bluuebunny/crossref_metadata_2025 huggingface dataset:
muscle microcirculation: effects of tissue pH, PCO2, and PO2 during systemic hypoxia
Authors: Morff R. J. , Harris P. D. , Wiegman D. L. , Miller F. N.
Published: December 2017

The responses of arterioles and venules to systemic hypoxia (fractional inspired O2 concentration 0.10) were determined for the rat cremaster muscle that was positioned with intact nerve and vascular supplies in a tissue bath that had controlled pH, O2 tension (PO2), CO2 tension (PCO2), and temperature. Blood pressure and heart rate were decreased significantly during systemic hypoxia. First- and second-order arterioles actively constricted during systemic hypoxia, whereas most first-, second-, and third-order venules had biphasic responses (dilation followed by constriction). There were no significant differences in the active arteriolar responses to systemic hypoxia when cremaster bath pH was altered from 6.9 to 7.2, or when bath PCO2 was changed from 60 +/- 2.2 to less than 5 mmHg; but, there was significantly greater arteriolar constriction with high bath PO2 (139 +/- 1.3 mmHg) in comparison to low bath PO2 (4.5 +/- 0.5 mmHg). Decreased bath pH, decreased PO2, and increased PCO2 had no effect on the dilation responses of first-, and second-, and third-order venules to systemic hypoxia; however, these bath alterations attenuated the constriction responses of third-order venules. alpha-Adrenergic receptor blockade did not alter the arteriolar responses to systemic hypoxia. Our data indicate 1) that there is a centrally mediated stimulus for constriction of first-order arterioles during systemic hypoxia, 2) that changes in local cremaster PO2, but not PCO2 or pH, can attenuate this centrally mediated arteriolar constriction, and 3) that the centrally mediated arteriolar constriction does not involve alpha-adrenergic receptors.
Effect of adenosine and dipyridamole on cerebral blood flow
Authors: Heistad D. D. , Marcus M. L. , Gourley J. K. , Busija D. W.
Published: December 2017

The purpose of these experiments was to determine whether infusions of adenosine and of dipyridamole, which raise levels of endogenous adenosine, increase cerebral blood flow (CBF). In anesthetized dogs and cats, intracarotid infusions of adenosine increased blood flow to cranial muscle but did not alter CBF (measured with microspheres). Anatomical limitations may prevent satisfactory examination of cerebral vascular responsiveness during intracarotid infusion of vasodilator drugs in these species. In anesthetized rabbits, infusion of adenosine 10 microM/min in the carotid artery produced a 2-fold increase in CBF. Infusion of dipyridamole 20 microM/min increased CBF 2.7-fold. Dipyridamole produced a small decrease in cerebral oxygen consumption, which indicates that the vasodilator effect of the drug is not an indirect effect secondary to increased metabolism. These data indicate that exogenous and endogenous adenosine increase CBF in rabbits.
Carotid chemoreceptors and vagi in hypoxic and cyanide-induced tachycardia in the dog
Authors: Gupta P. D. , Singh M.
Published: December 2017

We investigated the mechanisms underlying heart rate changes resulting from systemic hypoxia in anesthetized artificially ventilated dogs with low control heart rate (less than or equal to 93 beats/min). We observed that systemic hypoxia evoked tachycardia in intact dogs that was not significantly different from that evoked in dogs with beta-adrenergic blockade (BB). Also, tachycardia elicited in dogs with BB plus spinal section at C3 (BBSS) was significantly greater than in dogs with BBSS plus bilateral section of carotid sinus nerves. Furthermore, under various anesthetics, intracarotid injection of sodium cyanide induced a tachycardia response in dogs with low control heart rate (less than or equal to 97 beats/min) and a bradycardia response in dogs with high control heart rate (greater than or equal to 130 beats/min). These results suggest that 1) when the resting cardiac parasympathetic tone is high, systemic hypoxia evokes tachycardia which is mediated predominantly through efferent vagus nerves and 2) the stimulation of carotid chemoreceptors causes excitation of both cardioacceleratory and cardioinhibitory reflexes, the resultant response being dependent on the prevalent autonomic drive.
Blood flow in the hypertrophied right ventricular myocardium of unanesthetized ponies
Authors: Manohar M. , Bisgard G. E. , Bullard V. , Rankin J. H.
Published: December 2017

To examine the effects of right ventricular (RV) hypertrophy on regional myocardial blood flow and coronary vascular reserve, hemodynamics and myocardial blood flow (15-micrometers radio-nuclide-labeled microspheres) were studied in 12 unanesthetized adult ponies before and during intravenous isoproterenol HCl infusion (1 microgram.kg-1.min-1). Six ponies served as controls, whereas in each of the others the main pulmonary artery (PA) had been banded 35-90 days prior to the study. Marked RV hypertrophy was present in PA-banded animals. In these ponies, there was a significant increase in RV systolic pressure (147%), heart rate (88%), RV tension-time index (279%), and RV myocardial blood flow (137%), while their RV coronary vascular resistance was only 40% of that for control ponies. Blood flow in right side of the interventricular septum was also significantly higher in the PA-banded ponies. Endo/epi perfusion ratio exceeded 1.00 for both ventricular freewalls in all animals. With isoproterenol infusion, there was a marked increase in myocardial blood flow in both groups. However, in PA-banded ponies the endo/epi flow ratio decreased precipitously below 1.00 in both ventricular freewalls. In control ponies this did not happen in the RV freewall, and RV coronary vascular resistance decreased to 19% of its control value. In PA-banded ponies, the magnitude of decline in RV coronary vascular resistance was much smaller, only 32% of that for control ponies. It is concluded that, unlike in LV hypertrophy, transmural myocardial blood flow per unit mass is much higher in the hypertrophied RV myocardium of adult resting ponies, and this higher RV perfusion occurs at the expense of curtailed RV coronary vascular reserve.
Cardiac catecholamine stores after cardiac sympathectomy, 6-OHDA, and cardiac denervation
Authors: Priola D. V. , O'Brien W. J. , Dail W. G. , Simpson W. W.
Published: December 2017

Sympathetic nerves are known to reach the heart via classical vagal pathways. Bilateral cervicothoracic sympathectomy (CS) might be expected therefore to leave significant amounts of releasable catecholamines in the myocardium if the vagi are left intact. Cardiac responses to tyramine (500 micrograms intracoronary) were compared in animals with CS, extrinsic cardiac denervation (CD), and chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Dogs were placed on cardiopulmonary bypass and isovolumic pressures were recorded from the heart. In control animals, tyramine caused profound increases in rate (58%) and isovolumic pressures (86-170%). Ten CS animals demonstrated responses indistinguishable from control animals. Four CD and four 6-OHDA animals showed no response to tyramine. Cervical vagal stimulation after atropine in the CS animals produced tachycardia. Histofluorescent studies demonstrated the presence of significant numbers of cardiac adrenergic fibers in this group. The normal tyramine responsiveness of the CS animals was attributed to 1) significant numbers of vagal adrenergic fibers remaining in the heart after cervicothoracic sympathectomy, and 2) denervation supersensitivity, rendering the heart very responsive to the catecholamine that remains.
Effect of volume expansion on pressor response to angiotensin II in pregnant ewes
Authors: Matsuura S. , Naden R. P. , Gant N. F. , Parker C. R. , Rosenfeld C. R.
Published: December 2017

Vascular refractoriness to infused angiotensin II (AII) characterizes normal human and ovine pregnancy. To ascertain whether the refractoriness in the gravid ewe is mediated by either endogenous plasma concentrations of renin and AII or vasomotor reflexes, effects of acute volume expansion (VE) on the pressor response to AII were studied in chronically instrumented nonpregnant and near-term pregnant sheep. Dose-response curves describing the pressor response (delta BP) were determined before and after infusions of 1.0 1 of isotonic saline (NS) or 0.5 1 of 10% dextran (D). In nonpregnant sheep, hematocrit (Hct) and plasma renin activity (PRA) fell in all animals after NS (n = 7) and D (n = 6) (P less than 0.005). After VE with NS and D, delta BP increased at each dose of AII (P less than 0.05). The pressor response to AII in pregnant sheep was not altered by NS although decreases in Hct and PRA were comparable to those in nonpregnant sheep. Baroreceptor responses were not altered. Vascular refractoriness to infused AII in pregnant sheep is not due primarily to changes in plasma concentrations of renin-AII but more likely to another factor, vessel wall refractoriness. In this respect, the ewe is similar to the human.
Stability of an experimental atrioventricular reentrant tachycardia in dogs
Authors: Simson M. B. , Spear J. F. , Moore E. N.
Published: December 2017

The factors leading to spontaneous block and instability of a reentrant tachycardia were studied with a computer model and in eight anesthetized dogs with an electronically simulated atrioventricular (AV) bypass tract. The bypass tract delay could be changed in a programmed sequence. AV nodal refractoriness in the dogs was increased with verapamil. Stability of the reentrant tachycardia was assessed by noting how rapidly cycle-length changes from a transient alteration in the bypass-tract delay time would dampen out and the tendency of the reentrant tachycardia to spontaneously block. There was close agreement between computer model predictions and experimental results. After a transient change in bypass tract delay time, dampened oscillations of the cycle length were noted. The degree of dampening was related to the slope of the AV nodal refractory curve. When the reentrant tachycardia operated on a steep portion of the refractory curve (slope steeper than -1), spontaneous oscillations and block developed. In the dog, the reentrant tachycardias terminated spontaneously either by an increase in amplitude of oscillations or by an increase in AV nodal refractoriness. We conclude that, for stable reentry, a reentrant circuit must have no conduction block and must be able to dampen out transient perturbations.
Effects of verapamil on heart and circulation in hemorrhagic shock in dogs
Authors: Hackel D. B. , Mikat E. M. , Reimer K. , Whalen G.
Published: December 2017

Myocardial blood flow and left ventricular oxygen utilization were studied in verapamil-treated and untreated pentobarbital-anesthetized dogs subjected to hemorrhagic shock. Blood loss was similar in both groups. The dogs treated with verapamil (n = 15) during shock had a slower heart rate and lower left ventricular oxygen utilization than the untreated dogs (n = 14). Nevertheless, the treated dogs had a significantly higher myocardial blood flow and were able to maintain a higher cardiac index. Thus, verapamil has beneficial hemodynamic and metabolic effects that preserve myocardial function. These effects may explain the improved survival and protection of the heart against anatomic lesions, which have been demonstrated previously in dogs treated with verapamil during hemorrhagic shock.
Prostacyclin-thromboxane interactions in the platelet-perfused in vitro heart
Authors: Schror K. , Kohler P. , Muller M. , Peskar B. A. , Rosen P.
Published: December 2017

A preparation of an isolated platelet-perfused guinea pig heart is described, which was utilized to study prostacyclin-thromboxane interrelationships. Infusion of washed human platelets (4 X 10(8)/min) through the coronary vascular bed stimulated the vascular PGI2 production from 114 +/- 27 to 350 +/- 30 pg/ml (P less than 0.01) and was associated with a significant increase in platelet cAMP from 1.2 +/- 0.4 to 2.6 +/- 0.9 pmol/10(8) platelets (P less than 0.05). Administration of arachidonic acid (AA) (45 micrograms) to the system led to a further increase (eight- to ninefold) of PGI2 and yielded marked thromboxane formation (20-25 ng/ml). Treatment of the hearts with aspirin (1 mM) prevented the PGI2 formation and AA-induced increase in platelet cAMP. Treatment of platelets with aspirin prevented thromboxane formation but did not influence AA-induced changes in platelet cAMP and vascular PGI2 production. Bioassay data of PGI2 and rabbit aortic contracting substance gave results comparable to radioimmunoassay of 6-keto-PGF1 alpha and thromboxane B2. AA always decreased the coronary vascular resistance whether thromboxanes were formed or not.
Pulmonary vascular smooth muscle function in porcine splanchnic arterial occlusion shock
Authors: Greenberg S. , McGowan C. , Glenn T. M.
Published: December 2017

Pulmonary complications are a major cause of death in patients in various forms of shock. The exact causes of the pulmonary complications are unknown. This study evaluates the functional characteristics of intralobar pulmonary arteries (IPA) and veins (IPV) obtained from swine subjected to splanchnic arterial occlusion (SAO) shock ans subsequent cardiovascular collapse and sham-shocked swine subjected to surgery but no occlusion. The contractile response of pulmonary arteries to norepinephrine (NE) and serotonin (5-HT) were depressed when obtained from pigs subjected to SAO shock. The depression in the sensitivity to 5-HT and maximal tension development to 5-HT and NE was selective, since the responses to potassium ion were not depressed. IPA obtained from swine with SAO shock were more sensitive to the relaxant actions of arachidonic acid, a precursor for bisenoic prostaglandins, than were IPA from sham-shocked swine. This was not observed when prostaglandins were used as agonists. This suggests that synthesis of prostaglandin differs in the pulmonary vasculature of sham-shocked and SAO-shocked animals. IPV obtained from swine in SAO shock were less sensitive to 5-HT and NE but more sensitive to arachidonic acid and 9 alpha, 11 alpha-epoxymethano-PGH2, a thromboxane like compound. IPV obtained from swine in SAO shock converted more arachidonic acid into a substance with the chromatographic mobility of thromboxane B2. The data suggest that alterations in the prostaglandin system within the pulmonary artery and vein may contribute to the pulmonary complications of SAO shock. The alterations appear to include an enhanced synthesis of prostacyclin as well as thromboxane-like substance. Because the veins were more sensitive than the arteries to 9 alpha, 11 alpha-epoxymethano-PGH2, thromboxanes or endoperoxides may elevate venous tone and contribute to the pulmonary edema associated with shock states.
Prostaglandin modulation of adrenergic vascular control during hemorrhagic shock
Authors: Bond R. F. , Bond C. H. , Peissner L. C. , Manning E. S.
Published: December 2017

This study was designed to evaluate 1) whether the initial compensatory skeletal muscle vascular constriction induced by hemorrhagic hypotension is primarily the result of increased adrenergic neural tone rather than circulating vasoconstrictor agents, and 2) whether the secondary skeletal muscle decompensatory vasodilation is caused by inhibitory action of prostaglandins on peripheral adrenergic nervous system. A constant-flow vascularly isolated double canine gracilis muscle preparation in which one muscle served as innervated control for the contralateral muscle was used. Dogs were subjected to standard stepwise hemorrhagic shock protocol. In series 1, perfusion pressures of control muscles were compared to denervated muscles with the result that innervated muscle perfusion pressures increased initially from 105 to 175 mmHg but subsequently fell significantly (P less than 0.05) to 147 mmHg. Only modest increases in perfusion pressures with no significant secondary fall were noted in denervated muscles. Series 2 compared innervated control perfusion pressures to pressures perfusing muscles pretreated with prostaglandin-synthesis inhibitor sodium meclofenamate (MCF). The MCF-treated muscle perfusion pressures rose to 260 mmHg where they remained without the secondary fall noted in control muscles. These data support the two hypotheses tested.
Involvement of adenosine in cerebral hypoxic hyperemia in the dog
Authors: Emerson T. E. , Raymond R. M.
Published: December 2017

Theophylline, a competitive adenosine antagonist, was used to evaluate the role of adenosine in cerebral hypoxic hyperemia. Cerebral venous outflow was measured by the Rapela-Green technique in mongrel dogs anesthetized with pentobarbital sodium and ventilated artificially. Theophylline was infused locally into the cerebral arterial system during moderate [cerebral venous O2 tension (PO2) 27-29 mmHg] or severe (cerebral venous PO2 = 10-15 mmHg) hypoxia; theophylline had no direct vascular effects at the concentration used. Cerebral hyperemia was completely reversed during moderate hypoxia, but only partially reversed during severe hypoxia when theophylline was infused during maintained hypoxia. Theophylline had no effect on cerebral; perfusion pressure, blood flow, or vascular resistance during normoxia. In another group, theophylline had no effect on the cerebral hyperemia induced by hypercapnia. In separate experiments, local cerebral arterial infusion of adenosine or AMP during normoxia had no effect on cerebral hemodynamics at any infusion rate tested (up to 100 micrograms/min). This study supports the hypothesis that adenosine is involved in the hyperemia associated with cerebral hypoxia. However, the degree of involvement may be dependent on the degree of hypoxia.
Early ischemia after complete coronary ligation in the rabbit, dog, pig, and monkey
Authors: Harken A. H. , Simson M. B. , Haselgrove J. , Wetstein L. , Harden W. R. , Barlow C. H.
Published: December 2017

The character and extent of the myocardial ischemic "borderzone" was assessed in the rabbit, dog, pig, and monkey. A fluorophotographic technique permitting high resolution (+/- 50 micrometers) display of myocardial ischemia has been developed. Reduced intracellular NADH (ischemia) fluoresces and may be photographed while oxidized NAD (perfused tissue) does not. A coronary artery was ligated for 5 min in open-chest rabbits, dogs, pigs, and monkeys. A fluorescent dye was injected into the left atrium as a coronary vascular marker, and the tissue was quick-frozen. The ischemic margin was well seen and was jagged in all species. The distance from anoxic to perfused tissue (borderzone) was less than 50 micrometers in all species. A narrow "oxygen-diffusion zone" of nonperfused non-anoxic tissue is visible in isolated heart perfused with blood-free solution. The width of this zone is inversely related to myocardial oxygen consumption and is less than 50 micrometers in a working blood-perfused heart. We have not yet correlated the oxygen diffusion zone with the clinically defined salvageable borderzone. In dogs, collateral vessels provide a heterogeneous border to the ischemic region so that the canine ischemic pattern differs from that of pigs, rabbits, and monkeys.
In vivo and in vitro effects of lead on vascular reactivity in rats
Authors: Webb R. C. , Winquist R. J. , Victery W. , Vander A. J.
Published: December 2017

The effects of lead on vascular responsiveness were examined in rats. Adult rats, which had received levels of lead acetate in their drinking water to produce blood levels similar to those seen in some urban human populations, consistently had higher systolic blood pressures compared to age-matched controls. Helical strips of tail arteries from the lead-treated rats displayed a greater force-generating ability in response to the cumulative addition of methoxamine to the muscle bath. There were no differences in ED50 between the two groups. Similar results were obtained when norepinephrine was used. The calcium-entry blocker, D 600, was less effective in reducing in reducing contractions induced by methoxamine in lead-treated rats than in controls. There were no differences between the two groups in responses to KCl or electrical stimulation of nerve endings. Contractile responses to norepinephrine, methoxamine, KCl, and nerve stimulation in arteries from untreated rats were unaltered by addition of lead acetate to the muscle bath. These results demonstrate that hypertension induced by moderate levels of lead intake is associated with an increased vascular responsiveness to alpha-adrenergic agonists.
Filament systems in the Purkinje fibers of the heart
Authors: Thornell L. E. , Eriksson A.
Published: December 2017

The presence of a specialized cell system designed to conduct the electrical impulses for the sequential contraction of heart muscle is well known. This conduction system of the heart exhibits special morphological features and differs from the contractile myocardium in several respects, including cell form and size, intercellular contacts, and the absence of T tubules. This review is focused on another distinguishing feature, the specific filament systems present in the conduction cells. The conduction cells contain myofibrillar material with different histochemical, biochemical, and morphological properties compared with the contractile myocardium. The conduction cells also contain specific myofilament-polyribosome complexes, of unknown function, never seen in ordinary myocardial cells. Intermediate filaments, present in all eukaryotic cell types, are extremely abundant in conduction cells, especially in birds and larger mammals. Other filamentous organelles of the conduction cells include leptofibrils, microtubules, and microfilaments. The combined results from several investigations indicate that the filamentous systems maintain the structural integrity of the conduction cell bundles functioning as a cytoskeleton. Extracellular elements, such as the surrounding connective tissue sheath, may aid in this respect. Other functions have been ascribed to the filamentous systems of the conduction cells, but these are unproven.
Baroreflex control of heart interval in conscious renal hypertensive dogs
Authors: Thames M. D. , Eastham C. L. , Marcus M. L.
Published: December 2017

The purpose of this study is to determine if baroreflex control of heart interval is abnormal in conscious dogs with renal hypertension. Changes in heart interval in response to transient nitroglycerin-induced decreases in arterial pressure and transient phenylephrine-induced increases in arterial pressure were determined in nine normotensive [mean arterial pressure 92 +/- 4 (SE) mmHg] and nine renal hypertensive conscious dogs (mean arterial pressure 139 +/- 10 mmHg). Data were acquired before and after beta-adrenergic blockade with 2 mg/kg iv propranolol and before and after parasympathetic blockade with 0.5 mg/kg iv atropine. Control heart rates for the normotensive and hypertensive dogs were not different (91 +/- 4 and 93 +/- 7 beats/min, respectively). Before autonomic blockade, the responses of normotensive and hypertensive dogs to nitroglycerin were not different. However, prolongation of the heart interval in response to phenylephrine in hypertensive dogs was significantly less than in normotensive dogs. In both groups, atropine nearly abolished the decrease in heart interval in response to nitroglycerin and the increase in heart interval in response to phenylephrine, although there were small but significant residual responses. Propranolol was without significant effect on heart interval responses to nitroglycerin and phenylephrine. We conclude that the baroreflex control of heart interval during transient decreases in arterial pressure is preserved in hypertensive dogs and is mediated mainly by decreases in parasympathetic outflow to the heart. In contrast, baroreflex control of heart interval during transient increases in arterial pressure is impaired in hypertension and is mediated mainly by activation of parasympathetic cholinergic mechanisms.
Tris does not inhibit isolated vascular or intestinal smooth muscle contraction
Authors: Karaki H. , Suzuki T. , Urakawa N.
Published: December 2017

There are conflicting reports on the effect of tris(hydroxymethyl)aminomethane (Tris) on smooth muscle contraction. Therefore, the effect of substitution of Tris for bicarbonate in physiological saline solution on smooth muscle contractility was investigated. Tris (25 mM) increased the amplitude without changing the frequency of spontaneous contractions in rat portal vein. Tris did not inhibit either norepinephrine-induced contractions in rat portal vein and aorta or histamine-induced contractions in taenia coli. When the pH of the Tris-buffered solution was lowered from the control value of 7.4 to 7.0, spontaneous contractions in portal vein as well as agonist-induced contractions in all of the above preparations were inhibited. Tris did not inhibit contractions induced by calcium in potassium-depolarized smooth muscle preparations if the Tris-buffered solution contained sufficient amounts of sodium ion (as did bicarbonate-buffered solution). These results suggest that Tris does not inhibit contractile responses of isolated vascular and intestinal smooth muscle preparations provided that the conditions other than the buffer system (especially pH of solution) are similar to those in bicarbonate-buffered solutions.
Skimming of microspheres in vitro: implications for measurement of intrarenal blood flow
Authors: Ofjord E. S. , Clausen G. , Aukland K.
Published: December 2017

Skimming could result in erroneous estimation of renal cortical blood flow distribution as measured by microspheres. Skimming of microspheres with diameters 10, 12, and 15 micrometers and red blood cells was therefore studied in a model in which an interlobular artery and its first arteriolar branch were simulated by 80- and 30-micrometers-wide slits between glass prisms. The experiments were performed with citrated blood at a hematocrit (Hct) of 40, flow velocities of 3 and 6 cm/s, and branch flow varying from 2 to 25%. At a branch flow fraction comparable to that of a deep arteriole in the dog kidney (3%), Hct in branch blood was 24% lower than that of input blood, whereas 10-, 12-, and 15-micrometers microsphere concentrations were 75, 81, and 87% lower, respectively. The size-dependent skimming was probably caused by wall exclusion in the main channel. Differences in particle inertia did not affect skimming. The results suggest that the disparate local flow values obtained by use of microspheres of different sizes in dog and rat kidneys are due to a size-dependent skimming of the microspheres.
Effects of short- and long-term left ventricular hypertrophy on coronary circulation
Authors: Marcus M. L. , Mueller T. M. , Eastham C. L.
Published: December 2017

Although most studies suggest that coronary vasodilator responses are impaired in dogs with cardiac hypertrophy, the factors that contribute to this impairment have not been elucidated. To determine if the duration of hypertrophy was an important determinant, we studied coronary vasodilator responses in awake dogs with two-kidney renal hypertension of 6 wk (n = 11) and 6 mo (n = 8) duration. The dogs with hypertension (6 wk and 6 mo) and left ventricular hypertrophy (LVH) had about a 25% (P less than 0.05) increase in LV mass and mean arterial pressure. During maximal coronary vasodilation induced with 4.7 microM . kg-1 . min-1 iv adenosine, maximal flow was significantly decreased in both groups of hypertensive dogs, and minimal coronary vascular resistance was increased by about 50% (P less than 0.05). Minimal coronary vascular resistance was similar in dogs with 6 wk and 6 mo of hypertension and LVH. These experiments suggest that 1) mild LVH (25% increase in LV mass) can significantly decrease coronary dilator reserve and 2) within the time frame examined (6 wk to 6 mo), the duration of hypertension and LVH does not increase the coronary vascular abnormalities associated with cardiac enlargement.
Regional oxygen consumption and supply in heart: effect of methoxamine-induced pressure rise
Authors: Weiss H. R.
Published: December 2017

The effect of raising arterial blood pressure 50 mmHg with methoxamine on regional left ventricular O2 supply and consumption was studied in 27 pentobarbital-anesthetized open-chest rabbits. Three groups of animals were studied: 1) control, 2) methoxamine infusion sufficient to raise pressure 50 mmHg, and 3) methoxamine infusion sufficient to raise pressure 50 mmHg with atrial pacing to maintain heart rate. Subepicardial (epi) and subendocardial (endo) O2 saturations were determined with a microspectrophotometric technique. Regional flow was determined with radioactive microspheres and regional O2 consumption by the Fick principle. In the control group, endo venous O2 saturation [31 +/- 3% (SE)] was lower than epi (42 +/- 2%). There were no significant regional differences in blood flow (avg 128 +/- 2 ml . min-1 . 100 g-1). With methoxamine when heart rate fell, there were no differences in regional flow or consumption when compared to control. During methoxamine infusion, when heart rate was maintained, there was higher coronary blood flow (361 +/- 52 ml . min-1 . 100 g-1) and O2 consumption (27 +/- 4 ml O2 . min-1 . 100 g-1). No regional differences, epi vs. endo, were found in this group. After a 50-mmHg pressure rise, the endo region of the left ventricle had an increased O2 consumption mediated by an increased coronary blood flow without a significant rise in O2 extraction, similarly to epi.
Myocardial mechanical alterations during gradual onset long-term hypertension in rats
Authors: Capasso J. M. , Strobeck J. E. , Sonnenblick E. H.
Published: December 2017

Although a suddenly produced load leads to depressed myocardial contractility, the effects of a slowly induced physiological overload have not been defined. Therefore, a more gradual pressure overload was produced in female Wistar rats by hypertension due to constriction of the left renal artery. Hypertension (systolic blood pressure greater than or equal to 150 mmHg) developed within 3 wk, and blood pressure continued to increase for the next 5 wk. Heart weights in hypertensive animals were elevated by 34% after the onset of hypertension. Isometric and isotonic contractions from left ventricular papillary muscles were recorded at 5, 10, 20, and 30 wk after the onset of hypertension. Total and actively developed isometric tension at all initial muscle lengths were significantly greater in hypertensive animals throughout the 30-wk period. Time to peak tension and time to half relaxation were significantly prolonged. Force-velocity curves demonstrated a significant depression in velocity of shortening at all relative loads in hypertensive muscles that progressed with the duration of hypertension. These studies suggest that myocardial hypertrophy may impart the ability to maintain ventricular performance in terms of force development while speed of shortening decays.
Metabolic responsiveness of spontaneously hypertensive rat to isoproterenol
Authors: Katovich M. J. , Barney C. C. , Fregly M. J.
Published: December 2017

The metabolic responsiveness of spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) normotensive rats to administration of the beta-adrenergic agonist, isoproterenol, was assessed by changes in tail-skin temperature, heart rate, and plasma glucose concentration after administration of graded doses of isoproterenol. The increases in mean tail-skin temperature accompanying administration of isoproterenol at doses of 5, 10, and 40 micrograms/kg sc were significantly (P less than 0.05) greater for SH than for WKY rats. Resting colonic temperatures of the SH rats were also significantly (P less than 0.01) higher than those of the WKY normotensive rats. Mean maximal heart rates of unanesthetized SH rats after administration of isoproterenol at doses of 5, 10, and 20 micrograms/kg sc increased to levels significantly (P less than 0.05-0.01) higher than those of WKY normotensive rats. Resting heart rates were similar in both groups. Increases in plasma glucose concentration after administration of isoproterenol at doses of 5, 10, and 20 micrograms/kg sc were significantly (P less than 0.05) greater in the SH rats compared with the WKY rats. These results suggest that the SH rat has a significantly greater metabolic responsiveness to beta-adrenergic stimulation, as assessed by three separate tests of beta-adrenergic function, than does the WKY rat.
Length-dependent sensitivity in vascular smooth muscle
Authors: Price J. M. , Davis D. L. , Knauss E. B.
Published: December 2017

Dose-response curves were obtained from dog anterior tibial artery rings at various lengths (L) to determine whether sensitivity to norepinephrine (NE) and potassium (K+) depends on arterial circumference. The dose for half maximal response (ED50) was determined by graphical estimation and by calculation from a best fit curve. For both NE and K+: 1) ED50 was lowest (most sensitive) at L for maximum active force (Lmax) and increased significantly as L decreased from Lmax; 2) ED50 at 1.0 and 1.15 Lmax was not significantly different; 3) ED50 of repeated dose-response curves at Lmax was not significantly different; and 4) when the direction of length change was reversed (from decreasing to increasing), the direction of change in ED50 was also reversed (from increasing to decreasing). Change in the dose for 10% maximal response was the same as ED50. The results did not depend on the method of determining ED50 or on whether responses were expressed as absolute values or as relative values. The results show that sensitivity of vascular smooth muscle depends on L and that the length-sensitivity relation is similar to the length-active tension relation. Similarity of results for NE and K+ indicate that length-dependent sensitivity does not depend on the method of stimulation.
Effects of experimental volume-overload hypertrophy on myocardial blood flow and cardiac function
Authors: Badke F. R. , White F. C. , Le Winter M. , Covell J. , Andres J. , Bloor C.
Published: December 2017

To examine the effects of volume-overload hypertrophy on regional myocardial perfusion, we determined myocardial blood flows with microspheres at rest, during exercise, and during exercise with adenosine infusion in dogs with aortocaval fistulas for 12 wk (group 2) and sham-operated controls (group 1). A subgroup of six animals (group 3) was studied both before and after shunt closure in order to separate the influences of hypertrophy from the hemodynamic effects of the fistula. Epicardial blood flows in animals with patent fistulas were significantly greater than in controls under all conditions (P less than 0.05). However, endocardial blood flows were lower at maximal exercise and with adenosine, so that the endocardial-to-epicardial blood flow ratios were reduced 36 and 28%, respectively(P less than 0.05). These flow abnormalities were reversed by closing the fistula prior to regression of hypertrophy. Moreover, coronary resistance per unit of myocardium was not different for the three groups. These results suggest that the blood-flow abnormalities seen in the exercising dog with an aortocaval fistula are secondary to hemodynamic considerations and not to hypertrophy itself. Low aortic diastolic pressures and high myocardial oxygen demands during exercise may combine to produce subendocardial hypoperfusion in this model.
Long-term vascular access in the rat: importance of asepsis
Authors: Popp M. B. , Brennan M. F.
Published: December 2017

Chronic indwelling vascular catheters have been used in the rat for many types of experimental studies. Most experiments have been of short duration with little attention to aseptic technique during catheter placement. In this study, rats subjected to a sterile superior vena cava (SVC) catheterization technique, a convential clean but nonsterile SVC catheterization technique, or sham operation were compared. Male Fischer 344 rats (wt 175-200 g) were catheterized or sham operated and then received food and water ad libitum for 25 days. At time of spontaneous death or being killed the SVC was examined grossly and microscopically for infection. Three of six nonsterile conventionally catheterized animals died, and five of these six animals had infected catheters. All sterilely catheterized and sham-operated rats lived 25 days, and none had catheter infection. Sterilely catheterized rats gained weight (1.9 g/day), were in positive nitrogen balance, and had organ weight and blood studies similar to sham-operated noncatheterized controls. Nonsterile catheterization resulted in catheter infection such that normal physiological studies would be uninterpretable.
Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate
Authors: Hirsch J. A. , Bishop B.
Published: December 2017

The relationship of respiratory sinus arrhythmia amplitude (RSA) to tidal volume and breathing frequency was quantified during voluntarily controlled tidal volume and breathing frequency and spontaneous quiet breathing. Seventeen seated subjects breathed via mouthpiece and nose-clip, maintaining constant tidal volumes at each of several breathing frequencies. Inspiratory breath hold was zero frequency. Log RSA was plotted vs. log frequency for each tidal volume. The large stable RSA for frequencies less than 6 cycles/min was called low-frequency intercept (LFI, 20 +/- 5 beats/min). Low-frequency intercept was inversely proportional to a subject's age only to 35 yr. At higher breathing frequencies above a characteristic corner frequency (fC, 7.2 +/- 1.5 cycles/min) RSA decreased with constant slope (roll-off; 21 +/- 3.4 dB/decade). The RSA-volume relationship was linear permitting normalization of RSA-frequency curves for tidal volume to yield one curve. Spontaneous breathing data points fell on this curve. Voluntarily coupling of heart rate to breathing frequency in integer ratios reduced breath-by-breath variability of RSA without changing mean RSA. In conclusion, low-frequency intercept, corner frequency, and roll-off characterize an individual's RSA-frequency relationship during both voluntarily controlled and spontaneous breathing.
Capillarity and blood flow of transplanted skeletal muscles of cats
Authors: White T. P. , Maxwell L. C. , Sosin D. M. , Faulkner J. A.
Published: December 2017

After transplantation, skeletal muscle fibers and the microvasculature degenerate and then regenerate. The structural and functional characteristics of autografted muscle change with time and ultimately stabilize. Capillarity, blood flow, or fatigability was measured in control (total n = 22) and in autografted (total n = 42) extensor digitorum longus muscles of cats. From 10 to 180 days after transplantation, the capillaries per square millimeter in peripheral areas of autografts averaged 65% of control, and from 180 to 518 days, 45% of control. Resting blood flow in autografts increased eventually from total ischemia at the time of transplantation to values 400% of control. After 400 days, resting blood flow returned to control values. The blood flow of autografts increased in response to twitch stimulation, reaching maximal value (24.4 +/- 1.4 ml . 100 g-1 . min-1) at 1 twitch . s-1 . The maximal blood flow of autografts was comparable to the submaximal blood flow at 1 twitch . s-2 of controls and was 30% of the maximal flow of controls obtained at 4 twitches . s-1. The maximal blood flow in autografts did not increase from 80 to 460 days. When stimulated with repetitive twitches, autografts fatigued more rapidly than controls.
Adenine nucleotide transport during cardiac ischemia
Authors: LaNoue K. F. , Watts J. A. , Koch C. D.
Published: December 2017

The suggestion that long-chain acyl coenzyme A (CoA) derivatives may inhibit mitochondrial adenine nucleotide transport in heart cells during ischemia has been reevaluated. The effectiveness of media palmitoyl-CoA as an inhibitor is a function of mitochondrial protein and media adenine nucleotide concentrations. Extrapolation to the protein and adenine nucleotide levels of the cardiac cell suggest that physiological concentrations of cytosolic long-chain acyl-CoA would not inhibit adenosine 5'-triphosphate (ATP) transport. Palmitoyl-CoA was varied in the mitochondrial matrix by incubating the isolated mitochondria with and without palmitoyl carnitine. Intramitochondrial nucleotides were depleted by incubating the isolated mitochondria for various periods of time with arsenite and phosphate. Even at low substrate (matrix ATP) concentrations, no palmitoyl-CoA inhibition of ATP transport could be demonstrated. Further experiments showed that endogenous nucleotide levels are significantly depleted in mitochondria isolated from hearts made ischemic for 30-90 min. Since mitochondrial adenine nucleotide transport occurs by an exchange mechanism, this depletion of the internal pool of nucleotides from ischemic heart mitochondria may result in an irreversible diminution of ATP transport.
Sensitivity differences of SA and AV node to vagal stimulation: attenuation of vagal effects at SA node
Authors: Loeb J. M. , Dalton D. P. , Moran J. M.
Published: December 2017

The present study sought to characterize vagally induced desensitization at the sinoatrial (SA) node of the intact dog and to determine whether these findings could be extended to atrioventricular (AV) Nodal conduction. Autonomically decentralized anesthetized dogs were instrumented to record electrocardiograms, arterial pressure, and electrograms from the SA node, right atrium, right ventricle, and His bundle. During right- or left-vagal stimulation for 60 s, cycle length (CL) increased initially, followed by a gradual recovery toward control during stimulation; atrio-His (AH) interval remained prolonged throughout the stimulation. Atrial drive increased AH interval during stimulation, but AH prolongation was maintained throughout the stimulation period. To rule out acetylcholine (ACh) depletion, ACh was administered before and during vagal stimulation. Although control CL and AH interval were lengthened by ACh, no significant CL increases occurred when ACh was given during stimulation, but the AH interval became longer. Propranolol increased control CL and AH interval but did not alter the relationship between vagal stimulation and CL or AH interval. Thus the negative chronotropic effect of ACh at the SA node is diminished upon prolonged vagal stimulation, whereas the negative dromotropic effect upon AV nodal conduction remains unaltered. These results suggest differences in muscarinic receptor behavior at the SA and AV nodes.
Efficacy of sympathetic influences as related to initial vascular tonicity
Authors: Rodionov I. M. , Koshelev V. B. , Meshcheryakova O. D. , Stavskaya O. N.
Published: December 2017

The efficacy of vasoconstrictor influences as dependent on the initial vascular tone (initial rate of perfusion) and perfusion pressure was investigated in rat and frog hindlimb preparations perfused with saline solution. Efficacy was determined as the ratio of the preparation resistance (R) induced by sympathetic stimulation to the initial resistance R0. At a pressure normal for the experimental animal, the relationship between R/R0 and flow is expressed by a dome-shaped curve. At a pressure twice the normal, it is low at all points; at a pressure half the normal, different responses were obtained from the two species used in the experiment: in rats elevation of vascular tone induced by sympathetic stimulation resulted in a complete cessation of flow, whereas in frogs the initial high efficacy diminished with increasing vascular tone. A mathematical model devised to study the dependence of the efficacy of sympathetic stimulation on initial tonicity is described. The good consistency of experimental and calculated results is regarded as evidence that the prerequisites stipulated in the model, i.e., the capacity of closure and the heterogeneity of arterioles, in regard to the effort developed by their smooth muscle, are actually inherent in the vascular system of organs.
Collagen synthesis and content in right ventricular hypertrophy in the dog
Authors: Bonnin C. M. , Sparrow M. P. , Taylor R. R.
Published: December 2017

The fractional synthesis rate of collagen (the percent of total ventricular collagen synthesized in one day) was measured in the hearts of normal dogs and those with pulmonary artery stenosis using a continuous 6-h intravenous infusion of [14C]proline. The fractional synthesis rate in normal ventricles was slow, 0.56%/day, and it increased eightfold to 4.8%/day in the hypertrophying right ventricle after 5 days. After 12 and 28 days the synthesis rate was still significantly greater than in the control left ventricle, being 2.6 and 1.3%/day, respectively. However, the synthesis rate of noncollagen protein was significantly greater than normal at 5 days only. The collagen content (expressed as a mass fraction) of the right ventricle decreased over the first 12 days of hypertrophy but by 28 days was restored to the normal right ventricular value of 9.6 mg/g wet wt tissue. The total amount of collagen in the hypertrophied ventricle calculated from the synthesis rates was in accord with that measured chemically. In normal dogs the collage content of the right ventricle was greater than that of the left, and the epicardium contributed substantially to the total collagen in the ventricular walls.
Abnormal lanthanum accumulation due to ischemia in isolated myocardium: effect of chlorpromazine
Authors: Burton K. P. , Hagler H. K. , Willerson J. T. , Buja L. M.
Published: December 2017

The progression of functional, structural, and membrane permeability alterations in the isolated, perfused rabbit interventricular septal preparation was examined at 1, 1.5 or 2 h of ischemia and during 1 h of postischemic reflow. Two other groups of rabbits were pretreated with chlorpromazine (15 and 25 mg/kg), a drug with inhibitory effects on Ca influx and phospholipase activation. The ability of the septa to contract decreased markedly during the ischemic period, but a graded recovery response in physiological contractile parameters was observed upon reperfusion. In septa with comparable preischemic contractile function, pretreatment with chlorpromazine resulted in better functional recovery than that of nontreated septa. Ultrastructural examination showed more extensive and severe damage with increasing periods of ischemia. Ionic La-probe studies of altered membrane integrity showed extensive abnormal intracellular La deposition with ischemic periods of 1.5 h or longer followed by reperfusion. Septa pretreated with chlorpromazine showed better preservation of cell integrity and less intracellular lanthanum deposition. Thus, in this model, a good correlation was found between the extent of functional, structural, and membrane permeability alterations caused by ischemia, and a protective effect of chlorpromazine was shown.
Reflex sympathetic augmentation of left-ventricular inotropic state in the conscious dog
Authors: Yoran C. , Higginson L. , Romero M. A. , Covell J. W. , Ross J.
Published: December 2017

Cardiac reflex responses to a series of partial inferior vena caval occlusions were studied in conscious previously instrumented dogs. Heart rate responses during the fall of systemic arterial pressure were mediated both by increased sympathetic tone and withdrawal of parasympathetic tone. Responses of the left-ventricular inotropic state, estimated from changes in left ventricular pressure rise (LV dP/dt), were studied early after release of a series of partial vena caval occlusions, and a positive linear relation between the prior fall in the systemic arterial pressure and the increase in LV dP/dt was demonstrated. Serial studies showed this effect of persist for at least 12 s beyond the reflex slowing of heart rate early after release of vena caval occlusion. The positive inotropic response was markedly attenuated by beta-adrenergic blockade and also occurred at a constant heart rate. It was present after adrenalectomy. These studies suggest that the integrated baroreceptor responses that are activated by a simultaneous decrease in the venous return and systemic arterial pressure play an important role in the regulation of left-ventricular inotropic state in the conscious dog.