bluuebunny/crossref_metadata_2025 huggingface dataset:
Ouabain effect on myocardial mechanical function and sodium pump in the fetus
Authors: Nakanishi T. , Shimizu T. , Uemura S. , Jarmakani J. M.
Published: December 2017

Effects of ouabain (0.75, 1, 1.5, 2.5 or 5 X 10(-6) M) on the mechanical function and sodium pump were studied in the isolated arterially perfused fetal and newborn rabbit heart. Measurement of myocardial 86Rb+ active uptake was used as a marker of the sodium pump activity. The inotropic effect of ouabain in the fetus was not significantly different from that in the newborn; 2.5 X 10(-6) M ouabain caused mechanical toxicity (decrease in +dT/dtmax and increase in resting tension) in the fetus but not in the newborn. After ouabain infusion, both the inhibition of Rb+ uptake and the significant decrease in tissue potassium content were similar in the fetus and the newborn. In the fetal muscle perfused with low calcium (0.5 mM) solution, mechanical toxicity of ouabain was significantly less than in the control (1.5 mM Ca2+) solutions. High extracellular calcium (30 mM) per se caused mechanical toxicity in the fetus but not in the newborn. These data indicate that, in the isolated arterially perfused heart preparation, mechanical toxicity in the fetus is observed at lower ouabain concentrations than in the newborn. This difference in mechanical toxicity may not be explained by the age-related difference in sodium pump activity. The greater calcium toxicity in the fetus may be the reason for the increased ouabain toxicity in this age group.
Transmural pH gradient in canine myocardial ischemia
Authors: Watson R. M. , Markle D. R. , Ro Y. M. , Goldstein S. R. , McGuire D. A. , Peterson J. I. , Patterson R. E.
Published: December 2017

The subendocardium is more susceptible to ischemia than the subepicardium. Studies during critical coronary stenosis have demonstrated subendocardial hypoperfusion relative to the subepicardium and transmural gradients in certain tissue metabolites. Although ischemia causes acidosis, the existence of a transmural pH gradient has never been demonstrated or quantitated. Thus we reduced coronary blood flow to 20 +/- 5% of normal in eight open chest anesthetized (morphine sulfate and pentobarbital) dogs and to 45 +/- 5% in two dogs. We implanted specially designed miniature fiber-optic pH probes in normal and ischemic subendocardium (depth 5.5-8 mm) and subepicardium (depth 3-4 mm). Separate experiments validated use of the fiber-optic pH probe system to measure tissue pH. Although both probes were located in the ischemic zone, there was a large transmural gradient, i.e., from normal pH values (7.36) in the subepicardium to severely acidotic (pH 6.94) 2 mm deeper in the subendocardium. This marked difference in pH between nearby transmural layers may have important implications regarding arrhythmogenesis in the setting of acute myocardial ischemia.
cAMP-dependent reduction in membrane fluxes during relaxation of arterial smooth muscle
Authors: Jones A. W. , Bylund D. B. , Forte L. R.
Published: December 2017

Forskolin, an activator of adenylate cyclase, inhibited contractures induced in rat aorta by norepinephrine (NE) and angiotensin II and by KCl depolarization. The concentration of forskolin required to inhibit NE-induced contractures was significantly lower than required to inhibit KCl-induced contractures (IC50 0.18 +/- 0.01 vs. 2.2 +/- 0.2 microM). Forskolin effectively relaxed NE-induced contractures when active Na+-K+ transport was inhibited. Stimulation of 42K and 36Cl effluxes by NE was inhibited by low concentrations of forskolin. The IC50 for forskolin inhibition of 42K efflux, 0.17 +/- 0.02 M, was similar to that for relaxation of NE contraction. The time course for forskolin-induced increases in adenosine 3',5'-cyclic monophosphate (cAMP) was consistent with that for forskolin-mediated relaxation and its maintenance. Fifty percent inhibition of both NE-induced contractures and NE-stimulated 42K effluxes occurred at levels of cAMP that were 1.4 times basal, and 90% inhibition of both processes was associated with a two to threefold increase in cAMP content. In sharp contrast, the level of tissue cAMP associated with inhibition of KCl contractures was 6-10 times higher than that associated with inhibition of NE-induced contractures. We postulate that cAMP-dependent regulation of membrane fluxes stimulated by receptor occupancy represents a primary mechanism for relaxation of a NE contracture, whereas the processes that regulate depolarization-dependent channels and the phosphorylation of myosin light chain kinase occur at much higher cAMP content and apparently function in a secondary capacity.
Cardiopulmonary response of the rat to gram-negative bacteremia
Authors: Pass L. J. , Schloerb P. R. , Pearce F. J. , Drucker W. R.
Published: December 2017

Hemodynamic and respiratory effects of a continuous 5-h intravenous infusion of live Escherichia coli were studied in rats. Control animals were infused with saline. Rats infused with 1.8 +/- 0.4 X 10(10) bacteria/h did not survive a 5-h infusion. These animals developed early hypotension and reduced cardiac output (CO) measured by thermal dilution technique. Rats infused with 8.0 +/- 0.4 X 10(9) bacteria/h survived a 5-h infusion with hypotension and reduced CO occurring later in the course of bacteremia. Heart rate was markedly elevated in both septic groups. Arterial blood gas measurements revealed that partial pressure of O2 was not affected by bacteremia, but partial pressure of CO2 was significantly decreased. Arterial pH remained within the normal range indicating respiratory compensation of a metabolic acidosis. Since hypotension and reduced CO were accompanied by a fall in right atrial pressure (RAP) during bacteremia, a third septic group was studied to evaluate cardiac performance during volume loading. After 3-5 h of bacteremia, a 40% reduction in CO was associated with a significant drop in arterial pressure and RAP. Despite volume loading, ventricular stroke work and arterial pressure were significantly reduced compared with control animals. The results indicate that severe gram-negative bacteremia produces myocardial depression in the rat. This model can be useful for further studies of cardiac dysfunction during sepsis.
Oxidation of carbohydrates and palmitate by intact cultured neonatal rat heart cells
Authors: Ross P. D. , McCarl R. L.
Published: December 2017

The rates of uptake and oxidation of glucose, lactate, pyruvate, and palmitate were measured for "mixed" cultures of rat heart cells that exhibit a myocyte-to-fibroblast ratio similar to that observed in vivo. Glucose uptake and conversion to lactate were also measured using enriched cultures of myocytes and fibroblasts. The metabolism of mixed cultures, which contain 70-80% myocytes, closely resembles that of enriched myocyte cultures. The energy production and substrate oxidation rates of cultured neonatal heart cells, adult myocytes, and perfused hearts are compared. It appears that the energy requirements of cultured heart cells are much lower than that of whole tissue. The results suggest that the metabolism of cultured heart cells may be basically the same as those in vivo but appears to be different because of reduced energy requirements in culture.
Comparison of renin-specific IgG and antibody fragments in studies of blood pressure regulation
Authors: Dzau V. J. , Kopelman R. I. , Barger A. C. , Haber E.
Published: December 2017

The use of antirenin antibody and its fragments as specific tools for the analysis of the role of renin in blood pressure regulation is assessed in this study. Specific immunoglobulin G (IgG) or its antibody fragments (Fab) raised against purified canine renal renin were employed. These agents had no effect on blood pressure in the sodium-replete unanesthetized dog but induced systemic vasodepressor response (16.4 +/- 2 mmHg mean pressure) and suppression of plasma renin activity in sodium-deplete animals. Renin-specific IgG or Fab restored mean systemic pressure of acute renovascular hypertensive dogs to normotensive levels (132 +/- 2 to 90 +/- 5 mmHg) associated with inhibition of plasma renin activity (11.2 +/- 2 to 1.4 +/- 0.7 ng angiotension I X ml-1 X h-1). A linear relationship was demonstrated between the reduction in mean systemic pressure and fall in plasma renin activity (r = 0.87, P less than 0.005). The onset of action of both agents occurred within minutes. However, the peak effect of Fab was observed within 1-2 min, while that of IgG was delayed by approximately 20 min. The duration of action of Fab was short lived (about 30 min) whereas that for IgG was prolonged (up to 24 h). The results demonstrate the usefulness of renin-specific IgG and Fab as tools in physiological studies.
Increased number of myocardial blood flow measurements with radionuclide-labeled microspheres
Authors: Baer R. W. , Payne B. D. , Verrier E. D. , Vlahakes G. J. , Molodowitch D. , Uhlig P. N. , Hoffman J. I.
Published: December 2017

We evaluated the use of a least-squares radionuclide separation technique to allow an increased number of myocardial blood flow measurements with radionuclide-labeled microspheres in dogs. Two sets of labeled microspheres were studied: a set of eight labeled with 125I, 153Gd, 57Co, 51Cr, 113Sn, 85Sr, 95Nb, and 46Sc; and a set of nine in which 125I and 46Sc were replaced with 114In, 54Mn, and 65Zn. For each microsphere label the nuclide activities determined by least-squares separation compared favorably with those actually added to in vitro samples containing a fixed amount of the other nuclides in the set. For the set of eight radionuclide-labeled microspheres, myocardial flow measurements made with the least-squares separation technique and the reference sample method were usually within 15% and almost all within 20% of direct measurements of coronary venous outflow in a right heart bypass preparation. Serial left atrial injections of 15-micron microspheres totaling 48 X 10(6) caused no significant changes in systemic hemodynamics, regional myocardial flows, or coronary pressure-flow relations, whether the coronary bed was autorelating or vasodilated with chromonar. We conclude that at least nine myocardial blood flow measurements can be made in dogs with acceptable accuracy and without evidence of dysfunction due to embolization of the coronary vascular bed. With appropriate validation, this method should be applicable to other organs and animal models as well.
Baroreflex sensitivity and susceptibility to systolic hypertension induced by DOCA-salt in the Sabra rat
Authors: Weinstock M. , Schorer-Apelbaum D. , Ben-Ishay D.
Published: December 2017

Rats of the salt-resistant Sabra strain (SBN) have a more sensitive baroreflex control of heart rate than do normotensive hypertension-prone salt-sensitive (SBH) rats. To test the hypothesis that increased baroreflex sensitivity confers resistance to hypertension, aortic baroreceptor deafferentation (ABD) was performed in 7- to 10-wk-old SBN rats. This treatment reduced the slope of the mean arterial pressure-heart period (MAP-HP) relationship in response to infusions of increasing doses of phenylephrine in conscious rats, from 1.92 +/- 0.21 to 0.66 +/- 0.11 ms X mmHg-1 (P less than 0.01). The latter value did not differ significantly from that of untreated SBH rats (0.56 +/- 0.07 ms X mmHg-1). Treatment of uniphrectomized SBH, SBN-ABD, and sham-operated SBN rats for 3 wk with deoxycorticosterone acetate (DOCA; 25-mg pellet) and 0.9% NaCl + 0.4% KCl (to maintain normal serum K+ values) as drinking fluid caused increases in systolic blood pressure from 126 +/- 3 to 147 +/- 5 mmHg and 104 +/- 6 to 130 +/- 8 mmHg in the former two groups, respectively, but no significant change (105 +/- 3 to 110 +/- 4 mmHg) in SBN rats when measured by an indwelling arterial catheter in the tail artery. The slopes of the MAP-HP relationships of each of the above three groups of rats were not significantly altered by DOCA-salt treatment. It is concluded that a decrease in baroreflex control of the heart by ABD can render SBN rats sensitive to DOCA-salt-induced systolic hypertension.
Effects of graded insulin therapy on cardiac function in diabetic rats
Authors: Rubinstein M. , Schaible T. F. , Malhotra A. , Scheuer J.
Published: December 2017

To determine the effects of graded insulin therapy on cardiac function and biochemistry, rats were made diabetic by streptozotocin (50 mg/kg) and subsequently treated with either 3 U of insulin per day (D3) or 5 U/day (D5) and compared with untreated diabetic rats (D phi) and a nondiabetic control group (C). Blood glucose, water consumption, and heart and body weights in D3 and D5 showed dose-dependent responses between those of D phi and C. Cardiac function was studied at similar heart rates and similar left atrial and aortic pressures in an isolated working heart apparatus. Hearts from D phi showed significant decreases in end-diastolic pressure, peak left ventricular systolic pressure, and positive dP/dt, whereas these values in D3 and D5 were similar to those in C. The isovolumic relaxation period was significantly longer in the D phi group, intermediate between D phi and C in D3, and the same in D5 and C. Ca2+-ATPase activity of myosin and actin-activated Mg2+-ATPase activity was depressed in D phi, partially corrected in D3, and completely corrected in D5. Myosin isoenzyme distribution displayed a shift from the predominant V1 pattern observed in C to a predominant V3 pattern in D phi. Treatment with 3 U of insulin per day partially corrected the isoenzyme abnormality, and treatment with 5 U/day restored the isoenzyme distribution to normal. These results indicate that gross cardiac contractile function can be normalized with insulin dosages that are not sufficient to correct hyperglycemia, polydipsia, or body and heart weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of thoracic spinoreticular and spinothalamic cells to intracardiac bradykinin
Authors: Blair R. W. , Weber R. N. , Foreman R. D.
Published: December 2017

The response characteristics of spinoreticular and spinothalamic cells to intracardiac injection of bradykinin were determined in cats anesthetized with chloralose. Extracellular potentials of individual spinoreticular and spinothalamic cells were recorded from the T2-T4 segments of the spinal cord. Only those cells with cardiopulmonary sympathetic afferent input were tested for responses to intracardiac bradykinin (1-6 micrograms/kg). Thirty-seven of the 64 cells studied responded to bradykinin; 36 were excited and one was inhibited. For excited cells, discharge rate increased from 4 +/- 1.0 (SE) spikes/s to a peak of 20 +/- 2.4 spikes/s, a fivefold increase. Latency to onset of cell response was 13 +/- 1.1 s, and latency to peak response was 24 +/- 1.4 s after drug injection. Tachyphylaxis to additional doses of bradykinin was observed in 17 of 32 cells. Occurrence of tachyphylaxis was sometimes altered after bilateral cervical vagotomy. The projection sites in the caudal medulla and thalamus were similar for responsive and nonresponsive cells. Laminar cell locations in the spinal cord had no significant influence on likelihood of cell response to bradykinin. We conclude that spinoreticular and spinothalamic cells have a role in transmitting noxious information from the heart to the brain.
Adenosine and calcium alter adrenergic-induced intact heart protein phosphorylation
Authors: Fenton R. A. , Dobson J. G.
Published: December 2017

Adenosine reduces cardiac mechanical and metabolic manifestations of catecholamine stimulation possibly by attenuating catecholamine-enhanced adenylate cyclase activity and sarcolemmal Ca2+ flux. The effects of adenosine and Ca2+ on catecholamine-induced myocardial protein phosphorylation were investigated using isolated rat hearts perfused with a 32P-enriched medium. Isoproterenol (10(-7) M, 1 min) elicited a 107-379% increase in 32P incorporation into proteins having molecular weights of 155, 92, 30, 28, 22, and 20 kdaltons. The left ventricular pressures and maximum rates of ventricular pressure development and ventricular relaxation were significantly elevated. These effects of isoproterenol were inhibited by propranolol (10(-5) M). Adenosine (10(-5) M, 2 min) decreased the isoproterenol-elicited increases in 32P incorporation by 50-86% and decreased the contractile responses but had no effect in the absence of isoproterenol. Raising the perfusion Ca2+ concentration from 1 to 4 mM did not alter the 32P incorporations but increased contractile parameters. The increase in Ca2+ augmented the isoproterenol 32P responses but not the contractile responses to isoproterenol. These results are consistent with the proposal that catecholamines augment cardiac metabolism and contractility by enhancing myocardial protein phosphorylation. Adenosine and Ca2+ modulate these responses.
Changes in circulating blood volume influence aortic characteristic impedance in awake dogs
Authors: Stone D. N. , Dujardin J. P. , Klopfenstein H. S. , Brooks H. L. , Pieper H. P.
Published: December 2017

Experiments on five chronically instrumented dogs were performed to study the effects of changes in circulating blood volume on the aortic smooth muscle activity in awake animals. The external diameter of the proximal descending aorta was measured with a sonomicrometer. Aortic pressure was measured in the same cross-sectional area with a catheter-tip transducer. Acute hemorrhage of 15% of the estimated blood volume was performed 17 times by quickly withdrawing blood through a jugular cannula. At any given arterial pressure within the range of overlap the aortic diameter (D) was always decreased after hemorrhage compared with control, and the pressure-strain elastic modulus (Ep) and the characteristic impedance (Zc) were always increased. For example at 140 kdyn X cm-2 (104.5 mmHg) delta D = -0.61 +/- 0.12 mm or delta D = -3.44 +/- 0.68% of control, delta Ep = 31.0 +/- 8.6%, and delta Zc = 22.6 +/- 4.5%. Each of these changes was significant with P less than 0.01. Volume expansion of 30% was performed eight times by infusing warm saline. At any given arterial pressure D was always increased and Ep and Zc were always decreased. At 140 kdyn X cm-2 delta D = 0.55 +/- 0.15 mm or delta D = 3.12 +/- 0.95% of control, delta Ep = -12.4 +/- 3.2%, and delta Zc = -12.0 +/- 2.1%. Each of these changes was significant with P less than 0.01. Since in these awake animals the changes in circulatory blood volume modified the arterial pressure only slightly, the contribution of viscoelasticity and myogenicity to the observed responses was minimal.
Synchronization of automatic cells in S-A node during vagal stimulation in dogs
Authors: Yang T. , Jacobstein M. D. , Levy M. N.
Published: December 2017

In anesthetized, open-chest dogs, one burst of stimuli was delivered to the left or right vagus nerve each cardiac cycle. The timing of the stimulus bursts relative to the cardiac cycle was varied by a constant, small amount on successive cardiac cycles, until the entire cardiac cycle was scanned. The level of vagal activity was changed by varying the number of stimulus pulses in each burst; two levels of activity were used in each experiment. For a given level of vagal activity, the mean cardiac cycle length and the amplitude of the phase-response curve were significantly greater during right than during left vagal stimulation. These response characteristics increased as the level of vagal activity was augmented. The minimum-to-maximum phase differences of the phase-response curve were less during right than during left vagal stimulation and when the level of vagal activity was increased. The disparities between the minimum-to-maximum phase differences for the right and left vagi are probably ascribable to the associated differences in the overall magnitudes of the chronotropic responses, rather than to any fundamental difference in the innervation of the effector cells by nerve fibers originating from the right and left sides.
Transmural changes in porcine and canine hearts after circumflex artery occlusion
Authors: McDonough K. H. , Dunn R. B. , Griggs D. M.
Published: December 2017

The distribution of the coronary collateral circulation is an important determinant of the myocardial response to acute coronary artery occlusion. The dog shows an unequal response across the ventricular wall, whereas the pig seems to have more uniform transmural changes. This study was undertaken to compare the metabolic and blood flow response in pigs and dogs to acute occlusion of the circumflex artery. Microspheres (8-10 micron) were used to determine control blood flow and flow 5 min after occlusion. A transmural tissue sample from the center of the ischemic zone was taken at 8 min after occlusion, and inner, middle, and outer layers were analyzed for high-energy phosphates and lactate. The remainder of the heart was analyzed for microsphere distribution. The epicardium in the dog showed less severe damage than the subendocardium. High-energy phosphates were higher and lactate lower in this region. In the pig high-energy phosphates and lactate were the same in the subepicardium and subendocardium. Blood flow to regions surrounding the central ischemic zone in pigs was generally uniform across the ventricular wall or greater in the inner wall than in the outer wall. These results verify that dogs as a group have a greater subepicardial protection during coronary artery occlusion. Pigs, however, demonstrate uniform ischemia or even slightly less severe ischemia in the subendocardium in regions of restricted blood flow.
Effect of angiotensin II and deoxycorticosterone infusion on vascular angiotensin II receptors in rats
Authors: Schiffrin E. L. , Gutkowska J. , Genest J.
Published: December 2017

The effect of angiotensin II (ANG II) and deoxycorticosterone acetate (DOCA) on the density (Bmax) and affinity (Kd) of binding sites for 125I-ANG II was investigated in a particulate fraction prepared from rat mesenteric arteriolar arcades. Rats were infused with ANG II via Alzet osmotic minipumps at a dose of 200 ng X kg-1 X min-1 intraperitoneally or 60 and 200 ng X kg-1 X min-1 intravenously for 5 days. Bmax was 127 +/- 5 fmol/mg protein, and Kd was 0.8 +/- 0.1 nM in controls and was reduced significantly after the intraperitoneal infusion (111 +/- 10 fmol/mg) or the lower intravenous dose (111 +/- 9 fmol/mg), whereas after the higher intravenous dose Bmax did not change (144 +/- 14 fmol/mg). Kd was unaffected in all groups. Plasma renin activity (PRA) was reduced, and plasma ANG II increased in a dose-dependent fashion after ANG II infusion. Plasma aldosterone concentration increased only in the group infused with ANG II at 200 ng X kg-1 X min-1 intravenously (to 33.8 +/- 8.0 ng/dl from 11.6 +/- 3.4). In rats implanted subcutaneously with silicone rubber impregnated with DOCA, Bmax for 125I-ANG II was significantly increased (to 142 +/- 4 fmol/mg), whereas rats receiving 1% NaCl in their drinking water had no change in binding capacity, although PRA was lower in both groups. DOCA infusion, when combined with the intravenous dose of ANG II that reduced Bmax, antagonized this action of ANG II. DOCA infusion into sodium-depleted rats partially corrected the down-regulation of vascular ANG II receptors independent of changes in PRA.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytochrome P 450-linked monooxygenase: involvement in the lamb ductus arteriosus
Authors: Coceani F. , Hamilton N. C. , Labuc J. , Olley P. M.
Published: December 2017

CO and metyrapone were tested on isolated ductus arteriosus preparations from mature fetal lambs equilibrated at low (4-12 Torr) and high (511-712 Torr) O2 partial pressure (PO2). CO completely reversed the contractile tension of the ductus at either PO2 value and was equally effective in the absence and presence of indomethacin. CO relaxation still occurred when the tissue was exposed to a gas mixture having a CO-to-O2 ratio of 0.27. The inhibitory effect of CO on the O2-contracted ductus was variably reversed by light. Metyrapone was also a relaxant agent, and its action was greater at low than at high PO2. Unlike the lamb ductus, the O2-constricted guinea pig ductus did not respond to CO (maximum CO-to-O2 ratio around 1), whereas it was relaxed by metyrapone. These findings implicate a cytochrome P450-catalyzed enzymic process in the maintenance of muscle tone of the lamb ductus arteriosus and in the contractile response of the vessel to O2.
Ouabain-induced reflex coronary vasodilatation mediated by cardiac receptors
Authors: Trimarco B. , Chierchia S. , Ricciardelli B. , Cuocolo A. , Volpe M. , Sacca L. , Condorelli M.
Published: December 2017

Experiments were performed to determine the effects of digitalis-induced stimulation of cardiac receptors on the coronary circulation. In chloralose-anesthetized dogs, left circumflex coronary artery was perfused at constant flow, and heart rate was maintained constant by electric pacing. Ouabain injection in the perfused coronary artery produced a significant decrease in coronary perfusion pressure. Epicardial application of lidocaine completely blocked the reflex response. Vagotomy also prevented this reflex response. Sympathetic blockade with intravenous guanethidine or intracoronary phentolamine partially reduced the reflex coronary vasodilatation. Intracoronary atropine also partially reduced the coronary vasodilator response to ouabain. The combined administration of guanethidine and atropine completely abolished the coronary reflex response. These data demonstrate that ouabain can evoke reflex coronary vasodilation by stimulating cardiac receptors. This reflex response is mediated by activating cholinergic vasodilator fibers and inhibiting sympathetic vasoconstrictor fibers.
Pressor effects of brief and prolonged infusions of epinephrine in the conscious rat
Authors: Zabludowski J. , Clark S. , Ball S. G. , Brown A. J. , Inglis G. C. , Lever A. F. , Murray G.
Published: December 2017

Plasma epinephrine may be increased in some patients with essential hypertension, and prolonged infusion of this catecholamine has been claimed to raise blood pressure. The objectives of our experiments were to determine whether continuous intravenous infusion of epinephrine raised blood pressure in a rat preparation known to respond in this way to angiotensin II in low dose and, if so, the plasma concentration of epinephrine required to raise pressure in comparison to the physiological range of plasma catecholamine concentration in the rat. Intravenous infusion of epinephrine at a rate of 400 ng X kg-1. min-1 or less for 30 min into Wistar rats did not increase mean arterial pressure (MAP); pressure did rise when the rate was increased to 800 ng X kg-1. min-1. However, when rats were given epinephrine at 400 ng X kg-1. min-1 for 4 days with continuous blood pressure recording, average MAP showed a progressive rise on successive days of infusion, reaching a maximum increase of 12 mmHg on the 4th and final day of infusion (P less than 0.02). Blood pressure did not change significantly during epinephrine infusion at 10 and 70 ng X kg-1. min-1. Plasma epinephrine was raised more than 13 times basal at the highest rate of infusion. In comparison, blood pressure and catecholamine concentrations increased only slightly although significantly during a period of restraint. We confirm the existence of a slowly developing pressor effect of epinephrine, but it is small and requires a large sustained increase of plasma epinephrine for its development.
Instantaneous renal arterial pressure-flow relations in anesthetized dogs
Authors: Ehrlich W. , Baer R. W. , Paidipaty B. B. , Randazzo R.
Published: December 2017

Instantaneous renal arterial pressure-flow (P/ Qra ) relations were investigated in 11 anesthetized dogs using the nonpulsatile fall in aortic pressure and renal arterial flow ( Qra ) during cardiac arrest caused by vagal stimulation. We found that P/ Qra relations were linear with an extrapolated zero flow intercept (Ped, effective downstream pressure) of 20.8 +/- 1.9 mmHg and the reciprocal of the slope (Ra, arterial resistance) of 0.6 +/- 0.04 mm Hg X ml-1 X min. These values are markedly lower than the values found in similar experiments in coronary and femoral arteries. Raising renal venous pressure (5 dogs) decreased Qra and elevated Ra and Ped in the ipsilateral renal artery while decreasing Qra and elevating Ra but not Ped in the contralateral renal artery. Carotid artery occlusion (6 dogs) decreased Qra and elevated Ra and Ped. Alpha-Adrenergic blockade (4 dogs) lowered Ped and Ra. Arterial resistance seems to be more important for change in P/Q relations in the renal arterial bed than it is in other arterial beds investigated so far. We suggest that the effective downstream pressure to renal arterial flow is downstream from the glomerular capillaries. The location of the "vascular waterfall " phenomenon appears to be between the intrarenal veins and the veins outside the capsule.
Photoaffinity labeling of adenosine transporter in cardiac membranes with nitrobenzylthioinosine
Authors: Kwan K. F. , Jarvis S. M.
Published: December 2017

The kinetic and molecular properties of the adenosine transporter in guinea pig cardiac membranes were studied using nitrobenzylthioinosine (NBMPR), a potent and specific inhibitor of nucleoside transport. [3H]-NBMPR bound tightly but reversibly to guinea pig cardiac membranes (apparent dissociation constant 0.24 +/- 0.07 nM; maximum binding capacity 1.24 +/- 0.45 pmol of NBMPR bound/mg protein). Reversible high-affinity [3H]NBMPR binding was inhibited in an apparent competitive manner by adenosine (apparent inhibition constant 0.14 mM). L-N-phenylisopropyladenosine (L-PIA) had no effect on NBMPR binding. Exposure of cardiac membranes in the presence of [3H]-NBMPR and dithiothreitol, a free-radical scavenger, to ultraviolet light resulted in covalent incorporation of 3H into polypeptides of apparent molecular weight 66,000-50,000. Covalent attachment of [3H]NBMPR under equilibrium binding conditions was inhibited by adenosine, nitrobenzylthioguanosine , and dipyridamole but was unaffected by the adenosine receptor agonist L-PIA. These data suggest that the photolabeled molecular weight protein (apparent mol wt 66,000-50,000) is involved in adenosine permeation by guinea pig cardiac membranes.
Structural compensatory mechanisms in rat heart in early spontaneous hypertension
Authors: Anversa P. , Melissari M. , Beghi C. , Olivetti G.
Published: December 2017

The response of the left ventricle (LV) during the development of spontaneous hypertension (SH) in rats was studied morphometrically at 21, 28, 35, and 45 days after birth and compared with that of normotensive (WK) controls. LV hypertrophy, varying from 24 to 27%, was characterized by the preservation of the volume fraction of capillary lumen and capillary luminal surface in the myocardium, as a result of capillary proliferation. From 21 to 45 days the number of capillaries per unit area of myocardium increased 68% in SH rats by the insertion in parallel of new capillary elements among the myocytes. This estimation was obtained by correcting the value of capillary density at 45 days for the amount of spreading produced by myocyte growth during this interval. On a similar basis capillary proliferation was only 24% in WK rats. Myocyte growth in experimental animals (151%) was achieved by a 77% enlargement in myocyte cross-sectional area (MCSA) and by a 42% lengthening of the cells. In controls myocyte expansion (124%) was the result of comparable increments in MCSA (47%) and myocyte length (53%).
Coronary, collateral, and perfusion territory responses to aortic banding
Authors: Scheel K. W. , Eisenstein B. L. , Ingram L. A.
Published: December 2017

The objectives of this study were 1) to separate anatomic from functional variables causing the increased minimal coronary resistance seen with hypertrophy; 2) to investigate whether increased intraluminal pressure and tangential wall stress lead to collateral proliferation; 3) to define changes in vascular perfusion territories resulting from hypertrophy. Coronary and collateral resistances of the four coronary arteries were determined in empty, beating hearts from 10 control dogs and 11 dogs with myocardial hypertrophy produced by 4 wk of aortic banding. In hypertrophied hearts the coronary flow per gram at 100 mmHg and the slope of the pressure-flow line were significantly decreased. Coronary flow-to-body weight ratios were not different; thus the decreased flow per gram tissue with hypertrophy was due to increased tissue mass rather than changes in vascular resistance. Collateral flows were similar for both groups, indicating that increased pressure and wall stress did not cause significant collateral growth. Both ventricles hypertrophied and all vascular beds were equally affected, but distribution of the increased mass varied for different vascular beds.
Dimensional analysis of the left ventricle during PEEP: relative septal and lateral wall displacements
Authors: Cassidy S. S. , Ramanathan M.
Published: December 2017

We studied the effects of ventilation with positive end-expiratory pressure (PEEP) on left ventricular (LV) shape and wall motion with emphasis on the relative positions of the septum and lateral LV wall. In seven dogs we implanted radiopaque markers in the LV wall and septum to represent the major and two minor axes of a nonprolate LV ellipsoid and measured their spatial positions using 90 degrees biplane cineradiography. The relative positions of the septum and lateral LV wall were determined with respect to the central longitudinal axis of the heart defined by the apex and base markers. Animals were studied in the supine position during positive-pressure ventilation without PEEP, during PEEP before and after dextran administration to elevate stroke volume, and again without PEEP while blood was withdrawn to lower stroke volume. We found that ventilation with PEEP reduced all three LV chamber end-diastolic dimensions and distorted its shape primarily by restricting the outward expansion of the lateral LV wall during diastole, a change that persisted after stroke volume had been restored. The relative position of the septum was not displaced into the LV by PEEP to any greater degree than were the anterior or posterior walls. The inordinate reduction of the end-diastolic septal to lateral wall dimension, and specifically the lateral wall component thereof, was associated with a proportional reduction in the respective stroke lengths. We conclude that deformation of the LV is more likely caused by lung compression than by right ventricular dilation. This deformation contributes to the reduction in LV filling and thereby contributes to the reduction in stroke volume.
Delayed reversal of Goldblatt hypertension by angiotensin II infusion in the rat
Authors: Kumar A. , Bing R. F. , Swales J. D. , Thurston H.
Published: December 2017

Reversal of early Goldblatt two-kidney, one-clip hypertension is associated with a fall in plasma renin. To define the role of this in blood pressure normalization we maintained preoperative hypertension for 12 h after unclipping or removal of the ischemic kidney, by angiotensin II or norepinephrine infusions during continuous blood pressure monitoring. High infusion rates of angiotensin II (1 microgram X kg-1 X min-1) were needed to reproduce hypertensive pressures. On stopping angiotensin II there was a rapid initial fall in blood pressure but not to normal (176 +/- 3.1 to 138 +/- 4.3 mmHg at 1 h), and a later slower fall to normal by 24 h (114 +/- 3.9). This response was identical to that of dextrose-infused animals (180 +/- 8.2 to 146 +/- 7.0 at 1 h and 113 +/- 5.6 at 24 h), apart from a transient rise in blood pressure associated with hyperreninemia in unclipped animals 12 h postinfusion. In contrast, after norepinephrine blood pressure fell immediately to normal. Similar responses were seen in normal rats after 12-h pressor infusions of angiotensin II or norepinephrine. These results show that the fast and slow components of the blood pressure fall following reversal of Goldblatt hypertension are delayed but otherwise unaltered specifically by angiotensin II. The need for pharmacologic doses, however, suggests that mechanisms in addition to the direct vasopressor action of angiotensin II are involved.
Role of site of microsphere injection and catheter position on systemic and regional hemodynamics in rat
Authors: Kobrin I. , Kardon M. B. , Oigman W. , Pegram B. L. , Frohlich E. D.
Published: December 2017

The influences of the site of microsphere injection (intra-atrial vs. intraventricular) and positioning of the left ventricular catheter (aortoventricular vs. atrioventricular) on systemic, renal, and coronary hemodynamics were evaluated in anesthetized rats. The effect of anesthesia on aortoventricular catheter positioning was also evaluated. In anesthetized and open-chest preparations, the systemic and renal hemodynamics were not affected by catheter position or site of microsphere injection; however, myocardial blood flow was dependent on these variables. Variations in coronary blood flow were significantly greater when the catheter was in the aortoventricular position (34 +/- 3%) than with an atrioventricular catheter (11 +/- 2%, P less than 0.01), irrespective of whether the microspheres were injected into the atrium or ventricle. Comparison of anesthetized and conscious rats with aortoventricular catheter indicated lesser variability in coronary blood flow in the conscious rats (P less than 0.01). Therefore, the greater variability of coronary flow measurements in anesthetized rats was caused by the position of the cardiac catheter in the aortoventricular route. However, the variability caused by the aortoventricular catheter was much less in conscious rats. Therefore, coronary flow hemodynamic measurements (microsphere technique) are less variable when they are made in conscious rats.
Rhythmic variations in R-R interval during sleep and wakefulness in puppies and dogs
Authors: Haddad G. G. , Jeng H. J. , Lee S. H. , Lai T. L.
Published: December 2017

We studied the short-term oscillations in the R-R interval in five puppies at 4 wk of age and five adult dogs during sleep and wakefulness. The R-R interval was measured using an R-R preprocessor, and respiration was recorded using barometric plethysmography. Puppies showed much smaller fluctuations in the R-R interval (SD between 6 and 40 ms) than adult dogs (SD between 124 and 367 ms) in both rapid eye movement (REM) and quiet sleep. Spectral analysis demonstrated that these oscillations were primarily of low frequencies, and the contribution of respiratory sinus arrythmia (RSA) to total power was low. In contrast, in adult dogs during sleep, the spectral distributions were peaked in frequency bands corresponding to mean respiratory rate, and the percent contribution of low frequencies to power was small. Furthermore, the mean R-R interval was considerably larger during expiration than during inspiration in adult dogs (showing 20-140% increase), but not in puppies (showing only -0.4 to 4.4% increase). We conclude that 1) the mechanisms responsible for RSA mature postnatally in the dog; 2) the magnitude of RSA depends on the state of consciousness in the adult dog, being greater in sleep than during wakefulness; and 3) low-frequency oscillations, not related to breathing and independent of sleep state, characterize the variations in the R-R interval in early life but are insignificant in the adult dog.
Short-term memory in the in situ canine myocardium
Authors: Nwasokwa O. , Sagawa K. , Suga H.
Published: December 2017

We studied the effect of intracycle (short-term) mechanical history on canine myocardial performance. Intracycle muscle force and/or length history was varied, and the resultant changes in end-systolic force-length relationship were analyzed. Antecedent isotonic shortening impaired, whereas isometric force development enhanced end-systolic myocardial performance. A history of shortening concurrent with force development produced an intermediate effect. We conclude that decreasing force or length impairs whereas increasing length or force enhances performance in the same cycle. Different combinations of antecedent force and length changes affect end-systolic performance by algebraic summation (superposition) of their disparate effects. Time measurements established that 1) total systolic time varied little with altered history, 2) isotonic shortening took longer than isometric contraction in reaching a point P in the force-length plane, and 3) less time was therefore available for contraction after P with antecedent isotonic shortening than with antecedent isometric force development. This history-dependent time differential accounts for the corresponding differential in performance.
Hemodynamics and interstitial fluid pressure in the rat tail
Authors: Aukland K. , Wiig H.
Published: December 2017

Blood flow in the rat was measured during pentobarbital anesthesia by plethysmographic and thermometric techniques. Tail arterial and venous pressures (Pa and Pv) were measured by glass micropipettes and interstitial fluid pressure (PIF) by wick-in-needle technique. Large pressure gradients were measured along the tail, Pa decreasing and Pv increasing toward the tip. In the vasoconstricted tail, distal arterial and venous pressures (Pad and Pvd, respectively, 10 cm from the tail root) were 55 and 11% of aortic pressure (PA), while PIF was 0-2 mmHg. Plasma volume expansion increased blood flow by a factor of 10 to 35. Pad rose to 74% and Pvd to 20% of PA. PIF increased to 15 mmHg, in parallel with Pv. Venous stasis (cuff pressure 14.7 mmHg) increased PIF and Pv by 3.5 and 9 mmHg, respectively, while tail volume increased by 0.4 to 1.2%. In conclusion, the large flow increase induced by plasma volume expansion depends strongly on dilation of the tail artery, with two- to threefold increase in internal radius. Simultaneously the tail veins relax and expand. Subcutaneous tissue is compressed between the expanding vessels and the tight skin, and PIF increases almost sufficiently to prevent a rise in net capillary filtration pressure. This immediate edema-preventing mechanism is less efficient during venous stasis, which presumably does not induce "active" dilation of the tail vessels. Similar mechanisms probably exist in other "encapsulated" tissues.
Circus-movement tachycardia in frog atrium monitored by voltage-sensitive dyes
Authors: Sawanobori T. , Hirano Y. , Hirota A. , Fujii S.
Published: December 2017

Circus-movement tachycardia was studied using voltage-sensitive merocyanine-rhodanine dyes (dye XVII and NK2761). Excitatory waves were optically measured simultaneously from eight different regions of a ring of tissue formed from frog atrium. Application of acetylcholine in Ca2+-free solution (10(-10)-10(-9) g/ml) shortened the duration of optical action signals to cause nonuniform change in optical signal durations in about 60% of the preparations. Circus-movement tachycardia was produced by proper reduction and regional nonuniformity of optical signal durations. Under these circumstances it is easy to evoke circus-movement tachycardia by giving an extra stimulus to the site that shows a difference in optical signal durations.
Splanchnic vasomotor and metabolic adjustments to hypoxia and exercise in humans
Authors: Rowell L. B. , Blackmon J. R. , Kenny M. A. , Escourrou P.
Published: December 2017

To determine whether hypoxia increases splanchnic vasoconstriction and impedes splanchnic metabolism during exercise, 11 subjects were exercised for 72 min at O2 uptake (VO2) of 1.8 1/min; 11% O2 was breathed during 30-50 min. Splanchnic blood flow (SBF), arterial and hepatic venous concentrations of indocyanine green (ICG), O2, CO2, metabolites, and catecholamines were determined in seven subjects; complete sets of all measurements were obtained from four. Arterial O2 content and tension fell from normal values to 12.3 ml/100 and to 32.2 Torr, respectively, during hypoxia; heart rate rose to 159 from 117 beats/min, arterial blood pressure was unchanged, and plasma norepinephrine (NE) and epinephrine (E) concentrations rose from 0.79 (NE) and 0.2 (E) ng/ml (normoxia) to 2.7 and 0.72, respectively, during hypoxia. SBF rose insignificantly from 1.14 (normoxia) to 1.35 l/min during hypoxia and fell significantly to 1.01 1/min after return to normoxia. Splanchnic VO2 was maintained at normal levels by increased extraction as hepatic venous O2 fell to 1.7 ml/100 ml and hepatic venous O2 tension to 7.5 Torr. Hepatic glucose release rose from 642 (normoxia) to 1,164 mg/min (hypoxia); lactate uptake increased from 0.26 to 2.1 mM/min; NE uptake rose from 417 to 1,508 ng/min, but hypoxia reduced ICG extraction by 28%. Thus hypoxia did not cause splanchnic vasoconstriction normally accompanying increases in HR and NE concentration or reductions in maximum VO2. SBF was maintained at a level sufficient to maintain all metabolic functions except ICG extraction.
Contractions of the canine coronary artery in calcium-free solution
Authors: Rooke T. W. , Rimele T. J. , Vanhoutte P. M.
Published: December 2017

Prostaglandin F2 alpha, but not norepinephrine, augments the maximal contractile response to potassium. To examine the mechanism underlying this augmentation, rings of canine coronary artery were studied isometrically in physiological salt solutions of various composition. The contractions evoked by prostaglandin F2 alpha were larger in high-potassium, calcium-free solution than in calcium-free solution. Similar results were obtained using canine saphenous vein and femoral artery. Isoproterenol, but not nimodipine, relaxed the contractions produced by prostaglandin F2 alpha in high-potassium, calcium-free solution. Unlike prostaglandin F2 alpha, norepinephrine failed to constrict rings in high-potassium, calcium-free solution. In calcium-free solution, prostaglandin F2 alpha-induced contractions increased with increasing potassium concentrations, but no enhancement occurred when lithium was substituted for potassium. Rings of coronary artery incubated with calcium-45 did not show changes in prostaglandin F2 alpha-induced calcium-45 efflux following changes in potassium concentration. These results suggest that potassium enhances coronary vascular smooth muscle contraction to prostaglandin F2 alpha, but not norepinephrine, independently of calcium entry.
H+-induced membrane depolarization in canine cardiac Purkinje fibers
Authors: Lauer M. R. , Rusy B. F. , Davis L. D.
Published: December 2017

The H+-induced membrane depolarization in canine cardiac Purkinje cells in false tendons was studied. In some electrically paced Purkinje cells ("sensitive" cells), exposure to a pH 6.0 superfusate produced a large membrane depolarization [44.5 +/- 6.7 (SD) mV], whereas other Purkinje cells ("resistant" cells) developed only a small depolarization (9.8 +/- 5.6 mV) even after 60 min of exposure to the low-pH superfusate. Cs+, Ba2+, tetraethylammonium, 9-aminoacridine, verapamil, or exposure to Ca2+- or K+-deficient or hypertonic solutions were capable of converting resistant cells to sensitive cells. Increasing extracellular K+ concentration [( K+]) or rapid electrical pacing failed to convert resistant cells to sensitive cells. Membrane depolarizations of approximately equal magnitude produced in Purkinje cells by either increasing [K+] to 18.2 mM, decreasing [K+] to 0.5 mM, reducing extracellular pH to 4.1, or ouabain administration were associated with membrane resistances of approximately 45, 377, 386, or 45%, respectively, of the membrane resistances in the control solution. The results suggest that the H+-induced membrane depolarization in sensitive Purkinje cells is caused by a mechanism similar to that responsible for a low [K+]-induced depolarization.