bluuebunny/crossref_metadata_2025 huggingface dataset:
Action potential duration in ventricular muscle during selective metabolic block
Authors: Hayashi H. , Watanabe T. , McDonald T. F.
Published: December 2017

We have examined whether maintenance of the cardiac action potential duration depends exclusively on energy from glycolysis. Oxidative phosphorylation in guinea pig papillary muscles was inhibited by superfusion with hypoxic solutions. After 60 min in 50 mM glucose solution, the action potential duration was 85% of aerobic control, but ATP content was only 25%; after 60 min in 0 mM glucose, both the duration and ATP content had declined to 15% control. When the glucose concentration of hypoxic solution was raised from 0 to 50 mM, there was nearly full recovery of the action potential duration but ATP only increased to about 25% control. We attribute action potential shortening during metabolic inhibition to suppression of calcium current and activation of potassium current; the latter are graded in intensity and expressed only at low ATP. When normoxic muscle was treated with 20 mM 2-deoxy-D-glucose (2-DG) to inhibit glycolysis, there was an early transient shortening of the action potential. This was attributed to ATP consumption related to early rapid 2-DG influx and phosphorylation. After the transient, the action potential duration was maintained for several hours in oxygenated 2-DG solution. The duration was also maintained in oxygenated muscle depleted of glycolytic substrate. Thus we found no evidence of an exclusive relation between action potential duration and glycolysis.
Left ventricular function in malnutrition
Authors: Alden P. B. , Madoff R. D. , Stahl T. J. , Lakatua D. J. , Ring W. S. , Cerra F. B.
Published: December 2017

Twenty-one dogs were chronically instrumented with ultrasonic left ventricular dimension transducers and micromanometers to elucidate the effects of acute protein-calorie malnutrition on cardiac function. Ten dogs received a regular diet for 3 wk, whereas 11 dogs received a protein-calorie-deficient diet designed to achieve a mean weight loss of 20-25% over a 3-wk period. Studies of cardiac function were performed in awake intact animals at base line (1 wk postoperatively) and after 3 wk. In the malnourished dogs, cardiac mass was lost in proportion to total body mass loss. Mean cardiac mass fell from 115 to 91 g. This was largely due to wall thinning in this group. Heart rate dropped from 125 to 79 beats/min with malnutrition and ejection fraction increased from 29.8 to 34.6%. Cardiac output fell from 2.98 to 2.38 l/min, but cardiac index normalized to body surface area was unchanged. No significant changes in hemodynamics were observed in the control group. In the malnutrition group, global ventricular contractility, as measured by the load-independent index of systolic function or the slope of linear relationship between end-systolic pressure and end-systolic volume (EmaxPV), decreased slightly from 3.56 to 2.81 mmHg/ml (P = 0.07). However, Emax calculated from circumferential stress and strain data was unchanged. This indicates that depressed contractility was due to loss of cardiac muscle mass rather than any change in the myocardium per se. Response to beta-adrenergic stimulation was unchanged with starvation. Acute protein-calorie malnutrition causes significant cardiac atrophy that is reflected in decreased cardiac output and slightly reduced contractility but not in intrinsic properties of the myocardium.
Temporal relation between energy metabolism and myocardial function during ischemia and reperfusion
Authors: Clarke K. , O'Connor A. J. , Willis R. J.
Published: December 2017

The purpose of the present investigation was to study the relation between energy metabolism and contractile function in the isovolumic guinea pig heart. 31P nuclear magnetic resonance spectroscopy was used to measure changes in the intracellular levels of creatine phosphate, ATP, inorganic phosphate, and pH during 2.43 min total global ischemia and 2.43 min reperfusion, with a time resolution of 9.7 s. From these data, cytosolic changes in the phosphorylation potential, [ATP]-to-[ADP] ratio, free-energy change of ATP hydrolysis, and concentration of free ADP were estimated. The simultaneous monitoring of functional and biochemical parameters allowed them to be directly correlated with respect to time and with respect to each other. No significant changes in ATP were detected at any time, but changes in all other biochemical data were highly correlated with changes in contractile function. Kinetic analysis, using a nonlinear least-squares fit of the experimental points, revealed that the changes in most parameters fitted monoexponential functions. Each parameter was ranked according to its half time, which revealed that the phosphorylation potential was the only metabolic parameter to change at a rate faster than loss of contractile function during ischemia, and all metabolic changes, with the exception of pH, led the recovery of contractile function during reperfusion, the most rapid change occurring in the free ADP concentration. It is concluded that the cytosolic phosphorylation potential controls the contractile function of the heart and that cytosolic free ADP is important in the control of mitochondrial oxidative phosphorylation.
Effect of MCA occlusion on brain O2 supply and consumption determined microspectrophotometrically
Authors: Buchweitz-Milton E. , Weiss H. R.
Published: December 2017

This study compared oxygen extraction, oxygen consumption, and cerebral blood flow (CBF) in the ischemic and contralateral cortex of middle cerebral artery (MCA)-occluded feline brain using a microspectrophotometric technique. This technique was further validated in several experiments. A transorbital approach exposed the right MCA. After preocclusion blood pressure, heart rate, and blood gas values were determined, radioactively labeled microspheres (15 +/- 3 microns diam) were injected intra-atrially. The right MCA was then occluded. These same measurements were taken 1 h later. Arterial and venous oxygen saturations were determined in the center and surrounding area of the occluded ischemic cortex and other brain regions. Regional cerebral oxygen consumption was determined as the product of CBF and oxygen extraction. CBF decreased significantly from 54.0 +/- 5.0 to 26.6 +/- 4.8 (mean +/- SE) ml X min-1 X 100 g-1 in the center of the ischemic cortex and from 49.6 +/- 7.0 to 30.6 +/- 5.0 ml X min-1 X 100 g-1 in the surrounding ischemic cortex. Oxygen extraction was significantly increased from 3.7 +/- 0.4 ml O2/100 ml blood to 4.6 +/- 0.6 ml O2/100 ml blood in the center of the occluded cortex but was not significantly altered in the surrounding moderately ischemic cortex. Oxygen consumption was not significantly altered in either ischemic cortical region when compared with the contralateral cortices. Unilateral MCA occlusion caused a decreased regional CBF associated with increased brain oxygen extraction in the cortical region directly supplied by the MCA. The feline brain appears to maintain oxygen consumption in the occluded cortex by increasing oxygen extraction.
Relaxation time constant of isolated rabbit left ventricle
Authors: Schiereck P. , Nieuwenhuijs J. H. , de Beer E. L. , van Hessen M. W. , van Kaam F. A. , Crowe A.
Published: December 2017

Experiments were performed on isolated rabbit left ventricles. Controlled ejections during otherwise isovolumic contractions were studied. The time constant of relaxation was defined as the slope of the linear approximation of the ln(P)-t relation over a 40-ms period starting 20 ms after the minimum of the first time derivative of left ventricular pressure (dP/dt) of the isovolumic contraction. Variations in time of ejection, its amplitude, and velocity are applied independently. No direct effect of the variations in time and velocity of the ejection on the time constant of relaxation was found. This is in conflict with the findings of Hori et al. (Circ. Res. 55: 31-38, 1984). The difference is due to the influence of the recovery of pressure directly after the end of ejection in their study. This effect is present especially when ejection was timed to take place late in the contraction phase. The effect of the variation of the amplitude of the ejection on the time constant was similar to the effect of the end-diastolic pressure on the end-diastolic volume. It is concluded that the time constant of relaxation depends linearly on the same processes that are responsible for the height of the end-diastolic pressure.
Effects of aminophylline on behaviorally induced coronary blood flow increases
Authors: Billman G. E.
Published: December 2017

It has been proposed that adenosine is a metabolic vasodilator that matches myocardial oxygen supply to demand by regulating coronary blood flow. In the present study, the adenosine antagonist aminophylline (Am) was used to evaluate the role adenosine plays in the coronary blood flow increase elicited by a controlled aversive stress, namely, classical aversive conditioning (a 30-s tone reinforced with a 1-s shock). Fifteen mongrel dogs were chronically instrumented to measure left circumflex coronary blood flow (CBF), left ventricular pressure (LVP), and heart rate. Am significantly (P greater than 0.01) attenuated the CBF response to the aversive stress without affecting the prestress levels (pre-Am control 40.9 +/- 2.4, peak 64.6 +/- 3.3 ml/min; post-Am control 41.7 +/- 2.2, peak 55.0 +/- 2.5 ml/min). The maximal CBF increase was reduced by 38.9 +/- 6.7% when compared with the control (no drug) condition. In a similar manner, neither heart rate nor LVP was affected by Am. However, Am significantly increased prestress level of first derivative of left ventricular pressure with reference to time [LV dP/dt] (pre-Am control 3,793.5 +/- 289.8 and Am 4,599.6 +/- 331.2 mmHg/s, respectively). These data suggest that adenosine contributes significantly to the regulation of CBF during a controlled emotional stress.
Role of eicosanoids in hypoxic vasoconstriction in isolated lamb lungs
Authors: Raj J. U. , Chen P.
Published: December 2017

To determine the role of eicosanoids in hypoxic pulmonary vasoconstriction, we studied 42 isolated, blood-perfused lamb lungs during normoxia and hypoxia. We used the lung micropuncture technique to measure microvascular pressures in 20- to 80-micron diameter arterioles and venules and estimated segmental vascular resistance. In separate experiments, lungs were untreated or treated with either indomethacin (a cyclooxygenase inhibitor), Dazmegrel (a thromboxane synthetase inhibitor), SQ 29548 (a thromboxane receptor blocker), FPL 57231 (a leukotriene receptor blocker), or U 60257 (a 5'lipoxygenase inhibitor). In control untreated lungs both pulmonary arteries and veins constricted during hypoxia. Addition of indomethacin, Dazmegrel, or SQ 29548 to the perfusate resulted in abolition of venous constriction during hypoxia but enhancement of arterial constriction. FPL 57231 or U 60257 resulted in complete abolition of the pulmonary hypoxic vasoconstrictor response. Our results indicate that during hypoxia, leukotrienes mediate arterial and venous constriction with thromboxane A2 being necessary for venous constriction. We conclude that the interaction between 5'lipoxygenase and cyclooxygenase products of arachidonic acid results in the characteristic pulmonary hypoxic vasoconstrictor response in isolated, perfused lamb lungs.
Dynamics of cardiac muscle: analysis of isotonic, isometric, and isochronal curves
Authors: Nwasokwa O. N.
Published: December 2017

Canine papillary muscle force-length-time relation (F-L-t) was investigated under pentobarbital sodium anesthesia. The time intervals taken from end diastole to any point (P) on the force-length plane was determined for isometric (t1) and isotonic (t2) systole and corrected for excitation contraction coupling duration. The ratio t1/t2, designated km, was approximately constant for widely scattered positions of P chosen systematically. The km in the 10 dogs ranged from 0.36 to 0.94 with means +/- SD of 0.66 +/- 0.16; km correlated negatively with muscle average cross-sectional area (r = -0.82; P less than 0.005). Assuming constancy of km, a general relationship was derived between (delta F/delta t)t1L, the rate of isometric force development at P; (delta L/delta t)t2F, the velocity of isotonic shortening at P; (delta F/delta L)(t1,t2)t, the stiffness; and (delta L/delta F)(t1,t2)t, the compliance of the myocardium (all taken at P) as follows (delta F/delta L)t1,t2t = -km(delta F/delta t)t1L/(delta L/delta t)t2F and (delta L/delta F)t1,t2t = -km-1(delta L/delta t)t2F/(delta F/delta t)t1t. The ratio of (delta F/delta t)t1L to (delta L/delta t)t2F defines functional proclivity and measures the differential propensity to force development relative to shortening. Thus myocardial stiffness or compliance determines functional proclivity by acting as an impedance-matching transformer that steps up or steps down force development of shortening as warranted by the loading conditions.
Quinidine-induced inhibition of transient outward current in cardiac muscle
Authors: Imaizumi Y. , Giles W. R.
Published: December 2017

Quinidine is frequently used as a class I antiarrhythmic agent in the management of cardiac rhythm disturbances. It depresses the rapid initial depolarization of the action potential by blocking the sodium current, INa. In addition, quinidine increases the duration of the action potential and lengthens the refractory period. We have used a whole cell voltage-clamp technique to study the ionic mechanism underlying the lengthening of the action potential in single cells from the atrium and ventricle of the rabbit heart. Our data show that quinidine at therapeutic doses (3-10 microM) is a potent and selective inhibitor of a transient outward current, which controls the early repolarization of the action potential. In contrast, neither the calcium current, ICa, nor the time-independent background K+ current, IK1, is changed significantly by 10 microM quinidine. The reduction in the transient outward current can explain the lengthening of action potential and provides new insight into the mechanism of action of quinidine as an antiarrhythmic agent.
Free radical-producing enzyme, xanthine oxidase, is undetectable in human hearts
Authors: Eddy L. J. , Stewart J. R. , Jones H. P. , Engerson T. D. , McCord J. M. , Downey J. M.
Published: December 2017

Samples from four human hearts were analyzed for both their xanthine dehydrogenase and xanthine oxidase content. We used the conventional spectrophotometric assay and a more sensitive fluorometric assay to determine the content of enzyme in these samples. In no case could any activity be detected. We conclude that human hearts must contain less than 2.0 nU/g of activity. This makes it unlikely that xanthine oxidase is a significant source of O2 free radicals in the ischemic human heart or that xanthine oxidase inhibitors will be of therapeutic value in that setting.
Electrophysiological properties of automatic fibers in rabbit atrioventricular valves
Authors: Rozanski G. J.
Published: December 2017

Subsidiary atrial automaticity generated by cardiac fibers of the rabbit tricuspid valve was studied in vitro with the use of standard microelectrode techniques. The time course of diastolic depolarization of leading pacemaker fibers was characteristically biphasic over a potential range of -80 to -55 mV, with a brief primary phase of relatively steep slope and a longer secondary phase of lesser slope. The regenerative upstroke of pacemaker potentials was suppressed by cobalt ions and varied with changes in extracellular Ca2+ concentration in a manner suggesting a slow channel process. The time course of each diastolic phase, estimated by measuring slope, varied in a reproducible manner with changes in membrane potential elicited with long duration current pulses. Cesium ions reduced the slope of both diastolic phases at all potentials with greater effects on the primary diastolic phase, but spontaneous activity in the absence of current pulses was not significantly altered. Furthermore, pacemaker activity varied with changes in extracellular K+ concentration and in response to barium ions in manners suggesting the presence of a decaying K+ conductance. These experiments demonstrate the utility of valve tissue as a model of subsidiary atrial pacemaker activity and suggest the presence of current systems qualitatively similar to those observed in the sinoatrial node.
Attenuation of baroreceptive mechanisms by cardiovascular sympathetic afferent fibers
Authors: Gnecchi Ruscone T. , Lombardi F. , Malfatto G. , Malliani A.
Published: December 2017

By sectioning spinal dorsal roots from C8 to T6, we analyzed the contribution of sympathetic cardiovascular afferent fibers to the reflex bradycardia induced by arterial pressure rises in 24 anesthetized and in 21 decerebrate cats. In anesthetized cats, the reflex bradycardia was obtained in 16 animals with occlusions of the thoracic aorta and in 8 animals with phenylephrine injections (25-75 micrograms/kg). In both experimental conditions, the dorsal root section enhanced the bradycardia response, which thus increased from 15 +/- 3 to 20 +/- 3% during aortic constrictions and from 11 +/- 3 to 19 +/- 6% during phenylephrine injections (P less than 0.05). The enhancement, after rhizotomy of the reflex bradycardia during aortic occlusion, was more pronounced in eleven decerebrate cats as it increased from 21 +/- 4 to 34 +/- 4%, P less than 0.05. In five vagotomized and decerebrate cats, the reflex bradycardia was also increased after rhizotomy despite the overall reduction of the reflex response. In five decerebrate cats with beta-adrenergic receptor blockade (propranolol 0.2-0.4 mg/kg iv), aortic occlusion resulted in a small reduction in heart rate which was not significantly affected by dorsal root section. Our data indicate that excitatory reflexes mediated by dorsal roots are likely to modulate the inhibitory supraspinal reflexes that determine the heart rate reduction during acute rises in arterial blood pressure.
Endothelium inhibits responses of rabbit carotid artery to adrenergic nerve stimulation
Authors: Tesfamariam B. , Weisbrod R. M. , Cohen R. A.
Published: December 2017

Transmural electrical stimulation of isolated ring segments of the rabbit carotid artery caused frequency-dependent contractions; these were blocked by tetrodotoxin or prazosin. Mechanical or chemical removal of the endothelium markedly augmented responses to electrical stimulation. Inhibition of norepinephrine uptake and metabolism with cocaine, hydrocortisone, and pargyline increased contractions in rings with endothelium more than those without endothelium, but responses remained greater in rings denuded of endothelium. Methylene blue, an inhibitor of guanylate cyclase, enhanced responses to electrical stimulation of rings with intact endothelium only. Combined inhibition of guanylate cyclase and norepinephrine disposition increased the contractions and abolished the difference between the responses of rings with and without endothelium. In a perfusion-cascade system, the perfusate of donor segments with endothelium relaxed a bioassay ring without endothelium. Electrical stimulation of the segment caused no further relaxation of the bioassay ring. However, contractions caused by electrically stimulating the bioassay ring were depressed during superfusion with the perfusate of segments with, but not without, endothelium, indicating that vasodilators spontaneously released from the endothelium inhibit responses to nerve stimulation. These observations suggest that inhibition by the endothelium of the response to adrenergic nerve stimulation results from 1) spontaneous release of endothelium-derived vasodilators and 2) disposition of norepinephrine by the endothelial cells.
Subendocardial segment length shortening at lateral margins of ischemic myocardium in dogs
Authors: Gallagher K. P. , Gerren R. A. , Choy M. , Stirling M. C. , Dysko R. C.
Published: December 2017

The lateral borders of an infarcted area are sharply delineated in terms of perfusion, but functional impairment extends a limited distance into adjacent nonischemic myocardium. To determine the distribution of functional impairment we arrayed three ultrasonic dimension gauges to measure two subendocardial segment lengths in series. The center crystal, placed at the perfusion boundary (PB) between left anterior descending and circumflex arteries, radiated ultrasound to receiver crystals 7-17 mm to either side of the PB. The locations of the functional measurements relative to the PB were determined with myocardial blood flow (microsphere) "maps" constructed from multiple small tissue samples obtained circumferentially. On the nonischemic side of the PB, segment shortening (dL) increased from 2.00 +/- 0.37 mm during control conditions to 2.20 +/- 0.43 mm (P less than 0.05) after left circumflex coronary occlusion. Similar results were obtained in four conscious chronically instrumented dogs, supporting the conclusion that segment function adjacent to the ischemic margin is well preserved after coronary occlusion. On the ischemic side of the PB, dL decreased from 2.24 +/- 0.54 to 0.42 +/- 0.39 mm (P less than 0.01). By adding the data from the two segments in series, a combined measurement of dL across heterogeneously perfused myocardium was derived that decreased by 38% from control. The level of shortening represented an integral of normal and abnormal motion that was proportional to the mean reduction in blood flow (-44%) in all of the muscle spanned by the crystals. We conclude that subendocardial segment lengths "average" shortening in the muscle they subtend when arrayed across the perfusion boundary.
Limited capacity for renal vasodilatation in anesthetized diabetic rats
Authors: Ha H. , Dunham E. W.
Published: December 2017

Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled streptozotocin (STZ)-induced diabetes is attributable to diabetes-induced structural changes in the renal vasculature. Vehicle-treated control rats (CR) and rats that were injected with STZ (STZR) after pretreatment with 3-O-methylglucose (3-OMG), an agent that prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (ml.min-1.g kidney wt-1, electromagnetic flow probe), systemic arterial pressure (BP, mmHg), and renal vascular resistance (RVR, BP/RBF) in pentobarbital-anesthetized rats during a control period were 5.4 +/- 0.3 (P less than 0.01 vs. CR), 116 +/- 3, and 21.9 +/- 1.0 (P less than 0.01 vs. CR) in STZR (n = 12) and 8.2 +/- 0.4, 121 +/- 2, and 15.3 +/- 1.0 in CR (n = 11), respectively. Basal values of RBF, BP, and RVR in 3-OMG-pretreated STZR were identical to CR. The relative capacity of STZR and CR kidneys for vasodilatation in situ in response to intrarenal arterial infusions of acetylcholine (ACh) and bradykinin (BK) and systemically administered sodium nitroprusside (NP) was evaluated. The capacity of STZR to exhibit active renal vasodilatation in response to intrarenal arterial ACh and BK was significantly less than that of CR (P less than 0.01). The minimum level to which RVR was suppressed after 50 micrograms NP/kg iv was higher in STZR than in either CR or 3-OMG-pretreated STZR (14.8 +/- 1.5 vs. 9.0 +/- 0.7 and 9.3 +/- 1.5 mmHg.ml-1.min.g kidney wt, respectively; P less than 0.05). This dose of NP exerted effective functional antagonism of renal vasoconstriction induced by exogenous norepinephrine and angiotensin II. These in vivo studies suggest that the elevated RVR in STZR might be attributable in part to structural changes in the renal vasculature that are associated with the diabetic state and limit the capacity for renal vasodilatation. However, there was no difference in pressure-flow relationships between the two groups in maximally dilated isolated kidneys perfused with Krebs buffer containing 5% albumin, and the RBF deficit in STZR kidneys was corrected by perfusion with blood from CR. Thus the decreased RBF exhibited by STRZ in vivo cannot be attributed solely to renal vascular structural changes associated with diabetes. These findings suggest that undefined humoral factors or abnormal interaction of formed blood elements with vessel walls may account for elevated RVR in STZR.
Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs
Authors: Busija D. W. , Leffler C. W.
Published: December 2017

We examined effects of hypothermia on cerebral metabolic rate and cerebral blood flow in anesthetized, newborn pigs (1-4 days old). Cerebral blood flow (CBF) was determined with 15-micronS radioactive microspheres. Regional CBF ranged from 44 to 66 ml . min-1.100 g-1, and cerebral metabolic rate was 1.94 +/- 0.23 ml O2.100 g-1 . min-1 during normothermia (39 degrees C). Reduction of rectal temperature to 34-35 degrees C decreased CBF and cerebral metabolic rate 40-50%. In another group of piglets, we examined responsiveness of the cerebral circulation to arterial hypercapnia during hypothermia. Although absolute values for normocapnic and hypercapnic CBF were reduced by hypothermia and absolute values for normocapnic and hypercapnic cerebrovascular resistance were increased, the percentage changes from control in these variables during hypercapnia were similar during normothermia and hypothermia. In another group of animals that were maintained normothermic and exposed to two episodes of hypercapnia, there was no attenuation of cerebrovascular dilatation during the second episode. We conclude that hypothermia reduces CBF secondarily to a decrease in cerebral metabolic rate and that percent dilator responsiveness to arterial hypercapnia is unaltered when body temperature is reduced.
Interaction of hypoxia and hypercapnia on cerebral hemodynamics and brain electrical activity in dogs
Authors: McPherson R. W. , Eimerl D. , Traystman R. J.
Published: December 2017

The interaction of hypoxic hypoxia, hypercapnia, and mean arterial blood pressure (MABP) was studied in 15 pentobarbital-anesthetized ventilated dogs. In one group of animals (n = 5) hypercapnia [arterial CO2 partial pressure (PaCO2) approximately 50 Torr] was added to both moderate hypoxia and severe hypoxia. Moderate hypoxia [arterial O2 partial pressure (PaO2) = 36 mmHg] increased MABP and cerebral blood flow (CBF) without changes in cerebral O2 uptake (CMRO2). Superimposed hypercapnia increased CBF and MABP further with no change in CMRO2. In another group of animals (n = 5), a MABP increase of approximately 40 mmHg during moderate hypoxia without hypercapnia did not further increase CBF, suggesting intact autoregulation. Thus, during moderate hypoxia, hypercapnia is capable of increasing CBF. Severe hypoxia (PaO2 = 22 mmHg) increased CBF, but MABP and CMRO2 declined. Superimposed hypercapnia further decreased MABP and decreased CBF from its elevated level and further decreased CMRO2. Raising MABP under these circumstances in another animal group (n = 5) increased CBF above the level present during severe hypoxia alone and increased CMRO2. The change in CBF and CMRO2 during severe hypoxia plus hypercapnia with MABP elevation were not different from that severe hypoxia alone. We conclude that, during hypoxia sufficiently severe to impair CMRO2, superimposed hypercapnia has a detrimental influence due to decreased MABP, which causes a decrease in CBF and cerebral O2 delivery.
Influence of reduced red cell deformability on regional blood flow
Authors: Simchon S. , Jan K. M. , Chien S.
Published: December 2017

The effects of a reduction in red blood cell (RBC) deformability on regional blood flow and RBC distribution were studied in rats anesthetized with pentobarbital sodium. RBCs were subjected to minimum hardening by incubation in a very diluted solution of glutaraldehyde (0.025%). Normal and partially hardened RBCs, labeled with 51Cr or 111In, were injected into the femoral vein, while an equal volume of blood was simultaneously withdrawn from the femoral artery. Approximately 70% of the labeled, partially hardened RBCs disappeared from the circulating blood within 25 min after injection, compared with less than 2% of the labeled normal RBCs. The relative distribution of RBCs with reduced deformability to normal RBCs in tissues was determined from radioactivity counting; this ratio (mean +/- SD) was 7.95 +/- 0.85 in the spleen, 7.44 +/- 0.43 in the sternum, 7.10 +/- 1.09 in the lung, 4.54 +/- 0.31 in the liver, and 3.50 +/- 0.61 in the femur bone. The results indicate a significant degree of trapping of RBCs with reduced deformability in these regions. This ratio of relative distribution of RBCs with reduced deformability as compared with normal RBCs was 1.06 +/- 0.13 in the heart, indicating the absence of preferential trapping of RBCs with reduced deformability in this organ. Regional blood flows were determined with 15-microns microspheres in the control period and after infusion of RBCs with reduced deformability (experimental).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of adenosine in noradrenergic neurotransmission in spontaneously hypertensive rats
Authors: Jackson E. K.
Published: December 2017

The purpose of this study was to compare the in vivo role of adenosine as a modulator of noradrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto control rat (WKY). In the in situ blood-perfused rat mesentery, vascular responses to periarterial (sympathetic) nerve stimulation (PNS) and to exogenous norepinephrine (NE) were enhanced in SHR compared with WKY. In both SHR and WKY, vascular responses to PNS were more sensitive to inhibition by adenosine than were responses to NE. At matched base-line vascular responses, compared with WKY, SHR were less sensitive to the inhibitory effects of adenosine on vascular responses to PNS, but SHR and WKY were equally sensitive with respect to adenosine-induced inhibition of responses to NE. Antagonism of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine shifted the dose-response curve to exogenous adenosine sixfold to the right yet did not influence vascular responses to PNS or NE in either SHR or WKY. Furthermore, PNS did not alter either arterial or mesenteric venous plasma levels of adenosine in SHR or WKY, and plasma levels of adenosine in both strains were always lower than the calculated threshold level required to attenuate neurotransmission. It is concluded that in vivo 1) exogenous adenosine interferes with noradrenergic neurotransmission in both SHR and WKY; 2) SHR are less sensitive to the inhibitory effects of exogenous adenosine on noradrenergic neurotransmission than are WKY; 3) endogenous adenosine does not play a role in modulating neurotransmission in either strain under the conditions of this study; and 4) enhanced noradrenergic neurotransmission in the SHR is not due to defective modulation of neurotransmission by adenosine.
Beta-receptor-mediated increase in cerebral blood flow during hypoglycemia
Authors: Hollinger B. R. , Bryan R. M.
Published: December 2017

We tested the hypothesis that beta-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin (15 U/kg); normoglycemic control rats were given saline. Propranolol (1.5 mg/kg) was administered to some control and some hypoglycemic rats to block the beta-adrenergic receptors. Regional CBF was measured using 4-[N-methyl-14C]iodoantipyrine. Plasma glucose in the normoglycemic and hypoglycemic groups was approximately 6 and 1.4 mumol/ml, respectively. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied from approximately 60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. We conclude that beta-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia.
Acute resetting of arterial baroreflexes in hypertensive rats
Authors: Heesch C. M. , Carey L. A.
Published: December 2017

Acute baroreflex resetting was studied in one-kidney, one-clip renal hypertensive (HT) and normotensive (NT) control male Wistar-Kyoto rats. Systolic blood pressure (SBP) was monitored weekly in conscious rats by the indirect tail-cuff occlusion method. At the time of experimentation (4-6 wk after placement of the clip), SBP in the HT rats (238 +/- 9 mmHg) was elevated compared with NT rats (117 +/- 5 mmHg). Baroreflex control of lumbar sympathetic nerve activity (LSNA) was assessed in alpha-chloralose (120 mg/kg)-urethan (600 mg/kg)-anesthetized rats by raising and lowering mean arterial pressure (MAP) between 50 and 200 mmHg (phenylephrine and nitroprusside infusions). The baroreflexes of the hypertensive rats were less sensitive to increments in pressure compared with normotensive rats as evidenced by a decreased slope of the baroreflex curve (-0.396 +/- 0.064 HT vs. -0.637 +/- 0.042 NT). In both groups, curves were obtained before (control) and after (reset) base-line MAP was increased by 30-55 mmHg for 15 min. The MAP for 50% maximum inhibition of LSNA (EP50) was increased in both groups of rats after exposure to the elevated pressure (NT, control = 109 +/- 5.2, reset = 120 +/- 5.0 mmHg; HT, control = 114 +/- 6.5, reset = 131 +/- 10.0 mmHg) with no significant change in slope. There was no significant difference in degree of upward resetting between the two groups (NT, 21 +/- 4%; HT, 30 +/- 7%). Thus, although hypertensive rats exhibited the depressed baroreflex function associated with chronic resetting, the ability to reset acutely was maintained.
Changes in LV papillary muscle performance and myosin composition with aortic insufficiency in rats
Authors: Apstein C. S. , Lecarpentier Y. , Mercadier J. J. , Martin J. L. , Pontet F. , Wisnewsky C. , Schwartz K. , Swynghedauw B.
Published: December 2017

Aortic insufficiency was induced in rats. Left ventricular papillary muscle function was studied after 5, 12, and 40 wk and compared with the papillary muscles from sham-operated animals. The maximum unloaded velocity of shortening, Vmax, was decreased in the rats with aortic insufficiency relative to controls by 15, 20, and 34% at 5, 12, and 40 wk, respectively. The decrease in Vmax occurred concomitantly with a change in the myosin isoenzyme composition such that the V1 isoform content decreased and the V3 isoform increased. Relative to age-matched controls, the V3 content in the hearts with aortic insufficiency had increased by 80, 180, and 125% at 5, 12, and 40 wk, respectively. The decrease in Vmax in the aortic insufficiency group muscles correlated with the change in myosin isozyme composition and could not be explained by changes in collagen content. Thus aortic insufficiency induced changes in myosin isozyme content and Vmax similar to those previously observed with aortic stenosis, thus suggesting a common mechanism of myocardial adaptation to different types of mechanical overload.
Lesions of A1 noradrenergic cells affect AVP release and heart rate during hemorrhage
Authors: Head G. A. , Quail A. W. , Woods R. L.
Published: December 2017

The role of A1 noradrenergic cells of the ventrolateral medulla in the changes in mean arterial pressure (MAP), heart rate (HR), and plasma arginine vasopressin (AVP) after slow continuous hemorrhage (2% blood vol/min up to 35%) was examined by comparing responses in conscious rabbits before and 3 wk after a sham operation or A1 lesions. In the control experiments, MAP fell minimally up to the withdrawal of 20% of blood volume after which it fell abruptly to 20-30 mmHg below control by the 35% level. Plasma AVP increased nonlinearly during progressive hemorrhage with significant increases occurring only after 25% of blood volume was removed. In contrast, HR increased linearly after the onset of bleeding. After A1 lesions, which destroyed 84% (range 80-94%) of the noradrenergic cells, the amount of AVP released and the tachycardia during hemorrhage were reduced by 83 and 61%, respectively (P less than 0.005), but the fall in MAP was minimally affected. Basal values of MAP, HR, or plasma AVP were not affected by the lesions. These results suggest that during hemorrhage in conscious rabbits A1 noradrenergic neurons are important for the secretion of AVP and the reflex tachycardia but play little role in the maintenance of blood pressure.
Sarcolemmal Na+-Ca2+ exchange activity in hearts subjected to hypoxia reoxygenation
Authors: Dixon I. M. , Eyolfson D. A. , Dhalla N. S.
Published: December 2017

Although the occurrence of intracellular Ca2+ overload is known to be an important factor in hypoxia-reoxygenation injury, the exact mechanisms for this abnormality are not presently clear. Since Na+-Ca2+ exchange in the sarcolemmal membrane is considered to be involved in Ca2+ efflux, this study was undertaken to examine the effect of hypoxia reoxygenation on this system. Isolated rat hearts were made hypoxic by perfusing with a substrate-free medium gassed with 95% N2-5% CO2 and then reperfused with oxygenated normal medium. Hypoxia was found to markedly increase the resting tension and depress the ability of the heart to generate contractile force; reoxygenation resulted in partial recovery of these parameters. Sarcolemmal vesicles were isolated from control, hypoxic, and hypoxia-reoxygenated hearts, and the Na+-dependent Ca2+ uptake activity was measured at different times of incubation as well as at different concentrations of calcium. Sarcolemmal ATP-dependent Ca2+ accumulation was also measured for the purpose of comparison. A significant decrease in Na+-dependent Ca2+ uptake was observed in preparations from hearts made hypoxic for 10 min. Reoxygenation of 10-min hypoxic hearts resulted in a further depression of Na+-Ca2+ exchange activity. ATP-dependent Ca2+ accumulation was also depressed in hypoxic as well as reoxygenated hearts. These results suggest a defect in the Na+-Ca2+ exchange system and the ATP-dependent Ca2+ pump in the heart sarcolemmal membrane, and this may contribute to the occurrence of intracellular Ca2+ overload and functional abnormalities due to hypoxia-reoxygenation injury.
Differential vagal effects on antegrade vs. retrograde atrioventricular conduction
Authors: Mitsuoka T. , Mazgalev T. , Dreifus L. S. , Michelson E. L.
Published: December 2017

The influence of postganglionic vagal stimulation (PGVS) on antegrade and retrograde atrioventricular nodal conduction was studied in 17 isolated rabbit heart tissue preparations by pacing at the crista terminalis or His bundle, respectively. The effect of short bursts of PGVS on prolongation of atrioventricular conduction was phase dependent with respect to the cardiac cycle. This phasic dependency was more pronounced during antegrade atrioventricular conduction. Although the control retrograde atrioventricular conduction time was longer than the antegrade (P less than 0.05) at or near the time in the cycle during which vagal stimulation caused maximal prolongation of conduction time (optimal phase), PGVS-induced maximal prolongation of the antegrade atrioventricular conduction time was significantly greater than that of the retrograde (P less than 0.02). Moreover, when PGVS was introduced at a fixed phase in the cycle, but with increasing amplitude, antegrade atrioventricular conduction time was progressively prolonged, and block was observed first in the antegrade direction, whereas retrograde atrioventricular conduction continued. Microelectrode recordings during these experiments showed consistently that PGVS-induced hyperpolarization in the N region of the atrioventricular node was greater during antegrade atrioventricular conduction. This suggests that vagal effects depended not only on the intensity and phase of stimulation, but also on electronic influences which apparently are different during antegrade and retrograde conduction.
Electrophysiological derangements induced by lipid peroxidation in cardiac tissue
Authors: Nakaya H. , Tohse N. , Kanno M.
Published: December 2017

Recently it has been postulated that oxygen-derived free radicals may be involved in reperfusion-induced arrhythmias. This study was undertaken to evaluate cellular electrophysiological alterations produced by peroxidation of membrane lipids in isolated cardiac tissues. In retrogradely perfused guinea pig hearts, perfusion of organic hydroperoxides, cumene hydroperoxide (CH), and tert-butyl hydroperoxide (TBH) caused conduction disturbances and arrhythmias, concomitantly with an increase in malondialdehyde (MDA) content of the myocardium. The hydroperoxides decreased the maximum diastolic potential, action potential amplitude, and maximum upstroke velocity of phase 0 in both canine Purkinje fibers and guinea pig papillary muscles. They also induced abnormal automaticity, such as depolarization-induced automaticity, delayed afterdepolarizations, and triggered activity. Mechanical abnormalities including increased resting tension and aftercontractions, presumably resulting from intracellular Ca2+ overload, were produced by the hydroperoxides. Pretreatment with butylated hydroxytoluene, an antioxidant, significantly inhibited the hydroperoxide-induced electrophysiological derangements and MDA accumulation in the myocardium. These results suggest that lipid peroxidation of membranes causes various electrophysiological and mechanical abnormalities and may play a role in the genesis of reperfusion-induced arrhythmias.
Interactions in nucleus tractus solitarius between right and left carotid sinus nerves
Authors: Felder R. B. , Heesch C. M.
Published: December 2017

Bilateral carotid sinus nerve stimulation was used as a model for studying cardiovascular afferent interactions in the nucleus tractus solitarius (NTS) region of dorso-medial medulla. Extracellular action potential recordings were made from 69 single units, 33 of which were excited independently by both right and left carotid sinus nerves (CSNs). Fifteen of these were located in NTS. Peak latencies to electrical stimulation of NTS neurons were 17.7 +/- 2.1 ms to ipsilateral CSN and 20.9 +/- 1.5 ms to contralateral CSN. Summation of afferent input was routinely demonstrated. In 10 units in NTS, a conditioning stimulus applied to one CSN caused prolonged inhibition of the response to a test stimulus to the same or the other CSN. The duration of inhibition was dependent on the intensity of the conditioning stimulus, not on prior excitation of the unit by the conditioning stimulus. In five additional excitability testing experiments, we found limited evidence to suggest that primary afferent depolarization of the central fibers of one CSN by stimulation of the contralateral CSN might be contributing to this inhibitory interaction. The data suggest that the outcome of integrative interactions between right and left CSN inputs to NTS neurons may depend largely on the temporal sequence of convergent afferent impulses.
Relative importance of hypertension after coronary occlusion in chronic hypertensive dogs with LVH
Authors: Inou T. , Lamberth W. C. , Koyanagi S. , Harrison D. G. , Eastham C. L. , Marcus M. L.
Published: December 2017

We have shown that there was a 50% increase in infarct size and a threefold increase in the incidence of sudden death following coronary occlusion in dogs with hypertension and left ventricular hypertrophy (LVH). To further investigate this problem, we separated the effects of hypertension from those of LVH by decreasing arterial pressure either by renal anastomosis or intravenous administration of nitroprusside in dogs with chronic renal hypertension and LVH. In 123 conscious dogs, the circumflex coronary artery was acutely occluded. Hemodynamics were monitored, myocardial perfusion was measured with labeled microspheres, the risk area was defined by postmortem angiography, and infarct size was determined pathologically 48 h after occlusion. The incidence of sudden death following acute coronary occlusion decreased dramatically in dogs with LVH if the arterial pressure was decreased with either nitroprusside or renal anastomosis. In addition, if arterial pressure was decreased with nitroprusside or renal anastomosis, infarct size in dogs with LVH was not augmented. In conclusion, normotension induced by renal anastomosis or nitroprusside returned infarct size and the incidence of sudden death in dogs with chronic hypertension and LVH toward control values. Thus it is likely that hypertension, as opposed to LVH, is the critical factor responsible for the increase in infarct size and the high incidence of sudden death observed in dogs with hypertension and LVH following sudden coronary occlusion.
Ischemia- and agonist-induced changes in alpha- and beta-adrenergic receptor traffic in guinea pig hearts
Authors: Maisel A. S. , Motulsky H. J. , Ziegler M. G. , Insel P. A.
Published: December 2017

We have used radioligand binding techniques and subcellular fractionation to assess whether changes in expression of myocardial alpha 1- and beta-adrenergic receptors are mediated by a redistribution of receptors between various membrane fractions. Three fractions were prepared from the left ventricles of guinea pigs that underwent either 1 h of ischemia or injection of epinephrine (0.25 mg/kg ip): a crude membrane, a purified sarcolemma, and a light vesicle fraction. In control animals alpha 1-adrenergic receptors ([3H]prazosin binding) in light vesicles was only 25% of the total alpha 1-receptor density found in sarcolemmal and light vesicle fractions as compared with 50% for beta-adrenergic receptors ([125I]iodocyanopindolol binding sites). Although ischemia was associated with a 53% decrease in the number of light vesicle beta-adrenergic receptors and a 42% increase in the number of sarcolemma beta-receptors (P less than 0.05), there was no change in the number of light vesicle alpha 1-receptors, even though the number of sarcolemmal alpha 1-receptors increased 34%. Epinephrine treatment promoted internalization of beta-adrenergic receptors; sarcolemma beta-receptors decreased 37% and light vesicle beta-receptors increased 28% (P less than 0.025). For alpha 1-receptors, epinephrine treatment decreased the number of sarcolemmal receptors 41% (P less than 0.025) but failed to increase the number of receptors in the light vesicle fraction. The changes in receptor binding to beta-adrenergic receptors in sarcolemmal fractions were mirrored by parallel changes in isoproterenol-stimulated adenylate cyclase activity. These results indicate that alpha 1- and beta-adrenergic receptors may undergo a different cellular itinerary in guinea pig myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Polarity of arachidonic acid metabolism by bovine aortic endothelial cell monolayers
Authors: Shasby D. M. , Stoll L. L. , Spector A. A.
Published: December 2017

Monolayers of bovine aortic endothelial cells cultured on micropore filters were used to determine the polarity of endothelial uptake, release, and transfer of arachidonic acid and some of its metabolites. Uptake and spontaneous release of arachidonic acid were more rapid at the luminal than at the interstitial surface. Transfer of arachidonic acid was more rapid from the luminal to the interstitial compartment than from the interstitial to the luminal compartment. After stimulation with the ionophore A23187, monolayers released arachidonate metabolites, including prostacyclin, to both the luminal and the interstitial compartments. The ability of the endothelium to rapidly take up and release arachidonic acid from the luminal surface and the ability to release biologically active eicosanoids to both the lumen and interstitium could be important for endothelial modulation of vascular events.