bluuebunny/crossref_metadata_2025 huggingface dataset:
Inotropic effect, binding properties, and calcium flux effects of the calcium channel agonist CGP 28392 in intact cultured embryonic chick ventricular cells.
Authors: Laurent S , Kim D , Smith T W , Marsh J D
Published: June 2012

CGP 28392 is a recently described dihydropyridine derivative with positive inotropic properties. To study the mechanism of action of this putative calcium channel agonist, we have related the effects of CGP 28392 on contraction (measured with an optical video system) and radioactive calcium uptake to ligand-binding studies in cultured, spontaneously beating chick embryo ventricular cells. CGP 28392 produced a concentration-dependent increase in amplitude and velocity of contraction (EC50 = 2 X 10(-7) M; maximum contractile effect = 85% of the calcium 3.6 mM response). Nifedipine produced a shift to the right of the concentration-effect curve for CGP 28392 without decreasing the maximum contractile response, suggesting competitive antagonism (pA2 = 8.3). Computer analysis of displacement of [3H]nitrendipine binding to intact heart cells by unlabeled CGP 28392 indicated a KD = 2.2 +/- 0.95 X 10(-7) M, in good agreement with the EC50 for the inotropic effect. CGP 28392 increased the rate of radioactive calcium influx (+39% at 10 seconds) without altering beating rate, while nifedipine decreased radioactive calcium influx and antagonized the CGP 28392-induced increase in calcium influx. Our results indicate that, in intact cultured myocytes, CGP 28392 acts as a calcium channel agonist and competes for the dihydropyridine-binding site of the slow calcium channel. In contrast to calcium channel blockers, CGP 28392 increases calcium influx and enhances the contractile state.
Intramural reentry as a mechanism of ventricular tachycardia during evolving canine myocardial infarction.
Authors: Kramer J B , Saffitz J E , Witkowski F X , Corr P B
Published: June 2012

We evaluated the contribution of intramural electrical events in initiation and maintenance of ventricular tachycardia in 15 dogs 3-8 days after either permanent (n = 2) or transient (n = 13) coronary artery occlusion. Seven of the dogs (47%) demonstrated eight distinct monomorphic ventricular tachycardia patterns which were mapped by means of a recently designed computerized system capable of simultaneously detecting, storing, and assessing information from 232 individual cardiac sites. Using both epicardial and intramural electrodes, we found definitive evidence for intramural reentry in seven of the eight monomorphic tachycardias analyzed. Furthermore, five of these animals (71%) demonstrated microreentry, in which small epicardial conduction loops exited intermittently into nonrefractory subendocardium to initiate succeeding beats, while, in the remaining two dogs, ventricular tachycardia was due to macroreentry, during which the broad subendocardial wavefronts depolarizing the ventricle constituted the proximal (fast) reentry limbs. Detailed anatomical analysis of the resultant infarcts demonstrated the thin surviving epicardial tissue rim to be the site of conduction delay necessary for reentry, whereas "preferred pathways" of exit into the subendocardial plane occurred at the infarct borders and were of variable configuration. Successful interruption of these rhythms should accompany interference with the process of exit into nonrefractory subendocardial tissue.
Heart rate modulates the disposition of neurally released norepinephrine in cardiac tissues.
Authors: Masuda Y , Levy M N
Published: June 2012

We determined the effect of heart rate on the disposition of neurally released norepinephrine from the cardiac tissues in open-chest, anesthetized dogs with complete atrioventricular block. After injecting desipramine to block the neuronal uptake of norepinephrine, we stimulated the cardiac sympathetic nerves supramaximally for about 3 minutes at a mean frequency of 2.7 Hz. In one series of experiments, we allowed coronary sinus blood flow to change spontaneously in response to cardiac pacing and sympathetic stimulation. The mean coronary sinus blood flows just before cessation of sympathetic stimulation were 67.4 +/- 4.2 (SE) and 37.4 +/- 2.7 ml/min during pacing at a high (150/min) and a low (60/min) frequency, respectively. The mean norepinephrine overflow into the coronary sinus blood during steady state sympathetic stimulation was 45.0 +/- 14.2% greater during high frequency pacing than during low frequency pacing. After cessation of neural stimulation, the norepinephrine overflow decayed more rapidly during high frequency pacing than during low frequency pacing. This difference in decay rates was mainly ascribable to the difference in coronary blood flows. In a second series of experiments, we adjusted the coronary sinus blood flow during sympathetic stimulation so that the flows were not significantly different during pacing at the two frequencies. During the initial 30-second period, after cessation of sympathetic stimulation, the mean decrements of norepinephrine overflow were 95.9 +/- 21.4 and 59.2 +/- 17.3 ng/min at the high- and low-pacing frequencies, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Ventricular action potentials, ventricular extracellular potentials, and the ECG of guinea pig.
Authors: Watanabe T , Rautaharju P M , McDonald T F
Published: June 2012

Action potentials were recorded from different regions of the guinea pig ventricle to characterize regional differences in waveform configuration, and to acquire insight into the generation of the T-wave of the electrocardiogram. Isolated tissue preparations were driven at 1 Hz, and microelectrodes were used to map accessible surface regions of the epicardium, endocardium, and septum. There were minimal differences in regional resting potentials (mean -87 mV) and amplitudes (mean 122 mV), but Vmax in the epicardium (mean 110 V/sec) was much smaller than elsewhere (mean 247 V/sec). The action potential duration at the -80 mV repolarization level was longest in the papillary muscles (mean 154 msec), shortest in the septum (mean 126 msec), and generally 10-15 msec longer at the base than at the apex. The characteristics of intramural action potentials were inferred from measurements on enzymatically isolated myocytes, the rationale being that most dissociated myocytes originated from intramural cell layers. The action potentials in about 40% of the myocytes had durations similar to those recorded from the tissue surface (110-170 msec), and the remainder ranged from 170-290 msec long. The existence of longer-than-surface action potentials in the ventricle was also inferred from the body surface electrocardiogram and from bipolar electrograms of isolated left ventricles. In both cases, the Q-T intervals could be accounted for only by action potentials longer than those recorded from the ventricular surface.
Lidocaine's negative inotropic and antiarrhythmic actions. Dependence on shortening of action potential duration and reduction of intracellular sodium activity.
Authors: Sheu S S , Lederer W J
Published: June 2012

The mechanisms by which lidocaine brings about negative inotropic effects and antiarrhythmic actions in the heart have been examined. Using sheep cardiac Purkinje fibers, we studied the effects of "therapeutic" concentrations of lidocaine (20 microM lidocaine = 5.4 micrograms/ml) on electrical activity, intracellular sodium activity, and tension. For the preparation with a normal, physiological level of intracellular sodium activity (5-9 mM), the application of lidocaine leads to the following actions: action potential duration is decreased, intracellular sodium activity falls, and twitch tension is reduced. If intracellular sodium activity is first elevated (e.g., by sodium pump inhibition) so that arrhythmogenic transient depolarizations (and the underlying transient inward current are seen) then lidocaine has the following actions: The action potential duration is reduced. There is a reduction of the magnitude of the arrhythmogenic transient depolarization (or the underlying membrane current transient inward current). The magnitude of the aftercontraction that accompanies the transient depolarization (or transient inward current) is reduced. If, after sodium pump inhibition, intracellular sodium activity is still rising-then, the application of lidocaine leads to a reduction of the rate of rise of intracellular sodium. From these results, parallel voltage-clamp experiments, and recent work by others, we conclude that lidocaine leads to the reduction of the arrhythmogenic transient depolarization and a reduction of twitch tension by decreasing the inward sodium current. These actions are mediated by a reduction in action potential duration and a reduction of intracellular sodium activity and of intracellular calcium activity (by the sodium-calcium exchange mechanism).
The renal sympathetic baroreflex in the rabbit. Arterial and cardiac baroreceptor influences, resetting, and effect of anesthesia.
Authors: Dorward P K , Riedel W , Burke S L , Gipps J , Korner P I
Published: June 2012

Curves relating renal sympathetic nerve activity and mean arterial pressure were derived in conscious rabbits during ramp changes in mean arterial pressure, elicited by perivascular balloon inflation. The renal sympathetic nerve activity-mean arterial pressure relationship consisted of a high-gain sigmoidal region about resting, where renal sympathetic nerve activity rose or fell in response to moderate falls and rises of mean arterial pressure. With larger pressure rises, renal sympathetic nerve activity first fell to a lower plateau and then reversed at even higher mean arterial pressure. When mean arterial pressure was lowered below resting, renal sympathetic nerve activity rose to an upper plateau and then reversed abruptly toward resting at low mean arterial pressure. Both arterial and cardiac baroreceptors exerted substantial inhibitory influences on renal sympathetic nerve activity at all pressure levels. These effects appeared additive over the central high gain region of the curve, but beyond this region there were non-additive interactions. The latter were affected considerably by alfathesin anesthesia. In other experiments, we studied the effects of sustained alterations in resting mean arterial pressure induced by infusing nitroprusside and phenylephrine, which produced rapid resetting of the renal baroreflex. The latter could be accounted for, in part, by resetting of the threshold of the arterial baroreceptors and in part by contributions from other afferents, probably the cardiac receptors. During resetting associated with nitroprusside-induced falls in resting blood pressure, high-gain reflex adjustments in renal sympathetic nerve activity to moderate changes in mean arterial pressure were preserved, but during resetting associated with phenylephrine-induced rises in resting mean mean arterial pressure, the resting renal sympathetic nerve activity lay on the lower curve plateau, resulting in reduction in the apparent gain of the reflex renal sympathetic nerve activity response to moderate changes in mean arterial pressure.
The genesis of arrhythmias during myocardial ischemia. Dissociation between changes in cyclic adenosine monophosphate and electrical instability in the rat.
Authors: Manning A S , Kinoshita K , Buschmans E , Coltart D J , Hearse D J
Published: June 2012

It has been proposed that increases in tissue cyclic adenosine monophosphate during ischemia may be responsible for the induction of arrhythmias that occur during the early minutes of ischemia. We have tested this hypothesis using the isolated perfused rat heart with coronary artery occlusion for 30 minutes. In control hearts, after a transient small rise, cyclic adenosine monophosphate content remained close to its preischemic value (3.0 +/- 0.1 nM/g dry weight) throughout the period of occlusion. Eight percent (1/12) of the hearts fibrillated. Ninety-two percent (11/12) of the hearts exhibited ventricular tachycardia, and the mean total number of premature ventricular complexes was 528 +/- 121. Inclusion of epinephrine (1.0 microM) in the perfusion fluid elevated cyclic adenosine monophosphate prior to coronary occlusion (to 10.7 +/- 0.6 nM/g dry weight) and also throughout the ischemic period. It also increased arrhythmias such that 83% (20/24) of hearts fibrillated, 100% exhibited ventricular tachycardia, and the mean number of premature ventricular complexes increased to 747 +/- 86. Inclusion of forskolin (0.2 microM), which stimulates adenyl cyclase independently of the beta-receptor, increased cyclic adenosine monophosphate content to a greater extent than epinephrine, to 14.1 +/- 0.9 nM/g dry weight before the onset of ischemia and to 8.2 +/- 0.4 nM/g dry weight after 30 minutes of ischemia. Despite the large increase in cyclic adenosine monophosphate, there was no increase in rhythm disturbances which were less than those seen in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Ventricular trabeculations in the chick embryo heart and their contribution to ventricular and muscular septal development.
Authors: Ben-Shachar G , Arcilla R A , Lucas R V , Manasek F J
Published: June 2012

Sixty-two chick embryo hearts were studied at incremental stages of development (Hamburger-Hamilton stages 16 to 39) by scanning electron microscopy following 3% glutaraldehyde fixation and critical point drying. Early in cardiac development, the primitive ventricle becomes homogeneously trabeculated with highly organized sheets of myocytes lined by endocardial cells, with the trabeculae generally oriented in the dorsoventral direction. Coalescence of these trabecular sheets begins at stage 26, initially at the area of the bulboventricular flange, and later proceeding caudally toward the floor of the ventricle. The fusion process is finished by stage 30, resulting in a muscular ventricular septum that has now divided the primitive ventricle into right and left ventricles. Further growth of the ventricular septum is by continued fusion of the adjoining trabecular sheets. Remnants of the apposing trabecular sheets are found in the solidified muscular septum in the form of endocardial channels. We suggest that persistent patency of these channels results in muscular ventricular septal defects.
The relationships of high energy phosphates, tissue pH, and regional blood flow to diastolic distensibility in the ischemic dog myocardium.
Authors: Momomura S , Ingwall J S , Parker J A , Sahagian P , Ferguson J J , Grossman W
Published: June 2012

Myocardial ischemia due to increased oxygen demand (pacing tachycardia plus critical coronary stenoses) alters diastolic distensibility and relaxation more than ischemia of comparable duration due to coronary occlusion. To investigate the relationship between myocardial diastolic function and metabolism, we compared myocardial high energy phosphate content, tissue pH, and regional blood flow for these two types of ischemia in anesthetized open-chest dogs. Myocardial biopsies were done with a high-speed air-turbine biopsy drill, permitting rapid (less than 1-second) freezing of tissue samples from both nonischemic and ischemic areas, while myocardial pH was measured with a hydrogen ion-selective polymer membrane implanted in the subendocardium. After 3 minutes of pacing tachycardia in dogs with critical coronary stenoses (demand-type ischemia, n = 14), regional systolic function (% segment shortening by ultrasonic crystals) was mildly depressed (from 19 +/- 2% control to 13 +/- 2% post-pacing, P less than 0.01), while left ventricular diastolic pressure-segment length relations shifted upward, indicating decreased distensibility of the ischemic myocardial segment. Associated with these changes in function, subendocardial adenosine triphosphate decreased (from 31.3 +/- 1.5 to 27.9 +/- 1.0 nmol/mg protein, P less than 0.01), as did creatine phosphate (53.8 +/- 2.1 to 39.6 +/- 2.5 nmol/mg protein, P less than 0.01), while myocardial pH declined slightly (delta pH = -0.14 +/- 0.02, P less than 0.01). In contrast, at 3 minutes of coronary artery occlusion (primary ischemia, n = 14), regional segment shortening was replaced by systolic bulging (% shortening decreased from 17 +/- 2% to -2 +/- 1% during occlusion, P less than 0.01), while left ventricular pressure-segment length relations were not shifted upward, and there was no decrease in diastolic distensibility of the ischemic segment. With coronary artery occlusion, subendocardial adenosine triphosphate declined slightly (33.2 +/- 0.5 to 29.2 +/- 2.0 nmol/mg, P less than 0.05), while creatine phosphate decreased substantially (51.1 +/- 2.3 to 7.8 +/- 1.4 nmol/mg protein, P less than 0.01). Myocardial pH fell strikingly (delta pH = -0.33 +/- 0.03, P less than 0.01), and the decline was 236% of that seen with demand-type ischemia. Regional myocardial blood flow (microsphere technique) showed a decreased endocardial:epicardial (endo:epi) ratio (1.04 +/- 0.04 control vs. 0.40 +/- 0.05 during pacing, P less than 0.01) and absolute subendocardial flow (1.02 +/- 0.47 to 0.47 +/- 0.05 ml/min per g, P less than 0.01) with demand-type ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
The interaction of convection and diffusion in the transport of 131I-albumin within the media of the rabbit thoracic aorta.
Authors: Tedgui A , Lever M J
Published: June 2012

The interaction of convection and diffusion in the transport of 131I-labeled albumin within the wall of rabbit thoracic aorta was studied in vessels excised at in vivo length. They were pressurized with a solution containing no tracer and immersed in a solution containing labeled albumin. The label then entered the wall tissue via the adventitia and had to diffuse against the convective flux which occurred from the lumen to the adventitia. Experiments were performed on intact and deendothelialized vessels pressurized to 70 and 180 mm Hg. At the end of each experiment the vessels were subjected to sequential frozen sectioning parallel to the lumenal surface. The radioactivity of the 20-micron-thick sections was determined and expressed as a tissue:labeled solution concentration ratio. Transmural profiles of these ratios were thus obtained. The steady state was found to be achieved by about 90 minutes. When the convection was enhanced by removal of the endothelium, the average ratios were lower than when the endothelium was intact, and the profile was much flatter. The results suggest that convection influenced macromolecular transport within the arterial wall, even in vessels with intact endothelium.
Peripheral dopamine synthesis and metabolism in spontaneously hypertensive rats.
Authors: Racz K , Kuchel O , Buu N T , Tenneson S
Published: June 2012

We have studied several parameters of peripheral dopamine synthesis and metabolism in spontaneously hypertensive rats during the development of hypertension. Compared to Wistar-Kyoto rats, there was an increased dopamine content in 8-week-old spontaneously hypertensive rats in the adrenals (1.6 +/- 0.1 vs. 1.2 +/- 0.1 nmol/pair in Wistar-Kyoto rats) and kidneys (97 +/- 12 vs. 63 +/- 7 pmol/g tissue in Wistar-Kyoto rats), but the dopamine content in peripheral organs from normotensive 4-week-old spontaneously hypertensive rats did not differ from Wistar-Kyoto rats. In the heart, the dopamine increase was observed in 14-week-old spontaneously hypertensive rats (systolic blood pressure: spontaneously hypertensive rats, 189 +/- 9; Wistar-Kyoto rats, 106 +/- 2 mm Hg;) in both atrium (spontaneously hypertensive rats, 133 +/- 14; Wistar-Kyoto rats, 86 +/- 20 pmol/g tissue) and ventricle (spontaneously hypertensive rats, 41 +/- 6; Wistar-Kyoto rats, 23 +/- 5 pmol/g tissue). Urinary free dopamine and dihydroxyphenylacetic acid, but not norepinephrine or normetanephrine, in spontaneously hypertensive rats significantly increased between the ages of 7 and 11 weeks, reflecting the dopamine changes in tissue and suggesting a selective increase of the rate of dopamine synthesis and release.(ABSTRACT TRUNCATED AT 250 WORDS)
The combined effects of hypoxia, high K+, and acidosis on the intracellular sodium activity and resting potential in guinea pig papillary muscle.
Authors: Wilde A A , Kléber A G
Published: June 2012

Several reports have shown that electrical and ionic changes occurring in acute myocardial ischemia can be closely mimicked by exposure of tissue to hypoxic, acid-, and glucose-free solutions at elevated [K+]o. In the present work, this approach was chosen to distinguish between the combined effects of hypoxia, substrate withdrawal, and acidosis, and the effects of two different levels of [K+]o (4.7 mM and 11.5 mM) on intracellular sodium activity and resting membrane potential. Measurements were made with microelectrodes in isolated guinea pig papillary muscles. In normoxia at 4.7 mM [K+]o, intracellular sodium activity was 7.5 mM (+/- 1.9 mM, SD) during stimulation at 1 Hz. Combined hypoxia, substrate withdrawal, and acidosis increased intracellular sodium activity significantly, by 3-4 mM in 4.7 mM [K+]o and by approximately 2 mM in 11.5 mM [K+]o, after 9-10 minutes. Increasing [K+]o in normoxic solution decreased intracellular sodium activity by 1.9 mM (+/- 1.3 mM, SD). The transition from normal (4.7 mM [K+]o) Tyrode's solution to "ischemic solution" (hypoxia, acidosis, substrate withdrawal, 11.5 mM [K+]o) was associated with a small initial increase and a subsequent decrease of intracellular sodium activity. The steady state level after 12 minutes was not significantly different from the level in normal Tyrode's solution. The secondary decrease of intracellular sodium activity coincided with the gradual development of inexcitability and was absent in quiescent preparations. Combined hypoxia, acidosis, and glucose-withdrawal produced a depolarization by 7-10 mV at 4.7 mM and at 11.5 mM [K+]o, probably reflecting cellular potassium loss and extracellular potassium accumulation in the restricted extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine 3',5'-cyclic-monophosphate-dependent regulation of alpha 1-adrenergic receptor number in rabbit aortic smooth muscle cells.
Authors: Colucci W S
Published: June 2012

The purpose of this study was to determine whether a cyclic adenosine 3',5'-monophosphate-dependent process can be involved in the regulation of vascular smooth muscle alpha 1-adrenergic receptor responsiveness. Experiments were performed in cultured rabbit aortic smooth muscle cells which were characterized previously according to alpha-adrenergic receptor-binding characteristics and receptor-coupled norepinephrine-stimulated 45Ca++ efflux. The addition of dibutyryl-cyclic adenosine monophosphate to the cell culture medium for 24 hours resulted in a concentration-related decrease in maximal [3H]prazosin-binding capacity (41 +/- 4% decrease with 1 mM dibutyryl-cyclic adenosine monophosphate) without an effect on [3H]prazosin-binding affinity. Prostaglandin E1 (10 microM) and forskolin (10 microM) caused similar decreases in maximal [3H]prazosin-binding capacity, whereas butyrate (1 mM) and dibutyryl-guanosine-3',5' cyclic-monophosphate (1 mM) had no effect. Dibutyryl-cyclic adenosine monophosphate (1 mM) caused significant potentiation of the decrease in [3H]prazosin-binding caused by a submaximal (10 nM) but not a maximal (10 microM) concentration of norepinephrine, suggesting that cyclic adenosine monophosphate may act at a distal step in common with norepinephrine to reduce alpha-adrenergic receptor number. Despite the approximately 41% reduction in alpha-adrenergic receptor number following 24-hour incubation of cells with dibutyryl-cyclic adenosine monophosphate, maximal norepinephrine-stimulated 45Ca++ efflux was not reduced, consistent with the markedly nonlinear relationship between alpha-adrenergic receptor occupancy and maximal norepinephrine-stimulated 45Ca++ efflux in this cell system. These data provide evidence for a novel mechanism by which hormones or drugs which increase cyclic adenosine monophosphate levels can modulate alpha-adrenergic responsiveness in vascular smooth muscle.
Pharmacology and force development of single freshly isolated bovine carotid artery smooth muscle cells.
Authors: Warshaw D M , Szarek J L , Hubbard M S , Evans J N
Published: June 2012

Most studies of mammalian vascular smooth muscle cell mechanics and pharmacology have relied upon data from intact tissue preparations. The purpose of this study was to determine how single mammalian vascular smooth muscle cell pharmacological sensitivity to histamine and force development compared to the intact tissue from which it was derived. Thus, techniques were developed for isolating large numbers (5 X 10(5) cells/ml) of cells from bovine carotid arteries. Single cells were spindle-shaped with dimensions of 117 +/- 11 (SE) micron in length by 7 +/- 1 (SE) micron in diameter (n = 27). The effect of histamine concentration on cell length was studied in suspensions of freshly isolated cells. Histamine concentration-response curves revealed that single smooth muscle cells shortened to histamine concentrations in a graded fashion, and that shortening was mediated through histamine H1 receptors. The threshold for 10% of maximum response occurred at 8.0 X 10(-11) M histamine. This threshold was at least three orders of magnitude lower than the threshold for 10% of maximum tension in the intact tissue under isometric conditions. In addition to cellular pharmacology, mechanical studies were performed by tying a single cell to an ultrasensitive force transducer. Active stresses of 0.5 +/- 0.1 X 10(5) N/m2 (n = 4) were measured in response to electrical stimulation for cells in low extracellular calcium (0.5 mM). These data suggest that histamine sensitivity and smooth muscle cell mechanics may best be determined in single cell studies that minimize diffusional barriers to agonist and avoid intercellular interactions that are present in the intact tissue.
Functional characteristics of intramyocardial capacitance vessels during diastole in the dog.
Authors: Kajiya F , Tsujioka K , Goto M , Wada Y , Chen X L , Nakai M , Tadaoka S , Hiramatsu O , Ogasawara Y , Mito K
Published: June 2012

In order to evaluate the functional characteristics of the intramyocardial capacitance vessels during prolonged diastole, we analyzed the response of coronary vein flow after stepwise changes of coronary artery pressure in anesthetized open-chest dogs by using our newly developed laser Doppler velocimeter with an optical fiber. The peripheral portion of the great cardiac vein was isolated and the optical fiber tip was inserted into the vessel. The left anterior descending coronary artery was cannulated and connected to a reservoir to regulate coronary perfusion pressure. Intracoronary adenosine administration was carried out to avoid any change in coronary vasomotor tone. After 15 seconds of occlusion of the perfusion route, the heart was arrested by pacing-off. Two seconds later, coronary perfusion pressure was increased stepwise to a preset target pressure. This procedure was repeated by changing target pressure at 4 (or 5) different pressure levels (31-105 mm Hg). The great cardiac vein flow became zero due to the cardiac arrest and remained at zero for a moment (dead time) after the initiation of reperfusion. Then the flow reappeared and increased with first order time delay. The presence of dead time indicates the existence of unstressed volume, and the first order time delay represents the product of resistance and capacitance. The unstressed volume with a minimal vasomotor tone for perfusion pressure of 60-90 mm Hg was 5.2 +/- 2.2 ml per 100 g left ventricle, which is comparable to coronary blood flow for several beats. The capacitance at perfusion pressure of 60-90 mm Hg was 0.08 +/- 0.04 ml/mm Hg per 100 g left ventricle, while that at low perfusion pressure (30-50 mm Hg) was 0.14 +/- 0.09 ml/mm Hg per 100 g left ventricle. These results indicate that the intramyocardial capacitance vessels have two functional components, and that the phasic nature of coronary vein flow is solely the result of the myocardial squeezing of the blood in the capacitance vessels.
The effect of pericardiectomy on maximal oxygen consumption and maximal cardiac output in untrained dogs.
Authors: Stray-Gundersen J , Musch T I , Haidet G C , Swain D P , Ordway G A , Mitchell J H
Published: June 2012

To test the hypothesis that the pericardium limits maximal oxygen consumption by limiting stroke volume and cardiac output, we studied 10 untrained dogs during submaximal and maximal exercise before and after pericardiectomy. Seven additional dogs were studied before and after a sham operation. All dogs were instrumented chronically with aortic and pulmonary artery catheters. Dogs were tested by running on a motor-driven treadmill, 4-6 times before and after pericardiectomy or sham operation. We measured cardiac output (dye dilution), heart rate, and arteriovenous oxygen difference. Oxygen consumption and stroke volume were calculated from these variables. After pericardiectomy, there were significant (P less than 0.01) increases in maximal oxygen consumption, maximal cardiac output, and maximal stroke volume. Maximal oxygen consumption decreased significantly in the sham group. There was no change in maximal heart rate following pericardiectomy, or in maximal cardiac output, heart rate, or stroke volume following sham operation. Both groups of dogs experienced similar significant decreases in hematocrit, arterial and venous oxygen contents, and arteriovenous oxygen difference. Neither pericardiectomy nor sham operation had any effect on oxygen consumption during submaximal exercise. However, the sham group had significant increases in cardiac output and heart rate during submaximal exercise, and the pericardiectomy group demonstrated a trend toward an increased cardiac output during submaximal exercise. These results support the hypothesis that the pericardium limits maximal oxygen consumption by limiting stroke volume and cardiac output during maximal exercise in untrained dogs. Further, these findings suggest that maximal oxygen consumption is limited by the oxygen transport capacity of the cardiovascular system, and not by the oxidative capacity of skeletal muscle in the untrained dog.
Effects of sympathetic tone on vagally induced phasic changes in heart rate and atrioventricular node conduction in the anesthetized dog.
Authors: Salata J J , Gill R M , Gilmour R F , Zipes D P
Published: June 2012

We examined the effects of stellate ganglia stimulation on the phase-dependent chronotropic and dromotropic responses to brief vagal bursts in open-chest anesthetized dogs. Stellate stimulation affected the phasic vagal effects on heart rate by shortening the latent period, shifting the phase at which maximum decrease in heart rate occurred to earlier phases, and reducing the maximum decrease in heart rate. These effects were due primarily to an increase in the basic heart rate. No significant sympathetic-parasympathetic interaction occurred for heart rate, indicating that accentuated antagonism did not occur with brief vagal bursts. Stellate stimulation primarily decreased the amplitude of the phasic vagal effects on atrioventricular nodal conduction, regardless of the underlying heart rate, and a significant sympathetic-parasympathetic interaction was associated with this effect. The peak of the phase-dependent vagal effects on heart rate and atrioventricular nodal conduction were phase-shifted with one another. From these findings, we postulate the small changes in sympathetic tone might shift the predominant phase-dependent vagal effect from one on heart rate to one on atrioventricular nodal conduction. Furthermore, our results suggest that dynamic vagal control of heart rate and atrioventricular node conduction involves both phase-dependent and phase-independent factors. Sympathetic activity appears to affect only the phase-independent factor(s) in the control of heart rate, whereas it affects both phase-dependent and phase-independent factors in the control of atrioventricular node conduction.
Role of the renin-angiotensin system in the control of vasopressin secretion in conscious dogs.
Authors: Brooks V L , Keil L C , Reid I A
Published: June 2012

The present studies were designed to evaluate the physiological significance of angiotensin II in the control of vasopressin secretion in conscious dogs. They demonstrated that exogenous angiotensin II (10 ng/kg per min) increased vasopressin secretion more when the pressor effect of angiotensin II was abolished. The fact that endogenous angiotensin II levels are normally increased without an increase in arterial pressure suggests that angiotensin II may play a greater role in the control of vasopressin secretion than was previously thought. The present study also evaluated the role of endogenous angiotensin II in the control of vasopressin secretion during sodium depletion, a state in which angiotensin II levels are elevated. Intracarotid infusion of a low dose of the angiotensin II antagonist, saralasin, decreased plasma vasopressin concentration, suggesting that endogenous angiotensin II acts in an area of the brain perfused by the carotid arteries to stimulate vasopressin secretion in sodium-deprived dogs. Finally, the present experiments evaluated the role of angiotensin II in baroreceptor reflex control of vasopressin secretion. Baroreflex function was assessed by examining the relationship between the change in blood pressure and the log of the change in vasopressin secretion over a range of blood pressure levels. Exogenous angiotensin II (10 ng/kg per min) altered baroreflex function by causing a shift of this relationship to a higher pressure level in sodium-replete dogs. In sodium-depleted dogs, inhibition of the renin-angiotensin system with saralasin or captopril produced an opposite shift. These results suggest that endogenous angiotensin II may be necessary for the maintenance of normal baroreflex control of vasopressin secretion during sodium depletion. Collectively, these results support the hypothesis that endogenous angiotensin II plays a role in the control of vasopressin secretion.
Changes in postjunctional alpha-adrenoceptors during postnatal growth in rabbit arteries.
Authors: Tayo F M , Bevan R D , Bevan J A
Published: June 2012

The pharmacological characteristics of the postjunctional alpha-adrenoceptors of vascular smooth muscle were studied in ring segments of thoracic aorta, superior mesenteric, and central ear arteries of 4- and 8-week-old, and young adult (12- to 16-week-old) rabbits. Norepinephrine (alpha 1, alpha 2-agonist), phenylephrine (alpha 1-agonist), and UK 14,304-18 (alpha 1-agonist) caused a concentration-dependent contraction of all three arterial segments from 4- and 8-week-old animals. Norepinephrine and phenylephrine but not UK 14,304-18 contracted the young adult thoracic aorta and superior mesenteric artery, whereas all the agonists contracted the central ear artery. The effects of the alpha 1-adrenoceptor antagonists, prazosin and thymoxamine, and the alpha 2-adrenoceptor antagonists, rauwolscine and yohimbine, on these responses were studied. In the 4-week-old rabbits, responses to norepinephrine, phenylephrine, and UK 14,304-18 were reduced by all four antagonists with nominal pA2 values in the range of 7-8.5. The action of the antagonists was competitive. Between 4 and 8 weeks, there was a significant decrease in the pA2 values of rauwolscine against norepinephrine and UK 14,304-18 in the aorta and between rauwolscine and UK 14,304-18 on the superior mesenteric artery. The pA2 values of rauwolscine and yohimbine, but not prazosin and thymoxamine, were lower in the young adult compared with values from the 8-week-old rabbit. In the interpretation of these results, there are two possibilities.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of calcium channel blockade on renal vascular resistance responses to changes in perfusion pressure and angiotensin-converting enzyme inhibition in dogs.
Authors: Navar L G , Champion W J , Thomas C E
Published: June 2012

We conducted these experiments to evaluate the selectivity of calcium channel blockade on the renal autoregulatory mechanism and on angiotensin II-mediated renal vasoconstriction. Experiments were performed in anesthetized dogs in which renal arterial pressure, renal blood flow, and glomerular filtration rate were measured at normal and reduced renal arterial pressure. At control arterial pressures, renal arterial infusions of verapamil increased renal blood flow and glomerular filtration rate significantly. The decreases in renal vascular resistance elicited with verapamil (n = 13) and nifedipine (n = 4) occurred only at renal arterial pressure levels within the normal autoregulatory range. Renal blood flow autoregulatory efficiency was markedly attenuated, and the pressure-flow relationship obtained during calcium channel blockade approached that of a passive system. Systemic infusions of an angiotensin-converting enzyme inhibitor (captopril) during continued verapamil infusion caused further vasodilation at all renal arterial pressure values, as evidenced by an increase in slope of 27% of the pressure-blood flow relationship. This response was reversed by angiotensin II infusions. This shift indicates a reduction in minimal vascular resistance elicited by captopril, not obtainable with verapamil alone, and sensitive to angiotensin II. The effects of verapamil and nifedipine on renal blood flow autoregulation suggest a specific effect at preglomerular sites of potential operated membrane calcium channels in the autoregulatory phenomenon. The additional vasodilation elicited with captopril and reversed by angiotensin II indicates the presence of an angiotensin-sensitive postglomerular resistance component which is not influenced by calcium entry blockers.
Role of central catecholamines on the potentiation of the baroreflex produced with vasopressin. A study using 6-hydroxydopamine.
Authors: Undesser K P , Trapani A J , Morgan W W , Bishop V S
Published: June 2012

This study compares the effect of arginine-vasopressin and phenylephrine on renal sympathetic nerve activity, arterial pressure, and heart rate in vehicle- and intraventricular 6-hydroxydopamine-treated conscious rabbits. In addition, this study examines the involvement of forebrain structures on these variables. In vehicle-treated rabbits, compared to phenylephrine, vasopressin produces a greater decrease in renal sympathetic nerve activity and heart rate for a given increase in pressure. After administration of intraventricular 6-hydroxydopamine, the responses produced with vasopressin are similar to those produced with phenylephrine. Analysis of catecholamine content in the nucleus of the solitary tract, parabrachial nucleus, area postrema, and spinal cord indicates that the only regions of significant catecholamine depletion are in the nucleus of the solitary tract and the spinal cord. Transection at the mid-collicular level does not alter significantly the responses of vasopressin or phenylephrine on renal sympathetic nerve activity or heart rate. This indicates that forebrain structures are not involved in mediating the enhanced buffering effect produced with vasopressin.
The influence of resting tension on immunoreactive atrial natriuretic peptide secretion by rat atria superfused in vitro.
Authors: Schiebinger R J , Linden J
Published: June 2012

Atrial natriuretic peptide is a potent diuretic hormone secreted by the atria in response to volume expansion. We examined the effect of resting tension on atrial natriuretic peptide secretion by rat atria superfused in vitro. Left atria were hooked between an electrode and force transducer and superfused with medium 199. The atria were studied at a pacing frequency of 0 or 3 Hz. Atrial natriuretic peptide content of the superfusate was measured by radioimmunoassay. In nonpaced and paced atria, increasing resting tension three- to five-fold caused immunoreactive atrial natriuretic peptide secretion to increase by 35 +/- 5% (mean +/- SEM, n = 6, p less than 0.01) and 30 +/- 3% (n = 4, p less than 0.01), respectively. Lowering resting tension by 50% in nonpaced and paced atria lowered immunoreactive atrial natriuretic peptide secretion by 30 +/- 3% (n = 7, p less than 0.01) and 24 +/- 3% (n = 6, p less than 0.01), respectively. To exclude the possibility that release of norepinephrine or acetylcholine from endogenous nerve endings was mediating this effect, the atria were superfused with the combination of propranolol 0.1 microM, phentolamine 1.0 microM, and atropine 10 microM. These concentrations of the antagonists were 125-fold or higher than their Kd for binding to their respective receptors. The antagonists did not block the rise in immunoreactive atrial natriuretic peptide secretion; neither did they inhibit an established rise in immunoreactive atrial natriuretic peptide secretion induced by increasing the resting tension.(ABSTRACT TRUNCATED AT 250 WORDS)
von Willebrand's disease prevents occlusive thrombosis in stenosed and injured porcine coronary arteries.
Authors: Nichols T C , Bellinger D A , Johnson T A , Lamb M A , Griggs T R
Published: June 2012

We studied the role of von Willebrand factor in coronary thrombosis in normal, heterozygous, and homozygous von Willebrand's disease pigs by producing coronary stenosis with a Goldblatt clamp positioned around the left anterior descending coronary artery. Flow velocity was assessed by a 20-MHz Doppler velocity probe distal to the Goldblatt clamp. Myocardial extracellular potassium levels were measured by potassium-sensitive electrodes in myocardium supplied by the left anterior descending artery. Whereas stenosis sufficient to block reactive hyperemia to a 20-second occlusion produced an elevation of myocardial extracellular potassium, it produced neither spontaneous cyclic flow reductions nor permanent cessation of coronary blood flow velocity. Injury of the coronary artery at the stenosis site with spring-loaded forceps produced cyclic flow reductions or permanent cessation of flow in eight of nine phenotypically normal pigs. On the other hand, flow variations occurred in none of the 10 von Willebrand's disease pigs, including four given purified von Willebrand factor at a dose that failed to correct the bleeding time (p less than 0.001, chi 2 test). Permanent cessation of flow was caused by an occlusive platelet-fibrin-red-blood-cell thrombus. Scanning electron micrographs from pigs with cyclic flow variations and from von Willebrand's disease pigs showed injured endothelium covered by adherent platelets, red and white blood cells, and fibrin. These data suggest an important role of native von Willebrand factor in sudden occlusive arterial thrombosis following stenosis and intimal injury.
Time dependence of the oxygen cost of force development during systole in the canine left ventricle.
Authors: Teplick R , Haas G S , Trautman E , Titus J , Geffin G , Daggett W M
Published: June 2012

To determine whether the oxygen cost of force development in the canine left ventricle is constant throughout systole, we inserted fluid-filled Latex balloons into eight isolated canine left ventricles perfused via support dogs. Balloon volumes were varied by a hydraulic servoactuator designed to withdraw preset volumes rapidly (0.5 ml/msec) beginning at a specified ejection pressure. Oxygen consumption was related to force-time integrals for 9-12 different ejections patterns formed by ejecting three or four different volumes from the same end-diastolic volume, each ejection beginning at three different pressures, isovolumic beats with four or five different end-diastolic volumes, including those used for the ejections. The force-time integral vs. oxygen consumption data are nonlinear for ejections that began at low pressures, with oxygen consumption exceeding that predicted from regression lines fitted to the isovolumic data. This difference appeared to peak at relatively low force-time integrals and then curve back to converge with the isovolumic line. This pattern was not evident for ejections that began late in systole. Although these results suggest that the energy required for force development is greater than expected early in systole, they also are consistent with the hypothesis that oxygen consumption is a function only of instantaneous ventricular volume.
Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart: mechanism and characteristics of steady contractile activation in intact myocardium.
Authors: Marban E , Kusuoka H , Yue D T , Weisfeldt M L , Wier W G
Published: June 2012

Rapid (8-12 Hz) stimulation of intact heart muscle treated with ryanodine results in steady contractile activation known as tetanus, the amplitude of which can be graded by changing extracellular Ca2+ concentration ([Ca2+]o). The mechanism of the sustained force generation was explored in ferret papillary muscles by measuring membrane potential and by determining the responsiveness of force and intracellular free Ca2+ concentration ([Ca2+]i, estimated with aequorin) to dihydropyridine Ca channel ligands. Membrane potential during tetani ranged from -25 to -60 mV, suggesting that fast or slow Ca channels, or Na-Ca exchange, might be mediating Ca2+ entry. Dihydropyridine effects indicated that slow Ca channels play a predominant role: The agonist Bay K 8644 (0.3-1 microM) increased force and aequorin luminescence, whereas the antagonist nitrendipine (1-30 microM) abolished the tetanus. Under conditions analogous to those in the papillary muscle experiments, tetani were produced in whole Langendorff-perfused ferret hearts following exposure to ryanodine. Contraction saturated as a function of [Ca2+]o in both papillary muscles and whole hearts; i.e., as [Ca2+]o was increased above 10 mM, no further increase in force or pressure generation occurred. In contrast, aequorin luminescence measured in the papillary muscles showed no such saturation. Thus, maximal Ca2+-activated force (or pressure) was achieved during tetani at [Ca2+]o greater than or equal to 10 mM. Calculations of wall stress during tetani in whole heart (15 mM [Ca2+]o) agree well with direct measurements of maximal tension in papillary muscles (5.84 g/mm2 vs. 6.41 g/mm2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)