bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of diastolic function with Doppler echocardiography: the PDF formalism
Authors: Kovacs S. J. , Barzilai B. , Perez J. E.
Published: December 2017

A new parametrized diastolic filling (PDF) formalism for evaluation of holodiastolic (left and right) ventricular function via Doppler echocardiography is presented. It is motivated by the empiric observation that during diastole the heart behaves as a suction pump whose dynamics, in certain respects, are those of a damped harmonic oscillator. An expression for elastic recoil (suction) initiated ventricular diastolic fluid inflow velocity v(t) is obtained by differentiation from the solution x(t) of the linear differential equation that describes the motion of a forced, damped harmonic oscillator. It is solved for “over-damped” motion, for zero initial velocity and initial displacement = xo cm. An explicit forcing term F(t) = Fosin(omega t) is included to account for late diastolic (atrial) filling. The quantitative parameters of the model include inertia (mass; m), viscosity (damping constant; c), source of stored energy for suction (spring constant; k), and its initial displacement xo, the amplitude and frequency of the (atrial) forcing term Fo, omega. The mathematical behavior of the solution v(t) and its dependence on the parameters xo, c, and k, which characterize the contour of the Doppler velocity profile (DVP), is discussed. When clinical examples of normal and abnormal transmitral DVPs are compared with v(t) calculated using the harmonic oscillator model, excellent agreement [DVP-v(t)]/v(t) approximately 0.05 is obtained throughout diastole. Thus the model allows accurate qualitative and quantitative characterization of global ventricular diastolic behavior by noninvasive means in a variety of normal and abnormal stiffness-compliance states. In addition, it may serve as a prototype for a class of mathematical models that can encompass the essential dynamic elements of ventricular diastolic function that couple to flow and further enhance the role of the heart as a suction pump.
Sympathoadrenal mechanisms in cardiovascular responses to naloxone after hemorrhage
Authors: Rutter P. C. , Potocnik S. J. , Ludbrook J.
Published: December 2017

Five rabbits were allotted to each of six treatments on a matched-individual basis. Treatments were none, sham, total adrenalectomy with adrenocorticoid replacement, intravenous guanethidine (15 mg X kg-1 X day-1), adrenalectomy + guanethidine, and adrenal medullectomy. The conscious rabbits were bled 20 ml/kg over 5 min. Naloxone (6 mg/kg) was injected intravenously. The responses of arterial pressure and of plasma epinephrine (E) and norepinephrine (NE) concentrations were measured. Factorial analysis was used to calculate the effects of sympathetic noradrenergic nerves (SYM) and the adrenal medulla (ADR) on the responses. In combination, SYM + ADR fully accounted for the pressor response observed in normal and sham-treated rabbits. SYM and ADR each made independent and approximately equal contributions to the response, but the SYM X ADR interaction was strongly antagonistic. The responses of plasma E and NE were fully accounted for by the adrenal glands and sympathetic nerves, respectively. The pressor responses after total adrenalectomy and adrenal medullectomy were similar. Thus hemorrhage-stimulated adrenal corticosteroid release was not essential to naloxone's action, and adrenal enkephalins were not responsible for naloxone's action on sympathetic pathways.
O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase
Authors: Kim M. S. , Akera T.
Published: December 2017

The role of O2 free radicals in the reduction of sarcolemmal Na+-K+-ATPase, which occurs during reperfusion of ischemic heart, was examined in isolated guinea pig heart using exogenous scavengers of O2 radicals and an inhibitor of xanthine oxidase. Ischemia and reperfusion reduced Na+-K+-ATPase activity and specific [3H]ouabain binding to the enzyme in ventricular muscle homogenates and also markedly lowered sodium pump activity estimated from ouabain-sensitive 86Rb+ uptake by ventricular muscle slices. These effects of ischemia and reperfusion were prevented to various degrees by O2-radical scavengers, such as superoxide dismutase, catalase, dimethyl-sulfoxide, histidine, or vitamin E or by the xanthine oxidase inhibitor, allopurinol. The degree of protection afforded by these agents paralleled that of reduction in enhanced lipid peroxidation of myocardial tissue as estimated from malondialdehyde production. These results strongly suggest that O2 radicals play a crucial role in the injury to sarcolemmal Na+-K+-ATPase during reperfusion of ischemic heart.
Calcium exchange, structure, and function in cultured adult myocardial cells
Authors: Langer G. A. , Frank J. S. , Rich T. L. , Orner F. B.
Published: December 2017

Cells digested from adult rat heart and cultured for 14 days demonstrate all the structural elements, in mature form, associated with the process of excitation-contraction (EC) coupling. The transverase tubular (TT) system is well developed with an extensive junctional sarcoplasmic reticulum (JSR). In nonphosphate-containing buffer contraction of the cells is lost as rapidly as zero extracellular Ca concentration ([Ca]o) solution is applied (less than 10 s) and a negative contraction staircase is produced on increase of stimulation frequency. Structurally and functionally the cells have the characteristics of adult cells in situ. 45Ca exchange and total 45Ca measurement in N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid (HEPES)-buffered perfusate define three components of cellular Ca: a rapidly exchangeable component (t1/2 less than 25 s) accounting for 36% of total Ca, a slowly exchangeable component (t1/2 53 min) accounting for 7% of total Ca, and the remaining 57% cellular Ca is “inexchangeable” (demonstrates no significant exchange within 60 min). The slowly exchangeable component can be increased 10-fold within 60 min by addition of phosphate to the perfusate. The Ca distribution and exchange characteristics are little different from those of 3-day cultures of neonatal rat heart previously studied [Langer, G. A., J. S. Frank, and L. M. Nudd. Am. J. Physiol. 237 (Heart Circ. Physiol. 6): H239-H246, 1979]. The results suggest that the cells are representative of adult cells in situ and that both sarcolemmal-bound and sarcoplasmic reticular Ca contribute to the component of Ca that is rapidly exchangeable.
Prolonged support of working rabbit hearts using Fluosol-43 or erythrocyte media
Authors: Segel L. D. , Ensunsa J. L. , Boyle W. A.
Published: December 2017

We compared the perfluorochemical emulsion Fluosol-43 and an erythrocyte-based solution as support media for ex vivo working rabbit hearts functioning with a physiological workload. Both groups of hearts (n = 5/group) exhibited stable function (left ventricular peak systolic pressure, peak rates of left ventricular pressure rise and relaxation, aortic flow, peak aortic flow rate, stroke work, and peak power) for the first 6 h of perfusion. Coronary flow, coronary venous O2 content, and O2 supply-to-demand ratio declined similarly in both groups during the first 6 h. Both groups of hearts preferentially utilized pyruvate to glucose. The Fluosol-43-perfused hearts had higher heart rate, left ventricular peak systolic pressure, peak rate of left ventricular pressure rise, aortic flow, coronary flow, and myocardial O2 consumption compared with the erythrocyte-perfused hearts. The Fluosol-43 hearts produced more lactate and released more creatine phosphokinase than did the erythrocyte-perfused hearts, but the rates were low and constant throughout perfusion, indicating that the hearts were not progressively ischemic. After the first 6 h, function of the Fluosol-43 hearts declined, resulting in their earlier failure compared with the erythrocyte-perfused hearts. The data indicate that Fluosol-43 had sufficient O2- carrying capacity to support stable function of a rabbit heart at a physiological workload for 6 h, and differences in function and ex vivo longevity of the two groups of hearts suggested that a component or contaminant of Fluosol-43 altered sarcolemmal function and/or that a component needed for membrane integrity was lacking in the Fluosol-43 perfusate.
Cardiac depressant and circulatory effects of prostaglandin D2 in developing lambs
Authors: Drummond W. H. , Carter R. L.
Published: December 2017

Pulmonary and systemic vascular and cardiac effects of intravenous prostaglandin D2 (PGD2), given at 0.1, 1.0, and 10 micrograms/kg, were measured in chronically instrumented lambs during normoxia and hypoxia at ages 2–3, 9–14, and greater than or equal to 21 days. During normoxia, PGD2 was not a pulmonary vasodilator at low dose and caused mild pulmonary vasoconstrictor changes at 10 micrograms/kg in young lambs; normoxic older lambs had pulmonary vasoconstriction at both 1 microgram/kg and 10 micrograms/kg doses. With hypoxemia, PGD2 caused mild pulmonary vasodilation at all doses in the youngest lambs, converted the normoxic 9–14-day-old lambs' pressor response to a nonresponse, and attenuated the high-dose pulmonary vasoconstriction in the greater than or equal to 21 day lambs. PGD2 was a directly dose-related systemic pressor (+5-20 mmHg) at all ages during both normoxia and hypoxia. Heart rate and cardiac output decreased in a dose-dependent fashion during both normoxia and hypoxia. The PGD2-induced cardiac depression was unaltered by age or ventilatory hypoxemia. PGD2 response of the lamb pulmonary circulation changes from marginal dilation to constriction during the late postnatal development. During the same period, PGD2 dose-related systemic pressor and cardiac depressant effects remain stable. Thus, the circulatory effects of PGD2 are complexly interrelated with age, dose, and presence of hypoxemia.
Exacerbation of central baroreflex impairment in Dahl rats by high-salt diets
Authors: Miyajima E. , Bunag R. D.
Published: December 2017

To determine whether baroreflex impairment progresses in hypertensive Dahl rats, we recorded reflex responses to drug-induced changes in blood pressure in hypertension-sensitive (DS) and hypertension-resistant (DR) rats maintained on low- or high-salt diets for 7 wk. Chronotropic responses, manifested as either bradycardia for phenylephrine or tachycardia for sodium nitroprusside, were always smaller in awake DS rats on high-salt diet than in any others. When the same rats were later anesthetized, related changes in afferent aortic and efferent splanchnic nerve activity were similarly reduced. Regardless of dietary salt intake, reflex bradycardia elicited by electrical stimulation of aortic nerve afferents was also weaker in DS than in DR rats, but attendant decreases in mean aortic pressure and splanchnic nerve activity did not differ significantly. These results are compatible with an impairment of afferent and central components of the reflex arc. Even though exact sites of dysfunction were not identified, our findings suggest that in hypertensive DS rats high-salt diets may aggravate baroreflex impairment, at least in part, by acting centrally.
Time-dependent coronary blood flow distribution in left ventricular wall
Authors: Beyar R. , Sideman S.
Published: December 2017

A mathematical model of the coronary circulation in the left ventricular (LV) wall, which describes the time-dependent local blood perfusion throughout the myocardium and the coronary flow in the epicardial vessels, is presented. The myocardial perfusion is essentially controlled by the intramyocardial resistance and the coronary pressure driving force, whereas the epicardial arterial flow is dominated by the epicardial and intramyocardial arterial capacitance and the local transmural pressure on the vessels. The temporal and spatial intramural pressure [P im(y,t)], calculated based on a nested-shell spheroidal model of the LV, is used to evaluate the local intramural resistance to flow and the corresponding zero flow pressure. The calculation of the instantaneous flow in each layer is based on a local, time-dependent modification of the back-pressure concept. A function representing the local tonus of the small blood vessels [T wf(y)] is used to adjust the average coronary flow rate to the metabolic demand of each layer. The calculated results are compared with experimental data, and the assumptions of the model are examined against a variety of experimental conditions. The model provides a qualitative tool for comprehending the distributed flow phenomenon within the myocardium and its relation to cardiac mechanics and autoregulation.
Endothelium-dependent relaxation of human pulmonary arteries
Authors: Greenberg B. , Rhoden K. , Barnes P. J.
Published: December 2017

Although endothelial cell (EC)-dependent relaxation has been described in most mammals, there have been no detailed reports of its existence in humans. Consequently, we evaluated human pulmonary artery segments taken from uninvolved regions of resected lung from 11 patients. EC removal did not significantly alter relaxation to vasoactive intestinal peptide (VIP). However, relaxation to acetylcholine (ACh) was observed only in segments with EC. Preincubation with either 1 microM propranolol or 10 microM indomethacin failed to block relaxation, but the addition of either 30 microM quinacrine hydrochloride or 100 microM nordihydroguaiaretic acid prevented it entirely. EC-dependent relaxation to ATP was also demonstrated. These data demonstrate that EC-dependent relaxation occurs in human pulmonary arteries. Neither beta-adrenergic pathways nor prostaglandin intermediaries are utilized. An oxidized breakdown product of arachidonic or some other fatty acid from EC phospholipid appears to be involved. These data suggest that interactions between endothelium and smooth muscle may be important in modulating tone in the vessel wall and that damage to the endothelium may play a role in the development of pulmonary hypertension in humans.
Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia
Authors: Beck T. , Krieglstein J.
Published: December 2017

The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O2. Hypoxia affected a marked hypotension, hypocapnia, and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate, lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40–70% of control values in gray matter and by 80–90% in white matter. Under hypoxia, columns of increased and decreased LCGU were detectable in cortical gray matter. Local cerebral blood flow (LCBF) increased by 50–90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggest a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur.
Effects of thyroid hormone on beta-adrenergic responsiveness of aging cardiovascular systems
Authors: Tsujimoto G. , Hashimoto K. , Hoffman B. B.
Published: December 2017

We have compared the effects of beta-adrenergic stimulation on the heart and peripheral vasculature of young (2-mo-old) and older (12-mo-old) rats both in the presence and absence of triiodothyronine (T3)-induced hyperthyroidism. The hemodynamic consequences of T3 treatment were less prominent in the aged hyperthyroid rats compared with young hyperthyroid rats (both in intact and pithed rats). There was a decrease in sensitivity of chronotropic responsiveness to isoproterenol in older pithed rats, which was apparently reversed by T3 treatment. The number and affinity of myocardial beta-adrenergic receptor sites measured by [125I]cyanopindolol were not significantly different in young and older control rats; also, beta-receptor density increased to a similar extent in both young and older T3-treated rats. The ability of isoproterenol to relax mesenteric arterial rings, markedly blunted in older rats, was partially restored by T3 treatment without their being any change in isoproterenol-mediated relaxation in the arterial preparations from young rats. The number and affinity of the beta-adrenergic receptors measured in the mesenteric arteries was unaffected by either aging or T3 treatment. The data suggest that effects of thyroid hormone and age-related alterations of cardiovascular responsiveness to beta-adrenergic stimulation are interrelated in a complex fashion with a net result that the hyperkinetic cardiovascular manifestations in hyperthyroidism are attenuated in the older animals.
Effects of left circumflex coronary flow transducer implantation on posterior wall innervation
Authors: Knight D. R. , Thomas J. X. , Randall W. C. , Vatner S. F.
Published: December 2017

To determine whether dissection around a coronary artery and implantation of a flow transducer resulted in partial regional denervation of the heart, the effects of bilateral stimulation of the ansae subclaviae were evaluated on regional left ventricular (LV) wall thickening (WT) and tissue norepinephrine content in four groups of dogs following 1) sham operations (n = 6),2) implantation of a Doppler flow transducer on the left circumflex coronary artery (n = 6), 3) selective circumflex coronary artery denervation with topical phenol application (n = 5), and 4) selective denervation of the posterior LV wall by extensive surgical stripping of the left circumflex coronary artery and local application of phenol (n = 6). One week later after anesthesia (chloralose 100 mg/kg) and a second thoracotomy for implantation of ultrasonic WT crystals, stimulation of the ansae subclaviae increased posterior WT by 67 +/- 9% in the sham group, 71 +/- 14% in the flow probe group, and did not increase systolic WT in the denervated group. In the posterior LV wall, norepinephrine levels were reduced (P less than 0.01) in the denervated group (6 +/- 4 pg/mg) but not in the flow probe group (629 +/- 4 pg/mg) compared with the sham group (589 +/- 88 pg/mg). Selective left circumflex coronary artery denervation did not result in either diminished norepinephrine levels in the posterior LV wall nor diminished response of WT to sympathetic nerve stimulation. Thus chronic instrumentation applied properly to the left circumflex coronary artery does not result in significant regional denervation of the posterior myocardium.
Vascular effects of infused adenosine are not mediated by prostacyclin release in humans
Authors: Nowak J. , Wennmalm M. , Edlund A. , Wennmalm A. , Fitzgerald G. A.
Published: December 2017

Adenosine may contribute to the regulation of tissue blood flow directly and via release of vasoactive substances. For example, in the isolated, perfused heart, the nucleoside has been reported to release prostacyclin, a potent vasodilator. In humans, minor variations in prostacyclin release into the circulation result in readily detectable changes in the urinary excretion of its metabolite, 2,3-dinor-6-ketoprostaglandin (PG) F1 alpha, as measured by negative ion-chemical ionization gas chromatography-mass spectrometry. To test the hypothesis that prostacyclin participates in or mediates the vascular effects of adenosine, we administered adenosine (5.1 mg/min) or vehicle to healthy volunteers in random order as a 2-h infusion into the femoral artery under double-blind conditions. The plasma levels of adenosine, inosine, and hypoxanthine increased significantly during infusion of active drug, but the urinary excretion of adenosine and uric acid were unchanged, implying efficient tissue uptake of the infused nucleoside. Adenosine, but not vehicle, significantly (P less than 0.01) increased leg blood flow (from 2.7 +/- 0.3 to 8.7 +/- 2.5 ml X 100 ml tissue-1 X min-1), heart rate (from 66 +/- 3 to 80 +/- 4 beats/min), and urinary epinephrine excretion (from 2.8 +/- 0.4 to 5.4 +/- 0.8 ng/mg creatinine). In contrast, the excretion of 2,3-dinor-6-keto-PGF1 alpha was unaltered by infusion of adenosine. We confirmed that biologically significant alterations in prostacyclin release in the lower limb vascular bed would be reflected by the urinary metabolite in experiments involving local infusion of prostacyclin at a rate below the threshold necessary to alter limb blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Fibrinogen receptors in platelet adhesion to surfaces of extracorporeal circuit
Authors: Gluszko P. , Rucinski B. , Musial J. , Wenger R. K. , Schmaier A. H. , Colman R. W. , Edmunds L. H. , Niewiarowski S.
Published: December 2017

The role of platelet fibrinogen receptors and platelet-protein interaction in platelet consumption during simulated cardiopulmonary bypass was investigated. In five recirculation experiments, with whole blood, the platelet count fell to 13% of initial values and in two experiments, with blood from patients with Bernard-Soulier syndrome, to 3% of normal values. However, in three experiments with blood from the patients with Glanzmann's thrombasthenia, the platelet count decreased to 69% of initial values. The extent of platelet consumption in normal blood was diminished to only 72% by addition of 0.5 microM prostaglandin E1 (PGE1) (5 experiments) and to 80% by precoating surfaces of the circuit with 2.5% human albumin (5 experiments). beta-Thromboglobulin antigen (beta TG) loss from platelets was associated with thrombocytopenia. The extent of beta TG loss was significantly reduced by the addition of PGE1 to blood or precoating surfaces with albumin. Proteins adsorbed on the surface of the circuit exposed to normal blood were removed with 0.5% Triton X-100. Some of these proteins were identified to be glycoprotein IIIa (GPIIIa) (3.4–4.3 micrograms/ml), beta TG (1.0–1.6 micrograms/ml), and fibrinogen (1.9–3.7 micrograms/ml). The amount of GPIIIa recovered in the Triton X-100 eluates correlated with the number of platelets lost during recirculation. These studies indicate that exposure of fibrinogen receptors associated with GPIIb-GPIIIa complex contributes to platelet consumption during cardiopulmonary bypass.
Atrial natriuretic factor secretion in dogs with experimental high-output heart failure
Authors: Villarreal D. , Freeman R. H. , Davis J. O. , Verburg K. M. , Vari R. C.
Published: December 2017

The temporal changes in the plasma concentration of immunoreactive atrial natriuretic factor (iANF) were studied in six conscious dogs with an arteriovenous (AV) fistula, a model of chronic high-output heart failure. Following the creation of the AV fistula, the dogs retained sodium avidly for 5 days, and plasma renin activity, plasma aldosterone concentration, and right atrial pressure increased significantly from controls. During this initial stage, iANF increased only modestly. From day 6 to 14, the dogs increased their daily sodium excretion and approached sodium balance. This natriuretic response was associated with a significant rise in iANF, with the return of renin and aldosterone levels to base line, and with a progressive significant elevation in right atrial pressure. Thus, in dogs with an AV fistula and cardiac volume overload, chronic increases in atrial pressure appear to be a sustained stimulus for the release of ANF. It is suggested that following the initial period of sodium retention in this experimental mental model of heart failure, chronic endocrine adjustments for the reestablishment of sodium balance involve an increase in ANF which subsequently can exert a tonic inhibitory action on the renin-aldosterone axis. It is concluded that the ANF endocrine system might function as an effective chronic compensatory mechanism to help promote sodium and water excretion in dogs with an AV fistula through the suppression of the renin-aldosterone system and possibly through its direct renal actions.
Thromboxane does not mediate pulmonary vascular response to monocrotaline pyrrole
Authors: Ganey P. E. , Roth R. A.
Published: December 2017

The possible involvement of thromboxane (Tx) in the pulmonary hypertension caused by monocrotaline pyrrole (MCTP) administration to rats was investigated by pharmacological intervention of Tx synthesis and action. The cyclooxygenase inhibitor, ibuprofen, at doses that inhibited platelet function and suppressed plasma Tx levels, did not attenuate MCTP-induced right ventricular hypertrophy or increased lung weight. Dazmegrel, an inhibitor of Tx synthetase, did not affect the MCTP-induced increase in lung weight or the elevation of lactate dehydrogenase activity or protein concentration in bronchopulmonary lavage fluid, despite significant reduction of the plasma concentration of Tx. Dazmegrel also did not alter the vascular leak or right ventricular hypertrophy due to administration of MCTP to rats. Finally, the Tx receptor antagonist L-640,035 was tested using a dosing regimen that reduced the increase in right ventricular pressure caused by a stable endoperoxide analogue in MCTP-treated rats. Cotreatment with L-640,035 did not attenuate the increase in lung weight, lavage fluid lactate dehydrogenase activity or protein concentration, or the pulmonary hypertension caused by MCTP. These results indicate that interference with Tx synthesis or action does not attenuate the toxic effects of MCTP and suggest that Tx is not necessary for the cardiopulmonary response to MCTP.
Effect of altered thyroid status on in vitro cardiac performance in rats
Authors: McDonough K. H. , Chen V. , Spitzer J. J.
Published: December 2017

Effect of a chronic excess or deficit of thyroid hormone on intrinsic myocardial performance in rats was assessed. Animals were thyroidectomized or treated with thyroid hormone or vehicle 6-7 wk before the study. Body weight and heart weight were decreased in the hypothyroid group, and heart weight was elevated in the hyperthyroid group. Hearts were removed from thyroidectomized, euthyroid or thyroid-treated animals and studied as isolated, perfused working heart preparations. Ventricular function curves were generated by increasing left atrial filling pressure, whereas outflow resistance was not varied. Coronary flow, aortic outflow (and thus cardiac output), heart rate, and peak aortic systolic pressure were measured as a function of preload. These studies showed that performance of hearts from hyperthyroid animals was similar to that of euthyroid controls. Hearts from hypothyroid rats had decreased rate, pressure, and cardiac output but normal stroke volume. Since heart weight was 55% lower than control, normalization of volume work to dry heart weight reversed the difference in cardiac output. Comparison of hearts from hypothyroid animals to control rats of similar weight showed minimal differences in pump function. Thus hyperthyroidism did not result in altered in vitro cardiac output or peak systolic pressure as a function of changing preload when compared with age-matched euthyroid controls, hypothyroidism resulted in a decreased in vitro heart rate but greater cardiac output normalized to heart weight when compared with age-matched controls and hyperthyroid animals; external pacing of hypothyroid hearts yielded myocardial work parameters that were comparable to euthyroid control rats of similar body weight; and cardiac efficiency was significantly greater in hypothyroid hearts than in hyperthyroid hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of nisoldipine on vascular resistance and vasoconstrictor responses in cats
Authors: Armstead W. M. , Lippton H. L. , Hyman A. L. , Kadowitz P. J.
Published: December 2017

The influence of nisoldipine, a calcium entry antagonist, on vascular resistance and vasoconstrictor responses was investigated in the anesthetized cat. Nisoldipine, a dihydropyridine calcium entry blocking agent, decreased total peripheral resistance and dilated the intestinal vascular bed. This calcium antagonist blocked intestinal vasoconstrictor responses to BAY K 8644, a nifedipine analogue, which promotes calcium entry. The calcium entry antagonist decreased intestinal vasoconstrictor responses to sympathetic nerve stimulation, norepinephrine, and tyramine. Nisoldipine also reduced intestinal vasoconstrictor responses to potassium chloride and agonists that elicit vasoconstriction by specific receptor-mediated actions including stimulation of alpha 1- and alpha 2-adrenoceptors. The vasodilator and inhibitory effects of nisoldipine on vasoconstrictor responses were reversible, and responses returned to control value over a 60-min period. The present data suggest that an extracellular source of calcium is required for maintenance of tone and for vasoconstriction induced by neuronally released or exogenous norepinephrine as well as a diverse group of agents that act through specific receptor mechanisms or depolarize vascular smooth muscle. The present results suggest that similar sources of calcium are required for vasoconstriction elicited by alpha 1- and alpha 2-adrenoceptor agonists in the feline intestinal vascular bed.
Paradoxical positive inotropic effect of K+ in the rat heart
Authors: Ng Y. C. , Hume J. R. , Akera T.
Published: December 2017

In cardiac muscle isolated from most mammalian species, an elevation of extracellular K+ concentration decreases developed tension. This is explained from stimulation of the Na pump. In rat myocardium, however, developed tension increased when K+ concentration was raised from 3.5 to 9.5 mM, seemingly inconsistent with the above explanation. Activation of isolated Na+,K+-adenosinetriphosphatase by K+ was not different in rat and guinea pig heart. The K+-induced increase in developed tension observed in left atrial muscle preparations obtained from rat heart was not blocked by phentolamine and propranolol or by reserpine pretreatment but attenuated by stimulation at higher frequency, incubation at a lower temperature, or by veratridine, all of which have been shown to increase Na+ loading of myocardial cells. K+ slightly prolonged action potential duration and partially depolarized resting membrane potential; however, K+-induced changes in electrophysiological parameters or possible inactivation of early outward current observed in myocytes isolated from rat heart are unlikely to be the primary cause of the positive inotropic effect. Caffeine or Cd2+ eliminated the inotropic effect of K+ but ryanodine was ineffective. An increase in extracellular K+ from 1 to 3.5 mM decreased developed tension. These results indicate that K+ has dual effects on developed tension in rat myocardium: a negative inotropic effect resulting from Na pump stimulation and a positive inotropic effect. The latter effect is due to a process that is either unique or more strongly expressed in the rat myocardium and masks the former effect in the range of physiological K+ concentrations.
Minimum intracellular PO2 for maximum cytochrome turnover in red muscle in situ
Authors: Gayeski T. E. , Connett R. J. , Honig C. R.
Published: December 2017

Probability distributions of myoglobin (Mb) saturation and intracellular PO2 were determined with subcellular spatial resolution in dog gracilis muscles during steady-state twitch contraction at 5-100% of maximal rate of O2 consumption (VO2). Calculations (Clark, A., and P. A.A. Clark. Biophys. J. 48: 931-938, 1985) and measurements (Gayeski, T. E. J., and C. R. Honig. Adv. Exp. Med. Biol. 200: 487-494, 1986) indicate that the PO2 in equilibrium with Mb is virtually identical to the PO2 at cytochrome aa3. Median intracellular PO2 and PO2 in the lower tails of probability distributions were poorly correlated with VO2. The variability of cell PO2 was greatly diminished when median PO2 was less than the PO2 for half saturation of MB, since Mb acts as a PO2 buffer. The lower tails of PO2 distributions contained almost no anoxic loci even when median PO2 was less than 1 Torr. VO2 was well correlated with the concentration ratio of phosphocreatine to free creatine (PCr/Crf) over a wide range of PO2. PO2 greater than or equal to 0.5 Torr supported maximal VO2 and energy demand. We conclude that 1) the mechanism of action of cytochrome aa3 is the same in red muscle in vivo as in mitochondria in vitro, and 2) an upper bound on the apparent Michaelis constant for maximal VO2 of red muscle is approximately 0.06 Torr.
Influence of norepinephrine and angiotensin II on vasomotion of renal blood supply in humans
Authors: Hollenberg N. K. , Meyerovitz M. , Harrington D. P. , Sandor T.
Published: December 2017

Oscillatory behavior of smooth muscle, including arterial smooth muscle, has been identified in many preparations. In this study we have extended observations on vasomotion of the renal blood supply in humans by assessing the response to norepinephrine or angiotensin II infused directly into the renal artery in doses sufficient to reduce renal blood flow by 25-33% but not influence blood pressure. In placebo-treated patients, renal blood flow and the indexes of vasomotion determined by an estimation of power spectral density of xenon transit through the human kidney did not change. Norepinephrine induced a striking increase in the amplitude but not the cycle length of oscillatory activity, whereas angiotensin (despite a somewhat larger reduction in renal blood flow) induced only a modest change in amplitude. The phasic response to norepinephrine infused continuously makes it unnecessary to invoke phasic norepinephrine release in the response to maneuvers that increase sympathetic nervous system activity. Moreover, oscillatory activity reflects phenomena that may be related to but are not dependent on changes in mean renal blood flow. The results of this study may provide insight into the pathogenesis of the increase in vasomotion evident in the renal blood supply of some patients with essential hypertension.
Active force during hypoxia of hypertrophied rabbit right ventricular trabeculae
Authors: Capeless M. A. , Hamrell B. B.
Published: December 2017

Hypertrophy is often accompanied by increased myocardial oxygen demand, but any unique effects of hypoxia on contraction in hypertrophy are unknown. Trabeculae from normal [n = 9; 0.119 +/- 0.014 mm2 (means +/- SE) cross-sectional area] and hypertrophied (pulmonary artery constriction; n = 7; 0.108 +/- 0.028 mm2) rabbit right ventricles were subjected to graded hypoxia (Krebs-Ringer solution, 28 degrees C, 1 Hz stimulus frequency). During normoxia, peak active isometric (Pmax) and resting stress (Prest) at optimum length and peak rate of stress development (dP/dt) in hypertrophy were the same as normal and time to peak stress was longer than normal. Time to peak stress and dP/dt decreased with hypoxia, but time to peak stress remained longer than normal in hypertrophy; Prest was unchanged. The ratio of peak active stress (P) during hypoxia to Pmax decreased linearly with superfusate PO2, but the hypertrophy relationship (y = 4.00 X 10(-3) x + 0.084) is the same as normal (y = 3.70 X 10(-3) x + 0.154; p greater than 0.05). Therefore, a normal level of P was preserved in hypertrophied myocardium and prolonged time to peak stress might have been important for that preservation.
Hepatic plasma flow: accuracy of estimation from bolus injections of indocyanine green
Authors: Burczynski F. J. , Pushka K. L. , Sitar D. S. , Greenway C. V.
Published: December 2017

Experiments were performed to determine the validity of the indocyanine green (ICG) clearance technique, with and without allowances for incomplete hepatic extraction, as an estimate of hepatic plasma flow. This technique was compared with that of directly measured hepatic blood flow using a hepatic venous long-circuit preparation in the anesthetized cat. This preparation allowed direct measurement and alteration of hepatic blood flow and collection of arterial, portal, and hepatic venous blood samples without depletion of the animal's blood volume. Measurements of ICG by spectrophotometry and high-pressure liquid chromatography (HPLC) were equally accurate, but the HPLC was 100 times more sensitive and allowed smaller sample volumes. It was determined that systemic clearance of ICG after a bolus dose (1.3 mumol/kg) was much smaller than hepatic blood flow. Allowance must be made for the incomplete extraction. When the clearance was multiplied by extraction, mean estimated hepatic plasma flow exceeded the measured flow values by 20-30%, and this difference was attributed to temporary extrahepatic distribution. In all experiments estimated hepatic plasma flows were highly variable, and reasons for this are discussed. In hepatectomized cats ICG was found to be distributed into extrahepatic tissues.
Quantification of effect of pericardium on LV diastolic PV relation in dogs
Authors: Junemann M. , Smiseth O. A. , Refsum H. , Sievers R. , Lipton M. J. , Carlsson E. , Tyberg J. V.
Published: December 2017

The aim of the present study was to quantify the effect of the pericardium on the left ventricular (LV) diastolic pressure-volume relation. The experiments were done in 10 anesthetized closed-chest dogs. Pericardial and cardiac volumes were determined by computed tomography. Pericardial effusion (n = 5) and volume loading (6% dextran iv; n = 5) were used to increase pericardial volume. Volumes were normalized as multiples of the LV volume measured when LV transmural pressure was 6 mmHg (VLV6). Using the data from the pericardial effusion experiments, we calculated the best-fit exponential equations for the pericardial pressure-volume relations. From these equations we calculated that the changes in pericardial volume necessary to shift the LV diastolic pressure-volume curve upward by 2, 5, 10, and 20 mmHg were 0.6 +/- 0.1, 1.1 +/- 0.2, 1.6 +/- 0.2, and 2.2 +/- 0.3 times VLV6, respectively. Using the data from the volume loading experiments, we also calculated the degree of upward shift of the LV pressure-volume relation caused by volume loading, which increased LV mean diastolic pressure by 12 mmHg. (The upward shift is that increment in pericardial pressure caused by the total increase in volume of the extra-LV contents of the pericardium, i.e., the atria, the right ventricle, and any pericardial effusion.) This volume loading increased the total volume of the right ventricle and the atria by 1.0 +/- 0.1 VLV6, which, in itself, increased pericardial pressure by 3.6 +/- 0.8 mmHg. We conclude that in situations in which heart or pericardial volume increases acutely, the pericardium shifts the diastolic pressure-volume relation of the LV upward by a significant amount.
Left ventricular mechanical adaptation to chronic aortic regurgitation in intact dogs
Authors: Florenzano F. , Glantz S. A.
Published: December 2017

Increased end-diastolic wall stress has been hypothesized to stimulate left ventricular (LV) hypertrophy following volume overload. We instrumented intact-chest dogs with radiopaque markers in both ventricles and created volume overload by puncturing one aortic valve cusp. End-diastolic stress increased immediately, then fell over 3 mo as the heart hypertrophied. End-systolic stress did not change significantly. Chamber contractility, quantified as Emax, the end-systolic pressure-volume line slope, increased. Emax normalized by multiplying by LV mass increased following the lesion before but not after beta-blockade with propranolol and did not change significantly over time, suggesting that chamber contractility changed because of increased mass and sympathetic tone rather than changed intrinsic muscle function. LV mass did not initially correlate with lesion size, but steady-state mass did. Over the range of lesions we produced, increased end-diastolic wall stress appears to stimulate hypertrophy at a fixed rate, which stops when end-diastolic wall stress has been reduced to an acceptable level.
Persistence of mitochondrial competence during myocardial autolysis
Authors: Rouslin W.
Published: December 2017

The rate of irreversible loss of mitochondrial phosphorylating respiratory function with NAD-linked substrates during zero flow myocardial autolysis at 37 degrees C was gradual and relatively linear with time, progressing at about 1% of the control activity per minute. State 3 respiratory rates and initial rates of inner membrane potential development dropped off in close parallel with one another as well as with NADH-coenzyme Q (CoQ) reductase activity, suggesting that oxygen uptake as well as membrane potential development were rate limited by the increasing impairment of electron flow through complex I. Although the initial rate of membrane potential development dropped off gradually, the time course for the loss of the ability to ultimately develop and hold a full potential was slower still, there being only a moderate impairment of this ability at 80 min of autolysis. This sustained ability to develop and hold a membrane potential after more than 1 h of autolysis suggested that inner membrane leakiness contributed little or not at all to the functional impairment observed. The irreversible loss of mitochondrial inner membrane competence emerged in these studies as a relatively late development in the sequence of cellular alterations which characterize the myocardial ischemic process.
Transient vs. steady end-systolic pressure-volume relation in dog left ventricle
Authors: Igarashi Y. , Goto Y. , Yamada O. , Ishii T. , Suga H.
Published: December 2017

We compared transient slope of end-systolic pressure-volume line (T-Emax) with steady Emax (S-Emax) in isolated cross-circulated canine left ventricles. T-Emax is the slope of the end-systolic pressure-volume line (ESPVL) determined from the last steady-state ejecting contraction (SEC) and the first transient isovolumic contraction produced by end-diastolic volume clamp. S-Emax is the slope of ESPVL determined from five steady-state contractions by linear regression analysis. We obtained three T-Emax values in the same contractile state by changing ejection fraction (EF) of SEC to three levels (range 14-58%) from the same end-diastolic volume. T-Emax variably increased with EF in any contractile state. The ratios of the three T-Emax values to the same S-Emax value was 1.08 +/- 0.04 (11 ventricles, means +/- SE) for high EF, 0.87 +/- 0.06 for middle EF, and 0.69 +/- 0.07 for low EF in control contractile state. These ratios decreased under epinephrine and increased under propranolol. We conclude that T-Emax depends not only on EF but also on contractile state in isolated dog left ventricles.
Contractile responses to sympathetic activation after coronary instrumentation
Authors: Heusch G. , Guth B. D. , Roth D. M. , Seitelberger R. , Ross J.
Published: December 2017

The consequences of acute coronary dissection and chronic coronary instrumentation on contractile responses to sympathetic activation were examined in dogs. Stimulation of the left ventrolateral cervical cardiac nerve in seven anesthetized dogs after acute dissection of the left circumflex coronary artery (CX) did not change the increase in systolic shortening velocity. After acute dissection of the left anterior descending coronary artery (LAD), nerve stimulation increased shortening velocity of the posterior wall in all dogs but enhanced that of the anterior wall in only five dogs. In six conscious dogs with chronic instrumentation of the CX, reflex sympathetic activation induced by occlusion of the inferior vena cava comparably increased thickening velocities of both the anterior wall and posterior walls both at 1 and 3 wk after instrumentation. In six other dogs with chronic instrumentation of the LAD, responses to caval occlusion were nonuniform and correlated to the morphological degree of sympathetic denervation. Therefore, acute dissection and chronic instrumentation of the LAD may produce sympathetic denervation but do not cause functionally significant sympathetic denervation of the CX region.
Effect of high calcium intake on pressor responsivity in hypertensive rats
Authors: Stern N. , Golub M. , Nyby M. , Berger M. , Eggena P. , Lee D. B. , Tuck M. L. , Brickman A. S.
Published: December 2017

Some proposed mechanisms for the hypotensive effect of high calcium intake involve reduction in vascular responsivity. To assess the effect of dietary calcium on vascular responsivity, spontaneously hypertensive rats (SHR) were placed on normal (N-Ca; 0.4%) or high (H-Ca; 2.8%) casein-based synthetic diet for 4 wk. Intraarterial pressure, pressor response to graded intravenous infusion of norepinephrine (NE) and angiotensin II (ANG II), and in vitro vascular reactivity of tail artery segments to NE and transmural nerve stimulation (TNS) were studied. Urinary electrolyte excretion, plasma renin activity (PRA), aldosterone, NE, and epinephrine (EPI) were also determined. H-Ca SHR had a lower intraarterial systolic and diastolic pressure. However, H-Ca SHR had greater in vivo pressor response to both ANG II and NE. Maximal contractile force developed by tail artery segments in vitro in response to NE and TNS was slightly, but not significantly, higher in H-Ca SHR. In vitro dose-response curves to NE and TNS were not significantly different. Although H-Ca SHR had increased urinary excretion of sodium throughout the study period, PRA and aldosterone levels were similar in both groups. Plasma NE and EPI levels in the two groups were also not different. Despite lowered intra-arterial blood pressure, H-Ca SHR exhibited enhanced pressor response to ANG II and NE in vivo and a similar in vitro vascular reactivity to NE and TNS when compared with N-Ca SHR. Our results do not support a role for alterations in vascular reactivity to NE or ANG II in the hypotensive effect of high calcium intake in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Tissue-fluid pressure measured in perfused rabbit hearts during osmotic transients
Authors: Anderson S. E. , Johnson J. A.
Published: December 2017

To resolve discrepancies between models used to calculate myocardial capillary solute permeability we measured tissue-fluid pressure (Pi), perfusion pressure (Pp), and heart weight continuously after a step change in the NaCl or inulin concentration of crystalloid solutions perfusing isolated rabbit hearts. Linear regression analysis of the mean values for near steady-state Pi plotted against Pp showed significantly different (P less than 0.01) slopes of 0.77 and 0.40, respectively, for the inner and outer halves of the left ventricular free wall. Tissue compliance (Tcm) was measured as the fractional change in whole heart weight divided by the concurrent change in Pi. For NaCl and inulin osmotic transients Tcm values were 0.005 +/- 0.001 (SE) and 0.014 +/- 0.004 ml X cmH2O-1 X g tissue-1, respectively. A model for heart weight change based on the Starling hypothesis predicts significantly different tissue compliance (Tcc) values of 0.031 +/- 0.004 and 0.040 +/- 0.005 ml X cmH2O-1 X g tissue-1 for the same transients, respectively. This model shows myocardial capillary permeability for inulin and NaCl are overestimated by 25% if tissue compliance is not included in the analysis. The discrepancy between Tcm and Tcc is discussed.