Angiotensin II in arterial and renal venous plasma and renal lymph in the dog.

Angiotensin II was determined by radioimmunoassay in systemic arterial, pulmonary arterial, and renal venous plasma and in renal hilar lymph in dogs. Levels of the peptide were determined prior to and during progressive graded hemorrhage or reduction in renal perfusion pressure. Levels of angiotensin II in plasma consistently rose during transit through the lung indicating pulmonary conversion of angiotensin I to angiotensin II. On the other hand, angiotensin II in the renal vein plasma was less than that in arterial plasma indicating renal extraction of the peptide from plasma. When renal hilar lymph was sampled under similar conditions, angiotensin II in lymph was consistently higher than that in arterial or renal venous plasma. Furthermore, in some experiments angiotensin II in lymph increased at a time when the concentration in plasma was undetectable. No evidence was found to indicate that angiotensin II in plasma entered renal lymph. It was concluded that angiotensin II levels in lymph reflected the concentration of angiotensin II in renal tissue. The data further suggested that angiotensin II is partially removed from arterial plasma by hydrolysis during transit through the kidney.

Measurement of intracellular pH of skeletal muscle with pH-sensitive glass microelectrodes.

We used three methods to examine the relationship among intracellular pH, transmembrane potential, and extracellular pH. Single-barreled electrodes permitted the determination of resting potential and intracellular pH with a minimum of cellular injury. Double-barreled electrodes, which incorporated a reference as well as a pH-sensitive electrode in a single tip, facilitated the direct measurement of intracellular pH without the interposition of the transmembrane potential. Triple-barreled electrodes permitted measurement of intracellular pH during the controlled hyperpolarization or depolarization of the cell membrane. The results of all three methods were in close agreement and disclosed that the H(+) activity of intracellular and extracellular fluid is in electrochemical equilibrium at any given transmembrane potential. This implies that the determinants of intracellular pH are the transmembrane potential and the blood pH. The actual pH of the normal resting muscle cell is 5.99, as estimated from the normal transmembrane potential and blood pH, or as determined by direct measurements of intracellular pH.

Functional characteristics of the diluting segment of the dog nephron and the effect of extracellular volume expansion on its reabsorptive capacity.

The functional characteristics of the ascending limb of Henle's loop were examined during hypotonic saline infusion by measuring solutefree water clearance (C(H2O)) at varying rates of solute delivery. The influence of expansion of extracellular volume was studied by comparing C(H2O) during hypotonic saline diuresis in normal dogs with dogs whose extracellular volume had been expanded acutely by saline infusions or chronically by the administration of deoxycorticosterone acetate and salt. In normal animals hypotonic saline infusions greatly increased urine flow (V) and C(H2O) without appreciably augmenting osmolar clearance (C(osm)). C(H2O) was, therefore, analyzed as a function of V, rather than C(osm), since V was the best estimate of delivery of filtrate to the diluting segment. C(H2O) increased as a linear function of V without any evidence of saturation.The validity of interpreting increases in C(H2O) and V as indications of increased sodium reabsorption and delivery was reinforced by tissue studies that disclosed a rise in papillary osmolality with rising urine flows. The observed increase in C(H2O) and V could not, therefore, be due to a decrease in back diffusion of solute-free water as a result of a diminished osmotic driving force, but probably represented increased formation consequent to augmented delivery as a result of decreased fractional reabsorption in the proximal tubule. In animals whose extracellular volume was acutely or chronically overexpanded before the infusion of hypotonic saline, sodium excretion was greater, and C(H2O) less, at any given V. Although the curve relating C(H2O) to V was flatter than in the control group, no tubular maximum was observed. The diminished C(H2O) in this group was interpreted to mean that massive expansion of extracellular volume inhibits sodium reabsorption in the ascending limb of Henle's loop.

The mechanism of suppression of proximal tubular reabsorption by saline infusions.

The mechanism by which expansion of extracellular fluid volume with isotonic saline suppresses reabsorption in the proximal tubule was studied in rats by examining the relations among glomerular filtration rate (GFR), absolute and fractional reabsorption of filtrate, intrinsic reabsorptive capacity (rate of reabsorption per unit tubular volume), transit time, and tubular volume. Saline infusions reduced the per cent of the glomerular filtrate reabsorbed in the proximal tubule from 50% during antidiuresis to 25% during saline diuresis. The suppression of proximal reabsorption was the result of two factors: 1) a 30% reduction of intrinsic reabsorptive capacity, and 2) a 26% reduction of tubular volume per unit GFR.GFR invariably rose during saline diuresis. However, prevention of the rise in GFR by aortic clamping had no effect on either the inhibition of intrinsic reabsorptive capacity or the reduction in tubular volume per unit GFR produced by saline infusions. Expansion of extracellular fluid volume with isotonic saline, therefore, depressed intrinsic reabsorptive capacity and tubular volume per unit GFR by some mechanism completely independent of GFR. The effects of furosemide administration were contrasted with those of saline infusions. Furosemide inhibited intrinsic reabsorptive capacity by 40% but had no significant effect on proximal fractional reabsorption. The failure to suppress fractional reabsorption was the consequence of a disproportionate rise in tubular volume (relative to GFR) that was sufficient to completely overcome the inhibition of intrinsic reabsorptive capacity. Inhibition of intrinsic reabsorptive capacity alone, therefore, will not result in a net suppression of reabsorption of filtrate in the proximal tubule. We concluded that, although intrinsic reabsorptive capacity was inhibited during saline diuresis, the critical factor responsible for translating this inhibition into effective net suppression of proximal reabsorption was the observed reduction in tubular volume per unit GFR.

Direct determination of PCO2 in the rat renal cortex.

The mechanism by which the kidney reabsorbs sodium bicarbonate could be a result of (a) H+ secretion, (b) direct HCO3- reabsorption, or (c) a combination of both processes. Most of the studies which have supported the H+ secretory theory have involved the assumption that tubular fluid and arterial PCO2 were equal. We have utilized a new PCO2 microelectrode to directly determine in situ PCO2 of tubular fluid and stellate vessel blood in the cortex of the rat kidney during control conditions and after alterations in acid-base status. In 21 control rats, proximal tubular fluid PCO2 exceeded systemic arterial PCO2 (deltaCO2) by 25.9 +/- 0.92 mm Hg (P less than 0.001). The values obtained for both distal tubular fluid and stellate vessel blood were not significantly different from proximal tubular PCO2. Evaluation of PCO2 in the proximal tubules of Munich-Wistar rats did not reveal evidence for a declining profile for PCO2 along the length of the nephron. When proximal bicarbonate reabsorption was increased or decreased acutely by alterations in acid-base status, deltaPCO2 changed in paralle. Furthermore, benzolamide administration significantly reduced deltaPCO2. We conclude: (a) that the PCO2 in tubular fluid is significantly greater than systemic arterial PCO2, (b) that there is no tendency for the observed PCO2 to fall along the proximal tubule, (c) the mean PCO2 in the proximal and distal tubules as well as the stellate vessle is not significantly different, thereby rendering the concept of a "diffusion barrier" for CO2 in the proximal tubule unlikely, and (d) the level of renal cortical PCO2 appears to vary directly with the magnitude of bicarbonate reabsorption.

Dietary modulation of active potassium secretion in the cortical collecting tubule of adrenalectomized rabbits.

Addisonian patients can maintain potassium homeostasis despite the absence of mineralocorticoid. The present in vitro microperfusion studies examine what role the cortical collecting tubule might play in this process. All studies were performed on tubules harvested from adrenalectomized rabbits, which were maintained on 0.15 M NaCl drinking water and dexamethasone 50 mug/d. Perfusion and bath solutions were symmetrical Ringer's bicarbonate with [K] of 5 meq/liter. Initial studies on cortical collecting tubules from adrenalectomized animals ingesting a high potassium chow (9 meq K/kg body wt) demonstrated net potassium secretion against an electrochemical gradient (mean collected fluid [K] 16.5+/-2.6 meq/liter with an observed transepithelial voltage of -6.3+/-4.1 mV; predicted voltage for passive distribution of potassium being -28.2 mV). To examine whether this active potassium secretion could be modulated by dietary potassium, independent of mineralocorticoid, two diets identical in all respects except for potassium content were formulated. Potassium secretion was compared in cortical collecting tubules harvested from adrenalectomized animals on low (0.1 meq K) and high (10 meq K) potassium intake. Mean net potassium secretion by cortical collecting tubules was 2.02+/-0.54 peq mm(-1) min(-1) in the low potassium diet group and 5.34+/-.74 peq.mm(-1).min(-1) in the high potassium group. The mean transepithelial voltages of the collecting tubules did not differ between the two dietary groups. While net Na reabsorption was significantly greater in tubules from the high K group, this could not account for the differences in K secretion. These data demonstrate that: (a) the cortical collecting tubule can actively secrete potassium and that the magnitude of this potassium secretion correlates with potassium intake; (b) this active potassium secretory process in independent of mineralocorticoid. These findings support the hypothesis that the cortical collecting tubule may contribute to K homeostasis in Addison's disease.

Mineralocorticoid modulation of rabbit medullary collecting duct acidification. A sodium-independent effect.

Rabbit medullary collecting duct (MCD) from inner stripe of outer medulla has been identified as a major distal nephron acidification site. The isolated, perfused tubule technique was used to examine the roles of mineralocorticoid and glucocorticoid in regulation of MCD acidification. Surgical adrenalectomy reduced bicarbonate reabsorptive rate (JHCO3, pmol X mm-1 X min-1) from the normal of 9.79 +/- 1.21 to 0.67 +/- 1.1. Chronic administration of deoxycorticosterone acetate (DOCA) increased JHCO3 of MCD significantly to 18.02 +/- 1.62 whereas chronic dexamethasone administration did not affect JHCO3. The direct effects of aldosterone and dexamethasone upon MCD acidification were examined by perfusing tubules harvested from adrenalectomized rabbits in the presence of aldosterone or dexamethasone. Aldosterone, at 5 X 10(-8) M, increased JHCO3 significantly from 1.27 +/- 0.28 to 3.09 +/- 0.34. At 10(-6) M, aldosterone produced a greater increase in JHCO3 from 0.67 +/- 1.1 to 9.39 +/- 1.59. In vitro dexamethasone treatment had no effect on JHCO3. Studies examining the sodium dependence of aldosterone-stimulated acidification demonstrated that JHCO3 in tubules harvested from normal and deoxycorticosterone acetate-treated animals was unaffected by total replacement of sodium with tetramethylammonium. Likewise, luminal amiloride (5 X 10(-5) M) had no effect on JHCO3 in tubules harvested from adrenalectomized and normal animals. Moreover, the acute, in vitro stimulatory effect of aldosterone was seen to occur in the presence of luminal amiloride. These studies define a mammalian distal nephron segment that possesses major acidifying capacity, which is modulated by mineralocorticoid but independent of luminal sodium.

Anion dependence of rabbit medullary collecting duct acidification.

Rabbit medullary collecting duct (MCD) acidification has been demonstrated to occur by means of a sodium-independent, aldosterone-stimulated mechanism. We have examined the anionic dependence of this process by means of the isolated perfused tubule technique. Total replacement of perfusate chloride with gluconate enhanced tubular bicarbonate reabsorption (JHCO3), from a basal rate of 10.7 +/- 1.0 pmol X mm-1 X min-1 to a rate of 15.01 +/- 1.0 pmol X mm-1 X min-1. Removal of bath chloride, with and without removal of perfusate chloride completely abolished acidification. Bath, but not luminal 4-acetamido-4' isothiocyano-2,2'-disulfonic stilbene provoked a marked decrease in JHCO3 from 10.1 +/- 1.2 pmol X mm-1 X min-1 to 2.3 +/- 0.3 pmol X mm-1 X min-1. Measurement of chloride reabsorptive rate (JCl) revealed colinearity between JHCO3 (9.18 +/- 0.9 pmol X mm-1 X min-1) and JCl (9.75 +/- 1.18 pmol X mm-1 X min-1). We propose a model of mammalian distal nephron acidification in which (a) cellular base exit is effected by means of a basolateral membrane Cl-base exchanger and (b) net electroneutrality of electrogenic proton secretion is maintained by the parallel movement of an anionic species, functionally chloride.

Factors governing the transepithelial potential difference across the proximal tubule of the rat kidney.

Previous measurements of the transepithelial potential difference (PD) of the proximal tubule have yielded widely conflicting values (range -20 to +3 mV). In a recent study, Kokko has demonstrated that the PD of the in vitro perfused isolated proximal tubule of the rabbit varies in a predictable way from -6 to +3 mV, depending on the concentration of chloride, bicarbonate, glucose, and amino acids in the perfusing solution. The present micropuncture study examines the effect of tubular fluid composition on the PD profile along the proximal tubule of the in vivo rat kidney. Low resistance measuring electrodes with large tips (3-5 microns OD) filled with 3 M KCl, were used to provide stable PD recordings. Experiments were performed to validate the use of these electrodes. Transepithelial PD measurements were made in immediate postglomerular segments identified by injection of dye into Bowman's space of accessible surface glomeruli and in randomly selected more distal segments of the proximal tubule. In the control state, the first loop was found to have a small but consistently negative PD which could be obliterated by an infusion of phloridzin. In contrast, the PD in later segments was consistently positive. Infusion of acetazolamide abolished the positive PD in the later segments. Acetazolamide and glucose infusion resulted in a negative PD which was abolished by the additional infusion of phloridzin. These data provide evidence that glucose reabsorption is electrogenic and can account for the small negative PD normally present in the early proximal tubule. The positive PD in later segments appears to be a passive chloride diffusion potential. This positive potential is discussed as an important electrochemical driving force for significant passive reabsorption of sodium in the proximal tubule.

Resting transmembrane potential difference of skeletal muscle in normal subjects and severely ill patients.

The resting membrane potential difference (Em) of skeletal muscle was measured in 26 normal human subjects, 7 patients with mild illness, and 21 patients with severe, debilitating medical disorders. A closed transcutaneous approach to the muscle was made by needle puncture and the Em was measured utilizing standard Ling electrodes. Measurements revealed an Em of -88 +/-3.8 mv in healthy subjects and -89 +/-2.1 mv in patients hospitalized for minor medical problems. The mean Em in 21 in-hospital patients, judged to be severely ill clinically from a variety of causes, was -66.3 +/-9.0 mv. Open deltoid muscle biopsies were performed in 7 of the healthy subjects and in 13 of the severely ill group. Estimation of the intra-extracellular water partition was made by calculating the chloride space from the previously measured Em. Analysis of the muscle samples revealed no significant difference in the intra-extracellular potassium ratios of the two groups biopsied. Intracellular Na(+) concentrations were uniformly increased in the muscle samples of the severely ill subjects and averaged 42.3% higher than those of the normal subjects. The mechanisms which might account for the elevation of intracellular Na(+) and a depression of Em independent of changes in intra-extracellular K(+) ratios are discussed and it is suggested that this defect may be a generalized cellular abnormality which is a common quality of serious illnesses.

Characteristics of salt and water transport in superficial and juxtamedullary straight segments of proximal tubules.

The purpose of the present studies was to characterize the nature of salt and water transport out of the superficial (SF) and juxtamedullary (JM) straight segments of rabbit proximal tubules as examined by in vitro microperfusion techniques. When the perfusate consisted of a solution simulating ultrafiltrate of plasma, there were no differences between SF and JM straight tubules in either net reabsorption of fluid (SF=0.47 nl/mm per min; JM=0.56 nl/mm per min) or in transtubular potential difference (PD) (SF=-2.1 mV; JM=-1.8 mV). Removal of glucose and alanine from the perfusate had no effect on the magnitude of the PD in either straight segment. Ouabain decreased both the net reabsorptive rates and the PD. Isosmolal replacement of NaCL by Na-cyclamate (a presumed impermeant anion) in the perfusate and the bath caused an increase in luminal negativity in both segments wheras similar substitution of NaCL by choline-CL (nontransported cation) changed the PD TO NEAR ZERO. These studies, therefore, suggest that sodium is transported out of the proximal straight tubules by an active noncoupled process that generates a PD (electrogenic process). When the perfusate consisted of a solution with a high chloride concentration (resulting from greater HCO3 than CI reabsorption in the proximal convoluted tubule), different PDs in SF and JM tubules were generated: SF=+1.6 plus or minus 0.2 mV; JM=-1.3 plus or minus 0.3 mV. This difference in PD was attributed to relative differences in Na and CI permeabilities in these two segments. Electrophysiological and isotopic estimates of the chloride to sodium permeability revealed that the SF tubule is about twice as permeant to chloride than to sodium whereas the JM tubules are approximately twice as permeant to sodium than to chloride. It is concluded that the mechanism of active sodium transport in the straight segment of proximal tubule differs from that of the convoluted segment and that both the SF and JM straight segments differ from each other with respect os sodium and chloride permeability.

Effect of variation in dietary NaCl intake on the intrarenal distribution of plasma flow in the rat.

The effect of dietary variation in sodium chloride intake on the intrarenal distribution of plasma flow was investigated in rats using the antiglomerular basement membrane antibody technique. Rats were placed on a liquid diet containing either 9.86 (n = 9) or 0 (n = 9) mEq NaCl/daily portion for 2 wk. Labeled antibody was injected and the diets were reversed. After an additional 2 wk period, antibody labeled with a different radionuclide was injected and the animals were sacrificed. Fractional plasma flow distribution was then calculated for each dietary period. No change in flow to any cortical region could be detected. In six additional awake rats on identical dietary regimen, total plasma flow was estimated by the clearance of hippuran-(131)I. No change in this parameter occurred with changes in NaCl intake. We conclude, therefore, that no change in either total renal plasma flow or intracortical distribution of plasma flow occurs with wide variations in dietary sodium chloride intake in the rat. The implications of this constancy of regional plasma flow are discussed with reference to presumed concomitant alterations in the intrarenal distribution of nephron filtration rate.

Effective glomerular filtration pressure and single nephron filtration rate during hydropenia, elevated ureteral pressure, and acute volume expansion with isotonic saline.

Free-flow and stop-flow intratubular pressures were measured in rats with an improved Gertz technique using Landis micropipets or a Kulite microtransducer. In hydropenia, average single nephron glomerular filtration rate was 29.3 nl/min, glomerular hydrostatic pressure (stop-flow pressure + plasma colloid osmotic pressure) was 70 cm H(2)O and mean glomerular effective filtration pressure was 12.7-14.3 cm H(2)O, approaching zero at the efferent end of the glomerulus. Thus, the glomerulus is extremely permeable, having a filtration coefficient four to five times greater than previously estimated. Mean effective filtration pressure and single nephron glomerular filtartion rate fell with elevated ureteral pressure and rose with volume expansion, more or less proportionately. Changes in effective filtration pressure were due primarily to increased intratubular pressure in ureteral obstruction and to reduced plasma colloid osmotic pressure in volume expansion; glomerular hydrostatic pressure remained constant in both conditions and thus played no role in regulation of filtration rate.

Effect of saline infusions on intrarenal distribution of glomerular filtrate and proximal reabsorption in the dog.

The effect of acute extracellular volume expansion with saline on the intrarenal distribution of glomerular filtrate, was studied in dogs utilizing micropuncture techniques in which samples were obtained by both recollection and from new tubules. Recollection was examined in seven dogs during continuous hydropenia and in five dogs during continuous saline diuresis. Recollection was associated with an increase in nephron flow rate of 8% during hydropenia and 27% during saline diuresis. In addition, during continuous saline diuresis, shortened transit times and lowered intratubular pressures were recorded in previously punctured tubules. Despite increased tubular flow, fractional reabsorption was unchanged. Nephron glomerular filtration rates (gfr) were measured during hydropenia and then after acute volume expansion in 10 dogs. In the repunctured tubules gfr rose 38% more than total glomerular filtration rate (GFR). In contrast, when new tubules were punctured during volume expansion, nephron gfr and total GFR changed proportionately. The disproportionate rise in nephron gfr after volume expansion noted with the recollection technique appears to be artifactual when contrasted to micropuncture of new tubules. With acute volume expansion, fractional reabsorption decreased 15% in recollected samples and 16% in newly sampled tubules. Increased nephron gfr cannot account for the fall in fractional reabsorption. It is concluded that in dogs, saline diuresis is not associated with redistribution of filtrate from deep to superficial nephrons, and that the fall in proximal fractional reabsorption is caused by diminished absolute reabsorption.

Demonstration of a hormonal inhibitor of proximal tubular reabsorption during expansion of extracellular volume with isotonic saline.

Evidence for the elaboration of a hormonal inhibitor of renal tubular reabsorption in response to expansion of extracellular fluid volume was obtained by examining the effects of plasma from rats and dogs undergoing saline diuresis on the rate of proximal tubular reabsorption measured both directly by micropuncture techniques and indirectly by clearance techniques. Intravenous infusion of plasma from salineloaded rats and dogs, but not plasma from control animals, inhibited the intrinsic reabsorptive capacity of the proximal tubule (as estimated from the shrinking-drop technique) by 35%, and reduced fractional reabsorption (as estimated from the tubular fluid-to-plasma ratio) by 20%. In addition the natriuretic plasma increased urine flow, solute-free water clearance, and potassium excretion in rats with hereditary diabetes insipidus, indicating an increase in the delivery of filtrate out of the proximal tubule to the more distal diluting segments of the nephron. The hormonal inhibition of proximal tubular reabsorption had an extremely rapid onset of action (within seconds after instillation into the tubular lumen) and a short duration of action (less than 30 min after cessation of an intravenous infusion). Inhibitory activity was lost from natriuretic plasma upon dialysis and could be recovered in the dialysate. Dialysates of natriuretic plasma, when injected directly into the tubular lumen, also inhibited proximal reabsorption, indicating an action on the luminal side of the cell.

Peak regional acceleration: a method to identify subtle regional ventricular dysfunction from gated blood pool scans at rest in patients with coronary artery disease.

Peak regional acceleration images were obtained from gated blood pool scans at rest in 10 normal subjects, 16 patients who underwent cardiac catheterization for unstable angina or nontransmural infarction and were found to have normal ejection fraction and wall motion and 10 patients with prior infarction and regional dyssynergy. The second derivative of the time-activity curve of each pixel was generated and the maximal systolic value of the derivative for each pixel was displayed as a functional image (peak regional acceleration). Anterior and left anterior oblique views were evaluated for abnormalities and the presence and location of defects were correlated with the coronary anatomy. The scans from the 10 normal subjects were used to establish the normal range for regional second derivative values. Both gated blood pool scans and second derivative images showed regional abnormalities in all 10 patients with prior transmural infarction. Regional abnormalities were present in the second derivative images in the distribution of 17 of the 20 coronary arteries with greater than 50% stenosis; there were no regional abnormalities in the distribution of 7 of the 8 arteries with less than 50% stenosis. In addition, regional second derivative image abnormalities were present in 15 of the 16 patients with unstable angina and normal wall motion and global ejection fraction. These 16 patients showed regional abnormalities on second derivative images in the distribution of 19 of the 23 coronary arteries with significant stenosis and no regional abnormalities in the distribution of 21 of the 23 coronary arteries without significant stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of infarct size measured from antimyosin single-photon emission computed tomographic scans on left ventricular remodeling.

To evaluate the effect of infarct size on left ventricular volumes and geometric remodeling, 26 patients with a first acute Q wave myocardial infarction (anterior in 14, inferior in 12) had the infarct sized from single-photon emission computed tomographic (SPECT) imaging of indium-111 antimyosin. All patients underwent gated blood pool scintigraphy before hospital discharge for determination of ejection fraction and end-diastolic and end-systolic volume indexes. Infarct size was quantitated from indium-111 antimyosin uptake in coronal slices with use of a threshold technique for edge detection. Nineteen of 26 patients had additional simultaneous acquisitions of indium-111 and thallium-201 uptake and the infarct was expressed as a percent of the total left ventricle. Infarct size was larger (59 +/- 16 vs. 33 +/- 16 g), predischarge ejection fraction lower (35 +/- 5% vs. 60 +/- 9%) and end-systolic volume index higher (57 +/- 13 vs. 36 +/- 10 ml/m2) in the group with anterior infarction. Despite these differences, predischarge end-diastolic volume index was not significantly different between the group with anterior (88 +/- 17 ml/m2) versus inferior (89 +/- 14 ml/m2) infarction. There was a significant inverse correlation between percent infarct size and ejection fraction for patients with dual isotope imaging (r = -0.90) and a significant direct correlation between infarct size and end-systolic volume index (r = 0.79, p less than 0.01). Fourteen patients without subsequent myocardial infarction or coronary artery bypass grafting had a repeat gated blood pool study late (26 +/- 15 months) after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase analysis of gated blood pool scintigraphic images to localize bypass tracts in Wolff-Parkinson-White syndrome.

The ability of radionuclide techniques to localize bypass tracts in patients with Wolff-Parkinson-White syndrome to sites around the atrioventricular (AV) ring using a three view triangulation method was investigated. In 17 patients with Wolff-Parkinson-White syndrome, phase images were generated from gated blood pool scans using the first Fourier harmonic of the time-activity curve of each pixel. In addition, the difference between left and right ventricular mean phase angles was calculated for each patient and for 13 control subjects. Bypass tracts were localized to one or more sites on a 10 site grid schematically superimposed on the AV ring (Duke grid) by electrophysiologic study in all patients and by intraoperative mapping in 7 of the 17 patients. These same 10 anatomic sites were projected onto three scintigraphic views and the site of earliest ventricular phase angle was located in each view. The 10 sites around the AV ring were divided into two anatomic groups: free wall and septal/paraseptal. Phase image locations correlated with electrophysiologic locations within one grid site in 11 of 11 patients with free wall tracts and were confirmed at surgery in 5 of the 11. In five of six patients with septal/paraseptal tracts, electrophysiologic study could not localize the bypass tract to one site, whereas phase images localized two of the five as free wall adjacent to the septum, one as paraseptal and two as true posteroseptal. One posteroseptal site was confirmed at surgery. In one patient, in whom phase image analysis and electrophysiologic study showed different sites, existence of both tracts was confirmed at surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial.

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.