bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulatory effects of splanchnic nerve stimulation in developing swine
Authors: Buckley N. M. , Brazeau P. , Frasier I. D. , Gootman P. M.
Published: December 2017

The relative maturity of immediate intestinal circulatory responses to efferent splanchnic nerve stimulation for 20 s was tested in 34 piglets (1 day-1 mo old) under pentobarbital anesthesia (15-30 mg/kg). Aortic pressure, heart rate, and superior mesenteric arterial flow (measured by electromagnetic flow transducers) were recorded simultaneously. Intestinal vascular resistance was calculated as mean aortic pressure/mean arterial flow. Resistance increased in most animals during experimental inhibition of the carotid sinus baroreceptor reflex. Transection of the splanchnic nerve decreased mesenteric resistance in all animals. Nerve stimulation at 2 Hz was not effective in all of the youngest animals; at 3 Hz, mesenteric resistance increased in all animals. The latency of this response was shorter at each increase in stimulation frequency. The aortic pressure rise associated with splanchnic nerve stimulation was greater with each increase in frequency. This rise was attenuated or absent after adrenalectomy and during postganglionic fiber stimulation. The vasoconstrictor effect of splanchnic nerve stimulation was attenuated after alpha-adrenergic receptor blockade with phentolamine in a dose (0.25-0.75 mg/kg) that blocked vasoconstrictor effects of norepinephrine (0.5 micrograms/kg). We conclude that alpha-adrenergic mechanisms are functional, although not mature, and that sympathetic vasoconstrictor tone is present in the intestinal circulation of swine at birth.
Development of a cardiomyopathy in a model of noninsulin-dependent diabetes
Authors: Schaffer S. W. , Tan B. H. , Wilson G. L.
Published: December 2017

Wistar rats were injected with streptozotocin (SZ) at 3 days of age. This maneuver produced a marked glucose intolerance, as determined by intraperitoneal glucose tolerance tests, but plasma fasting and nonfasting glucose values remained at or near normal throughout the 12-mo study period. Hearts obtained from these glucose-intolerant rats exhibited a progressive cardiomyopathy that consisted of both contractile and metabolic abnormalities. Contractile abnormalities were characterized by reductions in aortic output, ventricular pressure, and cardiac work. Associated with these mechanical defects was a decrease in glucose utilization. These abnormalities were not ameliorated by acute exposure to insulin or changes in the work load of the heart. These results demonstrate that, in the rat, a progressive cardiomyopathy results from persistent glucose intolerance in the absence of fasting hyperglycemia. This cardiomyopathy is reminiscent of that described in human noninsulin-dependent diabetes.
Reflex sympathetic effects on liver vascular space and liver perfusion in dogs
Authors: Cousineau D. , Goresky C. A. , Rose C. P. , Lee S.
Published: December 2017

The effects of sympathetic fiber activation on liver vascular volume and on the perfusion of the liver were ascertained in dogs by use of the multiple indicator-dilution technique. Portal vein-hepatic vein dilution patterns were obtained following injection of a mixture containing 51Cr-labeled red blood cells (a vascular reference), 14C-labeled sucrose (an interstitial reference), and 3H-labeled water (a cellular reference). Liver vascular, interstitial, and cellular water spaces were measured from the dilution data under control conditions and following activation of the sympathetic system by bilateral occlusion of carotid arteries. Carotid occlusion significantly increased plasma norepinephrine values without changing plasma epinephrine concentration, indicating that the resulting reflex sympathetic activation was selective for peripheral fibers. Although average blood flow did not change, liver vascular volume decreased by 40% during the sympathetic activation, and sucrose interstitial space and accessible cellular water space were unchanged. These findings indicate that there were no areas of no flow in the liver during the sympathetic activation, despite the observed large diminution in vascular blood content.
Uptake and metabolism of norepinephrine by endothelium of dog pulmonary artery
Authors: Rorie D. K. , Tyce G. M.
Published: December 2017

The contribution of endothelium of dog pulmonary artery to the extraneuronal metabolism of norepinephrine was determined. Pulmonary artery was cut into helical strips; the endothelium was removed from half of the strips by gently stroking them with a wooden applicator stick. All strips were immersed in l-[3H]norepinephrine (2 X 10(-7) M) and mounted for superfusion. Superfusate was collected continuously before, during, and after electrical stimulation (10 V, 2 ms, 2 Hz). Column chromatography was used to separate [3H]norepinephrine and its radiolabeled metabolites in superfusate. Quantitation was by liquid scintillation spectrometry. Previous studies have established that 3,4-dihydroxyphenylglycol is of neuronal origin and that O-methylated metabolites are of extraneuronal origin. Since cocaine prevented neuronal uptake of norepinephrine, the reduction in metabolites of norepinephrine of extraneuronal origin in arteries with endothelium removed represented the contribution of endothelium to extraneuronal metabolism. O-Methylated metabolites were decreased from 3.50 to 2.17 X 10(3) dpm/2 ml of superfusate during basal conditions preceding electrical stimulation and from 11.16 to 6.94 X 10(3) dpm/2 ml of superfusate during electrical stimulation when endothelium had been removed. Decreases in extraneuronal metabolite production continued throughout the basal periods following stimulation. These studies suggest that in small pulmonary artery a substantial amount of the total norepinephrine that is released at the neuroeffector junction may be metabolized following uptake into endothelium.
Sciatic nerve blood flow measured by laser Doppler flowmetry and [14C]iodoantipyrine
Authors: Rundquist I. , Smith Q. R. , Michel M. E. , Ask P. , Oberg P. A. , Rapoport S. I.
Published: December 2017

Blood flow was examined in sciatic nerves of pentobarbital-anesthetized rats by means of laser Doppler flowmetry (LDF) and intravenous [14C]iodoantipyrine infusion. Continuous LDF signals demonstrated slow oscillations and acute, pressure-related changes in flow. The steady-state LDF signal was related linearly to nerve blood flow, as measured with [14C]iodoantipyrine, in intact nerves and nerves stripped of the epineurium. In 14 intact nerves, nerve blood flow averaged 0.27 +/- 0.03 (SE) ml X min-1 X g-1, whereas it averaged 0.13 +/- 0.01 in 5 stripped nerves. Autoradiographs of [3H]-nicotine-infused nerves and intra-arterial injection of 57Co-labeled microspheres demonstrated that flow was not uniform throughout the nerve cross section. The results indicate that LDF can be used to examine nerve blood flow in vivo, demonstrate a linear relation between the LDF signal and flow, and establish absolute values for blood flow in intact and stripped nerves of the anesthetized rat.
Role of alpha-receptors in estrogen-induced vasodilation in nonpregnant sheep
Authors: Naden R. P. , Rosenfeld C. R.
Published: December 2017

Estradiol-17 beta (E2) produces vasodilation in several systemic vascular beds, but most extensively in the nonpregnant uterus. It has been postulated that E2 induces this vasodilation via blockade of vascular alpha-adrenergic receptors. This hypothesis was tested in six chronically instrumented, nonpregnant sheep by comparing the systemic and uterine hemodynamic responses to intravenous E2, to an alpha-adrenergic receptor blocker, phentolamine, and to both agents given together. Uterine blood flow (UBF) increased significantly after E2 administration, from 20 +/- 7 to 233 +/- 37 (SE) ml/min. In contrast, phentolamine had no detectable effect on UBF or on the UBF response to E2 when both were given together. Similar contrasting responses were observed in the effects of E2 and/or phentolamine on the systemic vasculature. When responses to alpha-agonists were evaluated, there was no evidence of alpha-blockade following E2 despite the substantial vasodilation; in contrast, alpha-blockade was present during phentolamine administration when no vasodilation was noted. Therefore, we conclude that E2-induced vasodilation in chronically instrumented sheep is not mediated through blockade of vascular alpha-adrenergic receptors.
Low sodium attenuation of the Ca2+ paradox in the newborn rabbit myocardium
Authors: Uemura S. , Young H. , Matsuoka S. , Jarmakani J. M.
Published: December 2017

The effect of low sodium (Na 24 mM) perfusate during Ca2+ depletion on mechanical function, tissue high-energy phosphate, creatine kinase (CK) release, and tissue potassium was studied in the arterially perfused newborn and adult rabbit heart. During Ca2+ depletion, the time for DT and +dT/dtmax to decline to half-maximal value in newborn muscles perfused with low Na (46 +/- 3 S) was significantly (P less than 0.05) longer than the value obtained with normal Na (14 +/- 1 S). Similar values were obtained in the adult. During Ca2+ repletion, the increase in resting tension and CK release was attenuated in the low Na groups, and the values in the newborn were significantly less than in the adult. The recovery of +dT/dtmax and tissue high-energy phosphates in the low Na groups were significantly greater than in the normal Na groups, and the values in the newborn were significantly greater than in the adult. These data suggest that low Na during the Ca2+-free period delays both cellular Ca2+ depletion during the Ca2+-free period and Ca2+ influx during Ca2+ repletion. This effect in the newborn is greater than in the adult and might be explained by Na+-Ca2+ exchange.
Frequency modulation and synchronization of spontaneous oscillations in cardiac cells
Authors: Capogrossi M. C. , Lakatta E. G.
Published: December 2017

Both intact mammalian cardiac muscle and single adult Ca2+-tolerant myocytes, under appropriate experimental conditions, exhibit periodic, spontaneous myofilament oscillations that originate locally within a cell and propagate longitudinally as contractile waves. We have used microscopic imaging techniques to study the effect of electrical stimulation on the oscillation characteristics in single rat and rabbit myocytes. Unstimulated rat cells bathed in Cao of 1-3 mM exhibited these oscillations. During stimulation at rates between 6 and 120 min-1, oscillations did not occur in the interval between stimulated contractions, and following termination of stimulation a transient suppression of the spontaneous oscillation frequency occurred. Conversely, with higher cell Ca2+ loading, achieved by increasing the [Ca2+]o or by addition of isoproterenol or ouabain, stimulation caused de novo oscillations in rabbit cells and increased the spontaneous oscillation frequency in rat cells to levels that resulted in their appearance between stimulated contractions. The tendency for myofilament motion to occur simultaneously at multiple foci was also increased by stimulation at high frequencies, and partial synchronization of these foci resulted in oscillations of an increased amplitude. The modulation of the spontaneous oscillation characteristics in single cells by stimulation may explain, in part, some effects of stimulation on Ca2+-dependent oscillatory phenomena in intact cardiac tissues.
Norepinephrine-induced phasic activity in tail arteries from genetically hypertensive rats
Authors: Myers J. H. , Lamb F. S. , Webb R. C.
Published: December 2017

The effects of norepinephrine on contractile force development were studied in tail artery strips from spontaneously hypertensive stroke-prone (SHRSP) and Kyoto-Wistar normotensive rats (WKY). The strips were mounted in physiological salt solution between a fixed base and force transducers; isometric contractions were recorded. Norepinephrine-induced were characterized by fluctuations in contractile activity, whereas contractile responses in arteries from WKY remained constant with time. The magnitude and frequency of phasic responses in SHRSP arteries varied directly with increasing concentrations of norepinephrine (1.8 X 10(-9) to 1.8 X 10(-6) M). The phasic responses induced by norepinephrine in SHRSP arteries were reversed by the following experimental interventions: 1) 10(-4) M ouabain; 2) 20 degrees C; 3) potassium-free solution; 4) 1.0 mM BaCl2; 5) 20 mM KCl; 6) 30 mM tetraethylammonium chloride; 7) chloride-free solution; and 8) 10(-7) M D 600 (calcium channel blocker). It is proposed that the phasic contractile responses to norepinephrine in SHRSP are related to altered movements of calcium and potassium across the cell membrane. This study demonstrates a very distinct functional individuality in the arterial vascular smooth muscle cell membrane of SHRSP.
Central nervous system cardiovascular effects of bombesin in conscious rats
Authors: Fisher L. A. , Cave C. R. , Brown M. R.
Published: December 2017

The effects of intracerebroventricular administration of bombesin on mean arterial pressure and heart rate were studied in conscious, freely moving rats. Injection of bombesin produced dose-dependent elevations of mean arterial pressure and reductions of heart rate. These effects were not caused by leakage of bombesin into the peripheral circulation. Adrenalectomy abolished the pressor action of bombesin but did not alter bombesin-induced bradycardia. Systemic phentolamine pretreatment prevented bombesin-induced changes of mean arterial pressure, whereas rats treated intravenously with captopril or a vasopressin antagonist still exhibited pressor responses to bombesin administration. Bombesin-induced bradycardia was partially antagonized by intravenous atropine methyl nitrate administration, whereas systemic injections of propranolol did not modify this response. It is concluded that bombesin acts within the central nervous system to elevate mean arterial pressure through an adrenal-dependent mechanism involving alpha-adrenergic receptors and to reduce heart rate through an adrenal-independent mechanism involving, at least in part, cardiac parasympathetic nervous activation.
Interaction of CO2 and ammonia on cerebral blood flow and O2 consumption in dogs
Authors: Barzilay Z. , Britten A. G. , Koehler R. C. , Dean J. M. , Traystman R. J.
Published: December 2017

Studies of acutely induced hyperammonemia and chronic hyperammonemia associated with liver dysfunction suggest that cerebral blood flow (CBF) and O2 consumption (CMRO2) become uncoupled and that CMRo2 may depend on arterial CO2 tension (PaCO2). We examined CBF (radiolabeled microspheres) and CMRO2 during hypercapnia (PaCO2 congruent to 74 Torr) and hypocapnia (PaCO2 congruent to 21 Torr) both before and during intravenous ammonium acetate infusion in pentobarbital-anesthetized dogs. Continuous infusion over 120 min produced stable increases of arterial ammonia levels (1,400 mumol/l) by 30 min, whereas CBF, CMRO2, and O2 extraction (measured at sagittal sinus) remained unchanged when PaCO2 was held constant (congruent to 35 Torr). Acute hyperammonemia attenuated the increase in CBF during hypercapnia by 44% and abolished the decrease in CBF during hypercapnia. Regional blood flow to pons and midbrain increased under normocapnic conditions, and midbrain blood flow increased further during hypocapnia. Sodium acetate infusion did not affect CBF responses to CO2. Thus we failed to observe an uncoupling of global CBF and CMRO2 during normocapnic hyperammonemia, or an interaction of CO2 and ammonia on CMRO2, although the increased pons and midbrain blood flow may reflect regional effects of ammonia on reticular activating system metabolism. On the basis of the literature, we suggest that the attenuated hypercapnic CBF response may arise from impaired glial regulation of extracellular potassium and bicarbonate concentrations and that lactic acid production, enhanced by combined alkalosis and hyperammonemia, may contribute to the abolition of hypocapnic vasoconstriction.
Effects of vasopressin on the coronary circulation: reserve and regulation during ischemia
Authors: Khayyal M. A. , Eng C. , Franzen D. , Breall J. A. , Kirk E. S.
Published: December 2017

In 18 dogs, intracoronary infusion of vasopressin produced a 40% reduction in coronary flow without significantly affecting systemic hemodynamics. The blood flow reduction occurred in a uniform transmural pattern without evidence of a gradient. The reduction in coronary flow resulted in a decrease in regional contractility as determined by isometric strain gauge arches. The decrease in regional contractility was transiently reversed by bolus injection of adenosine into the perfusion line. This suggests that the reduction of blood flow due to vasopressin was causing ischemia. Evidence for ischemia was also supported by measurements of local vein and tissue lactate production. Despite the apparently ischemic conditions, the vascular bed demonstrated evidence for significant reserve and regulation. Pressure-flow relationships performed under control and during vasopressin infusion demonstrated that the coronary vasculature retained its ability to regulate or defend a given level of coronary flow over a range of coronary perfusion pressures. Vasopressin produced a mild decrease in the peak hyperemic flow after a 15-s coronary occlusion and shortened the duration of reactive hyperemia. These overall findings are compatible with a predominant vasoconstrictor effect on the distal coronary vasculature. A role for a myogenic factor in the control of the coronary circulation is suggested, which is amplified by vasopressin.
Flow restriction of one carotid artery in juvenile rats inhibits growth of arterial diameter
Authors: Guyton J. R. , Hartley C. J.
Published: December 2017

Blood flow has long been hypothesized to be a primary determinant of arterial diameter growth. To verify this hypothesis, we placed a flow-restricting silver clip on one carotid artery and a completely nonocclusive clip on the contralateral artery in 13 rats (45-65 g). After 6-12 wk, measurements of vessel diameters and pulsed Doppler velocity wave-forms were obtained proximal to the clips, where flows differed from one side to the other, but mean pressures could be assumed approximately equal. Rats were anesthetized prior to these determinations and were fixed by perfusion at normal arterial pressure immediately thereafter. Flow reduction on the tightly clipped side averaged 35%. Flow-restricted arteries consistently showed reduction of diameter growth, averaging -10.2% of control diameters (P = 0.001). Thicknesses of the tunica media were similar on the flow-restricted and control sides. Side-to-side lumen circumference ratios were not correlated with mean blood flow velocities but were correlated with peak velocity (r = 0.62) and with an index of velocity pulsatility (r = 0.80). These results confirm a relationship between blood flow and arterial diameter and raise the possibility of a role for flow pulsatility.
Brain stem area with C1 epinephrine neurons mediates baroreflex vasodepressor responses
Authors: Granata A. R. , Ruggiero D. A. , Park D. H. , Joh T. H. , Reis D. J.
Published: December 2017

In anesthetized, paralyzed rats, bilateral electrolytic lesions of rostral ventrolateral medulla (RVL) containing epinephrine neurons of the C1 group 1) abolished the reflex hypotension and bradycardia elicited by electrical stimulation of the left vagus nerve or stretch of the left carotid sinus and 2) reduced arterial pressure (AP) and heart rate (HR) to values comparable to spinal cord transection. Combined lesions of the right nucleus tractus solitarii (NTS) and left or right C1 area did not alter AP. However, lesions of right NTS combined with lesions or microinjection of kainic acid into the left, but not right, C1 area abolished vasodepressor reflexes. Vasodepressor reflexes were unchanged by midcollicular decerebration, bilateral lesions of the parabrachial complex of the pons, or (after right NTS lesions) by lesions of the raphe or other reticular areas of the left half of the medulla. We conclude that neurons of the RVL, possibly belonging to the C1 epinephrine group, mediate vasodepressor responses from arterial baro- and other cardiopulmonary receptors, the pathway may be via a direct NTS-RVL projection, neurons in the C1 area of RVL are necessary for maintaining resting levels of arterial pressure.
Atriopeptins: renal-specific vasodilators in conscious dogs
Authors: Hintze T. H. , Currie M. G. , Needleman P.
Published: December 2017

Conscious dogs were instrumented to study the effects of atriopeptins (I, II, III) on renal, iliac, mesenteric, and coronary blood flow. Intravenous injection of atriopeptins II and III caused a dose-related increase in renal blood flow, whereas atriopeptin I had no effect. Atriopeptins II and III at 5 micrograms/kg increased renal blood flow 27 +/- 5.0% from 252 +/- 29 ml/min and 18 +/- 2.9% from 238 +/- 32 ml/min and reduced renal vascular resistance 24 +/- 3.2% from 0.431 +/- 0.048 mmHg X ml-1 X min and 15.1 +/- 1.2% from 0.443 +/- 0.023 mmHg X ml-1 X min, respectively. Atriopeptin I, II, or III exerted no significant effect on systemic arterial pressure, heart rate, coronary, mesenteric, or iliac blood flows. Doses of nitroglycerin (25 micrograms/kg) that increased renal blood flow (28 +/- 5.0%) to a degree comparable to atriopeptins II and III also caused increases in coronary, iliac, and mesenteric blood flows and produced falls in systemic blood pressure and a reflex tachycardia. Thus in the conscious dog, atriopeptins II and III are potent selective renal vasodilators that do not exhibit systemic hemodynamic effects in contrast to nitroglycerin, a nonselective vasodilator. Cleavage at the carboxy terminal end of these peptides to yield atriopeptin I abolishes the renal vasodilator action entirely.
Beta-adrenergic modulation of direct defibrillation energy in anesthetized dog heart
Authors: Ruffy R. , Schechtman K. , Monje E.
Published: December 2017

Catecholamines facilitate ventricular defibrillation in animals. We examined the effects of beta-adrenergic stimulation and blockade on ventricular defibrillation threshold in anesthetized dogs. Calibrated shocks were delivered between epicardial and superior vena caval electrodes, and defibrillation threshold was measured before and after administration of isoproterenol and propranolol. Eight dogs (group 1) received isoproterenol before propranolol. Nine dogs (group 2) received propranolol before isoproterenol. In group 1, the minimum energy required to defibrillate before isoproterenol was 10.6 +/- 1.7 (SE) J and decreased to 5.9 +/- 1.3 with isoproterenol (P less than 0.001). In group 2, the minimum energy required to defibrillate was 8.3 +/- 2.4 J before propranolol and increased to 10.7 +/- 2.2 after propranolol (P less than 0.001). In group 1, propranolol after isoproterenol increased defibrillation threshold (P less than 0.07), whereas in group 2 isoproterenol after propranolol produced no significant change in defibrillation threshold. Thus beta-stimulation decreased defibrillation threshold significantly in the anesthetized dog heart, an effect that was blocked by propranolol. Conversely, propranolol increased defibrillation threshold, an effect that occurred despite prior beta-stimulation, probably because of the short half-life of isoproterenol.
Renin-angiotensin mechanisms in oral contraceptive hypertension in conscious rats
Authors: Fowler W. L. , Johnson J. A. , Kurz K. D. , Payne C. G.
Published: December 2017

Rats were placed on powdered chow containing either no additives (controls), mestranol (a synthetic estrogen), norethynodrel (a synthetic progestin), or both mestranol and norethynodrel. After 6 mo on these diets, catheters were placed in the carotid artery and jugular vein of each rat. An arterial blood sample was obtained for plasma renin activity (PRA), plasma renin concentration (PRC), and plasma renin substrate concentration (PRS). Mean arterial pressure was measured in each rat. The angiotensin II (ANG II) antagonist, [Sar1-Ile8]ANG II, was infused intravenously for 30 min while blood pressure was recorded. Rats treated with mestranol and/or norethynodrel had PRA and PRC values that were not different from the control rats; however, mestranol-treated rats and rats treated with mestranol plus norethynodrel had PRS values that were substantially (P less than 0.01) higher than the controls. Arterial pressures in rats treated with mestranol and with mestranol plus norethynodrel were significantly (P less than 0.01) elevated when compared with the controls and with the rats treated with norethynodrel alone. Infusion of the ANG II antagonist failed to alter arterial pressure in any of the groups of rats. These results indicated that, in the steroid combination found in the oral contraceptive Enovid, it is the estrogenic component that results in hypertension in this rat model. Also this study found no evidence that ANG II plays a role in maintaining the elevated arterial pressure following long-term treatment with mestranol in rats.
Geometry of cell and bundle appositions in cardiac muscle: light microscopy
Authors: Sommer J. R. , Scherer B.
Published: December 2017

A strand each of cardiac conduction and working cells of the left ventricle is studied in serial sections with the light microscope to define the geometry of cell appositions that form networks of cardiac muscle cells. Anatomic and thus electrical coupling is very frequent among all cells; it is accomplished within a few hundred micrometers axially regardless at which point of the strand electrical current is assumed to originate. Most individual cardiac myocytes are not only connected in longitudinal direction but also make lateral contacts. Only a few bundles of varying diameters remain unconnected over appreciable distances of greater than 200 micron (so-called unit bundles). Thus abnormal current vectors are averted, at least in normal cardiac tissue, even if excitation were to originate from a point. Plastic thick sections studied with the light microscope were unsuitable to define cell lengths.
Development of myocardial dysfunction in endotoxin shock
Authors: Parker J. L. , Adams H. R.
Published: December 2017

Isolated heart muscle preparations were used to investigate the onset and development of myocardial inotropic dysfunction during endotoxin shock in guinea pigs. Left atrial muscles were removed from separate groups of animals at increasing time intervals after administration of either 4 mg/kg purified Escherichia coli endotoxin (shock groups) or an equivalent volume of isotonic saline (control groups). Peak developed contractile tension (CT) and maximal rate of tension development (+dT/dtmax) were significantly depressed in shock tissues as early as 2 h postendotoxin (P less than 0.01), with the magnitude of the contractile deficit progressively increasing during 4, 6, and 12 h postendotoxin. Contractility remained significantly depressed (P less than 0.001) at 16 and 24 h postendotoxin but progressively recovered toward control levels during 16, 24, 48, and 72 h postendotoxin. Shock-induced myocardial dysfunction was characterized by altered contractile responsiveness to low-Ca2+ medium (0.5 mM), gentamicin (4 mM), and hypoxia; altered inotropic reactivity to these interventions followed similar temporal development as the postendotoxin changes in basal contractile parameters. Left ventricular papillary muscles obtained at 16 h postendotoxin corroborated the shock-induced contractile depression observed in atria. These studies provide evidence for early and progressive intrinsic myocardial dysfunction in endotoxin shock and demonstrate that this dysfunction can be unmasked through the study of in vitro atrial and ventricular heart muscle preparations isolated from in vivo shocked animals.
Alveolar inflammation and arachidonate metabolism in monocrotaline-induced pulmonary hypertension
Authors: Stenmark K. R. , Morganroth M. L. , Remigio L. K. , Voelkel N. F. , Murphy R. C. , Henson P. M. , Mathias M. M. , Reeves J. T.
Published: December 2017

We tested the hypothesis that monocrotaline would activate arachidonic acid metabolism in rats. If activation occurred before the pulmonary hypertension developed, arachidonate metabolites could play a role in the hypertensive monocrotaline injury. We found that 1 wk after monocrotaline administration 6-ketoprostaglandin F1 alpha and leukotriene C4 were increased in lung lavages. At 3 wk when pulmonary hypertension was well developed, lung lavage contained increased 6-ketoprostaglandin F1 alpha and thromboxane B2. In addition, the number and activity of white blood cells in the lavages was increased, and abnormal alveolar macrophages were present. The lung extract contained slow-reacting substances including leukotriene D4. Indomethacin administration inhibited the formation of cyclooxygenase metabolites but did not prevent pulmonary hypertension. Diethylcarbamazine administration reduced the numbers and activity of inflammatory cells, increased pulmonary hypertension, prevented right ventricular hypertrophy, and inhibited the formation of slow-reacting substances. We concluded that arachidonate metabolism was activated before pulmonary hypertension developed, that the inflammatory cells in the alveolus accompanied the hypertensive process, and that diethylcarbamazine attenuated both the monocrotaline-induced inflammatory response and the pulmonary hypertension.
Left ventricular failure induced by myocardial infarction. II. Tissue morphometry
Authors: Anversa P. , Loud A. V. , Levicky V. , Guideri G.
Published: December 2017

Three days after myocardial infarction involving 57% of the left ventricle in rats, the viable tissue of the left ventricle expanded 29%, whereas myocardial hypertrophy in the right ventricle was 19%. To determine whether tissue oxygenation in the hypertrophied ventricles was supported by a proportional growth of the capillary network, morphometric analysis was used to measure capillary luminal volume and surface densities and the diffusion distance for O2. The volume fraction of capillary lumen and the luminal surface of capillaries, related to O2 availability and diffusion, were altered by -21 and -19%, respectively, in the left ventricle and by -23 and -20%, respectively, in the right ventricle. The path length for O2 transport was found to be increased by 12 and 15% in the left and right ventricle, respectively. In contrast, myocyte mass expanded in proportion to tissue growth in the left ventricle and exceeded tissue growth by 5% in the right ventricle. Myocyte mitochondria and myofibrils both grew in proportion to the cells, so that their volume ratio was not changed in either ventricle. The relatively inadequate adaptation of the capillary vasculature suggests that hypertrophy after severe myocardial infarction may initially leave the heart more vulnerable to additional ischemic episodes.
Physiological effects of pH changes on colloid osmotic pressures
Authors: Will B. R. , Brace R. A.
Published: December 2017

Our purpose was to explore the effects of variations in pH, particularly in the physiological range, on the colloid osmotic pressure (COP) of the body's fluids. Theoretically, changing pH would alter the electrical charge density on plasma proteins and the interstitial ground substance, thereby altering plasma and interstitial protein osmotic pressure as well as interstitial fluid pressure. We found that the COP of human plasma, human albumin, bovine albumin, and Wharton's jelly from human umbilical cords increased linearly as pH increased over the range of 6.0–8.0. COP of plasma and the albumins all displayed essentially the same sensitivity to pH. At equal concentrations, hyaluronate in umbilical cords was approximately 16 times more sensitive to pH than was plasma. Dextran 70 displayed no COP dependency on pH. For plasma, the albumins, and hyaluronate the pH dependence of COP on pH also decreased linearly with concentration (C in g/dl). For plasma and the albumins over the physiological range of pH, COP = COPpH 7.4 [1.00 + 0.01C (pH -7.40)] at 37 degrees C. The data suggest that, relative to the normal net transcapillary pressure gradient, physiological variations in pH affect plasma COP as well as interstitial fluid pressure and thus may play a significant role in regulating the body's fluid distribution.
Reflex cardiovascular effects of intracoronary acetylstrophanthidin in the conscious dog
Authors: Barron K. W. , Bishop V. S.
Published: December 2017

The present experiments were designed to examine the reflex cardiovascular effects of intracoronary administration of acetylstrophanthidin in the conscious dog. Administration of 4 micrograms/kg of this agent into the left circumflex coronary artery increased left ventricular dP/dtmax but had no effect on mean arterial pressure, heart rate, renal resistance, or iliac resistance. The positive inotropic effects of acetylstrophanthidin were less under control conditions (+599 mmHg/s) than during bilateral cervical vagal cold block (+850 mmHg/s, P less than 0.05); however, interruption of vagal efferent influences (atropine) alone did not alter the contractile effects of acetylstrophanthidin. Interruption of sympathetic efferent influences on the heart with either the nicotinic ganglionic receptor antagonist, hexamethonium, or the beta 1-adrenergic receptor antagonist, metoprolol, also augmented the inotropic effects of acetylstrophanthidin to a degree similar to that observed with vagal cold block. In contrast to the effects observed with acetylstrophanthidin, the inotropic effects of intracoronary administration of calcium gluconate were not altered by vagal cold block or any other conditions examined in this study. We conclude that interruption of vagal afferents results in an augmentation of the positive inotropic actions of acetylstrophanthidin and that this augmented inotropic effect can be accounted for by interruption of cardiac vagal afferent-mediated restraint on sympathetic outflow to the heart.
A re-examination of late outward plateau currents of cardiac Purkinje fibers
Authors: Jaeger J. M. , Gibbons W. R.
Published: December 2017

Two outward currents, IX1 and IX2, are thought to be activated by depolarization of the Purkinje fiber. One of these, IX1, is presently believed to play a critical role in repolarization of the action potential. The IX currents were originally analyzed in voltage-clamp experiments in sheep Purkinje fibers. These experiments were designed to minimize interference by other currents, and it was assumed that changes of the net current were produced entirely by the IX currents. We have tried to repeat the original experiments and the analysis that led to acceptance of the existence and roles of the IX currents, without success. Moreover, tests of how membrane current should behave if the IX current hypothesis is correct did not give satisfactory results. Our data suggest the original conclusions about IX1 and IX2 may need substantial revision.
Polarographic measurement of ascorbate washout in isolated perfused rabbit hearts
Authors: Arts T. , Kuikka J. T. , Reneman R. S. , Bassingthwaighte J. B.
Published: December 2017

To study the myocardial washout of ascorbate, the applicability of polarographic detection of ascorbate ions by a platinum electrode (sensitive area 0.03 mm2) was investigated, in both a calibration setup (sampling flow along the electrode: 100 microliter X s-1) and isolated, retrogradely perfused rabbit hearts. In the calibration setup at pH 7.4, the sensitivity of the electrode was 70 microA/mol. This sensitivity increased moderately with increasing pH (13%/unit pH) and increasing sampling flow rate (14% at an increase from 100 to 150 microliter X s-1). In the isolated hearts, ascorbate infused into the aorta was detected in a right ventricular drain by the electrode as well as by the use of 14C-labeled ascorbate. Both recorded time courses were similar except for a scaling factor dependent on flow velocity. During continuous infusion the arteriovenous difference of ascorbate was 2 +/- 2% (SD), indicating a relatively low consumption of ascorbate by the isolated heart. We conclude that polarographic measurement of ascorbate in the coronary effluent of an isolated rabbit heart can be performed on-line and relatively easily.
Capillary pressures in rat intestinal muscle and mucosal villi during venous pressure elevation
Authors: Davis M. J. , Gore R. W.
Published: December 2017

Whole-organ experiments designed to estimate the capillary filtration coefficient require information about the numerical relationship between capillary pressure and venous pressure. Indirect estimates using isogravimetric and isovolumetric methods indicate that 62-85% of a step change in venous pressure reaches the intestinal capillaries, taken as a whole. We have made direct measurements of capillary pressure with a servo-null micropressure system in the microcirculation of both the intestinal muscle and the mucosal villi of rats during local elevation of venous pressure. Consistent regional differences in the relationship between capillary pressure and venous pressure were observed. During increased venous pressure, submucosal arterioles constricted, while muscularis arterioles dilated. The diameter changes of the small arterioles were consistent with blood flow redistribution from mucosa to muscle during venous pressure elevation, but inconsistent with a pure myogenic response. These data raise questions about the exact role for the expression of the myogenic response during venous pressure elevation in the intestine and about previous interpretations of whole-organ experiments concerned with intestinal blood flow and fluid exchange.
A simple method for reducing cardiac output in the conscious lamb
Authors: Fahey J. T. , Lister G.
Published: December 2017

We have developed a method for reducing cardiac output in a controlled stepwise fashion using awake, intact, unsedated lambs. The method involves placing a balloon-tipped (Foley) catheter into the right atrium from a jugular vein isolated by a small neck incision. Systemic venous return and cardiac output are limited by balloon inflation. With each balloon inflation the animal reaches a new and stable cardiac output, which allows the measure of steady-state hemodynamic and metabolic variables. We have been able to decrease cardiac output to as low as 20% of the resting cardiac output and maintain a stable preparation. The reductions in cardiac output are quickly reversible by balloon deflation. Animal survival allows repeated study. We present data from five lambs studied between 26 and 36 days of age. Alterations in O2 consumption, O2 transport, O2 extraction, blood pressure, and arterial lactate concentration are examined in response to decrements in systemic blood flow and are consistent with changes seen in response to a reduction of cardiac output by other methods.
Hyperresponsiveness of monoaminergic mechanisms in DOCA/NaCl hypertensive rats
Authors: Chen Y. F. , Nagahama S. , Winternitz S. R. , Oparil S.
Published: December 2017

To examine the role of the sympathetic nervous system in the development of deoxycorticosterone acetate (DOCA)/NaCl hypertension and to test the hypothesis that the responsiveness of the sympathetic nervous system to stress is enhanced during the developmental phase of hypertension in this model before resting sympathetic activity becomes increased, DOCA/NaCl-treated rats and uninephrectomized control animals were studied after 3, 7, 14, and 28 days of treatment. Basal plasma norepinephrine and epinephrine in conscious, unrestrained resting DOCA/NaCl-treated rats were the same as in controls at 3, 7, and 14 days but were significantly elevated at 28 days of treatment. Ganglionic blockade resulted in a significantly greater decrease in mean arterial pressure in DOCA/NaCl rats than in controls at 14 and 28 days of treatment. At 14 days, DOCA/NaCl rats exhibited significantly greater increments in plasma norepinephrine and epinephrine following cold stress than did H2O controls. Basal plasma prolactin levels were elevated and release of dopamine from isolated superfused mediobasal hypothalami reduced in 28-day DOCA/NaCl hypertensive rats. These results indicate that sympathetic nervous system activity increases progressively during the development of DOCA/NaCl hypertension and that the sympathoadrenal system is hyperresponsive to environmental stress even early in the course of DOCA/NaCl treatment and suggest that hypothalamo-hypophyseal function is altered in this model of hypertension.
Atrial extract: hemodynamics in Wistar-Kyoto and spontaneously hypertensive rats
Authors: Pegram B. L. , Kardon M. B. , Trippodo N. C. , Cole F. E. , MacPhee A. A.
Published: December 2017

Partially purified low (LMW) and high-(HMW) molecular-weight atrial natriuretic extracts were administered intravenously (540 micrograms protein/kg) to conscious Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Both LMW and HMW atrial natriuretic extracts produced an immediate decrease in mean arterial pressure that reached maximum within 5 min and returned to control levels within 30 min. In both strains, cardiac output decreased approximately 14% following administration of LMW. Total peripheral resistance increased only in SHR. Organ blood flow was significantly decreased to skin, brain, heart, kidneys, and splanchnic organs of WKY and to skin, muscle, heart, and splanchnic organs of SHR following administration of LMW. Corresponding increases in organ vascular resistance index were observed in brain, heart, and splanchnic organs of WKY and in skin, heart, and splanchnic organs of SHR. To some extent, the changes in organ blood flow may be a reflection of the decrease in cardiac output induced by LMW. After administration of HMW, no significant changes were observed in cardiac output or total peripheral resistance, although they tended to decrease. Organ vascular resistance was decreased to skin, muscle, brain, and splanchnic organs of SHR. Little difference was observed between WKY and SHR responses to atrial natriuretic extracts. These data indicate that atrial natriuretic extracts have an effect on systemic and regional hemodynamics in conscious rats that differs markedly from those of vasodilators such as nitroglycerin or hydralazine.
Mechanism for dynamic changes in stenotic severity
Authors: Higgins D. R. , Santamore W. P. , Bove A. A. , Nemir P.
Published: December 2017

The mechanism responsible for rapid changes in stenotic severity or resistance due to alterations in perfusion pressure and distal resistance is addressed by this study. An in vitro, eccentric arterial stenosis model was created using 15 canine carotid arteries cannulated with silicone plugs containing special pressure-transducing catheters designed to measure pressure directly, within the stenosis. The vessels were perfused at perfusion pressures of 150, 100, and 75 mmHg and at two levels of distal resistance while perfusion pressure, distal pressure, stenotic pressure, and flow were recorded. Orthogonal arteriograms were performed. Stenotic resistance was calculated as (perfusion pressure--distal pressure)/flow. All variables changed significantly (P less than 0.05) with decreases in perfusion pressure. Stenotic resistance always increased (P less than 0.02) as perfusion pressure or distal resistance decreased. These dynamic changes in stenotic resistance occurred at stenotic pressures well above the atmospheric, extraluminal pressure. Arteriographic data demonstrated decreasing stenotic luminal area with decreasing stenotic pressure. These results confirm the assertion that rapid changes in stenotic resistance are related to changes in stenotic luminal area and are not due to extrinsic forces. The principles of the Starling resistor are, therefore, not applicable to dynamic arterial stenoses. This information is immediately relevant to clinical situations in which complaint, severe stenosis results in ischemia.
Intestinal hemodynamics in dogs with chronic one-kidney, one-wrapped hypertension
Authors: Bell D. R. , Overbeck H. W.
Published: December 2017

In pentobarbital-anesthetized dogs with chronic one-kidney, one-wrapped perinephritic hypertension, the status of blood flow and resistance differs among vascular beds. There is normal blood flow with elevated resistance in the limb and elevated blood flow with normal resistance in the ileum. In the present study we investigated the mechanism of elevated flow and normal resistance in the ileum by measuring blood flow, pressure, O2 consumption, reactive hyperemia, pressure-flow relationships, resistance at maximal vasodilation, and nonentrapment (shunting) of 9-microns microspheres in vascularly isolated, blood-perfused ilea of 11 24-h fasted dogs with chronic (greater than 4 wk duration) one-kidney perinephritic hypertension [1KH; PA = 163 +/- 8 (SD) mmHg] and 15 fasted normotensive one-kidney, sham-wrapped dogs (1KC; PA = 108 +/- 7 mmHg). In 1KH ileal blood flow was elevated by 35% (P less than 0.001), but ileal vascular resistance was unchanged. Pressure-flow relationships were similar in hypertensive and normotensive ilea, with little evidence for significant autoregulation in either. We also noted no significant differences in ileal O2 consumption, reactive hyperemia, or resistance at maximal vasodilation. However, we found nonentrapment of microspheres to be a positive function of perfusion pressure (P less than 0.02) and to be increased by 40% during ileal perfusion at levels of perfusion pressure within the hypertensive range (150-200 mmHg). Thus the increased ileal blood flow in 1KH may reflect the effects of a poorly autoregulating tissue, as well as "shunt" flow through pressure-activated channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Attenuation of muscarinic cholinergic inhibition by islet-activating protein in the heart
Authors: Endoh M. , Maruyama M. , Iijima T.
Published: December 2017

Experiments were carried out to investigate the influence of islet-activating protein (IAP), a pertussis toxin, on the autonomic regulation of cardiac function. In atria isolated from rats given intravenous IAP (0.125-1.0 micrograms/100 g body wt) 12-72 h prior to experiments, the negative chronotropic and inotropic actions of carbachol were attenuated in a dose- and time-dependent manner. The inhibitory action of carbachol in the absence of isoproterenol and its attenuation by IAP were not associated with any changes in tissue adenosine 3',5'-cyclic monophosphate (cAMP) levels. In addition, carbachol decreased the isoproterenol-induced elevation of cAMP levels and inhibited the positive chronotropic and inotropic responses to isoproterenol. The inhibitory action of carbachol on the isoproterenol-induced functional and cAMP responses was also reduced by the IAP treatment. The increase in tissue guanosine 3',5'-cyclic monophosphate (cGMP) levels produced by carbachol was likewise abolished by the IAP treatment. These results indicate that IAP treatment attenuates the inhibitory actions of carbachol elicited via muscarinic receptors through both cAMP-dependent and cAMP-independent subcellular processes.