bluuebunny/crossref_metadata_2025 huggingface dataset:
Phasic volumetric coronary venous outflow patterns in conscious dogs
Authors: Canty J. M. , Brooks A.
Published: December 2017

We performed the present study to characterize phasic venous outflow patterns in conscious chronically instrumented dogs. An implantable ultrasonic transit-time flow probe capable of measuring volumetric venous outflow was placed on the coronary sinus (n = 9) and/or great cardiac vein (n = 5). Under resting conditions, great cardiac vein flow was predominantly systolic [systolic index 61 +/- 6%/beat (means +/- SD), diastolic index 39 +/- 6%/beat]. In contrast, coronary sinus volumetric flow was predominantly diastolic (systolic index 36 +/- 13%/beat, diastolic index 64 +/- 13%/beat). During adenosine vasodilation both great cardiac vein and coronary sinus flow patterns were predominantly systolic (systolic index 58 +/- 12%/beat for the coronary sinus and systolic index 75 +/- 6%/beat in great cardiac vein flow). In addition, the time at which peak venous flow occurred shifted from end systole to midsystole after vasodilation. The variation in coronary venous flow patterns with position suggests that outflow patterns are significantly influenced by a venous compliance between the great cardiac vein and distal coronary sinus. The lack of a predominantly systolic outflow pattern in the coronary sinus under resting conditions contrasts with previous findings in open-chest anesthetized animals and raises the possibility that cannulation of the coronary sinus and/or changes in vasomotor tone caused by anesthesia alter resting venous flow patterns.
Vagal stimulation attenuates sympathetic enhancement of left ventricular function
Authors: Henning R. J. , Khalil I. R. , Levy M. N.
Published: December 2017

We studied the effects of stimulation of the vagal and sympathetic cardiac nerves on left ventricular contraction and relaxation in 16 anesthetized dogs. In each experiment, we paced the ventricles at a fixed rate of 120 beats/min, and we kept the systemic arterial pressure constant. We used the maximum rates of left ventricular pressure rise (dP/dtmax) and fall (dP/dtmin) as our indexes of ventricular contraction and relaxation. Sympathetic nerve stimulation at a frequency of 6 Hz increased dP/dtmax by 802 mmHg/s and raised dP/dtmin by 847 mmHg/s above the control level. The effect of vagal nerve stimulation was directly dependent on the level of sympathetic stimulation. In the absence of sympathetic stimulation, vagal nerve stimulation at a frequency of 5 Hz decreased dP/dtmax by 187 mmHg/s and reduced dP/dtmin by 199 mmHg/s below the control level. When the sympathetic stimulation was 6 Hz, vagal nerve stimulation at 5 Hz decreased dP/dtmax by 513 mmHg/s and reduced dP/dtmin by 709 mmHg/s. Furthermore, propranolol, in doses of 1.5 mg/kg, abolished any significant vagal effect on ventricular contraction or relaxation. We conclude that combined sympathetic-vagal stimulation results in a substantial antagonistic interaction such that vagal stimulation significantly attenuates the sympathetic enhancement of left ventricular function.
EDRF from rat intestine and skeletal muscle venules causes dilation of arterioles
Authors: Falcone J. C. , Bohlen H. G.
Published: December 2017

Communication from venules to arterioles through the release of endothelial-derived relaxing factor (EDRF) was evaluated. To demonstrate that the rat intestinal and the spinotrapezius muscle arterioles can respond to EDRF, the vessels were dilated by iontophoretically applied acetylcholine (ACh), and this dilation was greatly attenuated by the inhibitors of EDRF actions, methylene blue (100 microM) and dithiothreitol (50 microM). The EDRF inhibitors did not suppress arteriolar dilation to typically applied adenosine (10(-4) M), an endothelium-independent dilator. Although ACh release onto the venular wall had minimal effects on the diameter of the venule, the paired arteriole would dilate 20-30% in the intestine and 50-60% in the spinotrapezius muscle. After EDRF inhibition, venular ACh exposure did not cause arteriolar dilation. ACh diffusion from venules to arterioles was not the cause of arteriolar dilation, because release of ACh into the tissue at the same distance as from the arteriole to the venular ACh release site caused minimal arteriolar dilation. Neither blockade of neural reflexes with tetrodotoxin (3 X 10(-6) M) nor suppression of prostaglandin formation with indomethacin (10(-5) M) prevented the arteriolar dilation during release of ACh onto the venular wall. The overall study indicated that communication from venules to arterioles through the release of EDRF from the venule did occur and caused substantial arteriolar vasodilation. Therefore circumstances within and around venules may influence regulation of nearby arterioles through an EDRF-mediated mechanism.
Effects of deafferentation or sequential occlusions on cardiac sympathetic activity during ischemia
Authors: Neely B. H. , Hageman G. R.
Published: December 2017

In 39 anesthetized dogs, we compared the effects of selective afferent sympathectomy, vagotomy, epicardial phenol painting, or a previous coronary occlusion on cardiac sympathetic activities recorded during 30 min of acute myocardial ischemia. Efferent innervation patterns were verified by electrical stimulation, and cardiac efferent activities were simultaneously recorded from two thoracic sympathetic nerves. One nerve was selected for recording because it was shown to innervate the proposed ischemic region, whereas the other nerve was selected because it was shown to innervate nonischemic regions. Left ventricular ischemia was produced by occlusion of a small branch of either the left anterior descending (LAD) or left circumflex (LCX) coronary arteries. Heart rate was paced. Reflex changes in sympathetic activities to ischemic regions were prevented by elimination of afferent fibers with either phenol or bilateral vagotomy. Ablation of sympathetic afferents prevented ischemia-induced reflex changes to nonischemic regions but did not prevent reflex changes to ischemic regions. Reflex changes in cardiac sympathetic activities during a second coronary occlusion of 30 min were vastly different from the initial occlusion but were similar to those observed after local deafferentation. Our findings indicate that 1) differential reflex changes in cardiac sympathetic activities during 30 min of left ventricular ischemia are due to afferent signals originating from the ischemic region, 2) both sympathetic and vagal afferent fibers participate in the ischemia-induced cardio-cardiac reflex, and 3) the nature of the sympathetic reflex response to acute ischemia is influenced by a previous ischemic insult.
Regulation of blood pressure in pregnancy: pressor system blockade and stimulation
Authors: Pan Z. R. , Lindheimer M. D. , Bailin J. , Barron W. M.
Published: December 2017

Contributions of the autonomic nervous system (ANS), renin-angiotensin system (RAS), and arginine vasopressin (AVP) to basal mean arterial pressure (MAP) were evaluated in near-term pregnant and virgin rats as follows. MAP and heart rate (HR) were measured before and after ganglionic, alpha-adrenoreceptor, RAS, and/or AVP blockade. In addition, pressor responses to angiotensin II (ANG II), norepinephrine, phenylephrine, or AVP were determined in ganglionic-blocked animals. In both groups decrements in MAP were greatest after ganglionic or alpha-blockade, intermediate after RAS blockade, and negligible after AVP-V1 antagonism ([d(CH2)5Tyr(Me)]AVP). Recovery of MAP was also similar in the two groups except after phentolamine when MAP and HR remained lower in gravid rats. Superimposition of RAS or AVP blockade during phentolamine infusion suggested that ANG II and AVP were less effective in supporting MAP during alpha-blockade in pregnancy. Pressor responses to ANG II and norepinephrine during ganglionic blockade were markedly blunted during pregnancy; however, those to phenylephrine and AVP were unchanged. We conclude that contributions of ANS, RAS, and AVP to basal MAP are similar in pregnant and virgin rats; neural mechanisms dominating in both groups. However, recovery during alpha-blockade is impaired during gestation, apparently due to blunted HR responses and decreased pressor contributions of ANG II and AVP. This may be explained, in part, by decreased vascular reactivity to ANG II, although a similar mechanism cannot be invoked for AVP.
Hemodynamic and hormonal effects of renin inhibition in ovine heart failure
Authors: Fitzpatrick M. A. , Rademaker M. T. , Frampton C. M. , Charles C. J. , Yandle T. G. , Espiner E. A. , Ikram H.
Published: December 2017

The effects of renin inhibition have not previously been documented in established heart failure (HF). Accordingly, we investigated the acute hemodynamic and hormonal effects of a renin inhibitor (EMD 52297) in an ovine model of HF induced by rapid ventricular pacing (LVP). In seven sheep, recordings were made for 1 h before, during a 2-h infusion of renin inhibitor (RI) or vehicle, and after each infusion on the 5th and 6th day after commencing LVP. The RI (20 micrograms.kg-1.min-1) or vehicle was given in random order. RI infusion induced a rapid fall in plasma renin activity (PRA) and angiotensin II, reaching a nadir at 20 min. The vasodilator response was characterized by a 16% fall in mean arterial pressure (MAP), which was related to the fall in PRA (r = 0.78, P less than 0.05). MAP and PRA remained suppressed throughout the infusion period, and both returned to preinfusion levels within 10 min of terminating infusions. Left atrial pressure and plasma aldosterone were not significantly altered, while renal function was preserved despite the fall in perfusion pressure. RI has significant hemodynamic actions in a model of established HF.
Effect of neurotransmitters on the activation sequence of the isolated atrium
Authors: Schuessler R. B. , Bromberg B. I. , Boineau J. P.
Published: December 2017

Unipolar electrograms were recorded from 360 sites in 20 isolated, perfused canine right atria. In 52% of the preparations, spontaneous activation started in the sinus node region. In 32% of the preparations, spontaneous activation was initiated at the junction of the intercaval band and the crista terminalis. Simultaneous multicentric initiation occurred from both sites in 16% of the preparations. With infusion of incrementally increasing doses of norepinephrine, the superior sinus node site consistently assumed dominance. Infusion of incrementally increasing doses of acetylcholine produced no consistent pattern of pacemaker dominance. Propagation velocity during pacing was unaffected by either neurotransmitter. The results demonstrate the presence of two different pacemaker sites in the posterior right atrium that function spontaneously, devoid of any active or significant autonomic input. Exchange of dominance between the two sites occurs in the presence of norepinephrine and acetylcholine. The two sites appear to have a differential sensitivity to norepinephrine but are not differentially sensitive to acetylcholine. Changes in the pattern of activation seen with either neurotransmitters are mediated exclusively by the site of initiation and not by changes in conduction.
Cardiac microdialysis to estimate interstitial adenosine and coronary blood flow
Authors: Van Wylen D. G. , Willis J. , Sodhi J. , Weiss R. J. , Lasley R. D. , Mentzer R. M.
Published: December 2017

The purpose of this study was twofold: 1) to investigate the feasibility and usefulness of cardiac microdialysis for the simultaneous estimation of regional cardiac interstitial fluid (ISF) adenosine (ADO) concentration and coronary blood flow (CBF); and 2) to determine the changes in the ISF levels of ADO and CBF during cardiac stimulation or regional myocardial ischemia. Cardiac microdialysis probes were implanted in the left ventricular myocardium of chloralose-urethan-anesthetized dogs and perfused with Krebs-Henseleit buffer. The concentration of ADO in the effluent dialysate was used as an index of intramyocardial ISF ADO concentration while local CBF was measured by H2 clearance via a platinum wire within the dialysis fiber. Dialysate ADO was elevated immediately after insertion of the microdialysis probe, declined rapidly in the first 20 min, stabilized by 60 min, and remained constant for 2 h. Based on the relationship in vitro and in vivo between microdialysis probe perfusion rate and dialysate ADO concentration, ISF ADO concentration within the left ventricular myocardium was estimated to be 0.9-1.3 microM. Dobutamine (10 micrograms.kg-1.min-1) infusion resulted in a 36% increase in CBF and a 2.5-fold increase in dialysate ADO (n = 9; P less than 0.05). Regional myocardial ischemia, induced by occlusion of the left anterior descending artery (LAD), caused a 13-fold increase in dialysate ADO in the LAD perfused myocardium (n = 9; P less than 0.05). These results are consistent with the ADO hypothesis and suggest that cardiac microdialysis provides a reliable technique for the sampling of regional intramyocardial ISF.
Attenuation of pressor responses to arginine vasopressin in right-sided congestive heart failure
Authors: Stone C. K. , Imai N. , Sladek C. D. , Liang C. S.
Published: December 2017

Although arginine vasopressin (AVP) is elevated in heart failure, inhibition of the vasopressinergic V1-receptor produces minimal changes in blood pressure. To determine whether the V1 vasoconstrictor effect is attenuated in heart failure, we randomly administered three increasing doses of AVP and methoxamine intravenously to 11 dogs with right-sided congestive heart failure (RHF) and 7 sham-operated dogs. Plasma AVP was elevated in RHF (21 +/- 3 pg/ml) compared with sham-operated dogs (3.8 +/- 0.6 pg/ml). While the pressor response to methoxamine was similar in the two groups, AVP caused a smaller increase in mean aortic pressure in RHF dogs than sham-operated dogs. To determine whether the difference in the pressor response to AVP was caused by greater reflex withdrawal of the sympathetic activity in RHF than sham-operated dogs, we also administered AVP after these animals had been pretreated with prazosin and propranolol. Adrenoceptor blockade exaggerated the pressor response to AVP; however, the increase in mean aortic pressure was still smaller in RHF than sham-operated dogs. The diminished pressor response in adrenoceptor-blocked RHF dogs was associated with a smaller increase in total peripheral vascular resistance compared with similarly treated sham dogs. Thus, although the pressor response to AVP was offset by baroreflex activation, the attenuated pressor effect of AVP in heart failure cannot be explained by sympathetic withdrawal alone. AVP probably exerts a smaller direct vasoconstrictor effect when the vasopressinergic system is chronically activated in heart failure.
Venular-arteriolar diffusion of adenosine in hamster cremaster microcirculation
Authors: Hester R. L.
Published: December 2017

During increases in blood flow, both the terminal and the proximal arterioles dilate. The mechanism behind the dilation of the proximal arterioles is not known but may be the result of the diffusion of a vasoactive metabolite from adjacent venules. To determine whether an increase in venous adenosine (ADO) concentration could affect an adjacent arteriole, venules were perfused using a micropipette containing 10(-7)-10(-4) M ADO. During the venular perfusion, arteriolar diameter and red blood cell velocity were measured at a site 0.5 to 6 mm from the micropipette tip. The adjacent arteriole of the venular arteriolar pair dilated 29 +/- 3% with a 5-s 10(-4) M ADO perfusion, 32 +/- 4% with a 10-s 10(-4) M ADO perfusion, and 85 +/- 22% with a 60-s 10(-4) M ADO perfusion. One and 2-min perfusions with 10(-5) M ADO resulted in a 36 +/- 6% and 33 +/- 4% increase in diameter of the paired arteriole, respectively. The red blood cell velocity responses were variable, yet, on average, calculated blood flow increased in each group of experiments. Venular perfusions with saline resulted in a 2% change in arteriolar diameter. To rule out nondiffusional effects, venular perfusions were performed when the arteriole was not paired with the venule but crossed the venule. Venular perfusion with 10(-6) and 10(-7) M ADO resulted in a significant increase in diameter of the crossing arteriole of 19 +/- 3% and 6 +/- 2%, respectively. Therefore, the diffusion of a vasoactive metabolite from a venule to an arteriole may provide a mechanism by which the tissue can send a signal to cause a dilation of the more proximal arterioles.
α-Tocopherol attenuates myocardial membrane-related alterations resulting from ischemia and reperfusion
Authors: Massey K. D. , Burton K. P.
Published: December 2017

Page H1194: K. D. Massey and K. P. Burton. “α-Tocopherol attenuates myocardial membrane-related alterations resulting from ischemia and reperfusion.” The second sentence under results, Tocopherol levels, should read: “Tissue tocopherol levels were 20.2 ± 1.6 μg/g wet tissue (n = 9) in nontreated controls compared with 30.4 ± 0.8 μg/g wet tissue (n = 11) in vitamin E pellet-treated hearts (P < 0.001).”
Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity
Authors: Griffith T. M. , Edwards D. H.
Published: December 2017

Page H1175: T. M. Griffith and D. H. Edwards. “Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity.” In Fig. 4, the correct values of conductance are exactly 1/100 smaller than those originally shown. In the second and third line of the left-hand column, the unit of incremental conductance is mmHg–1, not mmHg·min·ml–1.
Leukocyte repletion reverses protective effect of neutropenia in thrombin-induced increase in lung vascular permeability
Authors: Lo S. K. , Garcia-Szabo R. R. , Malik A. B.
Published: December 2017

We examined the role of leukocytes in the pathogenesis of lung vascular injury induced by thrombin in awake sheep prepared with the lung lymph fistulas. Thrombin (80 U/kg) infusion in control sheep (n = 6) increased pulmonary arterial pressure (Ppa) twofold and pulmonary vascular resistance (PVR) three-fold for the 5-h experimental period. Thrombin also increased pulmonary vascular permeability to protein as assessed by decrease in the reflection coefficient (sigma) from 0.70 +/- 0.03 to 0.61 +/- 0.01. Thrombin caused similar initial pulmonary hemodynamic changes in sheep rendered neutropenic (n = 7; 2% neutrophil count of controls) by treatment with hydroxyurea; however, both Ppa and PVR returned toward base-line values within 120 min postthrombin challenge. The increases in pulmonary lymph flow and transvascular protein clearance also recovered rapidly beginning at 60 min after challenge with thrombin in neutropenic sheep. Neutropenia prevented the increase in lung vascular permeability as the sigma value of 0.71 +/- 0.02 was similar to the control value. Leukocytes isolated from control donor sheep were infused intra-arterially into recipient neutropenic sheep (n = 4) to assess the effects of neutrophil repletion on the pulmonary vascular responses. Thrombin (80 U/kg) challenge infused at 1-3 h after infusion of leukocytes increased lung lymph flow twofold and transvascular protein clearance fourfold and produced increases in Ppa and PVR comparable with the control group. The increases in these parameters were sustained for the 5-h experiment duration. The data indicate the essential pathogenetic role of neutrophils in mediating the thrombin-induced increase in lung vascular permeability.
Differential responses of uterine and umbilical vasculatures to angiotensin II and norepinephrine
Authors: Clark K. E. , Irion G. L. , Mack C. E.
Published: December 2017

Although the uterine vascular responses to endogenous vasoactive substances have been extensively investigated in pregnant sheep, the fetal umbilical responses to angiotensin II (ANG II) and norepinephrine (NE) have not been well characterized. Twenty-five pregnant ewes between 105 and 115 days of gestation were anesthetized and instrumented for hemodynamic measurements, systemic fetal and maternal intravenous infusions, and local maternal uterine arterial infusions of ANG II and NE. Fetal and maternal arterial pressure and heart rate, maternal uterine blood flow (total of left and right middle uterine arteries), and fetoplacental blood flow (common umbilical artery) were measured during continuous infusions of ANG II or NE. Fetal infusions of ANG II (0.03–1.0 micrograms.min-1.kg estimated fetal body wt-1) increased fetal arterial blood pressure by as much as 44% over base-line values, decreased umbilical blood flow by as much as 63%, and increased umbilical vascular resistance by up to 345%. Fetal infusions of NE (0.1–3 micrograms.min-1.kg-1) increased fetal arterial pressure 42% and increased umbilical vascular resistance by up to 38% but did not significantly alter fetoplacental blood flow. No significant maternal changes were observed during fetal infusions. Maternal infusion of ANG II increased maternal arterial pressure by as much as 59% and significantly increased uterine vascular resistance at the two highest doses but significantly decreased uterine blood flow only at the highest dose (17%; P less than 0.05). Maternal infusions of NE increased arterial pressure by as much as 113%, decreased uterine blood flow by as much as 76%, and increased uterine vascular resistance 3- to 10-fold over the base-line value.(ABSTRACT TRUNCATED AT 250 WORDS)
Saline infusion into lumen of resistance artery and small vein causes contraction
Authors: Bevan J. A. , Joyce E. H.
Published: December 2017

Infusion of saline into the lumen of a resistance artery from the rabbit ear at rates between 0.5 and 20 microliters/min causes a rate-dependent maintained contraction. This contraction is independent of the direction of saline flow and of the endothelium. The contraction is prevented by pretreatment with the vasodilator papaverine (0.1 mM), which also reversed the contraction during flow. Exclusion of calcium from the physiological saline solution plus ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1 mM) prevents the contraction, as does pre-exposure to cobalt (1 mM) and manganese (1 mM). Both these ions depress saline flow contraction once it is established. Saline flow-dependent contraction changes in a complex manner with temperature. It is greatest in resistance arteries from the pial, ear (skin), and femoral (muscle) segments, moderate to poor in coronary, mesenteric, and renal segments, and absent in the pulmonary segments. A small ear vein adjacent to the ear resistance artery also contracts to saline infusion. Although an explanation based on the washout of a vasodilator metabolite cannot be excluded, we favor the hypothesis that saline flow-induced shear stress of the inner surface of the vessel wall mechanically activates the vascular smooth muscle cells causing an extracellular Ca2(+)-dependent contraction. This response takes place through indomethacin-insensitive calcium-dependent mechanisms in vascular smooth muscle that differ from those associated with commonly studied surface receptors and with stretch.
High-speed digital imaging of cytosolic Ca2+ and contraction in single cardiomyocytes
Authors: O'Rourke B. , Reibel D. K. , Thomas A. P.
Published: December 2017

A charge-coupled device (CCD) camera, with the capacity for simultaneous spatially resolved photon counting and rapid frame transfer, was utilized for high-speed digital image collection from an inverted epifluorescence microscope. The unique properties of the CCD detector were applied to an analysis of cell shortening and the Ca2+ transient from fluorescence images of fura-2-loaded [corrected] cardiomyocytes. On electrical stimulation of the cell, a series of sequential subimages was collected and used to create images of Ca2+ within the cell during contraction. The high photosensitivity of the camera, combined with a detector-based frame storage technique, permitted collection of fluorescence images 10 ms apart. This rate of image collection was sufficient to resolve the rapid events of contraction, e.g., the upstroke of the Ca2+ transient (less than 40 ms) and the time to peak shortening (less than 80 ms). The technique was used to examine the effects of beta-adrenoceptor activation, fura-2 load, and stimulus frequency on cytosolic Ca2+ transients and contractions of single cardiomyocytes. beta-Adrenoceptor stimulation resulted in pronounced increases in peak Ca2+, maximal rates of rise and decay of Ca2+, extent of shortening, and maximal velocities of shortening and relaxation. Raising the intracellular load of fura-2 had little effect on the rising phase of Ca2+ or the extent of shortening but extended the duration of the Ca2+ transient and contraction. In related experiments utilizing differential-interference contrast microscopy, the same technique was applied to visualize sarcomere dynamics in contracting cells. This newly developed technique is a versatile tool for analyzing the Ca2+ transient and mechanical events in studies of excitation-contraction coupling in cardiomyocytes.
Atrial natriuretic peptide augments forearm capillary filtration in humans
Authors: Groban L. , Cowley A. W. , Ebert T. J.
Published: December 2017

Low-dose infusions of atrial natriuretic peptide (ANP) into humans reduce cardiac filling pressures without enhancing renal excretion or producing vasodilation. The present human study was undertaken to seek an effect of ANP on capillary filtration in humans and to determine its relationship to reductions in cardiac filling pressures. Heart rate (electrocardiogram), blood pressure (cuff method), and renal excretion of salt and water were determined, and central venous pressure (jugular vein cannulation, strain-gauge transducer) and forearm venous compliance and capillary filtration coefficient (strain-gauge plethysmography) were derived by computer. Forearm girth and venous pressure (peripheral vein catheter) measurements were obtained while the arm was elevated above heart level, and an upper arm blood pressure cuff was intermittently inflated to venous occluding pressures of 20, 30, and 40 mmHg. Forearm measurements, hematocrit, plasma proteins, albumin and plasma levels of ANP were determined from euvolemic volunteers before and during 60 min intravenous infusions of ANP (5 ng.kg-1.min-1, n = 9) or placebo (isotonic saline, n = 7). ANP infusions produced physiological increases (4- to 5-fold) in plasma ANP (from a base line 35 +/- 6 pg/ml) (P less than 0.05). Hemodynamic responses to ANP consisted of a reduction in central venous pressure (P less than 0.05) and no change in heart rate, mean arterial pressure, or renal excretory parameters. ANP increased forearm capillary filtration between 37 and 63% (P less than 0.05) from base line but did not significantly alter forearm compliance measurements.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelium-dependent and -independent relaxations to adenosine in guinea pig aorta
Authors: Headrick J. P. , Berne R. M.
Published: December 2017

Effects of endothelial removal and hypoxia on responses to adenosine, 5'-(N-ethylcarboxamido)-adenosine (NECA), 2-chloroadenosine, N6-cyclohexyladenosine (CHA), sodium nitroprusside, and acetylcholine were examined in guinea pig aortic rings. Rings contracted with 2 microM prostaglandin F2 alpha (PGF2 alpha) relaxed in a dose-dependent manner in response to all drugs. The order of potency of adenosine compounds was NECA greater than 2-chloroadenosine greater than adenosine greater than CHA. Endothelial rubbing potentiated the PGF2 alpha response by 11 +/- 3%, eliminated the acetylcholine (ACh) response, but had no effect on nitroprusside and CHA responses. Responses to adenosine, NECA, and 2-chloroadenosine were significantly depressed by rubbing (P less than 0.05). Oxyhemoglobin (5 microM) and metyrapone (0.1 mM) reduced ACh responses in intact rings but had no effect on the adenosine and nitroprusside responses. Indomethacin treatment (10 microM) did not alter ACh, nitroprusside, or adenosine responses in intact rings. Hypoxia (10% O2) potentiated maximal responses to adenosine (+26 +/- 3%) and nitroprusside (+28 +/- 4%) in intact and rubbed rings and reduced the maximal response to ACh in intact rings (-28 +/- 3%). It is concluded that 1) adenosine mediates relaxation in guinea pig aorta by endothelial-dependent and -independent mechanisms, 2) receptors involved in both endothelial-dependent and -independent relaxations are characteristic of the A2 adenosine subtype, 3) the endothelial response appears unrelated to EDRF or prostanoid release, and 4) the adenosine response is significantly potentiated by hypoxia.
Inhibition of hypoxic pulmonary vasoconstriction by increased left atrial pressure in dogs
Authors: Lejeune P. , De Smet J. M. , de Francquen P. , Leeman M. , Brimioulle S. , Hallemans R. , Melot C. , Naeije R.
Published: December 2017

To further explore the mechanism of hypoxic pulmonary vasoconstriction, we studied the mean pulmonary arterial pressure (Ppa)/left atrial pressure (Pla) relationship at fixed cardiac index (Q) and the Ppa/Q relationship at several levels of fixed Pla in pentobarbital sodium-anesthetized dogs ventilated alternately in hyperoxia [fraction of inspired O2 (FIO2) 0.4 or 1.0] and in hypoxia (FIO2 0.1). In all experimental conditions, Ppa/Q plots were linear with extrapolated pressure intercepts (Pi) not significantly different from Pla. Hypoxia increased the slope of Ppa/Q plots and did not affect Pi. In hyperoxia, increasing Pla (3 to 26 mmHg) induced approximately equal increases in Ppa at fixed Q and shifted Ppa/Q plots toward higher pressures in a parallel manner. In hypoxia, increasing Pla (4 to 25 mmHg) did not affect Ppa at fixed Q until Pla exceeded 16 mmHg and shifted Ppa/Q plots toward higher pressures with a decrease in slope. Consequently, the hypoxia-induced increases in Ppa at constant Q and constant Pla were attenuated at higher Pla. Thus, in anesthetized dogs, hypoxia increases the slope of Ppa/Q plots without affecting Pi at fixed Pla, and an increase in Pla inhibits hypoxic pulmonary vasoconstriction. These results can be explained without invoking a hypoxia-induced Starling resistor mechanism in the pulmonary circulation.
Can pulsed Doppler technique measure changes in aortic blood flow in conscious rats?
Authors: Gardiner S. M. , Compton A. M. , Bennett T. , Hartley C. J.
Published: December 2017

To determine whether the pulsed Doppler (PD) system could be used to measure cardiac output we compared estimates of changes in aortic flow obtained from PD or electromagnetic (EM) probes on the ascending aorta in separate groups of conscious Long-Evans and Brattleboro rats under a variety of conditions. EM probes showed significant increases and decreases in aortic blood flow after administration of nitroprusside or methoxamine, respectively, but 20-MHz PD probes connected to a PD mainframe with a pulse repetition frequency (PRF) of 62.5 kHz showed no systematic changes in Doppler shift, due to "aliasing" of the Doppler signal. Aortic blood flow was significantly increased with intravenous volume expansion or isoprenaline administration, but these changes were not reliably detected by PD probes operating in a system with a PRF of 62.5 kHz. Calculation of expected peak Doppler shift signals from the phasic EM flow signal showed that these exceeded the Nyquist limit (PRF/2, i.e., 31.25 kHz) for the commercially available pulsed Doppler system. However, a modified pulsed Doppler module capable of resolving aliases and operating at a PRF of 125 kHz produced reliable results for changes in thoracic aortic Doppler shift, in good agreement with the EM probe data. In addition, placement of a cuff around the thoracic aorta did not alter cardiac baroreflex sensitivity.
Independent influence of left atrial pressure on regional peak lengthening rates
Authors: Hoit B. D. , LeWinter M. , Lew W. Y.
Published: December 2017

We examined the influence of left atrial pressure on regional peak lengthening rates in six open-chest dogs. Sonomicrometers were implanted in the midwall of the anterior apex, the midanterior wall, and the posterior wall of the left ventricle. A bolus of blood was injected into the left atrium during ventricular systole by a computer-driven power injector to produce an isolated increase in left atrial pressure without altering the peak rate of left ventricular pressure fall, regional systolic shortening, or end-systolic length. Several left atrial injections of different volumes were performed over a wide range of left ventricular end-diastolic pressure (LVEDP) (from 7 to 22 mmHg). The peak lengthening rate increased in direct proportion to the increase of left atrial pressure. This effect was significantly greater in the apical than midanterior or posterior sites and decreased at all sites at higher LVEDP. Similar size left atrial injections produced greater increases in atrioventricular pressure gradient but smaller increases in left atrial pressure at low compared with high LVEDP. We conclude that left atrial pressure is an independent determinant of regional peak lengthening rates in the intact left ventricle. The influence of left atrial pressure is attenuated at higher LVEDP because of a smaller change in the diastolic pressure gradient, although viscoelastic effects may play a role.
Studies of collateral perfusion to canine middle cerebral artery territory
Authors: Loftus C. M. , Greene G. M. , Detwiler K. N. , Baumbach G. L. , Heistad D. D.
Published: December 2017

Previous studies of intracranial collateral circulation have not distinguished between true "collateral" blood flow (flow to a region that occurs only when a primary artery is occluded) and "overlap" flow (flow to a region that is present under both normal and demand conditions). These experiments had three purposes: 1) to identify tissues that were truly collateral dependent, 2) to determine potential for true collateral flow in the absence of overlap flow, and 3) to determine whether an anatomical basis for overlap flow could be demonstrated. Branches (700-900 microns) of the dog middle cerebral artery (MCA) were perfused with autologous blood. The perfused region, which was the area at risk, was identified by intravenous injection of neutral red dye. Microspheres were used to measure regional cerebral blood flow (rCBF). Overlap flow was determined by perfusion of the artery with microsphere-free blood. True collateral flow (total rCBF minus overlap flow) was determined by analysis of rCBF to the risk area after cessation of vessel perfusion. Most of the risk area had substantial levels of overlap flow (about one-third of base line). In the center of the area at risk, the true collateral-dependent area was identified [mean overlap flow 4 +/- 1 (mean +/- SE) ml.min-1.100 g-1], which had high levels of perfusion from collateral vessels (102 +/- 14) within 30 s of vascular occlusion. Microfil injection into two adjacent MCA branches showed discrete borders between vascular territories, with no overlapping vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Ca exchange under non-perfusion-limited conditions in rat ventricular cells: identification of subcellular compartments
Authors: Langer G. A. , Rich T. L. , Orner F. B.
Published: December 2017

Freshly prepared ventricular myocytes from rat hearts, aliquots of which were tested for sarcolemmal integrity by La exposure, were labeled at high 45Ca specific activity. Isotope was subsequently washed out at a perfusion rate of 2.8 ml/s with washout solution sampled each 1 s. No initial unrecorded period of washout was imposed. Four compartments were distinguishable: 1) a "rapid" compartment (RC) containing 2.6 mmol Ca/kg dry wt of La-displaceable Ca, half time (t1/2) less than 1 s; 2) an "intermediate" compartment(s) (IC) containing 2.1 mmol, t1/2 = 3 and 19 s; 3) a "slow" compartment (SC) containing 1.6 mmol, t1/2 = 3.6 min; 4) an "inexchangeable" compartment that demonstrated no 45Ca uptake after 60-min labeling containing 1.2 mmol. Introduction of 10 mM caffeine as a probe for sarcoplasmic reticulum (SR) content at various times during the washouts caused an increased release of 45Ca. The net increased 45Ca release plotted as a function of time at which caffeine was introduced produced a biexponential curve with t1/2s of 2 and 22 s, very similar to the t1/2s of the IC. Ryanodine (1 microM) significantly reduced the caffeine-induced 45Ca release, confirming the SR locus of the IC. Cells were perfused with 10 mM NaH2PO4 to specifically increase mitochondrial 45Ca labeling. Subsequent removal of PO4 at various times during washouts produced large increases in effluent 45Ca. A plot of the net peak release of 45Ca vs. time of PO4 removal was monoexponential with t1/2 = 3.3 min, very similar to the SC t1/2. The large La-accessible RC remains unlocalized, but the rapidity of its exchange places it in the sarcolemma and/or at sites in rapid equilibrium with the sarcolemma.
Long-lasting openings of single slow (L-type) Ca2+ channels in chick embryonic heart cells
Authors: Tohse N. , Sperelakis N.
Published: December 2017

Single-channel currents were recorded in cultured embryonic chick (3-day-old) cardiomyocytes in cell-attached patch-clamp experiments. The patch electrode contained 50 mM Ba2+. The cell was bathed in an external solution containing 150 mM K+ (pH 7.4) at room temperature. Depolarizing pulses above -30 mV, from a holding potential of -80 mV, elicited inward unitary currents. The conductance of the channel for this unitary current was 26 pS. The activity of these channels was completely blocked by nifedipine (3 microM). These results indicate that the channel is a slow (L-type) Ca2+ channel. The channels exhibited long-lasting openings, in addition to conventional brief openings. These long openings resembled the long openings produced by the dihydropyridine Ca2+ agonist BAY K 8644 and resultant mode 2 behavior (Hess et al., Nature Lond. 311: 538-544, 1984). The long-lasting openings were observed in 25 patches out of a total of 29 patches in which single-channel activity was present. High open-state probability (Po) sweeps (with Po greater than 0.65), which mainly contain long-lasting openings, accounted for 20.7% of all sweeps. The open-time histogram for the Ca2+ channels was fitted by two exponential components. The time constants of the two components were 0.45 ms (fast) and 6.30 ms (slow). These kinetic properties were similar to those of the previous reports using BAY K 8644. Thus the slow (L-type) Ca2+ channels in young embryonic chick heart cells naturally produce many long-lasting openings in the absence of any added dihydropyridine Ca2+ agonist.
Role of prostanoids in cerebrovascular responses to asphyxia and reventilation in newborn pigs
Authors: Pourcyrous M. , Leffler C. , Busija D.
Published: December 2017

Cerebral hemodynamics during asphyxia and reventilation were investigated in normothermic, hypothermic (35 degrees C), and indomethacin-pretreated (5 mg/kg iv) anesthetized, newborn pigs. In the normothermic group, total cerebral blood flow (CBF) measured with radioactive microspheres was 57 +/- 12 ml.min-1 x 100 g-1 during baseline, 104 +/- 19 at 1 min of asphyxia, 39 +/- 5 at 5 min of asphyxia, 186 +/- 16 at 8 min of reventilation, and 95 +/- 20 at 16 min of reventilation. During asphyxia and reventilation blood flow to brain stem was better regulated than to cerebrum or cerebellum. Baseline CBF was similar in the indomethacin and hypothermic groups (32 +/- 2 and 41 +/- 5 ml.min-1 x 100 g-1, respectively; n = 5 for each group). However, during asphyxia, blood flow was never less in either one of these groups than in the normothermic group in spite of a lack of arterial hypercapnia at 1 min in the hypothermia group. During reventilation, blood flow was sometimes lower in the hypothermic and indomethacin groups than the normothermic group but never lower when considered on a percentage change from baseline basis. We conclude that inhibition of prostanoid production with indomethacin did not limit vasodilation during these conditions.
Autonomic pathophysiology in heart failure: carotid baroreceptor-cardiac reflexes
Authors: Sopher S. M. , Smith M. L. , Eckberg D. L. , Fritsch J. M. , Dibner-Dunlap M. E.
Published: December 2017

We evaluated reflex cardiac responses mediated by carotid baroreceptors in 14 patients with treated congestive heart failure and 14 age-matched healthy subjects. We used a neck chamber to deliver two types of pressure change: 5 s of continuous 50-mmHg suction and an R wave triggered, ramped neck pressure-suction sequence. Reflex latencies (functions of baroreflex arc duration) were comparable in heart failure patients and healthy subjects. However, the average maximum baroreflex slope (gain) was less in heart failure patients than healthy subjects (2.0 vs. 3.5 ms/mmHg, P less than 0.010), the R-R interval response range was smaller (91 vs. 188 ms, P = 0.002), and the resting R-R interval position on stimulus-response relation (operational point) was significantly (13 vs. 40%, P = 0.001) closer to threshold. Stepwise regression analysis suggested that baseline R-R interval variability, used as an index of ongoing vagal-cardiac nerve traffic, and the inverse of antecubital vein plasma norepinephrine level, used as an index of sympathetic nerve activity, contributed significantly to the prediction of abnormal carotid baroreceptor-cardiac reflex responses. Thus our results suggest that in heart failure patients, carotid baroreceptor-cardiac reflex abnormalities are related significantly to ongoing abnormalities of vagal and sympathetic cardiovascular outflow.
Transient inotropic effects of low extracellular sodium in perfused rat heart
Authors: Kolar F. , Cole W. C. , Ostadal B. , Dhalla N. S.
Published: December 2017

The inotropic effects of low concentrations of extracellular Na+ (35-110 mM) were studied using Langendorff-perfused rat hearts. Low Na+ induced an initial positive inotropic response proportional to the decrease of transsarcolemmal Na+ gradient. At 35 mM Na+, this effect was followed by a secondary fall in contractility and rise of resting force (RF) and then by a delayed positive inotropic effect and recovery of RF. The magnitude of these low Na(+)-induced transient changes was dependent on the extracellular Ca2+ concentration and was altered by amiloride (6 x 10(-4) and 2.5 x 10(-3) M), ouabain (5 x 10(-5) and 5 x 10(-4) M), ryanodine (2 x 10(-8), 1 x 10(-7) and 1 x 10(-6) M), and sodium azide (1 x 10(-3) and 5 x 10(-3) M) but not by verapamil (2 x 10(-8) and 1 x 10(-7) M) or vanadate (4 x 10(-6) M). The data indicate the initial positive inotropic response of the rat heart to low Na+ may be due to rapid loading of myocytes with Ca2+ through the Na(+)-Ca2+ exchange mechanism. The secondary depression of contractility and the rise of RF appear to be the consequence of the short-lived intracellular Ca2+ overload. Furthermore, the recovery of contractions and the delayed positive inotropic response may be the result of the intracellular redistribution of excessive Ca2+ into the sarcoplasmic reticulum with mitochondria and increased transsarcolemmal Ca2+ efflux apparently playing a more minor role.
Transcapillary adenosine transport in isolated guinea pig and rat hearts
Authors: Mohrman D. E. , Heller L. J.
Published: December 2017

Transcapillary adenosine transport was studied in isolated guinea pig and rat hearts perfused with a colloid-free solution. High-performance liquid chromatography techniques were used to measure adenosine concentration of venous and interstitial (epicardial surface) fluid during steady-state perfusion with various concentrations of adenosine. A mathematical model was used to analyze these data to obtain estimates of the following parameters of transcapillary adenosine transport: PSg, permeability-surface area product for adenosine movement through interendothelial cell channels; PSecl, permeability-surface area product for adenosine movement through the luminal plasma membrane of endothelial cells; and Gec, clearance rate constant for endothelial cell metabolism and/or sequestration of adenosine. In both guinea pig and rat hearts, PSg was estimated to be less than or equal to 3 ml.min-1.g-1. Estimates of PSecl and Gec of guinea pig hearts (7.2 +/- 0.4 and 230 +/- 157 ml.min-1.g-1) were significantly less than those of rat hearts (66 +/- 11 and 2,490 +/- 1,360 ml.min-1.g-1). That PSecl is greater than PSg in both species indicates that endothelial cells represent an important pathway for transcapillary adenosine transport. That Gec is much greater than PSecl in both species implies that endothelial cells act as a sink for adenosine from surrounding areas. Our results indicate that endothelium is a stronger sink for adenosine in rat hearts than in guinea pig hearts. Inosine infusion (10(-4)M) had little effect on the estimated PSecl and Gec in guinea pig hearts but reduced these parameters several-fold in rat hearts, suggesting that different transport mechanisms for adenosine exist in endothelia of guinea pig and rat hearts.
Effect of superoxide dismutase and catalase, given separately, on myocardial "stunning"
Authors: Jeroudi M. O. , Triana F. J. , Patel B. S. , Bolli R.
Published: December 2017

Controversy persists regarding which oxygen metabolites are cytotoxic. Although the combination of superoxide dismutase (SOD) and catalase has been shown to attenuate postischemic myocardial dysfunction ("stunning"), it is unknown whether this beneficial effect is due to scavenging of O2-., H2O2, or both. Accordingly, 85 open-chest dogs underwent a 15-min occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. In phase A, dogs received an intravenous infusion of saline (group I), SOD (5 mg/kg, group II), catalase (12,000 U/kg, group III), or the combination of SOD and catalase (same doses, group IV). Recovery of regional myocardial function (assessed as systolic wall thickening) after reperfusion was significantly improved by the combination of SOD and catalase but not by SOD alone or catalase alone. To determine whether higher doses of enzymes are more effective, in phase B dogs received an intracoronary infusion of normal saline (group V), SOD in low dose (1.5 mg/kg, group VI), SOD in high dose (6.3 mg/kg plus 1.5 mg/kg iv, group VII), catalase in low dose (18,000 U/kg, group VIII), or catalase in high dose (240,000 U/kg plus 40,000 U/kg iv, group IX). Despite the fact that the local plasma levels of enzymes were considerably higher than those achieved in phase A, none of the treatments in phase B significantly enhanced recovery of contractile function. This study demonstrates that the combination of SOD and catalase is more effective than either enzyme alone in attenuating postischemic myocardial dysfunction and that increasing the doses of SOD or catalase does not provide additional protection. The results suggest that both O2-. and H2O2 contribute significantly to the pathogenesis of myocardial stunning after regional ischemia in the intact animal. Furthermore, the data imply that if SOD and catalase are to be used clinically to prevent postischemic dysfunction, protection may be achieved most effectively by combining the two enzymes.