole and diastole in 30 patients with constrictive pericarditis. Left ventricular end-diastolic volume was used to divide the patients into three arbitrary groups: severe constriction (EDV < 25 ml./M.²), moderate constriction (EDV 25 to 50 ml./M.²), and mild constriction (EDV > 50 ml./M.²).The patients had high ventricular diastolic and venous filling pressures (mean LVEDP = 23 ± 7 mm. Hg, mean RVEDP = 20 ± 7 mm. Hg). Measurements related to absolute fiber shortening (stroke index, stroke work index, and left ventricular ejection rate) were reduced and linearly related to the degree of constriction as assessed by the end-diastolic volume.Measurements of relative fiber shortening or lengthening (ejection and filling fraction and circumferential fiber shortening) were normal despite great reduction in ventricular volumes.Velocity measurements, peak LV $\text{dp}\text{dt}$ and mean velocity of circumferential fiber shortening were normal or slightly reduced.These changes were reflected in the systolic time interval measurements pre-ejection phase, left ventricular ejection time, and the ratio $\text{PEP}\text{LVET}$.Diastolic function of the ventricle was abnormal; the distensibility index of the ventriculo-pericardial system ($\text{ΔV}\text{ΔP}$) was low and the passive elastic modulus in-increased. The change in compliance correlated with the degree of constriction and there was a linear relationship between compliance and EDV.The ventricle was underloaded despite the high filling pressure and stroke work index was reduced; extrinsic compression raised the diastolic pressure and reduced left ventricular volumes.     

The relationship between the Gompertz constant and maximum potential lifespan; Its relevance to theories of aging

A correlation between the two aging parameters, the Gompertz constant, α and the maximum potential lifespan T is obtained. The product of α and T lies between 2 and 12 for mammals which have ceased to grow in their adult years, fish which continue to grow throughout life and rotifers, which have a constant number of cells. Since T is related to the metabolic rate, m, as $\text{m}{}^{\mathrm{<mtext>?</mtext><mtext>3</mtext><mtext>4</mtext>}}$, then α must be related to the metabolic rate as $\text{m}{}^{\mathrm{<mtext>+</mtext><mtext>3</mtext><mtext>4</mtext>}}$. It is suggested that somatic mutations play a lesser role than metabolism in aging.     

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.     

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.     

Temperature-dependency of the functional activities of dog cardiac sarcoplasmic reticulum: a comparison with sarcoplasmic reticulum from rabbit and lobster muscle.

Temperature-dependency studies of the functional activities of sarcoplasmic reticulum vesicles from different muscle sources have been carried out. The energies of activation of transport and hydrolytic processes of microsomes from dog heart have been found to be higher than those obtained with rabbit and lobster skeletal muscle. This difference is reduced in the presence of membrane perturbing agents as the detergent Triton X-100 or the Ca²⁺-ionophore A-23187, indicating that the different level of the functional ability of microsomal vesicles isolated from different tissues might be due mainly to differences in the lipid environment. Thermodynamic parameters ($\text{Δ}\text{G}{}^3$, $\text{Δ}\text{H}{}^3$, $\text{Δ}\text{S}{}^3$ of the Ca²⁺-transport and Ca²⁺-dependent ATPase reactions of cardiac microsomes pre-phosphorylated with cAMP-dependent protein kinase have been determined. The stimulatory effect of protein kinase can be interpreted as a change in the fluidity of the hydrophobic microenvironment of the ATPase molecules. The transport process if entropically more favourable in pre-phosphorylated than in control microsomes.     

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.     

Sex dependence of aldosterone response in rats

The dose/response relationship of aldosterone as measured by the urinary $\text{Na}{}^{\mathrm{+}}\text{K}{}^{\mathrm{+}}$ ratio was significantly different in male and female adrenalectomized rats: the males showing a greater physiologic response to aldosterone than females. This sex dependence also existed when the components of the physiologic response, antinatriuresis and kaliuresis, were determined individually. The correlation is made between the higher physiologic response to aldosterone and the greater metabolism of aldosterone in male rats.     

Adaptation to fresh water in the sea snake Hydrophis cyanocinctus: Tissue electrolytes and peripheral corticosteroids

Groups of mature sea snakes, Hydrophis cyanocinctus, were transferred from seawater to tanks of running fresh water and sampled at 10, 16, 21, 27, 31, 35, and 51 days after transfer. The following were measured as parameters of adaptation to fresh water and compared with control (seawater maintained) animals: rate of weight loss; muscle water and ion content; blood hematocrit; plasma osmolarity; plasma Na⁺, K⁺, Cl^?, and urea concentrations. Peripheral levels of corticosterone and aldosterone were measured using competitive protein binding assay and radioimmunoassay, respectively. Adrenal in vitro 18-oxygenase activity was determined radiometrically using [³H]corticosterone. The rate of weight loss was lower in snakes in fresh water, but hematocrit and tissue water composition were unaltered. Plasma ion concentrations and total osmolarity fell significantly within 10 days and stabilized after approximately 16 days. Only after 51 days did muscle ionic composition or plasma $\text{Na}{}^{\mathrm{+}}\text{K}{}^{\mathrm{+}}$ alter. Urea was below detectable levels in all animals. Peripheral aldosterone concentrations remained at 1 to 4 μg/100 ml plasma whereas mean corticosterone titers fell significantly from 8 to 3 μg/100 ml. Adrenal in vitro 18-oxygenase activity was, however, significantly increased after 51 days of freshwater treatment. It was concluded that H. cyanocinctus is an osmoconforming euryhaline reptile, and possible roles for the adrenal in hydromineral balance are discussed.