bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflex cardiovascular responses to chemoreceptor stimulation in conscious dogs with cardiac hypertrophy
Authors: Murray P. A. , Vatner S. F.
Published: December 2017

Carotid chemoreceptor reflex activation (CCRA) has been previously shown to result in intense alpha-adrenergic peripheral vasoconstriction, a biphasic coronary vascular response characterized by an early vasodilation and a late alpha-adrenergic vasoconstriction, and a cholinergic increase in cardiac cycle length in normal conscious dogs. In the present study, we investigated the extent to which these reflex cardiovascular responses to CCRA are modified after the development of pressure-overload right ventricular (RV) hypertrophy induced by chronic (9-12 mo) pulmonary arterial stenosis. With heart rate constant and respiration allowed to vary spontaneously, the magnitude of the late CCRA-induced (intracarotid nicotine) increase (P less than 0.01) in right coronary resistance was markedly attenuated (P less than 0.01) in conscious dogs with RV hypertrophy [0.29 +/- 0.07 (SE) mmHg X ml-1 X min] compared with normal dogs (1.87 +/- 0.36). When respiration was controlled to eliminate pulmonary inflation reflex activation, the late CCRA-induced increase (P less than 0.01) in right coronary resistance was still found to be depressed (P less than 0.01) in the RV hypertrophy group (1.11 +/- 0.20 mmHg X ml-1 X min) compared with normal dogs (3.65 +/- 0.75). This late CCRA-induced right coronary vasoconstriction was not potentiated by beta-adrenergic receptor blockade but was abolished (P less than 0.01) by alpha-adrenergic receptor blockade. In contrast to the depressed right coronary vasoconstriction, the CCRA-induced alpha-adrenergic constriction (P less than 0.01) of the iliac arterial vascular bed was similar in both groups, and the cholinergic increase (P less than 0.01) in cardiac cycle length was enhanced (P less than 0.01) in the RV hypertrophy group compared with normal dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
PGE2 does not act at carotid sinus to raise arterial pressure in conscious sheep
Authors: Breuhaus B. A. , Chimoskey J. E.
Published: December 2017

Conscious chronically instrumented adult female sheep were used to determine whether direct action of prostaglandin E2 (PGE2) on the carotid sinus baroreceptors contributes to the pressor response observed during infusion of PGE2 into the common carotid artery (CCA). During infusion of PGE2 into the CCA caudal to an intact carotid sinus, into the CCA caudal to a denervated carotid sinus, and into the external carotid artery, mean arterial pressure (MAP) rose 17, 22, and 17 mmHg, respectively (P less than 0.01). Heart rate (HR) rose 6, 6, and 8 beats/min, respectively (P less than 0.05). Cardiac output (CO) was also measured by indicator dilution using indocyanine green. In these experiments with infusion of PGE2 into the external carotid artery, MAP rose 15 mmHg (P less than 0.01), HR increased 6 beats/min (P less than 0.05), CO did not change, and total peripheral resistance (TPR) increased 23% (P less than 0.01). With infusion of PGE2 past a denervated carotid sinus, MAP rose 20 mmHg (P less than 0.01), HR rose 4 beats/min (P less than 0.05), CO did not change, and TPR increased 29% (P less than 0.01). There were no statistically significant differences in MAP or HR responses when PGE2 was infused past an intact carotid sinus, past a denervated carotid sinus, or beyond the carotid sinus. There is no evidence that direct action of PGE2 on carotid sinus baroreceptors either augments or inhibits the observed pressor effect of intracarotid PGE2. Intracarotid PGE2 acts rostral to the carotid sinus to increase MAP, HR, and TPR in conscious sheep.
Effects of prostaglandin E1 in diabetic heart
Authors: Miller T. B.
Published: December 2017

Isolated perfused hearts from normal and alloxan-diabetic rats were studied to determine the effects of prostaglandin E1 (PGE1) on phosphorylase activation in the insulin-deficient state. Perfusion of hearts from normal and diabetic rats with 3 X 10(-5) M PGE1 for the final 2 min resulted in activation to the same extent of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, cAMP-sensitive protein kinase, and phosphorylase kinase. Although phosphorylase activation was somewhat suppressed in both the normal and diabetic heart, PGE1 produced a 36% increase in phosphorylase a in normal hearts and a 44% increase in phosphorylase a in diabetic hearts. The decreased effectiveness of phosphorylase activation by PGE1 appears to be located beyond activation of phosphorylase kinase and perhaps involves an alteration in phosphorylase sensitivity to phosphorylase kinase. Further, the activation of phosphorylase by phosphorylase kinase is hypersensitive in hearts of diabetic rats, perhaps due to a diabetes-related alteration in calcium metabolism.
Effect of distal coronary pressure on rigid and compliant coronary stenoses
Authors: Schwartz J. S.
Published: December 2017

The effects of changes in distal coronary pressure on the hemodynamics of rigid and compliant coronary stenoses were studied in anesthetized open-chest dogs. In dogs with severe compliant circumflex stenoses produced with an external snare, pressure distal to the stenosis was lowered by closing a catheter connecting the carotid artery to the distal circumflex artery and was raised by reopening the catheter. Lowering mean distal circumflex pressure from 57 +/- 14 to 18 +/- 3 (SE) mmHg (P less than 0.01) increased stenotic resistance (2.1 +/- 0.7 to 14.1 +/- 7.8 units, P less than 0.01) and decreased circumflex flow (19 +/- 6 to 6 +/- 4 ml/min, P less than 0.01). Raising distal pressure (18 +/- 3 to 49 +/- 15 mmHg, P less than 0.05) decreased stenotic resistance (14.1 +/- 7.8 to 3.7 +/- 0.9 units, P less than 0.05) and increased circumflex flow (6 +/- 4 to 13 +/- 3 ml/min, P less than 0.05). In dogs with rigid stenoses produced with plastic tubing, a fall in distal pressure significantly increased flow without a change in stenotic resistance. Therefore, changes in resistance and flow through compliant coronary stenoses occur in response to changes in distal pressure. These hemodynamic changes are consistent with passive collapse and distension of the stenotic segment.
Isolated human coronary arteries in response to vasoconstrictor substances
Authors: Toda N.
Published: December 2017

In helical strips of human epicardial coronary arteries, norepinephrine produced a concentration-related contraction; the contractions relative to those induced by 30 mM K+ were greater in the proximal portion of the arteries than in the distal portion. The amine-induced contraction was suppressed by treatment with phentolamine. Acetylcholine contracted human coronary arteries but, in contrast, relaxed the monkey coronary arteries (both freshly excised and cadaver) previously contracted with prostaglandin F2 alpha. Both the contraction and relaxation induced by acetylcholine were suppressed by atropine. Removal of the endothelium abolished the relaxation of monkey arteries but did not significantly alter the contraction of human arteries. Human coronary arteries responded to histamine with contractions, which were reversed to relaxations following treatment with chlorpheniramine. It is concluded that, as far as the portions of human coronary arteries used in the present study are concerned, the arterial contraction mediated via alpha-adrenoceptors is inversely related to the distance from the coronary artery orifice. Acetylcholine produces contractions of human coronary arteries, possibly due to activation of muscarinic receptors on smooth muscle cells. Histamine-induced contractions appear to be mediated via H1-receptors.
Differences in myocardial alpha- and beta-adrenergic receptor numbers in different species
Authors: Mukherjee A. , Haghani Z. , Brady J. , Bush L. , McBride W. , Buja L. M. , Willerson J. T.
Published: December 2017

In the present study, we tested the hypotheses that 1) different species have different myocardial adrenergic receptor numbers and 2) selected “slow-channel” calcium antagonists compete with alpha-adrenergic antagonists for binding to varying degrees in different species. The data obtained in the present study demonstrate that there is a markedly decreased number of alpha 1-adrenergic and increased number of beta-adrenergic receptors in canine compared with rabbit and rat myocardium. The differences in adrenergic receptor numbers exist without major differences in alpha 1-adrenergic receptor affinity in the species studied. There was no significant difference in left ventricular or plasma catecholamine content between the rat and dog. Selected slow-channel calcium antagonists compete for alpha 1-adrenergic receptor binding in rabbit, rat, and canine myocardium. However, only in rabbit myocardium does verapamil antagonize alpha 1-adrenergic receptor binding at moderate concentrations, whereas verapamil in canine and rat myocardium and 1) 600 in all three species antagonize alpha 1-adrenergic receptor binding only at relatively high concentrations. Nifedipine, a dihydropyridine-type slow-channel calcium antagonist, had no effect on prazosin binding to rat, rabbit, and dog myocardial membranes.
Right and left ventricular pressure-volume response to positive end-expiratory pressure
Authors: Santamore W. P. , Bove A. A. , Heckman J. L.
Published: December 2017

Cardiovascular effects of positive end-expiratory pressure (PEEP) at 20 cmH2O were examined in six mongrel dogs (11.3-15.0 kg). The dogs were anesthetized through a combination of intramuscular Innovar and gaseous anesthesia (60% N2O-40% O2). For volume measurements, radiodense tantalum screws were placed on the endocardial surface of the left and right ventricle. Esophageal and left and right ventricular pressures were measured. With the use of this preparation, the effects of positive end-expiratory pressure (PEEP = 20 cmH2O) on cardiovascular function were examined. PEEP caused right ventricular transmural pressures to decrease, 3.4 +/- 1.0 to 2.0 +/- 1.0 mmHg end-diastolic (P less than 0.05) and 29.2 +/- 2.2 to 27.9 + 2.2 mmHg peak systolic; left ventricular transmural pressures decreased, 5.9 +/- 1.6 to 1.2 +/- 1.4 mmHg end-diastolic (P less than 0.05) and 117.2 +/- 8.0 to 76.2 +/- 7.4 mmHg peak systolic (P less than 0.05). After volume loading the animal (500 ml dextran), PEEP caused similar changes in right and left ventricular pressures. Plots of end-diastolic volume versus pressure showed an increase in the apparent diastolic stiffness in both ventricles with decreased end-diastolic volume.
Does vasopressin sustain blood pressure of normally hydrated healthy volunteers?
Authors: Bussien J. P. , Waeber B. , Nussberger J. , Schaller M. D. , Gavras H. , Hofbauer K. , Brunner H. R.
Published: December 2017

The inhibitor of the pressor effect of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP, at a dose of 5 micrograms/kg iv was shown in four healthy volunteers to antagonize the blood pressure, heart rate, and skin blood flow response to a lysine vasopressin infusion of 1 mIU X kg-1 X min-1. The inhibition lasted for more than 2 h. When the same dose of the vasopressin antagonist was administered to 10 healthy normally hydrated volunteers with their renin system intact or acutely blocked by 25 mg of captopril po, none of the above parameters changed. It is concluded that circulating vasopressin, even in the face of a blocked renin-angiotensin system, does not actively contribute to maintenance of cardiovascular homeostasis.
Role of angiotensin II, alpha-adrenergic system, and arginine vasopressin on arterial pressure in rat
Authors: Paller M. S. , Linas S. L.
Published: December 2017

Three pressor systems regulate arterial pressure (MAP): angiotensin II (ANG II), the alpha-adrenergic system, and arginine vasopressin (AVP). In this study we determined the ability of each system to support MAP in the conscious rat when the other two systems were inactivated. After administration of the converting-enzyme inhibitor teprotide (CEI) and the alpha-adrenergic receptor antagonist phenoxybenzamine (POB), MAP decreased 40% as a result of a 45% decrease in peripheral vascular resistance (PVR). Despite hypotension, plasma AVP levels were not increased, and an AVP pressor antagonist (AVP-A) did not result in a further decrease in MAP. Thus the profound hypotension after POB plus CEI was the result of inhibition of all three systems. POB, rather than CEI, prevented AVP release since following hypotensive hemorrhage, plasma levels reached 51 +/- 13 pg/ml with CEI but only 4.7 +/- 0.8 pg/ml with POB. To study the pressor effect of AVP alone, AVP was infused in POB plus CEI-treated rats. AVP increased MAP (from 68 +/- 4 to 92 +/- 5 mmHg; P less than 0.005) and plasma AVP (to 13.8 +/- 1.9 pg/ml). Since POB inhibited both the AVP and the alpha-adrenergic system, the role of ANG II alone was determined in POB-treated rats. In the presence of ANG II MAP was 97 +/- 1 mmHg. To study the alpha-adrenergic system, MAP was determined in CEI plus AVP-A-treated rats. In the presence of an intact alpha-adrenergic system MAP was 101 +/- 1 mmHg. We conclude that PVR and MAP are profoundly decreased in the absence of all three pressor systems.(ABSTRACT TRUNCATED AT 250 WORDS)
Baroreflex regulation of hindquarter vascular resistance during acute blood volume expansion
Authors: Guo G. B. , Richardson D. R.
Published: December 2017

The baroreflex control of hindquarter vascular resistance in response to a 30% blood volume expansion (BVE) was examined in constant-flow perfused hindlimbs of chloralose-urethan-anesthetized rats. Volume expansion initially increased both systemic arterial pressure (SAP) and central venous pressure (CVP) while decreasing hindquarter vascular resistance. After these initial changes, there was a parallel return of hindquarter-vascular resistance and CVP to pre-expansion levels, suggesting that cardiopulmonary afferents play a major role in the vascular resistance adjustments to volume expansion. This notion was supported in a separate set of experiments in which CVP was elevated selectively while SAP was held constant. This manipulation elicited a decrease in hindquarter vascular resistance, which was significantly attenuated following vagal cardiopulmonary denervation. The return of hindquarter vascular resistance following BVE also occurred in the presence of elevated SAP in rats with vagotomy and aortic nerve denervation, i.e., only the carotid sinus baroreflexes intact, but the time course was much faster compared with preparations with cardiopulmonary receptors intact. No response of hindquarter vascular resistance to BVE was observed in rats with both sinoaortic and cardiopulmonary baroreceptors denervated. These findings suggest that the return of hindquarter vascular resistance following BVE involves a gradual increase in sympathetic outflow to the hindquarters resulting from both a decrease in cardiopulmonary afferent activity and a rapid adaptation of arterial baroreflexes.
Heterogeneity of oxygen diffusion through hamster striated muscles
Authors: Ellsworth M. L. , Pittman R. N.
Published: December 2017

We determined the O2 diffusion coefficients (DO2) and resting O2 consumptions for three hamster muscles with differing histochemical fiber type composition using a nonsteady-state technique. The muscles ranged from an oxidative muscle (soleus) to a glycolytic muscle (sartorius) with a third, the cheek pouch retractor, having mixed metabolic properties. We found that the DO2 of the soleus (corrected to 37 degrees C) was 2.59 +/- 0.33 X 10(-5) cm2/s, whereas the DO2 of the sartorius was 1.15 +/- 0.14 X 10(-5). The value for the retractor was between these two values (1.39 +/- 0.14 X 10(-5) cm2/s). In addition, we observed a linear correlation between DO2 and the percent of transverse cross-sectional area occupied by oxidative fibers, suggesting that the differences in DO2 can be accounted for by differences in their histochemical fiber type composition. In light of known differences in capillary density and maximal O2 demand, these data imply an interplay between capillarity and O2 diffusion rate resulting in an appropriate O2 delivery to meet each muscle's maximal O2 demand.
Excess tachycardia: heart rate after antimuscarinic agents in conscious dogs
Authors: Rigel D. F. , Lipson D. , Katona P. G.
Published: December 2017

In conscious dogs the heart rate after atropine is higher than after bilateral vagotomy; we have termed the additional heart rate with atropine "excess tachycardia" (ET). In six dogs the cervical vagosympathetic trunks were exteriorized in skin tubes, and arterial and venous catheters were chronically implanted. Atropine sulfate (0.1 mg/kg iv) injected during cold blockade of the vagi increased the heart rate by only 6 +/- 4 (SE) beats/min (NS) but rewarming the vagi in five of the six dogs after atropine resulted in an additional heart rate increase (ET) of 26 +/- 6 beats/min (P less than 0.005). The ET (41 +/- 11 beats/min) tended to be larger when the animals were pretreated with 1 mg/kg propranolol (P = 0.09). Similar results were obtained when atropine methylbromide, a charged derivative of atropine sulfate, or glycopyrrolate, a synthetic antimuscarinic agent, was substituted for atropine sulfate (ET: 51 +/- 6 and 51 +/- 16 beats/min, respectively). Raising the arterial blood pressure with phenylephrine increased the heart rate further; lowering the blood pressure with sodium nitroprusside attenuated or abolished the ET. Our results show that ET is produced by antimuscarinic agents in general and is not mediated by the beta-adrenergic system. Furthermore, ET is present only when the cervical vagi are intact, probably because ET is mediated by cholinergic vagal efferent fibers via a mechanism that has not yet been recognized in cardiac rate control.
Effect of exercise on uterine blood flow in the pregnant Pygmy goat
Authors: Hohimer A. R. , Bissonnette J. M. , Metcalfe J. , McKean T. A.
Published: December 2017

Pygmy goats in the last third of pregnancy were trained to walk on a treadmill at rates up to 2.0 mph and up an inclination of 0-15 degrees. Electromagnetic flowmeters were placed unilaterally on a uterine artery, and measurements were made while the goats were standing quietly on the treadmill and during 5 min of exercise. Blood flow fell during exercise in all five animals studied, and this reduction was proportional to the level of exertion. At the highest level of exercise that these animals would voluntarily perform, uterine artery blood flow fell by 32 +/- 3 (SE) % (P less than 0.001) from control. In four additional animals the radioactive microsphere technique was used to measure uterine blood flow at rest and after 5-7 min of exercise. In these animals, exercise caused total uterine blood flow to fall by 18 +/- 10%; cotyledonary (placental) blood flow fell by 8 +/- 13%, while myoendometrial blood flow decreased by 52 +/- 12% (P less than 0.05). Thus nonplacental portions of the pregnant Pygmy goat uterus suffer major reductions in blood flow during exercise. This vasoconstriction may be due to exercise per se or to concomitant hypocapnia or hyperthermia. Singleton and twin kids born to animals that exercised were of normal birth weight.
Effect of sodium on calcium-dependent force in unstimulated rat cardiac muscle
Authors: Walford G. D. , Gerstenblith G. , Lakatta E. G.
Published: December 2017

It has previously been demonstrated that 1) changes in superfusate calcium concentration [Ca2+]o within the low millimolar range result in changes in "resting" force and in the light-scattering properties of unstimulated rat cardiac muscle, and 2) if [Ca2+]o is increased from zero to millimolar concentrations, i.e., reperfusion with Ca2+ after a Ca2+-free period, a large influx of Ca2+ occurs and is associated with a substantial increase in resting force. The present study determined whether the Ca2+ influx in either case was influenced by intracellular sodium (Na+i). In unstimulated isometric rat right ventricular papillary muscles equilibrated at 29 degrees C, [Ca2+]o was increased from 1 to 4 mM or from 0 to 2 mM under conditions that vary Na+i, and the resulting change in intracellular calcium concentration [( Ca2+]i) was monitored by changes in both resting force and the frequency of intensity fluctuations in laser light scattered by the muscle. In each case, lowering Na+i by equilibration in lowered extracellular sodium concentration [( Na+]o) or enhancing [Na+]i by equilibration in the absence of extracellular potassium or in the presence of ouabain markedly lowered and enhanced respectively the apparent Ca2+ influx in response to the step increase in [Ca2+]o. Thus, in unstimulated rat cardiac muscle, Na+i modulates the Ca2+ influx resulting from a step increase in [Ca2+]o both under physiological conditions and following a period of Ca2+-free superfusion, i.e., the "Ca2+ paradox." A passive influx of Ca2+ down its electrochemical gradient would not depend on Na+i, and the voltage-time dependent slow Ca2+o channel is inactivated under the experimental conditions employed. The results are best explained by a sarcolemmal Na+-Ca2+ exchange mechanism and suggest that the reversal potential of this electrogenic exchanger is exceeded during a step increase in [Ca2+]o even at the transmembrane potential of resting muscle.
Baroreceptor heart rate reflex in rabbits after reversal of renal hypertension
Authors: Fletcher P. J.
Published: December 2017

The baroreceptor heart rate reflex was studied in 26 renal hypertensive and 17 normotensive rabbits and in 13 rabbits after reversal of hypertension. Blood pressure and heart rate were varied by bolus injections of methoxamine or nitroglycerine in conscious rabbits, and a logistic sigmoid function was fitted to the pressure-heart rate data to estimate upper and lower heart rate plateaus, median blood pressure, and reflex sensitivity. In hypertensive rabbits, resetting of the blood pressure-heart rate curves to higher pressures was associated with reduced reflex sensitivity, increased lower heart rate plateau, and operating pressures significantly greater than the region of maximum reflex sensitivity, resulting in substantial attenuation of reflex bradycardia in response to hypertension. Reflex bradycardia after smoke inhalation was normal. Reversing the hypertension completely reversed the abnormalities in baroreflex control of heart rate. Renal hypertension in the rabbit produces functional changes that are completely reversible in the baroreceptor-heart rate reflex, probably in the afferent limb.
Rapid resetting of aortic nerves in conscious rabbits
Authors: Undesser K. P. , Lynn M. P. , Bishop V. S.
Published: December 2017

The effect of increased arterial pressure on aortic depressor nerve activity was studied in the conscious rabbit. Aortic baroreceptor resetting was observed following 15 min of sustained pressure elevation. At 15 min, there was a significant increase in the threshold arterial pressure for aortic nerve activity, but peak nerve activity did not change. This resulted in an increase in the slope of the pressure-nerve activity relationship. Therefore, except for peak nerve activity, aortic nerve activity was reduced at all pressures following 15 min of sustained pressure elevation. At 30 min, peak nerve activity also increased, resulting in a parallel shift in the pressure-activity curve. The early increase in slope of the pressure-activity relationship may be due to an early resetting of low threshold fibers with a high pressure differential between their threshold pressure and the sustained pressure elevation used to induce resetting. A late resetting of high threshold fibers with a low pressure differential between their threshold pressures and the pressure used to cause resetting of baroreceptors results in a parallel shift in the curve observed at 30 min. These data obtained from multiunit recordings provide unexpected evidence about baroreceptor resetting, which is not apparent from single-unit recordings.
Comparative responses of cerebellar and cerebral arterioles to changes in PaCO2 in cats
Authors: Wei E. P. , Seelig J. M. , Kontos H. A.
Published: December 2017

A modified cranial-window technique was devised that permits direct observation and study of the pial microcirculation of the cerebellum and comparisons of the responses of the microvessels in this location with those in the hemisphere. We used this technique in anesthetized cats to compare the responses of cerebellar and cerebral arterioles with alterations in arterial blood CO2 tension. Arterioles in these two locations responded with similar percentile changes in vessel caliber to both hypercapnia and hypocapnia.
Effect of platelet-activating factor on coronary circulation of the domestic pig
Authors: Feuerstein G. , Boyd L. M. , Ezra D. , Goldstein R. E.
Published: December 2017

The platelet-activating factor released by white blood cells and platelets has been shown to be 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC). To fully understand the cardiovascular actions of this substance, we examined the effects of AGEPC on coronary blood flow (CBF) and other hemodynamic parameters in anesthetized open-chest domestic pigs. Mean arterial blood pressure (MBP), electrocardiogram, heart rate (HR), left ventricular pressure, and CBF were continuously recorded. AGEPC was injected (bolus, 0.1 ml) into the left anterior descending coronary artery at increasing doses of 0.03-10 nmol. Intracoronary AGEPC produced biphasic changes in CBF: a dose-dependent increase in CBF (up to 50%) followed by a decrease (up to 92%) in CBF. The changes in CBF were not directly related to any systemic effect, although MBP was reduced consistently after a dose higher than 1 nmol of AGEPC. The increase in CBF produced by AGEPC was not affected by pretreatment with indomethacin (6 mg/kg) or FPL 55712 (1 or 3 mg), an inhibitor of slow-reacting substance of anaphylaxis (SRS-A). The decrease in CBF produced by AGEPC was attenuated by FPL 55712 and blocked by indomethacin. These data suggest that AGEPC release from aggregating platelets might play a major role in modulating CBF and cardiac function in states involving platelet-coronary interaction.
Transmural DC electrograms after coronary artery occlusion and latex embolization in pigs
Authors: Cinca J. , Figueras J. , Senador G. , Garcia-Moreno E. , Salas A. , Rius J.
Published: December 2017

Changes in epicardial and endocardial direct current (DC) electrograms and ventricular arrhythmias observed during 60 min of left anterior descending coronary artery (LAD) occlusion in nine anesthetized pigs were compared with those observed in eight other pigs after embolization of the LAD with latex, a procedure able to block collateral blood flow to the ischemic area. After LAD occlusion 1) T-Q segment depression and S-T segment elevation showed a faster rate of development, and monophasic potentials occurred earlier in the endocardium than in the epicardium; 2) T-Q segment depression was greater at the center than at the periphery of the ischemic area during the first 20-30 min, and later it become greater at the periphery than at the center; and 3) a period of transient recovery in the local activation beginning after 8-15 min and lasting for 10-20 min occurred in all cases, commonly associated with T-wave alternans. LAD embolization with latex induced greater T-Q and S-T segment changes in the epicardium than in the endocardium, increased the incidence of ventricular fibrillation, and failed to impede the appearance of the period of transient electrical recovery. Thus, within an acutely ischemic area in the in situ pig heart, there are inhomogeneities in the magnitude and time course of the electrical changes, which are not prevented by procedures able to block collateral blood flow to the ischemic area. Ventricular fibrillation was also not prevented by such a procedure.
In situ double-beam NADH laser fluorimetry: choice of a reference wavelength
Authors: Renault G. , Raynal E. , Sinet M. , Muffat-Joly M. , Berthier J. P. , Cornillault J. , Godard B. , Pocidalo J. J.
Published: December 2017

A double-beam laser fluorimeter, using a single optical fiber to guide the lights, was constructed for in situ and on-line monitoring of NADH concentration [( NADH]) from normally blood-perfused living tissues. The device was tested on an isolated blood-perfused rat heart system to determine the most efficient reference wavelength for the compensation of the hemodynamic artifact induced by blood circulation in the tissues on the fluorescence measure; 586 nm was found to be an accurate reference wavelength, and a mathematical relationship was established that allowed the digital treatment of the measured fluorescence to give a signal (compensated fluorescence) that varied only with [NADH] in the volume of tissue investigated.
Pantothenate kinase and control of CoA synthesis in heart
Authors: Robishaw J. D. , Neely J. R.
Published: December 2017

Control of coenzyme A (CoA) synthesis was studied in isolated perfused rat hearts. The data obtained support the hypothesis that phosphorylation of pantothenic acid by pantothenate kinase is the flux-generating reaction in the pathway of CoA synthesis. This reaction operated in the cell far removed from its thermodynamic equilibrium; it was saturated with substrates under all conditions studied; and the concentration of substrate changed in the opposite direction to flux when flux was altered. The reaction was subject to control by external factors associated with oxidation of glucose, pyruvate, or palmitate. CoA synthesis from 4'-phosphopantothenic acid was not inhibited by glucose and pyruvate, suggesting that pantothenate kinase is the only reaction in the pathway that is controlled in isolated hearts. Maximum rates of CoA synthesis in perfused hearts with pantothenate kinase stimulation were dependent on a supply of exogenous cysteine. Perfusate [14C]cysteine was incorporated into intermediates of this pathway and CoA. When protected from oxidation to cystine by low concentrations of dithiothreitol, 0.1 mM cysteine in the perfusate resulted in maximum rates of CoA synthesis. Evidence was obtained that indicates that addition of cysteine relieves a substrate limitation at the 4'-phosphopantothenyl cysteine synthase reaction.
New method for the collection of cerebrospinal fluid from the cisterna magna of conscious dogs
Authors: Suzuki H. , Ferrario C. M.
Published: December 2017

We have developed a catheter system than can be implanted chronically into the cisterna magna of the dog to obtain serial samples of cerebrospinal fluid (CSF) for up to 8 wk. A direct access to the CSF of the cisterna magna provided an opportunity to determine also base-line values of CSF sodium, potassium, norepinephrine, epinephrine, and angiotensin II immunoreactivity and compare relative differences in the concentration of these variables between the central and peripheral compartments.
Molecular analysis of intermediate filament cytoskeleton--a putative load-bearing structure
Authors: Price M. G.
Published: December 2017

Myocardial cells contain a cytoskeleton of intermediate filaments connecting the myofibrils. The present molecular analysis of the myocardial cytoskeleton was designed to identify the intermediate filament proteins and examine their assembly properties. The intermediate filament proteins desmin and vimentin were isolated from adult bovine myocardium by sequential extraction, urea solubilization, and chromatography on hydroxylapatite and DEAE columns. Desmin was obtained virtually pure in one peak and in a mixture of desmin and vimentin in the trailing fractions. Intermediate filaments of different morphologies polymerized in the desmin and the desmin-vimentin fractions. Isolated myocardial desmin occurs as three isozymes and isolated myocardial vimentin as two isozymes, which co-migrate on two-dimensional gels with corresponding isozymes from bovine skeletal and smooth muscle. Polypeptides of 200,000 and 220,000 daltons that fractionate with myocardial desmin and vimentin are also present in cytoskeletons of smooth and skeletal muscle. The results provide direct evidence that myocardial desmin can assemble to form intermediate filaments, suggesting that desmin is the major component of the cytoskeletal filaments in cardiomyocytes.
Effect of aminophylline on adenosine and exercise dilation of rat cremaster arterioles
Authors: Mohrman D. E. , Heller L. J.
Published: December 2017

The present study was undertaken to evaluate the role that adenosine may play in exercise vasodilation. Responses of rat cremaster muscle arterioles to either topically applied adenosine or muscle exercise were recorded via video-microscopy before and after topical administration of aminophylline (10(-4) M). In all experiments, alpha-adrenergic receptors were blocked by pretreatment with phentolamine. Under control conditions the average concentration of adenosine required to produce a 50% dilation response (ED50) was 1.9 X 10(-6) M, and the full dose-response curve spanned 2 log units from threshold to near maximum responses. Topical aminophylline increased the ED50 for adenosine dilation to 9.1 X 10(-6) M. Stepwise increases in muscle twitch rate produced a progressive arteriolar dilation, and the dilation associated with 2-Hz exercise approached the maximal dilation observed with adenosine. Topical aminophylline, however, had no effect on the arteriolar dilation response to cremaster muscle exercise. It is unlikely that our results can be explained by any influence that exercise might have on the arteriolar sensitivity to adenosine or on the efficacy of aminophylline blockade because aminophylline had no effect on the arteriolar response to even the lowest rates of exercise tested. We conclude either that adenosine does not mediate exercise dilation in rat cremaster muscle or that interstitial adenosine levels during exercise in the presence of 10(-4) M aminophylline are significantly higher (5X) than during exercise without aminophylline.
Is ischemia-induced pH decrease of dog myocardium respiratory or metabolic acidosis?
Authors: Ichihara K. , Haga N. , Abiko Y.
Published: December 2017

Ischemia causes myocardial acidosis and elevation of myocardial CO2 tension (PCO2). We performed the present study to examine whether accumulation of hydrogen ion is a cause or result of accumulation of CO2. The myocardial pH and PCO2 were measured simultaneously in the dog heart, and the concentration of HCO-3 [( HCO-3]) was calculated according to the Henderson-Hasselbalch equation. Ischemia was induced by either partial or complete occlusion of the left anterior descending coronary artery (LAD). After LAD occlusion, the myocardial pH decreased with a marked decrease in [HCO-3], indicating that metabolic acidosis occurred. We ascertained in experiments with blood sample in vitro that an addition of lactic acid into blood decreased both [HCO-3] and pH (metabolic acidosis), whereas an addition of CO2 gas into blood increased [HCO-3] and decreased pH (respiratory acidosis). These findings suggest that ischemic acidosis is not respiratory in nature, but metabolic. The myocardial pH decrease due to ischemia, however, cannot be explained by the tissue lactate accumulation alone, because the decrease of [HCO-3] is far greater than the increase of lactic acid during ischemia.
Hypercapnia potentiates renal vasoconstriction during hemorrhagic hypotension in awake rabbits
Authors: Busija D. W.
Published: December 2017

Although both hemorrhagic hypotension and hypercapnia increase renal vascular resistance (RVR) modestly, effects of interaction between these stimuli on RVR have not been examined systematically in unanesthetized animals. The purpose of this study was to test the hypothesis that renal vasoconstriction during hemorrhagic hypotension is affected by arterial CO2 tension (PCO2). Unanesthetized rabbits were placed into an environmental chamber, and six were exposed to normocapnia (PCO2 approximately 29 mmHg) and six to hypercapnia (PCO2 approximately 62 mmHg). Renal blood flow (RBF) was measured with 15-micrograms microspheres during 1) normotension [mean arterial pressure (MAP) 84-88 mmHg]; 2) moderate hemorrhagic hypotension (MAP 61-64 mmHg); and 3) severe hemorrhagic hypotension (MAP 44-50 mmHg). When MAP was normal, RBF was 437 +/- 59 and 345 +/- 59 ml X min-1 X 100 g-1 in the normocapnic and hypercapnic groups, respectively (NS; P greater than 0.05). In addition, RVR (MAP/RBF) was 0.22 +/- 0.04 in the normocapnic group and 0.32 +/- 0.08 mmHg X ml-1 X min X 100 g in the hypercapnic group (NS; P greater than 0.05). During moderate hypotension, RVR was 0.48 +/- 0.18 in the normocapnic group and 1.74 +/- 0.36 mmHg X ml-1 X min X 100 g in the hypercapnic group (P less than 0.05, comparison between groups). During severe hypotension, RVR was 0.46 +/- 0.14 and 3.13 +/- 1.13 mmHg X ml-1 X min X 100 g during normocapnia and hypercapnia, respectively (P less than 0.05, comparison between groups). Thus, in unanesthetized rabbits, although hypercapnia does not increase RVR compared with normocapnia when arterial pressure is normal, hypercapnia greatly potentiates renal vasoconstriction during hemorrhagic hypotension.
Comparison of slow response action potentials from normal and hypertrophied myocardium
Authors: Hemwall E. L. , Duthinh V. , Houser S. R.
Published: December 2017

Previous studies have shown that papillary muscles from hypertrophied cat right ventricles (RVH) exhibit altered mechanical properties which may be associated with defects in the excitation-contraction coupling process. Since calcium influx [as slow inward current (Isi) during the cardiac action potential is thought to be a major determinant of contractile state, we compared Isi-mediated slow response action potentials ( SRAPs ) in papillary muscles from cats with RVH, induced by chronic pulmonary artery constriction, to SRAPs from sham-operated controls. The results show that 1) when depolarized by elevated extracellular potassium (K+o, 22 mM), RVH muscles became inexcitable (as defined here) significantly faster than control muscles; 2) inexcitable RVH muscles required significantly more isoproterenol than controls to restore slow response activity; 3) at all isoproterenol concentrations tested, SRAPs from RVH muscles were reduced in amplitude and duration compared with controls; 4) SRAPs evoked by long duration stimulus pulses in the absence of isoproterenol were also markedly reduced in RVH; and 5) the relationship between resting potential and K+o was the same in both groups. If the alterations in SRAPs observed in RVH are produced by a smaller Isi, this change may be associated with the diminished inotropic state of cardiac muscle caused to hypertrophy due to pressure overload.
Limitations of thermodilution cardiac output measurements in the rat
Authors: Hayes B. E. , Will J. A. , Zarnstorff W. C. , Bisgard G. E.
Published: December 2017

Heat loss from the vascular system could introduce an error in thermodilution cardiac output determinations. Cardiac output measured in the rat via the thermodilution technique following right atrial injection yielded different values (P less than 0.001), depending whether sampling was from the pulmonary artery (460 +/- 31 ml X min-1 X kg-1), right ventricle (311 +/- 19), or thoracic aorta (245 +/- 15). Recirculation errors could not account for the differences. Heat loss from the vascular system was measured from extravascular thermistors within both the thorax and the abdomen. These dilutions were 22-57% in peak height of aortic curves recorded at approximately the same location. Differences in calculated cardiac output between sampling sites could be attributed to rapid heat conduction directly from the right atrium and inferior vena cava to the thoracic aorta with progressive loss of indicator from both the right ventricle and pulmonary artery.
Excitation-contraction in rat myocardium: alterations with adult aging
Authors: Wei J. Y. , Spurgeon H. A. , Lakatta E. G.
Published: December 2017

Simultaneous transmembrane action potential (TAP) and isometric contraction measurements were made in thin right ventricular papillary muscles isolated from senescent (S, 24-26 mo) and young adult (YA, 6-8 mo) rat hearts. At the peak of the length-tension curve in the steady state at 24 min-1 at 29 degrees C in perfusate [Ca2+] [( Ca2+]e) of 0.375 or 2.5 mM, contractile tension developed in response to excitation (DT) and the maximum rate of tension development (dT/dt) were not age-related; contraction duration (CD) was 17 and 27% greater in S than YA in the low and high [Ca2+]e, respectively (P less than 0.001); resting membrane potential was not age related. TAP time above zero mV, integrated area above zero mV, and times to 75% (T75) and 90% (T90) repolarization were approximately twofold greater in S than in YA in both [Ca2+]e (P less than 0.001). Changes in steady-state T75 and T90 due to an increase in [Ca2+]e from 0.375 to 2.5 mM were significantly correlated with those in CD, DT, and dT/dt in S but not in YA. We conclude that in the senescent myocardium a prolonged and greater extent of depolarization is related to the prolonged CD and may also be a determinant of the peak force developed in response to excitation under some conditions.
Effect of thiamylal on the response to carotid occlusion and mild hemorrhage in rabbits
Authors: Yamazaki T. , Sagawa K.
Published: December 2017

The effects of anesthesia (thiamylal, 30 mg/kg) on steady-state mean arterial pressure responses to bilateral carotid occlusion (BCO) and rapid 8% hemorrhage were studied in 11 rabbits chronically instrumented with an arterial pressure catheter and balloon occluders on the common carotid arteries. The BCO was repeated in the conscious and anesthetized states both before and after transecting the aortic nerves (AN). With the AN intact, the BCO response was an increase in mean systemic arterial pressure of 23.6 +/- 2.1 (SE) mmHg in the conscious state and 24.7 +/- 1.2 in the anesthetized state. With the AN cut (AN) BCO response was 46.2 +/- 1.7 mmHg in conscious state and 45.7 +/- 2.6 in anesthetized state. There was no significant difference in BCO response between conscious and anesthetized states, whether the AN was present or absent. The hemorrhage experiment was repeated on separate days under various conditions, including carotid sinus reflex elimination (CS). With AN intact the posthemorrhage fall in mean arterial pressure (delta MAPh) was 3.2 +/- 0.6 mmHg in the conscious state. Under anesthesia, delta MAPh was 3.4 +/- 0.6 mmHg in the AN intact condition, 7.3 +/- 0.9 in AN, and 34.5 +/- 6.8 in (AN + CS). There was no significant difference in delta MAP between the conscious and anesthetized states under the intact AN condition. We conclude that, in the rabbit, thiamylal anesthesia has little effect on the BCO response and the restoration of arterial pressure after a mild hemorrhage.
Effect of polycythemia on vascular volume in the newborn dog
Authors: Leblanc M. H. , Pate K.
Published: December 2017

The effect of polycythemia [hematocrit (Hct) 64-80] on blood volume (BV) was studied in 27 unanesthetized, splenectomized newborn dogs (age 6-14 days, postsplenectomy 5-13 days). Normovolemic polycythemia (N) was induced in nine pups by exchange transfusion with 75 ml/kg of adult, packed (to Hct 95) red blood cells (RBC). Hypervolemic polycythemia (H) was induced in 11 pups by transfusion of RBC (50 ml/kg). Seven pups received exchange transfusion with 75 ml/kg of whole blood and served as controls (C). Red cell volume (RCV, 51CrRBC) and plasma volume (PV, 125I-fibrinogen and Evans blue) were measured prior to and at 1, 2, and 4 h after transfusion, before the pups received fluid orally. The pups were fed 8 ml X kg-1 X h-1 after 4 h, and measurements were repeated at 8 and 24 h. BV fell in C prior to 4 h by 10 +/- 4% (SD) (P less than 0.01) and then rose to initial levels. BV rose in the N pups by 17 +/- 9 (P less than 0.01), 14 +/- 5 (P less than 0.01), 9 +/- 10 (P less than 0.1), 17 +/- 9 (P less than 0.01), and 31 +/- 17% (P less than 0.01) at 1, 2, 4, 8, and 24 h post transfusion. BV rose in the H pups by 41 +/- 8, 35 +/- 10, 23 +/- 11, 27 +/- 6, and 43 +/- 9% (all P less than 0.01). Thus newborn dogs with induced N or H equilibrate rapidly to a BV significantly higher than C levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of parasympathetic control of heart rate by a noninvasive method
Authors: Fouad F. M. , Tarazi R. C. , Ferrario C. M. , Fighaly S. , Alicandri C.
Published: December 2017

The degree of parasympathetic control of heart rate was assessed by the abolition of respiratory sinus arrhythmia with atropine. Peak-to-peak variations in heart periods (VHP) before atropine injection correlated significantly (r = 0.90, P less than 0.001) with parasympathetic control, indicating that VHP alone may be used as a noninvasive indicator of the parasympathetic control of heart rate. Pharmacologic blockade of beta-adrenergic supply in a separate group of normal volunteers did not alter the relationship between VHP and parasympathetic control, indicating that the condition of the experiment (complete rest in a quiet atmosphere) allows the use of VHP alone without pharmacologic interventions to characterize the vagal control of heart rate in humans.
Regulation of pyruvate dehydrogenase complex in ischemic rat heart
Authors: Patel T. B. , Olson M. S.
Published: December 2017

The effect of flow-induced ischemia on the rate of pyruvate decarboxylation and the activation state of the pyruvate dehydrogenase multienzyme complex was investigated in the isolated, perfused rat heart. Pyruvate dehydrogenase activity in the heart decreased significantly during flow-induced ischemia and was a function of changes in the activation state (i.e., active/total activity) of the enzyme complex. In the absence of pyruvate, the activation state of pyruvate dehydrogenase decreased from nearly 100% active at the normal flow rate (10 ml/min) to 20% active as the flow was reduced to 0.5 ml/min. At high pyruvate levels (5 mM), the activation state increased from nearly 70% active at control flow rates to 100% active during ischemia. At an intermediate pyruvate concentration (0.5 mM), the enzyme complex was maintained at a relatively low activation state (30–35% active) throughout the range of flow rates tested. Ischemia caused elevated perfusate lactate concentrations only when the flow rates were less than 5.0 ml/min. The activation state of the pyruvate dehydrogenase complex in hearts perfused with glucose was also decreased during ischemia.
Effect of sodium on calcium-dependent force in unstimulated rat cardiac muscle
Authors: Walford Gary D. , Gerstenblith Gary , Lakatta Edward G.
Published: December 2017

Page H222: Gary D. Walford, Gary Gerstenblith, and Edward G. Lakatta. “Effect of sodium on calcium-dependent force in unstimulated rat cardiac muscle.” Page H228: the equation should read

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