bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of ACh on electrical and mechanical activity in guinea pig coronary arteries
Authors: Keef K. D. , Bowen S. M.
Published: December 2017

The contractile and intracellular responses to acetylcholine (ACh) were measured in isolated segments of the guinea pig circumflex coronary artery. ACh (10(-5) M) led to hyperpolarization of the membrane in the presence or absence of the H1-receptor agonist 2-(2-aminoethyl)pyridine (AEP). This hyperpolarization was associated with relaxation of vessels precontracted with AEP. Hyperpolarization and relaxation were abolished after complete removal of the endothelium. Less endothelial coverage was required to obtain a relaxation with ACh (10(-5) M) than with bradykinin (BK, 10(-7) M). BK did not initiate hyperpolarization. A23187 (10(-8) to (10(-5) M) did not relax vessels precontracted with AEP. Three muscarinic antagonists were compared and the following order of potency was obtained: atropine greater than pirenzapine greater than AFDX116. Although atropine (10(-7) M) reduced the ACh (10(-5) M)-induced hyperpolarization by 83%, this same concentration of pirenzapine had no effect on hyperpolarization. Oxyhemoglobin (10(-5) M) significantly reduced relaxation to nitroglycerine but not ACh. Methylene blue (10(-5) or 5 x 10(-5) M) inhibited relaxation to submaximal but not maximal concentrations of ACh. In vessels precontracted with elevated potassium, ACh (10(-5) M) caused contraction rather than relaxation. The onset and time to peak hyperpolarization with carbachol was more rapid with luminal as opposed to adventitial application of drug. It is concluded that relaxation and hyperpolarization with ACh in the coronary artery are mediated via the endothelium. The results are compatible with the hypothesis that relaxation is initiated by both endothelial-derived relating factor stimulation of guanylate cyclase activity and hyperpolarization of the smooth muscle.
A sheath for repetitive insertion of high-fidelity micromanometer-tipped catheters
Authors: Held-Munzenmaier D. , Olinger G. N. , Boerboom L. E.
Published: December 2017

Implantation of micromanometer-tipped catheters into dogs and other animals for invasive high-fidelity blood pressure measurement is expensive and impractical. We have devised an implantable sheath that allows insertion of the transducer each time the animal is to be studied. This eliminates animal-inflicted damage and the need for multiple transducers if several animals are to be instrumented concurrently. The sheath is coextruded from hard and soft forms of polyurethane to form a soft, flexible, thrombus-resistant tubing with a hard thin inner lining having a low coefficient of friction. This allows chronic implantation of the sheath into the heart and major vessels with minimal trauma, yet enables a transducer to be advanced through a sheath only slightly larger than the transducer itself without the frictional resistance common to other soft tubing. The sheath can be tapered for ease of implantation into vessels or curved to the appropriate angle for implantation into the heart. Our polyurethane sheath is a versatile, convenient, and inexpensive alternative to chronic instrumentation with transducers for high-fidelity pressure measurement.
Role of adenosine in hypoxic alterations of anaphylaxis of isolated guinea pig hearts
Authors: Heller L. J. , Trachte G. J. , Regal J. F.
Published: December 2017

Previous studies suggest that high levels of adenosine may enhance histamine release and contribute to atrioventricular (AV) nodal conduction arrhythmias during anaphylaxis of isolated guinea pig hearts. To determine whether elevations in endogenous adenosine evoked by hypoxic conditions have similar effects, isolated hearts of guinea pigs passively sensitized by intracardiac injection were perfused with solutions equilibrated with 95% O2 (normoxia) or 30% O2 (hypoxia). When compared with normoxia, hypoxia before antigen challenge increased adenosine release, decreased vascular resistance, and prolonged P-R intervals, whereas hypoxia during anaphylaxis potentiated the increase in adenosine release, attenuated the increases in vascular resistance and atrial rate, and increased the occurrence of conduction arrhythmias without altering the antigen-induced release of either histamine or thromboxane. Addition of the adenosine receptor antagonist 8-(4-sulfophenyl)theophylline (SP-T) to the hypoxic perfusate significantly decreased antigen-induced release of histamine and thromboxane. These data indicate that 1) hypoxia-induced depression of antigen-induced mediator release may be counteracted by the stimulatory effect of the increased adenosine induced by hypoxia, and 2) under hypoxic conditions, adenosine's negative dromotropic, chronotropic, and vasodilatory effects may influence the anaphylactic reaction.
Role of calcium in U 46619 and PGF2 alpha pulmonary vasoconstriction in rat lungs
Authors: Santoian E. C. , Angerio A. D. , Schneidkraut M. J. , Ramwell P. W. , Kot P. A.
Published: December 2017

The role of calcium and calmodulin during U 46619 and PGF2 alpha-induced pulmonary vasoconstriction was studied in isolated rat lungs perfused with Krebs-Ringer bicarbonate (KRB) or calcium-free KRB. In lungs perfused with KRB, bolus injections of U 46619 (0.2 microgram) and PGF2 alpha (40.0 micrograms) resulted in a 48.0 +/- 4.0 and 23.9 +/- 2.5% increase in mean pulmonary artery pressure, respectively. During lung perfusion with KRB without calcium, the U 46619 response decreased to 31.1 +/- 7.5% whereas the PGF2 alpha response increased to 34.6 +/- 4.1%. Repeated challenges with PGF2 alpha in the KRB without calcium resulted in reduction of the response to 11.8 +/- 1.2%; the U 46619 response was unaltered. The intracellular calcium blocker, 8-(N,N-diethylamino)-octyl-3,4,5, trimethoxybenzoate HCL (TMB-8) significantly attenuated the pressor response to U 46619 at low doses and PGF2 alpha at high doses. The calmodulin inhibitor trifluoperazine (TFP 100 microM) attenuated the vasoconstrictor response to U 46619 by 54%, whereas the PGF2 alpha was unchanged. However, in the calcium-free KRB, TFP attenuated the pressor response to both U 46619 and PGF2 alpha. The U 46619 pressor response depends on intracellular and extracellular calcium to achieve calmodulin-dependent vasoconstriction. PGF2 alpha requires extracellular calcium to replenish depletable intracellular calcium pools and is independent of calmodulin activation.
Cardiovascular control by arterial and cardiopulmonary baroreceptors in awake dogs with atrioventricular block
Authors: Raymundo H. , Scher A. M. , O'Leary D. S. , Sampson P. D.
Published: December 2017

We studied reflex responses to pressure changes at arterial and cardiopulmonary baroreceptors in five awake dogs with atrioventricular block before and after baroreceptor denervation. We changed ventricular pacing rate and blood volume to vary cardiac output and arterial (MAP) and central venous pressure (CVP). We determined peripheral resistance (TPR) and atrial rate (HRA) as responses. In the intact animal, regression analysis showed an average relationship across dogs of TPR = 169-0.69 MAP-1.952 CVP + error. Correlation (r) between observed and predicted TPR was 0.83. For HRA, regression indicated HRA = 291.66-2.319 MAP + 8.144 CVP + error (r = 0.899). TPR and MAP are percent of control at 90 beats/min; CVP is in mmHg; HRA, in beats/min. Although its coefficient is smaller, MAP explains approximately 69% of the variation in TPR. After arterial baroreceptor denervation, effects of MAP on TPR were insignificant and the coefficient for CVP increased. Subsequent vagal block eliminated all reflex responses. Effects from the two receptor sites sum linearly. They act cooperatively with changes in blood volume, but oppose one another with cardiac output changes.
Microcirculatory adaptations in sickle cell anemia: reactive hyperemia response
Authors: Rodgers G. P. , Schechter A. N. , Noguchi C. T. , Klein H. G. , Nienhuis A. W. , Bonner R. F.
Published: December 2017

With the technique of laser-Doppler velocimetry, cutaneous blood flows in the forearm of patients with stable sickle cell disease after graded periods of proximal ischemia were compared with normal subjects matched for age, race, and sex, and with patients with anemia caused by beta(+)-thalassemia. In the sickle cell patients the reactive hyperemia was characterized by an increased time interval between the release of the occlusion and the peak amplitude response (time-to-peak) and by a greater period of blood flow above the base-line value (payback ratio) compared with controls. In addition, prolongation of the occlusion period led to an augmentation in the magnitude of the characteristic basal flow oscillations or an induction of this phenomenon at sites not exhibiting it before ischemia. Base-line or ischemia-provoked flow oscillations of either this magnitude or frequency were only observed in normal or thalassemic controls during brief intervals in the rapidly decaying portion of the hyperemic response and in one subject with homozygous hemoglobin C disease. These results would support a model of a local integrative control of microcirculatory blood flow, which appears to become augmented, synchronized, and sustained in sickle cell subjects.
ANF disappearance and tissue distribution in rats
Authors: Widimsky J. , Debinski W. , Kuchel O. , Buu N. T.
Published: December 2017

The disappearance of [125I]atrial natriuretic factor (ANF; Ser99-Tyr126) from the circulation and its tissue distribution with or without nonlabeled ANF pretreatment were investigated in normotensive Sprague-Dawley rats. Preadministration of the cold peptide increased plasma radioactivity levels for over 8 min following labeled ANF injection but did not change the half-life of circulating labeled ANF. The metabolic clearance rate (MCR) and volume of distribution in the first, second, and steady state phase were significantly decreased after cold ANF pretreatment. Circulating iodo-labeled ANF was taken up by several organs, even by tissues such as fat or bone, but its urinary excretion was very low. The highest uptake was found in the liver (16 +/- 1% of the injected dose), lung (14 +/- 1%), and kidney (12 +/- 1%), diminishing by 21, 89, and 59%, respectively, after cold ANF preinjection. The brain radioactivity was negligible implying an inability of [125I]ANF to cross the blood-brain barrier. Our data underscore the importance of the uptake-mediated, cold ANF preadministration suppressible clearance of ANF from the circulation, probably one of its basic elimination mechanisms. The liver, lung, and kidney are probably the most important participants in the MCR of ANF.
Influence of adenosine on left ventricular performance in conscious dogs
Authors: Freeman G. L. , Colston J. T. , Hultman J.
Published: December 2017

Adenosine, a potent vasodilator of both the peripheral and coronary vasculature, is increasingly used to produce controlled hypotension in the clinical and experimental setting. To define the influence of adenosine on left ventricular (LV) performance in conscious closed-chest dogs were studied six chronically instrumented autonomically blocked animals before and after the administration of 0.3, 0.6, and 1.2 microM.kg-1.min-1 infusions of adenosine. Systolic performance was quantified by the end-systolic pressure-volume (Pes-Ves) and stroke work end-diastolic volume (SW-EDV) relations. Active diastolic performance was quantified by the time constant of LV relaxation (T), whereas passive diastolic properties were assessed by comparing LV pressures at a common LV volume. Despite a decrease of mean arterial pressure of 51 mmHg, adenosine did not change the slope of the Pes-Ves relation or the end-systolic volume at a pressure of 100 mmHg. The slope of the SW-EDV relation was also unchanged, and its volume axis intercept was slightly reduced. There were no differences in T or in the diastolic pressure at a common LV volume. Thus adenosine appears to have little influence on systolic or diastolic LV performance aside from its marked affect on afterload, indicating it is a useful agent for producing controlled hypotension.
Microcirculatory responses to exogenous endothelial cell-derived relaxing factor
Authors: Rivers R. J. , Loeb A. L. , Izzo N. J. , Peach M. J. , Duling B. R.
Published: December 2017

Endothelium-derived relaxing factor (EDRF) plays an important role in the vasodilatory responses of large blood vessels. However, such a role has yet to be conclusively shown for the microvasculature. In this study we tested the sensitivity of arterioles in the cheek pouch of pentobarbital-anesthetized hamsters to the EDRF-dependent agonists bradykinin and A23187, as well as to exogenous EDRF from cultured bovine aortic endothelial cells. The pouch superfusion fluid was arranged to first pass through a column containing endothelial cells and then on to the tissue. Bradykinin (10–30 nM) or A23187 (0.3 microM) was introduced either upstream or downstream to the endothelial cells, and the resultant responses were measured with video microscopy. Bradykinin and A23187 both caused a dose-dependent release of a microvessel dilator from cultured endothelial cells. We take this dilator to be EDRF based on the characteristics of the responses to the stimuli. Indomethacin (7.7 microM) was present in the superfusate to eliminate the production of cyclooxygenase products from the endothelial cells, and the magnitude of the response was diminished if the superfusate was first passed through a 3-min delay coil before arrival at the pouch. The arterioles dilated to the direct application of bradykinin in a dose-dependent fashion. They did not respond however to the direct application of A23187. These studies demonstrate that arteriolar smooth muscle is able to respond to exogenous EDRF and support the premise that EDRF may play an active role in the regulation of blood flow in the microcirculation.
Unstimulated force during hypoxia of rat cardiac muscle: stiffness and calcium dependence
Authors: Leijendekker W. J. , Gao W. D. , ter Keurs H. E.
Published: December 2017

The stiffness of rat cardiac trabeculae was measured in vitro to distinguish between an increase in unstimulated force (Fu) caused by rapid cycling of cross bridges or caused by rigor bridges during hypoxia. The force was measured with a strain gauge, the sarcomere length was determined by laser diffraction techniques, and muscle length was controlled by means of a motor. Stiffness was analyzed by using small (less than 1% of muscle length) sinusoidal length perturbations of 1 and 100 Hz. The stiffness at 100 Hz increased linearly with force during tetani at a varied [Sr2+] (0.25-10 mM) in the Krebs-Henseleit (K-H) buffer, but remained virtually unchanged at 1 Hz. In contrast, the stiffness of both the passive muscle and the muscle exposed to either CN- or to PO2 less than 1.5 mmHg up to development of maximal Fu (Fumax) was similar at 1- and 100-Hz perturbations. Less profound hypoxia (PO2 6-10 mmHg) resulted in spontaneous sarcomere activity during the rise in Fu, and an increase in the ratio of stiffness at 100 Hz to stiffness at 1 Hz was detected. When oxidative phosphorylation was inhibited by CN- (2 mM) while the muscle was stimulated in the absence of both Ca2+ and Na+ (choline+substituted), the addition of Na+ at the time at which Fu had reached 30-40% of Fumax did not affect the rate of rise of Fu. These results show that the development of Fu during more complete anoxia in rat trabeculae is completely due to the formation of rigor links and that Ca2(+)-dependent cross-bridge activation can contribute to the rise in Fu during less severe hypoxia.
Measurement of left ventricular mass in rats using electrocardiogram-gated magnetic resonance imaging
Authors: Manning W. J. , Wei J. Y. , Fossel E. T. , Burstein D.
Published: December 2017

To evaluate the ability of electrocardiogram (ECG)-gated magnetic resonance (MR) imaging to assess in vivo left ventricular (LV) mass in the rat, we studied 20 healthy adult Sprague-Dawley and Fischer 344 rats and 8 additional rats that underwent scanning after induction of volume overload by aortic leaflet disruption. ECG-gated spin-echo pulse sequences were used to acquire a series of 1-mm thick modified short-axis images of the left ventricle. The area enclosed by the endocardial and epicardial borders of the left ventricle was multiplied by the interslice distance and specific gravity of myocardium to obtain calculated slice mass. Total LV mass was obtained by summing the individual slices. The calculated value for LV mass was then compared with the LV mass as determined at postmortem examination. Linear regression analysis showed an excellent correlation of MR-estimated mass (x) with autopsy-measured LV mass (y) (y = 0.90x + 65, r = 0.98). For this method intraobserved and interobserver slice correlations were 0.97 and 0.96, respectively. There was no significant difference in LV mass as determined from a series of diastolic vs. systolic images in a subset of six animals. Over a mean of 6.5 wk of observation, LV mass increased by 40% in the animals subjected to aortic leaflet disruption. These results demonstrate that MR imaging is highly accurate for the non-invasive in vivo assessment of LV mass in the adult rat.
Lung inflation evokes reflex dilation of microvessels in rat skeletal muscle
Authors: Yu J. , Roberts A. M. , Joshua I. G.
Published: December 2017

Lung inflation can reflexively decrease peripheral resistance, but effects on the microcirculation have not been determined. In this study, we examined the effects of lung inflation on microvessels in skeletal muscle. In anesthetized spontaneously breathing rats, the right cremaster muscle with intact circulation and innervation was exposed and suspended in a tissue bath filled with a physiological salt solution. Diameters of third-order arterioles (3As) were displayed by television microscopy and measured as an index of microcirculatory resistance. In other experiments, sympathetic activity (in the genital femoral nerve) to the cremaster was recorded. Lung inflation decreased systemic blood pressure by 32 +/- 3 mmHg and increased 3A diameter by approximately 23% (P less than 0.05, n = 17). The increase was abolished by cutting the cervical vagus nerves or the right genital femoral nerve. Furthermore, inflation decreased sympathetic nerve activity by 47.6 +/- 11.3% (P less than 0.05, n = 5) before vagotomy but not after. Dilation in response to inflation was also abolished by phentolamine or guanethidine. These results suggest that stimulation of vagal afferents by inflation reflexively decreases microvascular resistance by withdrawal of sympathetic tone.
Hemodynamic dependence of myocardial oxygen consumption indexes
Authors: Schipke J. D. , Burkhoff D. , Kass D. A. , Alexander J. , Schaefer J. , Sagawa K.
Published: December 2017

We tested the afterload and contractile state dependency of three indexes of myocardial oxygen consumption (MVO2): total energy requirement (Et), pressure work index (PWI), and pressure-volume area (PVA). MVO2 was measured in seven isolated canine hearts at four or five different end-diastolic volumes at each of three settings of afterload resistance and with the hearts contracting isovolumically. In several hearts, contractility was also varied by dobutamine infusion. Measured MVO2 (MMVO2) was compared with values predicted (PMVO2) by each index. There was always a high degree of correlation between MMVO2 and PMVO2 for each of the indexes. However, there was a large degree of variability in the coefficients of the MMVO2-PMVO2 relation from one heart to another. We also observed a statistically significant influence of both afterload and contractile state on the predictive power of each of the indexes. Thus each index that we tested had shortcomings in being able to predict MVO2 accurately over a wide range of hemodynamic conditions.
Maternal influences on sympathetic-adrenal medullary system in spontaneously hypertensive rats
Authors: Cierpial M. A. , Konarska M. , McCarty R.
Published: December 2017

The technique of reciprocal cross fostering was used to assess the influence of the maternal environment on the functioning of the sympathetic-adrenal medullary system in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats. Control, in-fostered, and cross-fostered rats were tested in adulthood to assess 1) the neural contribution to resting mean arterial blood pressure (MAP) and 2) sympathetic-adrenal medullary responses to acute footshock stress. Adult resting MAP was significantly lower in cross-fostered SHRs (139.6 mmHg) compared with control or in-fostered SHRs (162.1 and 159.3 mmHg). In addition, the decrease in MAP after sympathetic blockade (40.6 mmHg) was significantly less in cross-fostered SHRs compared with controls (50.1 mmHg). Sympathetic-adrenal medullary responses to foot-shock were greater in SHR than WKY rats; however, cross-fostered SHRs showed exaggerated responses compared with control and in-fostered SHRs. Altering the maternal environment did not produce any measurable effects on the neural contribution to resting MAP or sympathetic-adrenal medullary responsivity to acute stress in the WKY strain. These results indicate that the blood pressure-lowering effect of cross fostering in the SHR strain is caused in part by a dampening of the neural contribution to resting MAP; however, these animals retain their strain's characteristic adrenergic hyperreactivity to stressful stimulation.
Chronic effects of a physiological dose of ANP on arterial pressure and renin release
Authors: Kivlighn S. D. , Lohmeier T. E. , Yang H. M. , Shin Y.
Published: December 2017

To determine the long-term effects of a physiological dose of atrial natriuretic peptide (ANP) on renin release, the renin response to reductions in renal arterial pressure (RAP) was studied during 1) control conditions and 2) acute and 3) chronic (5 days) intravenous infusion (5 ng.kg-1.min-1) of alpha-human ANP in conscious dogs maintained on a normal sodium intake. Renal perfusion pressure was servo controlled at reduced levels with an inflatable occluder placed around the abdominal aorta just above the renal arteries. Under control conditions, reducing RAP by 30 and 40 mmHg increased plasma renin activity (PRA) 4- to 5- and 9- to 10-fold, respectively. Acute ANP infusion had no significant effect on either basal levels of PRA or the PRA response to reduced RAP. During chronic ANP infusion there was a two- to threefold increment in plasma ANP concentration and approximately a twofold increase in urinary sodium excretion on day 1; however, there were no significant long-term changes in mean arterial pressure, basal PRA, or the levels of PRA achieved during reductions in RAP. These findings indicate that the changes in plasma ANP concentration that occur under normal physiological conditions do not appreciably alter either basal PRA or renin release in response to renal hypotension in conscious sodium-replete dogs studied under resting conditions.
Systemic and local effects of endotoxin on canine gracilis muscle vascular conductance
Authors: Bond R. F. , Scott C. G. , Krech L. H. , Bond C. H.
Published: December 2017

To define the site and mechanism of action that endotoxin has on the peripheral vasculature, an in situ constant-flow double-canine gracilis muscle (GM) preparation was utilized. During systemic endotoxemia, one GM was innervated and the other was denervated during a 30-min intravenous infusion of 2 mg/kg endotoxin. Significantly increased vascular conductance (URP) in the denervated GM (106 +/- 26%) occurred compared with the innervated GM (50 +/- 7%), which suggests that decompensation is not totally dependent on neural depression. During local endotoxemia, with both GMs either intact or denervated, one GM was infused intra-arterially for 30 min with a dose of endotoxin calculated to provide a blood concentration similar to that achieved during systemic endotoxemia, whereas the other GM was infused with the vehicle. The URPs did not change significantly in either the saline or endotoxin GMs. Therefore, endotoxin does not act directly on peripheral vasculature or totally through depression of the autonomic nervous system. It apparently interacts with a systemically dependent mechanism to release a vasodepressor substance that is transported to the peripheral vasculature causing relaxation of vascular tone.
Duration of pressure overload alters regression of coronary circulation abnormalities
Authors: Ito N. , Isoyama S. , Kuroha M. , Takishima T.
Published: December 2017

Using a rat model of ascending aortic banding and debanding, we examined how the duration of pressure overload affects reversibility in coronary circulation abnormalities after relief of pressure overload. Four-week banding increased left ventricular dry weight-to-body weight ratio to 158 +/- 8% of that of sham-operated controls. In isolated nonworking hearts perfused with crystalloid solution, peak mean coronary flow rate (CFR) was measured after brief ischemia. CFR and CFR/dry tissue weight significantly decreased (75 +/- 5 and 54 +/- 3% of that of controls at 100 mmHg of coronary perfusion pressure; 75 +/- 5 and 54 +/- 4% at 150 mmHg, respectively). Four weeks after debanding was performed, CFR and CFR/dry tissue weight increased to similar levels in controls. On the other hand, 10-wk banding produced the same degree of myocardial hypertrophy and decreases in CFR and CFR/dry tissue weight as in 4-wk banded rats. Four weeks after debanding was performed, CFR had not changed. CFR/dry tissue weight increased because of regression of myocardial hypertrophy but was significantly lower than that in rats debanded after 4 wk of banding. Thus the duration of pressure overload does not affect the degree of coronary circulation abnormalities in the progression process but does affect it in the regression process.
Effect of ischemic zone size on nonischemic zone function
Authors: Aversano T. , Marino P. N.
Published: December 2017

To study the influence of ischemic zone size on function in nonischemic regions, wall thickening and the end-systolic pressure-thickness (ESPTR) relationship were measured before and during a 90-s coronary occlusion, which produced either a small or large (24 or 35% of left ventricular mass) area of ischemia. With both size ischemic areas, nonischemic zone isovolumic and ejection phase wall thickening increased during occlusion, primarily because of increased preload and, to a lesser extent, a reduced pressure component of afterload. The nonischemic region ESPTR was unchanged from preocclusion control with small ischemic mass. With larger ischemic mass, the nonischemic region ESPTR was shifted downward and to the left, indicating reduced end-systolic performance. The decline in the nonischemic zone ESPTR with large ischemic zone size was not due to reduced blood flow, shortening deactivation, reflex effects, or "tethering" but rather to the associated decline in coronary perfusion pressure. Thus the increase of nonischemic region wall thickening during acute ischemia is due to a change in ventricular loading conditions and not augmentation of contractile performance. Larger ischemic zone size can impair function in nonischemic myocardium by reducing the erectile component of end-systolic performance.
Distinction of NPY receptors in vitro and in vivo. II. Differential effects of NPY and NPY-(18-36)
Authors: Scott N. A. , Michel M. C. , Boublik J. H. , Rivier J. E. , Motomura S. , Crum R. L. , Landon M. , Brown M. R.
Published: December 2017

We have studied the hemodynamic effects of neuropeptide Y (NPY) and its COOH-terminal fragment NPY-(18–36) in conscious rats. Intra-arterial injection of NPY rapidly elevated systemic vascular resistance (SVR), which remained high for greater than 30 min. Cardiac output (CO) decreased, and it remained low for greater than 30 min. Accordingly, blood pressure rose only transiently and returned to base-line values within 5 min. The reduction of CO could be attributed to a decreased stroke volume with an only marginal reduction of heart rate. Thus a direct cardiodepressive effect of NPY rather than baroreflex activation appears to be the major cause of the reduced CO. In vitro experiments excluded the possibility that NPY has direct negative inotropic effects and suggest that its cardiodepressive action is caused by coronary vasoconstriction or by presynaptic inhibition of norepinephrine release. Intra-arterial injections of NPY-(18-36) caused different hemodynamic effects. NPY-(18–36) decreased CO in a manner similar to that seen with NPY but initially did not elevate SVR, resulting overall in a reduced blood pressure. Only later, when blood pressure was reduced, was an elevation of SVR observed, which could be associated with increased plasma levels of catecholamines, angiotensin II, vasopressin, and NPY. Thus NPY-(18–36) mimics the cardiac effects of NPY but does not elicit its vascular effects. As NPY-(18–36) discriminates between NPY receptor subtypes in vitro, we conclude that the cardiac and vascular effects of NPY are mediated by distinct receptor subtypes.
Transmural hematocrit gradient in left ventricular myocardia of rats
Authors: Vicaut E. , Levy B. I.
Published: December 2017

The transmural distribution of tissue hematocrit was determined in rat left ventricular myocardium. Intramyocardial distribution volumes of 99Tc-labeled red blood cells and 131I-labeled albumin were measured in hearts arrested in a relaxed state by KCl or in a contracted state by BaCl2. Hearts were frozen in situ immediately after arrest by bathing in a mixture of liquid nitrogen and isopentane. After excision of the heart, a parallelepipedic portion was cut in a transverse section of the left ventricular free wall and subjected to en face serial sectioning through the thickness of the wall from the epicardium to the endocardium. 99Tc and 131I activity allowed determination of red blood cell and plasma volume and consequently of tissue hematocrit in each section. In both the relaxed and the contracted states of the hearts, a significant decreasing gradient of tissue hematocrit was found from the outer to the inner layers of myocardium. Tissue hematocrit in the subendocardial layers was approximately 70% of its value in the subepicardial layers.
Relationship between diastolic shape (eccentricity) and passive elastic properties in canine left ventricle
Authors: Nikolic S. D. , Yellin E. L. , Dahm M. , Pajaro O. , Frater R. W.
Published: December 2017

This study was designed to investigate the relationship between left ventricular (LV) eccentricity, volume, and passive elastic properties. Eight open-chest fentanyl-anesthetized dogs were instrumented with an LV micromanometer, a remote-controlled mitral valve occluder, and two pairs of ultrasonic crystals to measure anterior-posterior and base-apex dimensions. We identified the presence of elastic recoil forces with negative LV diastolic pressure in nonfilling diastoles (end-systolic volume clamp). Using linear regression analysis we related midwall eccentricity to volume in nonfilling diastoles at the time of LVPmin and at end diastole, and in normal beats at end systole at LVPmin and at end-diastole. Intersection of the end-systolic and end-diastolic lines (transitional volume, Vt = 38.0 + 6.4 ml) divides cycles with and without the presence of elastic recoil forces. Vt is analogous to the equilibrium volume (V0), determined as the volume intercept of the logarithmic passive pressure-volume (P-V) relationship using LV volume estimated from LV weights (V0 nl = 37.6 + 4.4 ml), or the volume intercept of the linearized P-V relationship calculated from a prolate spheroidal model using measured minor and major diameters (V0 l = 44.5 + 3.5 ml). Linear regression analysis was also used to relate the square of peak mitral flow (MF2) with the corresponding atrioventricular pressure gradient (delta P); the slope represents a dissipative constant for the cycles without, P = 0.00058(MF)2 + 0.35 (n = 48, r = 0.73), and with elastic recoil P = 0.00035(MF)2 + 0.21 (n = 24, r = 0.81).(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of transmembrane potential of isolated cardiac myocytes by insulin and isoproterenol
Authors: Eckel J. , Reinauer H.
Published: December 2017

Isolated muscle cells from adult rat heart have been used to study the effects of insulin and catecholamines on transmembrane potential by following triphenylmethylphosphonium cation uptake. Insulin was found to hyperpolarize the cells with a maximal effect of 3.2 +/- 0.7 mV (n = 4) at an insulin concentration of 3 x 10(-9) mol/l. This insulin action was fully antagonized by isoproterenol (10(-5) mol/l), which depolarized the cardiocytes in a dose-dependent fashion with a maximal effect of 9.5 +/- 2.2 mV. Treatment of cardiocytes with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or CsCl resulted in a total loss of insulin action, whereas isoproterenol action was not affected. Cardiac myocytes from streptozotocin diabetic rats exhibited an unaltered hyperpolarization by insulin within the physiological concentration range. Isoproterenol now induced a biphasic response with a significant hyperpolarization at low doses and a decreased depolarization at maximal concentrations. In conclusion, 1) hormonal modulation of cardiac myocyte membrane potentials involves hyperpolarization by insulin and depolarization by beta-agonists, 2) insulin action appears to be related to an increased potassium conductance and may be antagonized by beta-stimulation, and 3) membrane potential modulation may be profoundly altered in the diabetic state.
Diminished responsiveness of human platelets to platelet-activating factor during pregnancy
Authors: Kornecki E. , Ehrlich Y. H.
Published: December 2017

Platelet-activating factor (PAF; PAF-acether) is a phospholipid that is synthesized and released by a number of inflammatory cells and is a potent inducer of platelet aggregation and secretion. In the present study we examined the responsiveness of human platelets to various concentrations of PAF during pregnancy and postpregnancy. We found that in pregnant individuals the responses of washed gel-filtered platelets to PAF were either absent or greatly reduced during the 22nd-30th wk of pregnancy and returned to normal in the postpartum period. In contrast, the responses of platelets to various concentrations of ADP were not altered during pregnancy. We propose that during pregnancy circulating levels of PAF in the maternal circulation, possibly originating from the fetus, may desensitize maternal platelet receptors to PAF, resulting in a diminished or a complete lack of response of platelets, specifically to PAF. These findings may have important implications for our understanding of the role of PAF in hemostasis during pregnancy and in embryonic and fetal development.
Effect of global myocardial stunning on Ca2(+)-sensitive myofibrillar ATPase activity and creatine kinase kinetics
Authors: Krause S. M.
Published: December 2017

Reperfusion of rabbit hearts after 15 min of global ischemia at 37 degrees C depressed developed pressure by 36% (myocardial stunning). Changes in myofilament function were investigated as causes of this depression. Kinetic analysis of the effects of stunning on myofibrillar catalyzed ATP hydrolysis showed that stunning lowered Michaelis constant (Km) slightly and left maximal enzyme reaction velocity unaltered in the stunned myofilaments. The myofilament end of the creatine kinase (CK) shuttle was also found to be unaffected in the stunned myofibrils. The Km ADP for myofibrillar CK from control and stunned hearts was 60.45 +/- 3.45 and 68.04 +/- 2.42 microM, respectively, and the CK activity at 100 microM ADP was 0.63 +/- 0.08 and 0.67 +/- 0.04 IU/mg myofibrillar protein from control and stunned hearts, a rate three times greater than the myofibrillar adenosinetriphosphatase (ATPase) rate and a rate sufficient to deliver ATP to the myofilaments. Myofilament Ca2+ sensitivity was assessed by measuring Ca2(+)-dependent myofibrillar Mg2(+)-ATPase activity at free [Ca2+] ranging from 10 nM to 32 microM and [Mg.ATP] of 0.8, 1.6, and 3.2 mM. The sensitivity of myofilaments to activation by Ca2+ was unaltered in the myofibrils isolated from stunned hearts. It is concluded from these analyses that the depression of pressure development observed in stunned hearts is not due to a defect in myofilament function.
Transient hypothermic reperfusion and postischemic recovery in isolated rat heart
Authors: Kempsford R. D. , Murashita T. , Hearse D. J.
Published: December 2017

The potential benefit of transient hypothermic reperfusion of the ischemic myocardium was investigated in isolated working rat hearts (n = 6/group) subjected to 25 min of global ischemia at 37 degrees C. Hearts were reperfused in the Langendorff mode at 5, 10, 20, 30, or 37 degrees C for 10 min plus 5 min at 37 degrees C before assessment of functional recovery (working mode). Compared with normothermic reperfusion (recovery of cardiac output = 42.3 +/- 6.1%), transient hypothermia failed to improve the recovery of cardiac output, which was 47.9 +/- 12.7 (P = NS), 54.3 +/- 11.5 (P = NS), 25.3 +/- 2.7 (P = NS), and 6.4 +/- 3.8% (P less than 0.05) in the 30, 20, 10, and 5 degrees C groups, respectively. Reduced recovery in the 5 degrees C group was reflected in increased creatine kinase leakage from 0.26 +/- 0.04 IU.ml-1.g dry wt-1 (37 degrees C reperfusion) to 0.62 +/- 0.12 IU. ml-1.g dry wt-1 (5 degrees C reperfusion; P less than 0.05). Brief periods (3 x 1 min) of hypothermic (5 degrees C) perfusion during normothermic Langendorff reperfusion (15 min) also reduced recovery of cardiac output to 12.1 +/- 7.2% (P less than 0.01). In additional studies, hearts were subjected to a 2-min preischemic infusion with the St. Thomas' Hospital cardioplegic solution before either 25 or 35 min of normothermic ischemia and reperfusion with transient hypothermia at 5, 10, 20, or 30 degrees C. Once again hypothermic reperfusion failed to improve recovery but detrimental effects were not observed in the 5 degrees C group. These results indicate no beneficial effect of transient hypothermic reperfusion on recovery of function measured following global normothermic ischemia.
Reduced beta-agonist sensitivity in single atrial cells from failing human hearts
Authors: Harding S. E. , Jones S. M. , O'Gara P. , Vescovo G. , Poole-Wilson P. A.
Published: December 2017

Human myocytes were isolated from right atrial appendage, and contractile responses to inotropic agents were studied. Responses to inotropic agents of cells isolated from patients with mild heart disease [New York Heart Association (NYHA) classes I and II] were compared with those of myocytes from rabbit atria. Maximally effective concentrations of calcium, forskolin, and isoproterenol increased contraction amplitude to a similar extent (11.9, 11.5, and 11.3% change in cell length, respectively), but histamine produced a smaller effect (7.1%). The maximum responses of rabbit atrial cells to calcium (18.5%) and isoproterenol (15.0%) were significantly greater than human. In human cells, the velocity of contraction or relaxation was accelerated more by isoproterenol (P less than 0.05) or forskolin (P less than 0.01) than by high calcium. Only relaxation velocity was increased by isoproterenol in rabbit cells (P less than 0.05). Rabbit myocytes contracted and relaxed 10-30% faster than human (P less than 0.05). Cells from the atria of patients with New York Heart Association (NYHA) heart failure class III or IV were less responsive to isoproterenol than those from class I or II (P less than 0.01). Omitting data from patients who had been taking calcium-channel blockers or beta-adrenoceptor agonist or antagonist drugs did not affect the conclusions. Analysis of variance revealed a significantly greater between-patient than within-patient variation (P less than 0.001), indicating that cells from the same patient have a tendency to respond in a similar way. Responses to high calcium did not differ among NYHA classes. The effect of forskolin was not reduced in NYHA class III, although there was a decreased response in cells from two patients in NYHA class IV.(ABSTRACT TRUNCATED AT 250 WORDS)
Defects in regulation of mitochondrial ATP synthase in cardiomyocytes from spontaneously hypertensive rats
Authors: Das A. M. , Harris D. A.
Published: December 2017

Control of mitochondrial ATP synthase capacity was investigated in cultured cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously hypertensive (SHR) rats. The basal ATP synthase capacity in quiescent cardiomyocytes was raised in the hypertensive rats (2.9 +/- 0.1 mumol.min-1.mg protein-1) compared with normotensive rats (2.2 +/- 0.1 mumol.min-1.mg-1). However, this high value is restored to normal after treatment of the cells with verapamil or ruthenium red; agents that do not affect ATP synthase capacity in normal cells. It is concluded that abnormally high intramitochondrial Ca2+ levels, or an abnormal mitochondrial response to Ca2+ concentration, are responsible for ATP synthase activation in quiescent SHR cells. Cardiomyocytes from normotensive rats respond to increased energy demand (caused by electrical stimulation or treatment with positive inotropic agents) by increasing their ATP synthase capacity up to twofold. Cells from SHR rats are unable to control their ATP synthase in this way. It is concluded that some defect in regulation of the mitochondrial ATP synthase occurs in myocytes from hypertensive rats.
Regional autoregulatory responses during infusion of vasoconstrictor agents in conscious dogs
Authors: Hellebrekers L. J. , Liard J. F. , Laborde A. L. , Greene A. S. , Cowley A. W.
Published: December 2017

We investigated pressure-dependent autoregulatory responses in mesenteric, iliac, and renal vascular beds of conscious dogs during intravenous infusion of angiotensin II, phenylephrine, or arginine vasopressin at rates which increased arterial pressure by 20-40 mmHg. The arteries supplying these beds were instrumented with an electromagnetic flow probe, a nonoccluding catheter, and an electromagnetic flow probe, a nonoccluding catheter, and an occluder cuff connected with a servo-amplifier, which enabled us to return perfusion pressure to control levels during infusion of the vasoconstrictor agents. We attempted to differentiate between the increase in vascular resistance due to the direct effect of the vasoconstrictor agent and the increase induced by an autoregulatory response induced by elevations of aortic perfusion pressure. We measured a strong degree of autoregulation in the renal vascular bed with a fractional compensation value close to 1. Moderate autoregulation occurred in the mesenteric vascular bed, where the compensation was 0.4-0.5 with angiotensin II and phenylephrine and between 0.74 and 0.94 with vasopressin. No autoregulatory capacity could be demonstrated in the hindlimb. The findings indicate that, under conditions of increased systemic blood pressure, both the renal and the mesenteric vascular beds contribute to the increase in total peripheral resistance by pressure-dependent vasoconstrictor responses.
Differential effects of caffeine on skinned fibers from control and hypertrophied ferret hearts
Authors: Baudet S. , Ventura-Clapier R.
Published: December 2017

The effects of caffeine on the mechanical properties of detergent-skinned fibers from control and pressure-overloaded ferret hearts have been compared. Right ventricle hypertrophy was studied 6 wk after pulmonary artery ligation, an intervention that increased the right ventricular weight-body weight ratio by 60%. Although no changes were observed in the Ca sensitivity of contraction between control [pCa for one-half-maximal activation (pCa50) = 5.80 +/- 0.05] and hypertrophied (pCa50 = 5.85 +/- 0.02) muscles, the leftward shift of the force-pCa relationship induced by caffeine was more pronounced in hypertrophied fibers than in control; pCa50, was 5.86 +/- 0.02, 5.94 +/- 0.01, 6.03 +/- 0.01 in control and 5.97 +/- 0.03, 6.10 +/- 0.03, 6.24 +/- 0.01 in control and 5.97 +/- 0.03, 6.10 +/- 0.03, 6.24 +/- 0.03 in hypertrophied fibers for 2, 5, 10 mM caffeine, respectively. This was accompanied in the hypertrophied muscles by a decrease in the Hill coefficient. On the other hand, maximal force was not affected by 10 mM caffeine. From these results it is possible that the site of action of caffeine in myofibrillar proteins is the thin filament. The increased responsiveness of hypertrophied fibers to caffeine may be mediated by a pressure overload-induced change in the thin filament regulatory proteins. Moreover, inotropic agents may act differently in hypertrophied than in control myocardium.
Cytochemical studies of hydrogen peroxide generation in postischemic hepatocytes
Authors: Babbs C. F. , Salaris S. C. , Turek J. J.
Published: December 2017

Reoxygenation injury that occurs when blood circulation is restored to previously ischemic tissues is currently discussed as a pathophysiological entity distinct from the primary anoxic injury that develops during ischemia per se. To test the hypothesis that reoxygenation injury in hepatocytes is caused by a postischemic burst of reactive oxygen species (ROS), including superoxide radicals, O2-., and hydrogen peroxide, H2O2, we performed a cytochemical study exploiting the peroxidase activity within peroxisomes as a sensitive ultrastructural detector of intracellular H2O2 generation. The osmiophilic polymer formed when tissue peroxidase is incubated with 3,3'-diaminobenzidine (DAB) and H2O2 was used as a marker for endogenous H2O2 in rat liver slices in short-term organ culture subjected to a cycle of 60-min ischemic anoxia and 30-min reoxygenation in the presence of DAB without exogenous H2O2. Peroxisomal reaction product was quantitatively evaluated in transmission electron micrographs of systematically sampled hepatocytes. Mean densities of positive peroxisomes per 1,000 micron2 (+/- SE) in liver slices subjected to various treatments were as follows: continuous anoxia (negative control) 0 +/- 0; normoxia + exogenous H2O2 (positive control) 45 +/- 12; normoxia only 26 +/- 2; ischemia-reoxygenation 13 +/- 6; ischemia-reoxygenation + xanthine oxidase inhibitor, oxypurinol 5 +/- 3; ischemia-reoxygenation + peroxidase inhibitor, aminotriazole 7 +/- 3. Endogenous H2O2 can be detected in hepatocytes by electron microscopic cytochemistry and may in part derive from xanthine oxidase, but it is not substantially increased in the postischemic state. We conclude that hepatocytes do not exhibit a postischemic burst of reactive oxygen species that could cause reoxygenation injury.
Renal sympathetic nerve and hemodynamic responses to captopril in conscious dogs: role of prostaglandins
Authors: Zucker I. H. , Chen J. S. , Wang W.
Published: December 2017

The angiotensin converting enzyme inhibitor captopril has been shown to cause resetting of the arterial baroreflex to a lower pressure without a change in gain. The present study was conducted to determine whether captopril altered the relationship between arterial pressure, heart rate, and renal sympathetic nerve activity in conscious quietly resting dogs. Fourteen instrumented dogs were given 2 mg/kg iv of captopril; 10 min later postcaptopril measurements were made. Six of the fourteen dogs were pretreated with cyclooxygenase inhibitor (indomethacin or meclofenamate) before administration of captopril. Renal nerve activity and hemodynamics were measured in a final group of eight dogs in which arterial pressure was lowered with a graded infusion of sodium nitroprusside. Captopril caused a small but significant decrease in arterial pressure. This decrease in arterial pressure was accompanied by a significant increase in heart rate; however, renal sympathetic nerve activity was significantly reduced. In contrast, dogs receiving nitroprusside exhibited an increase in both heart rate and renal sympathetic nerve activity in response to similar decreases in arterial pressure. Dogs that received cyclooxygenase inhibitor showed reduced arterial pressure in response to captopril, increased heart rate, and increased renal sympathetic nerve activity. This study is the first to report a decrease in sympathetic nerve activity in response to captopril in an awake chronically instrumented animals. These data suggest that captopril's ability to augment prostaglandin synthesis is responsible for the observed sympathoinhibition.