bluuebunny/crossref_metadata_2025 huggingface dataset:
Norepinephrine-induced beta 1-adrenergic peripheral vasodilation in conscious dogs
Authors: Vatner S. F. , Knight D. R. , Hintze T. H.
Published: December 2017

Norepinephrine (NE) elicits alpha-adrenergic vasoconstriction and beta 1-adrenergic increases in heart rate and myocardial contractility. To determine whether NE can also elicit peripheral beta 1-adrenergic vasodilation, conscious dogs were studied after recovery from instrumentation for the measurement of cardiac output, arterial pressure, and left ventricular (LV) pressure and calculations of LV dP/dt and total peripheral resistance (TPR). NE, after pretreatment with hexamethonium and phentolamine, reduced mean arterial pressure 40 +/- 5% from 117 +/- 9 mmHg and TPR 60 +/- 5% from 0.058 +/- 0.007 mmHg X ml-1 X min and increased cardiac output 55 +/- 11% from 2,159 +/- 188 ml/min. beta 1-Adrenergic blockade with atenolol reversed the vasodilation induced by NE completely, while at this time isoproterenol was still able to reduce peripheral resistance further, by 67 +/- 7%, indicating that beta 2-adrenergic receptors were not blocked. Administration of phentolamine to intact dogs caused a fall in mean arterial pressure (23 +/- 5%) and TPR (34 +/- 5.4%) and an endogenous increase in plasma NE (2,987 +/- 905 pg/ml) and epinephrine (584 +/- 92 pg/ml). These increases in cardiac output and decreases in TPR were also reversed by atenolol (0.5 mg/kg). Moreover, this dose of atenolol blocked the increases in iliac blood flow induced by local injection of NE in the limb. Thus, in the presence of alpha-adrenergic receptor blockade, either administration of NE or release of endogenous NE elicits potent peripheral vasodilation, which appears to involve a beta 1-adrenergic receptor mechanism.
Defining the mechanical border zone: a study in the pig heart
Authors: Sakai K. , Watanabe K. , Millard R. W.
Published: December 2017

Wall motion abnormalities can occur in nonischemic areas contiguous with ischemic myocardium. The extent of the mechanical border zone contiguous with an acute myocardial ischemic region was mapped in eight open-chest anesthetized pigs using sonomicrometer crystals implanted parallel with the visible ischemic border in the subepicardium of ischemic (IZ), proximal border (BZ1), distal border (BZ2), and remote normal (NZ) zones. Regional systolic shortening fraction was near 15%, and epicardial blood flow was approximately 1.5 ml X min-1 X g-1 in all locations before ischemia was induced. Blood flow fell to less than 0.05 ml X min-1 X g-1 and the left ventricular free wall supplied by the distal one-third of the left anterior descending artery exhibited holosystolic lengthening when the vessel was occluded. After occlusion, systolic shortening fraction was depressed by 45% in the BZ1 located 3.1 +/- 1.1 mm from the ischemic margin and by 25% in the BZ2, which was measured at 9.3 +/- 1.5 mm from the ischemic margin without significant flow reduction. The NZ, 22.3 +/- 4.6 mm from ischemic margin, was unaffected by occlusion. Computer analysis of the data shows that wall motion is depressed as far as 12 mm from the ischemic margin. This abnormal wall motion surrounding focal transmural myocardial ischemia is presumed to result from mechanical tethering.
Discrepancy between microsphere and diffusible tracer estimates of perfusion to ischemic myocardium
Authors: Yoshida S. , Akizuki S. , Gowski D. , Downey J. M.
Published: December 2017

This study critically tests the ability of microspheres to accurately measure perfusion to ischemic myocardium. The left anterior descending coronary artery was cannulated and perfused with arterial blood. The perfusion line was clamped, and a sidearm between the clamp and the cannula was opened to the atmosphere, allowing blood to flow retrograde from the distal segment of the artery. Measurement of regional blood flow during retrograde flow diversion with 15-micron microspheres revealed essentially zero flow to the perfused segment (0.005 ml X min-1 X g-1). Measurements under the same conditions by either 86Rb uptake or 133Xe washout revealed that an appreciable perfusion of the tissue persisted during retrograde flow diversion (0.043 and 0.11 ml X min-1 X g-1, respectively, for the 2 methods). Thus we have identified a condition during which microspheres indicate zero flow to the tissue but diffusible tracers can both be washed in and washed out at a brisk rate. We conclude that with simple occlusion there is a hidden component of perfusion to an ischemic zone that cannot be measured by microspheres, causing them to underestimate flow by about 25% in that condition.
Dynamic interactions between heart rate and atrioventricular conduction
Authors: Loeb J. M. , deTarnowsky J. M. , Warner M. R. , Whitson C. C.
Published: December 2017

We examined the beat-by-beat alterations in atrioventricular (AV) conduction time that accompany both linear and abrupt changes in heart rate (HR). We used alpha-chloralose-anesthetized and autonomically decentralized dogs (n = 10) and recorded electrocardiogram (ECG), arterial pressure, and electrograms from sinus node, right ventricle, and His bundle. Abrupt or linear HR changes of known slope were generated by computer and displayed graphically with AV interval as a function of time. HR was increased linearly from 10 to 110 beats/min above control over 15, 30, and 60 s and then decreased in a linear fashion. AV interval was dependent on direction of HR change with marked asymmetry between increases and decreases in HR. Similar data were apparent irrespective of whether the decrease followed the increase or vice versa. To study determinants of 1:1 conduction, HR was increased linearly by 200 beats/min above control over 15, 30, and 60 s. As rate of change of HR increased, 1:1 conduction continued to a higher HR; however, the last conducted AV interval was negatively correlated with rate of change of HR. Abrupt sustained increases in HR of 25, 50, 75, and 100% above control resulted in marked accommodation of AV interval only at higher levels of HR. Thus in the absence of autonomic neural tone, 1) cardiac cycle length is not associated with a fixed AV interval but is dependent on magnitude and direction of HR change; and 2) the HR at which 1:1 AV conduction fails is significantly altered by the rate of change of HR.
Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs
Authors: Soifer S. J. , Loitz R. D. , Roman C. , Heymann M. A.
Published: December 2017

The factors responsible for maintaining the normally low pulmonary blood flow and high pulmonary vascular resistance in the fetus are not well understood. Since leukotrienes are potent pulmonary vasoconstrictors in many adult animal species, we determined whether leukotrienes were perhaps involved in the control of the fetal pulmonary circulation by studying the effects of putative leukotriene end organ antagonists in two groups of fetal lambs. In six fetal lambs studied at 130-134 days gestation, FPL 55712 increased pulmonary blood flow by 61% (P less than 0.05) and reduced pulmonary vascular resistance by 45% (P less than 0.05). There was a small increase in heart rate but no changes in pulmonary and systemic arterial pressures and systemic arterial blood gases. In six other fetal lambs studied at 130-140 days gestation, FPL 57231 increased pulmonary blood flow by 580% (P less than 0.05) and decreased pulmonary vascular resistance by 87% (P less than 0.05). Pulmonary and systemic arterial pressures decreased (P less than 0.05), and heart rate increased (P less than 0.05). Leukotriene end organ antagonism significantly increases fetal pulmonary blood flow and decreases pulmonary vascular resistance. Leukotrienes may play a role in the physiological control of the fetal pulmonary circulation.
Heterogeneity of brain blood flow and permeability during acute hypertension
Authors: Baumbach G. L. , Heistad D. D.
Published: December 2017

The purpose of this study was to examine regional autoregulation of blood flow in the brain during acute hypertension. In anesthetized cats severe hypertension increased blood flow more in cerebrum (159%) and cerebellum (106%) than brain stem (58%). In contrast to the heterogeneous autoregulatory response, hypocapnia produced uniform vasoconstriction in the brain. We also compared vasodilatation during severe hypertension with vasodilatation during hypercapnia. During hypercapnia, blood flow increased as much in brain stem, as in cerebrum and cerebellum. Thus regional differences in autoregulation appear to be specific for autoregulatory stimulus and are not secondary to nonspecific differences in vasoconstrictor or vasodilator capacity. To determine whether the blood-brain barrier is more susceptible to hypertensive disruption in regions with less effective autoregulation, permeability of the barrier was quantitated with 125I-albumin. Severe hypertension produced disruption of the barrier in cerebrum but not in brain stem. Thus there are parallel differences in effectiveness of autoregulation and susceptibility to disruption of the blood-brain barrier in different regions of the brain.
New implanted chronic catheter device for determining blood pressure and cardiac output in conscious dog
Authors: Garner D. , Laks M. M.
Published: December 2017

The Vascular-Access-Port (VAP) is a subcutaneous implantable device designed for repeated venous blood sampling in humans. With slight modifications the device has been used in the arterial and venous systems of dogs. This device allows for chronic repeated arterial blood pressure monitoring, monitoring of cardiac outputs, and blood sampling in conscious dogs. Infection, vascular thrombosis, and catheter extraction have not occurred. This modified VAP has been used for 6 mo and in 25 dogs to date without any failure to determine arterial blood pressure and cardiac output.
Differences between cytoplasmic surfaces of deep-etched heart and liver gap junctions
Authors: Shibata Y. , Manjunath C. K. , Page E.
Published: December 2017

We have compared the ultrastructures of the cytoplasmic surfaces (CS) of isolated, glutaraldehyde-fixed gap junctional pellets from rat ventricles and liver by rapid freezing on a liquid helium-cooled surface, freeze fracture, deep etching, and double-axis rotary replication (J. Microsc. Oxford 137: 121-123, 1984). Deep-etched unproteolyzed cardiac junctions [protein subunit relative molecular wt (Mr) 44,000-47,000], isolated with phenylmethylsulfonylfluoride (PMSF) [Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H865-H875, 1984; C.K. Manjunath, G.E. Goings, and E. Page. Proteolysis of cardiac gap junctions during their isolation from rat hearts. J. Membr. Biol. In press.] had particulate CS, while proteolyzed cardiac junctions (subunit Mr 29,500) made without PMSF and liver junctions (Mr 28,000) made with or without PMSF had nonparticulate CS. Taken together with our previous findings that electron micrographs of thin-sectioned isolated unproteolyzed cardiac junctions have urea-resistant fuzzy CS coatings [Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H865-H875, 1984], that proteolyzed cardiac junctions and isolated liver junctions lack this fuzzy layer, and that the CS of in situ cardiac junctions is fuzzy [J. Membr. Biol. 78: 147-155, 1984; Am. J. Physiol. 246 (Heart Circ. Physiol 15): H865-H875, 1984], and published data that in situ freeze-etched liver gap junctions are nonparticulate (Cell 30: 395-406, 1982), these new observations strongly indicate that CS components of heart and liver gap junction proteins are structurally different.
Sustained increases in heart rate induced by timed repetition of vagal stimulation in dogs
Authors: Yang T. , Jacobstein M. D. , Levy M. N.
Published: December 2017

We determined the influence of the "free-running cycle length" (tau FR) on chronotropic responses to one burst of right vagal stimuli per cardiac cycle in anesthetized dogs (tau FR, cycle length that prevailed in absence of right vagal stimulation). We varied tau FR by the following methods: 1) tonic left vagal stimulation in pentobarbital-anesthetized animals; 2) tonic left vagal stimulation plus sinus node cooling in pentobarbital-anesthetized animals; and 3) anesthesia with fentanyl, droperidol, and pentobarbital. When tau FR was less than a critical value [1,019 +/- 60 (SE) ms], right vagal stimulus bursts always had the expected negative chronotropic effect. However, when the tau FR was increased beyond critical value, right vagal stimulus bursts delivered within a specific portion of cardiac cycle actually had a positive chronotropic effect; i.e., cycle lengths diminished to values below tau FR. As tau FR was progressively increased beyond critical value, positive chronotropic response became greater and could be evoked by stimulus bursts delivered within a greater fraction of cardiac cycle. The right vagal stimuli that elicited the maximum positive chronotropic effect were those that were given approximately 235 ms prior to beginning of next atrial depolarization. This critical time probably occurs near the end of the period of phase 4 depolarization of sinus node automatic cells.
Increased myocardial contractility during endotoxin shock in dogs
Authors: Kober P. M. , Thomas J. X. , Raymond R. M.
Published: December 2017

The slope of the left ventricular (LV) end-systolic pressure-diameter relationship (Ees) was analyzed in open-chest, pentobarbital-anesthetized dogs before and after endotoxin administration. A lead II electrocardiogram, systemic arterial pressure, LV pressure, LV dP/dt, and LV minor axis diameter were measured. After control measurements were taken, dogs were given either 1 mg/kg Salmonella enteritidis endotoxin (n = 5) or an equivalent volume of saline (n = 4). Control dogs were followed for 240 min. Endotoxic dogs were monitored until death (246 +/- 44 min). There were no significant changes in Ees in control dogs (17 +/- 3 mmHg/mm), which were hemodynamically stable for 4 h. Ees was significantly increased in endotoxic dogs even into the late stages of shock (41 +/- 11 mmHg/mm, P less than 0.01). Only during the terminal phase did Ees fall significantly below control (11 +/- 2 mmHg/mm, P less than 0.05). End-diastolic diameter decreased following endotoxin administration (P less than 0.05) but returned toward control by the terminal stage. Peak + LV dP/dt was depressed following endotoxin injection. Myocardial contractility was not depressed except as a terminal event. Early depression of cardiovascular performance in endotoxic dogs was therefore due to decreased preload and not cardiac dysfunction.
Differential effect of cyclooxygenase inhibitors on absorptive hyperemia
Authors: Proctor K. G.
Published: December 2017

To test whether the hydrolytic products of digestion could stimulate vasoactive prostaglandin synthesis in the intestine, the muscularis and mucosa of the rat jejunum were suffused with a bicarbonate-buffered Ringer vehicle containing cyclooxygenase inhibitors (meclofenamate or indomethacin; 3 X 10(-5) M). To evoke blood flow changes, either glucose (56 mM), oleic acid (20 or 40 mM), or sodium arachidonate was added to the mucosal vehicle. Bile salt (taurocholic acid, 10 mM) was added to emulsify oleic acid. Blood flow was calculated (BFc) in submucosal arterioles by use of video microscopy. Neither bile salt nor cyclooxygenase inhibitors altered resting BFc. Neither oleic acid concentration nor solution osmolality altered the magnitude of absorptive hyperemia. After 10 min of glucose, BFc increased 36 +/- 6% with vehicle (n = 16) and 39 +/- 8% with meclofenamate (n = 10). After 10 min of oleic acid, BFc increased 21 +/- 5% with vehicle (n = 17) and 34 +/- 6% with inhibitors (n = 17). In animals exposed twice to the same concentration of oleic acid, the paired difference between the vehicle and inhibitors (19 +/- 7%; n = 9) was significant. Arachidonate alone produced no dose-related (0.06-1.9 mM) effect on BFc (n = 41), but arachidonate (0.3 mM) combined with cyclooxygenase inhibitors (6 X 10(-5) M) produced a significant BFc increase of 35 +/- 7% (n = 6). These observations suggest that the absorption of oleic acid, but not glucose, stimulates the synthesis of a vasoactive metabolite of arachidonate. The mechanism for the differential effect of cyclooxygenase inhibitors is unknown but could involve nonprostaglandin metabolites of arachidonate, such as lipoxygenase or cytochrome P-450 products.
Substrate dependence of metabolic state and coronary flow in perfused rat heart
Authors: Starnes J. W. , Wilson D. F. , Erecinska M.
Published: December 2017

The effect of substrate source on the regulation of energy metabolism and coronary flow was studied in isolated perfused rat hearts. Compared with glucose-perfused hearts, those perfused at the same work load with palmitate or acetate demonstrated increases (P less than 0.01) in O2 consumption of 16 and 18%, respectively, and increases (P less than 0.01) in coronary flow of 30 and 32%, respectively. Parallel substrate-related changes occurred in the levels of high-energy phosphate compounds: tissue creatine, ADP free, and inorganic phosphate (Pi) were significantly decreased, leading to increases (P less than 0.01) in [creatine phosphate]/[creatine] and [ATP]free/[ADP]free[Pi]. These changes were accompanied by increased reduction of intramitochondrial pyridine nucleotides. Omitting orthophosphate from perfusate lowered intracellular Pi and modified cardiac function, but substrate-related differences were similar to those in Pi containing media. Differences in intracellular pH among substrates were observed, which may contribute in some instances to differences in energy metabolism and coronary flow. When work load was altered in glucose- and acetate-perfused hearts, both O2 consumption and coronary flow were linearly related to cytosolic [ATP]free/[ADP]free[Pi], and slopes of regression lines were similar for both substrates. These correlations support the view that [ATP]free/[ADP]free[Pi] is a major determinant of O2 consumption by cardiac cells and of coronary flow.
Arteriolar responses to norepinephrine and ouabain in early 1-kidney, 1-clip hypertension in rats
Authors: Overbeck H. W.
Published: December 2017

We assessed the role of putative circulating ouabainlike factors on in vivo arteriolar function in rats with very early (less than or equal to 7 days, mean 3 days), benign, one-kidney, one-clip (1K1C) hypertension. Thus we measured vascular responses in vasodilated (nitroprusside or adenosine), vascularly isolated, innervated hindlimb vascular beds of chloralose-anesthetized 1K1C rats perfused with their own blood at 1 ml/min. Complete dose-response curves to norepinephrine in 19 1K1C compared with 25 uninephrectomized (1K) normotensive control rats showed unchanged thresholds and 50% effective dosages. Magnitude of ouabain-induced leftward shifts of the dose-response curve in 29 1K1C and 30 1K rats were similar. In 1K1C, compared with 1K, limb resting resistance was elevated by 45% (P less than 0.001), and limb resistance at maximal vasodilation was elevated by 15% (P less than 0.02). These results provide no evidence in this form and stage of hypertension that humoral ouabainlike inhibitors of the sodium-potassium pump evoke physiologically significant inotropic effects in arterioles in vivo. However, the results suggest that significant increases in arteriolar wall-to-lumen ratio occur in the earliest stages (3 days) of hypertension and probably contribute to the elevated resistance.
Hemodynamic regulation: investigation by spectral analysis
Authors: Akselrod S. , Gordon D. , Madwed J. B. , Snidman N. C. , Shannon D. C. , Cohen R. J.
Published: December 2017

We investigated the hypothesis that beat-to-beat variability in hemodynamic parameters reflects the dynamic interplay between ongoing perturbations to circulatory function and the compensatory response of short-term cardiovascular control systems. Spontaneous fluctuations in heart rate (HR), arterial blood pressure, and respiration were analyzed by spectral analysis in the 0.02- to 1-Hz frequency range. A simple closed-loop model of short-term cardiovascular control was proposed and evaluated in a series of experiments: pharmacological blockades of the parasympathetic, alpha-sympathetic, beta-sympathetic, and renin-angiotensin systems were used to open the principal control loops in order to examine changes in the spectral pattern of the fluctuations. Atrial pacing was used to examine blood pressure variability in the absence of HR variability. We found that respiratory frequency fluctuations in HR are parasympathetically mediated and that blood pressure fluctuations at this frequency result almost entirely from the direct effect of centrally mediated HR fluctuations. The sympathetic nervous system appears to be too sluggish to mediate respiratory frequency variations. Low-frequency (0.02-0.09 Hz) fluctuations in HR are jointly mediated by the parasympathetic and beta-sympathetic systems and appear to compensate for blood pressure fluctuations at this frequency. Low-frequency blood pressure fluctuations are probably due to variability in vasomotor activity which is normally damped by renin-angiotensin system activity. Blockade of the alpha-adrenergic system, however, does not significantly alter low-frequency blood pressure fluctuations.
Invariant total heart volume in the intact thorax
Authors: Hoffman E. A. , Ritman E. L.
Published: December 2017

Fast multisliced computerized tomography (Dynamic Spatial Reconstructor or DSR) was used to study the change in total heart volume (content of the pericardial sac) between end diastole (ED) and end systole (ES) with lungs held at 0 and 15 cmH2O airway inflation pressure (Paw). Nine dogs were anesthetized and scanned in the DSR. At 0 cmH2O airway pressure, mean total heart volume changed, on the average, only 2.7 +/- 0.6% (SE) of its ED volume comparing ED with ES. With lungs inflated to 15 cmH2O Paw, total heart volume decreased 12 +/- 0.5%. However, at this new heart volume, the change in total heart volume between ED and ES was only 1.7 +/- 0.5%. The data indicate that the epicardial apex of the heart remains relatively stationary while the atrioventricular groove moves toward the apex during systole and away from the apex during diastole. Thus the atria and ventricles empty and fill reciprocally even when the pericardial contents do not fully distend the pericardial sac. The invariant total heart volume observed in these species would minimize the work of the heart by maximizing the percentage of work expended to move blood and minimizing the work expended to move tissue (i.e., lung).
Hemodynamic effects of neurohypophyseal peptides with antidiuretic activity in dogs
Authors: Schwartz J. , Liard J. F. , Ott C. , Cowley A. W.
Published: December 2017

Arginine vasopressin (AVP) is known to produce increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) and decreases in heart rate (HR), cardiac output (CO), and plasma renin activity (PRA). Some recent observations with AVP and synthetic analogues have suggested that under certain conditions, AVP can induce cardiovascular and reninsecretory responses in the opposite directions. To characterize the receptors mediating these responses, the effects of AVP, oxytocin, and synthetic neurohypophyseal analogues with specific antidiuretic, vasoconstrictor, or oxytocic activities were studied in conscious dogs. AVP and 2-phenylalanine-8-ornithine-oxytocin (Phe2Orn8OT, a selective vasoconstrictor agonist) produced similar responses when infused at 10 ng X kg-1 X min-1. That is, TPR and MAP increased, and CO, HR, and PRA decreased. Pretreatment with a selective vasoconstrictor antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid) 2-(O-methyl)tyrosine]AVP, abbreviated d(CH2)5Tyr(Me)-AVP (10 micrograms/kg), blocked the actions of Phe2Orn8OT. However, in the presence of d(CH2)5Tyr(Me)AVP, AVP actually decreased TPR and increased CO, HR, and PRA. An analogue with selective antidiuretic activity, 4-valine-8-D-AVP (VDAVP, 10 ng X kg-1 X min-1), produced the same effects as the combination of vasopressin plus d(CH2)5Tyr(Me)AVP. Neither the effects of VDAVP nor of AVP plus antagonist were blocked by propranolol (1 mg/kg). These data indicate that vasopressin, by its antidiuretic activity, produces cardiovascular effects that are opposite to many of those produced by its vasoconstrictor action and that these effects are not dependent on mediation by beta-adrenoceptors.
Hypertrophy and coronary and collateral vascularity in dogs with severe chronic anemia
Authors: Scheel K. W. , Williams S. E.
Published: December 2017

The purpose of this study was to determine 1) whether a severe hypoxic stimulus could produce an increase in coronary and collateral vascularization and 2) whether minimal coronary resistance, which increases with hypertension-induced hypertrophy, decreases when hypoxia is superimposed on volume load hypertrophy. Data were obtained on 11 dogs rendered anemic to a hematocrit of 11 +/- 0.2 vol% and maintained at this level for 4 wk. Eighteen dogs with a hematocrit of 42 +/- 0.02 vol% were used as controls. After chronic anemia the coronary and collateral flows were quantitated in a beating, vasodilated, isolated heart preparation perfused solely with blood from two normal donor dogs. The following variables were significantly increased in anemia-exposed hearts compared with controls: coronary flow per gram myocardium for the left anterior descending, the circumflex, the right, and the septal arteries; ratio of total coronary flow of each vessel to body weight; and the collateral flows to each coronary vessel. Both the right and left ventricles were hypertrophied. We conclude that severe chronic anemia produces a dissociation between hypertrophy and increased minimal coronary resistance. Severe chronic anemia appears to increase vascularization of both coronary and collateral circulation probably due to tissue hypoxia. In this model coronary collateral vascularity seems to increase in the absence of a pressure difference across collaterals.
Abnormal cardiac biochemistry in spontaneously diabetic Bio-Breeding/Worcester rat
Authors: Malhotra A. , Mordes J. P. , McDermott L. , Schaible T. F.
Published: December 2017

Diabetes produced by injection of alloxan or streptozotocin results in cardiac dysfunction in rats that is associated with lower cardiac contractile protein ATPase activity. The purpose of this investigation was to examine cardiac myosin biochemistry in the Bio-Breeding Worcester (BB/W) rat, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. Hearts from diabetic BB/W rats were studied at 1, 4, and 7 mo after the onset of diabetes and were compared with age-matched BB/W rats that were bred for resistance to diabetes. Calcium-stimulated myosin ATPase activity was significantly decreased after 4 and 7 mo of diabetes, and actin-activated myosin ATPase was significantly depressed at all time points. Differences between hearts from control and diabetic animals increased with the duration of diabetes. Closely associated with reductions in myosin ATPase activity in the diabetes was a shift in the isomyosin content from the normally predominant V1 to the V3 isoenzyme. Thus diabetes that results from genetic causes leads to depressed myosin enzymatic activity in the rat. Furthermore, since previous studies have shown that BB/W diabetic rats do not develop hypothyroidism, the present results support the view that altered thyroid function does not mediate the abnormalities in cardiac contractile proteins in diabetes.
Pulmonary and systemic vascular effects of SRS-A blockade in conscious lambs
Authors: Kulik T. J. , Schutjer R. K. , Howland D. F. , Lock J. E.
Published: December 2017

There is preliminary evidence suggesting that hypoxic pulmonary vasoconstriction may be mediated by slow-reacting substance of anaphylaxis (SRS-A), which is comprised of leukotrienes C4, D4, and E4. We studied the effects of the SRS-A antagonist FPL 57231 (FPL) on the hypoxic pulmonary vasoconstrictor response and on systemic vascular resistance in awake, chronically instrumented young lambs. Two other studies were performed to ascertain whether FPL's vasodilation was specific for hypoxic pulmonary vasoconstriction: the effect of FPL infusion in pulmonary and systemic vascular resistance was measured in six normoxic lambs, and the effect of FPL on 5-hydroxytryptamine (5-HT)-mediated vasoconstriction was determined. In seven lambs, mean pulmonary arterial pressure was 21 mmHg in room air and 28 mmHg in hypoxia (Po2 = 43 Torr). During hypoxia, FPL infusion (2 mg X kg-1 X min-1) reversibly decreased pulmonary arterial pressure to 15 mmHg; pulmonary arteriolar resistance also fell below normoxia levels with FPL. FPL also caused a fall in aortic pressure and systemic vascular resistance in these hypoxic lambs, but the decrease in systemic resistance was less than the fall in pulmonary resistance. beta-Adrenergic blockade using propranolol (1 mg/kg) did not affect the pulmonary vasodilation caused by FPL. In six normoxic lambs, FPL infusion also significantly decreased pulmonary and systemic vascular resistance (29% in each case). These data are consistent with the idea that leukotrienes may be involved in adjusting both pulmonary and systemic vascular tone, but further work is necessary to establish whether FPL's vasodilation is mediated via its leukotriene antagonism or is a nonspecific effect of FPL.
Vascular capacitance responses to severe systemic hypercapnia and hypoxia in dogs
Authors: Rothe C. F. , Stein P. M. , MacAnespie C. L. , Gaddis M. L.
Published: December 2017

The magnitude of vascular capacitance change induced by hypercapnia, hypoxia, or hypoxic hypercapnia was estimated during the administration of experimental gas mixtures to anesthetized dogs for 25 min. Mean circulatory filling pressure (Pcf) was determined by fibrillating the heart and equilibrating arterial and venous pressures with a pump. We assumed that the total blood volume remained constant and that the magnitude of change in peripheral venous volume equaled the sum of the changes in blood volume in the cardiopulmonary and arterial beds. We further assumed that active (reflex) peripheral venoconstriction occurred if the cardiopulmonary and arterial bed blood volumes, as well as the Pcf, increased. Within 3 min, severe hypercapnia and hypoxic hypercapnia induced a 5.2 and 7.3 ml/kg reduction in systemic vascular capacity, and, by 19 min of experimental gas presentation, increased Pcf by 5.5 and 7.0 mmHg, respectively. Severe hypoxia had less effect (0.7 ml/ kg and 2.5 mmHg, respectively) at 19 min. Severe hypercapnia also increased the central venous, systemic arterial, and pulmonary arterial pressures and decreased heart rate. Hypoxic hypercapnia additionally increased cardiac output. We conclude that severe systemic hypercapnia, whether alone or in combination with hypoxia, causes a significant active reduction in vascular capacitance, but severe hypoxia is less effective.
Superoxide anion selectively attenuates catecholamine-induced contractile tension in isolated rabbit aorta
Authors: Wolin M. S. , Belloni F. L.
Published: December 2017

Xanthine oxidase-derived oxygen metabolites caused a selective loss of norepinephrine-induced contractile tension in rings and helical strips from rabbit aorta. Phenylephrine-induced tension was not affected. The relaxation was selectively and completely blocked by superoxide dismutase but not by catalase. Isoproterenol-induced relaxation was also reversed by xanthine oxidase-derived oxygen metabolites. These observations are consistent with the chemical reaction of superoxide anion with catecholamines and suggest that the reaction may have significance at physiological concentrations of norepinephrine. The time course of the effects of superoxide generation on contractile tension was consistent with the properties of the chemical reaction (measured spectrophotometrically) and with the dependence of tone on norepinephrine concentration. These results indicate that superoxide anion, in situations at which submicromolar concentrations of this reduced oxygen metabolite are present, will selectively oxidize catecholamines, which may attenuate local adrenergic regulation.
Enzymatic activity of rat submandibular gland kallikrein released into blood
Authors: Berg T. , Johansen L. , Nustad K.
Published: December 2017

Enzymatic activity of submandibular gland (SG) kallikrein released into saliva and blood was studied at rest and after autonomic nerve stimulation. Kallikrein was measured by an immunometric assay that allows measurement of immunoreactive kallikrein in complex with inhibitors as well as simultaneous determination of kallikrein enzymatic activity. Measurements using the chromogenic substrate S2266 gave identical results to the natural substrate kininogen. Endogenous SG kallikrein secretory rate was, at rest, 0.9 +/- 0.1 ng/min. Kallikrein secretion into blood in response to autonomic nerve stimulation paralleled that into saliva, and secretion was greatly enhanced by alpha-adrenergic stimulation. In plasma, kallikrein was bound to several inhibitors that completely or partially blocked the enzyme activity. In arterial and SG venous control plasma, 93 +/- 3 and 72 +/- 10% inhibition of kallikrein enzyme activity was observed, respectively. Sympathetic stimulation after administration of a beta-adrenergic blocker increased kallikrein enzyme activity 62 and 11 times in arterial and SG venous plasma, respectively, with a corresponding 78 +/- 8 and 70 +/- 8% inhibition of kallikrein enzyme activity. A fraction containing kallikrein resembling “free kallikrein” was always present in plasma.
Adenosine is unimportant in controlling coronary blood flow in unstressed dog hearts
Authors: Kroll K. , Feigl E. O.
Published: December 2017

The adenosine hypothesis of local metabolic control of coronary blood flow was tested in the unstressed heart with adenosine deaminase, which converts adenosine to nonvasoactive inosine. If adenosine is normally an important physiological regulator, then adenosine deaminase should lower coronary blood flow. The left main coronary artery was perfused at constant pressure in anesthetized, closed-chest dogs. Adenosine deaminase was deposited in one region of the left ventricle by selective infusion into a branch of the left coronary artery. Coronary blood flow measured with radioactive microspheres was not lower in the region treated with adenosine deaminase than flow measured simultaneously in an untreated control region of the same heart. This finding is contrary to the prediction of the adenosine hypothesis. Coronary vasodilation elicited by intracoronary adenosine infusion was inhibited in the adenosine deaminase-treated region compared with the control region, indicating that adenosine deaminase lowered adenosine concentration at the vascular adenosine receptor. Inhibition of exogenous adenosine vasodilation was fully reversed by intracoronary infusion of a specific inhibitor of adenosine deaminase. Measurement of adenosine deaminase activity in cardiac lymph provided evidence that adenosine deaminase reached the myocardial interstitial space. These results demonstrate that introducing adenosine deaminase into the interstitial space of the unstressed heart did not lower coronary blood flow. This finding indicates that adenosine is normally below the vasoactive threshold and therefore is not important in mediating local metabolic control of blood flow in the unstressed heart.
Reversibility of diabetic cardiomyopathy with insulin in rabbits
Authors: Fein F. S. , Miller-Green B. , Zola B. , Sonnenblick E. H.
Published: December 2017

Diabetes mellitus causes a cardiomyopathy in human subjects, independent of atherosclerotic coronary artery disease. Ventricular papillary muscle function studies in chronically diabetic rats and rabbits have shown diminished contractility and a prolonged duration of contraction. In rats there was complete reversibility of these changes with insulin therapy. However, the effects of insulin on the myocardial mechanics of diabetic rabbits have not been studied. Therefore, rabbits diabetic for 3-4 mo (after alloxan injection) were treated with PZI insulin for 3-4 mo, and the mechanical performance of their right ventricular papillary muscles was compared with that of untreated diabetic animals and age-matched controls. Insulin therapy normalized serum glucose concentration. All abnormalities in papillary muscle function were completely reversed in insulin-treated animals. Norepinephrine (NE) dose responses were also evaluated in muscles from all groups. There were no differences in the positive inotropic effects of NE between groups. However, the data suggested, in diabetic animals a blunted response of peak relaxation rate to NE; this abnormality was reversed in muscles from treated animals. These findings indicate that previous work on diabetic rats can be extended to diabetic rabbits and suggest that chronic insulin therapy completely reverses the contractile alterations in hearts from these diabetic animals.
Interaction of right and left carotid sinus baroreflexes in the dog
Authors: Greene A. S. , Brunner M. J. , Shoukas A. A.
Published: December 2017

Carotid sinus reflex interactions were studied in 10 dogs anesthetized with pentobarbital sodium. The right and left carotid sinus regions were isolated and perfused at controlled pressures. Pressure in the right and left carotid sinuses were independently varied, and the resulting steady-state reflex changes in arterial pressure, heart rate, respiratory frequency, tidal volume, and total ventilation were measured. Reflex changes when carotid sinus pressure was changed on one side were strongly influenced by pressure in the contralateral carotid sinus (P less than 0.05). Right carotid sinus gain was found to be 0.628 +/- 0.058 at a left carotid sinus pressure of 50 mmHg and 0.148 +/- 0.027 when left carotid sinus pressure was 200 mmHg. Similar results were found for left carotid sinus gain. Suppression was also found for heart rate, respiratory rate, tidal volume, and total ventilation. The hypothesis that rapid resetting of one carotid sinus baroreflex might influence responses from the other side was also tested. Although ipsilateral resetting was consistently observed, no contralateral component of the resetting was detected. An additional inhibitory summation between the right and left carotid sinuses was found such that simultaneous excitation of both receptors resulted in a smaller reflex response than did the sum of individual responses. Sympathetic denervation of the carotid sinus region had no effect.
Lowering calcium in the nucleus tractus solitarius causes hypotension and bradycardia
Authors: Higuchi S. , Takeshita A. , Higashi H. , Ito N. , Imaizumi T. , Matsuguchi H. , Nakamura M.
Published: December 2017

It has been shown that saline microinjected into the region of the nucleus tractus solitarius (NTS) causes, but artificial cerebrospinal fluid (CSF) in the same volume does not cause, hypotension and bradycardia. This study was done to examine the possibility that the difference in effects between saline and artificial CSF may be due to the lack of calcium ions in saline. In anesthetized rats, saline or artificial CSF with or without calcium ions was microinjected into the region of the NTS. Saline microinjected in volumes of 0.2 and 0.5 microliter produced the volume-dependent decreases in arterial pressure and heart rate. Saline with added calcium ions and artificial CSF did not elicit the hypotensive and bradycardic response, but artificial CSF without calcium ions produced hypotension and bradycardia. These results suggest that the lack of calcium ions in the injected solutions is the factor that determines the hypotensive and bradycardic response. These results suggest that lowering the local availability of calcium to the NTS neurons results in hypotension and bradycardia.
Effects of changing Ca2+-to-H+ ratio on Ca2+ uptake by cardiac sarcoplasmic reticulum
Authors: Levitsky D. O. , Benevolensky D. S.
Published: December 2017

Ca uptake by fragments of cardiac sarcoplasmic reticulum (SR) in the absence of oxalate depends on the ratios between concentrations of free Ca2+ and H+ and on the level of Ca loading. Using a rapid quenching technique, we showed that at [Ca2+]f less than 1 microM or in short time intervals after ATP addition (less than or equal to 1 s), pH decrease led to a significant inhibition of Ca accumulation. If Ca transport was quenched in 1 s, [Ca2+]f for half-maximal stimulation of the process would be 0.3, 1.0, and 4.0 microM at pH 7.2, 6.8, and 6.2, respectively. At higher [Ca2+]f and at longer intervals, low pH increases the amount of Ca taken up by SR. These phenomena could not be explained by an interaction of ethyleneglycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) with the Ca2+-pump system since they were also demonstrated without application of Ca-EGTA buffers. Scatchard plot analysis of ATP-independent Ca binding to SR shows that apparent Kd for Ca increases from 0.3 microM at pH 7.2 to 7.4 microM at pH 6.2. pH shifts do not change the number of high-affinity Ca-binding sites. The results suggest a competition between Ca2+ and H+ for high-affinity binding sites on Ca2+-ATPase molecules. This may cause a delay of myocardial relaxation during ischemia when a decrease in intracellular pH takes place.
Regional differences of myocyte hypertrophy and three-dimensional deformation of the heart
Authors: Kuribayashi T. , Furukawa K. , Katsume H. , Ijichi H. , Ibata Y.
Published: December 2017

Cross-sectional area was compared between the latitudinally and longitudinally oriented muscle fibers of the hypertrophied left ventricle of the rat heart under aortic banding and isoproterenol infusion. In addition, end-diastolic three-dimensional deformation of the left ventricle as expressed by cavity volume and eccentricity was examined in the early and chronic stages of these treatments. Under aortic banding, myocyte hypertrophy occurred to a greater extent in the latitudinally oriented fibers of the midwall layer than in the longitudinal fibers of the inner and outer layers. Such a regional difference of hypertrophy was not seen under isoproterenol infusion. At the early stage of aortic banding, the left ventricle at end diastole was more dilated and spherical, whereas at the acute stage of isoproterenol infusion, it was more decreased in size and prolate than that of the controls. The deformation of the left ventricle at the early stage of aortic banding is considered to cause, during diastole, axial stretching and increase in tensile stress more on the latitudinal fibers, leading them to the predominant hypertrophy.
Dural sinus pressure: various aspects in human brain surgery in children and adults
Authors: Iwabuchi T. , Sobata E. , Ebina K. , Tsubakisaka H. , Takiguchi M.
Published: December 2017

To prevent air embolism and minimize neurosurgical venous hemorrhage, the dural sinus pressure (confluens sinuum pressure, CSP) was examined under various conditions in 47 cases, 11 of whom were children. Either the extracranial (group A) or catheter type (group B) pressure transducer was used. The latter gave approximately 30% higher values than the former. In any surgical position, children showed a tendency toward higher pressure than did adults. This was particularly the case in the sitting position; adults showed negative pressure [-8.6 +/- 2.3 (SD) mmHg, group A], whereas all eight children less than 9 yr of age (group A, 5 cases; group B, 3 cases) showed positive pressure. The youngest with negative CSP in a sitting position was a 9-yr-old boy. When the upper half of the body was raised, the CSP decreased linearly and became zero at approximately 25 degrees. In anteflexion of the neck, the CSP decreased significantly, and even with inclination of the upper half of the body of only 15-20 degrees or more upward, negative pressure was observed in adults. In children, right and left rotation of the neck showed remarkable increase of the CSP. In both supine and sitting positions, CSP was elevated sufficiently by bilateral jugular compression to prevent air embolism. Positive-pressure respiration did not raise the CSP, contrary to widely accepted knowledge. This study was originally performed in relation to brain surgery, but the results also seemed to be valuable in physiology.
Adriamycin stimulates low-affinity Ca2+ binding and lipid peroxidation but depresses myocardial function
Authors: Singal P. K. , Pierce G. N.
Published: December 2017

Studies have been performed to examine the effects of different concentrations of adriamycin (10(-9)-10(-3) M) on sarcolemmal ATP-independent Ca2+ binding, contractility, ultrastructure, energy [ATP and creatine phosphate (CrP)] stores, and lipid peroxide activity in the rat myocardium. Low-affinity Ca2+ binding was stimulated, whereas high-affinity Ca2+ binding was inhibited by adriamycin in sarcolemmal vesicles isolated from ventricles. These alterations were accompanied by changes in the number of Ca2+ binding sites without affecting the membrane affinity for Ca2+. Peak developed force as well as positive and negative dF/dt in the isolated papillary muscle were depressed. The percent changes in contractility due to adriamycin were not affected by extracellular Ca2+ concentration. Ultrastructural changes in the papillary muscles due to adriamycin included mitochondrial swelling, presence of intramitochondrial granules, increased lysosomes, and disruption of myofibrils. ATP and CrP content of the papillary muscles was significantly reduced by the drug. Lipid peroxides, estimated by quantitating malondialdehyde content, were elevated by adriamycin. Most of these changes due to adriamycin became apparent at 10 microM or higher concentrations of the drug, and the maximum effect was seen at 1 mM of adriamycin. The in vitro depressant effect of adriamycin may not be related to changes in the low-affinity Ca2+ binding sites, but instead it appears to be associated with a lower energy state and myocardial cell damage.
Blood flow through vasa vasorum in arteries and veins: effects of luminal PO2
Authors: Heistad D. D. , Armstrong M. L. , Amundsen S.
Published: December 2017

We have examined effects of chronic reduction of intraluminal PO2 on blood flow through vasa vasorum, by comparing large arteries and veins, and effects of acute hypoxia on flow through vasa. Microspheres were used to measure flow in anesthetized dogs. Values obtained with different sizes of microspheres suggest that spheres 9 and 15 micron in diam, but not 50 micron, are appropriate for measurement of blood flow through vasa vasorum. Flow [expressed as ml X min-1 X 100 g-1 (SE)] through medial vasa was similar in the aorta (9.0 +/- 2.1) and pulmonary artery (9.3 +/- 1.1) although, on the basis of wall thickness and number of lamellae, one would predict much higher levels of flow to aortic media. Two veins that we studied have a thick muscular wall. Both veins had high levels of flow through medial vasa: 33 +/- 4.4 to the subdiaphragmatic inferior vena cava and 18 +/- 5.4 to the portal vein. Two other veins are apparently conduit vessels, with dense connective tissue and minimal smooth muscle. Both veins had minimal flow through medial vasa: 2.4 +/- 1.0 to superior vena cava, and 1.9 +/- 0.8 to supradiaphragmatic inferior vena cava. Thus, because flow through vasa differs greatly in different veins, structure of the vessel (as well as intraluminal PO2) is an important determinant of flow through vasa. Acute hypoxia increased conductance of medial vasa vasorum of arteries and veins when neurohumoral constrictor effects were blocked by phenoxybenzamine.(ABSTRACT TRUNCATED AT 250 WORDS)