PubMed HealthSearch

Biomedical subjects

J I Hoffman

Publications and source records attributed to J I Hoffman.

At least 19 recordsLinked to original sources

Cardiac dimensions determined by cross-sectional echocardiography in the normal human fetus from 18 weeks to term.

Assessment of cardiac dimensions of the chambers, great arteries and veins in the human fetus is important to distinguish abnormal dimensions from normal. This study establishes normal values based on cross-sectional echocardiographic measurements over the gestational period where these measurements may be clinically useful. Ventricular and atrial dimensions were measured from the 4-chamber view, the short-axis dimension immediately below the mitral and tricuspid valve leaflets in diastole, and the long axis from the closed apposed atrioventricular valves to their respective apices. The ventricular walls and septum were measured at the level at which cavity dimensions in diastole were measured, defining both the left and right ventricular wall thickness, as well as that of the ventricular septum. Furthermore, the long axis of the right and left atria was measured from the center of the apposed atrioventricular valve leaflets to the posterior atrial wall, and the sizes of the atrial chambers were defined using their widths at the prospective broadest points through the area of foramen ovale. From a variety of views, diameters were measured at maximal expansion of the main, left and right pulmonary arteries, the ductus arteriosus, and the superior and inferior venae cavae. The data were evaluated longitudinally from 18 weeks to term, and regression analysis was performed using the best fit of a linear or polynomial equation. The data provide a means for evaluating the normal sizes and dimensions of the fetal heart chambers, as well as the thickness of the ventricular walls and septum.

Aorta

Does systolic subepicardial perfusion come from retrograde subendocardial flow?

To examine the influence of cardiac contraction on systolic coronary flow and transmural blood flow distribution, we measured phasic blood flow velocity in distal extramural coronary arteries by Doppler velocimeter and regional myocardial blood flow by radiolabeled microspheres while the heart was beating and during prolonged diastoles in 12 dogs. A servo-controlled coronary perfusion circuit allowed mean coronary pressure to be selected and maintained during beating and diastolic conditions. In epicardial arteries just proximal to their entrance into the myocardium, blood flow was either negligible or reverse in direction during systole. When the heart was beating, subepicardial blood flow was 24.2 +/- 12.3% higher than during asystole (5.05 +/- 0.91 and 4.11 +/- 0.79 ml.min-1.g-1 for beating and prolonged diastoles, respectively; P less than 0.01). In the subendocardium, flow was 49.8 +/- 14.7% lower in the beating condition than during prolonged diastoles (4.23 +/- 1.46 and 8.26 +/- 1.71 ml.min-1.g-1 for beating and asystole, respectively; P less than 0.01). When heart rate was increased stepwise from 60 to 150 beats/min, subendocardial flow fell approximately linearly; flow to the superficial layer was relatively unaffected. In beating hearts, lowering mean left main coronary artery (LMCA) pressure from 80 to 50 mmHg resulted in more systolic reverse flow and a fall in inner-to-outer flow ratio from 0.82 +/- 0.18 to 0.66 +/- 0.34 (P less than 0.05). Because mean LMCA pressure was held constant when the heart was stopped, differences in regional blood flow between beating and diastolic conditions were primarily due to cardiac contraction. Because little or no blood entered the myocardium from the extramural arteries during systole, we conclude that the decrease in subendocardial flow and the increase in subepicardial flow were caused by retrograde pumping of blood from the deep layer to the superficial layer of the left ventricle. Systolic retrograde flow to the subepicardium may help explain this layer's relative protection from ischemia.

Animals

New nonradioactive microspheres and more sensitive X-ray fluorescence to measure regional blood flow.

We developed new nonradioactive microspheres and used more sensitive X-ray fluorescence spectrometers than used previously to measure regional blood flow in the heart and other organs. We demonstrated the chemical stability of eight kinds of heavy element-loaded microspheres and validated their use for regional blood flow measurement by comparing duplicate flows measured with radioactive and/or nonradioactive microspheres in both acute and chronic dog experiments. The wavelength-dispersive spectrometer (Philips PW 1480) has a higher sensitivity than the previously described X-ray fluorescent system and reduced the number of microspheres required for accurate measurement. The fine energy resolution of this system makes it possible to increase the numbers of different kinds of microspheres to be quantitated, but at present only eight kinds are available. We also used a synchrotron radiation-excited energy dispersive spectrometer. The monochromatic synchrotron radiation allowed us to obtain much higher signal-to-background ratios of X-ray fluorescence spectra than with the wavelength-dispersive system (50 dB more for Zr-loaded microspheres) and will enable analysis of fluorescent activity in smaller regions (< 20 mg) than the radioactive method does.

Animals

Effect of neuropeptides released from sensory nerves on blood flow in the rat airway microcirculation.

Stimulation of sensory nerves in the airway mucosa causes local release of the neuropeptides substance P and calcitonin gene-related peptide (CGRP). In this study we used a modification of the reference-sample microsphere technique to measure changes in regional blood flow and cardiac output distribution produced in the rat by substance P, CGRP, and capsaicin (a drug that releases endogenous neuropeptides from sensory nerves). Three sets of microspheres labeled with different radionuclides were injected into the left ventricle of anesthetized F344 rats before, immediately after, and 5 min after left ventricular injections of capsaicin, substance P, or CGRP. The reference blood sample was withdrawn from the abdominal aorta and was simultaneously replaced with 0.9% NaCl at 37 degrees C. We found that stimulation of sensory nerves with a low dose of capsaicin causes a large and selective increase in microvascular blood flow in the extrapulmonary airways. The effect of capsaicin is mimicked by systemic injection of substance P but not by CGRP, suggesting that substance P is the main agent of neurogenic vasodilation in rat airways.

Animals

Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis.

BACKGROUND: Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts. METHODS AND RESULTS: We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01). CONCLUSIONS: The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow.

Animals

Needle penetration of the globe during retrobulbar and peribulbar injections.

The charts of 23 patients with needle penetration of the globe during retrobulbar or peribulbar injections between January 1980 and May 1990 were reviewed. Possible needle penetration risk factors included high myopia, previous scleral buckling procedures, injection by nonophthalmologists, and poor patient cooperation during the injection. Of the 23 cases of ocular penetration, 16 (70%) were from sharp (22-, 23-, and 25-gauge) needles, and 7 (30%) were from blunt (23- and 25-gauge) needles. Management options depended on the severity of the intraocular injury. Retinal breaks without retinal detachment were treated by laser photocoagulation (four cases) or cryopexy (one case) and were observed in three cases. More advanced complications (retinal detachment and vitreous hemorrhage) were usually treated by pars plana vitrectomy with or without a scleral buckle (12 of 14 cases). The final visual acuity was 20/400 or better in only 2 of the 14 retinal detachment cases. In cases without retinal detachment, the final visual acuity was 20/50 or better in 7 of 9 cases.

Adult

Cardiac contraction affects deep myocardial vessels predominantly.

To evaluate the roles of intramyocardial forces and systolic ventricular pressure in myocardial flow in the different layers separately, we measured myocardial flow in rabbit hearts during stable systolic contracture with left ventricular pressures of 60 (n = 5) and 0 mmHg (n = 5) and during stable diastolic arrest (n = 5). We also measured the number and size of the intramyocardial vessels after perfusion fixation (systolic arrest, n = 5; diastolic arrest, n = 5). In 25 rabbits, hearts were excised and perfused from the aortic root. Systolic arrest was achieved by perfusion of a low-Ca2+ Tyrode solution containing 2.0 mM Ba2+. Diastolic arrest was achieved by intraventricular injection of 700-1,000 mg pentobarbital sodium and was maintained by perfusion with St. Thomas cardioplegic solution. At perfusion pressure of 100 mmHg, subendocardial flow was lower than subepicardial flow during systolic arrest regardless of left ventricular pressure, whereas during diastolic arrest, subendocardial flow was higher than subepicardial flow. Subendocardial-to-subepicardial flow ratios for a physiological range of perfusion pressures were lower during systolic arrest with low rather than with high left ventricular pressure. Small arteriolar and capillary densities showed no difference between subendocardium and subepicardium. During systolic arrest, diameters of subendocardial terminal arterioles (4.6 +/- 1.3 microns) and capillaries (4.0 +/- 1.3 microns) were smaller than those in the subepicardium (8.8 +/- 1.7 and 7.1 +/- 1.6 microns, respectively; P less than 0.0001), whereas during diastolic arrest, diameters of subendocardial terminal arterioles (10.1 +/- 2.0 microns) and capillaries (7.6 +/- 1.8 microns) were slightly larger than those in the subepicardium (9.5 +/- 1.5 and 6.7 +/- 1.0 microns, respectively; P less than 0.01). We conclude that cardiac contraction predominantly affects subendocardial vessels and impedes subendocardial flow more than subepicardial flow regardless of left ventricular pressure.

Animals

Nonuniform blood flow in the canine left ventricle.

In order to investigate the relationship between coronary perfusion pressure and blood flow distribution in the left ventricle (LV), we measured myocardial blood flow in small regions using radioactive microspheres in six anesthetized, open-chest dogs. Mean coronary perfusion pressure (CPP) was controlled with a femoral artery to left main coronary artery shunt which included a pressurized, servo-controlled blood reservoir. In each dog, we measured flow in 192 regions of the LV free wall (mean weight per region = 206 +/- 38 mg) at different perfusion pressures. At CPP = 80 mm Hg, blood flow to individual regions varied fourfold (0.30 to 1.18 ml/min/g; relative dispersion (RD) = 21.8 +/- 2.3%). At CPP = 50 mm Hg, flow varied over sevenfold (0.08 to 0.60 ml/min/g; RD = 42.8 +/- 10%; P less than 0.01 vs 80 mm Hg). This relationship between flow variability and CPP was present within individual LV layers as well between layers and is much higher than the error associated with the microsphere technique. We conclude that blood flow to small regions of the LV is markedly nonuniform. This heterogeneity becomes more profound at lower CPP. These findings suggest that (1) global measurements of coronary flow must be interpreted with caution, and (2) even in hearts with normal coronary arteries some regions of the LV are more susceptible to ischemia than others. In addition, these findings may help explain the patchy nature of myocardial damage that occurs following periods of low coronary pressure or inadequate myocardial protection during cardiopulmonary bypass.

Animals

Congenital heart disease: incidence and inheritance.

Congenital heart disease occurs in approximately 1 per cent of liveborn children, but in a much higher percentage of those aborted spontaneously or stillborn. To detect as many as possible with CHD, including those with mild lesions, very intensive studies are needed. Studies that are not so intensive, especially those done before modern diagnostic techniques were in general use, considerably underestimated the incidence of CHD in liveborn children. It appears that the incidence of CHD and of the various individual lesions does not differ in different countries or at different times, providing the ascertainment of CHD is complete and accurate. The commonest form of CHD is the ventricular septal defect, which occurs in 30 to 40 per cent of all children with CHD. The risks of recurrence in siblings and of transmission to future generations depends on the exact mode of inheritance involved. Approximately 5 to 8 per cent of CHD is due to gross chromosomal abnormalities, and the recurrence risk is that of the chromosomal derangement itself. Because many children with these chromosomal lesions die in infancy or have reduced fertility, the risk to future generations is relatively low. About 3 per cent of CHD is due to classical Mendelian gene effects, with correspondingly high recurrence risks in first-degree relatives. Most CHD has lower risks of recurrence and transmission than those predicted by Mendelian single-gene action. The popular explanation for their inheritance has been the interaction of polygenic effects and the environment, but recent studies of the recurrence and transmission risks of various forms of CHD do not fit this model well. The alternative model is a single gene defect modulated by random events. The recurrence risks for future siblings are 2 to 6 per cent, and for offspring are 1 to 10 per cent, but in a few families the recurrence and transmission risks may be much higher.

Chromosome Aberrations

Local blood flow measured by fluorescence excitation of nonradioactive microspheres.

An X-ray fluorescence system with low Compton background and high counting efficiency was developed to measure regional blood flow with nonradioactive microspheres. The performance of the system was tested in vitro by counting mixed aqueous solutions of either Mo, Ag, and I; Nb, Ag, and Ba; or Zr, Mo, Rh, Ag, Sn, I, and Ba, as well as a mixture of Ag and Ba nonradioactive microspheres. Mixtures containing 2-20 ppm of each element were counted for 10 min by the fluorescence system, and the individual elements in mixtures of three to seven nonradioactive elements were measured with high accuracy. The best counting statistics were obtained for Ag. For 10-min counts, the system measures as few as 120 Ag microspheres with 30% standard deviation but measures 800 Ag microspheres per sample with 3.6% standard deviation. We compared regional myocardial blood flows determined simultaneously by fluorescence and radioactive microsphere methods; the latter samples were counted by a 3-in. NaI (Tl) well detector and pulse-height analyzer. The radioactive and nonradioactive measurements showed good correlations.

Animals

Pressure-flow relations in coronary circulation.

The blood vessels that run on the surface of the heart and through its muscle are compliant tubes that can be affected by the pressures external to them in at least two ways. If the pressure outside these vessels is higher than the pressure at their downstream ends, the vessels may collapse and become Starling resistors or vascular waterfalls. If this happens, the flow through these vessels depends on their resistance and the pressure drop from their inflow to the pressure around them and is independent of the actual downstream pressure. In the first part of this review, the physics of collapsible tubes is described, and the possible occurrences of vascular waterfalls in the body is evaluated. There is good evidence that waterfall behavior is seen in collateral coronary arteries and in extramural coronary veins, but the evidence that intramural coronary vessels act like vascular waterfalls is inconclusive. There is no doubt that in systole there are high tissue pressures around the intramyocardial vessels, particularly in the subendocardial muscle of the left ventricle. The exact nature and values of the forces that act at the surface of the small intramural vessels, however, are still not known. We are not certain whether radial (compressive) or circumferential and longitudinal (tensile) stresses are the major causes of vascular compression; the role of collagen struts in modifying the reaction of vessel walls to external pressures is unknown but possibly important; direct examination of small subepicardial vessels has failed to show vascular collapse. One of the arguments in favor of intramyocardial vascular waterfalls has been that during a long diastole the flow in the left coronary artery decreases and reaches zero when coronary arterial pressure is still high: it can be as much as 50 mmHg in the autoregulating left coronary arterial bed and approximately 15-20 mmHg even when the vessels have been maximally dilated. These high zero flow pressures, especially during maximal vasodilatation, have been regarded as indicating a high back pressure to flow that is due to waterfall behavior of vessels that are exposed to tissue pressures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Nonuniform loss of regional flow reserve during myocardial ischemia in dogs.

To determine whether coronary vasodilator reserve that persists during myocardial ischemia is present in all left ventricular regions, we measured regional blood flow in 192 left ventricular pieces (mean weight, 201 mg) in each of eight dogs by using radioactive microspheres while perfusing the left main coronary artery at 70, 50, 40, and 30 mm Hg. Flows were measured before and during adenosine infusion to determine flow reserve. Perfusion at 40 and 30 mm Hg produced ischemia in all dogs. At 70 mm Hg, 100% of left ventricular regions had significant flow reserve, compared with 92%, 55%, and 8% during perfusion at 50, 40, and 30 mm Hg, respectively. A greater amount of flow reserve and a greater number of regions responded to adenosine in the subepicardium than in the subendocardium at 50, 40, and 30 mm Hg. We conclude that coronary flow reserve persists in only a subset of left ventricular regions during ischemia and that the number of regions with persistent flow reserve decreases with perfusion pressure. These findings may best be explained by a model in which regional ischemia is a maximal coronary vasodilator and persistent pharmacological vasodilator reserve seen when global markers indicate ischemia simply reflects persistent endogenous flow reserve in myocardial regions not yet ischemic.

Adenosine

Profound spatial heterogeneity of coronary reserve. Discordance between patterns of resting and maximal myocardial blood flow.

We examined the ability of individual regions of the canine left ventricle to increase blood flow relative to baseline rates of perfusion. Regional coronary flow was measured by injecting radioactive microspheres over 90 seconds in seven anesthetized mongrel dogs. Preliminary experiments demonstrated a correlation between the regional distributions of blood flow during asphyxia and pharmacological vasodilatation with adenosine (mean r = 0.75; 192 regions in each of two dogs), both of which resulted in increased coronary flow. Subsequent experiments, during which coronary perfusion pressure was held constant at 80 mm Hg, examined the pattern of blood flow in 384 regions (mean weight, 106 mg) of the left ventricular free wall during resting flow and during maximal coronary flow effected by intracoronary adenosine infusion. We found that resting and maximal flow patterns were completely uncorrelated to each other in a given dog (mean r = 0.06, p = NS; n = 3 dogs). Furthermore, regional coronary reserve, defined as the ratio of maximal to resting flow, ranged from 1.75 (i.e., resting flow was 57% of maximum) to 21.9 (resting flow was 4.5% of maximum). Thus, coronary reserve is spatially heterogeneous and determined by two distinct perfusion patterns: the resting (control) pattern and the maximal perfusion pattern. Normal hearts, therefore, contain small regions that may be relatively more vulnerable to ischemia. This may explain the patchy nature of infarction with hypoxia and at reduced perfusion pressures as well as the difficulty of using global parameters to predict regional ischemia. Despite the wide dispersion of coronary reserve, we found, by autocorrelation analysis, that reserve in neighboring regions (even when separated by a distance of several tissue samples) was significantly correlated. This also applied to patterns of resting myocardial flow. Thus, both resting coronary blood flow and reserve appear to be locally continuous and may define functional zones of vascular control and vulnerability, respectively.

Adenosine

Heterogeneous delivery of cardioplegic solution in the absence of coronary artery disease.

The prevention of intraoperative myocardial damage with cardioplegic solution depends in large measure on the completeness of its delivery. We created a model to study the regional flow distribution of cardioplegic solutions in nondiseased, diastolically arrested, maximally vasodilated canine hearts. Global and regional myocardial flows were measured at different perfusion pressures in hearts perfused either with blood cardioplegic solution (n = 8) or oxygenated crystalloid cardioplegic solution (n = 2). As coronary perfusion decreased, flow in all layers fell significantly (p less than 0.001). This fall was most dramatic in the subendocardium (p less than 0.05). With both types of cardioplegic solutions, the relationship between pressure and flow was nonlinear: At low coronary perfusion pressures, a given change in pressure resulted in a smaller change in flow than at higher perfusion pressures. In addition, we found that in all dogs and at all pressures there was profound variability in the delivery of cardioplegic solution to different small regions of the left ventricular free wall. At a perfusion pressure of 40 mm Hg, the extremes of regional flow differed on average by 203%. This heterogeneity increased significantly with decreasing perfusion pressures. At the lowest perfusion pressure measured (20 mm Hg), the extremes of regional flow differed on average by 365%. These findings emphasize the importance of coronary pressure on the delivery of cardioplegic solution. At low perfusion pressures, not only is mean flow reduced, but a greater number of regions receive limited amounts of cardioplegic solution. These observations may explain the patchy nature of subendocardial damage seen with inadequate myocardial protection.

Animals

Quantitating error in blood flow measurements with radioactive microspheres.

Accurate determination of the reproducibility of measurements using the microsphere technique is important in assessing differences in blood flow to different organs or regions within organs, as well as changes in perfusion under various experimental conditions. The sources of error of the technique are briefly reviewed. In addition, we derived a method for combining quantifiable sources of error into a single estimate that was evaluated experimentally by simultaneously injecting eight or nine sets of microspheres (each with a different radionuclide label) into four anesthetized dogs. Each nuclide was used to calculate blood flow in 145-190 myocardial regions. We compared each flow determination (using a single nuclide label) with a weighted mean for the piece (based on the remaining nuclides). The difference was defined as "measured" error. In all, there were a total of 5,975 flow observations. We compared measured error with theoretical estimates based on the Poisson error of radioactive disintegration and microsphere entrapment, nuclide separation error, and reference flow error. We found that combined estimates based on these sources completely accounted for measured error in the relative distribution of microspheres. In addition, our estimates of the error in measuring absolute flows (which were established using microsphere reference samples) slightly, but significantly, underestimated measured error in absolute flow.

Animals

Usefulness and limitations of regional cardiac sympathectomy by phenol.

We evaluated the completeness and extent of regional sympathetic denervation of the left ventricle after epicardial painting with phenol in anesthetized dogs. In a region encircled by phenol, the effect of electrical stimulation of efferent sympathetic fibers on myocardial contractility and coronary vascular resistance was completely abolished within 30 min. Denervation extended to untreated regions innervated by sympathetic fibers crossing the phenol line. For at least 4 h after phenol application, intravenous infusion of isoproterenol or coronary arterial infusion of tyramine increased myocardial contractility in the denervated region; norepinephrine content and neurotransmitter uptake were normal, indicating that nerve terminals, postjunctional receptors, and myocardium remained functional. However, after 3-14 days, tissue catecholamine content and transmitter uptake in the encircled area were markedly reduced. The results suggest that careful evaluation is necessary in selecting a fully innervated control region in studies employing regional sympathetic denervation with phenol.

Administration, Topical

Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.

We ligated the left anterior descending coronary artery for 1 or 2 h in 31 purebred beagles. We did not detect any changes in beta-adrenergic receptor density or affinity when normal and ischemic zones were compared, either in the subendocardium or in the subepicardium. In the ischemic zones, there was a significant decline in all measures of adenylate cyclase activity, including activity mediated by the beta-adrenergic receptor. By contrast, after chronic beta-adrenergic blockade (1.5 mg/kg propranolol i.v. twice daily for 7 d), there was an increase in adenylate cyclase activity stimulated by (-)-isoproterenol relative to adenylate cyclase activity stimulated by guanyl-5'imidodiphosphate (GppNHp) in both normal and ischemic tissue, suggesting that one effect of chronic beta blockade may be to enhance coupling between the stimulatory guanine nucleotide regulatory protein (Gs) and the beta-adrenergic receptor, despite a reduction in the number or function of Gs units. Chronic beta blockade also led to up regulation of beta-adrenergic receptor density in subepicardial regions. After 20 min of reperfusion following 2 h of ischemia, adenylate cyclase activity tended to return to control levels, particularly in the subepicardium, where (-)-isoproterenol-stimulated adenylate cyclase activity was not different from normal myocardium. We conclude that chronic beta-adrenergic blockade may have beneficial effects during prolonged episodes of myocardial ischemia by preserving signal transduction mediated by the beta-adrenergic receptor.

Adenylyl Cyclases