Stanton Glantz' Animal Experiments

How does a mechanical engineer become a professor of medicine at a famous university without going through the hassle of acquiring a doctorate of medicine?  Why utilizing the anti-smoking shortcut available for con artists more concerned with ideology than with scientific rigor.  It also doesn't hurt to have climbed to the heights upon mounds of dead animals sacrificed to show how bad smoking is.

Although Glantz no longer has to sully his hands slicing and dicing lab animals, his past is replete with experiments upon dogs, cats, rabbits and lambs, some of which were conducted to prove how deadly secondhand smoke is to nonsmokers.

Rabbits - Secondhand smoke

To back up the epidemiology that contends that environmental tobacco smoke (ETS) causes death from heart disease in nonsmokers, 64 New Zealand rabbits were divided in groups where different levels of ETS pumped in after feeding them a cholesterol diet.

After 10 weeks all rabbits expired, but not from ETS.  Glantz killed them and extracted their organs for study.  After much examination, tabulating and comparisons of their entrails, the rabbits appear to have died in vain.

Since Glantz never refers to this study when touting his still unproven claim that secondhand smoke causes heart disease, it's obvious that this experiment was a failure.  So demoralized was he by this direct anti-tobacco research that Glantz now prefers juggling statistics, loony extrapolations and political coercion.1  

Glantz must not be considered squeamish, however.  He has plenty of notches on his belt for animals sacrificed to his career.


Fresh from the birthing chamber, six lambs were were acutely instrumented with micromanometer-tipped catheters and two pairs of ultrasonic crystals to measure left ventricular pressure and anterior-posterior and septal-free wall dimensions.  Their aortas artificially constricted, the lambs endured blood transfusions and fluctuating pressure.2


A three-element model describes excised cat papillary muscle elasticity.  It may just be cat gut to Glantz but the cats undoubtedly would have preferred keeping their papillary muscles inside their chests.3



Nearly two dozen pigs opened their chests for research on segment stroke work and metabolism dependant on coronary blood flow.  Pumps manipulated the flow of blood, sometimes flooding the veins and sometimes reducing flow to a trickle.  Fortunately for the pigs, Glantz notes that the porkers were anesthetized.4



Many of man's best friends bit the dust to give their all for Glantz' research on the heart.  Ranging from open chest experiments to study ventricular dynamic geometry to ventricle extractions to measure muscle stiffness, Glantz has done it all.  Specimens ranged from adult dogs to puppies.  Many were shot up with pharmaceuticals to examine how the dogs reacted to the outrages they were subjected to.

Rabbits - ETS

Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits.

Zhu BQ, Sun YP, Sievers RE, Isenberg WM, Glantz SA, Parmley WW.

Department of Medicine, University of California, San Francisco.

OBJECTIVES. We evaluated the influence of passive smoking on experimental atherosclerosis in cholesterol-fed rabbits. BACKGROUND. Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. METHODS. New Zealand male rabbits were randomly divided into three groups after 2 weeks of a 0.3% cholesterol diet. Sixteen rabbits were exposed to a high and 16 rabbits to a low dose of ETS; 32 rabbits located in another room served as an unexposed control group. After 10 weeks of ETS exposure, all rabbits were killed, and the percent of aortic and pulmonary artery endothelial surfaces covered by lipid lesions was measured by staining and planimetry. RESULTS. Average air nicotine, carbon monoxide and total particulate concentrations were 1,040 micrograms/m3, 60.2 ppm and 32.8 mg/m3 for the high dose ETS group, 30 micrograms/m3, 18.8 ppm and 4.0 mg/m3 for the low dose ETS group and < 1 microgram/m3, 3.1 ppm and 0.13 mg/m3 for the control group. The percent atherosclerotic involvement of the aorta and pulmonary artery increased significantly with ETS exposure (for the aorta, 30 +/- 19% [mean +/- SD] for the control group, 36 +/- 14% for the low dose ETS group and 52 +/- 21% for the high dose ETS group, p < 0.001; for the pulmonary artery, 22 +/- 15% for the control group, 29 +/- 25% for the low dose ETS group, and 45 +/- 12% for the high dose ETS group, p < 0.001). Bleeding time was significantly shorter in the two ETS groups than in the control group (86 +/- 17 vs. 68 +/- 15, 68 +/- 18 s, p < 0.001). There were no significant differences in serum triglycerides, cholesterol and high density lipoprotein cholesterol at the end of the study. CONCLUSIONS. Environmental tobacco smoke affects platelet function and increases aortic and pulmonary artery atherosclerosis. This increase of atherosclerosis was independent of changes in serum lipids and exhibited a dose-response relation. These results are consistent with data from epidemiologic studies demonstrating that ETS increases the risk of death due to heart disease.

PMID: 8417066 [PubMed - indexed for MEDLINE]


Pediatr Res 1993 Apr;33(4 Pt 1):359-64 Related Articles, Links

Mechanically increased right ventricular afterload alters left ventricular configuration, not contractility, in neonatal lambs.

Milstein JM, Glantz SA.

Department of Pediatrics, University of California, Davis 95616.

Left ventricular dysfunction has been observed in human infants with pulmonary hypertension. The purpose of this study was to establish whether mechanically increased right ventricular afterload alters left ventricular performance by altering its contractility, configuration, or both. Six neonatal 3- to 7-d-old lambs were acutely instrumented with micromanometer-tipped catheters and two pairs of ultrasonic crystals to measure left ventricular pressure and anterior-posterior and septal-free wall dimensions. The product of these two dimensions, denoted left ventricular area, was used as an index of left ventricular volume. Two levels of mechanically increased right ventricular afterload were induced with a closed pericardium under three levels of left ventricular preload produced by whole-blood transfusions. Four brief increases in left ventricular afterload were induced by constricting the aorta under each right ventricular afterload and preload condition. Using multiple linear regression, we found that the slope of the end-systolic pressure-area relationship, an index of contractility, was unchanged [0.90 +/- 0.11 mm Hg/mm2 (SEM)], and stroke area (65.8 +/- 7 mm2) and cardiac output (the product of stroke area and heart rate) (13,400 +/- 1,660 mm2/min) were maintained. However, the area intercept of the pressure-area line at zero pressure (499 +/- 13 mm2) shifted significantly to the left in the presence of both levels of increased right ventricular afterload (by -39.2 +/- 13 and -76.2 +/- 15 mm2, respectively). Mechanically increased right ventricular afterload alters left ventricular configuration and causes a shift in the operating volume (area) range of the ventricle with no change in contractility in 3- to 7-d-old lambs.


A three-element model describes excised cat papillary muscle elasticity.

Glantz SA.

The three-element model for skeletal muscle has been widely applied to cardiac muscle. It consists of an active contractile element (CE) that represents the muscle's response to stimulation, in series with an elastic element (SE) and the CE and SE in parallel with another elastic element (PE). There have been problems in interpreting experimental data on muscle elasticity using this model. Data seem to indicate that SE force depends not only on instantaneous length, but also initial length; it is not only elastic. Recent experiments seem to indicate that the SE has time-varying properties; it is not passive. This paper formulates a three-element model in which phi(x) = alpha[e beta(x-x*)-1] governs the elastic elements, where phi = force, alpha, beta = spring constants, x = length, and x* = rest length, which avoids these problems. The SE and PE have the same properties. (Typical values: alpha approximately equals .045 g/mm2, beta approximately equals 5.9 mm-1 for cat papillary at 29 degrees C.). By accounting for the nonlinearity of the SE-PE interaction, this three-element model leads to predictions that agree with published data on excised papillary muscle's elastic properties.

PMID: 1147020 [PubMed - indexed for MEDLINE] 


Segment stroke work and metabolism depend on coronary blood flow in the pig.

Stowe DF, Mathey DG, Moores WY, Glantz SA, Townsend RM, Kabra P, Chatterjee K, Parmley WW, Tyberg JV.

We determined the mechanical and metabolic effects of graded myocardial ischemia in 23 open-chest, anesthetized pigs. By connecting the midportion of the left anterior descending artery (LAD) to the carotid artery via a constant volume, calibrated pump, we reduced the flow in the LAD to 0, 25, 50, and 75% of control rates for periods of 1 h. Flows of 100% and 150% were also examined. Using pairs of ultrasonic crystals to measure segment dimensions, we calculated segment shortening and thickening, and total and systolic stroke work in the ischemic and normally perfused segments. Blood gases, pH, and lactate and inosine balances were determined from the regional coronary venous blood. At coronary blood flows of 0, 25, 50, and 75% of normal resting flow, total segment work was 8 +/- 8, 25 +/- 4, 51 +/- 5, and 80 +/- 6% of control, respectively, while systolic segment work was -2 +/- 5, -10 +/- 5, 40 +/- 5, and 86 +/- 7% of control, respectively (means +/- SE). Thus, the decrease in total segment stroke work is proportional to the decrease in flow over the range 0-100%. However, no useful work (i.e., systolic work) is done until flow exceeds 25%. Segment shortening and thickening are significantly depressed with flows diminished by only 25%. Segmental inosine production correlates with lactate production and parallels decreased mechanical performance.

PMID: 645926 [PubMed - indexed for MEDLINE]


Left ventricular dynamic geometry in the intact and open chest dog.

Walley KR, Grover M, Raff GL, Benge JW, Hannaford B, Glantz SA.

No approach to describing the heart's dynamic geometry has been widely adopted, probably because all require questionable assumptions of chamber shape, symmetry, or placement of the measuring devices. In other words, these approaches require assumptions about shape to reach conclusions about shape. We present an analysis that avoids such assumptions and provides an objective description of how the left ventricle deforms and rotates during the cardiac cycle. We only assume that the deformation of the left ventricular cavity is homogeneous, and explicitly validate this assumption. Our analysis yields the following new information about the contracting left ventricle: three principal directions of deformation and the relative length change alone these directions: the axis and angle of rotation, and relative volume. All these changes are referenced to the ventricle's configuration at end-diastole. We instrumented 13 dogs with tantalum screws without opening their chests. During systole, the three principal directions of deformation essentially are aligned along apex-base, anterior-posterior, and septum-free wall directions. There is little length change in the apex-base direction. The anterior and septal principal directions do not remain fixed with respect to the heart's anatomy during systole. During isovolumic relaxation and early filling, systolic shape changes are reversed. During slow filling, only small shape changes occur. Opening the pleura or performing a sternotomy and pericardiectomy makes the heart change orientation within the chest, but does not alter the magnitude of shortening, relative to the left ventricle's end-diastolic configuration.

PMID: 7067064 [PubMed - indexed for MEDLINE] 

A mechanism for shifts in the diastolic, left ventricular, pressure-volume curve: the role of the pericardium.

Tyberg JV, Misbach GA, Glantz SA, Moores WY, Parmley WW.

Attempts to explain acute shifts in the pressure-volume relationship by changes in myocardial stiffness have been unsupported by animal experimentation and discouraged by calculations showing that making half the ventricle rigid would hardly account for the clinically observed upward shifts in the curve. Data collected in open-chest anesthetized dogs during volume loading with the pericardium open and closed indicate that when the pericardium is closed, left ventricular enddiastolic pressure is better predicted by right ventricular pressure than by left ventricular dimensions. These data support the hypothesis that acute, upward shift in the pressure-volume curve may be caused by an increase in pericardial pressure, in turn caused by an increase in the volume of the intrapericardial contents. This follows from the fact that measured left ventricular diastolic pressure is equal to the sum of the pressure differences accross the myocardium and the pericardium. Thus, increases in pericardial pressure raise measured ventricular diastolic pressure without change in ventricular volume: hence, an upward shift in the pressure-volume curve.

PMID: 668760 [PubMed - indexed for MEDLINE] 

Left ventricular mechanical adaptation to chronic aortic regurgitation in intact dogs.

Florenzano F, Glantz SA.

Increased end-diastolic wall stress has been hypothesized to stimulate left ventricular (LV) hypertrophy following volume overload. We instrumented intact-chest dogs with radiopaque markers in both ventricles and created volume overload by puncturing one aortic valve cusp. End-diastolic stress increased immediately, then fell over 3 mo as the heart hypertrophied. End-systolic stress did not change significantly. Chamber contractility, quantified as Emax, the end-systolic pressure-volume line slope, increased. Emax normalized by multiplying by LV mass increased following the lesion before but not after beta-blockade with propranolol and did not change significantly over time, suggesting that chamber contractility changed because of increased mass and sympathetic tone rather than changed intrinsic muscle function. LV mass did not initially correlate with lesion size, but steady-state mass did. Over the range of lesions we produced, increased end-diastolic wall stress appears to stimulate hypertrophy at a fixed rate, which stops when end-diastolic wall stress has been reduced to an acceptable level.

PMID: 2953255 [PubMed - indexed for MEDLINE]

Pulmonary artery constriction produces a greater right ventricular dynamic afterload than lung microvascular injury in the open chest dog.

Calvin JE Jr, Baer RW, Glantz SA.

Investigators model noncardiogenic pulmonary hypertension by constricting the pulmonary artery to increase right ventricular afterload. To investigate this model's validity, we compared the right ventricular afterload, quantified as pulmonary input impedance, created by constricting the pulmonary artery and by inducing a pulmonary microvascular injury (with glass beads infused into the pulmonary circulation). The pulmonary injury constriction produced a different right ventricular afterload than the microvascular injury. The constriction increased both the input resistance and the characteristic impedance. Microvascular injury increased only input resistance. Physiological levels of lung inflation did not influence pulmonary impedance, but lung hyperinflation increased input resistance both before and while constricting the pulmonary artery or after producing microvascular injury. Total right ventricular power output and stroke work were unchanged during each vascular intervention. Pulmonary artery constriction did not affect power output distribution, whereas microvascular injury decreased oscillatory power and its relative contribution to total power. Lung hyperinflation dramatically reduced right ventricular power and left ventricular stroke work. These effects appeared mediated by right ventricular afterload increase uncompensated for by right ventricular preload increase. These observations help explain the hemodynamic consequences of acute pulmonary hypertension and the effects of lung hyperinflation with positive end-expiratory pressure respiration in such patients.

PMID: 3881198 [PubMed - indexed for MEDLINE]

Pulmonary injury depresses cardiac systolic function through Starling mechanism.

Calvin JE Jr, Baer RW, Glantz SA.

To determine whether pulmonary microvascular injury or lung hyperinflation changes left ventricular (LV) performance and whether ventricular interaction plays a role in mediating such changes, we studied seven open-chest, closed-pericardium, anesthetized dogs before and after right ventricular (RV) injections of 150- to 200-micron glass beads. Because people with pulmonary disease are often treated with positive end-expiratory pressure, we also hyperinflated the lungs before and after creating the pulmonary microvascular injury. Measurements of LV and RV pressures and dimensions were taken at end expiration during the basal state, during lung hyperinflation, and after microvascular injury at RV end-diastolic pressures of 5, 10, and 15 mmHg produced by volume loading. Acute volume loading produced upward shifts in the LV diastolic pressure-size curve both before and after microvascular injury. Neither microvascular injury nor lung hyperinflation substantially affected the LV diastolic pressure-size relationship. LV end-diastolic size determined LV stroke work with no consistent independent influence of microvascular injury or lung hyperinflation. Neither microvascular injury nor lung hyperinflation depressed systolic performance beyond that associated with changes in end-diastolic heart size.

PMID: 3766749 [PubMed - indexed for MEDLINE] 

Circ Res 1975 Dec;37(6):787-94 Related Articles, Links 

Muscle stiffness determined from canine left ventricular pressure-volume curves.

Glantz SA, Kernoff RS.

We measured pressure-volume curves in nine excised dog ventricles and stress-strain curves in two to five muscle specimens from each ventricle to verify a derived formula that relates muscle stiffness to the ventricular pressure-volume curve. The assumptions underlying this formula are: (1) the ventricle is a uniform spherical shell, (2) all muscle fibers carry average stress and deform as if they were at the midwall, (3) static equilibrium exists, (4) internal pressure induces the only load, and (5) the muscles exhibit an exponential stress-strain curve given by the equation sigma(epsilon) = alpha(ebeta epsilon - 1), where sigma = stress, epsilon = strain, and alpha and beta are constants. There was no significant difference between the stiffness constant, beta, inferred from the left ventricle pressure-volume curves (14+/-4.3[SD]) and that measured directly from the muscle stress-strain curves (16+/-2.8).

Age-related changes in ouabain pharmacology. Ouabain exhibits a different volume of distribution in adult and young dogs.

Glantz SA, Kernoff R, Goldman RH.

To better understand why one must administer much higher doeses of digitalis glycosides to immature than to mature humans and animals, we studied ouabain pharmacokinetics in adult and young dogs. Consistent with reported observations that ouabain-binding, metabolism, and excretion do not change with age, we found no significant differences in the transfer coefficients in a linear two-compartment open model for ouabain pharmacokinetics following a bolus of 0.05 mg/kg. We did find, however, that young dogs had nearly twice the ouabain volumes of distribution per kilogram of body weight as adults (155.4 +/- 1.2 (SE) ml/kg vs. 80 +/- 0.6, P less than 0.0005) and that one could account for this difference with the fact that young dogs had nearly twice the plasma volume 108 +/- 9.8, vs. 68 +/- 7.3, P = 0.001) and interstitial fluid space (318 +/- 35 vs. 190 +/- 6.5, P = 0.006) as the adults. For the same dose per kilogram, left and right ventricular ouabain concentrations were inversely related to the volume of distribution, with the adults having significantly higher tissue levels and incidence of arrhythmias. One must give more ouabain to a young dog to get the same plasma concentration as in an adult because the mass of ouabain in rapid equilibrium with the plasma is diluted in a larger volume of distribution.

A new approach to in situ left ventricular volume clamping in dogs.

Ohtani M, Nikolic SD, Glantz SA.

Cardiovascular Research Institute, University of California, San Francisco 94143-1024.

Major contributing factors modulating left ventricular (LV) diastolic behavior are active relaxation of myocardium and volume change during filling, the interaction of which complicates analysis of diastolic pressure-volume relationship, especially in early diastole. To separate the effect of active relaxation and filling, a method was introduced [E. L. Yellin, M. Hori, C. Yoran, E. H. Sonnenblick, S. Gabbay, R. W. M. Frater, Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H620-H629, 1986] to interrupt mitral inflow and keep LV volume constant throughout diastole. Their preparation requires replacing the mitral valve with an artificial valve using cardiopulmonary bypass, which might cause significant change in cardiac performance or produce detrimental systemic effects. We developed a new volume-clamping method that preserves the native mitral valve and apparatus intact and avoids cardiopulmonary bypass. A modified Bjork-Shiley prosthetic valve (20 mm orifice diam) in a special mounting ring was placed above the native mitral valve through the left atrium and secured from outside the heart. This prosthetic valve was controlled by a cable connected to solenoids outside the dog, triggered by the electrocardiogram or other physiological signal. We compared our method (n = 7) with that of Yellin et al. (n = 2) in nine random source dogs. In our method, no end-diastolic pressure gradient or regurgitant pressure wave was observed, and the prosthetic valve did not disturb movement of the native mitral valve. When the prosthetic valve was forced to a closed position at end systole, LV volume, measured with a conductance catheter, was maintained at or near end-systolic volume throughout diastole.(ABSTRACT TRUNCATED AT 250 WORDS)

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