bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrolase activities in the rat aorta. III. Effects of regular swimming activity and its cessation.
Authors: Wolinsky H , Goldfischer S , Katz D , Markle R , Gidez L , Wassertheil-Smoller S , Coltoff-Schiller B
Published: June 2012

It is possible that one of the consequences of regular physical activity could be a change of vascular metabolism. We studied the effects of regular swimming activity on specific activities of aortic hydrolases of male rats. Enzymes included: neutral alpha-glucosidase and lysosomal beta-galactosidase, N-acetyl-beta-glucosaminidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 8 or 16 weeks of a 1-hour/day swimming protocol, specific activities of four of the six aortic enzymes studied were increased over control levels, increases ranging from 7 to more than 42%. Acid cholesteryl esterase was one of the enzymes most affected by the exercise, increasing 25-30% above control levels. An 8-week sedentary period, after 8 weeks of a swimming regimen, resulted in return of the activity of acid cholesteryl esterase, but not those of the other hydrolases, to control levels. Decreases in body weight, blood pressure, and serum lipid levels also occurred in the swimming rats. Weight reduction per se was excluded as an explanation for the increases in aortic enzymes or decrease in serum cholesterol found with swimming. These findings show that regular physical activity is yet another factor with discrete and significant effects on the catabolic activity of vascular tissue.
The plasma membrane of leading pacemaker cells in the rabbit sinus node. A qualitative and quantitative ultrastructural analysis.
Authors: Masson-Pévet M , Bleeker W K , Gros D
Published: June 2012

We studied the fine structure of the plasma membrane of electrophysiologically identified leading pacemaker cells from the rabbit sinus node, using both ultrathin sections of fixed tissue and replicas of freeze-cleaved material. We found that differences exist between sinus node and working myocardial membranes, but these are only quantitative. The caveolae or sarcolemmal invaginations are present in very large numbers; they increase the surface area of the plasma membrane by about 100%. The small macular nexuses that are present represent 0.2% of the membrane surface area. Nexuses are therefore about 10 times less numerous in leading sinus node cells than in working myocardium cells. A single equivalent electrical representation of the sinus node shows, nevertheless, that an appreciable electrical coupling may be expected.
Modulating effect of regional myocardial performance on local myocardial perfusion in the dog.
Authors: Marzilli M , Goldstein S , Sabbah H N , Lee T , Stein P D
Published: June 2012

We studied the effect of regional contractile performance on regional coronary blood flow and flow distribution in 10 dogs. The left anterior descending (LAD) coronary artery was cannulated and perfused. Maximal vasodilation was obtained with adenosine. Consequently, variations of LAD flow reflected changes of extravascular resistance. Lidocaine injected in the LAD caused a localized reduction of contractile performance as shown by the absence of systolic wall thickening. Global left ventricular performance and pressure were unchanged. Coronary extravascular resistance diminished and LAD flow increased from 4.8 +/- 0.5 to 6.2 +/- 0.6 ml/min per g (P less than 0.02). The endocardial: epicardial ratio increased from 1.02 +/- 0.07 to 1.28 +/- 0.07 (P less than 0.001). Isoproterenol in the LAD augmented systolic wall thickening. Regional coronary flow diminished from 5.1 +/- 0.5 to 3.3 +/- 0.4 ml/min per g (P less than 0.001), and the endocardial:epicardial ratio diminished from 1.08 +/- 0.07 to 0.75 +/- 0.07 (P less than 0.01). These data indicate that myocardial contractility is a major component of extravascular coronary resistance and is a mechanical determinant of coronary blood flow and its transmural distribution.
Effects of spontaneous respiration on canine left ventricular function.
Authors: Summer W R , Permutt S , Sagawa K , Shoukas A A , Bromberger-Barnea B
Published: June 2012

The purpose of this study was to determine the mechanism of the decrease in left ventricular stroke volume during spontaneous inspiration. We determined the transmural pressures of the left heart by measuring left atrial and diastolic left ventricular pressures relative to esophageal pressure. We estimated the directional changes in end-systolic and end-diastolic volumes of the left ventricle by determining the transit time of sound transmission between two ultrasonic crystals facing each other across the minor axis of the left ventricle. Left ventricular stroke volume decreased with spontaneous inspiratory effort as pleural pressure fell, regardless of whether lung volume increased or remained constant. The stroke volume was decreased during the fall in pleural pressure because of an increase in end-systolic volume with an essentially unchanged diastolic volume. Thus, the decrease in stroke volume was due to a decrease in ejection, rather than a decrease in filling of the left ventricle. We believe that left ventricular ejection was impeded by the fall in pressure around the heart relative to the pressure in the aorta. In spite of the essentially constant diastolic volume, diastolic left ventricular transmural pressure rose, suggesting that spontaneous inspiration decreases the diastolic compliance of the left ventricle. The change in diastolic compliance contributed to the decrease in stroke volume but was not the primary cause.
Quantitative studies on plasmalemmal folds and caveolae of rabbit ventricular myocardial cells.
Authors: Levin K R , Page E
Published: June 2012

Plasmalemmal folds and caveolae were investigated by qualitative and quantitative analysis of electron micrographs obtained by freeze fracture and transmission electron microscopy (TEM) of rabbit right ventricular papillary muscles whose mean sarcomere lengths ranged from 1.64 to 2.28 micron. In passively extended muscles, folds were observed at sarcomere lengths of 2.3 micron and could be shown by extrapolation to become completely extended at a maximum sarcomere length of 2.8 micron. It was concluded that the plasmalemma does not contribute to resting tension in the physiological range of sarcomere lengths. Caveolae are present in both the external plasmalemmal envelope and T-tubular plasmalemma. They show no preferential distribution with respect to underlying myofibrillar striations or membrane folds and are nearly devoid of membrane particles in freeze-fractured material. The surface density of caveolar necks (4.0/micron2 apparent plasmalemmal area) is only 16-20% of that reported for frog skeletal muscle. Caveolae augment plasmalemmal area by 21-32%, assuming two or three caveolae per neck, respectively. Caveolar membrane does not serve as a reservoir of membrane to be recruited into external plasmalemma, at least over the physiological range of sarcomere lengths. In heart muscle they do not account for the T-tubular access resistance, and their function in this tissue remains unknown.
The relationship between ultrasonic pulsatility index and proximal arterial stenosis in a canine model.
Authors: Evans D H , Barrie W W , Asher M J , Bentley S , Bell P R
Published: June 2012

Although the ultrasonic pulsatility index (PI) is used as a test of arterial inflow, the relationship between proximal arterial stenosis and PI has not been fully evaluated. In a series of experiments on dogs, over 200 measurements of pressure, flow (using an indwelling electromagnetic flowmeter), and PI were made distal to implanted arterial stenoses of varying length (0.5--9 mm) and cross-sectional area (36--94% reduction in area). It was shown that, whereas the reduction of PI correlates broadly with stenosis severity, the scatter of results is wide for all but the tightest stenoses. This scatter is due at least in part to the variability of the vascular bed distal to the site of measurement.
Synthesis and pharmacology of a noncompetitive antagonist of angiotensin-induced contractions of vascular smooth muscle. [Sarcosyl]1-[cysteinyl (s-methyl)]8-angiotensin II.
Authors: Freer R J , Sutherland J C , Day A R
Published: June 2012

The synthesis of an angiotensin II (A II) antagonist, sarcosyl1-cysteinyl(S-methyl)8-angiotensin II [Sar1-Cys(Me)8-A II], showing partial organ selectivity and properties of a noncompetitive antagonist, is described. The compound was found to be an extremely potent antagonist on vascular smooth muscle both in vitro (pA2 for rabbit aorta approximately equal to 9.2) and in vivo on rat blood pressure (dose ratio of 103 for ED25 mm Hg during 1 microgram/kg per min infusion of antagonist). It was without effect on norepinephrine responses in both assay systems. In contrast, it was a considerably weaker antagonist on visceral smooth muscle (pA2 for guinea pig ileum = 8.5; pA2 for rat uterus = 7.9). Interestingly, in the vascular smooth muscle preparations, the compound also exhibited elements of a noncompetitive antagonist in that both the slope and maximum of the A II dose-response curves were reduced markedly. Qualitatively similar results were obtained with sarcosyl1-alanyl8-angiotensin II (Saralasin) on rabbit aorta. Moderate depression of maximum response was seen in guinea pig ileum but not in rat uterus. These effects on vascular smooth muscle were reversible in vitro but only partially reversible in vivo.
Characterization of high and low pressure baroreceptor influences on renal nerve activity in the primate Macaca fascicularis.
Authors: Echtenkamp S F , Zucker I H , Gilmore J P
Published: June 2012

We characterized the influence of high pressure and low pressure intravascular receptors on renal nerve activity in the pentobarbital sodium-anesthetized nonhuman primate Macaca fascicularis. Epinephrine-induced increases in arterial pressure were used to stimulate high pressure receptors, and intravascular volume expansion was used to stimulate both high and low pressure receptors. In addition, the intravascular mechanoreceptors were stimulated directly by intravenous veratrine administration. All interventions produced large decreases in renal nerve activity in the intact state. Denervation of the carotid sinus or bilateral cervical vagal section dimished, whereas sinoaortic denervation with vagotomy completely abolished all responses of renal activity to these interventions. We conclude that the nonhuman primate possesses very sensitive renal nerve sympathetic reflexes that are modulated by intravascular mechanoreceptors whose afferents traverse the carotid sinus nerves and the vago-aortic trunks. The carotid sinus nerves and the vago-aortic trunks appear to be equally effective in inhibiting renal nerve activity in response to increases in arterial pressure. In addition, there are no afferent pathways mediating intravascular mechanoreceptor modulation of renal nerve activity outside the carotid sinus nerves and the vago-aortic trunks.
Morphometry of pinocytotic vesicles in the capillary endothelium of rabbit lungs using automated equipment.
Authors: Gil J , Silage D A
Published: June 2012

Pinocytotic vesicles are one of several anatomic factors relevant to the permeability for macromolecules of capillary endothelia. We quantitified the number and distribution of pinocytotic vesicles present in the endothelium of pulmonary capillaries. Several similar studies have been reported in the past for endothelia of systemic capillaries, but the technical difficulties involved in this difficult application of morphometry never have been discussed. In the present work, an on-line microprocessor was used to assist with the processing of the point-counting data. The average figures from nine rabbit lungs for parameters thought to be relevant to characterize the population of vesicles are: thickness of the endothelium (TAUen) 0.192 microns; number of vesicles per volume unit of cell (NVen), 131 vesicles/microns3; vesicular load of each cell front (N/S)b, 196 vesicle/microns2, and (N/S)i, 181 vesicles/microns2. The number of vesicles per volume unit (NVen) is smaller than that which has been described for systemic capillaries.
Linearity of the vascular pressure-volume relationship of the canine intestine.
Authors: Rothe C F , Bennett T D , Johns B L
Published: June 2012

To test whether the pressure-volume relationship of the canine small intestinal vasculature is linear over the normal range of portal venous pressures (5 to 35 mm Hg), we used two methods to measure volume: (1) the integral of inflow minus outflow (IFD), and (2) tissue activity of 51Cr-labeled erythrocytes (Cr-51). Venous pressures were changed in steps of 5 mm Hg with a servo-controlled system. The tissue was perfused at a constant rate. With venous pressures of 3.6 to 38.6 mm Hg, the vascular compliance was 2.19 +/- 0.42 (SD) ml/kg x mm Hg using IFD, and 1.87 +/- 0.50 ml/kg x mm Hg using Cr-51. Although a quadratic term significantly improved the fit, the effect was small (less than 3 ml/kg with a 30 mm Hg venous pressure change). The control blood volume of the intestinal loop at a venous pressure of 8.6 +/- 1.5 (SD) mm Hg was 86.2 +/- 19.1 ml/kg tissue weight using the mean transit time of a step input of indocyanine green at a perfusion pressure of 106 +/- 29 mm Hg and a flow of 556 +/- 147 ml/min x kg. We conclude that there is no significant change in compliance over the normal venous pressure range of 5-35 mm Hg.
Comparison of Ca2+, Sr2+, and Mn2+ fluxes in mitochondria of the perfused rat heart.
Authors: Hunter D R , Komai H , Haworth R A , Jackson M D , Berkoff H A
Published: June 2012

The amount of readily exchangeable Ca2+ in mitochondria of an isolated working rat heart is less than 10 ng-ions/g heart. We therefore conclude that either no Ca2+ enters mitochondria or that the Ca+ which does enter is removed continuously. Using Sr2+ and Mn2+, we obtained evidence that the mitochondrial Na+-Ca2+ exchanger was indeed operational in releasing metal from mitochondria of the heart. When Ca2+ in the perfusate was replaced by Sr2+, we found that a significant amount of Sr2+ (approximately 100 ng-ions/g heart) entered mitochondria. When the heart then was returned to a Ca2+-containing perfusate, over 80% of the Sr2+ was washed out of mitochondria within 30 seconds. When low levels of Mn2+ were added to the perfusate, we found that Mn2+ accumulated in mitochondria irreversibly. This is evidence for the operation of the Na+-Ca2+ exchanger because Na+ was found to release Ca2+ and Sr2+ but not Mn2+ from isolated rat heart mitochondria. Our estimates indicate that when the Na+-Ca2+ exchanger is maximally operative, as in the Sr2+-perfused heart, the flux of Sr2+ through mitochondria is at most 10% of the total flux needed for the activation of contraction. The low level of Ca2+ in the mitochondria of Ca2+-perfused hearts suggests a much smaller flux of Ca2+ through the mitochondria in this case. We therefore conclude that mitochondria play little if any role in the beat-to-beat regulation of normal Ca2+ fluxes in the rat heart.
Relationship of cardiac oxygen usage, adenosine content, and coronary resistance in dogs.
Authors: Saito D , Nixon D G , Vomacka R B , Olsson R A
Published: June 2012

Analysis of the relationships between cardiac oxygen usage (MVO2), cardiac muscle adenosine levels([Ado]), and coronary vascular resistance (R) in open-chest, anesthetized dogs tested the hypothesis that adenosine is a physiological regulator of coronary flow. Experiments using each dog as its own control showed that [Ado] varied directly with MVO2 as the latter changed spontaneously or in response to atrial pacing, paired pacing, aortic constriction, of beta-adrenergic blockade. In turn, R varied inversely with changes in [Ado]. Stimulating MVO2 with isoproterenol significantly increased the slope of the regression of [Ado] on MVO2 as well as of R-1 on [Ado]. The effect of beta-adrenergic stimulation on [Ado] is unexplained, but its effect on R-1 seems to reflect the combined effects of adenosine and direct beta-adrenergic coronary relaxation. These results support the hypothesis that adenosine mediates the coronary flow responses to changes in MVO2.
An analysis of the pulsatile hemodynamic responses of the pulmonary circulation to acute and chronic pulmonary venous hypertension in the awake dog.
Authors: Hopkins R A , Hammon J W , McHale P A , Smith P K , Anderson R W
Published: June 2012

In this study we measured high fidelity pulsatile pressure and flow waveforms at the inlet to the pulmonary vascular bed to assess the differences in adaptation to acute and chronic pulmonary venous hypertension in awake dogs. Acute elevations in left atrial pressure (P1a) were effected by inflation of left atrial balloons, while chronic elevations were accomplished by placement of aorta to left atrial shunts. Pulmonary artery hydraulic impedance was calculated and analysis of these data revealed marked differences between the responses to acute and chronic elevations of left atrial pressure. The acutely stressed dogs (n = 12) had significantly decreased pulmonary vascular resistance (when P1a = 16.9 +/- 1.0 mm Hg, PVR = 212 +/- 57 dynes sec/cm5; when P1a = 28.6 +/- 1.4 mm Hg PVR = 18 +/- 115 dynes sec/cm5; control P1a = 6.1 +/- 1.5 mm Hg, and PVR = 355 +/- 69 dynes sec/cm5) and normal characteristic impedances (ZO) (210 +/- 36, 227 +/- 39, 178 +/- 14 dynes sec/cm5, respectively), indicating recruitment of arteriolar-capillary perfusion density and no change in proximal pulmonary arterial physical properties. The chronic pulmonary venous hypertension group (n = 11) retained normal PVR (496 +/- 30 dynes sec/cm5) but demonstrated a markedly higher characteristic impedance, ZO = 361 +/- 11 dynes sec/cm5 (P < 0.001). This indicated a measurably different and extremely potent effect of chronic venous hypertension on the physical properties of the pulmonary vessels with an apparently increased arterial stiffness correlating with a 4-fold increase in Young's elastic modulus. These changes were not reversed by alpha-adrenergic blockade or acute lowering of left atrial pressures.
Vasoactive intestinal polypeptide and the canine cerebral circulation.
Authors: Wilson D A , O'Neill J T , Said S I , Traystman R J
Published: June 2012

A potential role for cerebrovascular nerves containing vasoactive intestinal polypeptide (VIP) was examined in 24 anesthetized, ventilated dogs. Cerebral blood flow (CBF) was measured by either the cerebral venous outflow or microsphere method. Plasma VIP concentration was measured by radioimmunoassay. Hypercapnia (5% and 10% CO2) and hypoxia (7% O2) produced significant increases in cerebral venous outflow, but had no affect on arterial or cerebral venous VIP concentrations. Measurements of VIP in cerebrospinal fluid (CSF) made during 5% and 8% CO2 breathing also were not different from control values. VIP produced large dose-dependent increases in common carotid artery and temporalis muscle blood flow when injected or infused intraarterially; however, VIP had no effect on total or regional cerebral blood flow (rCBF) within the brain when administered in a similar manner. Unilateral perfusion of the cerebral ventricles with VIP produced significant increases (range: 11-80%) in rCBF. These data are consistent with the possibility that local release of VIP from perivascular nerve endings could affect CBF. The unresponsiveness of canine cerebral vessels to blood-borne VIP may be due to the blood-brain barrier, since VIP dilates cerebral vessels when the barrier is bypassed by intraventricular infusion. These studies do not support the hypothesis that CBF changes induced during hypercapnia or hypoxia are mediated by VIP.
Effects of intracoronary administration of bradykinin on the impulse activity of afferent sympathetic unmyelinated fibers with left ventricular endings in the cat.
Authors: Lombardi F , Della Bella P , Casati R , Malliani A
Published: June 2012

In anesthetized and artificially ventilated cats, we recorded the impulse activity of 23 afferent sympathetic unmyelinated fibers with left ventricular endings, dissected from the left sympathetic rami T3 and T4. All fibers displayed a spontaneous discharge at a rate of 0.79 +/- 0.2 (mean +/- SE) impulses/sec. During constriction of the thoracic aorta, the discharge increased to 1.92 +/- 0.2 impulses/sec. During myocardial ischemia, produced by interruption of left main coronary artery perfusion, supplied through an extracorporeal pump, the impulse activity increased to 1.73 +/- 0.3 impulses/sec. The mean latency for this excitation was 16.5 +/- 1.5 sec. The intracoronary administration of bradykinin (5 and 10 ng/kg) elicited a marked increase in impulse activity that, following 5 ng/kg, reached 2.06 +/- 0.2 impulses/sec, after a latency of 18 +/- 2 sec and in absence of significant hemodynamic changes. Myocardial ischemia and bradykinin never revealed the existence of silent afferent fibers included in the split nerve strand. The results obtained with this experimental model indicate that the ventricular endings of these afferent sympathetic unmyelinated fibers act as "polymodal" receptors. We hypothesize that the peripheral mechanism for cardiac nociception involves intensive excitation of fibers discharging spontaneously and not recruitment of silent fibers which are purely nociceptive in function.
Characteristics of sarcomere shortening in single frog atrial cardiac cells during lightly loaded contractions.
Authors: Tarr M , Trank J W , Leiffer P
Published: June 2012

We studied sarcomere performance in single isolated intact cardiac cells using techniques that allow direct measurement of sarcomere length and force. This investigation dealt primarily with sarcomere performance during twitch contractions under lightly loaded conditions. In such contractions, there was a significant portion of the contraction in which sarcomere shortening occurred at constant velocity over a significant range of sarcomere lengths. The constant velocity phase of shortening was followed by a phase of shortening in which sarcomere velocity decreased markedly. Both the velocity and extent of sarcomere shortening depended on the stimulus parameters used to excite the cell. With threshold stimulation, sarcomere velocities during the constant velocity phase of shortening ranged from 1 to 5.5 micron/sec in different cells and significant slowing of sarcomere shortening began at sarcomere lengths of 1.8-2.0 micron. In contrast, when cells were stimulated with a long duration stimulus (200 msec) of large current strength, sarcomere velocities during the constant velocity phase ranged from 6 to 12 micron/sec, and significant slowing did not occur until a sarcomere length of about 1.6 micron was reached. The threshold stimulus strength-stimulus duration relationship was determined on the single cell, and it was found to be of the type expected for a cell having an intact excitable membrane capable of generating an action potential when depolarized to a fixed voltage threshold. The data presented in this paper give direct evidence that the lightly loaded cardiac sarcomere has a velocity of shortening which depends on the level of contractile activation but is independent of sarcomere length at sarcomere lengths greater than about 1.6 micron.
Relative contributions of arginine vasopressin and angiotensin II to maintenance of systemic arterial pressure in the anesthetized water-deprived rat.
Authors: Andrews C E , Brenner B M
Published: June 2012

We used a structural analogue of arginine vasopressin (AVP) and investigated the role of AVP in the maintenance of mean arterial pressure (AP) in anesthetized, water-deprived rats. The administration of [1(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 4-valine-8-D-arginine] vasopressin, d(CH2)5VDAVP, completely inhibited to 30-40 mma Hg rise in AP which normally accompanied the administration of 50 mU exogenous AVP (group 1). Thus, d(CH2)5VDAVP is a specific antagonist of the vascular effects of AVP. d(CH2)5VDAVP failed to significantly alter AP in water diuretic rats (group 3) and was without effect on urine osmolality during water diuresis or antidiuresis. However, bolus injection of d(CH2)5VDAVP into water deprived rats (group 2) prompted an abrupt fall in AP from 112 +/- 4 to 94 +/- 4 mm Hg (P less than 0.001). This fall in AP was transient, with return of AP to 110 +/- 4 mm Hg within 15 minutes. Administration of saralasin, an angiotensin II antagonist, not only prevented the compensation in AP, but also significantly magnified the maximal hypotensive response seen following d(CH2)5VDAVP (group 4). Discontinuing the saralasin allowed AP to return to baseline. Bilateral nephrectomy (group 5) also prevented the return of AP, further implicating endogenous angiotensin II as the specific mediator of the compensation in AP following d(CH2)5VDAVP administration. These studies clearly demonstrate that circulating AVP contributes to the maintenance of AP during water deprivation in the anesthetized rat. When this vascular action of AVP is blocked, angiotensin II assumes major responsibility for blood pressure regulation in the antidiuretic state.
Inhibitory action of adenosine on histamine- and dopamine-stimulated cardiac contractility and adenylate cyclase in guinea pigs.
Authors: Baumann G , Schrader J , Gerlach E
Published: June 2012

Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of cardiac contractile force development elicited by bolus injections of histamine (7.5 X 10(-9) mol) or dopamine (1.5 X 10(-8) mol). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) was obtained at 3 X 10(-5) M. Adenosine in the effective concentration range did not alter Ca2+-induced increases in contractile force. The rise in tissue levels of cAMP induced by equieffective doses of histamine (7.5 X 10(-9) mol) and dopamine (1.5 X 10(-8) mol) was inhibited by adenosine (3.5 X 10(-5) M) by about 60%. In a particular membrane preparation of guinea pig ventricles the adenylate cyclase activity stimulated by the histamine (10(-5) M) and dopamine (10(-4) M) was inhibited in a dose-dependent manner by adenosine. This effect could be reversed by theophylline (5 X 10(-5) M) in a competitive manner. The hormone-insensitive adenylate cyclase of a Lubrol-PX solubilized membrane preparation stimulated by NaF or 5'-guanylylimido-diphosphate (GppNHp) was also inhibited by adenosine (40% and 90% inhibition at 10(-5) M and 10(-4) M, respectively). Adenosine did not influence the Km value of the adenylate cyclase for ATP, but markedly lowered Vmax of the enzyme. From additional studies with purine-substituted (N6-methyl-adenosine, N6-phenylisopropyl-adenosine) and ribose-substituted (2'-deoxy-adenosine and arabino-furanosyl-adenine) adenosine analogues, we conclude that adenosine may inhibit the inotropic responses to hormones as well as the adenylate cyclase activity by specifically interacting with at least two different sites associated with the adenylate cyclase.
The effect of the carotid sinus baroreceptor reflex on blood flow and volume redistribution in the total systemic vascular bed of the dog.
Authors: Brunner M J , Shoukas A A , MacAnespie C L
Published: June 2012

To quantify the relative contribution of blood flow redistribution and active changes in vascular capacity in the regulation of cardiac output, blood flow and volumes in two parallel vascular beds were measured in response to varying carotid sinus pressures. In nine dogs, carotid sinuses were isolated and intrasinus pressure was controlled. Two external reservoirs were placed between the caval veins and the right heart to measure changes in vascular capacity in splanchnic and extrasplanchnic vascular beds. At intrasinus pressures of 50 and 200 mm Hg, we have simultaneously measured arterial resistances, compliances, changes in flows, and "unstressed vascular volume," and time constants of venous drainage in the splanchnic and extrasplanchnic vascular beds. Compliances and time constants of venous drainage were found to be nearly equal in the two beds. A decrease in intrasinus pressure from 200 to 50 mm Hg resulted in a small redistribution of blood flow (about 5% of cardiac output) from the extrasplanchnic compartment to the splanchnic vascular bed. Changes in reservoir volumes were found to be around 7.0 ml/kg. The splanchnic vascular bed was responsible for a greater change in reservoir volume for a given change in intrasinus pressure. With any change in intrasinus pressure, the change in arterial resistance in the extrasplanchnic vascular bed was greater than that of the splanchnic vascular bed. Blood flow redistribution was not found to be a significant factor contributing to changes in reservoir volume. The changes in reservoir volume seen, must have been due to active changes in vascular capacity in the two channels chosen.
Acute hypertension after the local injection of kainic acid into the nucleus tractus solitarii of rats.
Authors: Talman W T , Perrone M H , Reis D J
Published: June 2012

Kainic acid (KA), an analogue of L-glutamate, was microinjected in 0.1 microliter of saline into the nucleus tractus solitarii (NTS) of adult rats. In rats anesthetized with halothane or alpha-chloralose, KA injected unilaterally elicited hypotension, bradycardia, and apnea. The threshold dose was 0.1-0.2 ng (10(-13) mol). Doses greater than 0.2 ng blocked responses to subsequent injections for at least 30 minutes. Doses of KA greater than 15 ng reduced the reflex bradycardia elicited by raising the arterial pressure with phenylephrine and produced arterial hypertension in rats anesthetized with alpha-chloralose or in other rats within 15 minutes of terminating halothane anesthesia. Bilateral injection of KA in doses greater than 15 ng completely blocked baroreflexes and resulted in a dose-dependent elevation of arterial pressure (167 +/- 9.4; P less than 0.001) both in alpha-chloralose-anesthetized rats and in awake rats after the termination of halothane anesthesia. The hypertension rapidly led to pulmonary edema and death. Procaine microinjected also elicited fulminating hypertension; vehicle did not. Doses of KA producing hypertension caused no histological or biochemical evidence of neuronal death. The cardiovascular responses to KA were restricted to sites in the intermediate one-third of NTS and could not be elicited by injection into adjacent sites in brainstem. The results indicate that, in low doses, KA injected into NTS stimulates neurons which mediate the baroreflex, whereas, in higher doses, it produces baroreflex blockade and neurogenic hypertension. The results suggest that fulminating hypertension can be produced by nondestructive perturbations of neurochemical transmission in brain. Since the cardiovascular responses of KA are similar to those produced by microinjection into NTS of the amino acid neurotransmitter glutamic acid, the study adds further support to the hypothesis that L-glutamate is the neurotransmitter released by baroreceptor afferent nerves.
The effect of nitroglycerin and nitroprusside on intramural carbon dioxide tension during acute experimental myocardial ischemia in dogs.
Authors: Hillis L D , Davis C , Khuri S F
Published: June 2012

There is continuing controversy over the effects of nitroglycerin and nitroprusside on myocardial ischemia. In 36 open-chest, anesthetized dogs with normal left ventricular filling pressures, intramural carbon dioxide tension (PmCO2) was measured directly with a mass spectrometer during repeated 10-minute coronary artery occlusions separated by 45-minute periods of reflow. Simultaneously, regional myocardial blood flow (RMBF) in the ischemic area was quantified by the microsphere technique. In all dogs the increase in PmCO2 from before to 10 minutes after the first occlusion (delta PmCO2) exceeded that during subsequent occlusions. In those dogs not receiving an intervention (controls), delta PmCO2 during the third occlusion was similar to that during the second occlusion. When nitroglycerin was administered before the third occlusion, it caused a significantly smaller elevation in delta PmCO2 than that which occurred during the control second occlusion, and transmural RMBF to the ischemic region was not altered. In contrast, sodium nitroprusside sufficient to reduce mean systemic arterial pressure to the same extent as nitroglycerin caused no change in delta PmCO2 and a significant decrease of transmural RMBF to the ischemic region. Thus, in the dog with normal left ventricular filling pressures, nitroglycerin reduces myocardial carbon dioxide tension, but nitroprusside given to produce similar hemodynamic alterations exerts not effect on intramural PCO2.
Carnitine transport in isolated adult rat heart myocytes and the effect of 7,8-diOH chlorpromazine.
Authors: Bahl J , Navin T , Manian A A , Bressler R
Published: June 2012

We studied the carnitine transport system in isolated adult rat heart myocytes able to tolerate physiological concentrations of calcium. Carnitine uptake occurred against a concentration gradient and was inhibited by 2,4-dinitrophenol (2,4-DNP). The transport system had a Km of 60 microM and a Vmax of 110 pmol/mg protein per hour. The carnitine precursor deoxycarnitine, acetylcarnitine, and both the D and L isomers were effective inhibitors of uptake. The transport of carnitine was not dependent on sodium ions, but was stimulated by decreasing concentrations of calcium ions. Decreased uptake was observed in the presence of beta-adrenergic agonists and antagonists, dibutyrl cyclic AMP, local anesthetics, and ouabain. No significant alteration of uptake was effected by atropine, carbachol or a variety of tricyclic agents. The auto-oxidation product of 7,8-dihydroxychlorpromazine (7,8-diOH CPZ) decreased carnitine efflux from myocytes, which were highly permeable to low molecular weight compounds. We found that this effect was not substrate specific, and is discussed as possibly resulting from a change in the arrangement or state of polymerization of subcellular structural components.
Adaptation to prolonged beta-blockade of rabbit atrial, purkinje, and ventricular potentials, and of papillary muscle contraction. Time-course of development of and recovery from adaptation.
Authors: Raine A E , Vaughan Williams E M
Published: June 2012

Groups of littermate rabbits were treated for various periods up to 6 weeks with twice daily subcutaneous injections of saline, D-propranolol, DL-propranolol, or metoprolol, the latter two at doses equivalent to those used in clinical therapy. Investigations were made at a sufficient time (20-24 hours after the most recent dose) to ensure that the drugs would have been eliminated from the body, so that any observed changes would represent an adaptation to treatment, not effects due to the presence of the drugs. The ECG was recorded in vivo at regular intervals during treatment. After several days, Q-Tc was prolonged by the beta-blockers, reaching a peak effect at about 3 weeks from the start of treatment, and returned to control values at 3 weeks after cessation of treatment. Action potential duration, measured in vitro by intracellular recording, was also prolonged uniformly in atria and ventricles over a similar time-course, unrelated to cardiac frequency, but shortened in distal Purkinje cells. Peak tension was not altered in propranolol-adapted papillary muscles, but the relationship of rate of rise of tension was steeper. It is concluded that these effects represent a myocardial adaptation to prolonged beta-blockade.
Muscle extract infusion in rabbits. A new experimental model of the crush syndrome.
Authors: Blachar Y , Fong J S , de Chadarévian J P , Drummond K N
Published: June 2012

Previous studies provide inconclusive data concerning the nephrotoxicity of myoglobin following muscle injury. We investigated the possibility that released muscle constituents other than myoglobin may be associated with renal damage, and studied accompanying hematological and coagulation changes. An extract of homologous or autologous muscle was infused intravenously in rabbits in a dose of 100 mg of muscle extract protein/kg; equine myoglobin was given to control animals. Experimental animals developed proteinuria, cylindruria, and a 50% reduction in glomerular filtration rate. Leukopenia, thrombocytopenia and evidence of intravascular coagulation also were seen. The muscle extract was shown to have thromboplastic activity; however inhibition of this by phospholipase C did not prevent the changes induced by muscle extract infusion possibly because the intrinsic changes coagulation pathway still was activated. Although moderate hypotension and ECG changes developed in some rabbits, these were not consistent and the renal functional changes appeared to be independent of these factors. Pulmonary and glomerular microthrombi were seen in experimental animals and there was vacuolation of the renal proximal tubular cells. The studies indicate that a number of biological systems are activated following muscle extract infusion and that these may be more important than the nephrotoxicity of myoglobin in the pathogenesis of the renal injury.
The influence of vagal afferents on the left ventricular contractile response to intracoronary administration of catecholamines in the conscious dog.
Authors: Barron K W , Bishop V S
Published: June 2012

We studied the effect of vagal afferents on the left ventricular contractile response (LVdP/dtmax) to administration of sympathomimetic amines into the left circumflex coronary artery in conscious dogs. The positive inotropic effects of bolus administration of epinephrine, norepinephrine, and isoproterenol were greater during bilateral vagal cold block (BVB) that in the control state with the vagi intact (P less than 0.001). The inotropic potentiation observed with BVB was not due to vagal efferent interruption, since parasympathetic efferent block with atropine did not potentiate the inotropic effects of intracoronary epinephrine (P greater than 0.05). BVB also potentiated the inotropic effects of constant intracoronary infusion of epinephrine (P less than 0.01). BVB alone had no significant effect on LVdP/dtmax; dtmax (P less than 0.05). We propose that the potentiation of the inotropic effects during BVB could result from either interruption of a vagal afferent-mediated negative feedback reflex and/or an unmasking of a sympathetic afferent-mediated positive feedback effect induced by BVB. However, the observations that ganglionic blockade also potentiated the contractile effects of epinephrine supports the concept that a negative feedback reflex does attenuate the inotropic effect of catecholamines in the control state. In conclusion, these data suggest that vagal afferents attenuate the positive inotropic effects of intracoronary administration of catecholamines via a cardiocardiac negative feedback reflex which occurs through a vagal afferent inhibition of sympathetic efferent activity back to the left ventricle.
Redistribution of canine left ventricular myocardial blood flow in unloaded systole.
Authors: Williams R B , Tremer H M , Sobin S S
Published: June 2012

The left coronary arteries of dogs were cannulated and perfused with blood from support dogs. The experimental hearts were unloaded by severing the aortas to maximize strains and minimize fiber stress. In each heart we compared the transmural distribution of blood flow in two states: (1) provision of perfusion pressure (40 mm Hg) only during systole and then (2) provision of perfusion pressure throughout the cardiac cycle. The distribution of flow in each of these perfusion states was labeled with a diffusible radioisotope (42K or 86Rb, one labeling the first state; the other labeling the second). Quantitative, paired autoradiography was used to visualize the two flow distributions. The differences between the two distributions after standardization was plotted as differences between activity vs. depth in the myocardium (r = 0.91). This was fitted with a line by least squares, the slope of which was significantly different from zero at the 0.005 level. The magnitude of the gradient of the systolic flow was represented by the ratio of deep to shallow flow. The mean of these ratios was 0.54 +/- 0.12 (95% confidence interval). A graphical analysis shows that the data are consistent with a gradient of extravascular compression across the left ventricular wall.
Passive stiffness of pressure-induced hypertrophied cat myocardium.
Authors: Williams J F , Potter R D
Published: June 2012

The effect of myocardial hypertrophy on passive stiffness was determined from the stress (sigma)-strain relationship of right ventricular papillary muscles from 18 pulmonary artery-banded and 21 non-banded cats. By use of Lagrangian strain, (1-lo)lo is initial muscle length, and instantaneous stress elastic constants beta and alpha were calculated from the equation sigma = alpha(ebeta epsilon - 1). Elastic stiffness (d sigma/d epsilon) was determined from the formula d sigma/d epsilon = beta alpha + alpha beta. Banding produced an average increase in RV mass of 70%. Beta averaged 14.2 +/- 0.9 (SEM) and 16.0 +/- 0.8 in the non-hypertrophied and hypertrophied muscles, respectively (NS). However, elastic stiffness was significantly greater in hypertrophied muscles over the entire stress range. Contractile function varied widely among hypertrophied muscles but was not related to changes in stiffness. Thus, moderate degrees of pressure-induced hypertrophy are associated with a modest increase in the passive stiffness properties of the muscle, independent of changes in contractile function.
Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits.
Authors: El-Sherif N , Smith R A , Evans K
Published: June 2012

We made simultaneous recordings from 48 bipolar electrodes to obtain epicardial isochronal maps during induced ventricular arrhythmias in dogs 3-5 days after ligation of the left anterior descending artery. There was strong evidence of a reentrant circuit (RC) that was discernible largely on the epicardial surface in 21% of ectopic beats that were analyzed. Epicardial recordings were of limited value in analyzing the arrhythmia in other beats. The reentrant circuit consisted of an arc of conduction block around which the activation front advanced in a circular fashion at slow but uneven speeds while the rest of the ventricle was activated by radial spread. The arc of conduction block around which the RC was formed was usually functional in nature, since the same area of myocardium was excitable at relatively long cardiac cycle lengths. Both the length of the arc of conduction block which defines the length of the reentrant circuit and the degree of conduction delay were crucial factors for the occurrence of reentry. A premature beat that initiated reentry resulted in a longer arc of conduction block and slower conduction compared to one that failed to induce reentry.
Effect of mechanical work load on the transmural distribution of glucose uptake in the isolated perfused rat heart, studied by regional deoxyglucose trapping.
Authors: Takala T E , Hassinen I E
Published: June 2012

The applicability of the 2-deoxyglucose tracer method to the study of the transmural distribution of glucose uptake in the left ventricle of the isolated, Langendorff-perfused rat heart was validated for the myocardium. The total 2-deoxy[3H]glucose trapped in the myocardium was proportional to the glucose uptake which was varied by the mechanical work load and availability of other oxidizable substrates. When the mechanical work of the heart was eliminated by K+-induced arrest, the glucose uptake of 2.0 mumol/min per g protein was evenly distributed across the left ventricular wall. In the beating heart, glucose uptake averaged 4.7 mol/min per g protein, and was about 40% higher in the subendocardial layer than in the subepicardium (P less than 0.001). Measurement of the transmural distribution of coronary flow by the microsphere method indicated that there were no areas of underperfusion in the left ventricle. The transmural gradient in glucose uptake probably is caused by uneven distribution of the mechanical work load.
Myocardial morphometric characteristics in swine.
Authors: Singh S , White F C , Bloor C M
Published: June 2012

We have quantified the ultrastructure of myocardial cells in tissue samples obtained from six adult normal Yucatan swine. Tissue samples were obtained from 20 different sites in the left ventricle, right ventricle, and interventricular septum. The samples were processed for electron microscopy and quantitative morphometric analysis. The percent relative volumes of myofibrils, mitochondria, transverse tubular system, sarcoplasmic reticulum, and clear intracellular space were determined using stereological morphometric methods. Overall, the data were distributed homogeneously among the 20 individual sites. However, when certain subcellular components were examined regionally, some differences appeared. The mitochondrial:myofibril volume ratios were significantly increased in the left ventricle and interventricular septum compared to the right ventricle. They also were greater in the endocardial region compared to the epicardium, which is consistent with higher metabolic activity of these zones. Similarly, the sarcoplasmic reticulum:myofibril ratio was greater in the endocardial region vs. the epicardial region and the basal layer compared to the mid-layer, suggesting the greater need for provision of calcium ions in these particular zones. Since the swine is a convenient large animal for physiological studies, the results indicate that swine can also be used for quantitative morphometric measurements of myocardial changes in normal and pathologic hearts, and for the study of regional changes in various layers and regions of heart walls.
Effects of indomethacin, renal denervation, and propranolol on plasma renin activity in conscious dogs with chronic thoracic caval constriction.
Authors: Echtenkamp S F , Davis J O , DeForrest J M , Rowe B P , Freeman R H , Seymour A A , Dietz J R
Published: June 2012

The role of renal prostaglandins and the adrenergic nervous system in the control of renin release was studied in conscious dogs with thoracic caval constriction. Indomethacin reduced plasma renin activity (PRA) in intact animals with thoracic caval constriction by 43% but failed to change PRA after surgical renal denervation and during chronic propranolol administration; adrenergic blockade reduced the initial control level of PRA before indomethacin from 15 to 4 ng angiotensin I/ml per hr. Renal hemodynamic function was markedly reduced by indomethacin both before and after adrenergic blockade. These observations indicate that prostaglandins are involved in the control of renin release, but they appear to have a more important role in the control of renal arterial resistance. The adrenergic nervous system also plays a role in the hyperreninemia of caval constriction and, possibly, a greater role than the renal prostaglandins. In the first experimental design, surgical renal denervation and daily oral propranolol administration in dogs with caval constriction reduced PRA to normal in two of seven dogs and a natriuresis occurred. In four of the five remaining animals, PRA fell, but not to normal, and renal sodium excretion failed to increase. In a second experimental design, the kidneys were denervated and propranolol was given before the dogs were subjected to caval constriction and propranolol was continued for 5 days; PRA increased markedly, sodium retention occurred, and ascites formed. Under these circumstances, compensatory mechanisms secondary to caval constriction led to increased PRA in spite of adrenergic blockade.