bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined effect of neonatal sympathectomy and adrenal demedullation on blood pressure and vascular changes in spontaneously hypertensive rats.
Authors: Lee R M , Borkowski K R , Leenen F H , Tsoporis J , Coughlin M
Published: June 2012

Neonatal sympathectomy using a combined treatment with antiserum to nerve growth factor and guanethidine during the first 4 weeks after birth was carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Bilateral adrenal demedullation was performed in 4-week-old sympathectomized SHR and WKY rats. The development of hypertension in SHR was prevented by sympathectomy, but the blood pressure (BP) was still higher than in age-matched WKY rats. Demedullation reduced the BP of sympathectomized SHR to the same level as that of WKY rats. Heart rates of SHR and WKY rats were not affected by the treatments. Morphometric measurements of the mesenteric arteries showed that sympathectomy significantly reduced the medial mass in the mesenteric arteries of SHR, mainly through a reduction in the number of smooth muscle cell layers. In sympathectomized SHR, demedullation increased the lumen size of muscular arteries under maximally relaxed conditions, which might explain the further reduction in BP in these animals. Demedullation in sympathectomized SHR and WKY rats caused a decrease in smooth muscle cell layers in the superior mesenteric artery, but the same treatment resulted in a slight increase in the number of smooth muscle cell layers in the large and small mesenteric arteries of SHR and WKY rats. Adventitial area was increased in some mesenteric arteries of SHR and WKY rats by sympathectomy, and demedullation caused a further increase in the size of adventitia in WKY rats. Heart weight in SHR was normalized to the level found in WKY rats by sympathectomy and demedullation. We conclude that in sympathectomized SHR, the elevated BP was maintained by the adrenal medulla.
Angiotensin-induced desensitization of the phosphoinositide pathway in cardiac cells occurs at the level of the receptor.
Authors: Abdellatif M M , Neubauer C F , Lederer W J , Rogers T B
Published: June 2012

Previous studies show that angiotensin II (Ang II) increases phosphoinositide turnover in cultured neonatal heart cells. Ang II has also been shown to transiently increase spontaneous beating behavior in these cells. In this study we seek to identify the molecular mechanism underlying this rapid (3-5-minute) desensitization. Time-course studies on the accumulation of [3H]inositol phosphates indicate that the loss in functional responsiveness correlates with reduced efficacy of Ang II to activate the phosphoinositide path. Binding studies with 125I-Ang II revealed that there was no change in surface receptor binding capacity during the time in which desensitization developed. Normal phosphoinositide and functional responses are observed when desensitized cells are treated with probes that activate the cardiac phosphoinositide pathway at discrete steps. These studies reveal that the functional status of the major components of the phosphoinositide signaling pathway, including G proteins, phospholipase C, and protein kinase C (PKC), are normal during maintained Ang II desensitization. To study the potential role of PKC in Ang II desensitization, the cells are treated with TPA for 24 hours, which downregulates PKC activity. PKC-depleted cells rapidly desensitize after Ang II application. We conclude that the selective Ang II-evoked biochemical/functional desensitization involves inhibition at the level of the receptor, rather than at a component downstream in the path, and that this process is independent of PKC and loss of surface binding capacity.
Intracellular calcium transients and arrhythmia in isolated heart cells.
Authors: Thandroyen F T , Morris A C , Hagler H K , Ziman B , Pai L , Willerson J T , Buja L M
Published: June 2012

Intracellular calcium ([Ca2+]i) elevation may mediate cardiac arrhythmias. However, direct measurement of the rapid alterations of [Ca2+]i on a beat-to-beat basis using fast temporal resolution and without signal averaging in the spontaneously beating in vivo heart is lacking. Furthermore, data from an isolated spontaneously beating myocyte preparation that develops arrhythmia similar to that in the in vivo heart are unavailable. We measured rapid changes of [Ca2+]i with fast temporal resolution in isolated spontaneously beating neonatal rat ventricular myocytes with cell-to-cell communication and characterized the interrelation between [Ca2+]i and arrhythmia. An elevated extracellular calcium ([Ca2+]o) concentration of 10.8 mM induced premature beats, a rapid beating rate (tachyarrhythmia), and chaotic or fibrillatory beating activity in a small group of myocytes. [Ca2+]i levels during systole increased from the nanomolar to micromolar concentration range before arrhythmia development. Spontaneous oscillations of [Ca2+]i during diastole could evoke a spontaneous tachyarrhythmia. In the presence of [Ca2+]i elevation, a spontaneous tachyarrhythmia could induce severe [Ca2+]i overload. Reduction of [Ca2+]i with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid AM (5 microM) in the presence of 10.8 mM [Ca2+]o reversed the arrhythmia. In single ventricular myocytes superfused with 10.8 mM [Ca2+]o, oscillations of membrane potential characteristic of transient inward current occurred that were prevented by ryanodine (0.1 microM), an inhibitor of Ca2+ flux across the sarcoplasmic reticulum. This study characterizes 1) an isolated multicellular myocyte model of arrhythmia similar to that evident in in vivo hearts, 2) elevation of [Ca2+]i with systolic [Ca2+]i levels of 1-3 microM and diastolic [Ca2+]i oscillations before the initiation of arrhythmia, 3) tachyarrhythmia as a cause of severe [Ca2+]i overload, which may be important in the perpetuation and degeneration of arrhythmias, and 4) reversal of arrhythmia with reduction of [Ca2+]i. The results in the isolated myocyte model may have relevance to the generation and perpetuation of certain cardiac arrhythmias associated with calcium overload.
Dose-dependent inhibition of stretch-induced arrhythmias by gadolinium in isolated canine ventricles. Evidence for a unique mode of antiarrhythmic action.
Authors: Hansen D E , Borganelli M , Stacy G P , Taylor L K
Published: June 2012

Transient diastolic dilatation of the isolated canine left ventricle predictably elicits arrhythmias. To test the hypothesis that such arrhythmias may be mediated by sarcolemmal stretch-activated channels, we attempted to inhibit stretch-induced arrhythmias with gadolinium (Gd3+), a potent stretch-activated channel blocker. In experiments with six isolated canine hearts, left ventricular volume was increased for 50 msec during early diastole and then returned to initial volume by a computerized servopump. The stretch volume was adjusted to yield a probability of eliciting a stretch-induced arrhythmia of 95 +/- 2% before treatment with Gd3+. When Gd3+ (1-10 microM) was administered, dose-dependent suppression of stretch-induced arrhythmias was observed. The probability of a stretch-induced arrhythmia was reduced to 13 +/- 10% (p less than 0.05) with 10 microM Gd3+. Washout of Gd3+ completely reversed this effect. Since Gd3+ is known to be a calcium channel antagonist, we compared the effect of Gd3+ on stretch-induced arrhythmias with that of verapamil and nifedipine. These calcium channel blockers produced no demonstrable inhibition of stretch-induced arrhythmias when administered at concentrations (1 microM) that substantially depressed left ventricular pressure development. Thus, our results indirectly implicate stretch-activated channels in the genesis of stretch-induced arrhythmias and provide preliminary evidence for a potential new mode of antiarrhythmic drug action--blockade of stretch-activated channels.
Mechanisms of contraction induced by human leukocytes in normal and atherosclerotic arteries.
Authors: Mügge A , Heistad D D , Padgett R C , Waack B J , Densen P , Lopez J A
Published: June 2012

Activation of leukocytes results in the release of a variety of vasoactive substances that may modulate vascular tone. We studied the effect of human polymorphonuclear (PMN) and mononuclear (MONO) leukocytes on quiescent femoral arteries in vitro. Arteries were obtained from normal and atherosclerotic cynomolgus monkeys. In normal arteries, stimulation of PMNs (3 and 5 x 10(6) cells/ml) with either thrombin (5 units/ml) or complement C5a (0.5 micrograms/ml) resulted in endothelium-independent contraction (approximately 25% of maximum contraction with 80 mM KCl). Vasocontraction was augmented in the presence of superoxide dismutase (150 units/ml) and was significantly impaired in the presence of the hydroxyl radical scavengers mannitol (20 mM) and deferoxamine (1 mM). Catalase (1,200 units/ml) or L-alanine (20 mM) did not modify this effect of PMNs. In contrast to PMNs, vasocontraction in response to MONOs was not altered by the addition of radical scavengers. Pretreatment of PMNs and MONOs with indomethacin (10 microM) or nordihydroguaiaretic acid (20 microM) did not influence vascular responses. Supernatant of thrombin-stimulated PMNs and MONOs also produced vasocontraction (approximately two thirds of the effect of intact cells). This vasocontractor factor (or factors) was heat stable (30 minutes, 95 degrees C) and had a molecular weight less than 1,000 as determined by ultrafiltration. Stimulation of MONOs or PMNs (3 and 5 x 10(6) cells/ml) produced a similar response in normal arteries. In contrast, the constrictor response in atherosclerotic arteries to MONOs (5 x 10(6) cells/ml) was significantly greater than to PMNs. We conclude that stimulated human PMNs and MONOs contract arteries in vitro by release of at least two factors. One factor appears to be heat stable, with a molecular weight less than 1,000. The vascular response to PMNs, but not to MONOs, appears to involve the generation of hydroxyl radicals. The response to MONOs is greater than the response to PMNs in atherosclerotic, but not in normal, arteries.
Phospholipid metabolism in cardiomyopathic hamster heart cells.
Authors: Kawaguchi H , Shoki M , Sano H , Kudo T , Sawa H , Okamoto H , Sakata Y , Yasuda H
Published: June 2012

We demonstrated that the activities of phosphatidylinositide-specific phospholipase C, inositol 1,4,5-trisphosphate (IP3) kinase, and IP3 phosphatase were enhanced in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) in comparison to control hamsters (F1b). Release of both arachidonic acid and prostacyclin was markedly enhanced by norepinephrine in the cardiomyopathic hamsters. Phospholipase C in heart has high substrate specificity to phosphatidylinositol. IP3 production was markedly enhanced in the cardiomyopathic hamsters. We also determined the intracellular calcium concentration, which was higher in BIO 53.58 hamsters than in BIO 14.6 hamsters at 5-20 weeks of age. There was no significant difference in the intracellular calcium level between F1b and BIO 14.6 hamsters at 5 weeks of age. These results suggest that phosphatidylinositol turnover stimulated by norepinephrine may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in BIO 53.58 hamsters, some mechanism such as the sarcoplasmic reticulum, which controls the intracellular calcium level, may deteriorate in function. We concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes.
Calcium homeostasis in rabbit ventricular myocytes. Disruption by hypochlorous acid and restoration by dithiothreitol.
Authors: Eley D W , Korecky B , Fliss H , Désilets M
Published: June 2012

Hypochlorous acid (HOCl) is a toxic oxidant produced by neutrophils at sites of cardiac inflammation. To examine the effect of this oxidant on Ca2+ homeostasis in the heart, isolated rabbit ventricular myocytes were iontophoretically loaded with the Ca2+ indicator fura 2 and superfused with 100 microM HOCl under voltage-clamp conditions. Ca2+ transients and the corresponding Ca2+ currents were elicited by 300-msec depolarizing pulses from -40 to 0 mV. Within 200 seconds after HOCl addition, the amplitude of the Ca2+ transients was reduced from 402 +/- 89 to 82 +/- 29 nM (p less than 0.01) while intracellular free ([Ca2+]i increased from 78 +/- 16 to 265 +/- 48 nM (p less than 0.01). During this time, the amplitude of the slow inward currents increased by 10%, while steady-state holding current remained stable. This sustained steady-state rise in [Ca2+]i occurred even in the absence of extracellular Ca2+ but was virtually abolished by a 20-second preexposure to 10 mM caffeine, suggesting that the major source of this Ca2+ was the sarcoplasmic reticulum. Although washout of HOCl failed to induce recovery, subsequent exposure to the dithiol reducing agent dithiothreitol caused a rapid restoration of both the steady-state [Ca2+]i and Ca2+ transient amplitude. We conclude that 1) HOCl caused a rise of [Ca2+]i by inducing the release of Ca2+ from internal stores and impairing cellular extrusion mechanisms and 2) these effects occur through alteration of protein thiol redox status.
Specific block of the anti-ischemic actions of cromakalim by sodium 5-hydroxydecanoate.
Authors: McCullough J R , Normandin D E , Conder M L , Sleph P G , Dzwonczyk S , Grover G J
Published: June 2012

The potassium channel activators cromakalim and pinacidil were recently shown to have anti-ischemic properties in isolated globally ischemic rat hearts. The effects of two reported blockers of ATP-sensitive potassium channels, glibenclamide (glyburide) and sodium 5-hydroxydecanoate, on the anti-ischemic efficacy of cromakalim were determined in this model. Buffer-perfused rat hearts were subjected to 25 minutes of ischemia followed by 30 minutes of reperfusion. Pretreatment of these hearts with 60 microM cromakalim significantly decreased indexes of contractile function but caused a significant improvement of postreperfusion function and a significant decrease in release of lactate dehydroxygenase and in end-diastolic pressure. Pretreatment with glibenclamide at concentrations that reversed the preischemic effects of cromakalim (0.05 and 1.0 microM) also significantly reversed its postischemic protective effects. Sodium 5-hydroxydecanoate (100 and 300 microM) had no effect on the preischemic (negative inotropic) effects of cromakalim but completely reversed its cardioprotective effects. Sodium 5-hydroxydecanoate did not reverse the cardioprotective effects of the calcium entry blocker diltiazem. In phenylephrine-contracted rat aorta, glibenclamide (0.1-10 microM) inhibited cromakalim-induced relaxation, whereas sodium 5-hydroxydecanoate (10-1,000 microM) had no effect. Similarly, the ability of cromakalim to shorten cardiac action potential duration in guinea pig papillary muscle and to increase outward whole-cell potassium currents in isolated myocytes was inhibited by glibenclamide, whereas sodium 5-hydroxydecanoate was without effect. Thus, both glibenclamide and sodium 5-hydroxydecanoate inhibited the effects of cromakalim after reperfusion; however, sodium 5-hydroxydecanoate, unlike glibenclamide, had no effect in nonischemic preparations. These results suggest that sodium 5-hydroxydecanoate is an ischemia-selective inhibitor of ATP-sensitive potassium channels.
Higher Ca2+ sensitivity of triton-skinned guinea pig mesenteric microarteries as compared with large arteries.
Authors: Boels P J , Troschka M , Rüegg J C , Pfitzer G
Published: June 2012

Small mesenteric resistance arteries and the main branch of the mesenteric artery (outer in situ diameter 115 +/- 3 microns [n = 76] and greater than 1,000 microns, respectively) were skinned with 1% Triton X-100. Both preparations were mounted as rings for circumferential force measurement in an EGTA solution (free Ca2+, less than 10 nM; calmodulin, 0.3 microM; pH 6.7). Force-pCa curves were obtained by increasing free Ca2+ (0.05 to 30 microM). The resulting dose-dependent contractions, after normalization to maximal force development (arteries, 21.4 +/- 2.4 [n = 3]; arterioles, 15.3 +/- 2.1 mN/mm2 [n = 5]) were fitted to sigmoidal force-pCa curves. Values of ED50 and of the cooperativity factor h were 6.08 and 2.39 in arterioles and 5.64 and 1.64 in arteries. The higher Ca2+ sensitivity of arteriolar preparations remained at pH 7.0 at higher calmodulin concentrations and after inhibition of smooth muscle phosphatase with okadaic acid. Total myosin light chain kinase activity in crude arteriolar extracts (using [gamma-32P] ATP and isolated gizzard light chains as substrates) was approximately 25% of arterial kinase. Both kinase preparations had identical Ca2+ sensitivities. Likewise, total arteriolar phosphatase activity (using 32P-labeled gizzard light chains) was approximately 25% of the arterial activity; both phosphatases had an identical sensitivity toward okadaic acid. The ratio of kinase/phosphatase activities was identical in both tissues. Extracts of both tissues contained two isozymes of the myosin heavy chain as determined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac myocyte necrosis induced by angiotensin II.
Authors: Tan L B , Jalil J E , Pick R , Janicki J S , Weber K T
Published: June 2012

Although the role of angiotensin II (Ang II) in the pathogenesis and progression of the failing heart is uncertain, previous reports have suggested that myocyte injury may be a component in this process. In this study, we investigated this possibility in more detail. Cardiotoxic effects of nonacutely hypertensive doses of Ang II were examined in 90 rats, including those receiving an angiotensin infusion (200 ng/min i.p.) and those with renovascular hypertension, where endogenous stimulation of Ang II occurred. Myocyte injury and wound healing resulting from these treatments were evaluated by 1) immunofluorescence after in vivo monoclonal antibody labeling of myosin to detect abnormal sarcolemmal permeability, 2) [3H]thymidine incorporation into DNA, to detect fibroblast proliferation, and 3) light microscopic evidence of myocytolysis and subsequent scar formation. We found that exogenous Ang II produced multifocal antimyosin labeling of cardiac myocytes and myocytolysis, which were maximal on days 1-2 of the infusion. Subsequently, DNA synthesis rates were increased, with fibroblast proliferation reaching peak levels on day 2 (Ang II-treated rats, 90.0 +/- 18.6 cpm/micrograms DNA; control rats, 11.4 +/- 2.3 cpm/micrograms DNA; p less than 0.05); microscopic scarring was found on day 14 and represented 0.12 +/- 0.02% of the myocardium. Concurrent treatment with both propranolol (30 mg/kg/day s.c.) and phenoxybenzamine (5 mg/kg/day i.m.) did not attenuate Ang II-induced antimyosin labeling. Increased endogenous Ang II, resulting from renal ischemia after abdominal aortic constriction, produced both antimyosin labeling and increased rates of DNA synthesis like that observed with Ang II infusion. Both myocyte injury and fibroplasia were prevented with captopril (65 mg/day p.o.), but this protective effect was not seen with reserpine pretreatment. Infrarenal aortic banding without renal ischemia, on the other hand, produced hypertension without necrosis. We conclude that pathophysiological levels of endogenous as well as low-dose exogenous Ang II were associated with altered sarcolemmal permeability and myocytolysis with subsequent fibroblast proliferation and scar formation. Myocyte injury was unrelated to the hypertensive or enhanced adrenergic effects of Ang II or to hypertension per se. Captopril was effective in preventing myocyte injury in renovascular hypertension. The mechanism(s) responsible for Ang II-induced necrosis will require further study.
Growth-dependent alterations of intracellular Ca(2+)-handling mechanisms of vascular smooth muscle cells. PDGF negatively regulates functional expression of voltage-dependent, IP3-mediated, and CA(2+)-induced Ca2+ release channels.
Authors: Masuo M , Toyo-oka T , Shin W S , Sugimoto T
Published: June 2012

To examine the alterations of intracellular Ca2+ ([Ca2+]i)-handling mechanisms in cultured vascular smooth muscle cells (VSMCs) of rat aorta (Shin et al Circ Res 1991;69:551-556), we stimulated VSMCs by extracellular high K+, caffeine, and angiotensin II and evaluated Ca2+ influx through voltage-dependent Ca2+ channels, Ca(2+)-induced Ca2+ release, and inositol trisphosphate-dependent Ca2+ release from internal stores. Percentage of VSMCs responding to each stimulant (responder ratio) and degree of [Ca2+]i increase in the responding cells were analyzed by a two-dimensional fura-2 imaging system. The responder ratios to the three stimulants were high (70-90%) in the quiescent phase (days 1-2), although some cells selectively responded to one or two of the stimulants. Responder ratios prominently decreased to approximately 20% in the proliferating phase (days 2.5-3). In the subconfluent (days 3.5-4) and postconfluent (days 5-6) phases, the responder ratio to high K+ and angiotensin II recovered to the same level as during the quiescent phase, whereas that to caffeine remained low (approximately 10-20%). In responding cells, the degree of [Ca2+]i increase by caffeine and angiotensin II was stable (approximately 100%) during culturing, whereas that to high K+ was small (approximately 30-40%) in the quiescent and proliferating phases and rapidly increased threefold in the subconfluent and postconfluent phases. Furthermore, arrest of cell growth in serum-free medium prevented the reduction of responder ratios in the proliferating phase and restored the decreased ratio of the caffeine responder. Acceleration of VSMC proliferation by platelet-derived growth factor decreased the ratios in all phases. These results imply that 1) the functional expressions of [Ca2+]i-handling mechanisms in response to these vasoactive stimuli are influenced by cell growth and cytodifferentiation of VSMCs or platelet-derived growth factor and 2) they are regulated independently from each other.
Altered calcium handling in left ventricular pressure-overload hypertrophy as detected with aequorin in the isolated, perfused ferret heart.
Authors: Bentivegna L A , Ablin L W , Kihara Y , Morgan J P
Published: June 2012

The purpose of this study was to test the hypothesis that systolic and diastolic dysfunction in left ventricular pressure-overload hypertrophy is caused by abnormal intracellular calcium handling. Experiments were performed with intact, buffer-perfused, isovolumic ferret hearts (n = 9 hypertrophied, n = 9 control) that were loaded with the bioluminescent indicator aequorin to monitor changes in cytoplasmic calcium. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Compared with their age-matched controls, significant hypertrophy of the left ventricle developed 4 weeks after postvalvular aortic banding; at the time the animals were killed, the left ventricular weight/body weight ratio was increased in the banded animals (5.3 x 10(-3) versus 3.6 x 10(-3), p less than 0.001). As indicated by the diastolic pressure-volume relation, left ventricular distensibility was significantly diminished in the hypertrophied hearts. In comparison to the controls, the hypertrophied hearts demonstrated a prolonged duration of isovolumic contraction (time to 90% decline from peak: 278 +/- 5.4 versus 247 +/- 10.2 msec, p less than 0.05), but a marked decrease in peak systolic midwall stress (22.4 +/- 5.0 versus 38.6 +/- 5.7 g/cm2, p less than 0.05). The increased duration of isovolumic contraction correlated with a similar prolongation of the calcium transient (time to 90% decline from peak: 245 +/- 19.5 versus 127 +/- 13.2 msec, p less than 0.05), indicating that the rate of sequestration and perhaps release of calcium by the sarcoplasmic reticulum is decreased in hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Imaging of protein kinase C distribution and translocation in living vascular smooth muscle cells.
Authors: Khalil R A , Morgan K G
Published: June 2012

The subcellular distribution of protein kinase C was directly imaged in single living smooth muscle cells using a new fluorescent protein kinase C probe. The probe localized prominently to perinuclear organelles and, to a lesser extent, to the cytosol and surface membrane. The perinuclear signal did not detectably change over the time observed. The ratio between the surface membrane intensity and that in the cytosol (R) was measured in parallel with cell shortening. In 1 mM extracellular Ca2+, the time to peak R and time to peak shortening were not significantly different. In Ca(2+)-free solution, no significant increase in the surface membrane/cytosol fluorescence ratio was observed with time, and shortening was inhibited. These results provide a new method for monitoring protein kinase C localization in living cells and directly demonstrate that protein kinase C moves in a Ca(2+)-dependent fashion from the cytosol to the surface membrane simultaneously with contraction.
Effects of Increased Residual Volume, Increased Output Resistance and Autonomic Drugs on Ventricular Suction in the Turtle
Authors: KRANER JAMES C.
Published: June 2012

Immersed, isolated turtle ventricles were allowed to beat when filling only by suction. Obstruction of ejection at various volumes showed an inverse relationship between residual volume and volume aspirated. Diastolic aspiration occurred even with residual volumes of at least 0.55 ml. Ventricles, filling by suction only, maintained continuous output of up to 3 ml./min. working against pressures of 16 to 22 cm. H
2
O. In these circumstances ejection was diminished or abolished by acetylcholine and usually increased by epinephrine. This work amplifies and further quantitates recent work showing ventricular diastolic suction in a variety of species.
Transmembrane Potentials of the Normal and Hypothermic Human Heart
Authors: BROMBERGER-BARNEA BARUCH , CALDINI PAOLO , WITTENSTEIN GEORGE J.
Published: June 2012

Transmembrane cardiac potentials from the human ventricles were recorded in 10 subjects during corrective cardiac surgery under normothermic or hypothermic anesthesia. The amplitude and shape of these transmembrane potentials are compared with simultaneously recorded electrocardiograms, and their relationships are discussed.
Relative Effects of Heart Chambers, Lungs, and Mitral Insufficiency on the Shape of Indicator Dilution Curves
Authors: EMANUEL RICHARD W. , LACY WILLIAM W. , NEWMAN ELLIOT V.
Published: June 2012

The shape of dilution curves obtained by sampling from different sites was studied in dogs following superior vena caval injections of dye. Synchronous sampling from paired sites enabled observations to be made on the separate effects of the right heart, left ventricle and aorta on the dye dilution curves, with and without mitral insufficiency.

The results show that tile left ventricle and aorta have little effect on the final slope of a dilution curve across the lungs in dogs with normal hearts. In the presence of mitral incompetence the final slope across both lungs and heart was slower than in the normal, but these changes were related to cardiac output and increase in lung mixing volume rather than primarily to the incompetence of the valve.
Sodium Gradient, Smooth Muscle Tone, and Blood Pressure Regulation
Authors: FRIEDMAN SYDNEY M. , JAMIESON JAMES D. , FRIEDMAN CONSTANCE L.
Published: June 2012

Rat colon strips respond to an acute reduction of sodium concentration in the medium (Na
o
) by an immediate increase in tension, followed by relaxation to the basal tension as the tissue equilibrates. Following equilibration in low Na
o
the responsiveness to drug-induced contraction is increased, while in high Na
o
it is decreased. A contraction cycle, variously induced, can be aborted by the acute addition of sodium to the medium. The applicability of these findings to vascular smooth muscle in the whole animal can be demonstrated by appropriate acute sodium infusions. The effects in all cases can be referred to sodium, although modified by the anionic component of the salts used. The results are considered to support the view that smooth muscle tension is governed in part by the concentration gradient Na
o
/Na
i
and the theoretic implication of this for chronic hypertensive and hypotensive states is developed.
Activation of the Free Wall of the Right Ventricle Experimental Right Bundle Branch Block
Authors: CONRAD LOYAL L. , CUDDY T. EDWARD
Published: June 2012

Right bundle branch block was produced in dogs, and activation of the free wall of the right ventricle was studied by means of multipolar electrodes. After block, accession spread radially at the earliest activated endocardial point and tangentially at later activated points. Direct current stimulation of selected endocardial points resulted in patterns of activation resembling those obtained after right bundle branch block in controls and after block. It is concluded that the Purkinje network does not participate in normal fashion in endocardial spread of the excitation impulse after right bundle branch block.
Electrical Activation and Mechanical Asynchronism in the Cardiac Cycle of the Dog
Authors: SAMET PHILIP , BERNSTEIN WILLIAM H. , LITWAK ROBERT S.
Published: June 2012

Right and left ventricular pressure curves and electrocardiogram were recorded in the dog during sinus rhythm and during mechanically induced right and left ventricular premature systoles. The normal range during sinus rhythm for the relationship between onset of right and left ventricular contraction was determined. At one extreme, right ventricular contraction commenced 0.02 second before the left; at the other extreme, left ventricular contraction started 0.03 second before the right. In most instances, the onsets of ventricular contraction were either temporally identical or one ventricle contracted 0.01 second prior to the other.
Relationship of Lipolytic and Esterolytic Activity of the Aorta to Susceptibility to Experimental Atherosclerosis
Authors: ZEMPLÉNYI T. , LOJDA Z. , GRAFNETTER D.
Published: June 2012

Aortic lipolytic (lipoproteinolytic) and esterolytic activity of various species were investigated by biochemical and histochemical methods. Lipolytic and esterolytic activities in the aorta of species susceptible to experimental atherosclerosis are lower than in the rat, a very resistant species. The histochemical technics permitted the localization of enzymatic activity in individual layers of vessel wall.
Production of Hypernatremia and Hyperosmolarity in the Diabetes Insipidus Dog Infused with Ringer's Solution
Authors: DREIFUS L. S. , STAMLER J. , LICHTON I. J.
Published: June 2012

Infusion of isotonic Ringer's solution led to hypernatremia and plasma hyperosmolarity in diabetes insipidus dogs. This phenomenon suggests a safe and reliable test for diabetes insipidus which does not require collection of urine.
Hypertensive Cardiovascular Disease Induced by Desoxycorticosterone in Hypophysectomized Rats Bearing Pituitary Autotransplants
Authors: HALL C. E. , HALL O.
Published: June 2012

The responsiveness of hypophysectomized female rats bearing pituitary autotransplants to chronic, low dosage treatment with desoxycorticosterone acetate was compared with that of intact females. Intact animals reacted rapidly, developed malignant hypertension, and died within 10 weeks. By contrast hypophysectomized autograft-bearing rats developed hypertension more slowly, and the majority of them were alive at 16 weeks when the experiment was concluded. At autopsy, as compared with intact animals which had died earlier from the sequelae of malignant hypertension, hypophysectomized animals were found to have far more severe periarteritis nodosa, but a lesser development of nephrosclerosis and an extremely low incidence of cardiac damage. Hypertensive cardiovascular disease occurred in these animals despite extreme atrophy of the thyroid and adrenal glands, of the ovaries and uteri, and cessation of somatic growth. Therefore, except for LTH which such autografts are known to elaborate, or trace amounts of the other principals, none of the known regulatory hormones of the anterior pituitary singly or in combination is essential to this effect of DCA.
Influence of Sympathomimetic Pressor Drugs on Arrhythmias Caused by Multiple Stimuli
Authors: GILBERT J. L. , LANGE GERTRUDE , McC. BROOKS C.
Published: June 2012

A technic of administering successive stimuli to the heart at various ectopic foci was devised. Under normal circumstances the heart had sufficient power of integration to resist disorganization of its action by these multiple stimuli. Methoxamine, mephentermine and metaraminol had less tendency to increase vulnerability to fibrillation than did levarterenol under these conditions of stress. A new compound (Lilly #20522) blocked for a time the arrhythmia-producing action of levarterenol.
Turnover of Cholesterol in the Artery Walls of Normal Chickens
Authors: DAYTON SEYMOUR
Published: June 2012

Studies of cholesterol metabolism in the walls of arteries of normal intact cockerels indicate that plasma cholesterol is the major precursor of the cholesterol in the artery wall, but that local synthesis may contribute a significant fraction. The fractional turnover of cholesterol in the wall of the abdominal aorta is faster than in either the thoracic aorta or the brachiocephalic arteries. However, considered in relation to endothelial surface area, the rate of cholesterol transfer from plasma is smallest in the abdominal aorta. The abdominal aorta also has a lower cholesterol concentration in this species than do the other large arteries.
Antihypertensive Effect of Hypophysectomy in Dogs with Hypertension Following Bilateral Carotid Sinus Constriction
Authors: HAWTHORNE EDWARD W. , GASPAR MARY
Published: June 2012

A chronic type of experimental hypertension has been produced in dogs by bilateral sinus area constriction. Hypophysectomy has a prolonged antihypertensive effect in dogs with persistent hypertension resulting from carotid sinus area constriction, while no decrease in mean arterial pressure is seen after hypophysectomy in normotensive control dogs. These findings suggest the possibility that altered hypophyseal function participates in the pathogenesis of this type of hypertension.
Effect of Ether Anesthesia on the Cardiac Output, Blood Pressure, and Distribution of Blood Flow in the Albino Rat
Authors: VIDT DONALD G. , BREDEMEYER ANTONIE , SAPIRSTEIN ELIZABETH , SAPIRSTEIN LEO A.
Published: June 2012

Rats anesthetized with ethyl ether were compared with rats anesthetized with sodium pentobarbital from the standpoint of cardiac output, peripheral resistance and regional blood flow. Cardiac output was measured by the indicator-dilution technic; regional blood flow was determined by the indicator-fractionation technic employing Rb
86
or I
131
-antipyrine. The cardiac output is one and a half times as great in ether anesthesia as in pentobarbital anesthesia; the peripheral resistance is about two-thirds as great with ether. Compared to pentobarbital, ether increases myocardial, cerebral, and carcass blood flow, while decreasing renal, splanchnic and cutaneous blood flow. The pronounced difference in the cardiovascular effects of the two agents indicates the need for caution in the interpretation of experiments in which cardiovascular measurements are made under anesthesia.
Influence of Local Temperature and of Digital Nerve Block on Critical Opening Pressure of Vessels in the Finger
Authors: GASKELL P. , DIOSY A.
Published: June 2012

Local cooling of the finger increased and local warming decreased the critical opening pressure of small vessels supplying the nailfold capillaries. Digital nerve block also decreased the critical closing pressure of these vessels independently of any concomitant change in local temperature.
Therapy of Experimental Pulmonary Edema in the Dog
Authors: AVIADO DOMINGO M. , DUFFY JOHN R.
Published: June 2012

The results of analysis of edema fluid and excised lungs show that there is leakage of protein-rich fluid into the lung tissue and ultimately into the respiratory passages. This leakage cannot be explained by the reduction in oxygen uptake as observed in lung tissue slices. The ultimate cause of pulmonary edema is not known. The survival time of anesthetized dogs suffering from thermal edema, can be prolonged by inhalation of oxygen and by administration of antihistaminic drugs and pulmonary vasodilators.
On the Relationship of Crystalline Lecithins to Cholesterol Esterase of Serum
Authors: WAGNER ARNOLD , ZIEBELL MARJORIE
Published: June 2012

When serum is incubated in the presence of 1-α-dimyristoyl lecithin, the expected disappearance of free cholesterol is greatly enhanced. This effect is not seen in replicate experiments employing two other crystalline lecithins.
Sodium Gradient and Renoprival Hypertension in the Rat
Authors: FRIEDMAN SYDNEY M. , FRIEDMAN CONSTANCE L. , NAKASHIMA MIYOSHI
Published: June 2012

Following nephrectomy in the rat blood pressure rises while the extracellular fluid volume increases, sodium concentration falls and potassium rises. These changes (without the potassium rise) can be mimicked by simple hyperosmotic loading while the reverse can be induced by dehydration. The rise in blood pressure is not due to either expansion of the extracellular space or the fall in sodium concentration alone but probably to the resultant decrease in the Na
o
/Na
1
gradient.
Studies of Actomyosin from Cardiac Muscle of Dogs with Experimental Congestive Heart Failure
Authors: DAVIS JAMES O. , TRAPASSO MARY , YANKOPOULOS NICHOLAS A. , CASPER ALFRED
Published: June 2012

Comparative studies were made on cardiac actomyosin from normal dogs and from dogs with experimental failure. Actomyosin was characterized by ultracentrifugal sedimentation velocity, viscosity and ATP-ase measurements. The data on actomyosin from normal cardiac muscle showed a striking similarity to the findings reported by others for skeletal muscle actomyosin. The only difference found between cardiac actomyosin front the normal and experimental material was an abnormal component ( S

20
W

= 5.0-6.7) in the sedimentation pattern for actomyosin from 4 of 11 dogs with cardiac failure. It seems likely that the changes in actomyosin which resulted in the abnormal sedimentation pattern were produced during extraction or preparation of the actomyosin and that they do not reflect an altered state of actomyosin in the functioning heart. The explanation for the occurrence of this slow sedimentation component solely in the experimental material is not clear.
Cardiac Index during Intravenous Levarterenol Infusion in Man
Authors: TUCKMAN JOHN , FINNERTY FRANK A.
Published: June 2012

Cardiac indices were determined by the Stewart-Hamilton indicator-dilution method during intravenous infusions of levarterenol in 25 human subjects. The rate and duration of the infusion as well as the increase in arterial pressure and bradycardia were varied in order to study their influences on the cardiac index.
Chronic nonocclusive coronary artery constriction impairs ventricular function, myocardial structure, and cardiac contractile protein enzyme activity in rats.
Authors: Capasso J M , Malhotra A , Li P , Zhang X , Scheuer J , Anversa P
Published: June 2012

To determine the effects of chronic nonocclusive coronary constriction on cardiac hemodynamics, structural integrity, and contractile protein enzyme activity, the left coronary artery was narrowed in rats, and measurements of ventricular performance, magnitude, and distribution of tissue damage and myofibrillar Mg2+ and Ca2+ myosin ATPase activities were evaluated 1 month later. In the presence of coronary artery stenosis averaging 58%, three levels of involvement of global cardiac performance were identified, and the rats were divided accordingly. In the first group, only left ventricular end-diastolic pressure (LVEDP) was increased; in the second group, LVEDP and left ventricular +dP/dt and/or -dP/dt were affected; and in the third group, LVEDP, left ventricular +dP/dt and -dP/dt, and right ventricular end-diastolic pressure were impaired. Thus, left ventricular moderate dysfunction, severe dysfunction, and failure occurred with coronary narrowing. On a structural basis, coronary constriction resulted in an ongoing process characterized by acute myocytolytic necrosis and foci of replacement fibrosis in different stages of healing. The number of these lesion profiles in the left ventricular myocardium increased 4.7-, 4.4-, and 8.3-fold in rats with moderate dysfunction, severe dysfunction, and failure, respectively. Biochemically, Mg(2+)-ATPase activity of myofibrils increased biventricularly when moderate dysfunction was present. However, this parameter decreased with the appearance of severe dysfunction, reaching control values in ventricular failure. Ca2+ myosin ATPase activity was reduced in the left ventricle of rats with severe dysfunction and failure, whereas it was elevated in the right ventricle of rats with severe dysfunction. In conclusion, a fixed lesion of the left main coronary artery with a modest reduction in vessel luminal diameter generates a conditioned state of the heart characterized by a continuous loss of myocytes and replacement scarring, which, in combination with alterations in contractile protein enzyme activity, may be responsible for a number of abnormalities in cardiac dynamics ranging from moderate dysfunction to pump failure.
Effect of spinal microinjections of an antagonist to substance P or somatostatin on the exercise pressor reflex.
Authors: Wilson L B , Wall P T , Matsukawa K , Mitchell J H
Published: June 2012

The purpose of this study was to determine the heart rate and arterial blood pressure changes to isometric skeletal muscle contraction and muscle stretch before and after microinjecting an antagonist to substance P (SP) or somatostatin (SOM) into the L-7 dorsal horn region of the spinal cord of anesthetized cats. Anesthesia was induced by administering an anesthetic gas mixture and was subsequently maintained with alpha-chloralose. Triceps surae contraction was induced by electrically stimulating the L-7 ventral root. Three muscle manipulations (all 1 minute in duration) were performed: 1) continuous tetanic contraction, 2) intermittent tetanic contractions (1 second of contraction, 1 second of relaxation), and 3) passive muscle stretch. Saline microinjections had no effect on the cardiovascular responses to these muscle manipulations. However, both peptide antagonists blunted the pressor response to a continuous tetanic contraction as mean arterial pressure increased 47 +/- 4 and 44 +/- 4 mm Hg before and 28 +/- 3 and 28 +/- 4 mm Hg after microinjecting the SP or SOM antagonist, respectively. In contrast, neither antagonist influenced the increase in mean arterial pressure produced by passive stretch; values were 43 +/- 6 versus 41 +/- 6 mm Hg (SP antagonist) and 39 +/- 7 versus 42 +/- 7 mm Hg (SOM antagonist) before and after injections, respectively. Microinjecting the SOM antagonist attenuated the pressor response to intermittent tetanic contractions (44 +/- 4 mm Hg before SOM antagonist versus 26 +/- 4 mm Hg after SOM antagonist), whereas the SP antagonist had no effect (35 +/- 3 mm Hg before SP antagonist versus 32 +/- 4 mm Hg after SP antagonist).(ABSTRACT TRUNCATED AT 250 WORDS)
Brain ouabain and central effects of dietary sodium in spontaneously hypertensive rats.
Authors: Huang B S , Leenen F H
Published: June 2012

High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to intracerebroventricular ouabain and to mental stress and intracerebroventricular alpha 2-adrenoceptor agonist guanabenz alone or preceded by intracerebroventricular ouabain were recorded in conscious SHR and Wistar-Kyoto (WKY) rats maintained from 4 to 8 weeks of age on different sodium diets: 1) low sodium intake (LNa, 17 mumol), 2) normal sodium intake (NNa, 101 mumol), and 3) HNa (1,370 mumol). SHR on NNa showed significantly higher MAP and RSNA compared with WKY rats on NNa. HNa or LNa significantly increased or decreased MAP but had no effects on resting RSNA in SHR and had no effects on resting MAP and RSNA in WKY rats. Intracerebroventricular ouabain induced dose-dependent increases in MAP, RSNA, and HR. In both SHR and WKY rats, LNa significantly enhanced these responses. In contrast, HNa significantly attenuated these responses only in SHR. Air stress increased and intracerebroventricular guanabenz decreased MAP, HR, and RSNA. The magnitudes of increases and decreases were significantly larger in SHR than in WKY rats. In WKY rats, dietary sodium did not change these responses. In contrast, in SHR, HNa significantly enhanced MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz.(ABSTRACT TRUNCATED AT 250 WORDS)
Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure.
Authors: Wolff M R , de Tombe P P , Harasawa Y , Burkhoff D , Bier S , Hunter W C , Gerstenblith G , Kass D A
Published: June 2012

The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3 +/- 2.9 days and compared with a separate control group (n = 8). STudies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29 +/- 0.94 versus 2.71 +/- 0.98 mm Hg/ml, p less than 0.01) and lowered end-systolic stiffness at a matched stress (956.1 +/- 123.5 versus 1,401.7 +/- 431.7 g/cm2, p less than 0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3 +/- 3.9 versus 21.9 +/- 7.6 ml, p less than 0.01). Inotropic response to increased heart rate and exogenous beta-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1 +/- 1.1 versus 2.9 +/- 1.4 ml O2.mm Hg-1.ml-1.100 g left ventricle-1, p less than 0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation-contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure.