bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid baroreceptor resetting is unaltered by chronic hypertension in rats
Authors: Andresen M. C. , Yang M. Y.
Published: December 2017

This study compares rapid baroreceptor resetting in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Single-fiber baroreceptor activity and aortic diameter were measured in in vitro preparations. Baroreceptor pressure threshold (Pth) and suprathreshold pressure sensitivity were measured during periods after various levels of conditioning mean arterial pressure (cMAP). The ability of a baroreceptor to reset was expressed as the resetting ratio (delta Pth/delta cMAP). Rapid resetting was successfully characterized in 30 baroreceptors (18 SHR and 12 WKY). SHR blood pressures were higher, and aortic distensibility was lower than in WKY. SHR baroreceptors showed signs of chronic resetting, i.e., elevated Pth (105.4 vs. 88.5 mmHg, SHR and WKY, respectively) and decreased suprathreshold sensitivity (0.92 vs. 1.42 spikes.s.-1.mmHg-1, SHR and WKY, respectively), but their resetting ratios were similar to WKY (0.260 and 0.237, SHR and WKY, respectively). Characterization of rapid resetting of more than one baroreceptor from single animals reveals that the resetting ratio can vary by greater than 50% within animals. During simultaneous discharge-diameter recordings, the strain threshold was better correlated to cMAP than Pth. We conclude that the ability of baroreceptors to rapidly reset is unaltered by chronic hypertension or chronic baroreceptor resetting, and we hypothesize that rapid resetting is probably a result of an intrinsic neural property rather than vessel mechanics.
Release of platelet-activating factor from ischemic-reperfused rabbit heart
Authors: Montrucchio G. , Alloatti G. , Tetta C. , De Luca R. , Saunders R. N. , Emanuelli G. , Camussi G.
Published: December 2017

This study shows that platelet-activating factor (PAF) is released in significant amounts (10.9 +/- 12.8 ng/min) during the initial reperfusion of the ischemic-isolated rabbit heart. When reperfusion was performed in the presence of autologous rabbit platelets, the electrical and mechanical alterations characteristic of this phase were significantly worsened. These alterations were antagonized by pretreatment of rabbit platelets with a PAF receptor antagonist (SDZ 63-675), suggesting a contribution of PAF released during reperfusion in the cardiac dysfunction. To discriminate whether the effect of PAF was platelet dependent, infusion of PAF (10-40 ng) was performed in nonischemic rabbit hearts perfused with or without autologous platelets. Although the effect of PAF per se was minimal, in the presence of platelets PAF induced a biphasic effect characterized by a transient positive inotropism followed by a dose-dependent decrease in coronary flow, negative inotropism, reduction of action potential duration, and conduction arrhythmias. These effects were abolished by pretreatment of platelets with SDZ 63-675, suggesting a PAF receptor-mediated platelet activation. In addition, a relative contribution of histamine, thromboxanes, and leukotrienes released from activated platelets was inferred by experiments performed with pyrilamine and cimetidine, imidazole, and FPL 55712, respectively.
Central oxytocin systems may mediate a cardiovascular response to acute stress in rats
Authors: Callahan M. F. , Kirby R. F. , Cunningham J. T. , Eskridge-Sloop S. L. , Johnson A. K. , McCarty R. , Gruber K. A.
Published: December 2017

The role of central nervous system arginine vasopressin (AVP) and oxytocin (OXY) in the cardiovascular response to acute stress was examined using three experimental models: pharmacological antagonism of central AVP-OXY receptors; lesions of the paraventricular nucleus (PVN); and rats genetically lacking in AVP synthesis, i.e., the Brattleboro strain. Central administration of an AVP-OXY antagonist abolished the increase in heart rate (HR) seen following acute footshock stress. The group receiving centrally administered antagonist increased HR 15 +/- 17 (SE) beats/min, whereas, in contrast, the group receiving intravenous administration of the antagonist showed a 66 +/- 17 beats/min increase, and the group receiving intraventricular antagonist vehicle showed a 101 +/- 14 beats/min increase in response to stress. In a second study, electrolytic lesions of the PVN also blocked the increase in HR seen following stress, 20 +/- 12 beats/min for PVN-lesioned rats, 74 +/- 25 beats/min for sham lesion rats, and 93 +/- 7 beats/min for rats with a lesion not destroying the PVN. In the final study, the responses of Brattleboro rats, i.e., rats genetically deficient in vasopressin synthesis, were equivalent to their Long-Evans controls (131 +/- 13 and 147 +/- 12 beats/min, respectively). In each of these studies, the blood pressure responses to the stressor were equivalent for control and experimental groups. The results of these studies suggest that a neuropeptide system originating in or passing through the PVN may play an important role in the cardiovascular responses to stress and further suggest that the central OXY system may be one pathway mediating this response.
Kinetics of adenine nucleotide catabolism in coronary circulation of rats
Authors: Fleetwood G. , Coade S. B. , Gordon J. L. , Pearson J. D.
Published: December 2017

We have used the rat isolated, perfused heart to study the metabolism of adenine nucleotides on a single passage through the coronary circulation. Low doses (3-30 nmol) of ATP, ADP, or AMP injected as a bolus were extensively catabolized by ectoenzymes. Increasing doses of each nucleotide demonstrated saturability of catabolism that occurred at significantly lower doses of AMP than of ADP or ATP. The patterns of catabolites formed in each case were consistent with the major pathway of metabolism being sequential dephosphorylation of ATP----ADP----AMP----adenosine, although from experiments in which [3H]ATP was co-injected with unlabeled ADP, it appears that some direct conversion of ATP----AMP can occur. Furthermore, particularly in the presence of excess unlabeled ATP, [3H]ADP was phosphorylated to [3H]ATP, indicating that ectoenzymes capable of interconverting nucleotides are present. By evaluating recovery and metabolism in serial samples collected rapidly after bolus injection, we were able to use the integrated form of the Michaelis-Menten equation as developed by Bronikowski et al. (Math. Biosci. 61: 237-266, 1982) to derive Michaelis constant (Km) and maximum velocity times capillary plasma volume (Amax) values for adenosinetriphosphatase, adenosine diphosphatase, and 5'-nucleotidase (450, 300, and 93 microM; and 5.3, 5.9, and 1.7 mumol/min, respectively). This analysis also indicated that there is a high degree of heterogeneity of path lengths within the coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Enalapril decreases angiotensin II receptors in subfornical organ of SHR
Authors: Nazarali A. J. , Gutkind J. S. , Correa F. M. , Saavedra J. M.
Published: December 2017

We studied brain angiotensin II (ANG II) receptors by quantitative autoradiography in adult normotensive Wistar-Kyoto (WKY) rats and in spontaneously hypertensive rats (SHR) after treating the rats with the converting-enzyme inhibitor enalapril, 25 mg/kg, po daily for 14 days. Enalapril treatment decreased blood pressure in only SHR, inhibited plasma angiotensin-converting enzyme activity by 85%, and increased plasma ANG I concentration and renin activity in both WKY and SHR. In the untreated SHR animals, ANG II receptor concentrations were higher in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the inferior olive when compared with the untreated WKY rats. Enalapril treatment produced a large decrease in only subfornical organ ANG II receptors of SHR. The selective reversal of the alteration in subfornical organ ANG II receptors in SHR may indicate a decreased central response to ANG II and may be related to the mode of action of angiotensin-converting enzyme inhibitors in this model.
Effect of ischemia on sarcolemmal Na+-Ca2+ exchange in neonatal hearts
Authors: Meno H. , Jarmakani J. M. , Philipson K. D.
Published: December 2017

We studied the effect of cardiac ischemia on sarcolemmal enzymes, Na+-Ca2+ exchange, Ca2+ binding, and Ca2+ efflux in the newborn and adult rabbit. Rabbit ventricle was made ischemic by incubation in hypoxic, glucose-free Tyrode solution at 37 degrees C for 60-120 min. Ischemia inhibited Na+-K+-ATPase and K+-p-nitrophenylphosphatase (PNPPase) activity in the adult myocardium more than in the newborn. In the oxygenated (control) hearts, Na+-Ca2+-exchange activity in the newborn sarcolemma [Michaelis constant (Km) 18 microM; maximum velocity (Vmax) 33] was similar to that in the adult (Km = 16 microM, Vmax = 32). After 60 min ischemia, however, Na+-Ca2+ exchange in the newborn (Km = 16 microM, Vmax = 18) was inhibited less than in the adult (Km = 25 microM, Vmax = 18). In the two age groups, Ca2+ binding and efflux rate were not increased after ischemia, which suggested that Ca2+ permeability did not increase during ischemia. In conclusion, ischemia inhibited sarcolemmal enzymes and Na+-Ca2+ exchange in the newborn less than in the adult, and this lesser inhibition might contribute to or be caused by the greater tolerance of the newborn heart to ischemia.
Cryosupernatant regulates accumulation of unusually large vWF multimers from endothelial cells
Authors: Frangos J. A. , Moake J. L. , Nolasco L. , Phillips M. D. , McIntire L. V.
Published: December 2017

In addition to the von Willebrand factor (vWF) multimers found in normal plasma, cultured human umbilical vein endothelial cells (HUVECs) synthesize and release unusually large vWF multimers (ULvWFM). ULvWFM are more effective than the largest plasma vWF forms in attaching to platelets and promoting platelet aggregation in the presence of elevated fluid shear forces (as in narrowed atherosclerotic vessels), and they may be involved in arterial thrombosis. ULvWFM are produced within HUVECs exposed for 48-60 h either to steady venous-like or pulsatile arterial-like wall shear stresses and are produced and released from HUVECs grown in serum-free as well as in serum (bovine or human)-containing media. An activity of 140,000-200,000 Da in the cryosupernatant fraction of both normal and severe von Willebrand's disease plasma, which is not obviously a protease, prevents specifically the accumulation of ULvWFM in the fluid above HUVEC monolayers but does not impair the release by HUVECs of ULvWFM in the retrograde direction into subendothelial collagen. The ULvWF regulatory activity in cryosupernatant may inhibit inappropriate platelet aggregation and thrombosis by preventing the accumulation of endothelial cell-derived ULvWFM in circulating blood.
Regional cerebral blood flow and glucose utilization during hypoglycemia in newborn dogs
Authors: Mujsce D. J. , Christensen M. A. , Vannucci R. C.
Published: December 2017

To assess alterations in regional cerebral blood flow and glucose utilization during perinatal hypoglycemia, newborn dogs (2-7 days postnatal age) were anesthetized with halothane, tracheostomized, paralyzed, and artificially ventilated with 70% N2O-30% O2 to maintain arterial normoxia and normocapnia (arterial PO2 greater than 60 mmHg; arterial PCO2: 35-42 mmHg; arterial pH: 7.35-7.45). Regional cerebral blood flow (rCBF) and glucose utilization (rCGU) were determined with iodo-[14C]antipyrine and 2-deoxy-[14C]glucose as the radioactive tracers, respectively. Hypoglycemia with blood glucose concentrations averaging 0.9 mmol/l was achieved within 90-120 min in 10 animals using intermittent intravenous injections of regular insulin; 10 control animals received 0.9% saline (blood glucose = 9 mmol/l). During hypoglycemia, mean arterial blood pressure was 81% of control, whereas heart rate was unchanged. Arterial O2 and acid-base balance were well maintained (arterial PO2 = 68 mmHg; PCO2 = 37 mmHg; pH = 7.35). Hypoglycemia was associated with significant increases in rCBF in all of 16 analyzed structures, ranging from 172% (parietal white matter) to 249% (thalamus) of control values (17-65 ml.100 g-1.min-1). During hypoglycemia, rCGU was relatively unchanged from normoglycemic values in 11 of 16 brain structures. Significant reductions in rCGU were seen only in occipital white matter (-31%) and in the cerebellar vermis and hemisphere (-31 and -43%, respectively). CGU actually increased slightly in the pons and medulla (+12 and +19%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Leukocyte margination and deformation in mesenteric venules of rat
Authors: Firrell J. C. , Lipowsky H. H.
Published: December 2017

White blood cell (WBC) margination and rolling were studied in venules (20-60 microns in diameter) in rat mesentery to examine the relationship between WBC rolling velocity (Vwbc), flux (Fwbc, cells/min), and deformation; and red blood cell (RBC) velocity (Vrbc), wall shear rate (gamma), and microvessel hematocrit (Hmicro). For a range of 1.0 less than or equal to Vrbc less than or equal to 5.0 mm/s, Vwbc remained constant (congruent to 50 microns/s). The volume flux of WBCs rolling along the venular wall (normalized to systemic WBC concentration) decreased nonlinearly from 30 to 5% of total luminal flux as gamma ranged from 50 to 800 s-1 and was more strongly correlated with gamma compared with Fwbc vs. gamma. As indicated by the rolling volumetric flux, margination was weakly affected by Hmicro, except for Hmicro greater than 50% where margination increased. Deformation of WBCs was quantitated during their rolling contact with the endothelium (EC) in terms of their length and height. As gamma increased from 50 to 800 s-1, WBCs elongated to 140% of their estimated undeformed diameter, and the contact area between WBC and EC increased 3.6-fold. These data suggest that with increased gamma rolling of WBCs along the EC decreases, since only the most deformable WBCs of the circulating population persist in maintaining contact with the endothelium. It is concluded that Vwbc is invariant with elevations in gamma, since the greater deformations of rolling WBCs at high shear result in greater adhesive forces attendant to increased WBC-EC contact area, which attenuate increases in Vwbc.
A simple technique for occlusion and reperfusion of coronary artery in conscious rats
Authors: Himori N. , Matsuura A.
Published: December 2017

A simple technique to occlude and reperfuse the coronary artery of conscious rats, which can freely move about, has been developed. After rats had been anesthetized and thoracotomized, the left coronary artery (LCA) was tied loosely (an occluder), and two other sutures (releasers) were tied to the knot so that it could be loosened to allow for reperfusion. Acute LCA occlusion (0.5 h) with reperfusion (3.5 h) or permanent LCA occlusion (4 h) was done to different groups of rats. Almost the same infarct size had formed in rats of either group (approximately 60% of the left ventricular weight); however, when arterial blood flow was restored (occlusion with reperfusion group), scattered bleeding and cell damage occurred. Plasma concentration of creatine phosphokinase (CPK) (4-h permanent occlusion group) increased by approximately 400%, which depended on infarct size (r = 0.89, P less than 0.001); whereas CPK concentrations in the occlusion with reperfusion group were significantly low. After permanent LCA occlusion or reperfusion occlusion, approximately 40% of the rats died of ventricular fibrillation within 4 h, and most of them died within the first 30 min. In the occlusion with reperfusion group, an additional number died as a result of reperfusion. Electromyocardiograms clearly reflected the regional ischemia as evidenced by an increase of 2-2.5 mV in the S-T segment; the phenomenon disappeared after reperfusion. In conclusion, our simple technique could be used to study the biochemistry, electrophysiology, and morphology of a conscious animal that has undergone occlusion with reperfusion of the LCA.
Left and right ventricular myocardial morphometry in fetal, neonatal, and adult sheep
Authors: Smolich J. J. , Walker A. M. , Campbell G. R. , Adamson T. M.
Published: December 2017

This study has examined left (LV) and right ventricular (RV) myocardial morphometry in perfusion-fixed hearts of late-gestation sheep fetuses, neonatal lambs, and adult sheep. During development, myocyte size, intercapillary distance, and myocyte myofibrillar and mitochondrial volume densities increased, whereas capillary density, the myocyte-to-capillary ratio, and the myocyte matrix volume density decreased. RV myocytes were larger than LV myocytes in cross section in fetuses and 4-day-old lambs. LV and RV myocytes were of similar size in 7-day-old lambs. LV and RV myocytes were of larger in older lambs and adult sheep. Differences between LV and RV myocyte volume densities of myofibrils, mitochondria, and matrix were also observed in fetuses and young lambs. As well, variation in capillary size and density was apparent between ventricles in the fetal and neonatal periods. We conclude that, in the sheep heart, 1) LV and RV morphometric differences exist during fetal and postnatal development, 2) fetal LV and RV myocardial morphometry is consistent with an RV dominance in utero, 3) rapid growth of LV and RV myocytes occurs in the perinatal period, and 4) the relative size of LV and RV myocytes does not reflect a postnatal LV dominance until between 1 and 4 wk after birth.
Electrical uncoupling and impulse propagation in isolated sheep Purkinje fibers
Authors: Jalife J. , Sicouri S. , Delmar M. , Michaels D. C.
Published: December 2017

Alterations in electrical coupling may have a major role in the development of cardiac rhythm and conduction disturbances. We have used microelectrodes and linear Purkinje fibers to analyze the relative importance of cell-to-cell coupling on action potential propagation and to study the changes in the relationship between conduction velocity (theta) and upstroke velocity (Vmax) induced by three agents (heptanol, hypertonic solution, and ouabain) known to alter gap junction resistance. Heptanol superfusion (1.5–3.0 mM) reversibly led to a major decrease in theta and ultimately to block at a time when Vmax had been reduced by approximately 38%. Conduction delay was closely correlated with an increase in intracellular resistance (Ri), calculated as the sum of myoplasmic and junctional resistances, assuming a one-dimensional cable model. Qualitatively similar results were obtained by superfusion with 0.1–0.5 mM ouabain or hypertonic Tyrode solution (up to 600 mM sucrose added) instead of heptanol. In contrast, when the Vmax vs. theta relationship was studied by changing the KCl from 4 to 20 mM, decreases in Vmax correlated well with changes in theta. No significant effects on Ri were observed during KCl superfusion. Finally, we developed a computer model of action potential propagation along a one-dimensional strand of 90 electrically coupled heart cells. By changing systematically the degree of electrical coupling or the maximum sodium conductance in the model and by studying the effects of these changes on propagation and Vmax, we obtained strong evidence supporting the validity of our experimental results. The overall data provide testable predictions regarding the role of electrical uncoupling on abnormal impulse propagation.
Estimating arterial resistance and compliance during transient conditions in humans
Authors: Yin F. C. , Liu Z. R.
Published: December 2017

Almost all existing methods for estimating hemodynamic parameters are valid only during steady-state conditions. There is often a need, however, for estimating peripheral resistance and total arterial compliance during beat-to-beat transients such as during atrial fibrillation. During such transients the pressure at the onset and end of a cardiac cycle usually differ. This pressure difference necessitates a modification of usual methods used for estimating these hemodynamic parameters. In this paper we formulate a method for estimating resistance and total arterial compliance during such beat-to-beat transients. For simplicity the expressions are derived for a two-element windkessel model of the circulation. The method is a generalization of one we previously proposed. Rather than using parameter estimation techniques or having to assume a monoexponential pressure decay during diastole, our method uses the areas under the systolic and diastolic portions of the aortic pressure versus time tracing to obtain explicit expressions for compliance; both for the case where it is constant and when it is assumed to be nonlinear (exponential) function of pressure. Aortic pressure and flow data from patients undergoing cardiac catheterization are employed to illustrate the method. Results illustrate the quantitative difference between uncorrected and corrected estimates of both resistance and compliance as a function of the pressure difference between the onset and end of each beat. The uncorrected parameters were found to be linearly and highly correlated with these pressure differences. Regressions of pressure difference against normalized values revealed that the pooled data for all patients defined a single relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of PAF and BN 52021 on cardiac function and regional blood flow in conscious rats
Authors: Siren A. L. , Feuerstein G.
Published: December 2017

The effect of intravenous injections (0.1–3 nmol/kg) of platelet-activating factor (PAF) on blood pressure, heart rate, cardiac output, and blood flow (hindquarter, renal, mesenteric) were studied in conscious rats. PAF decreased blood pressure and total peripheral resistance (TPR) but increased heart rate; cardiac output was reduced by the highest dose. Low doses of PAF increased blood flow and decreased vascular resistance in all vascular beds, whereas high doses reduced mesenteric blood flow in part by increasing mesenteric vascular resistance. The hypotensive and cardiac effects of PAF were blocked by intravenous infusions of the selective PAF-receptor antagonists, 15 mg/kg BN 52021 and 1 mg/kg SDZ 63–441. BN 52021 also attenuated the hindquarter and renal responses to PAF, but the mesenteric responses remained relatively unchanged. The results indicate that PAF is a potent vasodilator of mesenteric greater than hindquarter = renal vessels at low doses and a cardiac depressant at high doses. A therapeutic role for the PAF antagonists BN 52021 and SDZ 63–441 is suggested in endotoxemia, anaphylaxis, and other disease states in which increased release of PAF contributes to key hemodynamic derangements.
Postnatal changes in capillary density of rat sternomastoid muscle
Authors: Hansen-Smith F. M. , Watson L. , Joswiak G. R.
Published: December 2017

The changes in muscle capillarity during postnatal growth have been difficult to study using standard histochemical methods. This laboratory has proposed the use of a lectin, Griffonia simplicifolia I (GSI), as a histochemical marker that may be appropriate for developing muscle. The purpose of the study was to compare the capillary densities (capillaries per muscle fiber) determined by the GSI lectin method, alkaline phosphatase-periodic acid-Schiff (APase-PAS) staining method, and by direct counting from 1-micron plastic sections. Sternomastoid muscles from 10-day or 6-wk-old rats were used. Results from the 10-day rats showed that the GSI method and the 1-micron method gave comparable results (1.44, 1.58 capillaries per fiber), which were significantly higher than that with APase-PAS (0.56). Capillary densities in the white region of the sternomastoid from 6-wk-old rats were identical (2.80) using both the GSI and APase-PAS methods. In contrast, the GSI method yielded significantly higher capillary densities in the red region than did the APase-PAS method (4.80 vs. 3.83). These results indicate that the GSI method for visualizing capillaries is a sensitive method for visualizing capillaries in muscle during the postnatal and juvenile growth period.
Sarcolemmal Ca2+ transport activities in cardiac hypertrophy caused by pressure overload
Authors: Nakanishi H. , Makino N. , Hata T. , Matsui H. , Yano K. , Yanaga T.
Published: December 2017

To examine Ca2+ transport activities in sarcolemmal membrane in cardiac hypertrophy caused by pressure overload, rats were subjected to aortic banding for 28 days. Heart-to-body weight ratio was increased by 46% in aortic-banded animals in comparison with the sham-operated rats. Ouabain-sensitive Na+-K+-ATPase activity in sarcolemma (SL) from hypertrophied hearts was not different from that in the control preparation. The initial rate of Na+-dependent Ca2+ uptake in SL vesicles from the hypertrophied hearts was stimulated by 53% compared with the control vesicles. ATP-dependent Ca2+ uptake and Ca2+-stimulated adenosinetriphosphatase (ATPase) activities in SL from hypertrophied hearts were increased by 35%. The number of Ca2+ channels estimated by [5-methyl-3H]nitrendipine binding was decreased by 33% in SL from hypertrophied hearts. Total and individual phospholipid contents in the hypertrophied heart preparations were not different from those in the control, except that phosphatidylcholine and phosphatidylethanolamine contents were significantly increased. Sarcolemmal preparations from hypertrophied hearts from the 22-wk-old spontaneously hypertensive rats exhibited changes in Na+-Ca2+ exchange and Ca2+-pump activities (similar to those observed in banded hearts), whereas the Na+-K+-ATPase activity decreased, [3H]nitrendipine binding increased, and phospholipid contents were not different. Thus, although differences were defined between two types of hypertrophy, these results suggest alterations in the sarcolemmal Ca2+ transport activities that may serve as an adaptive mechanism for the removal of Ca2+ from the myocardial cells during the development of cardiac hypertrophy.
Low-density lipoprotein transport in blood vessel walls of squirrel monkeys
Authors: Tompkins R. G. , Yarmush M. L. , Schnitzer J. J. , Colton C. K. , Smith K. A. , Stemerman M. B.
Published: December 2017

Transmural accumulations of low-density lipoprotein (LDL) were examined in the blood vessel walls of four squirrel monkeys. Vascular wall concentrations of LDL were measured using quantitative autoradiography after 125I-labeled LDL circulation for 30 min. Profiles of relative tissue concentration from different sections in the same region were similar to each other, and there was little animal-to-animal variation. Concentrations were highest near the luminal endothelium, lower near the medial-adventitial border, and lowest within the media. Profiles from different regions fell into three groups: 1) aortic samples had steep intimal concentration gradients and near-zero media concentrations; 2) the iliac, femoral, popliteal, and common carotid arteries had higher intimal concentrations than group 1 but had similar concentrations deep within the media; and 3) the cerebral and coronary arteries, inferior vena cava, and pulmonary artery had intimal concentrations that were similar to group 2, but the concentrations deep within the media were greater than either groups 1 or 2. Arterial bifurcation profiles from the inner wall and the outer walls were similar to each other and to profiles from the upstream and downstream areas. Out of 280 total sites examined, 15 examples of profiles with substantially increased concentrations near the luminal endothelium were found scattered throughout the cardiovascular system, demonstrating that there are focal regions throughout the cardiovascular system which have greatly increased 125I-LDL transendothelial permeability.
Summation of sinoaortic baroreflexes depends on size of input signals
Authors: Yamazaki T. , Sagawa K.
Published: December 2017

We studied sinoaortic baroreflex summation in seven anesthetized rabbits by paying special attention to the sigmoidal nature of the open-loop characteristic curve of the two reflexes. Carotid sinuses were isolated to control carotid sinus pressure (CSP). Aortic nerves were cut, and the left aortic nerve was electrically stimulated. Initially, CSP was set between 75 and 95 mmHg, and the parameters for aortic nerve stimulation (ANS) were chosen so that mean arterial pressure (MAP) was between 80 and 100 mmHg. We then increased CSP and ANS mildly so that MAP would fall by 10-20 mmHg in each case. Comparison of the sum of these decreases with the decrease caused by simultaneous increases in CSP and ANS showed no statistical difference, indicating a simply additive summation. With mild decreases in CSP and ANS, a similar additive summation was observed in the reflex increases in MAP. When we input slightly larger changes in CSP and ANS so that MAP fell by 20-30 mmHg for each stimulus, comparison of the sum of the separate effects with the combined effect on MAP indicated a mildly inhibitory summation. By analyzing the total peripheral resistance calculated from aortic flow data, we found this inhibitory summation occurred in the reflex controls of the total peripheral resistance. We conclude that the summation of the sinoaortic reflex controls of arterial pressure can be regarded as simply additive when small input signals are given in the physiological range of both reflexes, but the summation is mildly to moderately inhibitory when moderately larger input signals are given.
CO2 reactivity and heterogeneity of cerebral blood flow in ischemic, border zone, and normal cortex
Authors: Jones S. C. , Bose B. , Furlan A. J. , Friel H. T. , Easley K. A. , Meredith M. P. , Little J. R.
Published: December 2017

Regional arterial CO2 tension (PaCO2) reactivity of cerebral blood flow (CBF) and the effect of PaCO2 on the spatial and temporal heterogeneity of CBF were investigated by using autoradiographically determined CBF in the rat middle cerebral artery occlusion model after a 2-h period under pentobarbital anesthesia to clarify the relation between PaCO2 reactivity, CBF heterogeneity, and the temporal cycling of CBF. PaCO2 was adjusted to one of four levels. CBF was determined in four cortical areas and white matter using the tissue fractionation of [14C]iodoantipyrine [( 14C]IAP) in combination with vessel mapping using in vivo 4% thioflavine S. Specific PaCO2 reactivity and CBF were normal in the nonischemic cortex, normal, although slightly depressed, in the border zone far from the ischemic core area, and depressed in the border zone adjacent to the ischemic core area (P less than 0.001) and the ischemic core (P less than 0.001). In normocapnic and hypocapnic animals, CBF heterogeneity in the form of regularly spaced CBF columns perpendicular to the cortical surface was observed in the nonischemic hemisphere but was absent in the ischemic core area. In hypercapnic rats, flow columns were present in the ischemic core areas and border zones but were absent on the nonischemic side. There was a highly significant interaction (P less than 0.0001) in observer-determined heterogeneity grades between PaCO2 level and each of three areas, normal, border zone, and ischemic core. In normal cortex, comparison of the thioflavine S-stained vessels with the flow columns provided evidence supporting the concept of capillary recruitment and cycling as a mode of normal cerebral blood flow control. The presence of flow columns in severely ischemic areas in hypercapnic animals indicates that a short period of high PaCO2 transiently augments microregional flow and could enhance the delivery of a therapeutic agent to these microregions of the ischemic core. The regional analysis of PaCO2 reactivity suggests an index of future tissue viability.
Influence of saline infusion on blood-tissue albumin transport
Authors: Renkin E. M. , Rew K. , Wong M. , O'Loughlin D. , Sibley L.
Published: December 2017

Anesthetized rats were infused with lactated Ringer solution (LR) at constant rate for 30 or 60 min; delivered volume loads ranged from 0.03 to 0.08 ml/g body wt. Controls were given only a sustaining infusion of saline at 0.002 ml.g-1.h-1. Only 7-14% of the LR remained in the plasma at the end of the infusion; 76-88% entered the interstitial compartment, and 7-17% was excreted. The amount of plasma protein lost from the circulation with the extravasated fluid was studied simultaneously by two methods: 1) material balance in the whole animal and 2) changes in 131I-labeled albumin uptake (VA) and water content (VW) in individual tissues. The extravasation of 0.03-0.06 ml fluid/g body wt (75-160% initial plasma volume) did not significantly increase plasma protein extravasation in the whole rat. Nearly all of the sampled tissues of LR-infused rats had higher VW than controls. Tissue VA tended to increase with VW, but the regression slopes (delta VA/delta VW), a measure of the tracer albumin concentration of capillary filtrate relative to plasma, were low; skin, 0.006; paw, 0.018; skeletal muscles, 0.007; heart, 0.057; jejunum, 0.095; ileum, 0.045; cecum, 0.026; and colon, 0.027. These ratios are consistent with the very small loss of total plasma protein observed and attest to high solvent-drag reflection coefficients (sigma approximately equal to 1 - delta VA/delta VW): greater than 0.98 in capillaries of skeletal muscles, skin, and paw and 0.91-0.97 in heart and intestine.
Tissue-specific isoform regulation of Na+-K+-ATPase by thyroid hormone in ferrets
Authors: Ng Y. C. , Yao A. Z. , Akera T.
Published: December 2017

We have shown previously that in the ferret heart there are two isoforms of Na+-K+-ATPase, alpha(+) and alpha, and that these isoforms undergo developmental changes. In the present study, we examine regulation of the isoenzymes by thyroid hormone, which is well known to increase activity of Na+-K+-ATPase in different tissue preparations. Ferrets were injected with L-thyroxine (T4) (0.5 mg/kg, sc) for 3 wk. The T4-treated ferrets gained 58 +/- 32 g body wt compared with 366 +/- 24 g for the control ferrets. Plasma 3,5,3'-triiodothyronine concentrations of the T4-treated animals increased about eightfold 16-18 h after the last injection. The number of alpha(+)- and alpha-subunits in heart homogenates estimated by [3H]ouabain binding was 3.5 +/- 0.1 and 2.5 +/- 0.1 pmol/mg protein, respectively [alpha(+)/alpha = 1.40]. In the T4-treated ferrets, there was no significant increase of the alpha(+)-isoform (3.2 +/- 0.2 pmol/mg protein), whereas the number of alpha-isoform increased significantly to 4.1 +/- 0.3 pmol/mg protein [alpha(+)/alpha = 0.78]. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partially purified cardiac plasma membrane preparations reveals similar pattern of changes of the isoenzymes. In the kidney, however, there was no significant change in the number of alpha-isoform, which is the predominant isoform in the kidney, and T4 does not appear to induce synthesis of alpha(+)-isoform in the kidney. It is concluded that thyroid hormone induces both isoform- and tissue-specific regulation of the Na+-K+-ATPase alpha-subunits in the ferret. These specific regulations of the isoforms seem to suggest important physiological roles of the isoenzymes.
Alterations in distribution of cardiac output in experimental diabetes in rats
Authors: Hill M. A. , Larkins R. G.
Published: December 2017

Alterations in blood flow distribution in streptozotocin-induced diabetes in the rat were examined. Blood flow between tissues was estimated by the distribution of radiolabeled microspheres, and a second series of experiments examined skeletal muscle microcirculation by in vivo microscopy. Studies were performed in anesthetized rats 1-8 wk after induction of diabetes. Cardiac index was transiently increased in diabetic animals (29.6 +/- 1.0 ml.min-1.100 g-1) in comparison with control animals (23.0 +/- 1.4 ml.min-1.100 g-1) at 2-wk duration. Cardiac index was similar in both groups of animals at all other time points studied. The increased cardiac index coincided with transiently increased blood flow to diaphragm and abdominal wall and a significant vasodilatation of small cremaster muscle arterioles. Blood flow to skin and some skeletal muscles was thereafter significantly decreased in the diabetic animals. Blood flow (ml.min-1.100 g-1) to the brain and main thoracic and abdominal organs was similar in nonfasting control and diabetic animals throughout the period of study. As a result of hyperplasia, blood flow to the small intestine (%cardiac output) was increased in the diabetic animals (at 4 wk of diabetes, 34.5 +/- 2.1 vs. 17.5 +/- 0.8%, P less than 0.001). Despite reduction in blood flow to the intestine, by dietary restriction, flow to skin and skeletal muscle remained significantly decreased. Insulin treatment, at a dose aimed at preventing body weight loss but maintaining hyperglycemia, led to renal hyperperfusion in comparison with untreated diabetic and control animals. The alterations in regional blood flow appear progressive in nature and are not simply related to each other but may reflect tissue adaptation to the metabolic disorder.
Left ventricular coordinate systems
Authors: Templeton G. H. , Seibert G. B. , Ramanathan M. , Cassidy S. S. , Johnson R.
Published: December 2017

Three-dimensional kinematics of radiopaque markers in anterior, posterior, septal, and lateral regions of a major equatorial plane were evaluated in anesthetized dogs by biplane fluoroscopy. Stationary coordinate systems measured marker locations recorded during diastole and systole from a contractile origin at the center of contraction at end systole and from a geometric origin at the intersection with the equatorial plane of the ventricular long axis at end diastole. A time-indexed system measured marker locations at end diastole and at end systole, respectively, from the locations of the geometric origin at end diastole and end systole. Compared to the stationary system with the geometric origin, both the stationary system with the contractile origin and the time-indexed system reduced the variability of the radial components of the contractile displacements between ventricular regions. In contrast to the other two systems, the system with the contractile origin reduced circumferential components to values not significantly different from zero. These results indicate that 1) abnormally contracting regions of the ventricle may be located and their size measured by determining the region where the radial component differs from that in the rest of the equatorial plane and 2) rotation in a major equatorial plane of the ventricle is significant, but the influence of rotation can be minimized by referencing ventricular dimensions to a coordinate system with an origin at the center of contraction.
Myocardial and systemic responses to arterial hypoxemia during cardiac tamponade
Authors: Crystal G. J. , Salem M. R.
Published: December 2017

Experiments were performed on 14 anesthetized, open-chest dogs to assess myocardial and systemic responses to cardiac tamponade alone (TAMP) and combined with arterial hypoxemia (HYP). Regional blood flow (RBF) was measured with radioactive microspheres and used to compute regional O2 supply. Myocardial oxygen and lactate extraction were determined. Myocardial oxygen consumption (MVO2) was calculated with Fick equation. An increase in pericardial pressure, sufficient to reduce mean aortic pressure (MAP) by 20%, caused proportional decreases in myocardial RBF and MVO2 but had no effect on endo-to-epi flow ratio or on myocardial lactate extraction. TAMP alone decreased RBF and O2 supply in kidney, splanchnic organs, skeletal muscle, and skin, but it had no effect in brain. HYP (arterial PO2, 35 +/- 2 mmHg) during TAMP restored MAP and caused transmurally uniform increases in myocardial RBF that were adequate to maintain MVO2 and lactate extraction. RBF increased sufficiently in brain to maintain regional O2 supply, whereas unchanged or inadequate increases in RBF in other tissues accentuated reductions in O2 supply. During combined TAMP and HYP, local vasodilator mechanisms were capable of maintaining adequate oxygen supply in myocardium and brain but not apparently in the nonvital tissues where these mechanisms were antagonized by reflex vasoconstriction.
Autonomic regulation of delayed rectifier K+ current in mammalian heart involves G proteins
Authors: Harvey R. D. , Hume J. R.
Published: December 2017

The role of adrenergic and cholinergic stimulation in regulating the delayed outward K+ current (IK) was examined by using isolated guinea pig ventricular myocytes. Isoproterenol (ISO) stimulated IK in a reversible manner. Similar effects were seen by directly stimulating adenylate cyclase with forskolin (FSK). The responses to ISO and FSK were reversed by concurrent application of acetylcholine (ACh), but ACh alone did not affect IK. When a nonhydrolyzable analogue of guanosine 5'-triphosphate was introduced intracellularly, in the presence of extracellular ISO, IK was irreversibly stimulated. In cells pretreated with pertussis toxin the ACh response was blocked. These results suggest that autonomic regulation of IK is similar to that of the Ca2+ current and involves guanine nucleotide-binding proteins. This has important implications with respect to autonomic control of action potential duration and pacemaker activity in the heart.
Tension and electrolyte changes with Na+-K+ pump inhibition in rat papillary muscle
Authors: Parsons D. , Burton K. P. , Hagler H. K. , Willerson J. T. , Buja L. M.
Published: December 2017

Myocardial ischemic injury results in altered membrane integrity, energy depletion, and electrolyte shifts leading to accumulation of intracellular Ca. However, analysis of the direct effects of Ca accumulation is complicated by other concomitant cellular changes produced by ischemia. The purpose of this study was to examine the effects of Ca loading in rat papillary muscles produced by Na+-K+ pump inhibition in oxygenated K+-free buffer. Changes in contractile characteristics, high energy phosphate, and elemental concentrations of subcellular compartments were measured. Electron probe X-ray microanalysis was used to assess elemental concentrations in cryosections. After 3 h of Na+-K+ pump inhibition, resting tension (RT) increased to 164% and developed tension (DT) fell to 16.8% of control values. One hour after return to complete buffer, RT and DT partially recovered but remained significantly different from the 180 to 240-min values for the control muscles. Electron probe X-ray microanalysis showed increases in cytoplasmic and mitochondrial Na and Ca and a decrease in K during Na+-K+ pump inhibition. Mitochondrial Ca was greater than 100-fold greater than Ca in control mitochondria. Morphologically, the majority of cells showed ultrastructural damage. The mean ATP level was 20% of control. After 1 h of recovery, the cells appeared more heterogeneous, and the mean mitochondrial Ca decreased, whereas mean cytoplasmic Ca increased. Further statistical analysis showed a bimodal distribution for Na, Ca, K, Mg, and Cl, which coincided with the morphologically mixed population of cells. This suggests that replacement of extracellular K+ was associated with restored electrolyte gradients in some cells and the persistent or further alteration of electrolytes in others. These results suggest that variable Ca accumulation and associated ATP depletion without the compounding effects of ischemia lead to cell injury similar to reperfusion injury reported in ischemic myocardium.
Hydrostatic pressure reduces thrombogenicity of polytetrafluoroethylene vascular grafts
Authors: Ritter E. F. , Vann R. D. , Wyble C. , Barwick W. J. , Klitzman B.
Published: December 2017

A prime factor in the thrombogenicity of synthetic materials in contact with blood is the blood-gas interface. Small pockets of gas, known as gas nuclei, are trapped within surface interstices. The resulting blood-gas interface denatures plasma proteins and activates clotting factors and platelets. Expanded polytetrafluoroethylene (ePTFE) vascular prostheses 1 mm in internal diameter were placed in saline under 6,000 psig hydrostatic pressure for 2 h in an attempt to dissolve all gas nuclei (i.e., to denucleate). Carotid-carotid bypasses were performed in rats using 280-mm lengths of ePTFE. All 10 control grafts lost patency in 5 min, whereas the 14 denucleated grafts had a median patency duration of 300 min (P less than 0.01). In 15-mm-long rat femoral artery interpositional ePTFE grafts, 90% of controls thrombosed within 10 min, whereas only 7% of denucleated grafts thrombosed over the duration of the 7-day observation period (P less than 0.001). Denucleation also resulted in a significant reduction (P less than 0.02) in 111In-labeled platelet adhesion to 36% of control. Scanning electron microscopy confirmed the reduced accumulation of platelets on denucleated grafts. These data suggest that the removal of trapped air with hydrostatic pressure significantly reduces the thrombogenicity of ePTFE microvascular prostheses and may have application to other clinical (catheters, valves, tubing, etc.) or experimental (micropipettes, electrodes, etc.) materials that interface with blood.
Role of lowering arterial pressure on maximal coronary flow with and without regression of cardiac hypertrophy
Authors: Canby C. A. , Tomanek R. J.
Published: December 2017

This study was initiated to test the hypothesis that attenuation of long-term hypertension with or without regression of left ventricular hypertrophy (LVH) will lower minimal coronary vascular resistance (MCVR). Six-month-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with captopril or hydralazine for a period of 3 mo. Myocardial perfusion, measured with microspheres, and hemodynamic data were obtained in awake, unrestrained rats aged 9 mo. MCVR was calculated from the quotient of mean/myocardial perfusion. Both drugs significantly lowered arterial systolic pressure in both strains of rats, but only captopril was effective in reducing heart mass. Left ventricular MCVR per 100 g was lower in captopril-treated WKY (0.064 +/- 0.012) and SHR (0.079 +/- 0.006) than the untreated controls (SHR: 0.124 +/- 0.006; WKY: 0.098 +/- 0.009), whereas total LV MCVR was unaltered by treatment. Hydralazine tended to lower LV MCVR per 100 g in both strains despite its tendency to increase ventricular mass. Captopril, but not hydralazine, treatment was associated with a significant increase in capillary density in both WKY and SHR. We conclude that the improvement in MCVR is related to both the regression of LVH and to the consequences of lowering arterial systolic pressure. In contrast, the increase in capillary density appears to be related to the decrease in ventricular mass after captopril treatment.
Differential sensitivity to endothelin in canine arteries and veins
Authors: Miller V. M. , Komori K. , Burnett J. C. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to compare the sensitivity of venous and arterial smooth muscle to endothelin and to determine whether contractions to the peptide could be inhibited by endothelium-derived relaxing factor and nitric oxide. Rings of canine left anterior descending coronary, femoral, and mesenteric arteries and femoral and saphenous veins with and without endothelium were suspended for measurement of isometric force. In the presence of indomethacin, phentolamine, and propranolol, endothelin initiated concentration-dependent increases in tension in all rings. The veins were more sensitive to the peptide than were the arteries. Endothelin depolarized the smooth muscle of the saphenous veins and mesenteric arteries; the threshold concentration for depolarization was approximately 100 times lower in the veins (10(-10) M) than in the arteries (10(-8) M). Removal of the endothelium enhanced the sensitivity only of venous smooth muscle to endothelin. However, stimulation of the endothelium in the arteries with either acetylcholine or the calcium ionophore A23187 rapidly inhibited the maximal tension developed to the peptide. Nitric oxide inhibited contractions to endothelin in arteries and veins without endothelium; the inhibition was greater in the arteries than in the veins. These results indicate that venous smooth muscle is more sensitive than arterial smooth muscle to endothelin. In both blood vessels, endothelium-derived relaxing factor(s) can inhibit contractions to the peptide.