bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrograde coronary flow is limited by time-varying elastance
Authors: Kouwenhoven E. , Vergroesen I. , Han Y. , Spaan J. A.
Published: December 2017

The study examined the influence of left ventricular pressure (PLV) on coronary arterial flow and pressure. In eight anesthetized open-thorax goats with cannulated and artificially perfused left main coronary artery, the PLV was disturbed by aortic occlusions. In the constant pressure perfusion (CPP) protocol the response of systolic arterial inflow on a change in PLV was studied with fixed perfusion pressure and at several perfusion pressure levels. Similarly, in the constant flow perfusion (CFP) protocol the response of systolic perfusion pressure was examined with fixed levels of perfusion flow and repeated for several flow levels. The results show an early systolic response determined by PLV for both protocols. Midsystolic responses were almost absent in the CPP protocol but present in the CFP protocol. At CPP, the effect of a change of PLV on arterial flow in mid systole was only 20% of that on early systolic flow with intact coronary tone and 33% with adenosine-induced vasodilation. At CFP the pulsations in perfusion pressure were 30% of PLV pulsations, both with intact tone and vasodilation; in contrast with the CPP results, no difference for this value was found in different stages of systole. We suggest that stiffness of cardiac muscle determines the influence of PLV on coronary flow. The difference in mid systolic relations between the CPP and CFP protocols is explained by the difference in time constants induced by the perfusion system. The results are best explained by a synthesis between the intramyocardial pump model and the elastance concept.
Inhibition of bovine retinal microvascular pericyte proliferation in vitro by adenosine
Authors: Jackson J. A. , Carlson E. C.
Published: December 2017

Adenosine acts on bovine retinal microvascular pericytes through one or more adenosine receptor subtypes present on the cell surface. Retinal pericytes cultured in medium containing adenosine at concentrations from 10(-6) to 10(-4) M showed significant reduction in proliferation following several days in vitro compared with control cultures. The effects of adenosine were mimicked by polyadenylic acid and inhibited by 8-phenyltheophylline, indicating involvement of a cell surface receptor. Metabolites of adenosine had no effect on pericyte proliferation. An A2 adenosine receptor-specific analogue also inhibited pericyte growth, suggesting that inhibition by adenosine is mediated by A2-receptors and might involve a transient increase in adenosine 3',5'-cyclic monophosphate levels. The results of the present study demonstrate that in addition to demonstrated stimulatory effects on capillary endothelial cells, adenosine also has a direct inhibitory effect on retinal pericytes. We hypothesize a dual function of adenosine within the capillary wall resulting in loss of inhibition of endothelial cells and suggest a role for this nucleoside in pathological neovascularization processes such as proliferative diabetic retinopathy.
Differences and similarities in albumin and red blood cell flows through cerebral microvessels
Authors: Tajima A. , Nakata H. , Lin S. -Z. , Acuff V. , Fenstermacher J.
Published: December 2017

Pages H1515–H1524: A. Tajima, H. Nakata, S.-Z. Lin, V. Acuff, and J. Fenstermacher. “Differences and similarities in albumin and red blood cell flows through cerebral microvessels.” Page H1521: right column, second paragraph, the first four lines read as follows:

If the cycling period is <10 s for the system, then all of the capillaries will be perfused and labeled within 10 s of the first appearance of RISA and radiotagged RBCs in cerebral capillaries. The time from intravenous injection to radiotracer appearance in cerebral capillaries is ≈7 s in the awake rat.
Bioassay of endothelium-derived relaxing factor in diabetic rat aorta
Authors: Pieper G. M. , Mei D. A. , Langenstroer P. , O'Rourke S. T.
Published: December 2017

The bioassay technique was utilized to quantitate endothelium-derived relaxing factor (EDRF) released from perfused donor segments of control and diabetic rat aorta. In the presence of indomethacin, perfusates of donor segments with endothelium were allowed to superfuse recipient detector rings of normal rat aorta without endothelium. Under basal conditions, relaxations of the bioassay rings to perfusates of control and diabetic donor segments were similar. Perfusion of donor segments with acetylcholine produced relaxation of bioassay rings, which was decreased from endothelial perfusion of diabetic donor segments. These relaxations were inhibited by addition of methylene blue to the detector ring or by perfusion of donor segments with nitro-L-arginine. Infusion of superoxide dismutase (SOD) at a site proximal to the donor segment normalized relaxations induced by acetylcholine addition to diabetic donors. In contrast, infusion of SOD distal to the donor had no effect on acetylcholine-stimulated relaxations of detector rings from control donors while attenuating, paradoxically, the relaxations of detector rings from diabetic donors. These results suggest that diabetic rat aortas release similar levels of EDRF in response to acetylcholine, but the action of EDRF arising from diabetic donors is attenuated by enhanced release of oxygen-derived free radicals, which limits EDRF-mediated relaxation of vascular smooth muscle.
Recovery of arterial pressure control after partial baroreceptor denervation in awake rabbits
Authors: Ohsumi H. , Scher A. M.
Published: December 2017

We examined recovery of control of heart rate (HR) and total peripheral resistance (TPR) by arterial baroreceptors after bilateral carotid sinus and aortic denervation or unilateral carotid sinus and aortic denervation in conscious rabbits. In one group of animals, HR responses to changes in mean arterial pressure (MAP) after injection of nitroglycerin or phenylephrine were measured in control studies and at 2, 5, 10, and 15 days after partial baroreceptor denervation. All denervation procedures increased MAP and HR at 2 and 5 days after denervation. Reflex sensitivity decreased to 57–67% of control on day 2 after denervation. HR responses recovered by day 10 after bilateral aortic or carotid sinus denervation; however, recovery following unilateral denervation was less complete. In a second group of animals, studied after implantation of aortic flowmeters, TPR changes following reduction in cardiac output by inferior vena caval occlusion were 49% of control responses on day 2 after denervation and returned close to control level on day 5. Controls of HR and TPR recovered substantially and were not significantly different from control 10 days after partial denervation. Recovery apparently occurred through the remaining arterial baroreceptors, possibly due to central reorganization of reflex pathways.
Factors involved in left ventricular dysfunction after massive sympathetic activation
Authors: Pilati C. F. , Bosso F. J. , Maron M. B.
Published: December 2017

We sought to determine whether catecholamines are responsible for the depressed left ventricular (LV) function that follows massive sympathetic nervous system (SNS) activation and whether the additional myocardial energy demands of SNS-induced hypertension contribute to this disorder. An intracisternal injection of veratrine was used to intensely activate the SNS of anesthetized rabbits, and 150 min later, LV function was evaluated in vitro using established techniques. To assess catecholamine involvement, rabbits were pretreated with phentolamine, propranolol, or saline prior to SNS activation. Control animals received veratrine intravenously. In separate experiments, angiotensin II (ANG II) was administered to rabbits to produce hemodynamic and plasma catecholamine profiles comparable to that produced by intense SNS activity. LV function of hearts after either massive SNS activation or ANG II administration was significantly diminished compared with control (P less than 0.01) and could be prevented by pretreatment with the catecholamine antagonists. LV function was also not diminished in another group of animals in which arterial pressure was maintained near baseline throughout the SNS discharge, thus suggesting that the increased myocardial energy demand associated with the development of arterial hypertension contributes to the LV dysfunction. We conclude that toxic concentrations of catecholamines are responsible for SNS-induced LV dysfunction and that hypertension, most likely because of its ability to increase myocardial energy demand, is one of the important events that leads to depressed cardiac function.
Effects of aging on baroreflex regulation of sympathetic activity in humans
Authors: Ebert T. J. , Morgan B. J. , Barney J. A. , Denahan T. , Smith J. J.
Published: December 2017

Arterial baroreflexes contribute importantly to blood pressure regulation through their influence on parasympathetic outflow to the sinus node and sympathetic outflow to the peripheral circulation. Baroreflex control of heart rate is known to be diminished in older individuals. Whether advancing age is associated with a parallel attenuation in baroreflex control of sympathetic outflow to the peripheral circulation has not been studied in humans. To provide such information, we made direct measurements of muscle sympathetic nerve activity (MSNA) in healthy males who ranged in age from 18 to 71 yr. The subjects were arbitrarily divided into three groups: younger (18–34 yr; n = 35), middle aged (35–50 yr; n = 15), and older (51–71 yr; n = 16). Although basal levels of MSNA were higher in older subjects than in younger and middle-aged subjects, the gains of baroreflex control of MSNA were the same in the older, middle-aged, and younger subjects (-4.6 +/- 0.6, -4.8 +/- 0.9, -5.1 +/- 0.5 U/mmHg, P greater than 0.10). In contrast, the gains of baroreflex control of cardiac intervals were attenuated in the older and middle-aged subjects compared with the younger subjects (9.8 +/- 1.2, 13.6 +/- 1.4, 21.7 +/- 1.3 ms/mmHg, P less than 0.05). Our data indicate that although the parasympathetic component of the arterial baroreflex becomes impaired with advancing age, the sympathetic component can be well maintained in healthy individuals even into the seventh decade.
Leukocyte adhesion in local versus hemorrhage-induced ischemia
Authors: Perry M. A. , Granger D. N.
Published: December 2017

The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia-reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion.
Thoracic aortic pressure-flow relationships and vascular impedance in fetal sheep
Authors: Langille B. L. , Adamson S. L.
Published: December 2017

Upper descending thoracic aortic pressures recorded from near-term fetal sheep resembled those recorded in mature animals, but diastolic thoracic aortic flows were much greater than those reported for adults. Furthermore, the pressure wave was not amplified during transmission along the aorta, as it is in adults. Descending thoracic impedance fell with increasing frequency to approximately 25% of resistance to steady flow and then showed oscillations typical of systems in which pulse wave reflections are important. Angiotensin II and norepinephrine infusions enhanced impedance oscillations and caused changes in apparent phase velocity in the aorta that were consistent with increased wave reflections. Angiotensin also increased aortic characteristic impedance from 0.0152 +/- 0.0013 to 0.0230 +/- 0.0024 mmHg.min.ml-1. The effects of nitroprusside infusions indicated reduced wave reflection effects. Embolization of the placenta and hindlimbs with 50-microns microspheres was used to elevate vascular resistance in these beds. Embolization caused aortic flow to fall to zero by late diastole, and changes in impedance and apparent phase velocity suggested increased wave reflections from the periphery. Characteristic impedance was increased to 0.0209 +/- 0.0031 mmHg.min.ml-1.
Na+ efflux mechanisms in ventricular myocytes: measurement of [Na+]i with Na(+)-binding benzofuran isophthalate
Authors: Borzak S. , Reers M. , Arruda J. , Sharma V. K. , Sheu S. S. , Smith T. W. , Marsh J. D.
Published: December 2017

We characterized the Na(+)-sensitive dye benzofuran isophthalate (SBFI) with fluorescence microscopy in isolated, adult rat ventricular myocytes. When cells were loaded with SBFI by incubation with 10 microM of the acetoxymethyl ester, fluorescence excitation spectra were markedly attenuated below 340 nm and the isoemissive point was blue shifted by approximately 25 nm when compared with spectra from SBFI acid in buffered solutions. Fluorescence intensity (49 +/- 3%) was partially released by permeabilization of the sarcolemma with digitonin, suggesting that one-half of the dye molecules are sequestered subcellularly in a compartment shown most likely to be mitochondrial. Intracellular Na+ concentration ([Na+]i) was determined by in situ calibration using cation-selective ionophores and was found to be 14 +/- 2 mM in cells studied at 37 degrees C. The relative importance of Na+ efflux mechanisms in myocytes was investigated. Substitution of Ca2+ and Mg2+ with EGTA in the superfusing medium resulted in a reversible rise of [Na+]i from 13 +/- 2 to 31 +/- 5 mM, which was blocked by 1 microM verapamil. Cellular efflux of Na+ after loading in this manner was found to be insensitive to blockade of Na(+)-Ca2+ exchange but was abolished when Na(+)-K(+)-ATPase was inhibited with zero extracellular K+ concentration. We conclude that SBFI can be used to measure [Na+]i in ventricular cells nondestructively and without impalement. Na+ efflux after loading by Ca2+ and Mg2+ withdrawal is mediated by the Na+ pump with no measurable contribution from Na(+)-Ca2+ exchange.
Long-term calorie restriction enhances baroreflex responsiveness in Fischer 344 rats
Authors: Herlihy J. T. , Stacy C. , Bertrand H. A.
Published: December 2017

Diet influences many aspects of cardiovascular function. Restriction of caloric intake represents a major nonpharmacological means of reducing blood pressure. The aim of the present work was to determine the effects of long-term calorie restriction on mean arterial pressure (MAP) and baroreflex responsiveness of the conscious, normotensive, nonobese Fischer 344 male rat. From 6 wk of age rats ate either ad libitum or 60% of the amount consumed by those eating ad libitum. Calorie restriction had no effect on MAP of rats 12-14 mo of age; the MAP for the ad libitum fed and calorie-restricted groups were 114.6 +/- 1.6 and 111.6 +/- 0.8 mmHg, respectively. Basal heart rate (HR), however, was reduced from 396 +/- 6 beats/min in the libitum-fed group to 333 +/- 5 beats/min in the calorie-restricted group. Administration of sodium nitroprusside (SNP) (both as bolus and constant infusion) and phenylephrine (PE) (bolus alone) elicited tachycardia and bradycardia in both groups. The calorie-restricted group exhibited greater baroreflex responsiveness to hypotensive stress than did the ad libitum-fed group. For constant infusion of SNP, the baroreflex gain of the calorie-restricted group (-5.43 +/- 0.56 beats.min-1.mmHg-1) was significantly greater than that of the ad libitum-fed group (-2.14 +/- 0.19 beats.min-1.mmHg-1). Bolus injections of SNP elicited similar results. Calorie restriction only minimally altered the baroreflex responsiveness to hypertensive stress elicited by bolus injections of PE, although the relationship between HR and MAP was shifted to the left in the calorie-restricted group.(ABSTRACT TRUNCATED AT 250 WORDS)
Spinal stimulation to locate preganglionic neurons controlling the kidney, spleen, or intestine
Authors: Taylor R. B. , Weaver L. C.
Published: December 2017

The organization of sympathetic preganglionic neurons may be a substrate for selective control of sympathetic outflow to different vascular beds. This study was done to determine the spinal segments containing preganglionic neurons controlling discharge of renal, splenic, and mesenteric postganglionic nerves. In urethan-anesthetized rats, preganglionic neurons were stimulated by microinjecting D,L-homocysteic acid (3 nl, 0.17 M) into the lateral gray matter of the third thoracic (T3) to the fourth lumbar (L4) spinal segments. Responses from all three nerves could be elicited from segments T4-T13. The greatest increases in renal nerve discharge were evoked from segments T8-T12, the largest increase of 59 +/- 9% elicited from T10. Increases in splenic and mesenteric nerve discharge were smaller and were evoked more uniformly from T4-L3. The largest increases in discharge of splenic and mesenteric nerves were 19 +/- 5% (from T5) and 26 +/- 4% (from T10), respectively. The widely overlapping spinal cord segments controlling these three organs suggest that location of the preganglionic neurons in different spinal segments is not part of the mechanism for selective sympathetic control. However, the larger renal nerve responses demonstrate that sympathetic output to these organs can be differentiated at the level of the spinal cord.
Cardiac adaptation of sarcomere dynamics to arterial load: a model of hypertrophy
Authors: Drzewiecki G. M. , Karam E. , Li J. K. , Noordergraaf A.
Published: December 2017

In the past, the dynamics of the left ventricle were studied by its response to altered venous and arterial load for a given heart. This led researchers to propose the concept of an arterioventricular match or optimal point of function. The model of this paper reverses that idea by fixing preload and afterload while computing cardiac function due to altered left ventricular size or shape, resulting from modification of the number of parallel and series sarcounits. A mathematical model of physiological hypertrophy is introduced. Series and parallel arrangements of sarcounits constitute a cylindrical model of the left ventricle. Filling occurs from a venous reservoir with constant pressure through a valve, while ejection takes place into a three-element model of the systemic arterial system through another valve. It is found that the dynamics of the myofibrils can be matched to those of the left ventricle by choosing a ventricular shape that results in a minimum in myocardial O2 consumption (MVO2) for any constant ventricular load. A unique solution for the size of the ventricle results if the rate of MVO2 is specified. The model is able to predict correctly hypertrophy due to hypoxia and due to pressure (concentric) and volume (eccentric) overloads.
Ischemic preconditioning protects against infarction in rat heart
Authors: Liu Y. , Downey J. M.
Published: December 2017

We examined the anti-infarct effect of ischemic preconditioning in the rat heart. All hearts were subjected to 30 min of regional coronary ischemia and 2 h of reperfusion. Infarct size was determined by tetrazolium. The control group had an average infarct size of 31% of the risk zone. Three 5-min cycles of preconditioning ischemia limited the infarct size to 3.7%. Neither the adenosine receptor blocker PD 115,199 nor the ATP-sensitive potassium channel blocker, glibenclamide, could block this protection. Intracoronary adenosine A1-receptor agonist 2-chloro-N6-cyclopentyladenosine offered a significant anti-infarct protection to the isolated rat heart, however. Although one 5-min cycle of preconditioning did not protect the rat heart from infarction (31% infarction in risk zone), it did attenuate arrhythmias. We conclude that 1) the rat heart can be preconditioned, which argues against mitochondrial adenosinetriphosphatase being the mechanism of preconditioning; 2) the threshold for preconditioning is higher in rat than rabbit or dog; 3) a role for adenosine in preconditioning was only partially supported; and 4) a role for ATP-sensitive potassium channels was not supported.
Interstitial exclusion of albumin in rat tissues measured by a continuous infusion method
Authors: Wiig H. , DeCarlo M. , Sibley L. , Renkin E. M.
Published: December 2017

Steady-state 125I-labeled rat serum albumin (125I-labeled RSA) concentration in plasma was maintained by intravenous infusion of tracer for 72-168 h with an implanted osmotic pump. At the end of the infusion period, the rat was anesthetized and nephrectomized, and extracellular fluid was equilibrated with intravenous 51Cr-labeled EDTA for 4 h. Five minutes before final plasma and tissue sampling, 131I-labeled bovine serum albumin (131I-labeled BSA) was injected intravenously as a plasma volume marker. Samples of skin, muscle, tendon, and intestine were assayed for all three tracers. Apparent distribution volumes were calculated as tissue tracer content/plasma tracer concentration. Interstitial fluid volume (Vi) was calculated as V51Cr-EDTA-V131I-BSA. Steady-state extravascular distribution of 125I-labeled RSA as plasma equivalent volume (Va,p) was calculated as V125I-RSA-V131I-BSA. Steady-state interstitial fluid concentrations of 125I-labeled RSA in skin, muscles, and tendon were measured with nylon wicks implanted postmortem, and steady-state interstitial albumin distribution volumes were recalculated as wick-fluid equivalent volumes (Va,w). Relative albumin exclusion fraction (Ve/Vi) was calculated as 1-Va,w/Vi. For skin and muscle, steady-state 125I-labeled RSA tissue concentrations were reached at 72 h. Ve/Vi for albumin averaged 26% in hindlimb muscle, 41% in hindlimb skin, 30% in back skin, 39% in tail skin, and 54% in tail tendon. For muscle, Ve/Vi corresponds to expectation if all tissue collagen and hyaluronan is dispersed in the interstitium. However, for skin and tendon, albumin exclusion is considerably lower than expected on this basis, suggesting that much of their collagen is organized into dense bundles of fibers containing no fluid accessible to 51Cr-labeled EDTA or 125I-labeled RSA.
Cytochemical detection of superoxide in cerebral inflammation and ischemia in vivo
Authors: Kontos C. D. , Wei E. P. , Williams J. I. , Kontos H. A. , Povlishock J. T.
Published: December 2017

We used a cytochemical technique for the detection of superoxide in cerebral inflammation and ischemia-reperfusion in anesthetized cats. The technique is based on the oxidation of Mn2+ to Mn3+ by superoxide; Mn3+, in turn, oxidizes diaminobenzidine. The oxidized diaminobenzidine forms an osmiophilic electron-dense product that is detected by electron microscopy. The reagents, manganese chloride (2 mM) and diaminobenzidine (2 mg/ml), were placed topically on the brain surface of anesthetized cats equipped with cranial windows. Inflammation was induced by topical carrageenan with or without phorbol 12-myristate 13-acetate to activate leukocytes. In inflammation, superoxide was detected in the plasma membrane and in the phagocytic vacuoles of leukocytes. In ischemia-reperfusion, superoxide was identified in the meninges in association with blood vessels. It was located primarily in the extracellular space and occasionally in endothelial and vascular smooth muscle cells. In both inflammation and ischemia, the reaction product was eliminated by superoxide dismutase or by the omission of either manganese or diaminobenzidine. It was unaffected by sodium azide, which inhibits peroxidases. No superoxide was detected in the brain parenchyma. The findings confirm the generation of superoxide is cerebral ischemia-reperfusion and show that it is produced in cerebral vessels.
Regional cerebrovascular responses to progressive hypotension after traumatic brain injury in cats
Authors: DeWitt D. S. , Prough D. S. , Taylor C. L. , Whitley J. M. , Deal D. D. , Vines S. M.
Published: December 2017

We investigated the effects of hypotension on cerebral blood flow (CBF) after traumatic brain injury (TBI) in cats. Isoflurane-anesthetized cats were prepared for TBI and for microsphere measurements of total (T) and regional (r) CBF. Four groups were studied: sham injury (group I, n = 6); TBI (group II, n = 6); isoflurane anesthesia, no TBI or hypotension (group III, n = 4); and isoflurane and TBI, no hypotension (group IV, n = 8). After TBI or sham trauma, mean arterial pressure (MAP) was reduced to 80, 60, and 40 mmHg by hemorrhage. Group I TCBF did not change significantly from baseline until MAP reached 40 mmHg, but rCBF was more dependent on MAP in anterior hemispheric than in brain stem regions. Group II TCBF was significantly lower than baseline, and group I TCBF at all levels of hypotension and autoregulation was impaired at higher MAP levels in anterior than in posterior brain regions. Groups III and IV indicated that decreases in TCBF were not due to duration of the preparation or to TBI in the absence of hemorrhagic hypotension. We conclude that global and regional autoregulation are absent in response to hemorrhagic hypotension after TBI.
Effect of anesthetic on sympathetic responses evoked from cerebellar uvula in decerebrate cats
Authors: Paton J. F. , Gilbey M. P.
Published: December 2017

The sympathetic mechanisms involved in the conversion of the tachycardia-pressor response evoked by electrical stimulation of the uvula (lobule IX of the posterior cerebellar cortex) in the unanesthetized decerebrate cat to a bradycardia-depressor response in the same, but anesthetized preparation, were investigated. Sympathoexcitation was produced in the inferior cardiac and renal sympathetic nerves in response to short train stimulation (2-5 pulses, 100-500 Hz) of the uvula in the unanesthetized decerebrate cat, and when paired stimuli (conditioning and test) were applied, the test-evoked potential in both nerves was similar to the response elicited by the conditioning stimulus. Anesthetic administered to these same animals caused the test response in both sympathetic nerves to be greatly decreased, yet the conditioning response was unchanged. The attenuation of the test response by the conditioning stimulus diminished during recovery from anesthesia. The recovery of the test response paralleled the time course of the return of the tachycardia-pressor effect evoked by long train stimulation of the uvula. It appears that anesthesia does not block the sympathoexcitatory response but acts to augment sympathoinhibitory processes associated with uvula stimulation; some possible mechanisms are discussed.
Effect of acute ventricular dilatation on fibrillation thresholds in the isolated rabbit heart
Authors: Jalal S. , Williams G. R. , Mann D. E. , Reiter M. J.
Published: December 2017

We examined the effects of ventricular dilatation on epicardial refractoriness and ventricular fibrillation threshold (VFT) in the isolated, retrograde-perfused rabbit heart. Ventricular size was modified by acutely changing the volume of a fluid-filled balloon secured within either the left or right ventricle. Left ventricular dilatation (to an end-diastolic pressure of 30-38 mmHg) significantly decreased left ventricular effective refractory period (ERP) and myocardial wavelength (calculated as ERP x conduction velocity). Left VFT (determined by scanning the vulnerable period with a train of pulses) decreased from 6.4 +/- 0.9 to 4.4 +/- 0.5 mA; P < 0.01) with left but not right ventricular dilatation. Right ventricular dilatation was associated with a decrease in the right ventricular ERP and myocardial wavelength, and right VFT decreased from 13.6 +/- 1.8 to 4.1 +/- 0.3 mA (P < 0.01). Changes in VFT correlated with the decrease in local refractoriness and shortening of local excitation wavelength.
Relative responses to luminal and adventitial adenosine in perfused arteries
Authors: Headrick J. P. , Northington F. J. , Hynes M. R. , Matherne G. P. , Berne R. M.
Published: December 2017

Responses to luminal and adventitial adenosine were compared in perfused rabbit central ear arteries. Perfused arteries precontracted with 0.5 microM norepinephrine relaxed dose dependently but asymmetrically to luminal and adventitial adenosine. Arteries were more responsive to luminal adenosine in the 0.1- to 1.0-microM range, but they were more responsive to adventitial adenosine at doses > 10 microM. Alternatively, 2-chloroadenosine, a metabolically stable and poorly transported analogue, was equipotent when applied luminally or adventitially. Endothelial damage reduced sensitivity and response asymmetry to luminal and adventitial adenosine. This was consistent with reduced responses to adenosine in luminally rubbed arterial ring segments. Transport inhibition (10 microM dipyridamole) enhanced arterial reactivity to luminal and adventitial adenosine and reduced response asymmetry but was without effect on responses to 2-chloroadenosine. A comparison of the inhibitory effectiveness of adventitial and luminal 8-phenyltheophylline revealed that adventitial antagonist was approximately threefold more effective in inhibiting responses to adventitial adenosine than luminal antagonist (P < 0.05). This "side-dependent" difference was reduced by prolonged antagonist incubation or endothelial removal. The data indicate that adenosine relaxes ear arteries by activation of smooth muscle [half-maximum effective concentration (ED50) approximately 11 microM] and endothelial (ED50 approximately 2 microM) receptors. Nevertheless, a sensitive endothelial-dependent response does not consistently enhance responses to luminal adenosine in perfused arteries. This appears to be attributable to relative differences in the smooth muscle and endothelium-dependent components of the dilator response and transvascular concentration gradients for luminally and adventitially applied adenosine. A transendothelial diffusion barrier also reduces the ability of luminally applied antagonists to inhibit responses to adventitial adenosine.
Analysis of systemic and pulmonary vascular responses to PACAP and VIP: role of adrenal catecholamines
Authors: Minkes R. K. , McMahon T. J. , Higuera T. R. , Murphy W. A. , Coy D. H. , Kadowitz P. J.
Published: December 2017

Systemic and pulmonary vascular responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide with 68% sequence homology to vasoactive intestinal peptide (VIP), were investigated in the anesthetized cat. Intravenous injections of PACAP in doses of 0.1–3.0 nmol/kg produced decreases in arterial pressure (AP) at low doses and biphasic changes (decreases followed by increases) at higher doses, which were accompanied by increases in central venous pressure (CVP) and cardiac output (CO), and decreases and biphasic changes in systemic vascular resistance (SVR). In contrast, VIP in doses of 0.1-3.0 nmol/kg produced only dose-dependent decreases in AP and SVR and produced little change in CVP and CO. PACAP produced increased pulmonary arterial pressure (PAP), left atrial pressure (LAP), and increases in pulmonary vascular resistance (PVR). PACAP increased heart rate (HR) and right ventricular contractile force (RVCF), while VIP had no effect. Increases in AP and SVR in response to PACAP were changed to decreases following the administration of phentolamine or after adrenalectomy. Under constant flow conditions, PACAP and VIP produced dose-dependent decreases in lobar arterial pressure when tone was elevated, with PACAP being threefold more potent than VIP. Meclofenamate and nitro-L-arginine methyl ester (L-NAME) had no effect on pulmonary responses to the peptides. PACAP produced dose-dependent biphasic changes in hindquarters perfusion pressure, whereas VIP produced only decreases that were unchanged by indomethacin, L-NAME, and glibenclamide. Phentolamine and adrenalectomy eliminated the hindquarters pressor response to PACAP and D-Phe2-VIP, a VIP antagonist, reduced responses to VIP but not to PACAP. These data suggest that responses to PACAP and VIP are mediated by distinct receptors and that pressor responses to PACAP are due to the release of catecholamines from the adrenal gland.
T-Q, S-T segment mapping and hyperemia in reperfused pig heart with ischemic preconditioning
Authors: Cinca J. , Worner F. , Carreno A. , Coronel R. , Soldevilla A. , Perez-Villa F. , Janse M. J. , Soler-Soler J.
Published: December 2017

The effects of ischemic preconditioning on epicardial T-Q and S-T segment mapping, local activation, and coronary blood flow were analyzed in nine barbiturate-anesthetized pigs during four coronary occlusion (5 min)-reperfusion (20 min) sequences. In seven sham pigs, one occlusion was performed after a control period of 75 min. The first reperfusion induced a marked coronary hyperemia [11 +/- 4 ml/min (baseline) to 33 +/- 16 ml/min, P < 0.005] and a rapid recovery (30 to 150 s) of epicardial activation delays, T-Q segment depression, and S-T segment elevation in the ischemia area. This recovery was transiently associated with enlargement of intersite T-Q potential variability (alpha: 2.5 +/- 0.6 to 3.4 +/- 0.7 mV, P < 0.05), T-Q segment overshoot to +1.4 +/- 0.9 mV, and S-T segment reelevation. A brief T-Q segment depression (-2.3 +/- 0.9 mV) occurred during early reperfusion in 60 of 91 electrodes overlying the normal myocardium. Compared with the first, the fourth occlusion induced lower S-T segment elevation (3.4 +/- 2.0 to 1.7 +/- 1.9 mV, P < 0.05), and the fourth reperfusion elicited a faster reversal of T-Q segment dispersion (53 +/- 21 to 43 +/- 16 s, P < 0.05), S-T segment elevation (149 +/- 101 to 81 +/- 45 s, P < 0.05), and coronary hyperemia (8 +/- 2 to 5 +/- 1 min, P < 0.05). This trend of changes was not observed during a fourth occlusion in sham pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
Pregnancy reduces serotonin-induced contraction of guinea pig uterine and carotid arteries
Authors: Weiner C. P. , Thompson L. P. , Liu K. Z. , Herrig J. E.
Published: December 2017

Because platelet activation and serotonin have been implicated in preeclamptic hypertension, we investigated the effect of pregnancy on the contractile response to this agent. Prior studies have shown that the vascular contractions to norepinephrine, angiotensin II, and thromboxane are reduced during normal pregnancy by the altered release of endothelium-derived vasoactive substances. We hypothesized that the contraction to serotonin would also be reduced during pregnancy by an endothelium-dependent mechanism. Isolated ring segments from uterine and carotid arteries of near-term pregnant and nonpregnant guinea pigs were studied after stimulating a small amount of active tone with prostaglandin F2 alpha. Serotonin (10(-8) to 10(-5) M) contractile responses of both arteries were reduced by pregnancy. Regardless of pregnancy status, the contractile responses of the uterine artery to serotonin were severalfold greater than that of the carotid artery whose maximum averaged only 10% of the 120 mM KCl contraction. Denudation of uterine artery abolished acetylcholine-stimulated relaxation in vessels from pregnant and nonpregnant animals. However, serotonin-induced contractions were enhanced by denudation only in ring segments obtained from pregnant animals. Nitric oxide synthase inhibition by either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine and cyclooxygenase inhibition by indomethacin had no effect on serotonin-induced contraction of intact uterine artery regardless of pregnancy. L-NMMA modestly enhanced the intact carotid arterial response to 10(-5) M serotonin independent of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of hypoxia, hyperoxia and hypercapnia on graded cerebral ischemic responses in rabbits
Authors: Takeuchi T. , Horiuchi J. , Terada N. , Nagao M. , Terajima H.
Published: December 2017

This study was designed to determine how several factors interact to modify the cerebral ischemic pressor response (CIR) in anesthetized rabbits. After the carotid sinus and aortic nerves were bilaterally sectioned, blood flow through the left internal carotid artery (ICF), which was surgically restricted as the sole route of blood supply to the brain, was reduced by a servo-controller during ventilation with room air, and 8% and 90% O2 and 2 and 5% CO2 gas mixtures. Blood flow (MBF), tissue PO2, PCO2, and interstitial pH were measured in the rostral ventrolateral medulla. Internal carotid arterial pressure, tissue PO2, and MBF decreased proportionately as ICF decreased in the range from 4 to 0 ml/min. Hypoxia significantly increased the rise in renal nerve activity (RNA) and CIR caused by cerebral ischemia, while hyperoxia significantly decreased them. Hypercapnia had almost no influence on the increases in RNA and mean arterial pressure produced by cerebral ischemia. CIR showed a much higher correlation with changes in tissue PO2 than with the other factors. We examined how these factors interact to modify CIR and found that central hypoxia is the main factor in producing CIR.
New nonradioactive microspheres and more sensitive X-ray fluorescence to measure regional blood flow
Authors: Mori H. , Haruyama S. , Shinozaki Y. , Okino H. , Iida A. , Takanashi R. , Sakuma I. , Husseini W. K. , Payne B. D. , Hoffman J. I.
Published: December 2017

We developed new nonradioactive microspheres and used more sensitive X-ray fluorescence spectrometers than used previously to measure regional blood flow in the heart and other organs. We demonstrated the chemical stability of eight kinds of heavy element-loaded microspheres and validated their use for regional blood flow measurement by comparing duplicate flows measured with radioactive and/or nonradioactive microspheres in both acute and chronic dog experiments. The wavelength-dispersive spectrometer (Philips PW 1480) has a higher sensitivity than the previously described X-ray fluorescent system and reduced the number of microspheres required for accurate measurement. The fine energy resolution of this system makes it possible to increase the numbers of different kinds of microspheres to be quantitated, but at present only eight kinds are available. We also used a synchrotron radiation-excited energy dispersive spectrometer. The monochromatic synchrotron radiation allowed us to obtain much higher signal-to-background ratios of X-ray fluorescence spectra than with the wavelength-dispersive system (50 dB more for Zr-loaded microspheres) and will enable analysis of fluorescent activity in smaller regions (< 20 mg) than the radioactive method does.
Atrial contractile performance after cessation of atrial fibrillation
Authors: Leistad E. , Christensen G. , Ilebekk A.
Published: December 2017

Atrial fibrillation is associated with a fall in cardiac output, and cardioversion to sinus rhythm is frequently attempted. After cardioversion, atrial contractile performance might be depressed. It is, however, unclear whether or not atrial contractile performance is altered following atrial fibrillation periods lasting < 1 wk. Atrial contractile performance after short-term paroxysmal atrial fibrillation was examined in seven barbiturate-anesthetized, open-chest pigs paced at constant ventricular rate after complete atrioventricular block. Percent left atrial systolic shortening (systolic shortening of left atrial diameter in percent of atrial diameter at onset of atrial contraction, %LASS) increased from 100 to 116.2% (107.7-121.8) (median and 95% confidence interval) immediately after cessation of a fibrillation period of 1 min. A brief phase of atrial hypercontractility (%LASS significantly above control) was also demonstrated after fibrillation periods of 5 and 15 min. A subsequent phase of atrial hypocontractility (%LASS significantly below control) was recorded after atrial fibrillation periods of 5, 15, and 30 min. After the 30-min fibrillation period, atrial hypocontractility was most pronounced and reached a nadir of 86.8% (75.1-93.3).
Shear stress regulates endothelin-1 release via protein kinase C and cGMP in cultured endothelial cells
Authors: Kuchan M. J. , Frangos J. A.
Published: December 2017

The effect of shear stress on the release of endothelin-1 (ET-1) from endothelial cells is at present controversial with various investigators observing an increase and others observing a decrease. Our data reveal that the release of ET-1 from primary cultures of human umbilical vein endothelial cells varies with the duration and the level of shear. Sustained exposure to low levels of shear (1.8 dyn/cm2) or a brief exposure (< 1 h) to 10 dyn/cm2 caused a sustained stimulation of ET-1 release. Staurosporine (STPN) completely blocked the stimulation in both cases, suggesting that ET-1 release is increased via activation of protein kinase C (PKC). Exposure to 6-25 dyn/cm2 for > or = 6 h dramatically inhibited ET-1 release and led to 0-70% inhibition of cumulative release by 16 h. Pretreatment with N omega-nitro-L-arginine (L-NNA) reversed this suppression in a dose-dependent manner, implicating either nitric oxide (NO) and/or guanosine 3',5'-cyclic monophosphate (cGMP) as a requirement for shear-mediated inhibition of ET-1 release. Treatment of stationary cultures with 8-bromo-cGMP and atrial natriuretic peptide mimicked the inhibition of ET-1 release caused by shear and revealed that cGMP is capable of inhibiting ET-1. Likewise, the inhibitory effects of shear were potentiated and diminished by 3-isobutyl-1-methylxanthine (IBMX) and methylene blue, respectively. Thus cGMP also appears to exert an inhibitory effect in cells exposed to shear.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered pineal adrenergic-stimulated cyclic nucleotide responses in spontaneously hypertensive rats
Authors: Chik C. L. , Ho A. K.
Published: December 2017

In this study, we examined the pineal adrenergic-stimulated cyclic nucleotide responses in spontaneously hypertensive rats (SHR) and their genetic control, Wistar-Kyoto rats (WKY). Treatment with norepinephrine stimulated cAMP and cGMP contents up to 50- and 12-fold in WKY pinealocytes, compared with a 35- and 4-fold increase in SHR. By contrast, there was no difference in the isoproterenol-stimulated cAMP and cGMP contents, suggesting a reduced alpha 1-adrenergic potentiation of beta-adrenergic-stimulated cGMP response in SHR pinealocytes. The altered potentiation mechanism was examined using agents that activate protein kinase C or elevate intracellular Ca2+. In the presence of a protein kinase C activator, the isoproterenol-stimulated cAMP response was potentiated to a similar degree in WKY and SHR pinealocytes. In contrast, the potentiating effects of ionomycin and KCl on the isoproterenol-stimulated cAMP and cGMP responses in SHR pinealocytes were markedly reduced. These results indicate that in the SHR pineal gland, an altered intracellular Ca(2+)-mediated event may account for the reduction in alpha 1-adrenergic potentiation of beta-adrenergic-stimulated cyclic nucleotide responses.
Adenosine protects ischemic and reperfused myocardium by receptor-mediated mechanisms
Authors: Janier M. F. , Vanoverschelde J. L. , Bergmann S. R.
Published: December 2017

To evaluate the role of adenosine receptors in the mediation of adenosine-induced protection of the heart during ischemia and reperfusion, isolated rabbit hearts were perfused at constant flow with 1 microM adenosine started before low-flow ischemia followed by reperfusion. Adenosine delayed the time of onset of ischemic contracture [to 28 +/- 19 (SD) min compared with 10 +/- 10 min in control hearts] and decreased the amplitude of ischemic contracture (29 +/- 16 vs. 48 +/- 14 mmHg; P<0.05 for each compared with controls). This protection was accompanied by an increase in tissue ATP content (1.72 +/- 0.78 vs. 0.96 +/- 0.23 mumol/g; P < 0.05) and stimulation of anaerobic glycolysis (lactate production of 0.78 +/- 0.28 mumol.g-1 x min-1 compared with 0.53 +/- 0.23 mumol.g-1 x min-1; P < 0.05). Functional recovery during reperfusion was enhanced by adenosine (developed pressure 88 +/- 16% compared with 57 +/- 23% of baseline; P < 0.05), and tissue necrosis, assessed by creatine kinase release, was decreased. The potent, nonselective adenosine receptor blocker 8-phenyltheophylline (10 microM) blocked all of the salutary effects of adenosine. Adenosine given only at reperfusion modestly attenuated reperfusion-induced contracture. The results suggest that exogenous adenosine attenuates ischemic injury by receptor-mediated stimulation of anaerobic glycolysis. During reperfusion its protective action is related to vasodilation.
Endogenous vasoconstrictor tone in intestine of normal and portal hypertensive rats
Authors: Joh T. , Granger D. N. , Benoit J. N.
Published: December 2017

The purpose of the present study was to determine the effects of endogenous norepinephrine, vasopressin (AVP), and angiotensin II (ANG II) on normal intestinal microvascular dimensions and to determine whether endogenous vasoconstrictor tone was altered in chronic portal hypertension. The intestine of normal and portal hypertensive rats was prepared for in vivo microscopic observation, and an arteriole (1A, 2A, or 3A) was selected for study. Arteriolar diameter and erythrocyte velocity were continuously monitored and used in the calculation of arteriolar blood flow. Once steady-state conditions were established, specific antagonists to alpha-adrenergic, AVP, or ANG II receptors were applied locally to remove the influences of each of these systems. In normal animals, blockade of alpha-adrenergic receptors produced a 1.3, 1.5, and 14.7% increase in the diameter of 1A, 2A, and 3A, respectively. AVP blockade in normal animals produced an 8.7, 1.6, and 1.5% increase in the diameter of 1A, 2A, and 3A, respectively; ANG II blockade only produced an increase in 3A diameter (5.8%). alpha-Adrenergic blockade produced a smaller increase in portal hypertensive 3A diameter (2.3%) compared with normal rats. AVP and ANG II blockade produced a significantly larger dilation of 3A (AVP, 4.8%) and 1A (ANG II, 3.8%), respectively, compared with control. Plasma AVP and ANG II levels were higher in portal hypertensive (AVP, 9.1 pg/ml; ANG II, 8.6 pg/ml) than in normal rats (AVP, 5.5 pg/ml; ANG II, 6.6 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Regulated secretion of atrial natriuretic factor from cultured ventricular myocytes
Authors: Irons C. E. , Sei C. A. , Glembotski C. C.
Published: December 2017

We have investigated endothelin (ET)-regulated secretion of atrial natriuretic factor (ANF) from primary neonatal rat ventricular myocytes, where hormone release is thought to be constitutive. In a dose-dependent, nifedipine-sensitive manner, ET acutely enhanced ANF release by two- to fivefold over control cultures within 15 min of agonist exposure, demonstrating that ventricular myocytes display a primary characteristic of a regulated secretory cell type. Unlike atrial cultures, ET enhanced ANF release during the first 30 min of exposure; thereafter, secretion rates returned to control levels. KCl, however, effectively enhanced ANF release only during the first 15 min of exposure. Subcellular fractionation of ventricular culture homogenates did not reveal atrial-type dense secretory granules, and pulse-chase labeling experiments showed that the transit time of newly synthesized ANF was short in ventricular myocytes [time required for half of labeled ANF to be released from cells (t1/2) = 0.5-1.5 h) compared with atrial myocytes (t1/2 = 4 h). These results suggest that, whereas ventricular myocytes possess some of the characteristics of a constitutively secreting cell type (e.g., few, if any, dense secretory granules and rapid transit time for newly synthesized hormone); however, they also display the capacity for regulated secretion of ANF in response to the physiological agonist ET.