bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha-adrenergic receptors on rat ventricular myocytes: characteristics and linkage to cAMP metabolism
Authors: Buxton I. L. , Brunton L. L.
Published: December 2017

When incubated with purified cardiomyocytes from adult rat ventricle, the alpha 1-antagonist [3H]prazosin binds to a single class of sites (8 X 10(4) per cell) with high affinity [dissociation constant (KD) = 82 pM]. Competition for [3H]prazosin binding by the alpha 2-selective antagonist yohimbine [inhibitor dissociation constant (KI) = 714 nM] and the nonselective alpha-antagonist phentolamine (KI = 168 nM) demonstrates that these receptors are of the alpha 1-subtype. In addition, incubation of myocyte membranes with [3H]yohimbine results in no measurable specific binding. Agonist competition for [3H]prazosin binding to membranes prepared from purified myocytes demonstrates the presence of two components of binding: 28% of alpha 1-receptors interact with norepinephrine with high affinity (KD = 36 nM), whereas the majority of receptors (72%) have a low affinity for agonist (KD = 2.2 microM). After addition of 10 microM GTP, norepinephrine competes for [3H]prazosin binding to a single class of sites with lower affinity (KD = 2.2 microM). Incubation of intact myocytes for 2 min with 1 microM norepinephrine leads to significantly less cyclic AMP (cAMP) accumulation (13.6 pmol/mg) than stimulation with either norepinephrine plus prazosin or isoproterenol (18 pmol/mg). Likewise, incubation of intact myocytes with 10(-6) M norepinephrine leads to significantly less activation of cAMP-dependent protein kinase (71 +/- 4%) than when myocytes are stimulated by both norepinephrine and the alpha 1-adrenergic antagonist, prazosin (95 +/- 1%), or the beta-adrenergic agonist, isoproterenol (100%).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of leukocytes in response to acute myocardial ischemia and reflow in dogs
Authors: Engler R. L. , Dahlgren M. D. , Morris D. D. , Peterson M. A. , Schmid-Schonbein G. W.
Published: December 2017

Recent evidence indicates that leukocytes (LEU) are large, stiff, viscous cells that naturally adhere to vascular endothelium. Their broad role in the early myocardial microvascular response to acute ischemia was suggested by 1) the role of leukocyte capillary plugging in the no-reflow phenomenon, 2) resistance increases in skeletal muscle with LEU infusions, and 3) salvage of ischemic myocardium by anti-LEU agents. We perfused the coronary circulation under matched, controlled conditions with whole blood or granulocyte-depleted whole blood. During 1 h of ischemia (left anterior descending occlusion) circumflex perfusion pressure was servocontrolled to a constant value. In whole blood-perfused hearts, flow measured by the radiolabeled microsphere method decreased in endocardium from 0.12 +/- 0.05 at 5 min of ischemia to 0.09 +/- 0.04 ml X min-1 X g-1 at 60 min of ischemia and in epicardium from 0.27 +/- 0.17 to 0.21 +/- 0.16 ml X min-1 X g-1, both P less than 0.05. In granulocyte-depleted blood-perfused hearts, flow increased over the same period from 0.18 +/- 0.15 to 0.29 +/- 0.18 ml X min-1 X g-1 in endocardium (P less than 0.05) and did not change significantly in epicardium (0.36 +/- 0.22 to 0.41 +/- 0.24 ml X min-1 X g-1). The LEU-depleted blood perfusate contained less than 33 granulocytes/microliter, whereas control perfusate contained 4,265/microliter. Reperfusion at normal pressures with carbon suspension allowed for histologic evaluation of the no-reflow phenomenon. With whole blood perfusion the no-reflow phenomenon in the endocardium was present with 27% of capillaries occluded, compared with nearly complete reperfusion in LEU-depleted animals (1% of capillaries occluded, P less than 0.05). Furthermore, LEU depletion prevented the increases in tissue water content seen in control hearts and decreased the incidence of ventricular arrhythmias. These studies demonstrate the significant participation of granulocytes in the unfavorable responses of flow, edema formation, and arrhythmias to the 1st h of myocardial ischemia and further document their role in the no-reflow phenomenon.
Cardiac autonomic efferent activity during baroreflex in puppies and adult dogs
Authors: Hageman G. R. , Neely B. H. , Urthaler F.
Published: December 2017

Blood pressure and heart rate were recorded in 15 anesthetized puppies (6-10 wk, 1-6 kg) and 18 adult mongrel dogs (greater than 1 yr, 18-26 kg) before and during acute blood pressure changes achieved with nitroglycerin or phenylephrine (4 and 8 micrograms/kg iv). Overall heart rate responses to blood pressure changes in adults were significantly (P less than 0.05) greater than those in puppies. Following control baroreflex responses, two multifiber efferent preparations from the discrete thoracic cardiac nerves (sympathetic, n = 48; parasympathetic, n = 18) were simultaneously recorded and analyzed by microprocessor. Severing of the nerves significantly attenuated the heart rate responses to blood pressure changes in puppies only, suggesting less redundancy of the neural regulation of the sinus node in the puppy. The pressure-induced reflex changes in the sympathetic or parasympathetic efferent nerve activities were not significantly different between adult dogs and puppies. There were no significant differences in reflex activities in right-sided (n = 29) vs. left-sided (n = 19) sympathetic nerves in either puppies or adult dogs. Preganglionic sympathetic fibers in puppies (but not adult dogs) were more responsive to blood pressure changes than were postganglionic sympathetic fibers. Thus baroreceptor reflex control in the puppy is less developed than in the adult canine heart, and the maturational difference in neural regulation of the heart is at or beyond the efferent nerve terminals.
Effects of leukotriene C4 on the cerebral microvasculature
Authors: Mayhan W. G. , Sahagun G. , Spector R. , Heistad D. D.
Published: December 2017

Leukotriene C4, which is synthesized during cerebral ischemia, may contribute to disruption of the blood-brain barrier. The purpose of this study was to determine whether leukotriene C4 constricts cerebral arterioles and disrupts the blood-brain barrier. We used intravital fluorescent microscopy in hamsters and compared responses of vessels in the cerebrum with vessels in the cheek pouch. Increases in permeability of the cheek pouch and disruption of the blood-brain barrier were quantitated after superfusion with leukotriene C4 (0.3, 3.0, and 30 nM) by the formation of microvascular leaky sites. Changes in diameter of arterioles in the cheek pouch and cerebrum also were examined. In the cheek pouch, leukotriene C4 produced a dose-related decrease in diameter of arterioles (maximum = 40 +/- 8%; mean +/- SE) and an increase in microvascular permeability (maximum = 16 +/- 2 leaky sites). In contrast, in the cerebrum, leukotriene C4 produced only modest constriction of arterioles (maximum = 12 +/- 5%) and minimal disruption of the blood-brain barrier (maximum = 2 +/- 1 leaky sites). Thus the findings indicate that leukotriene C4, in contrast to its potent vasoconstrictor effects and increase in permeability in the hamster cheek pouch, produces only modest cerebral vasoconstriction and minimal disruption of the blood-brain barrier.
Contribution of area postrema to pressor actions of angiotensin II in dog
Authors: Otsuka A. , Barnes K. L. , Ferrario C. M.
Published: December 2017

To generate quantitative data on the contribution of the area postrema (AP) to the pressor activity of angiotensin II (ANG II), the peptide (7 ng X kg-1 X min-1) was infused intravenously in 10 conscious dogs for 6 h before, and several weeks after, AP lesion. Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously, and plasma renin activity (PRA), ANG II immunoreactivity (ANG II-IR), aldosterone (ALDO), arginine vasopressin (AVP), norepinephrine (NE), epinephrine (EPI), and serum Na+ and K+ were measured at 3 and 6 h. Three hours into the infusion, MAP averaged 123 +/- 2 compared with 96 +/- 2 mmHg for controls (P less than 0.01). The increases in pressure were associated with unchanged HR, but increased lability of MAP and HR. PRA fell, whereas plasma levels of ANG II-IR and ALDO rose. Plasma levels of AVP, NE, serum Na+ and K+ did not change, but plasma EPI was significantly elevated at 6 h. Removal of the AP produced mild hypotension and decreased lability. Within 8 to 21 days after AP ablation, a significant decrease in the plateau phase (3-6 h) of the ANG II pressor response was recorded in all dogs. The attenuation of the pressor effects was not sustained, since 4-7 wk after AP lesion, the increases in pressure were equivalent to those obtained during the control period. These data indicate that the AP participates in the production of the pressor response to intravenous infusion of ANG II in conscious dogs. However, in the absence of this structure, alternative mechanisms are brought into play to restore the loss of its function.(ABSTRACT TRUNCATED AT 250 WORDS)
Estimation of total arterial compliance: an improved method and evaluation of current methods
Authors: Liu Z. , Brin K. P. , Yin F. C.
Published: December 2017

Determination of arterial compliance in vivo has long interested physiologists. Most current methods for estimating this parameter assume that compliance is constant, i.e., that arterial pressure-volume (P-V) relations are linear, and they also assume that diastolic aortic pressure decay is an exponential function of time. Both of these assumptions, however, are questionable. This study proposes improved methods of estimating compliance based on a Windkessel model of the arterial system but which utilize the area under the pressure tracing rather than the waveform itself. Formulations accounting for both linear and three hypothetical nonlinear arterial P-V relations (exponential, logarithmic, and parabolic) are presented. Data from patients with congestive heart failure and hypertension are used for illustration. Compliances assuming linear P-V relations are reasonably close to those assuming nonlinear P-V relations only at mean aortic pressure. At end-diastolic pressure the linear assumption underestimates and at peak systolic it overestimates the compliances obtained assuming nonlinear P-V relations. The simpler linear assumption still allows a first approximation to compliance, but we show that existing methods for obtaining compliance under this assumption have severe theoretical as well as practical shortcomings. Our proposed method avoids these shortcomings primarily because deviations from an exact exponential form of the pressure wave have less influence on these compliance estimates than currently used methods.
Myocardial mechanics in allylamine-induced myocardial fibrosis
Authors: Nakamura Y. , Wiegner A. W. , Aslanis J. T. , Apstein C. S. , Bing O. H.
Published: December 2017

To examine the effect of fibrosis on myocardial mechanics, we studied isolated left ventricular papillary muscles from 18 rats given 0.1% allylamine, an agent known to cause myocardial fibrosis, in drinking water for 4-8 wk. Six control rats were given tap water. Left ventricular hydroxyproline concentration was higher in the allylamine-treated group [3.47 +/- 2.12 vs. 2.10 +/- 0.66 (SD) micrograms/mg dry wt; P less than 0.01]. Because of variable and heterogeneous involvement of the ventricle by fibrosis, preparations from allylamine-fed rats were divided into two subgroups; data from four papillary muscles with more than 25% fibrosis by point counting (AL-B group) were compared with eight control muscles from nonallylamine-treated rats. A third subgroup of nine muscles from allylamine-treated rats but with normal left ventricular hydroxyproline concentration and fibrosis as determined by point counting served as another control group (AL-A) for the evaluation of effects of allylamine not due to fibrosis. Myocardial fiber diameters of AL-B preparations were significantly larger than other groups (controls, 12.1 +/- 1.7 microns; AL-A group, 12.7 +/- 1.7 microns; AL-B group, 18.0 +/- 1.2 microns; P less than 0.01). Passive and active stiffness constants in AL-B muscles were significantly increased compared with control and AL-A preparations (P less than 0.05). Electromechanical delay plus time to peak tension and the time for tension to fall from its peak to one-half of that value at the peak of the length-tension curve were significantly prolonged in AL-B muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Clearance of human platelet factor 4 by liver and kidney: its alteration by heparin
Authors: Rucinski B. , Knight L. C. , Niewiarowski S.
Published: December 2017

Human 125I-labeled platelet factor 4 (PF4) injected into rabbits showed a biphasic exponential pattern of disappearance from the circulation [half-life of the fast components was 0.75 min, that of the slow components was 20 min] that was not affected by a 1,000-fold excess of unlabeled PF4. Heparin resulted in a single-compartment disappearance of 125I-labeled PF4 (half-life = 25-40 min). Five minutes after injection of 125I-labeled PF4 greater than 40% radioactivity had accumulated in the liver and 4% in the kidney. At that time, accumulation of 125I-labeled beta-thromboglobulin (beta-TG) in the organs was low, approximately 4% in the kidneys and less than 3.0% in the liver. Nuclear imaging studies revealed rapid clearance of 131I-labeled PF4 from blood and its predominant accumulation in the liver. The half-lives of 131I-labeled PF4 radioactivity in liver and kidney were 96 and 252 min, fitting a single-compartment model. 131I-labeled beta-TG accumulated predominantly in the kidney. The half-lives of 131I-labeled beta-TG radioactivity in the kidney and in the liver were 84 and 414 min. Simultaneous or subsequent injection of heparin did not affect the distribution of 131I-labeled beta-TG but caused partial loss of 131I-labeled PF4 radioactivity from the liver and accelerated its appearance in the urinary bladder. Injection of heparin resulted in a 100-fold increase of excretion in the urine of 125I-labeled Pf4 precipitable by 10% trichloroacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Prostanoid mediation of pulmonary vascular response to acetylcholine in rabbits
Authors: el Kashef H. A. , Catravas J. D.
Published: December 2017

We studied the effects of acetylcholine (ACh) in the anesthetized, open-chest rabbit. ACh (5-20 nmol/kg), administered as a bolus into the right jugular vein, produced a dose-dependent increase in both pulmonary arterial pressure and pulmonary vascular resistance but a decrease in systemic arterial pressure and pulmonary blood flow. All these effects were prevented by atropine. Pretreatment with the phospholipase A2 inhibitor quinacrine reduced the pulmonary vascular responses to ACh without affecting systemic arterial pressure. Similarly, treatment with the cyclooxygenase inhibitors indomethacin or meclofenamate completely eliminated the pulmonary vascular response to ACh without affecting systemic arterial pressure or pulmonary blood flow. Treatment with the lipoxygenase inhibitor nordihydroguaiaretic acid, however, had no effect on the pulmonary or systemic vascular responses to ACh. Furthermore, administration of the thromboxane A2 synthetase inhibitor 7-(1-imidazolyl)-heptanoic acid or the thromboxane A2 receptor antagonist SQ 29,548 completely eliminated the pulmonary vascular responses to ACh without affecting systemic arterial pressure or pulmonary blood flow. Plasma levels of immunoreactive thromboxane B2 increased after ACh, in the absence but not in the presence of the thromboxane A2 synthetase inhibitor. The results of the present study indicate that in the rabbit ACh has opposite actions in the systemic (dilatory) versus pulmonary (constrictor) circulation, arachidonic acid metabolites mediate the pulmonary but not the systemic vascular response to ACh, and thromboxane A2 appears to mediate the pulmonary vasoconstrictor response to ACh.
Modeling ion channel blockade at guarded binding sites: application to tertiary drugs
Authors: Starmer C. F. , Courtney K. R.
Published: December 2017

Excitable membranes exposed to sodium channel blocking agents (D; local anesthetics and antiarrhythmic drugs) show a progressive reduction of peak sodium current when repetitively depolarized (use dependence). Thus, with repetitive excitation, use dependence reflects a net rightward shift in the balance between unblocked channels (U) and blocked channels (B): U + D in equilibrium with B. The modulated receptor hypothesis (a 7-parameter model) has been proposed to account for this shift and is based on a channel lumen binding site whose affinity varies with channel state and where drug-complexed channels exhibit modified inactivation gate kinetics. Alternatively, we consider use-dependent binding as the result of transient access to a constant-affinity binding site. In this setting, the channel gate conformation is viewed as controlling the flux of drug as it diffuses between drug pools and the binding site. Apparent variation in binding rates is therefore considered the result of variations in the fraction of accessible sites. This guarded receptor hypothesis, with three fewer parameters, is able to predict apparent changes in channel binding and apparent shifts in channel inactivation without incorporating modified gating parameters in drug-complexed channels. Furthermore, with this model one is able to characterize both relaxation kinetics and channel blockade associated with tertiary amines as well as hydrophobic and hydrophilic agents. The pH dependence of repriming rates is utilized to estimate several of the important parameters associated with this simplified hypothesis.
End-systolic and end-diastolic ventricular interaction
Authors: Slinker B. K. , Glantz S. A.
Published: December 2017

Right ventricular volume affects left ventricular volume via direct interaction across the interventricular septum and series interaction because the right and left hearts are connected in series through the lungs. Because it is difficult to sort out complex physiological mechanisms in the intact circulation, the relative importance of these two effects is unknown. We used statistical analyses of transient changes in left and right ventricular pressures and dimensions following pulmonary artery and venae caval constrictions to separate and quantitate the direct (immediate) from the series (delayed) interaction effects on left ventricular size at end systole and end diastole. With the pericardium closed, direct interaction was one-half as important as series interaction at end diastole and was one-third as important at end systole. With the pericardium removed, direct interaction was one-fifth as important as series interaction at end diastole and one-sixth as important at end systole. These results suggest that differences between transient and steady-state end-systolic pressure-volume relationships are largely explained by direct interaction and that direct end-systolic interaction is important for maintaining balanced right and left heart outputs.
The quiescent heart: excitability, compliance, and vascular resistance
Authors: Feinberg H. , Levitsky S. , Lee S. L.
Published: December 2017

A rat heart, perfused via the aorta and fitted with a balloon in the left ventricle, was rendered quiescent by a local injection of lidocaine into the region of the atrioventricular node. Once quiescence was established it was extended by injection of formaldehyde into the same site via a coaxial needle. The quiescent heart (QH) was responsive to electrical stimulation and exhibited the same isovolumic pressure development as seen during spontaneous beating. Over a range of ventricular volume, slightly greater left ventricular pressures were found in the QH as compared with the diastolic pressure at the same ventricular volumes in the beating heart (BH). Left ventricular diastolic pressures in the QH were less than those found in the KCl-arrested heart. The QH perfused at constant flow rate with a syringe pump exhibited a constant perfusion pressure. Infusion of vasopressin induced a dose-related increase in perfusion pressure, whereas adenosine or sodium nitroprusside reduced the perfusion pressure. The QH appears to be a useful preparation for the study of vascular resistance free of cyclical intramyocardial pressure and relatively uninfluenced by vasoactive metabolites arising from contracting muscle.
Influence of endurance training on glucose transport and uptake in rat skeletal muscle
Authors: Idstrom J. P. , Elander A. , Soussi B. , Schersten T. , Bylund-Fellenius A. C.
Published: December 2017

The paired tracer-dilution method applied to the rat hindlimb perfusion technique was used to investigate the effect of a 10-wk treadmill training program on glucose transport and net uptake in rat skeletal muscles. Glycolytic and oxidative marker enzyme activities were determined. The rats were allowed to rest for 2 days before the experiments were carried out, since long-term adaptive changes were to be studied. The endurance training program caused a 30% increase in the 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activities, but no changes in glycolytic enzymes, confirming that endurance training provokes an increase in the oxidative capacity of the muscle. No significant differences were found in glucose transport rate or net glucose uptake between trained and sedentary rats, which indicates that no long-term adaptive changes in glucose utilization occur in response to endurance training.
Collagen metabolism during right ventricular hypertrophy following induced lung injury
Authors: Turner J. E. , Oliver M. H. , Guerreiro D. , Laurent G. J.
Published: December 2017

Collagen synthesis and degradation rates were estimated in ventricles of normal rabbits and in those with right ventricular hypertrophy resulting from bleomycin-induced lung injury. Synthesis rates were estimated from the radioactivity in tissue [14C]hydroxyproline following a single intravenous injection of [14C]proline with a "flooding" dose of unlabeled proline (Biochem. J. 206: 535-544, 1982). The rate in the left ventricle was 5.8 +/- 1.0 compared with 2.9 +/- 0.4%/day in the right (P less than 0.02). Degradation rates, based on [14C]hydroxyproline levels in the tissue-free pool, indicated that in both normal ventricles about one-third of newly produced collagen was degraded rapidly following its synthesis. Six days after bleomycin, right ventricular collagen content fell by 35%, associated with a marked increase in tissue-free hydroxyproline levels. After 14 days the right ventricular weight and collagen content had increased by 49.4 +/- 3.7% (P less than 0.001) and 31.7 +/- 4.4% (P less than 0.05), respectively, and collagen synthesis rates increased to 9.7 +/- 1.8%/day (P less than 0.001). It is concluded that collagen is synthesized and degraded quite rapidly in normal heart tissue but that fractional rates differ between ventricles. The evidence also suggests that increased collagen synthesis and breakdown of mature collagen occurs as the connective tissue matrix is remodeled during adaptive cardiac growth.
Altered aortic reactivity and lowered blood pressure associated with high calcium intake
Authors: Bukoski R. D. , McCarron D. A.
Published: December 2017

The hypothesis that dietary calcium (dCa) alters functional properties of aortic smooth muscle in the spontaneously hypertensive rat (SHR) was tested. At 6 wk of age, Wistar Kyoto (WKY) and (SHR) rats were placed on a control diet containing 1% Ca. The experimental SHR group received a 2%-calcium diet. After an average of either 8 or 15 wk on the diets (WOD), aortic rings were prepared for measurement of passive elastic properties and isometric force development. Differences in blood pressure (BP) were not apparent until after 8 WOD when the BP of SHRs on 2% dCa were 10-15 mmHg lower than SHRs on 1% dCa (P less than 0.05). After 8 WOD, when the BP effect first emerged, no significant differences in aortic properties were observed between the SHR groups. However, after 15 WOD, aortas of SHRs on 2% dCa were more compliant than those of SHRs on 1% dCa and between 8 and 15 WOD the sensitivity to KCl decreased in aortas from the WKY group and the SHRs on 2% dCa, but not the SHR-1% dCa group (mean effective dose went from 14.4 +/- 0.4 to 18.5 +/- 0.9 mM for WKY and from 13.6 +/- 0.6 to 17.1 +/- 1.2 mM for SHRs on 2% dCa, P less than 0.05). In addition, between 8 and 15 WOD, a significant decrease in response to a calcium (Ca2+) challenge after removal of K+ and Ca2+ occurred in aortas of the SHRs on 2% dCa, but not in the control diet groups, indicating that a decrease in aortic reactivity was present in the Ca2+-supplemented SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Beat-by-beat modulation of AV conduction. II. Autonomic neural mechanisms
Authors: Warner M. R. , deTarnowsky J. M. , Whitson C. C. , Loeb J. M.
Published: December 2017

We examined the mechanism by which autonomic neural activity associated with respiration and blood pressure modulates atrioventricular (AV) conduction in conscious dogs. Mongrel dogs were anesthetized and instrumented under sterile conditions to record atrial and ventricular electrograms and blood pressure. In the conscious state, electrocardiogram (ECG), respiration, blood pressure, and electrograms were recorded continuously, and heart rate and AV interval were plotted graphically as a function of time. To delineate the role(s) of sympathetic and parasympathetic activity, AV conduction was studied during abrupt and linear changes in heart rate after administration of atropine, propranolol, or both. In the basal state and after propranolol, AV interval oscillated with respiration both in the absence of atrial pacing and at pacing rates 10–100 beats/min above control. Following atropine, oscillations in AV interval associated with respiration were abolished; however, linear and abrupt heart rate increases resulted in AV conduction changes that were associated with fluctuations in blood pressure. In contrast, after both atropine and propranolol, alterations in blood pressure or respiration did not influence AV conduction and rate-dependent prolongation of AV conduction occurred. We conclude that in the basal state, AV conduction is influenced predominately by changes in parasympathetic activity which is the major determinant of respiratory-related AV interval oscillations; after atropine, sympathetic activity produces fluctuations in both AV conduction and blood pressure; and intrinsic rate-dependent properties of the AV node are modulated continually by both divisions of the autonomic nervous system.
Disruption of the blood-brain barrier in cerebrum and brain stem during acute hypertension
Authors: Mayhan W. G. , Faraci F. M. , Heistad D. D.
Published: December 2017

The purpose of this study was to examine hemodynamic mechanisms of protection of the blood-brain barrier in the brain stem during acute hypertension. We used a new method to examine the microcirculation of the brain stem. Intravital fluorescent microscopy and fluorescein-labeled dextran were used to evaluate disruption of the blood-brain barrier during acute hypertension in rats. During control conditions, pressure (servo null) in arterioles (60 microns in diameter) was 50 +/- 2% (mean +/- SE) of systemic arterial pressure in the cerebrum and 67 +/- 1% of systemic arterial pressure in the brain stem (P less than 0.05 vs. cerebrum). In the cerebrum, pial venous pressure increased from 7 +/- 1 to 25 +/- 2 mmHg during acute hypertension, and there was marked disruption of the blood-brain barrier in venules (26 +/- 2 leaky sites). In contrast, in the brain stem, pial venous pressure increased from 4 +/- 1 to only 8 +/- 1 mmHg (P less than 0.05 vs. cerebrum), and there was minimal disruption of the blood-brain barrier in venules (1.5 +/- 0.6 leaky sites, P less than 0.05 vs. cerebrum). During acute hypertension, increases in blood flow (microspheres) were less in brain stem than in cerebrum. The findings suggest distribution of vascular resistance differs in the brain stem and cerebrum under control conditions, whereas large arteries account for a greater fraction of resistance in cerebrum; pial venous pressure increases less in brain stem than cerebrum during acute hypertension, so that the blood-brain barrier is protected.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of vasodilator stimuli on resistance of large and small cerebral vessels
Authors: Tamaki K. , Mayhan W. , Heistad D.
Published: December 2017

We have examined effects of vasodilator stimuli on segmental resistance in the cerebral circulation. Our hypothesis was that resistance of large arteries, as well as small vessels, contributes to cerebral vascular responses to vasodilator stimuli. We measured cerebral blood flow with microspheres in anesthetized rabbits and measured pressure in pial arteries approximately 100 microns diameter using a servo-null method. These values were used to calculate resistance of large arteries (greater than 100 microns diameter) and small vessels (less than 100 microns diameter). Under control conditions, resistance of large arteries accounted for one-third to one-half of total cerebral vascular resistance. Intracarotid infusion of acetylcholine (1 microgram/min) reduced large arterial resistance by 69% and small vessel resistance by 58%. Adenosine also produced marked reductions in resistance of both large and small cerebral vessels. In contrast, seizures reduced large arterial resistance by 50% and small vessel resistance by 85%. Pial arterial pressure, which depends on the ratio of large and small vessel resistance, increased during infusion of acetylcholine and adenosine, but decreased during seizures. We conclude that both large and small cerebral vessels are responsive to acetylcholine and adenosine, and seizures produce preferential reduction in resistance of small vessels.
Whole-blood red blood cell aggregometer for human and feline blood
Authors: Tomita M. , Gotoh F. , Tanahashi N. , Turcani P.
Published: December 2017

A whole-blood aggregometer of red blood cells (RBC) is described. It consists of a transparent 0.26-cm ID vinyl tube of approximately 30 cm in length containing freshly drawn heparinized blood and a densitometer head that is attached to the tube. The densitometer head consists of an infrared light source of gallium arsenide and a light detector (silicon photodiode) to monitor changes in optical density of the blood in the tube. The tube and densitometer head were installed in a temperature-controlled box at 37 degrees C. The blood in the tube was first subjected to rapid flow with a solenoid so that the wall shear rate of the blood was approximately 500 s-1. The shear gave rise to a rapid increase in optical density of the blood due to dispersion of the blood corpuscles. The blood was then brought abruptly to a full stop. After the flow had stopped the densitometer head revealed a gradual decrease in optical density in association with RBC aggregate formation. The resultant pattern was termed by us an “RBC aggregogram.” The RBC aggregogram exhibited an exponential decay in its initial part, which was followed by an asymptotic decrease. A simple mathematical procedure was employed to calculate the rate constant of the initial decrease from the two values on the RBC aggregogram at 10 and 20 s. The rate constant k10 was 0.192 +/- 0.028 (5.2 s as time constant; 3.6 s as half time) for feline blood and 0.129 +/- 0.012 (7.7 s as time constant; 5.3 s as half time) for human blood. The RBC aggregation rate varied linearly with the hematocrit below 40%.
Left ventricular pump function in renal hypertensive dogs with cardiac hypertrophy
Authors: Broughton A. , Korner P. I.
Published: December 2017

We compared open-chest left ventricular (LV) pump performance after autonomic blockade under controlled loading conditions in normal dogs and in dogs where chronic renovascular hypertension had produced moderate concentric LV hypertrophy (LVH). Mean LV pressure (MLVP) provided a measure of ventricular load independent of vascular properties. We found an inverse relationship between MLVP and cardiac index (CI) in both groups when peripheral resistance was altered at constant left atrial pressure. However, CI declined significantly less in LVH hearts as MLVP was increased. The slope of the linear MLVP-CI plot (LV source resistance) was 1.91 times the value observed in normal dogs. LVH hearts developed more steady-flow external power than their normal counterparts, and the power optimum was reached at a much higher mean arterial pressure. Isovolumic maximum rate of LVP rise was 1.28 times higher in LVH than normal dogs (P less than 0.01) in proportion to the increase in wall thickness. Our results suggest that additional muscle with normal contractile properties and greater emptying due to the increased wall-to-lumen ratio accounted for the increased pump performance in LVH.
Genetic basis for altered vascular responses to ouabain and potassium-free solution in hypertension
Authors: Bruner C. A. , Myers J. H. , Sing C. F. , Jokelainen P. T. , Webb R. C.
Published: December 2017

Many properties intrinsic to vascular smooth muscle are altered in hypertension. It is unknown whether these abnormalities are primary traits that may contribute to the etiology of hypertension or whether these vascular differences between the hypertensive and normotensive strains are inherited independently of genetic factors that predispose to hypertension. To determine if genetic factors responsible for the predisposition for hypertension may be the same as or linked to genetic factors determining a specific vascular response, adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and progeny of genetic crosses of SHRSP and WKY rats (F1, F2, F1 X WKY, F1 X SHRSP) were studied. Rats were killed and helical aortic strips were mounted in a tissue bath for isometric force recording. Contractile responses to 10(-3) M ouabain (expressed as a percent of force generated to a maximal depolarizing stimulus) were greater in aortas from SHRSP (90 +/- 9%) compared with aortas from WKY rats (38 +/- 5%, P less than 0.05). The half time for contraction in K+-free solution was more rapid in aortas from SHRSP (21 +/- 4 min) when compared with aortas from WKY rats (48 +/- 4 min, P less than 0.05). A significant positive correlation between blood pressure (tail-cuff method) and the contractile response to 10(-3) M ouabain was observed in the segregating F2 progeny. In contrast, no correlation between blood pressure and the half time for contraction in K+-free solution was observed in the segregating F2 progeny.(ABSTRACT TRUNCATED AT 250 WORDS)
Integrated cardiac and peripheral vascular response to atriopeptin 24 in conscious dogs
Authors: Shapiro J. T. , DeLeonardis V. M. , Needleman P. , Hintze T. H.
Published: December 2017

Little attention has been directed toward the action of atrial peptides on integrated cardiovascular function. In conscious dogs intravenous injection of atriopeptin 24 (10 micrograms/kg) reduced mean arterial pressure (11 +/- 3.2%), mean left atrial pressure (32 +/- 8.6%), left ventricular (LV) end-diastolic pressure (24 +/- 4.3%), and increased heart rate (25 +/- 6.2%). LV dP/dt and stroke volume increased 17 +/- 4.0 and 12 +/- 3.3%, respectively. Cardiac output increased 39 +/- 6.3%. These effects were only acute, lasting less than 10 min. The tachycardia and increase in LV dP/dt were abolished by combined beta-adrenergic and muscarinic cholinergic blocking agents. During an infusion of atriopeptin 24 (10 micrograms X kg-1 X min-1) blood flow, as measured with radioactive microspheres, increased to both the left (101 +/- 35%) and right kidney (122 +/- 37%) and to the spleen (140 +/- 50%). However, blood flow to the stomach, large and small intestine, pancreas, liver, and skeletal muscle did not change, indicating the selectivity of the atriopeptin. Blood flow in the right ventricle, septum, and in all layers of the left ventricle increased slightly, resulting in no change in the endocardial-to-epicardial blood flow ratio most likely due to the changes in myocardial function, i.e., heart rate and stroke volume. Thus, in conscious dogs, atriopeptins increase myocardial performance most likely indirectly secondary to baroreflex unloading after the direct hypotensive effects of atriopeptin 24. This serves to increase cardiac output at a time when renal and splenic blood flows are increased.
Phase resetting of spontaneously beating embryonic ventricular heart cell aggregates
Authors: Guevara M. R. , Shrier A. , Glass L.
Published: December 2017

The influence of isolated 20-ms duration current pulses on the spontaneous rhythm of embryonic chick ventricular heart cell aggregates was studied. A pulse could either delay or advance the time of occurrence of the next action potential, depending on whether it fell early or late in the cycle. As the stimulus amplitude was increased, the transition from delay to advance occurred over a narrower range of coupling intervals. At low-stimulus amplitudes the transition from delay to advance occurred in a smooth continuous fashion; at medium-stimulus amplitudes the transition was discontinuous; at high-stimulus amplitudes graded action potentials were seen. It was impossible to annihilate spontaneous activity in aggregates with a single stimulus. The phase-resetting response to hyperpolarizing pulses was qualitatively the reverse of that produced by depolarizing pulses. A very high-amplitude depolarizing or hyperpolarizing pulse could produce rapid repetitive activity. Theoretical aspects of these phenomena are discussed.
Four brief periods of myocardial ischemia cause no cumulative ATP loss or necrosis
Authors: Reimer K. A. , Murry C. E. , Yamasawa I. , Hill M. L. , Jennings R. B.
Published: December 2017

The effect of repetitive periods of coronary occlusion on myocardial adenine nucleotides, lactate, and infarct size was studied. In one series of dogs, the circumflex artery was occluded for one, two, or four 10-min episodes, each separated by 20 min of reperfusion. Hearts were excised and sampled for metabolic assays after one or more periods of ischemia before or after reperfusion. One 10-min period of ischemia caused a 61% loss of ATP and 41% loss of adenine nucleotides from the most severely ischemic subendocardial zone. Reperfusion resulted in rapid restoration of the adenylate charge but in only slight repletion of the adenine nucleotide pool. However, two or even four 10-min periods of ischemia caused no further adenine nucleotide loss. In contrast, 40 min of continuous coronary occlusion caused an 87% depletion of ATP and 67% of the adenine nucleotide pool from the same subendocardial region. Collateral blood flow was similar during all occlusions, but lactate accumulation was less during later occlusions. In a second series of experiments, myocardial necrosis was quantitated 4 days after four 10-min periods of ischemia. Necrosis was observed in only one of six dogs and, in this dog, was only 1.5% of the anatomic area at risk. Thus intermittent reperfusion prevents cumulative metabolic deficits and myocardial ischemic cell death, perhaps by restoring the capacity for high-energy phosphate (HEP) production and/or washing out deleterious catabolites. A first episode of ischemia also slows HEP utilization in subsequent episodes.
Interdependency of local capillary density, blood flow, and metabolism in rat brains
Authors: Klein B. , Kuschinsky W. , Schrock H. , Vetterlein F.
Published: December 2017

Previous investigations have established a strong correlation between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). In the present study the relationship between density of perfused brain capillaries and LCBF or LCGU was investigated in conscious and anesthetized rats. Perfused capillaries were stained by labeling the plasma with the gamma globulin-coupled fluorochromes, fluorescein isothiocyanate (FITC) and lissamine-rhodamine B 200 (RB 200). The density of perfused capillaries was determined in 12 different brain structures by fluorescence microscopy of embedded brain sections following coronal sectioning in a cryostat. Significant differences were found among brain structures investigated; the lowest density of perfused capillaries was found in the white matter (e.g., corpus callosum 162 fragments/mm2), whereas the highest values were determined in the structures of the auditory system (e.g., inferior colliculus 810 fragments/mm2). LCBF and LCGU were measured in two separate groups of rats using standard autoradiographic methods. In all three experimental groups, the same structures were identified and measured with a high degree of accuracy and local resolution. Density of perfused capillaries correlated well with LCBF (r = 0.93) and even better with LCGU (r = 0.97). In addition to the relationship between LCGU and LCBF established by earlier studies, these data show the intimate interrelationship between LCGU, density of perfused capillaries, and LCBF.
Length, width, and volume changes in osmotically stressed myocytes
Authors: Roos K. P.
Published: December 2017

Sarcomere lengths, cell widths, and cell volumes were determined from photomicrographs and direct optical imaging of Ca2+-tolerant myocytes dispersed from collagenase-perfused whole rat myocardium. Individual unattached cells were examined at rest first in the normosmotic Ca2+-Tyrode saline solution and then in a sequence of hypotonic or hypertonic Tyrode solutions. Myocytes swell and shrink in hypotonic and hypertonic media but not as much as expected for an ideal uniform osmotic system. Furthermore, these changes were not proportional in the longitudinal and radial directions. These data suggest an 18% osmotically inactive volume and significant internal radial and longitudinal load-bearing structures within these cardiac myocytes.
Choline and acetylcholine concentration in transplanted rat heart
Authors: Oda R. P. , Whiteis C. A. , Schmid P. G. , Lund D. D.
Published: December 2017

A liquid chromatographic assay was used to determine the choline and acetylcholine concentrations in the four chambers of rat hearts 2, 4, and 8 days after transplantation into an abdominal site. Corresponding measurements were made in the hearts of host rats. We found regional cardiac acetylcholine concentrations in controls follow the nonuniform pattern seen with choline acetyltransferase (CAT) activity, being highest in the atria (8–12 nmol/g) and lower in the ventricles (0.7–1.6 nmol/g). Following transplantation, acetylcholine levels decreased significantly only in the right ventricle after 8 days. Following a unilateral vagotomy (random, left or right), acetylcholine concentrations in the distal portion of the severed nerve decreased to half the value of the intact contralateral side by 4 days. The continued presence of acetylcholine, despite significantly reduced CAT activity in the severed nerve and transplanted heart, suggests that acetylcholine is preserved, perhaps by vesiculation in nonstimulated postganglionic terminals. The localized decrease in acetylcholine in the right ventricle after 8 days suggests that transplantation may interrupt the postganglionic fibers to this area.
Ontogeny of 6-keto-PGF1 alpha synthesis in rabbit aorta and the effect of premature weaning
Authors: Bydlowski S. P. , Yunker R. L. , Subbiah M. T.
Published: December 2017

A systematic study of the ontogeny of aortic 6-ketoprostaglandin F1 alpha synthesis from birth to adult life and the effect of premature weaning on this process was investigated in rabbits. Prostacyclin (PGI2) synthesis by both endogenous and exogenous arachidonic acid and its relation to aortic arachidonic acid content was determined. It was found that 1) PGI2 synthesis from endogenous arachidonic acid increased with age, whereas 2) PGI2 synthesis from exogenous arachidonic acid decreased. This correlated with a decrease in the incorporation of [14C]arachidonic acid into phospholipids with age. Aortic arachidonic acid concentration did not change from birth until 3 wk of life but increased markedly by 5 wk of age. Premature weaning caused a decrease in the synthesis of aortic PGI2 and in aortic arachidonic acid concentration initially, but the changes did not persist in later life. These studies suggest that the utilization of exogenous arachidonic acid by aorta decreases after birth perhaps due to maturity of the enzyme systems that synthesize and utilize endogenous substrates.
Relationship between mitochondrial volume density and capillarity in hamster muscles
Authors: Sullivan S. M. , Pittman R. N.
Published: December 2017

Mitochondrial volume density and lipid droplet-volume density were stereologically determined from electron micrographs of muscle fibers from three hamster muscles: retractor, sartorius, and soleus. The number of capillaries around a fiber, length of capillary-fiber contact, and muscle fiber area were also measured. Glycolytic fibers of the retractor and sartorius had larger cross-sectional areas, lower mitochondrial-volume densities, fewer subsarcolemmal aggregates of mitochondria, and lower capillary-fiber contact length in comparison to oxidative fibers of the retractor and soleus. Values for mitochondrial volume density in the different muscles correlated well (r = 0.97) with resting O2 consumption. The mitochondrial volume densities for each muscle correlated well (r = 0.99) with O2 diffusion coefficients of these muscles. Our results indicate that an analysis of the adequacy of O2 supply to an individual muscle fiber must take into account an interplay among fiber size, percent of the muscle fiber perimeter in contact with a capillary (capillary-fiber contact), and O2 demand of the fiber estimated by mitochondrial volume density.
Atrioventricular nodal activation during periodic premature stimulation of the atrium
Authors: Billette J.
Published: December 2017

To study the intranodal origin of the functional properties of the atrioventricular node, progressive changes in nodal cell activation time and cycle length occurring during complete sequences of periodic premature stimulation of the atrium were determined for 419 nodal cells recorded in 11 isolated rabbit heart preparations. The conduction time in proximal nodal cells including the N cells increased only at very short coupling intervals. Conduction time in the distal node (NH and H cells) first increased and then decreased with increasing prematurity. The major fraction of the basic and premature delays developed between N and NH cell activation, a period devoid of upstrokes. The effective and functional refractory periods were related to the minimum intervals between successive upstrokes at the node entrance and outlet, respectively. These results suggest that the cycle-length dependency of nodal conduction is the result of complex changes in propagation time occurring at three levels in the node, whereas the effective and functional refractory periods reflect reactivation limits of cells located at the node entrance and outlet, respectively.