bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial relaxant effect of exogenous nitric oxide in isolated ejecting hearts
Authors: Grocott-Mason R. , Fort S. , Lewis M. J. , Shah A. M.
Published: December 2017

In isolated myocytes and papillary muscles, both nitric oxide, acting through guanosine 3',5'-cyclic monophosphate (cGMP), and cGMP analogues exert a novel effect on myocardial contraction, influencing mainly the onset of relaxation. We studied the effect of the exogenous nitric oxide donor, sodium nitroprusside (0.1-10 microM), in isolated ejecting guinea pig hearts at constant filling pressure, afterload, and heart rate to identify its direct myocardial effects in the whole heart. Sodium nitroprusside induced concentration-dependent increases in coronary flow as well as premature and faster early left ventricular (LV) pressure decline, but did not change end-diastolic or peak LV pressure or peak rate of rise of LV pressure. There was no correlation between changes in coronary flow and LV pressure decline. Sodium nitroprusside effects were inhibited by hemoglobin, which inactivates nitric oxide. The cGMP-independent vasodilator nicardipine also increased coronary flow but did not influence early LV pressure fall. Thus exogenous nitric oxide exerts novel direct myocardial relaxant effects in the isolated ejecting heart, independent of its known vasodilator activity, and without compromising systolic function.
Inhibition of the calcium paradox in isolated rat hearts by high perfusate sucrose concentrations
Authors: Omachi A. , Kleps R. A. , Henderson T. O. , Labotka R. J.
Published: December 2017

If a colloid osmotic (oncotic) pressure gradient develops across the myocyte membrane during the calcium paradox, adding an oncotic agent to the perfusate should be inhibitory. After 10-min perfusion with Ca(2+)-free Krebs-Henseleit (KH) buffer under constant flow at 34 degrees C, myoglobin release was measured from Langendorff hearts reperfused with Ca(2+)-containing KH buffer. When the Ca(2+)-free medium contained 200 mM sucrose, myoglobin release was reduced to 5% of that observed in the absence of sucrose, a change that was not seen when 200 mosM NaCl, choline chloride, LiCl, or glycerol was added. Replacement of 75 mM NaCl in the perfusate with 150 mM sucrose resulted in myoglobin release values that were 4% of the control. Plots of myoglobin release against sucrose concentration under these hypertonic and isotonic conditions yielded similar though separate curves. Sucrose also inhibited increases in wet weight-to-dry weight ratio and decreases in ATP and phosphocreatine contents. These results support the hypothesis that an oncotic pressure gradient arises during the calcium paradox at the moment of increased membrane permeability and plays a major role in its development.
Endothelial actin cytoskeleton in rat mesentery microvasculature
Authors: Thurston G. , Baldwin A. L.
Published: December 2017

The actin cytoskeleton plays a key role in maintaining and modulating cellular morphology and thus is important in various aspects of endothelial cell function, yet few studies to date have studied the endothelial actin cytoskeleton in the microvasculature, where many of the specialized endothelial functions take place. We developed a method to fix and stain the microvasculature of the rat mesentery under physiological conditions and used a confocal microscope to observe the pattern of actin filaments in individual endothelial cells throughout the intact vascular network. We observed several distinct patterns of actin filaments in the endothelial cells depending on the caliber and type of vessel. The endothelial cells of large arterioles and venules (> 50 microns in diameter) displayed a prominent circumferential rim of actin, with few central actin fibers. Endothelium of midsized (20-50 microns) arterioles (and some midsized venules) displayed prominent abluminal actin fibers across the central portion of the cell, aligned parallel to the longitudinal axis of the vessel, in addition to a peripheral rim of actin. The endothelium of capillaries contained few actin fibers but instead typically displayed diffuse staining throughout the cell. The endothelial cells in the postcapillary venules generally displayed a thin peripheral rim of actin and occasional short central fibers. These results indicate that the local environment dictates the actin pattern in endothelial cells and suggests that specialized endothelial function is correlated with specialized endothelial actin architecture.
Hypertonic hydroxyethyl starch restores hepatic microvascular perfusion in hemorrhagic shock
Authors: Vollmar B. , Lang G. , Menger M. D. , Messmer K.
Published: December 2017

The influence of small-volume resuscitation (hypertonic saline-10% hydroxyethyl starch, HS/HES) on liver microcirculation (intravital fluorescence microscopy) was studied in a nonheparinized hemorrhagic shock model [mean arterial pressure (MAP) 40 mmHg for 1 h] in rats. Resuscitation was performed with Ringer lactate (RL, 4-fold shed volume/20 min; n = 7), 10% hydroxyethyl starch 200/0.6 (HES, shed volume/5 min; n = 6), or 7.2% NaCl-10% hydroxyethyl starch 200/0.6 (HS/HES, 10% shed volume/2 min; n = 7). One hour after resuscitation, MAP increased in all groups, but it did not return to preshock values (P < 0.05). HES (16 +/- 2% nonperfused sinusoids) and HS/HES (14 +/- 2% nonperfused sinusoids), but not RL (24 +/- 2% nonperfused sinusoids), reduced (P < 0.05) shock-induced sinusoidal perfusion failure (28 +/- 3%) with restoration of leukocyte velocity in sinusoids (S) and postsinusoidal venules (V). Shock-induced stasis/adherence of leukocytes was further increased (P < 0.05) after resuscitation with RL (S, 38 +/- 6%; V, 55 +/- 20%) and HES (S, 31 +/- 8%; V, 23 +/- 14%). In contrast, resuscitation with HS/HES prevented increased leukocyte stasis in sinusoids (-4 +/- 4%) as well as adherence to endothelial lining of postsinusoidal venules (-5 +/- 10%). We conclude that replacement of only 10% of actual blood loss by means of small-volume resuscitation (HS/HES) can restore hepatic microvascular perfusion and prevent reperfusion-induced leukocyte stasis/adherence.
Accelerated myocardial relaxation in conscious dogs during acute cardiac tamponade
Authors: Nishikawa Y. , Roberts J. P. , Talcott M. R. , Dysko R. C. , Tan P. , Klopfenstein H. S.
Published: December 2017

Eight chronically instrumented conscious dogs were used to test the hypothesis that left ventricular (LV) relaxation is accelerated during cardiac tamponade. The time constant of LV transmural pressure fall was measured before and during intrapericardial (IP) saline infusion (baseline) with and without beta-adrenergic blockade (propranolol 1 mg/kg iv). Heart rate was controlled by atrial pacing. Increasing IP pressure caused a progressive linear decrease in stroke volume before and during beta-blockade in each animal. The time constant of LV transmural pressure fall also decreased continuously with an increase in IP pressure from 26 +/- 7 ms during baseline to 18 +/- 5 ms during severe cardiac tamponade (P < 0.01) before beta-blockade. However, after beta-blockade, the time constant of LV transmural pressure fall was constant over a wide range of IP pressures despite a continuous decrease in LV end-diastolic volume. The time constant of LV transmural pressure fall was not altered by vena caval occlusions that caused the same decrease in LV preload observed during cardiac tamponade. We concluded that despite decreased pump function, LV relaxation was accelerated progressively during graded cardiac tamponade, and this change was dependent not on changes in loading conditions but on an intact beta-adrenergic influence.
Release of atrial natriuretic peptide in brief ischemia-reperfusion in isolated rat hearts
Authors: Arad M. , Zamir N. , Horowitz L. , Oxman T. , Rabinowitz B.
Published: December 2017

We studied the effects of short-term global ischemia and reperfusion on ANP secretion from Langendorff-perfused rat hearts compared with isolated ventricles. Effects of regional ischemia, with or without increased atrial pressure, were examined in Langendorff-perfused and working heart models. Five minutes of global ischemia were associated with elevated levels of atrial natriuretic peptide (ANP) in the coronary effluent immediately and for approximately 10 min after resumption of reperfusion, resulting in a net hormone excess of 23 +/- 5 ng/g wet wt. The ventricles produced on the average 11% ANP compared with the whole heart, and their contribution of to postischemic ANP overflow was approximately proportional to their basal production. In Langendorff-perfused hearts, regional ischemia increased the concentration of ANP in the coronary effluent 51 +/- 11%, whereas the secretion rate (per minute) decreased 18 +/- 5%. In the presence of atrial distension in the working heart model, a trend for increase in ANP secretion was apparent. We conclude that global ischemia, even of brief duration, has an independent stimulatory effect on ANP release, the ischemic atrium being responsible for most of the excess. Regional ischemia, when not accompanied by atrial distention, reduces the ANP secretion rate during the ischemic period. Heart failure secondary to ischemia stimulates ANP secretion, but this response seems to be both delayed and attenuated compared with atrial stretch alone.
Baroreflex modulation of blood pressure and heart rate variabilities in rats: assessment by spectral analysis
Authors: Cerutti C. , Barres C. , Paultre C.
Published: December 2017

The role of the baroreflex in the spectral characteristics of mean arterial pressure (MAP) and heart rate (HR) was investigated in 12 control rats and 9 rats with chronic sinoaortic baroreceptor denervation (SAD) during 1) basal conditions and 2) ganglionic blockade with chlorisondamine and restoration of the basal MAP level. In SAD rats, power spectral density of MAP, estimated by a fast Fourier transform, was reduced in the low-frequency (LF, 0.27- to 0.74-Hz) band. Ganglionic blockade highly decreased LF power spectral density of MAP in control rats. No relationship was found between the MAP response to chlorisondamine, taken as an index of the sympathetic vasomotor tone, and the basal LF power spectral density. Transfer function analysis between MAP and HR showed that, in control rats, coherence was high for frequencies surrounding the LF and high-frequency peaks. In SAD rats, coherence was abolished in the LF band but maintained in the high-frequency band. In conclusion, approximately 80% of the LF power spectral density of MAP depends on the sympathetic nervous system activity, and the baroreflex accounts for one-half of this power and for the coherence between MAP and HR oscillations in the LF band.
Nucleoside-induced arteriolar constriction: a mast cell-dependent response
Authors: Doyle M. P. , Linden J. , Duling B. R.
Published: December 2017

Adenosine (Ado) is a potent vasodilator that has occasionally been shown to cause vasoconstriction. Constrictor responses are generally attributed to A1-receptor stimulation or interactions with the renin-angiotensin system. We describe a previously unreported vasoconstrictor action of Ado and inosine (Ino) in hamster cheek pouch arterioles and examine the mechanism by which these nucleosides induce constriction. Arterioles were dissected from male Golden hamster cheek pouches, transferred to a 37 degrees C tissue chamber, and cannulated at both ends. Changes of luminal diameter in response to Ado were measured to generate cumulative concentration-response curves. The concentration-response curves were biphasic: 10(-6) M Ado elicited an intense, transient constriction, and higher concentrations induced dilator responses. Pretreatment with 8(p-sulfophenyl)theophylline, an Ado receptor antagonist, inhibited the dilator responses but did not alter the constriction. Inhibition of Ado uptake with S-(4-nitrobenzyl)-6-thio-inosine eliminated the constrictor response without altering dilator responses. Similar effects were found after pretreatment with an Ado deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride. Finally, Ino, a metabolite of Ado, induced constrictions of similar magnitude to those seen with Ado, but at higher concentrations. The constrictor response was focal in nature, suggesting discrete sites of action of Ado. Methylene blue staining after Ado application revealed degranulated mast cells closely associated with the vessel wall, indicating a possible role for mast cell degranulation in the constrictor response. Supporting this idea were the observations that inhibition of degranulation by 10 microM cromolyn blocked the constrictor response, and compound 48/80 (a mast cell secretagogue) caused constriction similar to that elicited by Ado.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of enalaprilat on splanchnic vascular capacitance during acute ischemic heart failure in dogs
Authors: Risoe C. , Hall C. , Smiseth O. A.
Published: December 2017

This study investigates the effect of angiotensin-converting-enzyme inhibition by intravenous enalaprilat (100 micrograms/kg) on splanchnic vascular capacitance during acute left ventricular failure induced by coronary microembolization in alpha-chloralose/urethan anesthetized dogs. Changes in hepatic and splenic vascular volumes were determined from organ diameters (sonomicrometry) at 15, 30, and 45 min after enalaprilat injection. Changes in vascular capacitance were assessed from organ pressure-diameter curves obtained during transient hepatic outflow occlusion. Thirty minutes after enalaprilat, hepatic volume was increased by 52 +/- 14 ml (P < 0.01), and portal and hepatic vein pressures were decreased from 10.2 +/- 0.9 to 8.7 +/- 0.8 mmHg (P < 0.01) and from 3.9 +/- 1.6 to 3.1 +/- 0.7 mmHg (P < 0.05), respectively. Splenic volume did not change. Enalaprilat shifted the hepatic pressure-diameter curve upward, resulting in a larger hepatic volume at any given pressure. Curve intercept was increased, suggesting an increase in unstressed vascular volume. Curve slope was unchanged. In conclusion, enalaprilat increased hepatic vascular volume during acute left ventricular failure in dogs. The pressure-diameter curve shift suggests a reduction in the smooth muscle tone of hepatic capacitance vessels.
Propionyl-L-carnitine prevents myocardial mechanical alterations due to pressure overload in rats
Authors: Micheletti R. , Giacalone G. , Canepari M. , Salardi S. , Bianchi G. , Reggiani C.
Published: December 2017

This study investigated if propionyl-L-carnitine (PLC) treatment can directly affect cardiac mechanics, secondary to increase in myocardial carnitine content, in rats with aortic constriction and sham-operated controls. After weaning, rats were fed one of the following diets for 8 wk: 1) a low-carnitine diet (containing 2 nmol/g carnitine); 2) the same diet supplemented with PLC (710 mumol/kg body wt); 3) L-carnitine (LC; 118 mumol/kg body wt, given in tap water; or 4) a standard diet (containing 56 nmol/g carnitine). A 4-wk constriction of the abdominal aorta caused left ventricular hypertrophy associated with significantly prolonged timing parameters and reduced rate of tension decay in papillary muscles. In group 2, however, PLC treatment prevented hypertrophy-induced changes in these parameters and the reduction in unloaded shortening velocity in skinned trabeculae. Finally, PLC treatment maintained the relative proportion of myosin heavy chain isoforms in left ventricular wall of animals subjected to aortic constriction. Both PLC and LC completely prevented carnitine depletion due to hypertrophy and to dietary restriction. Because LC did not modify papillary muscle contractile function, these results demonstrate that PLC affects hypertrophy-induced changes in muscle mechanics and ventricular wall composition independently of tissue carnitine levels.
Depressed [Ca2+]i responses to isoproterenol and cAMP in isolated cardiomyocytes from experimental diabetic rats
Authors: Yu Z. , Quamme G. A. , McNeill J. H.
Published: December 2017

Experimentally, diabetic rat hearts are characterized by diminished responses to beta-adrenergic stimulation. Among the aberrant responses are diminished beta-adrenoceptor number and depressed contractile protein activity. In this study, intracellular Ca2+ concentration ([Ca2+]i) was determined by microfluorescence in response to beta-adrenergic stimulation to understand the basis for the changes in the beta-adrenergic pathway in diabetic myocardium. In quiescent myocytes, isoproterenol caused a decrease in [Ca2+]i, which was blocked by timolol and thapsigargin. This suggests that the beta-agonist-induced [Ca2+]i changes are mediated, in part, by sarcoplasmic reticulum Ca-adenosinetriphosphatase. Diabetic myocytes showed a blunted response to isoproterenol, which was reversed by insulin treatment. In electrically stimulated myocytes, isoproterenol and 8-bromo-adenosine 3',5'-cyclic monophosphate (cAMP) increased [Ca2+]i and contraction in a concentration-dependent manner. Electrically stimulated diabetic myocytes demonstrated a depressed maximum [Ca2+]i response to isoproterenol and 8-bromo-cAMP without a change in sensitivity. These data suggest that in addition to alterations in beta-adrenoceptor function there are postreceptor defects in diabetic myocardium that may impair the regulation of [Ca2+]i in diabetic myocardium.
Prolongation and shortening of action potentials by electrical shocks in frog ventricular muscle
Authors: Knisley S. B. , Smith W. M. , Ideker R. E.
Published: December 2017

Effects of electrical shocks on myocardium are important for defibrillation. We measured effects of shocks (5 ms, 1–40 V/cm) in isolated frog ventricular strips. We recorded contraction strength and intracellular action potential (AP) with a shock-voltage cancellation technique to allow recordings immediately after shocks. Shocks of > or = 5 V/cm produced a dose- and latency-dependent prolongation of the AP ongoing during the shock. Stronger shocks of 28–40 V/cm decreased the duration, maximum diastolic potential, amplitude, and maximum rate of rise of the phase zero depolarization of paced APs that began after the shock. The contraction strength increased 43 and 59% during the 10 s after the stronger shocks. The transmembrane potential was shifted toward 0 mV immediately after the stronger shocks. We concluded that weak or strong shocks prolong the AP ongoing during the shock, whereas sufficiently strong shocks also shorten APs that begin after the shock. AP prolongation and shortening may be important for defibrillation and acceleration of tachycardia after failed cardioversion shocks.
Venoconstriction of hepatic capacitance vessels during hemorrhage in cats: efferent mechanisms
Authors: Greenway C. V. , Innes I. R. , Scott G. D.
Published: December 2017

Cats anesthetized with pentobarbital sodium were hemorrhaged (1 ml.min-1.kg body wt-1) until arterial pressure declined to 55 mmHg. Hepatic volume was recorded by plethysmography. In controls, 20 +/- 5 (SD) ml/kg was removed and hepatic volume decreased 3.6 +/- 0.8 ml/kg. Splanchnic nerve section or administration of hexamethonium-atropine reduced hemorrhage volumes (to 10.3 +/- 2.3 and 4.8 +/- 1.8 ml/kg, respectively) and liver volume changes (to 1.5 +/- 0.5 and 0.7 +/- 0.3 ml/kg, respectively). Section of only the hepatic nerves had no effect on hemorrhage volume or the decrease in hepatic volume. Section of the hepatic nerves after removal of the adrenals and kidneys also had no significant effect on hemorrhage volume or the decrease in liver volume. We conclude that the hepatic capacitance response to hemorrhage does not require direct sympathetic venoconstriction of the hepatic capacitance vessels. Changes in inferior vena caval pressure play a significant but small role. The splanchnic nerves (excluding hepatic nerves) play a major role, possibly by splanchnic arteriolar constriction. Whereas the liver comprises only 2.5% of the body weight, it contributed 18% of the hemorrhage volume.
Effects of high-dose intracoronary irradiation on vasomotor function and smooth muscle histopathology
Authors: Wiedermann J. G. , Leavy J. A. , Amols H. , Schwartz A. , Homma S. , Marboe C. , Weinberger J.
Published: December 2017

A significant component of restenosis after coronary angioplasty is due to medial proliferation. Targeted ablation of the proliferating cells by ionizing radiation may prevent restenosis. We delivered high-dose intracoronary gamma-irradiation in porcine coronary arteries and assessed vasomotor function acutely and at 32 days, with pathological analysis at 32 days. Changes in luminal area were assessed by intravascular ultrasound. Irradiated segments acutely displayed vasoconstriction to acetylcholine, with loss of smooth muscle response to nitroglycerin. Restudy revealed restoration of normal vasodilatory response to acetylcholine but persistent loss of response to nitroglycerin. Histopathology at 32 days revealed minor neointima formation without luminal compromise and diffuse fibrosis of the smooth muscle layer. The surrounding myocardium was normal. Focal medial fibrosis without significant endothelial or myocardial damage can be achieved via this technique; intracoronary irradiation, therefore, may be an effective way of impairing the restenosis process.
On the approximation of static open-loop characteristics of baroreceptor reflex
Authors: Burattini R. , Socionovo G. , Bellocchi F.
Published: December 2017

We investigated the adequacy of three different functions that have been used in the literature to characterize the relationship between mean systemic arterial pressure (SAP) and mean baroreceptor pressure (BP) in open-loop experimental preparations. These curves are the normal cumulative distribution function (CDF), the logistic (or growth) function (LF), and the third-order polynomial (TOP). Ten sets of experimental data from isolated carotid sinus preparations were selected from the literature as being representative of all baroreflex curves. Then, the Levenberg-Marquardt method was used to obtain best least-square approximation to these data and parameter estimates for each of the three approximating curves. The first derivative of each best-fit SAP-BP curve yielded a curve for the open-loop gain (G) as a function of BP. Our analysis indicated that both the CDF and the LF were superior to the TOP in fitting the SAP-BP data and in giving a realistic description of the G-BP curve. The operative range of BP was evaluated by estimating threshold (BPth) and saturation (BPsat) BPs using arbitrary definitions reported in the literature. The TOP did not allow this evaluation. The other two curves showed some disagreement due to different definitions of BPth and BPsat. After modifying the definition of these parameters associated with the LF, we could conclude that the analytical descriptions of SAP-BP and G-BP curves as obtained from the LF and the CDF were practically equivalent. Approximation method using the TOP should be avoided.
Corelease of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles
Authors: Koller A. , Sun D. , Huang A. , Kaley G.
Published: December 2017

We have studied the mechanisms responsible for the mediation of flow (shear stress)-induced dilation of isolated arterioles of rat gracilis muscle. Active diameter of arterioles at a constant perfusion pressure (PP, 80 mmHg) was approximately 92 microns, while their passive diameter (Ca(2+)-free solution) was approximately 165 microns. At a constant PP the stepwise increase in flow of the perfusion solution (PS, 0-60 microliters/min in 10-microliters/min steps) elicited a gradual increase in diameter up to approximately 140 microns. Flow-induced dilations were eliminated by the removal of the endothelium of arterioles (by air). Dilations were significantly reduced by the cyclooxygenase blocker, indomethacin (Indo, 10(-5) M), by the nitric oxide synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), or by the endothelium-derived relaxing factor inhibitor, oxyhemoglobin (Hb, 10(-5) M), as indicated by the significant changes in the slope of the regression lines of the flow-diameter curves. For example, during administration of the inhibitors, dilation to 60 microliters/min perfusate flow was reduced by 41.1, 54.3, and 39.3%, respectively. Combined application of Indo and L-NNA almost completely eliminated flow-induced dilation. Arteriolar dilation maintained calculated wall shear stress close to control values (approximately 30 dyn/cm2 at 60 microliters/min) despite increases in flow, but when the dilation was inhibited by removal of the endothelium or by the combined administration of Indo and L-NNA, wall shear stress was greatly increased as a function of increases in flow of the PS (approximately 125 dyn/cm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Nonreceptor-mediated intestinal vasoconstriction in portal hypertensive rats
Authors: Wu Z. Y. , Benoit J. N.
Published: December 2017

Previous studies have demonstrated that receptor-mediated vasoconstriction is impaired in chronic portal hypertension (PH). Furthermore, it has been suggested that altered vasoconstrictor effectiveness in chronic PH is due to a defect in the intracellular events associated with smooth muscle activation and not to impaired coupling of vasoconstrictors with vascular smooth muscle receptors. The present study was designed to determine whether nonreceptor-mediated vasoconstrictor responses are impaired in the PH intestinal microcirculation. Specifically, we examined the effects of aluminum fluoride-induced activation of G proteins, KCl-induced depolarization, caffeine-induced release of intracellular Ca2+, and l-indolactam-induced activation of protein kinase C on the intestinal microcirculation of normal (Norm, n = 39) and PH (n = 42) rats. The small intestine was prepared for microcirculatory studies and transferred to a video microscope. First-order arteriolar (1A) diameter and red cell velocity were measured on-line. Blood flow was calculated from the product of velocity and microvessel cross-sectional area. After a control period, the microvasculature was exposed to a solution containing aluminum chloride plus sodium fluoride, potassium chloride, caffeine, or l-indolactam. Maximal decreases in arteriolar diameter produced by aluminum fluoride, KCl, caffeine, and l-indolactam were significantly greater in Norm rats when compared with PH rats. Changes in arteriolar blood flow were also larger in Norm than in PH rats. The results of the present study provide the first direct evidence of an impaired response to second-messenger activation in the PH circulation.
Effect of pregnancy on contraction and endothelium-mediated relaxation of renal and mesenteric arteries
Authors: Kim T. H. , Weiner C. P. , Thompson L. P.
Published: December 2017

We have hypothesized that differences in the effect of pregnancy on mechanisms modulating vascular reactivity underlie the redistribution of cardiac output. Because pregnancy increases mesenteric blood flow by 75% and renal blood flow by only 10% in the guinea pig, we investigated the effect of pregnancy on vascular reactivity in these two beds. Relaxation in response to acetylcholine (ACh), an endothelium-dependent relaxing agent, and contraction induced by the thromboxane mimetic U-46619 were measured in ring segments of mesenteric and renal arteries from pregnant and nonpregnant guinea pigs. To determine the role of the endothelium, nitric oxide (NO), and vasodilator prostaglandins in modulating vascular response, rings were denuded, treated with N omega-nitro-L-arginine (L-NNA) to inhibit NO synthase, or treated with indomethacin to inhibit cyclooxygenase. Pregnancy increased ACh-stimulated relaxation of mesenteric arteries but not renal arteries. L-NNA significantly reduced ACh sensitivity (based on the concentration that produced 50% of the maximal response) in arteries from pregnant and nonpregnant animals, and indomethacin slightly decreased maximal relaxation only in the renal artery of nonpregnant animals. ACh sensitivity of mesenteric arteries was still increased after L-NNA or indomethacin. Pregnancy reduced the threshold concentration of U-46619 in mesenteric artery but had no effect on contraction of renal artery. Contraction of both arteries was enhanced by denudation. L-NNA and indomethacin were less effective than denudation in arteries from pregnant and nonpregnant animals, which suggests that pregnancy alters thromboxane contraction by endothelium-dependent mechanisms other than NO and prostaglandins. Thus, pregnancy differentially alters vascular reactivity of mesenteric and renal arteries in the guinea pig.
Metabolic recovery of isolated working rat heart after brief global ischemia
Authors: Goodwin G. W. , Taegtmeyer H.
Published: December 2017

Functional recovery following ischemia and reperfusion in the isolated working rat heart perfused with glucose (11 mM) was examined in relation to pre- and postischemic levels of ATP, glycogen, glucose 6-phosphate, and the lactate-to-pyruvate ratio. The following variables were studied: feeding and fasting in vivo, addition of L-lactate (10 mM), dl-beta-hydroxybutyrate (10 mM), glucagon (0.01 and 1 micrograms/ml), and a 15-min anoxic perfusion before ischemia in vitro. Recovery was assessed as the percentage of preischemic power. Good correlation was found between functional recovery and the postischemic content of glycogen. Glycogen depletion by anoxia or glucagon before ischemia impaired recovery. There was no relationship among lactate produced, or the lactate-to-pyruvate ratio, and recovery. The addition of lactate or beta-hydroxybutyrate to hearts from fed rats increased the content of glycogen and glucose 6-phosphate, whereas addition of lactate, but not beta-hydroxybutyrate, improved recovery. There was a linear relationship between glycogen content and glucose 6-phosphate levels. In conclusion, the degree of return of oxidative metabolism and of net glycogen resynthesis reflects postischemic recovery of function. The results also suggest a role for anaplerosis of the citric acid cycle as an additional determinant of postischemic recovery.
Importance of sodium for recovery of calcium control in reoxygenated cardiomyocytes
Authors: Siegmund B. , Ladilov Y. V. , Piper H. M.
Published: December 2017

The role of Na+ in the recovery from severe anoxic Ca2+ overload was investigated in isolated quiescent ventricular cardiomyocytes from adult rat. Changes of cytosolic Ca2+ and Na+ concentrations were followed by the fura 2 and Na(+)-binding benzofuran isophthalate techniques, respectively. When the fura 2 ratio (340/380 nm) reached saturation in anoxic cells, indicating a severe cytosolic Ca2+ overload, the cells were reoxygenated. This caused a rapid initial drop of cytosolic Ca2+ to a lower but still elevated level (phase I), followed by oscillatory Ca2+ transients at this level (phase II) and, within 10 min, the reestablishment of a stable cytosolic Ca2+ concentration at the normal resting level (phase III). As previously shown [B. Siegmund, R. Zude, and H. M. Piper. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1262–H1269, 1992], Ca2+ shifts in phase I and II are mainly due to uptake and release of Ca2+ by the sarcoplasmic reticulum. Phase I was unchanged, and phase II was much prolonged (> 60 min) in cells reoxygenated under Na+ pump inhibition (0.2 mM ouabain) or Na+ depletion. Phase III could only be reestablished (< 10 min) when ouabain was eluted or external Na+ replenished, respectively. The results show that full recovery of cytosolic Ca2+ control (phase III) requires an active sarcolemmal Na+ pump and the availability of external Na+. This indicates that phase III is determined by the transsarcolemmal extrusion of Ca2+ by a tandem mechanism consisting of 1) the Na+ pump, generating an extracellular-to-intracellular Na+ gradient, and 2) the sarcolemmal Na+/Ca2+ exchange, driven by that gradient to extrude Ca2+.
The blood pressure buffering capacity of nitric oxide by comparison to the baroreceptor reflex
Authors: Just A. , Wittmann U. , Nafz B. , Wagner C. D. , Ehmke H. , Kirchheim H. R. , Persson P. B.
Published: December 2017

To compare the contribution of nitric oxide (NO) to the buffering of short-term and circadian fluctuations of arterial blood pressure with that of the baroreceptor reflex, conscious foxhounds were subjected to continuous 24-h blood pressure recordings. A pressure transducer was placed into the lumen of the abdominal aorta. Telemetry recordings were done under control conditions, following blockade of NO formation by intravenous bolus injection of NG-nitro-L-arginine (L-NNA; 16.5 +/- 2 mg/kg body wt) and after total sinoaortic and cardiopulmonary denervation in five dogs each. L-NNA produced a sustained elevation of mean arterial pressure (MAP; 137.2 +/- 6.4 mmHg vs. control, 112.9 +/- 3.7 mmHg). After denervation, no significant increase of MAP was found (113.5 +/- 4.1 mmHg), but the standard deviation of the MAP histogram was significantly greater (22.5 +/- 3.1 vs. 10.6 +/- 0.9 mmHg, P < 0.05). Sequential spectral analysis showed that total power between 0 and 0.5 Hz was elevated more than twofold after L-NNA (P < 0.05). This was due primarily to increased power in the range above 0.1 Hz. After denervation, total power increased about three-fold (P < 0.05), almost exclusively occurring below 0.04 Hz. Power in the range above 0.2 Hz was diminished, although not significantly. It is concluded that in the conscious dog, NO, as well as the baroreceptor reflex, is an effective blood pressure buffer. NO is most effective above 0.1 Hz, whereas the baroreceptors primarily buffer fluctuations slower than 0.04 Hz.
Preservation of high regional blood flow at epicardial rim after coronary occlusion in dogs
Authors: Ishikawa K. , Kamata N. , Nakai S. , Akiyama H. , Koka H. , Ogawa I. , Katori R.
Published: December 2017

A thin myocardial layer adjacent to the epicardium (epicardial rim) often survives after transmural myocardial infarction. Regional myocardial blood flow (Qm) at this rim may be high enough to maintain myocardial viability during coronary occlusion. To test this hypothesis, we measured Qm in 12 anesthetized dogs during left anterior descending coronary artery occlusion using nonradioactive colored microspheres. Myocardium in the region supplied by the occluded artery was sliced into sections approximately 0.5 mm thick from the epicardial surface to the endocardium, and the Qm in each section was determined. During occlusion, the Qm of myocardium within 0.5 mm of the epicardial surface remained at 74.8 +/- 8.8% of the preocclusion level. Maintenance of this high Qm during occlusion was abolished when an epicardial incision approximately 1 mm deep was made around the occluded area. These findings suggest that Qm is maintained at a surprisingly high level at the epicardial rim after coronary occlusion through epicardial arterial communications, which may be sufficient to maintain myocardial viability.
Effects of oral calcium and potassium on endothelium-dependent relaxation in hypertensive rats
Authors: Peuler J. D. , Johnson B. A. , Schiebinger R. J. , Zemel M. B. , Iannucci A. R.
Published: December 2017

High oral potassium (K) decreases stroke incidence in aging high salt-fed stroke-prone spontaneously hypertensive rats (SHRSP). We have seen high oral Ca increase stroke incidence in aging high salt-fed SHRSP without increasing blood pressure (BP) but with signs of K wasting. Therefore, we sought to determine whether high oral Ca suppresses the previously reported oral K-related enhancement of arterial endothelium-dependent relaxation as seen in younger high salt-fed SHRSP before the appearance of strokes. Four groups of female SHRSP were fed high-salt diets containing either low (0.4%) or high (1.6%) K with low (0.4%) and high (1.6%) Ca from age 1 to 4 mos. High oral K decreased BP independent of Ca intake (P < 0.05). High oral Ca did not affect BP. In contrast to aging SHRSP, high oral Ca neither increased urinary excretion nor decreased plasma concentration of K in these young adult SHRSP. However, high (vs. low) oral K only significantly reduced the half-maximal effective dose for acetylcholine-induced relaxation of aortic rings from rats fed low (18 +/- 3 vs. 38 +/- 6 nM, P < 0.05) not high Ca (25 +/- 5 vs. 31 +/- 3 nM). Neither oral K nor Ca affected nitroprusside-induced relaxation. Thus high oral Ca by itself does not impair endothelium-dependent relaxation in young adult high salt-fed SHRSP, but yet it suppresses the enhancing effect of high oral K on such relaxation and does so without altering BP, K balance, or endothelium-independent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
G protein expression and adenylate cyclase regulation in ventricular cardiomyocytes from STZ-diabetic rats
Authors: Wichelhaus A. , Russ M. , Petersen S. , Eckel J.
Published: December 2017

Isolated adult ventricular cardiomyocytes have been used to study the effects of insulin-deficient diabetes on the expression of cardiac G protein alpha-subunits. Immunoblot analysis of plasma membranes revealed the presence of three different Gs proteins with molecular masses of 45, 47, and 52 kDa. Furthermore, cardiomyocytes were found to contain Gi-2 (41 kDa) and G(o) (39 kDa). Heart cells from streptozotocin-diabetic rats exhibited an unaltered expression of the Gs proteins, whereas Gi-2 and G(o) were reduced by 58 +/- 2 and 27 +/- 11%, respectively. In cells from diabetic rats, adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in response to isoproterenol decreased by approximately 30% at agonist concentrations of 10(-7) to 10(-5) M, with an unaltered maximum stimulation by forskolin. Treatment of cardiomyocytes with pertussis toxin resulted in an incremental increase of isoproterenol-stimulated cAMP formation, which was significantly lower in cardiac myocytes from streptozotocin-diabetic animals (19.2 +/- 1.7 vs. 11.5 +/- 2.4 pmol cAMP.5 x 10(4) cells-1 times 10 min-1). The inhibition of the isoproterenol-induced cAMP accumulation by carbachol in the intact cell was not altered in streptozotocin-diabetes. In conclusion, our data show that insulin-deficient diabetes is associated with a reduced expression and concomitant functional loss of Gi in ventricular cardiomyocytes. Receptor-mediated inhibition of adenylate cyclase remains unaffected by this process, whereas the beta-adrenergic stimulatory pathway involves an additional defect upstream of the adenylate cyclase/G protein system.
Assessment of ventricular relaxation in the developing chick embryo using a monoexponential model
Authors: Braunstein J. B. , Donovan M. , Hughes S. , Benson D. W.
Published: December 2017

In this study, the ventricular pressure decline during isovolumic relaxation in early diastole was modeled by regressing pressure and pressure change vs. time to a monoexponential formula: P(t) = P infinity+P0e-t/tau, where P(t) is ventricular pressure at time t, P infinity is the pressure in the fully relaxed ventricle, P0 is the pressure at the end of ventricular ejection, and tau is the ventricular relaxation rate constant. Analysis was performed on 330 ventricular pressure waveforms from 22 chick embryos, stages 17, 23, and 26, during baseline and following cardiac cycle length perturbation. Three computational models were evaluated. Based on analysis of the confidence intervals of estimates of P infinity and analysis of residuals, a least-squares nonlinear regression of pressure vs. time, which allowed estimates of tau and P infinity, best approximated the pressure decline. Isovolumic pressure decline in the embryonic heart is well approximated by a monoexponential model if both P infinity and tau are estimated. Negative values of P infinity during early stages of cardiac morphogenesis support the idea that diastolic suction plays a role in ventricular filling in the developing heart.
Transmyocardial impedance during single and multiple internal ventricular defibrillation shocks
Authors: Peters W. , Solingen S. , Kobayashi Y. , Scharf R. , Mandel W. J. , Gang E. S.
Published: December 2017

Little is known about the transmyocardial impedance during internal ventricular defibrillation. In a canine model, using high rate on-line digitization, random shock delivery, and titanium electrodes, we determined the relationship among voltage, current, and impedance, delivered energy, and defibrillation success within the individual and within successive defibrillation shocks. Impedance decreased with repeated defibrillation in 10 of 11 dogs. Impedance always increased during trapezoidal discharges, whereas voltage decreased. Impedance was lower with high energy-voltage shocks in all dogs. Visually, voltage and current waveform did not show a phase shift. There was no difference in the total energy delivered and the energy converted into heat by the resistive part of the impedance. With a formula valid only for resistive loads, the capacitance of the defibrillator was calculated to be within the measurement accuracy and tolerance of the factory-provided value of 132 microF. Polarization voltage was consistently observed. Thus the transmyocardial impedance during defibrillation is primarily resistive, nonlinear voltage dependent, and declines with successive shocks. Defibrillation success was not influenced by these phenomena.
Evidence against KATP channel involvement in adenosine receptor-mediated dilation of epicardial vessels
Authors: Makujina S. R. , Olanrewaju H. A. , Mustafa S. J.
Published: December 2017

The purpose of this study was to determine whether ATP-glyburide-sensitive K+ (KATP-glyburide) channels are involved in the adenosine-induced vasorelaxation of porcine and canine epicardial vessels in vitro. Adenosine and its analogues, 2-chloroadenosine (CAD), 5'-N-ethylcarboxamidoadenosine (NECA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), N6-cyclopentyladenosine (CPA), N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]adenosine (DPMA), 2-phenylaminoadenosine (CV-1808), 2-[m-(carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988), 2-[(2-cyclohexylethyl)amino]adenosine (CGS-22492), 2-[(p-amino)phenethylamino]adenosine (APE), and 2-(1-octynyl)adenosine (YT-146) (10 nM-100 microM), produced concentration-dependent relaxations in endothelium-intact and -denuded arterial ring segments contracted with 30 mM KCl, 10 nM endothelin-1, or 10 microM prostaglandin F2 alpha. Sodium nitroprusside (SNP; 1 nM-10 microM) and KATP-channel activator, pinacidil (10 nM-10 microM), also produced similar vasodilatory responses. Glyburide, a KATP-channel blocker, caused a rightward shift of the concentration-response curve to pinacidil but did not alter the responses elicited by SNP or adenosine and its analogues. The data suggest that KATP-glyburide channels are not involved in the mechanism whereby adenosine and its analogues elicit their vasorelaxant response in isolated porcine or canine epicardial vessels.
An experimental method for evaluating constitutive models of myocardium in in vivo hearts
Authors: Creswell L. L. , Moulton M. J. , Wyers S. G. , Pirolo J. S. , Fishman D. S. , Perman W. H. , Myers K. W. , Actis R. L. , Vannier M. W. , Szabo B. A. , et al.
Published: December 2017

A new experimental method for the evaluation of myocardial constitutive models combines magnetic resonance (MR) radiofrequency (RF) tissue-tagging techniques with iterative two-dimensional (2-D) nonlinear finite element (FE) analysis. For demonstration, a nonlinear isotropic constitutive model for passive diastolic expansion in the in vivo canine heart is evaluated. A 2-D early diastolic FE mesh was constructed with loading parameters for the ventricular chambers taken from mean early diastolic-to-late diastolic pressure changes measured during MR imaging. FE solution was performed for regional, intramyocardial ventricular wall strains using small-strain, small-displacement theory. Corresponding regional ventricular wall strains were computed independently using MR images that incorporated RF tissue tagging. Two unknown parameters were determined for an exponential strain energy function that maximized agreement between observed (from MR) and predicted (from FE analysis) regional wall strains. Extension of this methodology will provide a framework in which to evaluate the quality of myocardial constitutive models of arbitrary complexity on a regional basis.
Left ventricular size, mass, and function in relation to angiotensin-converting enzyme gene polymorphism in humans
Authors: Kupari M. , Perola M. , Koskinen P. , Virolainen J. , Karhunen P. J.
Published: December 2017

Angiotensin-converting enzyme (ACE) exhibits genetic variation related to insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene. The DD genotype results in high ACE activity and is overrepresented in diseases characterized by left ventricular (LV) hypertrophy and dysfunction. We studied whether the ACE gene polymorphism predicts LV mass or function in the absence of heart disease. Polymerase chain reaction of leukocyte DNA was used to determine the I/D genotype, and M-mode and Doppler echocardiography were used to quantify LV mass and function in 86 human subjects, 36-37 yr of age. All were free of clinical heart disease. The LV mass-to-body height ratio averaged 99 +/- 19 (SD) g/m in subjects with the II genotype (n = 25), 99 +/- 30 g/m in those with the ID genotype (n = 35), and 94 +/- 24 g/m in those with the DD genotype (n = 26; P = 0.790). The indexes of LV systolic and diastolic function were also unrelated to the ACE genotype. We conclude that in the absence of heart disease the ACE gene variation has no major influence on LV mass or function that is detectable at echocardiography.
Time course of postnatal changes in rat heart action potential and in transient outward current is different
Authors: Wahler G. M. , Dollinger S. J. , Smith J. M. , Flemal K. L.
Published: December 2017

The rat ventricular action potential shortens after birth. The contribution of increases in the transient outward current (Ito) to postnatal action potential shortening was assessed by measuring Ito in isolated cells and by determining the effect of 2 mM 4-aminopyridine (4-AP) on the action potentials of papillary muscles. 4-AP had no effect on 1-day action potential duration at 25% repolarization (APD25), and 1-day cells had little Ito. In 8- to 10-day muscles, 4-AP caused a small, but significant, increase in APD25. Ito increased slightly between day 1 and days 8-10, but this increase was not significant. Most of the increase in Ito (79%) and in the response to 4-AP (64%) occurred between days 8-10 and adult; however, approximately 75% of the APD25 shortening took place by days 8-10. Thus, while Ito may contribute to repolarization in late neonatal and adult cells, the different time courses of action potential shortening and increases in Ito suggest that changes in Ito are unlikely to be responsible for most of the postnatal action potential shortening.