bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgen and glucocorticoid mechanisms in exercise-induced cardiac hypertrophy
Authors: Hickson R. C. , Galassi T. M. , Kurowski T. T. , Daniels D. G. , Chatterton R. T.
Published: December 2017

Female rats were trained daily by means of two 2-h-long bouts of swimming separated by a 30- to 40-min rest period. Absolute ventricular weights of the swimmers were increased above sedentary control values by 6% after 2 days, 15% after 7 days, and 30% after 35 days of exercise. Resting levels of total and free serum testosterone and total 5 alpha-dihydrotestosterone were not altered by the training. Total serum corticosterone concentrations at rest were significantly lower in the 7-day (149 +/- 16 ng/ml) and 35-day (169 +/- 24) swimmers compared with the controls (293 +/- 26). However, free corticosterone was not significantly reduced from controls in any of the swimming groups. Ventricular muscle cytosol androgen receptor binding dissociation constants and receptor binding capacities, measured using [3H]methyltrienolone (R1881), were not significantly different from control values in the exercised groups. Glucocorticoid cytosol receptor binding capacity in ventricular tissue, determined using [3H]dexamethasone, was significantly increased as femtomoles per milligram protein (39.3 +/- 3.1 vs. 31.4 +/- 1.4) and femtomoles per milligram DNA (2,683 +/- 226 vs. 1,786 +/- 71). These findings show that glucocorticoids, rather than androgens, undergo adaptive changes in the circulation and in muscle during the development of exercise-induced cardiac hypertrophy.
Central abnormality in baroreflex control of renal nerves in hypertension
Authors: Thames M. D. , Gupta B. N. , Ballon B. J.
Published: December 2017

The purpose of our study was to determine if there is a central abnormality in the arterial baroreceptor reflex control of renal nerve activity in renal hypertension. We recorded simultaneously the changes in aortic (input) and renal (output) nerve traffic during phenylephrine-induced increases in arterial pressure in 14 normotensive and 11 hypertensive rabbits [mean arterial pressure (+/- SE) in conscious state 106 +/- 2 and 141 +/- 6 mmHg, respectively]. Changes in aortic nerve traffic were considered representative of changes in total arterial baroreceptor input to the central nervous system. Renal nerve traffic was inhibited by 5.2 +/- 0.5% per mmHg rise in arterial pressure in normotensive rabbits but by only 2.5 +/- 0.3% per mmHg in hypertensive rabbits (P less than 0.05). Increases of aortic nerve traffic during increases in arterial pressure were similar in the two groups. These data suggest that there is a central abnormality in the baroreflex control of renal nerve activity in renal hypertensive rabbits. This hypothesis was tested further by sectioning vagal, carotid, and aortic nerves and stimulating electrically the left aortic depressor nerve while recording changes in blood pressure and renal sympathetic nerve traffic. Decreases of renal traffic during stimulation of myelinated fibers alone were strikingly impaired (P less than 0.001) at all frequencies in hypertensive rabbits. Responses were not impaired significantly during stimulation of myelinated plus nonmyelinated fibers. Arterial pressure decreases were not different during stimulation of myelinated fibers or of both myelinated and nonmyelinated fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Occlusive summation of carotid and aortic baroreflexes in control of renal nerve activity
Authors: Thames M. D. , Ballon B. J.
Published: December 2017

We recently reported that denervation of aortic or carotid baroreceptors impaired baroreflex control of heart rate but not of hindlimb vascular resistance or lumbar sympathetic nerve activity. Since baroreflex control of sympathetic outflow to different vascular beds is nonuniform, we determined whether carotid or aortic baroreceptor denervation would impair baroreflex control of renal nerve activity. Experiments were performed in 23 alpha-chloralose-anesthetized rabbits. Phenylephrine and nitroglycerin were infused to raise or lower arterial pressure. Pressure elevation inhibited and pressure reduction increased renal nerve activity. The linear regression relationships between changes in arterial pressure and percent change in renal nerve activity were determined with baroreflexes intact and after aortic or carotid denervation. Neither carotid nor aortic denervation alone impaired baroreflex control of renal nerve activity. In nine experiments responses were determined first with vagi sectioned. The results were comparable to those obtained without prior vagotomy. Our data indicate that one group of baroreceptors (aortic or carotid) exerts full control of renal nerve activity and that aortic and carotid baroreflex influences on renal nerve activity add by occlusive or mutual inhibitory summation.
Cytoplasmic surface and intramembrane components of rat heart gap junctional proteins
Authors: Manjunath C. K. , Goings G. E. , Page E.
Published: December 2017

Gap junctions were purified from rat hearts in the presence of absence of proteolysis inhibitors and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and electron microscopy of thin sections. In absence of proteolysis inhibitors or in presence of ethylenediaminetetraacetic acid or leupeptin, gap junctions contained a single major protein band at relative molecular weight (Mr) 29,500 and minor bands at Mr 44,000–47,000, 17,750, and 16,500 and showed smooth cytoplasmic surfaces in electron micrographs. SDS-PAGE of junctions prepared with phenylmethylsulfonylfluoride (PMSF) showed markedly decreased intensity of the Mr 29,500 band and increased intensity of bands at Mr 44,000, 45,500, and 47,000; electron microscopy of these gap junctions showed presence of a fuzzy layer on their cytoplasmic surfaces. Urea (8 M) could not remove this fuzzy layer. In electron micrographs of rat ventricular myocytes, cytoplasmic surfaces of gap junctions were fuzzy. We conclude that rat heart gap junction protein consists of an intramembrane component (Mr 29,500) that extends into the “gap” and a cytoplasmic surface component (Mr 14,500–17,500) that corresponds to the fuzzy layer and is hydrolyzable by a serine protease.
An improved method for chronic His bundle recordings in conscious dogs
Authors: Schwartz J. B. , Herre J. M. , Lewis R. M.
Published: December 2017

Because anesthetics routinely used in cardiovascular experiments significantly alter the physiological state and electrophysiological function of the heart, our goal was to develop a surgically simple, inexpensive, and reliable animal model for chronic conscious electrophysiological studies. Our method differs from prior methods by implantation of bipolar stainless steel electrodes with pin length varied to adapt for the varied thickness of different cardiac chambers, electrode placement at the junction between the right atrium and aortic root posterior to the right coronary artery for recording the His potential, and unipolar His recordings.
A new method for estimating skeletal muscle capillary pressure
Authors: Korthuis R. J. , Granger D. N. , Taylor A. E.
Published: December 2017

Venous (Pc,vo) and arterial occlusion capillary pressures were simultaneously compared with isogravimetric capillary pressure (Pci) in isolated rat hindquarters and canine gracilis muscles perfused with blood or an artificial plasma. Arterial or venous pressure transients following rapid occlusion of arterial inflow or venous outflow, respectively, were analyzed for the inflection point between rapid and slow components. This transition point was assumed to represent the beginning of discharge of blood stored in (arterial occlusion) or the addition of blood to (venous occlusion) skeletal muscle microvessels and was defined as the effective capillary pressure. In all preparations, Pc,vo was identical to Pci. Arterial occlusion pressures were the same as Pci and Pc,vo in artificial plasma-perfused preparations but were significantly greater (P less than 0.01) than Pci and Pc,vo obtained in blood-perfused preparations. This inequality between arterial occlusion pressure and Pci may be related to a critical closure of small precapillary vessels or the non-Newtonian behavior of blood. In addition, venous occlusion pressures were highly correlated (r = 0.95, P less than 0.01) to calculated capillary pressures obtained following simultaneous equivalent elevations of arterial and venous pressure. These results indicate that the primary sites of vascular compliance and fluid filtration reside at or very near one another in the skeletal muscle microcirculation and that the more easily determined venous occlusion capillary pressure is an adequate measure of the effective capillary pressure in skeletal muscle.
Effect of histamine on coronary microvascular permeability
Authors: Pilati C. F. , Maron M. B.
Published: December 2017

The effect of histamine on coronary vascular permeability was assessed under conditions of elevated venous pressure in the spontaneously beating, isolated canine heart perfused with autologous blood. The apparent volume of fluid filtered from the vasculature to the interstitium (VF) was calculated from the increase in plasma protein concentration and also from the increase in hematocrit. The ratio of the protein-filtered volume to the hematocrit-filtered volume (VF,Pr/VF,Hct) was used to evaluate changes in permeability. In the absence of histamine, the VF,Pr/VF,Hct was near unity (1.05 +/- 0.11), which indicated that the blood proteins and the red blood cells had concentrated equally. Thus the transudate was essentially protein free. On exposure to histamine (3.8 +/- 0.3 microgram base/ml blood), VF,Pr/VF,Hct decreased to 0.37 +/- 0.06 (P less than 0.001), which indicated that coronary vascular permeability had increased. This value remained constant throughout the 60 min of histamine exposure. Aortic perfusion pressure decreased significantly (P less than 0.05) from 111 +/- 11 to 84 +/- 5 mmHg during the 1st min of histamine exposure and rose slowly thereafter. In four of the seven hearts, concomitant increases in left ventricular isovolumic pressure development (13-31 mmHg) and heart rate (4-29 beats/min) were observed. In the remaining hearts, neither variable was affected by histamine. We conclude that histamine causes an increase in the permeability of the canine coronary microvasculature but fails to increase heart rate or left ventricular performance consistently.
Pial vessel caliber and cerebral blood flow during hemorrhage and hypercapnia in the rabbit
Authors: Tuor U. I. , Farrar J. K.
Published: December 2017

We examined the relationship between cerebral blood flow (CBF) and pial vessel caliber responses to graded hemorrhagic hypotension at both normocapnia and hypercapnia in 31 anesthetized rabbits. Changes in CBF (hydrogen clearance) and pial arteriolar diameter (image splitting) were predictably related at all perfusion pressures (PP). Three autoregulatory regions were identified. 1) At PP greater than 65 mmHg, autoregulation was complete as CBF and the CBF response to hypercapnia remained at control levels. The pial vessels dilated progressively, and their response to hypercapnia increased. 2) At PP between 65 and 35 mmHg autoregulation continued but was incomplete. CBF decreased proportionately less than the corresponding reductions in PP due to continued pial vascular dilatation. Both the CBF and pial vessel responses to hypercapnia diminished. 3) At PP less than 35 mmHg, autoregulation was abolished. Pial arteriolar caliber and CBF decreased pressure passively, and there were no responses to hypercapnia. A comparison of changes in pial vascular resistance and total precapillary resistance indicated that the responses of pial vessels (particularly those less than 50 micron) paralleled the responses of the intraparenchymal arterioles.
Pathogenesis of one-kidney, one-clip hypertension in rats after renal denervation
Authors: Villarreal D. , Freeman R. H. , Davis J. O. , Garoutte G. , Sweet W. D.
Published: December 2017

This study examines the role of the renal nerves in the chronic and early developmental stages of one-kidney, one-clip (1K-1C) Goldblatt hypertension. Groups of uninephrectomized Sprague-Dawley rats underwent renal artery constriction with a clip of an internal diameter of 0.23 mm (groups 1 and 3) or 0.40 mm (groups 2 and 4) to produce severe or moderate hypertension. Two weeks later, groups 1 and 2 were subjected to renal denervation and groups 3 and 4 were denervated 6 and 7 wk after clipping, respectively. In all four groups, hypertension remained unchanged during the subsequent 2 wk after denervation. To study further the effects of renal denervation during the early onset of hypertension, groups 5, 6, and 7 received the smaller (0.23 mm) clip after uninephrectomy. Groups 5 and 6 were renal denervated immediately before clipping; group 7 was not denervated. In groups 6 and 7 the renin-angiotensin system was blocked with a continuous infusion of the converting-enzyme inhibitor captopril for 24 h before and 15 days after clipping. In group 5, renal denervation did not prevent a prompt and severe rise in the systolic blood pressure. In groups 6 and 7, infusion of captopril prevented the hypertension only during the first 4 days after clipping; at no time was there a difference in the systolic blood pressure curves of groups 6 and 7 during or after captopril infusion. These data demonstrate that regardless of the severity and duration of hypertension, renal denervation failed to attenuate either the development or the maintenance of 1K-1C Goldblatt hypertension in the rat. Thus the present results fail to provide support for the concept that the renal nerves modulate the hypertension in this experimental model.
Mechanism of the biphasic arteriolar response to angiotensin II
Authors: Fleming J. T. , Joshua I. G.
Published: December 2017

Male Sprague-Dawley rats (140-180 g) were anesthetized with alpha-chloralose and urethan. The cremaster muscle with intact blood supply and neural innervation was suspended in a tissue bath containing a modified Krebs solution. With the use of television microscopy the luminal diameters of third-order arterioles (14-32 micron) were measured before and after adding angiotensin II (ANG II, bath concn 10(-6) M). The arterioles responded to ANG II with an initial, transient constriction followed by a more prolonged dilation to a diameter larger than the control diameter. Pretreating the muscle with [Sar1, Ile8]ANG II significantly attenuated both the arteriolar constriction and subsequent dilation induced by ANG II. Treatment of the cremaster muscle with mefenamic acid or indomethacin, inhibitors of prostaglandin synthesis, produced a significant reduction in the diameter of the arterioles and abolished the dilator phase of the arteriolar response to ANG II without preventing the ANG II-induced constriction. These results demonstrate that within the intact microcirculation, ANG II produces both an arteriolar constriction and a dilation that are mediated by specific ANG II receptors. The ANG II-induced dilation of the arterioles appears to be caused by increased prostaglandin synthesis and release.
Effect of ischemia on calcium exchange in the rabbit myocardium
Authors: Nishioka K. , Nakanishi T. , Jarmakani J. M.
Published: December 2017

This study was designed to evaluate the effect of reperfusion after 60 min of ischemia on Ca2+ and Ba2+ exchanges in the newborn and adult myocardium. All studies were performed utilizing the isolated arterially perfused septal preparations of newborn and adult rabbit hearts that were maintained at 27, 33, or 37 degrees C and paced at 90 beats/min. After stabilization of mechanical function, 60 min of global ischemia was induced and then followed by 60 min of reperfusion. Tissue 47Ca2+ or 133Ba2+ uptake was measured by a juxtaposed gamma probe. 133Ba2+ uptake studies were utilized to determine sarcolemmal permeability to divalent cations. During reperfusion, there was an increase in the rate of Ca2+ and Ba2+ uptake at all temperatures in the adult and only at 33 and 37 degrees C in the newborn. The increase in the rate of divalent cations was proportionally related to the muscle temperature, and the increase in the newborn was significantly less than that in the adult. The net increase in tissue Ca2+ was inversely related to the recovery of myocardial mechanical function and ATP content after reperfusion. These data suggest that 1) an increase in sarcolemmal permeability to divalent cations on reperfusion may be responsible for the increase of Ca2+ uptake and this increase in the newborn was significantly less than in the adult, and 2) this increase in Ca2+ uptake is associated with myocardial ATP depletion.
Sarcolemmal enzymes and Na+ -Ca2+ exchange in hypoxic, ischemic, and reperfused rat hearts
Authors: Daly M. J. , Elz J. S. , Nayler W. G.
Published: December 2017

Isolated spontaneously beating rat hearts were perfused in the Langendorff mode and divided into four groups, i.e., control (aerobic), hypoxic (95% N2-5% CO2), ischemic, and ischemic reperfused. After a total of 90 min of perfusion, the sarcolemma was isolated and enzymatically characterized. Ouabain-sensitive Na+-K+-ATPase was inhibited in all three experimental groups, whereas K+-stimulated phosphatase activity was decreased only in the ischemic and reperfused groups compared with control. 5'-Nucleotidase activity was inhibited (P less than 0.05) only in the ischemic group. Mg2+-ATPase activity was not different from control. Passive Ca2+ uptake and Ca2+ efflux were not significantly altered by any of the interventions. Na+-Ca2+ exchange rate, but not capacity, was decreased (by 32-42%) in the ischemic group but this was partially reversed on reperfusion. These results suggest that changes secondary to lack of flow rather than O2 play a major role in the etiology of ischemic damage to the membrane and that a 15-min period of reperfusion after 60 min of ischemia does not exacerbate this damage.
Adrenergic-cholinergic interactions on membrane potential of K+ -depolarized ventricular muscle
Authors: Ehara T. , Mitsuiye T.
Published: December 2017

In guinea pig ventricular muscles exposed to K+-rich (27 mM) Tyrode solution containing 0.2 mM Ba, catecholamine elicited a slight depolarization of the resting membrane. Application of acetylcholine (ACh) during this catecholamine-induced response caused a repolarization, and removal of ACh induced a transient enhancement in the depolarization (rebound). These effects of ACh were abolished by atropine. Application of ACh alone and its removal had little effect on the membrane potential. Like the catecholamine-induced depolarization, the rebound depolarization after ACh removal was inhibited by slow channel blockers. Thus the rebound was attributed at least in part to enhanced changes in the catecholamine-sensitive conductance, i.e., a beta-receptor-mediated increase in the slow channel conductance. In driven muscles perfused with normal Tyrode solution, there was a rebound increase in twitch tension when ACh was removed in the presence of catecholamine, and this rebound was accompanied by an "extra" elevation of the action potential plateau. Thus cessation of the stimulation of myocardial muscarinic receptors may transiently lead to an enhanced activity of the beta-adrenoceptor-slow channel system in guinea pig ventricular muscle.
Time constant of isovolumic pressure fall: new numerical approaches and significance
Authors: Martin G. , Gimeno J. V. , Cosin J. , Guillem M. I.
Published: December 2017

The effects of left ventricular diastolic pressure changes on the values of the time constant (T) of isovolumic pressure fall are controversial. Normally, T is calculated either by linear regression of 1n left ventricular pressure (LVP) vs. time (TL) or by using an exponential model with asymptote (PB, extrapolated base-line pressure to which LVP would fall if decay continued indefinitely). This study, in intact dogs, has been designed to revise the effects that drugs that alter load (angiotensin and nitroprusside, without and with autonomic blockade) and inotropism (isoproterenol and propranolol) might have on the relaxation rate using different numerical methods. We found that 1) the upward or downward translation of the LVP curve had an important effect on the value of TL calculated by the semilogarithmic method; 2) when a model with asymptote was used, the simultaneous changes of T and PB, were not related to the dose of the drug; 3) the values of TL and the -dP/dt values extrapolated to 15 mmHg from a model with PB, were much more sensitive to beta-agonist or antagonist drugs than to others whose action was through load alteration. We feel that some of the earlier studies on relaxation rate determinants should be revised as possibly some of the conclusions have been based on artifacts introduced by the method chosen for the computation of the relaxation parameters.
Purkinje-muscle coupling and endocardial response to hyperkalemia, hypoxia, and acidosis
Authors: Gilmour R. F. , Evans J. J. , Zipes D. P.
Published: December 2017

Previously we found that combined hyperkalemia, hypoxia, and acidosis depressed the electrical activity of canine epicardium more than that of endocardium or Purkinje fibers. In this study, we determined whether the resistance of endocardium to these components of ischemia was due to electrotonic interactions with Purkinje fibers. The effects of combined hyperkalemia, hypoxia, and acidosis were tested on endocardial cells that were electrically uncoupled from Purkinje cells ("uncoupled" endocardium), due to their location or to prior exposure to elevated [Ca2+]. During control, action potentials in uncoupled endocardium had shorter durations than endocardium coupled to Purkinje ("coupled" endocardium), but had similar amplitudes, upstroke velocities, and resting potentials. During combined hyperkalemia, hypoxia, and acidosis, action potentials in uncoupled endocardium were more depressed than in coupled endocardium and resembled those in depressed epicardium. In addition, the combination of these components of ischemia produced electrical uncoupling at the Purkinje-muscle junction, although each component alone did not. Thus the resistance of endocardial cells to some components of ischemia appears to involve electrotonic interactions with Purkinje cells, which may be prevented by ischemia-induced electrical uncoupling.
Time course of jejunal blood flow, O2 uptake, and O2 extraction during nutrient absorption
Authors: Sit S. P. , Chou C. C.
Published: December 2017

Experiments were performed on anesthetized dogs to determine whether responses of jejunal blood flow, arteriovenous O2 difference, O2 uptake (VO2), and glucose absorption to luminal placement of predigested food or glucose would change with time during 30- and 60-min placement periods and to determine whether bile alters the responses. During the initial 15 min, food, glucose, food plus bile, and glucose plus bile produced a 13, 10, 51, and 30% increase in flow, respectively. During the next 15 min, flow returned to control levels, while arteriovenous O2 difference significantly increased with food or glucose; with glucose plus bile, flow decreased to 28% above control. In the case of food plus bile, flow decreased to 26% above control at 30 min and returned to control 50 min after placement. Despite the fluctuation in flow, the increase in VO2, and glucose absorption stayed at a steady level throughout the entire placement period. Bile significantly enhanced the increases in both flow and VO2 produced by food or glucose, prolonged the hypermia, delayed the significant rise in arteriovenous O2 difference, and had no effect on glucose absorption. In conclusion, the relative contributions of blood flow and O2 extraction to the enhanced VO2 produced by luminal food and glucose change with time, and bile significantly alters the magnitude or time course of changes in the above three variables.
Coronary artery reactivity in deoxycorticosterone acetate hypertensive rats
Authors: Hagen E. C. , Webb R. C.
Published: December 2017

Helical strips of coronary arteries from normotensive and deoxycorticosterone acetate (DOCA) hypertensive rats were studied in vitro for their responsiveness to a variety of vasoactive agents. After application of passive force (50-400 mg), arteries developed spontaneous tonic contractions. These tonic contractions were not different between the two groups, and the contractions were not altered by inhibitors of neurogenic, prostaglandin, peptidergic, or purine activity. Coronary arteries from DOCA rats were more sensitive (lower effective dose, 50%) to the contractile effects of norepinephrine, serotonin, and potassium chloride relative to those from normotensive rats. Following contraction induced by serotonin, coronary arteries from DOCA rats relaxed less to isoproterenol and adenosine compared with those from control rats. Relaxation of arteries from DOCA rats in response to prostacyclin, nitroprusside, and acetylcholine did not differ from that in coronary arteries from normotensive rats. These observations demonstrate increased vascular sensitivity to constrictor agents and altered relaxation responses to adenosine and isoproterenol in the coronary vasculature of DOCA hypertensive rats.
Sympathetic nerves reduce cerebral blood flow during hypoxia in awake rabbits
Authors: Busija D. W.
Published: December 2017

Effects of sympathetic nerves on cerebral blood flow (CBF) during normoxia or hypoxia combined with hemorrhagic hypotension were examined in awake rabbits. One superior cervical ganglion was excised and sham surgery was performed on the other side. Five rabbits each were exposed to normoxia [arterial O2 tension (Pao2) greater than or equal to 78 mmHg] or hypoxia (Pao2 less than or equal to 39 mmHg). Cerebral blood flow was measured with 15-micron microspheres three times in each group: normotension [mean arterial pressure (MAP) 80-86 mmHg]; moderate hypotension (MAP 62-65 mmHg); and severe hypotension (MAP 49-50 mmHg). During normoxia, blood flow to cerebrum was 70 +/- 8 (SE) ml X min-1 X 100 g-1 during normotension and did not decrease during hypotension. Sympathetic nerves had no effect on CBF during normoxia. During hypoxia, blood flow to cerebrum was 243 +/- 21 ml X min-1 X 100 g-1 during normotension and fell as arterial pressure was lowered. Blood flow to denervated cerebrum was higher than on the intact side during normotension (13 +/- 4%), moderate hypotension (11 +/- 5%), and severe hypotension (12 +/- 4%). Similarly, blood flow to denervated cortical gray matter was higher during normotension (19 +/- 4%), moderate hypotension (16 +/- 6%), and severe hypotension (17 +/- 6%) when compared with the innervated side. In addition, blood flow to denervated cerebellum was higher than the innervated side during severe hypotension (27 +/- 17%).(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial cell volume and coronary resistance during diminished coronary perfusion
Authors: Powers E. R. , DiBona D. R. , Powell W. J.
Published: December 2017

The present study was undertaken to determine whether diminished coronary blood flow without abrupt reperfusion results in myocardial cell swelling and, if so, whether the increment in tissue water is related to an increase in coronary vascular resistance. In 19 anesthetized open-chest dogs on right heart bypass with controlled coronary perfusion a decrease in coronary flow resulted in an increase in intracellular water and a progressive increase in coronary resistance. In 15 additional dogs, 180 min of ischemia produced by partially occluding the circumflex coronary artery resulted in significant increases in myocardial water content and progressive decreases in regional myocardial blood flow (microsphere technique). A significant correlation was found between the progressive decreases in myocardial flow and the increases in myocardial water (r = -0.82, P less than 0.001). In five experiments, hypertonic mannitol prevented water accumulation and progressive decreases in blood flow in the ischemic tissue. Thus myocardial ischemia produced by a decrease in antegrade coronary perfusion results in myocardial cell swelling and an associated progressive perfusion deficit.
Effects of myocardial contraction on ultrasonic backscatter before and after ischemia
Authors: Barzilai B. , Madaras E. I. , Sobel B. E. , Miller J. G. , Perez J. E.
Published: December 2017

To determine whether contraction and relaxation influence quantitative myocardial ultrasonic backscatter we measured systolic and diastolic integrated backscatter separately in 10 pentobarbital-anesthetized dogs with defined, paced heart rates, before and after coronary occlusion. Data were acquired from intramural sites by coupling a broadband 5-MHz transducer to the left ventricular epicardium. Integrated backscatter was obtained from seven sequential ECG gated intervals throughout the cardiac cycle over the frequencies of 2.5-7.5 MHz and referenced to values obtained with a steel reflector. Before coronary occlusion myocardium in all dogs exhibited a decrease in integrated backscatter from end diastole to end systole (P less than 0.05) in control zones and in zones destined to become ischemic (P less than 0.05). Thirty minutes after occlusion integrated backscatter did not change in control zones but was elevated in ischemic zones with blunting of the diastolic-to-systolic variation. Thus myocardium undergoing contraction exhibits a decrease in integrated backscatter, and measurement of integrated backscatter at end systole differentiates ischemic from normal myocardium.
Monitoring of mitochondrial membrane potential in isolated perfused rat heart
Authors: Kauppinen R. A. , Hassinen I. E.
Published: December 2017

Optical methods were tested for measuring the membrane potential changes of mitochondria in isolated perfused rat hearts. Safranin was found to be rapidly taken up by the Langendorff-perfused heart, and after loading with the dye there was practically no washout of the stain during perfusion with Krebs-Ringer bicarbonate solution. Staining with safranin induced the appearance of an intense absorption band in the reflectance spectrum of the heart, but the absorbance spectrum changes were not useful for monitoring the mitochondrial membrane potential changes because of interference by endogenous hemoproteins. The fluorescence intensity, however, responded in a manner which indicated that its changes originated from dye attached to the mitochondria. A decrease of the fluorescence was found on energizing the mitochondria by decreasing the cellular energy consumption by arrest induced by 18 mM K+ or by decreasing the beating rate of an electrically paced heart from 5 Hz to the endogenous ventricular frequency of 1.5 Hz. In hearts arrested by Ca2+ depletion, 18 mM K+ did not affect the safranin fluorescence. This was taken to indicate that under these conditions the safranin fluorescence was not sensitive to the plasma membrane potential. The uncoupler carbonyl cyanide m-chlorophenylhydrazone induced an intense enhancement of safranin fluorescence in the perfused heart, demonstrating that the probe is sensitive to mitochondrial membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Detection and quantification of small right-to-left shunts by the phase-plane method
Authors: Fonseca-Costa A. , Magrassi P. , Zin W. A. , Romeo L. J.
Published: December 2017

In six anesthetized dogs 70 indicator-dilution curves and phase-plane plots were recorded. Indocyanine green was injected into the superior vena cava and sampled through a dichromatic cuvette densitometer from the femoral artery. Dye-dilution curves were recorded from dogs with normal cardiovascular systems and repeated after right-to-left shunts of different magnitude were surgically produced. The percent of blood shunting was calculated according to standard indicator-dilution equations and also by means of oximetric determination of blood samples. They were compared with shunt estimates based on phase-plane loop measurements. Good correlation was found with standard indicator-dilution procedures (r = 0.890) but not with oximetry (r = 0.466). The phase plane shows its utility in the detection and evaluation of small right-to-left shunts. These shunts affect the initial portion of the phase plane and the alterations appear to be more evident than in the corresponding concentration-vs.-time curves.
Adenosine and hypoxic pulmonary vasodilation
Authors: Gottlieb J. E. , Peake M. D. , Sylvester J. T.
Published: December 2017

We have previously shown that after exposure to an inspired O2 tension less than 25 Torr, isolated lungs perfused with autologous blood exhibit vasoconstriction followed by dilation. Because adenosine has been implicated as a mediator of hypoxic vasodilation in the systemic circulation and because the concentration of adenosine in the lung has been shown to increase with hypoxia, we tested the hypothesis that adenosine is the mediator of hypoxic pulmonary vasodilation. We first confirmed that adenosine was a vasodilator in isolated lungs of adult male ferrets. Next we added the enzyme adenosine deaminase (ADase), which inactivates adenosine by converting it to inosine, to the perfusate before exposure to one of two levels of hypoxia [inspiratory PO2 (PIO2) 18 or 0 Torr]. In comparison with untreated lungs, the time course of pulmonary arterial pressure at constant flow in lungs treated with ADase (24 mg protein or 6,000 U) was not different; however, when the vessels were constricted at PIO2 25 Torr, ADase prevented vasodilator responses to adenosine administered into either the perfusate or the airways, indicating penetration of active ADase into the interstitium. Unless adenosine released endogenously into the interstitium during hypoxia was somehow protected from the ADase which reached the interstitium, these results indicate that hypoxic pulmonary vasodilation was not mediated by adenosine.
Isotonic length transient of cat heart muscle in Ba2+-induced contracture
Authors: Saeki Y. , Shibata T. , Yanagisawa K.
Published: December 2017

To characterize mechanical properties of activated heart muscle, the length response to step (4 ms) decrease in tension in Ba2+-induced contracture in kitten papillary muscle was analyzed. The amplitudes of tension steps were varied at the maximum contracture level (Tc), different initial muscle lengths [0.90 Lmax to Lmax], and different temperatures (20-35 degrees C). When the tension decrease was less than 0.7 Tc, the length response comprised four different phases. The amplitude of shortening in the second phase, after the initial rapid shortening in the first phase, increased up to approximately 3.5% of the initial muscle length quite linearly with increasing amplitude of tension reduction. The amount of lengthening in the third phase, however, increased to a maximum (up to approximately 1.4% initial length) at the tension reduction of approximately 0.4 Tc. The third phase of lengthening was larger at shorter initial muscle length. Increasing temperature markedly decreased the amplitude and shortened the duration of the length response in the second and third phase independently of initial muscle length. Unlike that of the muscle in contracture, the length response of the resting and of the rigor muscle changed in a nearly stepwise fashion. One explanation of these phenomena is that the transient length responses following a rapid tension reduction are mostly determined by the kinetics of the attachment and detachment of cross bridges between actin and myosin filaments.
Corticosterone and triiodothyronine control of myocardial Na+-K+-ATPase activity in rats
Authors: Klein L. E. , Bartolomei M. S. , Lo C. S.
Published: December 2017

Experiments were carried out to examine the effects of corticosterone and triiodothyronine on rat myocardial Na+-K+-ATPase activity. Corticosterone increased Na+-K+-ATPase activity when administered intravenously in multiple doses, a single dose, and different dosages. The possibility that enhancement of myocardial Na+-K+-ATPase activity by corticosterone is mediated by early changes in intracellular Na+ and K+ was investigated. Following a single dose of corticosterone (1 mg/100 g body wt), the increase in Na+-K+-ATPase activity preceded the changes in intracellular Na+ and K+. Corticosterone did not change the transition temperature and activation energy of the reaction in myocardial Na+-K+-ATPase. This implies that corticosterone does not act by altering the lipid matrix in the microenvironment of the Na+-K+-ATPase system. The interaction between the effects of corticosterone and triiodothyronine on myocardial Na+-K+-ATPase activity was examined. Our studies indicated that corticosterone and triiodothyronine regulate Na+-K+-ATPase activity via parallel independent pathways.
Effects of afferent renal nerve stimulation on renal hemodynamic and excretory functions
Authors: Stella A. , Golin R. , Busnardo I. , Zanchetti A.
Published: December 2017

In anesthetized cats (n = 9) renal afferent fibers were electrically stimulated for 11 min, and the response of the contralateral innervated kidney was compared with that of the ipsilateral denervated one. Before stimulation, renal blood flow, glomerular filtration rate, and water and sodium excretions were significantly lower in the innervated kidney than in the denervated one. Afferent renal nerve stimulation augmented arterial pressure and also increased sodium and water excretions from both kidneys without concomitant changes in glomerular filtration rates and renal blood flows. Absolute and percent changes in sodium and water excretions from the innervated kidney were similar to those observed in the denervated one. The same results were obtained in cats (n = 4) which underwent bilateral adrenalectomy to avoid the effect of circulating catecholamines. In another group of cats (n = 5), the increase in renal perfusion pressure due to the stimulation was prevented by an aortic snare: this resulted in a slight but equal decrease of all variables in both kidneys. These experiments do not show a reflex control of renal function from renal afferents.
Effects of fetal-maternal exchange transfusion on fetal oxygenation and blood flow distribution
Authors: Itskovitz J. , Goetzman B. W. , Roman C. , Rudolph A. M.
Published: December 2017

The effect of reducing hemoglobin affinity for O2 on fetal oxygenation was assessed in seven fetal lambs in which fetal blood was almost completely replaced by maternal blood 2-3 days postoperatively. Measurements of fetal blood gases and organ blood flow (radionuclide-labeled microsphere technique) were obtained before and 1 h after the exchange transfusion. Umbilical venous blood PO2 increased from 29 +/- 5 to 35 +/- 6 (SD) Torr (P less than 0.001) but hemoglobin O2 saturation decreased from 78.2 +/- 10.3 to 39.8 +/- 8.8% (P less than 0.001), resulting in a 46% decrease in umbilical venous blood O2 content. Since umbilical-placental blood flow also decreased (P less than 0.002), O2 delivery to the fetus decreased by 64% (P less than 0.002). Although O2 extraction increased from 32.5 +/- 6.8 to 50.9 +/- 9.0% (P less than 0.002), fetal O2 consumption fell from 7.28 +/- 1.97 to 4.10 +/- 1.20 ml X min-1 X kg-1 (P less than 0.02), and metabolic acidemia developed. No significant change in fetal cardiac output was observed. Blood flow increased significantly to the myocardium and adrenals but fell in the placenta, carcass, and lungs and was maintained in other organs. This resulted in a significant decrease in the amount of O2 delivered to all fetal organs except to the myocardium in which it was maintained. In the sheep the higher affinity of fetal blood hemoglobin for O2 helps maintain normal oxygenation during fetal life by facilitating O2 uptake at the placenta and unloading O2 in the tissues.
Polyamines and the development of monocrotaline-induced pulmonary hypertension
Authors: Olson J. W. , Hacker A. D. , Altiere R. J. , Gillespie M. N.
Published: December 2017

Previous work in our laboratory has shown that the development of monocrotaline-induced pulmonary vascular disease in rats is preceded by a prolonged activation of lung ornithine decarboxylase (ODC). We now report that significant increases in rat lung adenosylmethionine decarboxylase activity and levels of the diamine putrescine and the polyamines, spermidine and spermine, are produced by a single dose of monocrotaline (MCT). Lung putrescine levels were increased from days 7 through 21, and both spermidine and spermine were first elevated at day 10 following MCT administration. This sustained elevation of lung polyamine levels substantially preceded the development of right ventricular hypertrophy and pulmonary hypertension, which were first evident at days 14 and 16, respectively. Continuous treatment with alpha-difluoromethylornithine, a highly specific enzyme-activated, irreversible inhibitor of ODC activity, prevented the development of MCT-induced pulmonary toxicity. It thus appears that ODC and the polyamines may be important mediators of hypertensive pulmonary vascular disease that develops in response to monocrotaline administration.
Nitrendipine: effects on vascular responses and myocardial binding
Authors: McBride W. , Mukherjee A. , Haghani Z. , Wheeler-Clark E. , Brady J. , Gandler T. , Bush L. , Buja L. M. , Willerson J. T.
Published: December 2017

We have further defined the binding characteristics of [3H]nitrendipine to myocardial microsomal membranes of cats, dogs, rats, and rabbits and to canine coronary vasculature (1.5-3.0 mm OD), and we have studied nitrendipine's effect on contractile responses in isolated feline cardiac muscle and canine coronary arteries. [3H]nitrendipine binding is rapid, saturable, and reversible in all four species and in all of these tissues. Feline myocardium has a single binding site with a dissociation constant (KD) of 1.94 nM. Canine myocardium may have two classes of binding sites, with the high-affinity site having a KD of 0.17 nM. Nitrendipine depresses contractility in isolated feline cardiac muscle and canine coronary arteries in a dose-dependent manner [half-maximal dose (ED50) 0.20 microM in isolated feline cardiac muscle and 1.6-6.3 nM for potential dependent contractile responses in isolated canine coronary arteries] and severely blunts the contractile response to increases in extracellular calcium concentration in isolated feline papillary muscles. In contrast to verapamil and D 600, nitrendipine does not prevent the treppe phenomenon. In isolated feline cardiac muscle and large canine coronary arteries, the minimal nitrendipine concentration required for specific binding and for depression of contractile responses is similar. However, only in large canine coronary arteries is the ED50 for nifedipine's depression of contractility similar to the KD for [3H]nitrendipine binding in the respective tissue.
Effects of dipyridamole on myocardial adenosine and active hyperemia
Authors: Knabb R. M. , Gidday J. M. , Ely S. W. , Rubio R. , Berne R. M.
Published: December 2017

Dipyridamole, a vasodilator that potentiates the actions of exogenous adenosine, is known to inhibit cellular uptake of adenosine, but its effects on cellular adenosine release, and thus interstitial adenosine levels, are disputed. We used the accumulation of adenosine in pericardial infusates (PCI) as an index of interstitial adenosine concentration and observed the effects of dipyridamole on relationships among coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and PCI adenosine concentrations during steady-state alterations of cardiac work. Dipyridamole increased CBF and PCI adenosine concentration without altering MVO2. The relationship between PCI adenosine and CBF was unaltered, supporting a cause and effect relationship between interstitial adenosine concentration and CBF. In addition, we determined that unlike previous studies in isolated perfused hearts the washout of adenosine by coronary plasma was unaffected by dipyridamole. The results support previous suggestions that, whereas dipyridamole inhibits adenosine uptake, it does not alter cellular adenosine release, and therefore interstitial adenosine levels are increased. The constant relationship between PCI adenosine and CBF supports hypotheses that attribute the hyperemias associated with increased cardiac work or with dipyridamole to increased interstitial adenosine.
Acute resetting of carotid sinus baroreceptors. II. Possible involvement of electrogenic Na+ pump
Authors: Heesch C. M. , Abboud F. M. , Thames M. D.
Published: December 2017

In the accompanying manuscript [Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H824-H832, 1984] we demonstrated that a mechanical mechanism alone cannot account for acute resetting of baroreceptors. To determine if changes in the activity of a baroreceptor electrogenic Na+ pump contributed to resetting, single-unit baroreceptor discharge was recorded from the carotid sinus nerve while resetting protocols were performed before and after exposing the vascularly isolated carotid sinus to treatments known to block the Na+ pump [ouabain and low extracellular K+ concentration ([K+]o)]. Ouabain (0.1-0.5 microgram/ml) blocked the increase in baroreceptor threshold pressure that occurred when intrasinus pressure was increased by 30 mmHg for 15 min [delta threshold = 16 +/- 3 (SE) mmHg before and 1.2 +/- 2.3 mmHg after ouabain]. In 12 experiments carotid sinus pressure was increased from 70 to 160 mmHg for 5 min and then returned to 70 mmHg for 10 min in the presence of both normal [K+]o (5.8 mM) and low [K+]o. Exposure to the low K+ solution resulted in a significantly smaller increase in threshold pressure when intrasinus pressure was increased from 70 to 160 mmHg (9 +/- 2.7 vs. 18 +/- 2.1 mmHg). When K+ was replaced, threshold pressure again increased by 18 +/- 2.3 mmHg, the increase in threshold was reversed. Thus, since ouabain blocked and low [K+]o attenuated acute resetting of the baroreceptors, we propose that changes in the activity of an electrogenic Na+ pump contribute to acute resetting.
A hermetically sealed cardiac dimension transducer for long-term animal implantation
Authors: Olsen C. O. , Abert S. J. , Glower D. D. , Spratt J. A. , Tyson G. S. , Davis J. W. , Rankin J. S.
Published: December 2017

Pulse transit sonomicrometry is a well-accepted method for assessing cardiac dimensions and function in research animals. Unfortunately, this technique has been hampered in chronic applications by a significant incidence of transducer failure secondary to leakage of corrosive biological fluids into the piezoelectric material. The fluid leakage generally occurred at the interface between the encapsulating epoxy and the bioelectric cable and resulted in progressive functional deterioration with time. In this paper, a new hemispheric ultrasonic dimension transducer is described with a mechanical hermetic seal at the bioelectric cable-transducer interface. The hermetically sealed transducers withstood 400 psi compressed air without leakage, while conventional transducers routinely leaked at 60 psi. The performance characteristics of the new transducers were similar to those previously reported with omnidirectional designs, and no failures have occurred during 3 yr of experience with repeated transducer implantations.