bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic limit of the heart perfused at constant pressure
Authors: Weber K. T. , Janicki J. S. , Fishman A. P.
Published: December 2017

Autoregulatory adjustments in coronary vascular resistance (CVR) and O2 extraction (O2E) maintain O2 supply so that cardiac performance is not normally limited by O2 availability. The presence of an aerobic limit beyond which O2 availability is inadequate for the level of O2 need, however remains to be elucidated. Toward this end, 14 paced isolated canine hearts were used; coronary perfusion pressure was held constant at either 80 mmHg (8 hearts, group 1) or 40 mmHg (6 hearts, group 2). Work and O2 consumption were varied by increments in ventricular filling pressure (EDP, 16--20 mmHg) and heart rate (HR, 150--220 beats/min) and by infusion of dobutamine (D, 6--43 micrograms/min). In group 1, the aerobic limit was achieved when average EDP was 18 +/- 0.6 mmHg; HR, 181 +/- 5 beats/min; and D, 14 +/- 2 micrograms/min; CVRmin was 45 +/- 3% of control (nonworking state) and O2Emax 80 +/- 2%. Beyond this limit, additional increments in HR or D were not accompanied by further coronary vasodilatation and resulted in a marked reduction in lactate extraction (delta L/L) to -13 +/- 3%, the onset of lactate production (8 +/- 0.9 mg/100 ml), a decline in developed isovolumetric force (12 +/- 2%), and the appearance of pulsus alternans (6 hearts/. In group 2, delta L/L became negative when EDP was 19 +/- 1 mmHg; HR, 156 +/- 11 beats/min; D, 5 +/- 1 microgram/min; while O2Emax was 82 +/- 0.9% and CVR fell 13 +/- 6.6% from control; pulsus alternans appeared in 5 of these 6 hearts. We conclude that under the condition of constant coronary perfusion pressure an aerobic limit of the heart can be demonstrated. When aerobic demand exceeds O2 capacity, lactate production results, ventricular performance declines, and pulsus alternans appears.
Alterations in renal vascular resistance and reactivity in spontaneous hypertension of rats
Authors: Berecek K. H. , Schwertschlag U. , Gross F.
Published: December 2017

Vascular resistance and reactivity were investigated in isolated, constant flow perfused kidneys of stroke-prone spontaneously hypertensive rats (SHRSP) and age- and sex-matched normotensive Wistar-Kyoto control rats (WKY rats). Stroke-prone spontaneously hypertensive rats were studied at 4 wk, 2 mo, and 4 mo of age representing different stages of development of hypertension. Resistance in maximally vasodilated vascular beds was greater and the pressure-flow relationship was significantly shifted to the left in kidneys of SHRSP as compared to WKY rats. Responses to norepinephrine, vasopressin, serotonin, and angiotensin II were enhanced in the renal vascular bed of SHRSP. Dose-response curves were shifted to the left, had steeper slopes, decreased thresholds, and increased maximal responses. With longer duration of hypertension, resistance increased, the slopes of the dose-response curves were steeper, and maximum responses greater. The higher resistance and enhanced reactivity in the renal vasculature of SHRSP, already demonstrable in the prehypertensive stage appear to be due to primary structural and functional alterations of the resistance vessels.
Blood pressure, plasma catecholamines, and sympathetic outflow in pithed SHR and WKY rats
Authors: Yamaguchi I. , Kopin I. J.
Published: December 2017

After destruction, by pithing, of the central nervous system, the blood pressure (BP) of the spontaneously hypertensive (SHR) rat falls, but remains higher than in the pithed normotensive (WKY) rat. At all ages examined, stimulation of the sympathetic outflow evoked greater increases in BP of pithed SHR rats, but the increases in plasma catecholamines were similar in the two strains. The BP increase evoked by administered norepinephrine was greater in old SHR than in old WKY rats, but this increased response was not found in young animals. Both young and old SHR rats, however, were more sensitive than WKY rats to the pressor effects of epinephrine. Results of selective pharmacologic blockade of cardiac or vascular beta-adrenoceptors suggest that a smaller vasodilator response in young SHR rats to the beta-adrenergic effects of epinephrine is responsible for the greater pressor response than in WKY rats. This factor diminishes in older SHR rats in which, as suggested by Folkow, structural changes in the resistance blood vessel diameter may account for the enhanced pressor responsivity of SHR rats.
Evaluation of long-term chemical sympathectomy in adult rabbits
Authors: Fronek K.
Published: December 2017

Administration of 6-hydroxydopamine (6-OHDA) will produce long-term sympathectomy in newborn animals. This investigation was designed to determine whether or not a long-term sympathectomy can be achieved by repeated administration of 6-OHDA in adult rabbits. Chronic treatment with 6-OHDA lowered blood pressure on average of 9 mmHg; the carotid sinus reflex was depressed, in contrast to the pressure response to intravenously administered epinephrine, which was doubled. In a constant-flow hindlimb preparation, the response to norepinephrine (NE) in 6-OHDA-treated rats was 50% larger and lasted 3 times longer. NE uptake in vitro, which is proportional to the number of adrenergic nerve endings, was found to be diminished by 80-85% in aortas from 6-OHDA-treated animals, and the dose-response curve for NE was slightly shifted to the left. The number of ganglionic cells in the superior cervical ganglia in treated animals was decreased by 80%. In conclusion, results from 6-OHDA-treated adult animals were entirely consistent with the effects of long-term sympathectomy.
Effect of shape on pressure-volume relationships of ellipsoidal shells
Authors: Janz R. F. , Kubert B. R. , Pate E. F. , Moriarty T. F.
Published: December 2017

Previous theoretical procedures for determining the slope and intercept of the stiffness-stress relationship of the passive myocardium from diastolic pressure-volume (P-V) data assume that the eccentricity of the left ventricle (LV) is invariant. In this study a mathematical model for an ellipsoidal membrane was developed that does not contain that constraint. The model predicts a small (less than 10%) but significant decrease in eccentricity as transmural pressure increases. This result was confirmed by the use of a thick-wall finite element model. The implications of this result are as follows. 1) The slope and intercept of the stiffness-stress relationship of unconstrained ellipsodial shells can be determined by fitting a spherical model to the P-V relationships exhibited by the shells. 2) An ellipsoidal model that assumes that the eccentricity of such shells is invariant for all pressures would predict erroneous intercepts. 3) If the eccentricity of the diastolic LV initially decreases relative to its value at zero transmural pressure, then a thick-wall spherical model may be adequate for determining the slope and intercept of the myocardial stiffness-stress relationship.
A chronic arterial catheter and low compliance system for recording blood pressure and heart rate from the rat
Authors: Dworkin B. R. , Filewich R. J. , Da Costa J. , Eissenberg E. , Miller N. E.
Published: December 2017

A procedure for cannula construction, surgical implantation, and utilization is presented for recording arterial blood pressure and heart rate from the renal artery of unanesthetized mobile rats. The method involves unilateral nephrectomy, but the animals recover quickly and remain in excellent health. The cannula requies minimal maintenance; it has been used in cardiovascular experiments to make multiple periodic arterial blood pressure recordings. Patency for 2 mo or longer is common.
Plasma vasopressin in blood pressure homeostasis and in experimental renal hypertension
Authors: Pullan P. T. , Johnston C. I. , Anderson W. P. , Korner P. I.
Published: December 2017

The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension was investigated in the conscious dog. Intravenous infusion of synthetic arginine vasopressin to elevate plasma levels approximately fivefold to 31 pg/ml caused bradycardia in normal dogs, together with suppression of plasma renin activity and angiotensin II. This plasma level of vasopressin also caused elevation of mean arterial blood pressure in dogs with pharmacological total autonomic blockade. A similar degree of elevation of plasma vasopressin concentration was observed following mild nonhypotensive hemorrhage; more severe hemorrhage resulted in an approximate 100-fold increase in plasma vasopressin levels. Severe renal artery constriction in unilaterally nephrectomized dogs caused a marked rise in mean arterial blood pressure, but only a doubling of plasma vasopressin concentration. A suppressor infusion of vasopressin did not potentiate the pressor response to infused angiotensin II. It is concluded that vasopressin may play a role in normal cardiovascular homeostatic responses, but it is unlikely to have a significant direct vasoconstrictor role in the pathogenesis of this form of experimental renal hypertension.
Evaluation of presynaptic alpha-receptor function in the canine renal vascular bed
Authors: Robie N. W.
Published: December 2017

The functional significance of presynaptic alpha-receptor modulation of sympathetic nerves was examined in vivo in the canine renal vascular bed. In pentobarbital-anesthetized dogs, the vasoconstrictor response to renal nerve stimulation and exogenous norepinephrine was compared before and during intra-arterial infusions of epinephrine, oxymetazoline, clonidine, and norepinephrine. Only epinephrine produced a modest decrease in stimulation-induced vasoconstriction at 1 Hz. After pretreatment with desipramine, intra-arterial infusions of epinephrine or norepinephrine did not alter stimulation-induced vasoconstrictor responses relative to exogenous norepinephrine. Further, neither yohimbine nor phentolamine (10(-9) to 10(-3) g, intra-arterial) produced a distinctly increased vasoconstrictor response to nerve stimulation relative to exogenous norepinephrine. Thus, studies using alpha-receptor agonists, antagonists, and inhibition of neuronal uptake failed to reveal a physiologically significant alpha-receptor-mediated negative feedback mechanism for stimulation-induced vasoconstriction in the canine renal vascular bed.
Performance of diabetic rat hearts: effects of anoxia and increased work
Authors: Ingebretsen C. G. , Moreau P. , Hawelu-Johnson C. , Ingebretsen W. R.
Published: December 2017

An isolated perfused working rat heart preparation was used to assess the effect of alloxan-induced diabetes on myocardial performance. Ventricular performance was assessed under different aortic afterload, isoproterenol-stimulated and anoxic conditions. Basal left ventricular pressure development and rate of rise of ventricular pressure were depressed in hearts from diabetic animals. Neither coronary flow nor cardiac output were affected by diabetes. The dose and temporal responses to an infusion of isoproterenol were unaltered in diabetic hearts. Isoproterenol increased coronary flow by 50% and elevated ventricular pressure, dP/dt, and cardiac output by two- to threefold. Anoxia depressed ventricular pressure to below 20% of control within 5 min in both diabetic and normal hearts. Reoxygenation after 10 min of anoxia produced equivalent recovery in both groups working against a 52-mmHg aortic afterload, whereas recovery after 20 or 30 min of anoxia, was depressed in diabetic hearts. Elevating aortic afterload decreased performance of diabetic hearts and decreased their ability to recover from a 10-min anoxic exposure. Many of these observed differences in mechanical performance of diabetic hearts can be overcome by high glucose or insulin in the perfusion media.
Implantable stimulating electrode for baroreceptor afferent nerves in rabbits
Authors: Karemaker J. M. , Borst C. , Schreurs A. W.
Published: December 2017

An implantable stimulating electrode was developed for baroreceptor afferent nerves in the freely moving rabbit (nerve diam 0.1-0.2 mm). It consists of highly flexible electrode leads (coiled Pt-Ir wire) and silicone rubber (Silastic) as insulation. The electrodes were shown to be effective for up to 245 days after implantation in the neck. Electrode failure was due to dislodgment of the electrode (early failures) or (ultimately) cable breakage. Heart rate and blood pressure responses of separate and combined stimulation of depressor and carotid sinus nerves are shown. In vitro studies demonstrated some current leakage from the electrode to surrounding tissues, but the in vivo measurements show the validity of the method.
Contractile function in canine right ventricle
Authors: Meier G. D. , Bove A. A. , Santamore W. P. , Lynch P. R.
Published: December 2017

Regional right ventricular (RV) motion was examined in six acutely instrumented dogs by implanting radiopaque markers in three regions of the free wall: the apex, the midventricle, and the outflow tract. These markers were filmed at the paced heart rate of 180 beats/min with a high-speed biplane X-ray system, and their motion was analyzed with a digital computer. Local deformation was separated into percent length changes in the two mutually perpendicular principal directions. The major component exhibited shortening along a path from apex to conus. (apex - 13.6%, midventricle -13.1%, conus -8.7%); the minor component exhibited small amounts of lengthening and some shortening (apex +4.7%, midventricle +1.8%, conus -0.5%). From these two measurements we calculated the peak RV free wall thickening (apex 13.6%, midventricle 14.1%, conus 10.9%). The experimental technique developed for this study was found to be suitable for the repeated analysis of intact ventricular performance in chronic animal studies. The results reveal that in systole the RV free wall undergoes a sequential contraction, which begins at the apex and ends in the conus.
Cardiac cyclic nucleotides and norepinephrine during neural sympathetic stimulation
Authors: Pindok M. T. , Sukowski E. , Glaviano V. V.
Published: December 2017

The role of the cardiac cyclic nucleotides, adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP), and norepinephrine (NE) in cardiac responses to stimulation of the left ansa subclavia were studied in anesthetized open-chest dogs. In three groups of dogs undergoing stimulation for 6 min with impulse frequencies of 4, 10, or 20 Hz and 5 V, left ventricular levels of cAMP, cGMP, and NE were determined at the end of the stimulation period and compared to control dogs. A significant elevation in cAMP (avg 67%) was found at all three frequencies. Myocardial NE decreased by an average of 58% from control by the end of the stimulation period, regardless of the stimulation frequency. The rate of left ventricular pressure rise (LV dP/dt) was found to be linearly related to the increase in myocardial cAMP (P less than 0.01) rather than to NE levels found after stimulation. Propranolol administered before ansa subclavia stimulation caused significant decreases in both cAMP and LV dP/dt, whereas the muscarinic agonist carbachol, caused increases in cGMP and NE and a decrease in LV dP/dt accompanied by a nonsignificant decline in cAMP. The elevation in levels of cGMP and NE and the decrease in LV dP/dt to carbachol were blocked with atropine. Results from pretreating dogs with propranolol and carbachol followed by neural sympathetic stimulation indicated the importance of beta-adrenergic and muscarinic receptors in modifying cardiac function through the production of the cyclic nucleotides. Sustained cardiac responses during ansa subclavia stimulation at physiological levels could be related to the accelerated synthesis of endogenous cAMP.
Decreased membrane fluidity and beta-adrenergic responsiveness in atherosclerotic quail
Authors: Lurie K. G. , Chin J. H. , Hoffman B. B.
Published: December 2017

The effects of increased cholesterol on erythrocyte membrane fluidity and beta-adrenergic function were studied in a quail model of atherosclerosis. Birds fed a cholesterol-supplemented diet developed severe atherosclerosis and hypercholesterolemia after 6 wk. This cholesterol-enriched diet led to a markedly elevated serum cholesterol and a 26% increase in the cholesterol-to-phospholipid ratio in erythrocyte membranes. Electron paramagnetic resonance spectra measured with 5- and 12-doxyl-stearic acid spin-label probes were used to estimate the order of quail erythrocyte membranes. Membrane preparations from cholesterol-fed birds were more highly ordered near the membrane leaflet surface, as well as deeper in the membrane interior, compared with controls. beta-Adrenergic receptor stimulation of adenosine 3',5'-cyclic monophosphate accumulation was blunted in erythrocytes from the hypercholesterolemic quail. There was no change in beta-receptor density or affinity in the cholesterol-enriched membranes. These studies demonstrate that cholesterol incorporation into erythrocyte membranes in vivo is associated with decreased membrane fluidity and decreased beta-adrenergic responsiveness. The atherosclerotic quail may serve as a useful model to further probe the sequelae of hypercholesterolemia on the function of integral membrane proteins.
Apparent reduction in baroreflex sensitivity to adenosine in conscious dogs
Authors: Hintze T. H. , Belloni F. L. , Harrison J. E. , Shapiro G. C.
Published: December 2017

Relative effects of equihypotensive doses (-35 mmHg) of adenosine (5.0 mumol/kg) and nitroglycerin (25 micrograms/kg) on heart rate and, therefore, baroreflex sensitivity were studied in conscious dogs. Nitroglycerin increased heart rate 133 +/- 24% from 78 +/- 5.5 beats/min, whereas adenosine increased heart rate only 79 +/- 16% from 78 +/- 5.2 beats/min (P less than 0.01). Injection of nitroglycerin during combined beta-adrenergic and muscarinic receptor blockades caused arterial pressure to fall 38 +/- 3.4% from 107 +/- 3.2 mmHg without any significant change in heart rate (3.8 +/- 3.8 from 162 +/- 9.2 beats/min). During combined beta-adrenergic and muscarinic receptor blockades adenosine also reduced arterial pressure 45 +/- 2.7% from 106 +/- 2.9 mmHg but unexpectedly reduced heart rate as well by 37 +/- 1.7% from 160 +/- 9.7 beats/min. This bradycardia reflected an effect on the sinoatrial (SA) node rather than an induction of heart block, since the R-R interval increased by 70 +/- 7.8% from 371 +/- 20 ms (P less than 0.01), while the P-R interval increased only 13 +/- 2.3% from 97 +/- 7.2 ms (P less than 0.05) with no electrocardiographic evidence of nonconducted beats. Arterial plasma adenosine levels were 43 +/- 5 nmol/ml at this time. Adenosine also caused bradycardia during muscarinic blockade alone (-43 +/- 3.4% from 201 +/- 6.4 beats/min) and following bilateral vagal section (-33 +/- 1.9% from 151 +/- 5.9 beats/min). In summary, adenosine appears to alter normal baroreflex function in the conscious dog by reducing the tachycardia that normally follows a fall in systemic arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular regional work from wall tension-area loop in canine heart
Authors: Goto Y. , Suga H. , Yamada O. , Igarashi Y. , Saito M. , Hiramori K.
Published: December 2017

To quantitatively evaluate left ventricular (LV) regional work, LV pressure-volume relation and wall tension-regional area (TA) relation were analyzed in the excised cross-circulated left ventricle connected to a volume servo pump system. Wall tension was calculated using Laplace's law for a spherical model, and regional area was determined from orthogonal segment lengths measured with pairs of ultrasonic crystals. Data were obtained by changing LV end-diastolic volume or stroke volume before and after dobutamine infusion and before and after global ischemia. Regional work, assessed from the area within a TA loop during one cardiac cycle, correlated well with simultaneously obtained LV stroke work under all of the above experimental conditions (r = 0.90 +/- 0.09 to 0.97 +/- 0.02), and the linear regression line was not altered by changes in stroke volume, end-diastolic volume, or contractile state. Furthermore, measured regional work (RWm) proved to agree closely with the predicted value (RWp) calculated from LV stroke work and regional area [RWm = 0.91 RWp - 0.69 (mmHg . ml), r = 0.93]. Thus we conclude that TA relation may be useful for quantitative evaluation of regional work of the LV wall.
Noninvasive measurements of nonlinear arterial elasticity
Authors: Megerman J. , Hasson J. E. , Warnock D. F. , L'Italien G. J. , Abbott W. M.
Published: December 2017

To describe fully the compliance characteristics of an artery with nonlinear elastic properties, measurements must be obtained over a wide range of pressures. Furthermore, repeated measurements, as required in temporal studies of arterial implants, require that the measuring technique be noninvasive. The application of a pulsed ultrasound echo-tracking device is described, which fulfills both criteria. Nonlinear compliance-pressure (CP) curves were obtained from the femoral arteries of dogs, with the use of halothane anesthesia to vary systemic pressure, and were used to compare the gross elastic properties of different vessels. Studies using controlled hemorrhage or the vasoactive drugs, nitroprusside and levarterenol (norepinephrine), were used to verify that the CP curves obtained during halothane anesthesia did not reflect varying degrees of smooth muscle activation. However, surgical exposure did temporarily reduce arterial compliance at pressures between 60 and 140 mmHg. The effect of vasoactive intervention and of postsurgical changes in arterial or graft compliance can thus be quantitated by use of CP curves or by comparing incremental elastic moduli, which can also be estimated from the noninvasively derived measurements.
Vasopressin and renin response to plasma volume loss in spontaneously hypertensive rats
Authors: Sladek C. D. , Blair M. L. , Chen Y. H. , Rockhold R. W.
Published: December 2017

Abnormalities in the vasopressin (VP) and renin-angiotensin systems have been described in spontaneously hypertensive rats (SHR). Responsiveness of these systems to a decrease in plasma volume was examined in the SHR at 6, 8, and 18 wk of age and compared with responses in age-matched normotensive Wistar and Wistar Kyoto rats (WKY). Trunk blood was collected 3 h after administration of 2 ml/100 g body wt of 0.9% saline, 15 or 30% polyethylene glycol (PEG), and in one group of conscious 8- and 18-wk-old rats, mean arterial pressure was monitored following PEG administration. Hematocrit and serum VP increased significantly in both strains at all ages following PEG. At 6 and 8 wk of age, the VP response to the PEG injection was significantly greater in SHR compared with WKY (P less than 0.005), but at 18 wk the response was comparable in the two strains. Serum renin activity (SRA) also increased in both strains receiving PEG at 6 and 8 wk of age, but the response was suppressed in the SHR relative to the WKY (P less than 0.001). At 18 wk of age, SRA increased in WKY, but the response was totally suppressed in SHR. Renal renin content in a separate group of rats was reduced in 19-wk-old SHR compared with WKY (P less than 0.001) but was not different in 5- and 8-wk-old rats. Thus there appears to be a hyperresponsiveness in the VP system in young SHRs that is not present in the renin-angiotensin system. The divergence in the responsiveness of the renin and VP systems and the attenuation of responsiveness in the VP system in 18-wk SHRs indicate a differential effect of the hypertensive process on the VP and renin systems in the SHR.
Muscle mechanics and Ca2+ transport in atrophic heart transplants in rat
Authors: Korecky B. , Ganguly P. K. , Elimban V. , Dhalla N. S.
Published: December 2017

Isometric contractile activity and force-frequency relationship were investigated in heterotopically isotransplanted rat hearts that performed minimal external work for 8 wk and underwent atrophy. No changes were found in the isometric contraction phase of the papillary muscles from the transplants when compared with the hearts of recipient animals that carry full hemodynamic load. However, the relaxation phase of the transplants was impaired at higher frequencies (greater than 24 stimuli/min) of stimulation and at higher levels of calcium (greater than 2.0 mM Ca2+) in the medium. When Ca2+-accumulating activities of cardiac microsomes containing fragments of the sarcoplasmic reticulum (SR) were studied, a significant decrease was seen in the transplanted hearts in comparison with the host hearts. This decrease in Ca2+-uptake activity was observed at different times of incubation as well as different concentrations of free Ca2+ (10(-7) to 10(-5) M Ca2+). Although Ca2+-stimulated ATPase activity did not change, alterations in the phospholipid contents of the SR vesicles from the transplanted hearts were observed. These results provide some evidence for a depression in the SR Ca2+ uptake in transplanted hearts undergoing atrophy and may explain the underlying alteration in the relaxation phase of these hearts.
NO-mediated activation of heme oxygenase: endogenous cytoprotection against oxidative stress to endothelium
Authors: Motterlini R. , Foresti R. , Intaglietta M. , Winslow R. M.
Published: December 2017

We investigated the effect of nitric oxide (NO) on the induction of the stress protein heme oxygenase and its protective role in vascular endothelial cells exposed to hydrogen peroxide. Treatment of porcine aortic endothelial cells for 6 h with the NO-releasing compounds (0.1-1 mM) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1) resulted in a concentration-dependent increase in heme oxygenase activity. At 1 mM, the activity of heme oxygenase was augmented 8.5-fold with SNP, 5.8-fold with SNAP, and 5.7-fold with SIN-1 over the control value. In contrast, endothelial cells exposed to 100 microM S-bromoguanosine 3',5'-cyclic monophosphate, a tissue-permeable analogue that mimics the action of guanosine 3',5'-cyclic monophosphate, did not show any change in heme oxygenase activity. Activation of the inducible NO synthase by the synergistic action of bacterial lipopolysaccharide (250 ng/ml) and interferon-gamma (100 U/ml) also increased endothelial heme oxygenase activity by 3.2-fold (P < 0.05 vs control). Methylene blue (1 microM), an inhibitor of both NO synthase and guanylate cyclase activities, completely abolished this effect. Cells previously exposed to SNAP and SIN-1 exhibited a significant protection against the cytotoxicity mediated by hydrogen peroxide (250 microM) (P < 0.05). Conversely, SNP did not show any protective effects, possibly because of catalytic iron released during its chemical decomposition. In fact, the iron chelator deferoxamine (5 mM) completely suppressed the SNP-mediated cytotoxicity and partially attenuated the activity of heme oxygenase to a level equal to that mediated by SIN-1 and SNAP. These results indicate that NO is a determinant in the modulation of the activity of heme oxygenase leading to a major resistance of the endothelium to oxidative stress.
Exercise- and hypertension-induced collagen changes are related to left ventricular function in rat hearts
Authors: Burgess M. L. , Buggy J. , Price R. L. , Abel F. L. , Terracio L. , Samarel A. M. , Borg T. K.
Published: December 2017

Chronic hypertension, known to affect the collagen profile of the heart, and exercise result in impaired or improved heart function, respectively. Collagen types I [alpha 1(I)2 and alpha 2(I)] and III [alpha 1(III)3] are the predominant interstitial collagens thought to influence cardiac function, and the ratio of type III to I (collagen III/I) is thought to be a significant factor in the altered relaxation observed in hypertrophy. The present study tested the hypothesis that the myocardial structure and function are different in chronically exercise-trained vs. hypertensive rat hearts. Male rats were either chronically exercised (XTr) or submitted to experimental hypertension by coarctation of the abdominal aorta (Hyp) for 10 wks. Heart rate, blood pressure, and maximal rate of fall of the left ventricular pressure (-dp/dt) were recorded during isoproterenol stimulation. Results showed that both Hyp and XTr had higher heart weight and left ventricular weight-to-body weight ratios (P < 0.05). Mean arterial pressure (MAP) was higher in Hyp and lower in XTr (P < 0.05), whereas (-dP/dt)/MAP was diminished in Hyp but enhanced in XTr. Left ventricular collagen was higher in Hyp than XTr, whereas collagen III/I was reduced in Hyp compared with XTr (P < 0.05). Scanning and transmission electron microscopy also supported an accumulation of left ventricular collagen in Hyp compared with XTr. A negative correlation was observed between collagen III/I and (-dP/dt)/ MAP (r = -0.91; P < 0.05). These results suggest an important relationship between adaptations in left ventricular collagen and the changes in diastolic function observed in both chronic hypertension and exercise cardiac stress.
Regulation of NHE-1 promoter in mammalian myocardium
Authors: Yang W. , Dyck J. R. , Wang H. , Fliegel L.
Published: December 2017

The Na+/H exchanger (NHE-1) is an integral membrane protein responsible for intracellular pH regulation in the myocardium and other tissues. The NHE-1 isoform is universally distributed in mammalian cells. We examined regulation of a 1.1-kb fragment of the NHE-1 promoter in neonatal rat cardiomyocytes. Deletion of most of the promoter up to an AP-2 site reduced activity 75%. Further deletion of the promoter or mutation of the AP-2 site reduced or eliminated activity almost completely. Gel mobility shift assay showed that purified AP-2 protein or AP-2-like protein from nuclear extracts of isolated myocytes can bind to DNA of the NHE-1 protein. External acidosis did not cause increased transcription from the promoter. Removal of serum from the medium reduced activity of the NHE-1 promoter. The elements responsible for activation of the promoter by serum were contained within both the 1.1-kb and AP-2-containing region. The results show that the cis-acting putative AP-2 site and the presence of serum are important in NHE-1 expression, whereas external acidosis had no direct effect on the promoter.
Regional wall mechanics in the ischemic left ventricle: numerical modeling and dog experiments
Authors: Bovendeerd P. H. , Arts T. , Delhaas T. , Huyghe J. M. , van Campen D. H. , Reneman R. S.
Published: December 2017

The mechanics of the ischemic left ventricle during a complete cardiac cycle were simulated using a finite-element model accounting for the thick-walled ventricular geometry, the fibrous nature of the myocardial tissue, and the dependency of active muscle fiber stress on time, strain, and strain rate. Ischemia was modeled by disabling the generation of active stress in a region comprising approximately 12% of total wall volume. In the model simulations, the approximately 12% reduction in the amount of normally contracting tissue resulted in an approximately 25% reduction in stroke work compared with the normal situation. The more-than-proportional loss of stroke work may partly be attributed to storage of elastic energy in the bulging ischemic region. Furthermore the mechanical performance in the nonischemic border zone deteriorated because of reduced systolic fiber stress (if fibers were in series with those in the ischemic region) or reduced fiber shortening (if fibers were parallel). The deformation pattern of the ventricle was asymmetric with respect to the ischemic region because of the anisotropy of the myocardial tissue. Epicardial fiber shortening in and around the ischemic region, as predicted from the model simulations, was in qualitative agreement with shortening, as measured in four dogs in which ischemia was induced by occlusion of the distal part of the left anterior interventricular coronary artery.
Oxidative stress increases glyceraldehyde-3-phosphate dehydrogenase mRNA levels in isolated rabbit aorta
Authors: Ito Y. , Pagano P. J. , Tornheim K. , Brecher P. , Cohen R. A.
Published: December 2017

We have recently shown that inhibition of endogenous Cu,Zn superoxide dismutase (SOD) by diethyldithiocarbamate (DDC) increased superoxide anion levels in isolated rabbit aortic rings, describing a useful experimental model to examine the effects of oxidative stress on the vessel wall. The present study examined the effects of oxidative stress on the steady-state mRNA levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). Aortic rings were incubated in physiological salt solution at 37 degrees C for up to 6 h. DDC (2 mM) decreased total SOD activity to < 5% of control levels and increased superoxide anion level ninefold. Steady-state mRNA levels of GAPDH were increased under comparable conditions. Although decreased biological activity of endothelium-derived nitric oxide was indicated by lower basal guanosine 3',5'-cyclic monophosphate levels in aortic rings treated with DDC compared with those in control rings (1.2 +/- 0.1 vs. 1.9 +/- 0.3 fmol/microgram protein, P < 0.05), neither endothelium denudation nor NG-nitro-L-arginine methyl ester had any effects on the steady-state mRNA levels of GAPDH. The cell.permeable iron chelator 1,10-phenanthroline completely prevented the increases in GAPDH mRNA levels induced by DDC. These results suggest that oxidative stress resulting from inhibition of endogenous Cu,Zn SOD causes induction of GAPDH gene expression and that the hydroxyl radical, produced through the iron-catalyzed Haber-Weiss reaction, is the intracellular reactive oxygen species responsible for the DDC-stimulated increase in GAPDH mRNA.
ON THE SOURCES OF HEAT IN MUSCLE CONTRACTION
Authors: Snyder Charles D.
Published: December 2017

Volume LXVI, no. 2, October, 1923: The reader is asked to insert a division sign between the two numerical factors appearing in line 22 of page 233, and to read "1760" for the quotient instead of "1770." In line 5, page 234, again read "1760" instead of "1770."
THE EFFECTS OF ANOXEMIA DUE TO CARBON MONOXIDE AND LOW OXYGEN ON CEREBROSPINAL FLUID PRESSURE
Authors: Maurer Frank W
Published: December 2017

Volume 133. On page 188 change second reference to Maurer, F. W from "This Journal 132: 170, 1941" to read "Maurer, F. W. This Journal 133: 170, 1941."
Tetanic hyperpolarization of single medullated nerve fibers in sodium and lithium
Authors: Schoepfle GM
Published: December 2017

Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping.
Hemodynamic responses to stellate ganglion stimulation in mongrels and greyhounds
Authors: Cox RH , Peterson LH , Detweiler DK
Published: December 2017

A comparison of the effects of left stellate ganglion stimulation (SGS) on central and aortic hemodynamics has been made in chloralose-anesthetized mongrel (M), and greyhound (GH) dogs. Measurements of aortic pressure and flow, and left ventricular pressure were made during stimulation of the decentralized left SG at different frequencies from 0 to 20 Hz. The increases in aortic pressure and flow with SGS were larger in the GH, especially for low frequencies of stimulation. Stroke volume was increased with SGS in the GH at all stimulation rates, whereas in the M it was unchanged. A greater decrease in left ventricular end-diastolic pressure with SGS was found in the GH. These results suggest that differences exist in both the intrinsic and extrinsic control of cardiac output in the greyhound dog compared to the mongrel. These differences may be in part responsible for the elevated arterial blood pressure in the greyhound compared to the mongrel.
Calcium uptake by subcellular fractions of human umbilical artery
Authors: Clyman RI , Manganiello VC , Lovell-Smith CJ , Vaughan M
Published: December 2017

Two different mechanisms for the active accumulation of Ca2+ by subcellular fractions of human umbilical artery are described. One, located in the mitochondrial fraction, was induced by exogenous ATP or respiratory substrates (ADP and succinate) and was inhibited by azide. The other, located in the microsomal fraction, was induced by ATP and potentiated by oxalate, but not inhibited by azide. Increasing ATP concentrations up to 4-5 mM increased microsomal Ca2+ accumulation, whereas increasing ATP concentration above 2-3 mM caused inhibition of mitochondrial Ca2+ uptake. Although changing pH from 7.4 to 7.2 had no effect on mitochondrial Ca2+ accumulation, it doubled microsomal uptake. Neither adenosine 3',5'-monophosphate nor guanosine 3',5'-monophosphate in the presence or absence of protein kinase and kinase modulator affected Ca2+ uptake by or phosphorylation of the subcellular fractions. Partially purified protein kinases from umbilical and beef skeletal muscle contained a component(s) distinguishable from the kinase on the basis of its heat stability that enhanced ATP-induced Ca2+ uptake by mitochondrial fractions from the umbilical artery. It is suggested that alterations in Ca2+ sequestration induced by changes in ATP concentration and intracellular pH in mitochondrial and microsomal fractions, respectively, could play a role in the control of arterial patency and closure with changes in PO2.
Angiotensin II in antinatriuresis of low-level renal nerve stimulation
Authors: Zambraski EJ , DiBona GF
Published: December 2017

Low-level direct renal nerve stimulation increases both renal tubular sodium reabsorption and renal renin secretion rate without changing arterial pressure, glomerular filtration rate, renal blood flow, or intrarenal blood flow distribution. The possibility was considered that intrarenal angiotensin II formation might mediate the antinatriuretic effect by directly enhancing renal tubular sodium reabsorption. Low-level direct renal nerve stimulation was performed in anesthetized saline-loaded dogs before and after intrarenal blockade to angiotensin II with [1-sarcosine, 8-alanine]angiotensin II. The antinatriuretic response to low-level direct renal nerve stimulation was not altered by intrarenal blockade to angiotensin II. Renal renin secretion rate was increased by low-level direct renal nerve stimulation in the absence of changes in systemic or renal hemodynamics. The antinatriuretic effect of low-level direct renal nerve stimulation does not depend on the intrarenal action of angiotensin II.
Extracellular calcium and adrenergic and cholinergic effects on islet beta-cell function
Authors: Burr IM , Slonim AE , Burke V , Fletcher T
Published: December 2017

An in vitro perifusion system utilizing collagen-medium calcium on the dynamics of insulin release as induced by acetylcholine (ACh) stimulation (in the presence of glucose, 2.4 mM) and as modified by prior perfusion of islets in epinephrine. Continuous challenge with ACh produces a biphasic insulin release response, both phases of which are reduced when the medium calcium concentration is reduced during stimulation; when the calcium content is reduced during an initial perifusion period of 30 min and then replaced during subsequent stimulation only the first phase of the response to ACh is affected; perifusion with epinephrine prior to stimulation with ACh produces enhancement of both phases of ACh-induced insulin release when calcium in both media is normal. However,.when this experiment is repeated utilizing a medium with low calcium content during the period of exposure to epinephrine the priming effect of epinephrine on the subsequent insulin response to ACh is abolished (in fact, reversed). These studies provide direct evidence for a role for calcium in mediating an effect of epinephrine on insulin release. Further, the data suggest that epinephrine affects Ca transport in islets in some manner beyond stimulating net efflux from islets, perhaps by enhancing membrane binding of calcium.
Effect of ammonia via prepyriform cortex on regulation of food intake in the rat
Authors: Noda K , Chikamori K
Published: December 2017

Studies were made on whether ammonia, which is an obligatory intermediate of amino acid metabolism, depresses the food intake of rats fed a low-casein (basal) diet containing imbalanced amino acid mixtures (imbalanced diets). Bilateral lesions in the prepyriform cortex caused normalization of food intake of rats fed amino acid-imbalanced diets, confirming the work of Leung and Rogers (Am. J. Physiol. 221:929-935, 1971). Unlike normal rats, animals with prepyriform cortical lesions consumed as much of a diet containing 3% NH4Cl as they did of the basal diet. However, like normal rats, they rejected a diet containing a mixture of keto acids. Unilateral injection of NH4Cl into prepyriform cortical areas reduced the food intake to a greater extent than injection of NaCl into these areas or injection of NH4Cl into other parts of the brain. These results suggest that ammonium ions influence the appetite through their effect on prepyriform cortical areas.
Effects of chronic hypoxia and dietary restriction on myocardial enzyme activities
Authors: Barrie SE , Harris P
Published: December 2017

Enzyme activities were measured in homogenates of left and right ventricles of guinea pigs after 14 and 28 days' exposure to 400 mmHg barometric pressure. All animals developed anorexia and right ventricular hypertrophy. Two control groups of animals were used, one free fed and the other restricted to the amount of food chosen by the hypobaric group. The factorial design of the experiment allowed some distinction between the effects of anorexia, hypertrophy, and hypoxia. Dietary restriction was associated with a decrease in glycogen phosphorylase, hexokinase, and succinate dehydrogenase activity and an increase in the M-subunits of lactate dehydrogenase. Myocardial hypertrophy was associated with an increase in the activity of the enzymes of the glycolytic pathway down as far as phosphoglycerate kinase and an increase in the M-subunits of lactate dehydrogenase. Chronic hypoxia seemed specifically to be associated with an increase in the H-subunits of lactate dehydrogenase and possibly a slight transient increase in succinate dehydrogenase activity. Mixing studies indicated that changes in enzyme activities were likely to be due to changes in enzyme concentrations.
Effect of fasting on hepatic ligandin, Z protein, and organic anion transfer from plasma in rats
Authors: Stein LB , Mishkin S , Fleischner G , Gatmaitan Z , Arias IM
Published: December 2017

The effect of fasting on the rate of disappearance from plasma of bromsulphthalein (BSP) and dibromsulphthalein (DBSP), the hepatic content of BSP, and the concentration of ligandin and Z protein, two hepatic organic anion-binding proteins, was studied in the rat. Fasting for 48 h decreased the plasma disappearance of BSP and DBSP and the hepatic content of BSP as well as the amount of ligandin and Z protein. Phenobarbital given prior to fasting partially prevented these changes. A method of quantitation of Z by radioimmunoassay is described. Discrepancies in Z quantiation by dye binding and immunological methods in fasted but not control rats suggest the presence of competitors for organic anion binding to Z in fasting as well as after phenobarbital administration. Results of studies of ligandin turnover during fasting suggest decreased synthesis and increased degradation of the protein. Similar events may be of pathogenetic importance in nonhemolytic unconjugated hyperbilirubinemia observed during fasting in man, horses, and other animals.
Acute isovolemic anemia in anesthetized chickens
Authors: Nightingale TE
Published: December 2017

Acute isovolemic anemia was produced in anesthetized chickens by serial exchanges of 6% dextran 70 equal to 1% of body weight to quantitate cardiovascular and metabolic parameters. When hematocrit (Hct) and hemoglobin (Hb) levels were reduced by 50% (from 33.3 to 16.3 vol %, and from 10.3 to 5.4 g/100 g, respectively, P less than 0.001), tissue oxygen delivery was maintained by increases in cardiac output (CO), stroke volume (SV), oxygen extraction, and reduced total peripheral resistance (TPR). Heart rate, right atrial pressure, and oxygen consumption (Vo2) were unchanged. Further reductions in Hct and Hb (to 10.8 vol % and 3.7 g/100 g, respectively), were accompanied by cardiovascular failure, as evidenced by falling CO, SV, tissue oxygen delivery, and Vo2. Relative apparent viscosity determinations on the exchanged blood-dextran mixtures indicated that large viscosity changes occurred with the first exchange whereas subsequent exchanges had small incremental viscosity changes. These data indicate that in acutely anemic chickens, oxygen transport capacity was maintained by increased cardiac output and decreased peripheral resistance, unless the severity of the anemia resulted in cardiovascular failure.
Left ventricular function during acute elevation of aortic blood pressure in dogs
Authors: Ilebekk A , Thorvaldson J , Kiil F
Published: December 2017

Cardiac responses to mechanical constriction of the aorta proximal and distal to the arch arteries and to intravenous infusion of angiotensin were examined in open-chest atropinized dogs during continuous recording of left ventricular and aortic dimensions by means of ultrasonic elements. Proximal constriction reduced stroke volume by 18% both before and during isoproterenol infusion without changing left ventricular end-diastolic pressure, dimensions, or contractility, (dP/dt)IP; angiotensin induced less pronounced increments in stroke volume and end-diastolic volume. By combining proximal constriction with saline-dextran infusion, stroke volume and end-diastolic volume increased as during distal constriction. These results indicate that differences in preload account for the differences in stroke volume responses to proximal and distal aortic constriction. We propose that increased preload is caused by redistribution of blood from capacitance vessels rather than retention secondary to cardiac decompensation.
Effect of prostaglandin synthetase inhibitors on renal blood flow in the rat
Authors: Finn WF , Arendshorst WJ
Published: December 2017

Using a small-diameter electromagnetic flow transducer, the effect on the autoregulation of renal blood flow (RBF) of two structurally different prostaglandin synthetase inhibitors, indomethacin, 4 mg/kg BW, and meclofenamate, 5 mg/kg BW, was studied in nondiuretic rats anesthetized with either the oxybarbiturate, sodium pentobarbital, or the thiobarbiturate, Inactin. Regardless of the anesthetic agent, RBF remained relatively constant above a perfusion pressure of 105 mmHg. Treatment with either indomethacin or meclofenamate had no measurable effect on the autoregulatory response. Each agent, however, resulted in an increase in the renal vascular response to exogenous angiotensin II, an effect consistent with prostaglandin synthetase inhibition. Base-line RBF was significantly reduced by indomethacin or meclofenamate only in those animals that had previously received angiotensin. These results support the hypothesis that, in th rat, autoregulation of RBF occurs independently of prostaglandin activity, but that a relationship does exist between the renal vascular actions of angiotensin II and prostaglandins.