bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of digitalis on left ventricular function in exercising dogs.
Authors: Horwitz L D , Atkins J M , Saito M
Published: June 2012

The effect of ouabain on left ventricular function in nonfailing hearts was assessed in 14 chronically instrumented dogs during graded treadmill exercise. At rest, ouabain increased the maximum first derivative of the left ventricular pressure (dp/dtmax) and stroke volume by 38% and 16%, respectively. No change occurred in end-diastolic left ventricular diameter or peak systolic left ventricular pressure. During exercise, ouabain reduced maximum running speed and limited the increments in heart rate and systolic pressure but did not alter dp/dtmax, stroke volume, or end-diastolic diameter. When atropine and ouabain were given and severe exercise was performed, there were no differences from controls in running speed, heart rate, dp/dtmax, or other parameters. When ouabain and propranolol were given dp/dtmax increased at rest and during exercise, compared with results with propranolol alone. It is concluded that the inotropic effect of ouabain is negligible during strenuous physical activity because of the presence of high levels of sympathetic stimulation. However, during exercise in the presence of beta-adrenergic blockade, increases in myocardial contractility do occur in response to ouabain.
A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster.
Authors: Sole M J , Kamble A B , Hussain M N
Published: June 2012

The development of heart failure in the cardiomyopathic hamster is associated with a decrease in norepinephrine stores and parallel increases in cardiac sympathetic tone and tyrosine hydroxylase activity. Despite the increase in tyrosine hydroxylase, cardiac norepinephrine synthesis does not increase in heart failure. In this study, we have shown that an accumulation of cardiac dopamine accompanies the decline of cardiac norepinephrine. The abnormal content of norepinephrine and of dopamine in the decompensating hamster heart is restored to normal by peripheral ganglionic blockade. The acute increase in cardiac sympathetic tone induced by immobilization stress in control hamsters mimics the alterations in cardiac catecholamine distribution found in heart failure. Other investigators have demonstrated similar alterations in the catecholamine content of the rat submaxillary gland and adrenal medulla following an increase in sympathetic input to these organs. We conclude that the increase in cardiac sympathetic tone in the late stages of hamster cardiomyopathy appears to lead to a shift in the rate-limiting step for norepinephrine synthesis from the hydroxylation of tyrosine to the hydroxylation of dopamine. There is evidence that this shift which results in an accumulation of dopamine in the noradrenergic nerve terminals of the heart is a general manifestaion of augmented sympathetic nerve traffic rather than a peculiarity of hamster cardiomyopathy.
Functional morphology of the pressure- and the volume-hypertrophied rat heart.
Authors: Lin H L , Katele K V , Grimm A F
Published: June 2012

We studied hearts in which hypertrophy was caused by both pressure and volume overload. Pressure hypertrophy was induced by an aortic constriction; volume hypertrophy was induced by an iron-copper deficiency (anemia). The ventricular weight was increased by 34% in the pressure-hypertrophied hearts at the end of 6 weeks. The ventricular weight was increased by 54% in the volume-hypertrophied hearts at the end of 3 months. A potassium arrest-formalin fixation technique was used to produce a "diastole-like" ventricle. In the pressure-hypertrophied ventricle, the ventricular wall thickness and external radii were significantly increased, whereas the valve-to-apex distance and internal radii remained unchanged. We also found that in the volume-hypertrophied ventricle there was an increase in the valve-to-apex distance, external radii, internal radii, and wall thickness. Although external and internal dimensions increased, the ventricular shape did not change significantly in the volume-hypertrophied ventricle.
Pathophysiological differences between paired and communal breeding of male and female Sprague-Dawley rats.
Authors: Wexler B C , Greenberg B P
Published: June 2012

Sexually mature, male and female Sprague-Dawley rats were housed in large communal breeding cages or in smaller paired breeding cages. Virgin control rats of the same age were housed similarly but segregated by sex. Breeders became obese, developed a fatty liver, and showed elevated levels of triglycerides, free fatty acids, and cholesterol. Breeders had high blood pressure, enlarged hearts, hyperglycemia, and islet beta cell degranulation. Serum enzymes, creatine phosphokinase, serum glutamic oxalo-pyruvic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, and blood urea nitrogen levels were elevated in breeder rats. The adrenal glands of male breeders appeared hyperactive; the adrenal glands of female breeders were thrombosed and appeared to be hypoactive. Male breeder rats developed microscopic aortic lesions only; female breeders developed advanced calcific aortic sclerosis. Male breeders kept in active stud service manifested the most abnormal metabolic and pathophysiological changes. Female breeders developed similar pathophysiological changes after four pregnancies, irrespective of their paired or communal breeding environment. Virgin rats were normal regardless of housing conditions. Our findings suggest that repeated breeding in male and female rats causes resetting of the hypothalamic-pituitary-adrenal-gonadal axis. This may lead to disturbed hormonal and metabolic changes which culminate with the development of accelerated cardiovascular degenerative changes.
Enhanced renal prostaglandin production in the dog. The effect of sodium arachidonate in nonfiltering kidney.
Authors: Gerber J G , Data J L , Nies A S
Published: June 2012

Sodium arachidonate, 10(-5) g/kg per minute, was infused into the renal artery of a nonfiltering canine kidney in situ in order to determine the effects of enhanced prostaglandin synthesis on renal blood flow and its distribution in circumstances where prostaglandins produced in the medulla could not gain access to the cortex via tubular fluid. The contralateral normal kidney was also infused with sodium arachidonate and served as control. Radioactive microspheres were used to calculate the hemodynamic effects. In the nonfiltering kidney, the total renal blood flow increased after sodium arachidonate from a mean of 105 ml/min per 100 g to 146 ml/min per 100 g (P less than 0.01). This increase was completely abolished by prior treatment with indomethacin, 8 mg/kg, intravenously. The normal kidney responded qualitatively the same as the nonfiltering side. In both kidneys, blood flow increased significantly to all cortical zones except the outermost (zone 1), but the fractional distribution of renal blood flow was significantly increased only in the innermost cortex (zone 4). Since the kidneys were nonfiltering, the increase of renal blood flow during infusion of arachidonic acid cannot be explained by prostaglandins being transported from renal medulla to the cortex through renal tubules. Most likely prostaglandins are produced locally in the cortex and have only local effects.
Cardiovascular responses to PGI2 (prostacyclin) in the dog.
Authors: Fitzpatrick T M , Alter I , Corey E J , Ramwell P W , Rose J C , Kot P A
Published: June 2012

Arachidonic acid (AA) produces characteristic hemodynamic changes in the canine circulation. These responses are blocked by prostaglandin (PG) synthetase inhibitors, indicating that AA and its nonprostanoic metabolites are not vasoactive. The hemodynamic effects of the cyclic endoperoxides, thromboxanes, and PGD2, PG2, and PGF2a differ from those produced by AA. PGI2, a newly identified product of AA, is reported to relax arterial strips. However, its cardiac and systemic effects are unknown. In 12 open-chest, anesthetized dogs, PGI2 (0.25-5.0 microgram/kg) produced a dose-related decrease in systemic arterial pressure (BP) and myocardial contractile force (MCF). In five left ventricular bypass preparations, PGI2 produced only a slight decrease in MCF at all doses, whereas the BP decreases were parallel to those in the intact preparation. AA, PGD2, PGE2, and PGI2 were administered in random order by bolus intravenous injections in approximately equidepressor doses to intact dogs. BP fell with each agent (AA, 300 microgram/kg, -25 percent; PGD2, 5 microgram/kg, -26 percent; PGE2, 5 microgram/kg, -26 percent PGI2, 0.5 microgram/kg, -26 percent). The vasodepressor action of PGI2 was approximately 10 times greater than that of PGD2 and PGE2. Pulmonary arterial pressure (PAP) rose significantly with PGD2 and PGE2 (AA, -1 percent; PGD2 +66 percent; PGE2, +20 percent; PGI2, -1 percent). Only PGE2 had a significant effect on MCF (AA, +7 percent; PGD2, +5 percent, PGE2, +20 percent; PGI2, -0.3). At this dose, PGI2 resembles AA in that it has little effect on either PAP or MCF. Of all known AA metabolites the response to PGI2 most closely resembles that of exogenous AA in the dog.
Dynamic stiffness of cat heart muscle in Ba2+-induced contracture.
Authors: Saeki Y , Sagawa K , Suga H
Published: June 2012

We analyzed mechanical properties of kitten papillary muscles both at rest and in Ba2+ contracture by the frequency response method. The muscle length was perturbed sinusoidally, with an amplitude less than 0.3% of Lmax over a frequency range from 0.1 to 60 Hz to determine the dynamic stiffness, F(omega)/L(omega), in which F(omega) = amplitude of the force response wave, L(omega) = amplitude of sinusoidal length wave, and omega = frequency, and the phase shift of F(omega) relative to L(omega). In resting muscles, the dynamic stiffness increased minutely with increasing frequency and the phase relation showed a small lead over the entire frequency range. In muscles in contracture at low temperature (22-24 degrees C), the stiffness first decreased with increasing frequency from about 0.2 to 1 Hz, then increased with a slope of 10-fold/decade, and finally plateaued over the range above 8 Hz. The phase relation showed a small lag between 0.3 and 0.5 Hz, but a clear lead of up to 60 degrees between 0.8 and 16 Hz. With an increase in temperature to 36 degrees C, the peculiar decrease in stiffness and the phase lag in the low frequency region decreased in size and shifted to a higher frequency region (about 4 Hz). These findings led us to two alternative, approximate analogues, which are similar to but simpler than that previously proposed for a twitching papillary muscle.
Adenosine metabolism in canine myocardial reactive hyperemia.
Authors: Olsson R A , Snow J A , Gentry M K
Published: June 2012

In pentobrabital-anesthetized open chest dogs, myocardial adenosine content is elevated by 5 or 15 seconds of left coronary artery occlusion and falls exponentially to control levels during reactive hyperemia. The rate constants for adenosine dissipation are (mean +/- SEM): -0.08 +/- 0.01 and -0.034 +/- 0.007 sec-1 after 5- and 15-second occlusion, respectively. Kinetic analysis of the reactive hyperemia flow curves (Circ Res 14/15 (suppl I): 81-85, 1963) predicts rates of -0.069 +/- 0.009 sec-1 and -0.04 +/- 0.009 sec-1, indicating that changes in adenosine levels can account for the way coronary flow changes during this response. The log (dose-) response curve relating reactive hyperemia flow to tissue adenosine concentration has a steeper slope and is half-maximal at a lower adenosine concentration than the dose-response curve obtained by intracoronary infusions of adenosine in oxygenated hearts, indicating that the coronary vasoactivity of adenosine is enhanced during reactive hyperemia. This could explain why theophylline antagonizes the coronary vasocilatory effect of adenosine in oxygenated hearts but has relatively little effect on reactive hyperemia.
Regional myocardial blood flow after sudden aortic constriction in awake dogs.
Authors: Walston A , Rembert J C , Fedor J M , Greenfield J C
Published: June 2012

Hemodynamic and regional myocardial blood flow responses were studied 5 seconds (early) and 30 seconds (late) after abrupt proximal aortic constriction in chronically instrumented awake dogs. During the early phase, left ventricular end-diastolic pressure (LVEDP) increased and stroke volume (SV) decreased significantly. During the late phase, there was a positive inotropic response manifested by a decrease in LVEDP and increase in SV (Anrep effect). The late inotropic response was closely associated with a recovery from subendocardial underperfusion. Hemodynamic and regional flow responses after beta-adrenergic blockade with propranolol (0.4 mg/kg) were similar to those observed during control. Studies during coronary vasodilation induced by adenosine (0.75--1.0 mg/kg per minute) showed that, if subendocardial flow was elevated during the early phase, the early increase of LVEDP and decrease of SV were less than control; however, if subendocardial flow did not change from control in the early phase and did not subsequently increase, there was no late inotropic response. These data suggest that the Anrep effect in the awake dog is closely related to a recovery from subendocardial ischemia.
The relationship between body fluid volume, sodium ion concentration, and sensitivity to pressor effect of angiotensin II in dogs.
Authors: Cowley A W , Lohmeier T E
Published: June 2012

Extracellular fluid volume, plasma electrolyes, and plasma angiotensin II (A II) were individually controlled to determine their influence on the acute pressor responsiveness to A II. Hemodialysis of nephrectomized dogs was used to simulate and control the changes of major variables which occur in the intact state during changes in sodium balance. A II dose-pressure response curves were determined in 11 dogs at three volume states with plasma [Na+] maintained constant and in five dogs at low, normal, and high plasma [Na+] with body fluid volume maintained constant. Parallel shifts of the log dose-response curves were obtained in the three volume states. The same rise in arterial pressure with identical doses of A II was obtained at normal, contracted, and expanded volume states, with the change of arterial pressure based on the uncompensated basal pressure level at each volume state. When the fall in pressure observed during volume depletion was returned to control levels with norepinephrine, there was no change in the A II dose-response relationship from the control state. No difference in the A II dose-pressure response relationship was obtained between states of 140, 146, and 156 mEq/liter plasma [Na+] with body fluid volume held constant. The studies indicate that short-term alterations in either sodium or water balance do not alter the "real" vascular sensitivity to A II. The "apparent" changes normally observed result from preexisting endogenous levels of circulating A II present at the time the dose-response curve is determined which probably alter the availability of receptor sites to A II.
Age-related changes in the concentration of plasma cholesterol and triglycerides in two groups of rats with inherited widely different levels of spontaneous physical activity.
Authors: Rasmussen E W , Hłstmark A T
Published: June 2012

The plasma concentration of cholesterol and triglycerides was determined in two groups of rats with inherited widely different levels of spontaneous physical activity. Active as well as passive rats of each sex were divided into two subgroups, one with free access to wheel running activity (exercising group), and another for which admittance to the drum was closed (nonexercising group). Plasma concentrations of cholesterol and triglycerides were followed from the age of 3-8 months in females and 3 months to 1 year in males. A pronounced increase with age in the plasma concentration of these lipids was observed in the active male rats. In the passive male rats and in all females, there were no major changes in plasma levels of cholesterol and triglycerides. Corresponding groups of exercising and nonexercising rats had similar plasma levels of these components. The data for male rats show a positive association between the inherited tendency to perform spontaneously a high level of physical activity and an age-related increase in plasma lipids. However, running activity per se does not seem to have any influence on the level of plasma cholesterol and triglycerides in these rats.
The effect of an increase in inotropic state and end-diastolic volume on the pumping ability of the feline left heart.
Authors: Elzinga G , Westerhof N
Published: June 2012

In isolated ejecting cat hearts, the pumping ability of the left heart was described quantitatively by the relationship between mean left ventricular pressure and mean left ventricular output. This relationship was determined by making the heart eject against a series of different loads on a beat-to-beat basis. Left ventricular mean pressure-mean output relationships of control and potentiated beats (at the same end-diastolic pressure) have a common intercept on the output axis but diverge toward the pressure axis. When the mean pressure values of the potentiated beats in a given experiment are multiplied by a single factor, superposition of the two relationships is obtained. A change in left ventricular end-diastolic pressure caused a more parallel shift of the left ventricular mean pressure-mean output relationship. Here, superposition could be obtained by using one multiplication factor for the mean pressure data and one for the mean output data of the relationship found after the change in end-diastolic pressure. We concluded that, using the left ventricular mean pressure-mean output relationship, changes in cardiac pumping ability caused by given changes in inotropic state and ventricular end-diastolic volume can be quantified by one or two multiplication factors, respectively.
Nuclear proteins in the heart of the cardiomyopathic Syrian hamster. Phosphorylation of phenol-soluble nonhistone proteins.
Authors: Liew C C , Sole M J
Published: June 2012

We examined incorporation of 32P into phenol-soluble nonhistone nuclear acidic proteins (NHNP) obtained from myolytic, hypertrophic, and failing phases of hamster cardiomyopathy. NHNP from these dystrophic hamster hearts were phosphorylated much less than their controls, despite a 9-fold increase in uptake of 32P into their nuclei. After fractionation of NHNP by isoelectrofocusing polyacrylamide gel electrophoresis, two major fractions focusing from pH 6.0 to 6.2 and 6.6 to 6.8 were highly phosphorylated in both the control and dystrophic hearts. The latter fraction was much more phosphorylated in the control. Two fractions of NHNP focusing at pH 4.9 and 5.1 were more highly phosphorylated in the dystrophic hearts than in the controls. Autoradiographs obtained from the two-dimensional polyacrylamide slab gel electrophoresis showed that two proteins (pH 4.9 and 5.1; mol wt 25,000 and 60,000, respectively) were highly phosphorylated in the dystrophic heart. There was no detectable phosphorylation of these proteins in the controls. These changes in the phosphorylation of cardiac NHNP may be important in determining the alteration of gene expression in hamster cardiomyopathy.
Whole body vascular reactivity during the development of deoxycorticosterone acetate hypertension in the pig.
Authors: Berecek K H , Bohr D F
Published: June 2012

A change in vascular reactivity was characterized in the pig during the development of deoxycorticosterone acetate (DOCA) hypertension. Pigs, 8-12 weeks of age, were subjected to unilateral nephrectomy and instrumented with an electromagnetic flowprobe on the ascending aorta and with Tygon catheters in the aorta and thoracic vena cava. Approximately 2 weeks after surgery, Silastic strips impregnated with DOCA (100 mg/kg) were implanted subcutaneously. Within the first 3 days after implantation, mean arterial pressure (MAP) began to rise and reached levels approximately 40% greater than control during the 4th week. Graded intravenous infusions of norepinephrine or angiotensin II were given to unanesthetized pigs before, and at intervals during, the development of hypertension. Changes in total peripheral resistance were calculated from recordings of MAP and cardiac output. Comparison of pre-DOCA response curves with those obtained at intervals following DOCA implantation demonstrated a significant increase in vascular smooth muscle sensitivity (decrease in threshold infusion rates) to both drugs post-DOCA. There also was a shift to the left in the dose-response curves. These changes in systemic vascular reactivity occurred at the time the arterial pressure began to rise. The temporal relationship suggests that the increase in vascular reactivity may initiate the increase in mean arterial pressure.
Hydrolase activities in the rat aorta. II. Effects of hypertension alone and in combination with diabetes mellitus.
Authors: Wolinsky H , Capron L , Goldfischer S , Capron F , Coltoff-Schiller B , Kasak L E
Published: June 2012

Hypertension is an important risk factor for atherosclerosis and often occurs in association with diabetes mellitus. Specific activities of hydrolases in homogenates of aortas from rats with renal-clip hypertension, normotension following a period of hypertension, and hypertension combined with streptozotocin-induced diabetes mellitus were measured. Enzymes included: neutral alpha-glucosidase, and lysosomal N-acetyl-beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 6 or 12 weeks of hypertension, specific activities of all enzymes measured were significantly increased, levels ranging from 24% above normal for cathepsin C to 351% above normal for N-acetyl-beta-glucosaminidase. Six weeks of normotension following 6 weeks of hypertension resulted in restoration to normal of four of the six enzyme activities; the remaining two enzymes were significantly below normal levels. Combined hypertension and diabetes mellitus showed smooth muscle cell levels of four of the five hydrolases measured to be significantly lower than those present with hypertension alone. In every instance, histochemical studies of aortas showed acid phosphatase and N-acetyl-beta-glucosaminidase activities which corresponded to the biochemical findings. These findings indicate profound and discrete effects of two clinical risk factors on vascular smooth muscle cell lysosomes.
The pressor response to angiotensin II in patients with low renin essential hypertension.
Authors: Marks A D , Marks D B , Kim Y N , Moctezuma J , Adlin E V , Channick B J
Published: June 2012

The etiology of low renin essential hypertension (LREH) has not been established with certainty, but mineralocorticoid excess has been implicated frequently in its pathogenesis. The finding of several investigators of a normal exchangeable sodium space and extracellular fluid volume, however, does not support this hypothesis. To evaluate the possible role of sodium and water retention in LREH, the pressor response to infused angiotensin II (A II) was determined and compared to that of normal subjects and that of subjects with normal renin essential hypertension (NREH). This approach was based on the known suprasensitivity of vascular receptors to A II in situations in which sodium and water compartments are expanded as they are, for example, in proven hypermineralocorticoid states such as primary aldosteronism. In this study, we found that subjects with LREH demonstrated no increased pressor response to graded doses of A II; this suggests that LREH is not primarily mediated by sodium and water retention.
Renal function and renin secretion after administration of ouabain and ouabain plus furosemide in conscious sheep.
Authors: Blaine E H , Zimmerman M B
Published: June 2012

The effects of ouabain or ouabain and furosemide on renal function and renin secretion were studied in conscious isovolemic sheep. The sheep received a continuous renal arterial infusion of papaverine, 7 mg/min, throughout the experiment. Ouabain alone (7 X 10(-7) M in the renal plasma) produced significant decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) but not in renal perfusion pressure. Plasma [K+] rose after ouabain administration. Fractional (FENa) and absolute (UNaV) Na+ excretion were 2.9 +/- 1.0% (mean +/- SE) and 78 +/- 54 muEq/min, respectively, during the papaverine infusion and rose to 19 +/- 5.1% (P less than 0.05) and 528 +/- 116 muEq/min (P less than 0.01) after ouabain administration. Despite the large changes in Na+ reabsorption, renin secretion was not stimulated. During the control period, renin secretion was 281 +/- 131 ng/min and the average renin secretion after ouabain administration was 310 +/- 78 ng/min (not significant). A smaller dose of ouabain (2 X 10(-7) M) infused into the renal artery with 40 mg of furosemide, iv, did not decrease GFR but RPF was suppressed. FENa and UNaV averaged 4.4 +/- 1.6% and 121 +/- 44 muEq/min, respectively, while papaverine was infused into the renal artery and increased to 18 +/- 4.8% (P less than 0.05) and 636 +/- 209 muEq/min (P less than 0.05) after ouabain and furosemide were infused. Renin secretion was 118 +/- 62 ng/min during the control period and averaged 240 +/- 67 ng/min after ouabain plus furosemide. The difference was not statistically significant. Thus ouabain alone does not stimulate renin secretion in the conscious, isovolemic sheep despite a presumed increase in [NaCl] at the macula densa and inhibition of NaCl transport by the loop of Henle. Ouabain also blocks the normal stimulatory effects of furosemide on renin secretion.
Sequential unipolar strength-interval curves and conduction times during myocardial ischemia and reperfusion in the dog.
Authors: Levine H J , Avitall B , Pauker S G , Naimi S
Published: June 2012

Computerized techniques were employed to generate alternating anodal and cathodal or sequential anodal strength-interval curves during and following 15-minute coronary artery ligations in 14 anesthetized dogs. The right atrium was paced at 2.5 Hz, and unipolar ventricular strength-interval curves with simultaneous conduction times were recorded every 45-120 seconds during ischemia and reperfusion. Within 1--2 minutes of ligation, anodal midcurve and late diastolic thresholds fell sharply, and cathodal thresholds fell slightly or changed little. After 5 minutes of ischemia, anodal thresholds remained low, cathodal thresholds rose, and conduction times increased. At 10--15 minutes of ligation, if the ischemic zone was small, anodal thresholds were low, often approaching cathodal values, and conduction returned toward control values. When the ischemic zone was large, unipolar thresholds and conduction times increased late during the ligation period. Throughout the course of ischemia, the falling limb of the strength-interval curve shifted progressively to the left indicating shorter refractory periods. Following abrupt reperfusion, anodal phase 3 dips promptly reappeared; refractory periods returned toward control, and supernormal conduction was noted. By 3--5 minutes of reperfusion, the falling limb of the strength-interval curve had shifted to the right of control and conduction times increased. Thus, vulnerability to arrhythmias during early ischemia (i.e., 5 minutes) is characterized by low anodal midcurves and late diastolic thresholds, short refractory periods, and slow conduction. During the first minute of reperfusion, anodal excitability is increased during the early dip and conduction times are supernormal. Increases in anodal excitability correlate better with the peak incidence of early ligation and reperfusion arrhythmias than do changes in cathodal excitability.
Simulation studies of the electrocardiogram. I. The normal heart.
Authors: Miller W T , Geselowitz D B
Published: June 2012

A digital computer model is presented for the simulation of the body surface electrocardiogram (ECG) during ventricular activation and recovery. The ventricles of the heart are represented in detail by a three-dimensional array of approximately 4000 points which is subdivided into 23 regions. Excitation sequence and cellular action potential data taken from the literature are used to determine the spatial distribution of intracellular potentials at each instant of time during a simulated cardiac cycle. The moment of the single dipole representing each region is determined by summing the spatial gradient of the intracellular potential distribution throughout the region. The resulting set of 23 dipoles is then used to calculate the potentials on the surface of a bounded homogeneous volume conductor with the shape of an adult torso. Simulated isopotential surface maps during both activation and recovery are in good agreement with data for humans reported in the literature.
Effects of nifedipine on myocardial perfusion and ischemic injury in dogs.
Authors: Henry P D , Shuchleib R , Borda L J , Roberts R , Williamson J R , Sobel B E
Published: June 2012

To determine whether nifedipine, a calcium antagonist, protects ischemic myocardium, conscious dogs were subjected to coronary occlusion and given nifedipine by intravenous infusion beginning 30 minutes after the onset of ischemia and lasting for 24 hours while systemic arterial pressure, left atrial pressure, and cardiac output were monitored. Local myocardial perfusion at selected intervals after coronary occlusion was assessed with radioactive microspheres injected into the left atrium. In regions of myocardium exhibiting moderately depressed flow 29 minutes after occlusion in control dogs (n = 8), flow was significantly greater 3 and 23.5 hours later, reflecting increases in collateral perfusion. Corresponding zones of myocardium in treated dogs (n = 9) exhibited significantly greater increases in flow at each interval after occlusion (P less than 0.05). Furthermore, myocardial creatine kinase depletion (which correlated well with morphometric estimates of necrosis) in myocardium matched for ischemia prior to treatment was 1.5 to 3 times less in treated than in control dogs (P less than 0.05). Thus, nifedipine produced sustained increases in collateral flow and reduced myocardial ischemic injury.
Action of caffeine on calcium transport by isolated fractions of myofibrils, mitochondria, and sarcoplasmic reticulum from rabbit heart.
Authors: Blayney L , Thomas H , Muir J , Henderson A
Published: June 2012

We studied the effects of caffeine on calcium transport by subcellular organelles isolated from rabbit myocardium. Caffeine increased myofibrillar basic and calcium-activated ATPase activity at 20 mM but not at lower concentrations. Mitochondrial and sarcoplasmic reticulum (SR) calcium accumulation was measured both by dual wavelength spectrophotometry with the calcium-sensitive dye, murexide, and by Millipore filtration with 45Ca. In mitochondria, caffeine impaired phosphate-assisted calcium transport but did not alter the closely related parameters of oxygen uptake, P/O ratio (nmol adenosine diphosphate consumed/n ats oxygen consumed, state 3 respiration) or limited calcium loading. In SR, caffeine impaired calcium accumulation. New methods were used to characterize calcium accumulation in the absence of oxalate according to first order reaction kinetics. Caffeine increased the rate constant while decreasing the calcium accumulated. It also increased the associated calcium-activated ATPase activity at low (30 mM) but not high (240 micrometer) external calcium concentration. In the presence of oxalate, caffeine decreased the rate of calcium accumulation, more with low than high calcium concentration. Net efflux of 45Ca from preloaded SR also was increased by caffeine. The findings indicate that caffeine impairs active calcium accumulation by making SR vesicle membranes more permeable to calcium.
Experimental evaluation of streamline patterns and separated flows in a series of branching vessels with implications for atherosclerosis and thrombosis.
Authors: el-Masry O A , Feuerstein I A , Round G F
Published: June 2012

Flow conditions in four models representing the aortic bifurcation, iliac bifuraction, and a renal artery branch were investigated at volumetric flow rates corresponding to Reynolds numbers from 1000 to 4000 over the complete range of flow division between daughter vessels. Qualitative flow streamline patterns and quantitative definition of those flow conditions leading to disturbed flow (flow separation ) were determined primarily at steady flow with a limited set of pulsatie experiments. Under conditions of no flow separation, common characteristic streamline patterns not parallel to the center lines of parent or daughter tubes were found for all models. These effects were accentuated with increasing Reynolds number. Flow separation was inducible through alteration of flow division between daughter vessels or by an increase in flow rate. Each of the four models had distinct combinations of flow division ratio and flow rate which gave: (1) no flow separation, (2) flow separation at the outside of the right daughter tube, and (3) flow separation at the outside of the left daughter tube. Models representing the renal artery also had regions of simultaneous left- and righthand separation on the outside of their daughter tubes. The separated flows observed here displayed streamlines forming an open vortex with flows entering and leaving. These regions, which occur only at distinct combinations of flow rate and flow division, may be key centers where platelet aggregates may form, release constituents, and cause vessel injury.
Synthesis and degradation of myocardial protein during the development and regression of thyroxine-induced cardiac hypertrophy in rats.
Authors: Sanford C F , Griffin E E , Wildenthal K
Published: June 2012

Cardiac hypertrophy was induced in rats by daily injections of L-thyroxine (1.0 mg/kg). Regression from hypertrophy was studied 4 days after discontinuing thyroxine. Isolated, Langendorff-perfused hearts were perfused with Krebs-Henseleit buffer, glucose, insulin, and amino acids. To measure protein synthesis, left ventricular tissue was assayed for incorporation of tritiated phenylalanine into protein. Indices of rates of protein degradation were obtained by measuring the release of cold phenylalanine after blocking protein synthesis with cycloheximide. After 3 days of thyroxine (when cardiac growth was maximally increased), the rate of protein synthesis increased by 22% (P less than 0.001). After 1 week, synthesis was 8% greater than control (P less than 0.05), and by 2 weeks (when hypertrophy was stable and the rate of cardiac growth was similar to controls), synthesis had returned to control levels. In hearts regressing from hypertrophy, synthesis was reduced to 68% of control (P less than 0.001). The rate of protein degradation was decreased by 12% (P less than 0.05) after 3 days of thyroxine, but was not different from control at 1 or 2 weeks. During regression, degradation was 12% below control (P less than 0.05). Changes in the release of several amino acids that are synthesized or metabolized in heart (e.g., alanine, glycine, serine) were different from changes in phenylalanine release. In conclusion thyroxine-induced cardiac hypertrophy and regression are accompanied by changes in protein synthesis and degradation, and amino acid metabolism. The predominant change in hypertrophy is increased protein synthesis with a minor contribution from reduced degradation. Regression of hypertrophy is accompanied by decreased synthesis, not increased degradation.
Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia.
Authors: Kennett F F , Weglicki W B
Published: June 2012

Myocardial ischemia was produced for 2 hours by coronary ligation in 11 dogs pretreated with methylprednisolone (MP, 30 mg/kg). Myocardial blood flow (MBF) was measured with microspheres (15 micrometer) in each tissue sample used for enzymatic analysis. Homogenates of these tissue samples were separated by ultracentrifugation into lysosome-rich and microsomal fractions and were analyzed for N-acetyl-beta-glusosaminidase (NAGA), beta-glucuronidase (beta-gluc), rotenone-insensitive-NADH-cytochrome c reductase (RINCR), and cytochrome oxidase. The enzymatic data from centrifugal fractions were grouped according to MBF values for statistical analysis of inter-group effects of ischemia. Significant losses (P less than 0.001) of NAGA and beta-gluc were seen in all MP-treated lysosome-rich particulate fractions that were isolated from zones demonstrating MBF values less than 25% of control (L-ischemia). Similar significant losses (P less than 0.001) of RINCR were seen in microsomal fractions from L-ischemia zones. Samples with MBF values greater than 25% but less than 75% of control (M-ischemia) also demonstrated significant decreases of lysosomal and microsomal enzymatic activity in specific fractions. When the data of the above MP-treated group were compared with the untreated control group, no significant intergroup effects of treatment with MP were observed. In addition, enzymatic data (NAGA, RINCR) were normalized prior to performing linear regression analyses; percent loss of particulate enzymatic activity was plotted against percent decrease in MBF. The effects of 2 hours of ischemia on the above biochemical parameters were comparable between untreated and MP-treated groups. Finally, when myocardial samples were grouped according to similar levels of MBF, statistical analysis using the general linear models procedure revealed no beneficial effect of MP treatment on changes in lysosomal hydrolases, microsomal RINCR, or latency of lysosomes.
Staircase in frog ventricular muscle. Its dependence on membrane excitation and extracellular ionic composition.
Authors: Chesnais J M , Kavaler F , Anderson T W , Coraboeuf E
Published: June 2012

Staircase was studied in frog ventricle strip preparations where it was possible to alter extracellular ionic composition extremely rapidly in the diastolic interval between beats. Several findings strongly indicate that staircase in this tissue is a result of progressively increasing calcium influx per beat, rather than a beat-by-beat augmentation of an intracellular calcium pool which contributes to activation. After a steady state of force development, the very next beat could be graded, from approximately zero force to the steady state value attained during the staircase progression, by grading the calcium concentration of a new Ringer's solution switched to perfuse the muscle in the diastolic period immediately before that beat. Also, action potentials, elicited during the "quiescent" period in the virtual absence of contraction (in 0.025 mm calcium Ringer's solution), markedly increase force development and accelerate the staircase seen upon return to normal Ringer's solution. Staircase is augmented and accelerated by prior exposure of the muscle, during the quiescent period, to calcium-poor media and markedly suppressed by prior exposure to sodium-poor media. Tetrodotoxin, in a dose that markedly slows the action potential upstroke, has no effect on staircase. Finally, staircase is seen to occur during a train of depolarizations (by voltage clamp) to inside positive levels greater than the equilibrium potential for sodium. It is concluded that changes in intracellular sodium concentration will alter the staircase response and may contribute to its genesis, but that this cannot be the sole cause of staircase.
Lymph and pulmonary response to isobaric reduction in plasma oncotic pressure in baboons.
Authors: Zarins C K , Rice C L , Peters R M , Virgilio R W
Published: June 2012

Plasma colloid osmotic pressure was reduced by 76% (from 19.6 +/- 0.6 to 4.7 +/- 1.5 mm Hg) in five baboons while pulmonary capillary hydrostatic pressure was maintained at a normal level. This resulted in fluid retention, weight gain, peripheral edema and ascites, but no pulmonary edema. Thoracic duct lymph flow increased 6-fold and pulmonary lymph flow 7-fold. Thoracic duct lymph had a lower colloid osmotic pressure (2.0 +/- 0.7 mm Hg) than plasma (4.7 +/- 1.5 mm Hg), whereas the colloid osmotic pressure of pulmonary lymph (4.7 +/- 0.7 mm Hg) was the same as that of plasma. The lymph-plasma ratio for albumin fell in thoracic duct lymph but remained unchanged in pulmonary lymph. The difference between plasma colloid osmotic pressure and pulmonary artery wedge pressure decreased from 15.3 +/- 1.9 to -0.7 +/- 2.9 mm Hg. Despite this increase in filtration force, the lungs were protected from edema formation by a decrease of 11 mm Hg in pulmonary interstitial colloid osmotic pressure and a 7-fold increase in lymph flow.
An analysis of the effects of acetylcholine on conduction and refractoriness in the rabbit sinus node.
Authors: Prystowsky E N , Grant A O , Wallace A G , Strauss H C
Published: June 2012

The effects of acetylcholine (ACh) on sinus node automaticity, atrio-sinus conduction, and refractoriness were studied in 41 isolated rabbit right atrial preparations. Average control rate was 126 beats/min, and ACh 5 x 10(-8) M, 5 x 10(-7) M, and 5 x 10(-6) M significantly decreased heart rate by 7, 15, and 43%, respectively (P less than 0.01, 0.001, and 0.001). Atrio-sinus conduction time at a pacing cycle length of 400 msec did not significantly change during exposure to ACh 5 x 10(-8) and 5 x 10(-7) M. However, the mean effective refractory period (ERP) of the sinus node, at a pacing cycle length of 400 msec, increased from 183 +/- 16 msec to 210 +/- 24 msec during exposure to ACh 5 x 10(-7) M (P less than 0.025). The change in ERP followed the change in action potential duration. In contrast to the lack of effect of ACh 5 x 10(-7) M on atrio-sinus conduction time, ACh 5 x 10(-6) M caused 2:1 atrio-sinus block in 8 of 10 experiments. The site of block was identified using multiple microelectrode impalements, and occurred between the perinodal fibers bordering on the edge of the sinus node and the pacemaker area in the sinus node proper. When the pacing cycle length was increased and 1:1 atrio-sinus conduciton was present, conduction time did not significantly differ from control. At this longer pacing cycle length the mean ERP of the sinus node was 380 msec greater than control and lasted well after repolarization was completed. Thus, atrio-sinus block during exposure to ACh 5 x 10(-6) M resulted from a marked prolongation of refractoriness.
The relationship between atrioventricular nodal refractoriness and the functional refractory period in the dog.
Authors: Simson M B , Spear J , Moore E N
Published: June 2012

We studied the relationship between the atrioventricular nodal functional refractory period (FRP) and refractoriness by mathematical analysis and by measurement during antegrade Wenckebach cycles in 16 dogs. The FRP relates directly to the conduction time of the control beat, and inversely to the coordinates of the point on the A'-H' vs. A-A refractory curve where the slope is -1. The FRP can vary without any change in refractoriness as measured by the effective refractory period (ERP) or the refractory curve. In 16 dogs the ERP and the FRP were measured during 4:3 Wenckebach cycles. Because of changes in the control conduction times, the FRP declined and did not reflect the progressive increase in refractoriness recorded during Wenckebach cycles. The FRP is a complex parameter and does not reliably measure refractoriness.
Carotid sinus reflex coronary vasoconstriction during controlled myocardial oxygen metabolism in the dog.
Authors: Powell J R , Feigl E O
Published: June 2012

We studied carotid baroreceptor reflex coronary vasoconstriction in closed-chest dogs with controlled aortic blood pressure and myocardial oxygen metabloism. The dogs were anesthetized with morphine and chloralose. Left coronary blood flow was measured by a cannula-tip flowmeter, and myocardial oxygen metabolism was calculated by measuring the arterial-coronary sinus oxygen difference. A bilateral vagotomy was performed in all animals and they were treated with propranolol. Reduction of carotid sinus pressure to 40 mm Hg caused an increase in aortic pressure that was limited to 15 mm Hg by means of a pressure-control reservoir. During carotid hypotension, heart rate and myocardial oxygen metabolism were unchanged but diastolic conronary vascular resistance increased by 21%. Intracoronary artery infusion of norepinephrine had similar effects. After interruption of the reflex are with the alpha-adrenergic receptor antagonist, dibozane, carotid sinus hypotension and the same increase in aortic pressure (15 mm Hg) resulted in only a 5% increase in diastolic coronary resistance. Dibozane also reduced the coronary responses to norepinephrine. It is concluded that carotid sinus hypotension results in reflex sympathetic alpha-receptor coronary vasoconstriction and that this reflex vasoconstriction is independent of changes in myocardial oxygen metabolism or changes in aortic pressure.
A possible role for elastin ligands in the proteolytic degradation of arterial elastic lamellae in the rabbit.
Authors: Kagan H M , Milbury P E , Kramsch D M
Published: June 2012

Thoracic aortae of normal rabbits were perfused with pancreatic elastase in vitro at 37 degrees C and 70 mm Hg pressure in the presence or absence of elastin ligands previously shown to stimulate or inhibit the enzymatic degradation of elastin. Perfusion with elastase results in an average of 3.6 lamellae degraded, whereas addition of sodium linoleate before and during the perfusion with elastase increases this value to 7.9 (P less than 0.001). Conversely, perfusion with the cationic detergent, dodecyltrimethylammonium chloride, completely prevents the degradation of elastic lamellae by elastase. These effects do not reflect alterations of the intrinsic catalytic activity of elastase, but apparently indicate the formation of complexes between the elastin ligands and arterial elastic lamellae, as is consistent with prior studies indicating such interactions between fatty acids or detergents and purified elastin. These studies suggest that agents such as fatty acids may significantly alter the metabolic susceptibility of elastin in vivo and possibly contribute to the degradation of elastic lamellae seen in arteries with advanced atherosclerosis.
Cellular mechanisms of normal growth in the mammalian heart. I. Qualitative and quantitative features of ventricular architecture in the dog from birth to five months of age.
Authors: Legato M J
Published: June 2012

This paper describes the qualitative and quantitative composition of dog myocardium over the first 5 months of life. The quantitative composition of dog right and left ventricle over this period does not vary. A stereological analysis of electron micrographs representing 32,000 micron2 of tissue surface revealed that 79% of the heart is made up of myofibers, whereas 21% is extracellular space. Twenty-eight percent of the extracellular compartment by volume is vasculature (tissue was preserved by immersion rather than vascular perfusion); 72% is occupied by nonvascular elements and "empty" space. In contrast to the remarkable constancy of quantitative composition of the whole myocardium, myocyte shape and dimensions and the arrangement of intercellular connections vary dramatically over the age period studied. In early postnatal life, the morphology of blood vessels, many of which have completely partitioned lumina, also changes significantly.