bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle
Authors: Marino T. A. , Kent R. L. , Uboh C. E. , Fernandez E. , Thompson E. W. , Cooper G.
Published: December 2017

Pressure overload of cat right ventricle causes progressive abnormalities of in vitro contractile function at a time when in vivo contractile function is normal. In marked contrast, the same degree and duration of volume overload of cat right ventricle results in neither in vitro nor in vivo contractile dysfunction. The purpose of the present quantitative structural study was to determine whether there were any histological alterations in pressure-overloaded myocardium that might be causally related to the contractile dysfunction found only in this model. Four experimental groups of eight cats each were studied: a group with pulmonary arterial banding to create a pressure overload, sham-operated controls for this group, a group with atrial septal defects to create a volume overload, and sham-operated controls for this group. Seven to ten weeks after each operative procedure, right ventricular pressure was elevated only in the pressure-overloaded group, pulmonary-to-systemic blood flow ratio was increased only in the volume-overloaded group, and right ventricle-to-body weight ratio was significantly and comparably increased in both the pressure- and the volume-overloaded groups. There was a single striking histological distinction between myocardium hypertrophying in response to pressure as opposed to volume overload: the volume density of cardiocytes in papillary muscles from pressure-overloaded right ventricles was decreased significantly with a proportional increase in connective tissue. Given the critical importance of these two myocardial components to both systolic and diastolic cardiac function, these data provide a potential structural basis for at least some of the functional abnormalities observed in pressure but not in volume overload hypertrophy of the cat right ventricle.
Phentolamine-resistant neurogenic constriction occurs in small arteries at higher frequencies
Authors: Owen M. P. , Quinn C. , Bevan J. A.
Published: December 2017

The effect of the alpha 1, alpha 2-antagonist phentolamine (PTA) on neuromuscular transmission and exogenous norepinephrine (NE) was assessed in arteries of diminishing diameter possessing a substantial adventitiomedial junction adrenergic innervation in the rabbit ear, i.e., central ear artery (CEA), unstretched lumen diameter (ULD) approximately equal to 300 microns; main side branch (MSB) off the CEA (ULD approximately equal to 150 microns); and terminal branch (TB) off the MSB (ULD approximately equal to 75 microns). With increasing PTA concentrations, contractile responses to transmural nerve stimulation (TNS) were decreased proportionately less in TB than in MSB and CEA. PTA (4 X 10(-6) M, a competitive antagonist concentration) blocked the tetrodotoxin-sensitive TNS-induced contractions of CEA segments at 2, 4, and 8 Hz. The response at 8 Hz was reduced at least 98% in MSB and 86% in TB. However, responses to 8 Hz were not abolished in MSB and TB until 2 X 10(-5) and 3 X 10(-5) M PTA, respectively. PTA (3 X 10(-5) M) possessed nonspecific depressant properties in addition to its alpha-antagonist properties. We conclude that the sympathetic nervous system influences tone through alpha-adrenoceptors in the CEA and in the MSB and TB at lower frequencies. Responses in the MSB and TB at higher frequencies of nerve stimulation are mediated predominately through alpha-receptors. If the possibility of a nonadrenergic transmitter is discounted, the possibilities that the small PTA-resistant component of the neurogenic response is due to a high concentration of NE acting on alpha-adrenoceptors and/or a high threshold site cannot be distinguished.
Fluid volumes and hemodynamics in hypertension produced by chemical renal medullectomy
Authors: Taverner D. , Bing R. F. , Swales J. D. , Thurston H.
Published: December 2017

We have investigated the mechanisms by which chemical renal medullectomy with 2-bromoethylamine hydrobromide (200 mg/kg body wt) produces hypertension in rats. Groups of chemically medullectomized rats were compared with normal rats and rats that had been partially nephrectomized to produce an equivalent fall in glomerular filtration rate. Mean arterial pressure was elevated in the medullectomized (142 +/- 6 mmHg) compared with normal rats (124 +/- 3). In the medullectomized animals this was associated with significant tachycardia (483 +/- 15 vs. 450 +/- 6 beats/min) and an increase in cardiac output (61.1 +/- 5.0 vs. 49.9 +/- 2.2 ml X min-1 X 100 g body wt-1). Plasma volume was significantly reduced in medullectomized rats (2.16 +/- 0.15 vs 3.29 +/- 0.20 ml/100 g body wt), whereas exchangeable sodium was unchanged (39.9 +/- 0.5 vs. 39.7 +/- 0.5 meq/kg body wt). By contrast, both plasma volume and exchangeable sodium were increased in partially nephrectomized rats. These results are consistent with the hypothesis that chemical medullectomy produces hypertension by increased selective sympathetic efferent activity, raising cardiac output and postcapillary venular resistance. This may be the consequence of reducing the secretion of a renomedullary humoral substance that normally inhibits such activity.
Compartmented pyruvate in perfused working heart
Authors: Bunger R.
Published: December 2017

Pyruvate compartmentation and lactate dehydrogenase (LDH) were studied in isolated perfused working guinea pig hearts. The mean intracellular pyruvate (Pyr) contents increased with perfusate Pyr (0-2 mM) but varied only slightly with glucose (0-10 mM) and additional insulin (0.04-5 U/l), respectively. With 5-10 mM glucose plus 5 U/l insulin, but not with Pyr or lactate (Lac) as substrates, a near equilibrium between the LDH and the glycerol-3-phosphate dehydrogenase seemed to exist. Evidence for an inhibitory effect of Pyr on the activity of the LDH system of the perfused hearts was not obtained. With [U-14C]glucose as sole substrate, the specific activity of coronary venous Lac was near half that of precursor glucose. 14CO2 production was thus in quantitative agreement with rates of pyruvate oxidation that were determined as glucose uptake minus (Pyr + Lac) release. In contrast, with 0.2 mM [1-14C]Pyr plus 5 mM glucose, the ratio of 14CO2 production to specific activity of Lac overestimated Pyr oxidation judged from myocardial substrate balances and O2 uptake, respectively; here, at least three pools of [14C]HCO-3 and [14C]lac, respectively, were kinetically demonstrable during washout of trace amounts of 14C-labeled Pyr. Evidently, the specific activity of Lac was equivalent to that of mitochondrial oxidized Pyr provided [14C]glucose was the sole or major precursor of cellular pyruvate. However, exogenously applied [1-14C]Pyr of high specific activity seemed to induce intracellular formation of both a highly and lowly labeled Pyr; the latter Pyr compartment did not seem in ready equilibrium with the cell physiologically prevailing highly labeled Pyr pool.
Hypotension 1.5 min after 10% hemorrhage permits evaluation of rabbit's baroreflex
Authors: Yamazaki T. , Sagawa K.
Published: December 2017

In seven chronically instrumented rabbits, we studied the influence of the vasopressin system on the evaluation of acute reflex compensation of arterial pressure for a mild hemorrhage. Rabbits were bled 10% of estimated blood volume in 1 min. The hemorrhage was repeated before and after administration of a vasopressin antagonist [d(CH2)5Tyr(Me)arginine vasopressin, 10 micrograms/kg] and in the conscious and anesthetized (pentobarbital sodium 20 mg/kg) state. The efficacy of the vasopressin antagonist was preliminarily tested in each rabbit by confirming its antagonism against the hemodynamic effects of infused vasopressin (50 ng X min-1 X kg-1). Mean arterial pressure (MAP), heart rate (HR), mean aortic flow (MAF), and total peripheral resistance (TPR) were measured before and at 1.5 min after completion of hemorrhage. The hemorrhage caused statistically significant decrease in MAP (84 +/- 6 to 78 +/- 6 mmHg) and MAF (195 +/- 28 to 158 +/- 26 ml X kg-1 X min-1) and increase in TRP (0.44 +/- 0.05 to 0.51 +/- 0.07 mmHg X kg X min X ml-1) and HR (271 +/- 21 to 284 +/- 22 beat/min). However, there was no statistically significant interaction in any variables between vasopressin and hemorrhage, i.e., whether vasopressin was blocked or intact did not affect the fall in MAP by hemorrhage. We conclude that in the rabbit vasopressin's role in the acute compensation of arterial pressure for a quick 10% hemorrhage is small enough to permit accurate estimation of the arterial baroreflex gain from the depressor responses to mild hemorrhage with and without the reflex function.
Peptide 6A, a fibrin(ogen) degradation product, increases coronary blood flow
Authors: Mehta J. , Wargovich T. , Nichols W. W. , Saldeen K. , Wallin R. , Saldeen T.
Published: December 2017

The coronary hemodynamic effects of intracoronary administration of a fibrin(ogen)-derived pentapeptide, Ala-Arg-Pro-Ala-Lys (peptide 6A), were evaluated in open-chest anesthetized dogs. With administration of peptide 6A (2.5-30 mumol), coronary blood flow increased and coronary vascular resistance decreased promptly in a dose-related manner. Increase in coronary blood flow was independent of any change in indexes of myocardial O2 demand, indicating the peptide 6A exerts direct effects on coronary arterial tone. Systemic arterial and left ventricular end-diastolic pressures remained unchanged with smaller doses but decreased when higher doses of peptide 6A (greater than or equal to 20 mumol) were administered. Plasma concentrations of 6-ketoprostaglandin F1 alpha, stable hydrolysis product of prostacyclin, increased in coronary sinus blood samples in conjunction with increase in coronary blood flow. Administration of indomethacin (5 mg/kg iv) inhibited peptide 6A-induced release of prostacyclin and significantly attenuated the effects of peptide 6A on coronary hemodynamics. Pretreatment of animals with H2-receptor blocker cimetidine (500 mg iv) or with H1-and H2-receptor blocker diphenhydramine (50 mg iv) had no significant effects on peptide 6A-induced increase in coronary blood flow. This study suggests that this fibrin(ogen)-derived peptide has potent vasodilator effects on the coronary vascular bed of the dog, and these effects are in part mediated by stimulation of prostacyclin release.
Nicotine increases heart adenosine release, oxygen consumption, and contractility
Authors: Fenton R. A. , Dobson J. G.
Published: December 2017

The effect of nicotine on adenosine release, oxygen consumption, and contractility was investigated in perfused rat hearts. Continuous infusion of nicotine into the perfusing physiological saline (PS) elicited a propranolol (10(-6) M) sensitive transient elevation of developed left ventricular pressure (LVP) and maximum rates of left ventricular pressure development and relaxation (+/- dP/dtmax) within 20 s, which subsequently declined to maintained elevated plateau levels by 1 min. The continuous infusions of nicotine to achieve PS concentrations of 5 X 10(-4), 1 X 10(-4), or 5 X 10(-5) M, respectively resulted in significant increases in the mean plateau levels of LVP (33.4, 10.1, or 6.3%), +dP/dtmax (26.3, 10.8, or 6.9%) and-dP/dtmax (35.0, 11.9, or 9.0%) at 1 min. The inclusion of propranolol (10(-6) M) with or without atropine (10(-6) M) did not alter these maintained plateau responses to nicotine. During the plateau phase of the contractile response oxygen consumption of the hearts was significantly elevated by 36, 19, or 11%, and mean levels for adenosine in the coronary effluent rose by 261, 76, or 74% in response to 5 X 10(-4), 1 X 10(-4), or 5 X 10(-5) M nicotine, respectively. Nicotine did not influence [14C]adenosine uptake by the hearts. These results suggest that nicotine is capable of 1) augmenting cardiac contractility and oxygen consumption independent of beta-adrenergic or muscarinic influence, and 2) elevating the appearance of adenosine in the coronary circulation presumably by enhancing myocardial production of the nucleoside.
Cerebral vascular autoregulation of blood flow and tissue PO2 in diabetic rats
Authors: Rubin M. J. , Bohlen H. G.
Published: December 2017

The effect of chronic, severe diabetes mellitus on the morphology, blood flow regulation, and tissue PO2 of the cerebral cortex was evaluated in adult rats. The arterioles of the diabetic animals were enlarged in terms of both lumen diameter and vessel wall area. Although resting blood flow in the diabetic rats was greater than in the normal rats, the autoregulation of cerebral blood flow was very good within an arterial pressure range of 40-150 mmHg, just as in normal rats. The resting tissue PO2 in diabetic rats was 14.9 +/- 0.5 (SEM) compared with 12.7 +/- 0.6 mmHg in normal animals and in both groups remained at or near the resting PO2 at arterial pressures from 40 to 150 mmHg. There was no apparent loss of arterioles on the cortex surface or change in length of individual arterioles in diabetic animals but there was a 20-30% decrease in the number of venules and no change in the length of individual venules. These data indicate that although the arteriolar morphology and number of venules change in the brain during diabetes, physiological function in terms of tissue PO2 and blood flow regulation is maintained within normal limits.
Modeling of time-variant coupling between left ventricle and aorta in cardiac cycle
Authors: Tozeren A. , Chien S.
Published: December 2017

An analytical model is developed to study the interaction between the left ventricle and vascular system. Ventricular pressure is expressed as a function of the chamber volume, volumetric strain rate, and the degree of activation. A three-element Wind-kessel model is employed to represent the hydraulic properties of the vascular system. Conditions of interaction between the left ventricle and the vascular system are formulated in mathematical terms. Numerical solutions are obtained for the mechanical events occurring during a cardiac cycle as a function of time. The time variations of aortic pressure and ventricular volume predicted by the model compare well with the experimental results of Sunagawa and co-workers [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H346-H350, 1982, and Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H773-H780, 1983]. Furthermore, the application of the present model to the experimental data has allowed the derivation of the intrinsic contractility parameters in these experiments. The unique features of this analytical model are that 1) it provides the time-variant pressure and volume curves of the left ventricle in relation to the aorta, 2) it generates information on the effects of heart rate on these hemodynamic parameters, and 3) it allows the derivation of intrinsic contractility parameters from experimental data.
Measurement of peak systolic elastance in intact canine circulation with servo pump
Authors: Bogen D. K. , Ariel Y. , McMahon T. A. , Gaasch W. H.
Published: December 2017

Peak systolic elastance (Emax) was measured in the intact canine circulation by means of a new experimental technique. In this technique the heart is isolated from the circulation during a single systole and subjected to controlled ventricular loads. An electropneumatic aortic occluder is used to isolate the ventricle, and a servo-controlled syringe pump is used to control the ventricular load. Because the experimental load is applied for a single heartbeat only, ventricular function can be measured without the interference of regulatory feedback mechanisms. In eight dogs, weighing 17-42 kg, the relationship between changes in endsystolic pressure and volume was determined from the single-beat application of purely compliant loads. The end-systolic relations were linear, and their slope, Emax, was inversely related to weight. The observed relation between Emax and body weight allows comparisons to be made between different preparations in which Emax has been determined. Values of Emax obtained from the single-beat preparation were found to be 27-74% above those reported in isolated heart preparations and nearly identical to those reported for in vivo or denervated in situ preparations.
Electrophysiology of functional subsidiary pacemakers in canine right atrium
Authors: Rozanski G. J. , Lipsius S. L.
Published: December 2017

Glass microelectrodes were used to study the electrical activity of the subsidiary atrial pacemaker (SAP) cells that maintain atrial excitation after suppression of the sinoatrial node. Tissues with documented SAP activity were isolated from the canine inferior right atrium and superfused in vitro with Tyrode solution containing norepinephrine (NE, 10(-8)-10(-7) M). SAP action potentials exhibited prominent diastolic depolarization and a significantly lower maximum diastolic potential, take-off potential, overshoot, rate of rise, and amplitude than typical atrial muscle. Withdrawal of NE completely blocked SAP propagation, although SAP automaticity continued at a slower rate. Acetylcholine (ACh, 5 X 10(-8) M) usually produced complete exit block and decreased spontaneous rate. Higher concentrations of ACh (10(-6) M) elicited a prominent hyperpolarization (19.2 +/- 6.6 mV), completely suppressing SAP automaticity. In quiescent preparations exposed to NE greater than or equal to 10(-7) M, external stimuli at short cycle lengths (less than 1,000 ms) elicited action potentials with delayed afterdepolarizations, which frequently caused nondriven repetitive activity. This triggered activity was inhibited by verapamil or withdrawal of NE. These studies identify and characterize the electrical activity of functional subsidiary pacemakers located in a specific region of the inferior right atrium. In addition, fibers within this region display triggered activity. Spontaneous activity generated by fibers within the SAP region may cause atrial dysrhythmias.
Effects of anoxia and ischemia on thallium exchange in rabbit myocardium
Authors: Krivokapich J. , Watanabe C. R. , Shine K. I.
Published: December 2017

We investigated the effects of anoxia and ischemia on thallium (201Tl) exchange using isolated rabbit interventricular septa. Anoxia for 20 or 40 min caused a decrease in 201Tl tissue uptake due to an increased efflux of 201Tl with a smaller increase in 201Tl influx. Between 40 and 60 min of anoxia, the increased efflux of 201Tl was reversed and the increase in 201Tl influx was absent. After 60 min of reoxygenation, septa made anoxic for 20-60 min recovered at least 95% of the Tl lost. Mechanical recovery, however, was still significantly depressed. Reperfusion after total ischemia for 20-60 min was followed by resumption of 201Tl uptake despite continued mechanical dysfunction. Efflux rates during reperfusion after ischemia were significantly different from preischemic values but not in a predictable way. This unpredictability complicates interpretation of clinical 201Tl redistribution studies. These results represent important differences from those reported previously using 42K [Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H85-H94 and H564-H570, 1977]. Anoxia did not increase the influx of 42K. Also, 60 min of ischemia resulted in progressive losses of 42K. This implies there are different sensitivities and/or mechanisms for Tl compared with K uptake. Our results are consistent with 201Tl uptake by severely damaged and nonviable cells.
End-systolic pressure-volume, pressure-length, and stress-strain relations in canine hearts
Authors: Kaseda S. , Tomoike H. , Ogata I. , Nakamura M.
Published: December 2017

End-systolic pressure-volume relationship (ESPVR) of the in situ heart in the dog was measured during changes in contractile state and was compared with end-systolic pressure-length (ESPLR) or stress-strain relationship (ESSSR). Circumferential segmental length and wall thickness at the equator and external long and short axis diameters of the left ventricle (LV) were determined sonomicrometrically, and LV volume was calculated by an ellipsoidal model. Circumferential wall stress at the equator was calculated by a very thin shell model. Contractile state was enhanced by an intravenous infusion of dobutamine and was suppressed by propranolol. ESPVR, ESPLR, and ESSSR were determined during a reduction of arterial pressure by occluding temporarily the inferior caval vein (IVC). ESPVR, ESPLR, and ESSSR during changes in end-systolic pressure from 108 +/- 3 to 71 +/- 2 mmHg were linear, irrespective of inotropic states (r greater than 0.92). Slopes of these relationships increased similarly in case of dobutamine and were reduced after propranolol, yet the extrapolated X-axis intercept of ESPVR, ESPLR, and ESSSR remained unchanged. Thus the slope of ESPVR is unique to the inotropic state, and both ESPLR and ESSSR are useful as a substitute for ESPVR when there is no regional wall motion abnormality.
Microvascular, interstitial, and lymphatic interactions in normal heart
Authors: Laine G. A. , Granger H. J.
Published: December 2017

Control of transmicrovascular fluid exchange in the heart is of critical importance in the prevention of myocardial edema formation. To quantify the absolute values for, and the interrelationships between, the forces and flows governing fluid balance within the normal heart, the following variables were measured: arterial pressure (Pa), coronary sinus pressure (Pcs), myocardial interstitial fluid pressure (Pint), plasma protein concentration (Cp), and oncotic pressure (tau cap) along with interstitial protein concentration (CL), interstitial oncotic pressure (tau int), and left ventricular lymph flow rate (Jv). All parameters were recorded under control conditions and during graded venous pressure elevations. Control values were Pa, 125 +/- 21 mmHg; Pcs, 7.3 +/- 1.3 mmHg; Pint, 14.9 +/- 3.1 mmHg; CL/Cp, 0.82 +/- 0.12; and Jv, 7.0 +/- 2.7 ml/h. As Pcs was elevated to eight times control, Pint increased from 15 to 50 mmHg and lymph flow rose sixfold. A filtration-independent value for CL/Cp could not be obtained for total plasma protein, although a washdown CL/Cp value for beta-lipoprotein of 0.04 was obtained. Our data indicate that a large surface area of myocardial exchange vessels coupled with lymphatics of relatively low sensitivity to extravascular volume expansion produce a system that relies on a large increase in interstitial hydrostatic pressure to limit edema formation.
Evidence for existence of postjunctional alpha 1- and alpha 2-adrenoceptors in cat pulmonary vascular bed
Authors: Hyman A. L. , Kadowitz P. J.
Published: December 2017

The subtypes of postjunctional alpha-adrenoceptors in the feline pulmonary vascular bed were studied using selective alpha-adrenoceptor agonists and antagonists. Under conditions of controlled pulmonary blood flow and constant left atrial pressure, intralobar injections of the alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, and the alpha 2-adrenoceptor agonists, UK 14,304 and BHT 933, increased lobar arterial pressure in a dose-related manner. Prazosin, an alpha 1-adrenoceptor antagonist, reduced responses to phenylephrine and methoxamine to a greater extent than responses to UK 14,304 and BHT 933. Yohimbine, an alpha 2-adrenoceptor blocker, decreased responses to UK 14,304 and BHT 933 without altering responses to phenylephrine or methoxamine. The same pattern of blockade was observed in animals pretreated with 6-hydroxydopamine, an agent that destroys the integrity of adrenergic nerve terminals. However, in propranolol-treated animals, prazosin antagonized responses to phenylephrine and methoxamine without altering responses to UK 14,304 or BHT 933, and the selectivity of the blocking effects of yohimbine were preserved. Responses to intralobar injections of norepinephrine were markedly decreased by prazosin, whereas yohimbine had only a small effect. These data suggest the presence of both postjunctional alpha 1- and alpha 2-adrenoceptors mediating vasoconstriction in the pulmonary vascular bed. These results also indicate that the vasoconstrictor responses to injected norepinephrine in the cat pulmonary vascular bed are due mainly to activation of alpha 1-adrenoceptors.
Systemic and renal hemodynamic changes during acute unilateral renal arterial stenosis
Authors: Anderson W. P. , Kline R. L. , Woods R. L.
Published: December 2017

The acute effects of unilateral renal arterial stenosis on systemic and renal hemodynamics were studied in chronically instrumented, conscious dogs. Graded stenosis of one renal artery for 90 min produced graded increases in arterial blood pressure and plasma renin activity and falls in contralateral renal blood flow and total peripheral conductance. There were no significant changes in cardiac output. The changes were transient after mild or moderate renal arterial stenosis but were sustained after severe stenosis. Pentolinium treatment did not significantly affect the hypertension or contralateral renal vasoconstriction caused by moderate or severe renal arterial stenosis. This indicates that the autonomic nervous system did not play a major role in the response to stenosis. In contrast, teprotide abolished the increases in arterial pressure, the contralateral renal vasoconstriction, and the fall in total peripheral conductance in response to stenosis. Thus the acute hypertension following unilateral renal arterial stenosis was due to a decrease in total peripheral conductance caused by decreased conductance of the stenotic kidney due to the stenosis itself (about 20%); vasoconstriction of the contralateral kidney (about 20%), and vasoconstriction of other systemic vasculature (about 60%). The results suggest that angiotensin II was responsible for the vasoconstriction of both the contralateral kidney and the other systemic vasculature.
Acute pressure increase and intrarenal hemodynamics in conscious WKY and SHR rats
Authors: Kobrin I. , Pegram B. L. , Frohlich E. D.
Published: December 2017

Spontaneously hypertensive rats (SHR) develop proteinuria and glomerular lesions during the first year of their life. To determine whether an intrarenal hemodynamic abnormality might participate in the pathogenesis of these lesions, normotensive Wistar-Kyoto (WKY) and SHR rats were subjected to acute pressure increase with phenylephrine infusion (2.5 and 5 micrograms X kg-1 X min-1), and renal blood flow (RBF), afferent and efferent arteriolar resistances, glomerular filtration rate (GFR), and glomerular capillary hydrostatic pressure were measured or calculated. The results indicate that the two strains responded differently to the pressure rise. Thus, although the increment in renal perfusion pressure and afferent arteriolar resistance increased similarly in the two strains, efferent resistance increased only in the SHR (7.2 +/- 1.6 vs. 9.0 +/- 2.1 units, P less than 0.02) but decreased in the WKY (5.3 +/- 0.8 vs. 4.0 +/- 0.5 units, P less than 0.05). This was associated with a decreased RBF of SHR (8.31 +/- 0.71 vs. 7.22 +/- 0.57 ml X min-1 X g kidney-1, P less than 0.05) but stable RBF in WKY (7.36 +/- 0.55 vs. 7.79 +/- 0.51 ml X min-1 X g kidney-1); GFR remained unchanged in both strains. Calculated glomerular hydrostatic pressure, however, increased in the SHR (43.6 +/- 3.0 vs. 48.5 +/- 2.2 mmHg, P less than 0.05) but decreased in the WKY (33.2 +/- 2.5 vs. 28.8 +/- 1.7 mmHg, P less than 0.01). The observed higher base-line glomerular pressure in the SHR and a greater rise with phenylephrine infusion may participate in the pathogenesis of the SHR glomerular lesions and proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
Impaired arteriolar vasodilation induced by thrombosis of a coronary arterial stenosis
Authors: Gewirtz H. , Sasken H. , Steiner M. , Most A. S.
Published: December 2017

This study tested the hypothesis that aggregation of platelets and release of thromboxane A2 at the site of a coronary arterial stenosis may contribute to myocardial ischemia by impairing flow regulation of the distal coronary bed. Measurements of hemodynamics, flow (microspheres), lactate metabolism, and prostaglandin (PG) metabolites (thromboxane B2 and 6-keto-PGF1 alpha) were made in closed-chest anesthetized pigs instrumented with a stenosis (65% diam reduction) in the left anterior descending (LAD) coronary artery. Data were acquired prior to stenosis insertion (control) and 5 and 15 min after insertion, during which time thrombotic occlusion of the device was occurring. Heart rate was controlled by atrial pacing. Distal LAD zone endocardial flow (ml X min-1 X g-1) declined versus control (1.15 +/- 0.20, mean +/- SD) at 5 min (0.89 +/- 0.40, P less than 0.05) and 15 min (0.41 +/- 0.36, P less than 0.01) of occlusion. Distal endocardial resistance (mmHg X ml-1 X min X g), however, did not change versus control (72 +/- 12) at 5 (66 +/- 12) or 15 min (61 +/- 38). Distal epicardial resistance (mmHg X ml-1 X min X g) declined versus control (90 +/- 17) at 5 (66 +/- 35, P less than 0.05) and 15 min (43 +/- 26, P less than 0.01) postinsertion. Finally, lactate extraction (%) at control (42 +/- 19) changed to production 15 min postinsertion (-36 +/- 93, P less than 0.05) and arterial-anterior interventricular vein thromboxane B2 difference (pg/0.1 ml) changed from 13.1 +/- 17.8 pre to -15.8 +/- 30.0 at 5 min post (P less than 0.05). Thus platelet aggregation and release at a spontaneously thrombosing stenosis contribute to ischemia not only by reduction of stenosis diameter but also by impairment of flow regulation in endocardial layers distal to it.
Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion
Authors: Gunn M. D. , Sen A. , Chang A. , Willerson J. T. , Buja L. M. , Chien K. R.
Published: December 2017

Previous studies have suggested that the accumulation of free arachidonic acid may be of major importance in the pathophysiology of myocardial ischemia. The purpose of the present study was to determine if the release of arachidonic acid from myocardial cells was more dependent on the extent of ATP depletion than on the inhibition of fatty acid oxidation. In addition, these studies were designed to determine if arachidonic acid release only occurred when ATP was depleted beyond a critical threshold level. To examine the relationship between arachidonic acid release and ATP depletion, cultured myocardial cells from neonatal rat hearts were labeled with [3H]arachidonate and [14C]palmitate. In response to ATP depletion with various metabolic inhibitors, [3H]arachidonic acid and [14C]palmitic acid were released from phospholipids. Phosphatidylcholine,phosphatidylethanolamine, and phosphatidic acid were the major esterified sources of the arachidonate. The release of both fatty acids was related to the extent of ATP depletion and not whether a glycolytic or respiratory inhibitor was utilized. Various combinations and doses of metabolic inhibitors were used, and experimental conditions that produced a greater than 75% decrease in ATP content were associated with the accumulation of arachidonic acid. These results suggest that an ATP-dependent step may be linked to the accumulation of arachidonic acid during myocardial ATP depletion. It is suggested that myocardial cells may release arachidonic acid directly in response to ATP depletion.
Norepinephrine-induced β1-adrenergic peripheral vasodilation in conscious dogs
Authors: Vatner Stephen F. , Knight Delvin R. , Hintze Thomas H.
Published: December 2017

Page H49: Stephen F. Vatner, Delvin R. Knight, and Thomas H. Hintze. “Norepinephrine-induced β1-adrenergic peripheral vasodilation in conscious dogs.” Figure 1 and Figure 4 were reversed. The figures and their correct legends should appear as follows.

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Biplane ventriculography in the rat
Authors: Heckman J. L. , Garvin L. , Brown T. , Stevenson-Smith W. , Santamore W. P. , Lynch P. R.
Published: December 2017

Biplane ventriculography was performed on nine intact anesthetized rats. Images of the left ventricle large enough for analysis were obtained by placing the rats close to the radiographic tubes (direct enlargement). Sampling rates, adequate for heart rates of 500 beats/min, were obtained by filming at 500 frames/s. From the digitized silhouettes of the left ventricle the following information was obtained (means +/- SE): end-diastolic volume 0.60 +/- 0.03 ml, end-systolic volume 0.22 +/- 0.02 ml, stroke volume 0.38 +/- 0.02 ml, ejection fraction 0.63 +/- 0.02, cardiac output 118 +/- 7 ml/min, diastolic septolateral dimension 0.41 +/- 0.01 mm, diastolic anteroposterior dimension 0.40 +/- 0.01 mm, diastolic base-to-apex dimension 1.58 +/- 0.04 mm. To determine the accuracy with which the volume of the ventricle could be measured, 11 methyl methacrylate casts of the left ventricle were made. The correlation was high (r = 0.99 +/- 0.02 ml E) between the cast volumes determined by water displacement and by use of two monoplane methods (Simpson's rule of integration and the area-length method applied to the analysis of the anteroposterior films) and a biplane method (area-length). These results demonstrate that it is possible to obtain accurate dimensions and volumes of the rat left ventricle by use of high-speed ventriculography.
Verapamil preserves adenine nucleotide pool in cardiomyopathic Syrian hamster
Authors: Wikman-Coffelt J. , Sievers R. , Parmley W. W. , Jasmin G.
Published: December 2017

There is a decrease in total adenine nucleotides, cyclic AMP (cAMP), ATP/total ADP, and phosphocreatine (PCr)/creatine (Cr) both in situ and in the perfused heart in the heart failure stage of the cardiomyopathic Syrian hamster. There were decreases in developed pressure, dP/dt, and O2 consumption associated with the decrease in total adenine nucleotides and cAMP. Cardiomyopathic Syrian hamsters (180-240 days old) with congestive heart failure were given water with the calcium entry blocker, verapamil, as an additive 2 mo before death. In the cardiomyopathic group given verapamil the adenine nucleotides, cAMP, and high-energy phosphates were preserved and cardiac performance was not significantly different from that of the verapamil-treated healthy hamsters at the time of death. Pretreatment of cardiomyopathic animals with verapamil (6.6 mg verapamil/ml water consumed by drinking) resulted in significantly higher ATP/total ADP and PCr/Cr compared with nontreated cardiomyopathic hamsters. This is the first report demonstrating that a calcium entry blocker may improve cardiac performance and preserve total adenine nucleotides during the heart failure stage of the cardiomyopathic hamster.
Sensory denervation of the kidney attenuates renovascular hypertension in the rat
Authors: Wyss J. M. , Aboukarsh N. , Oparil S.
Published: December 2017

To determine the role of the renal afferent nerves in the pathogenesis of one-kidney, one-clip renovascular hypertension, the renal afferent nerves were selectively lesioned by dorsal rhizotomy, a procedure that eliminates renal sensory input to the spinal cord but does not directly damage the sympathomotor innervation of the kidney. One week after denervation, the proximal left renal artery was clipped in denervated and sham control rats. Blood pressure of the sham group rose progressively over the next 5 wk, to 185 mmHg (systolic). In contrast, blood pressure of the denervated rats leveled off in the borderline hypertensive range, a level significantly lower than that of the sham group but significantly higher than that of non-clipped rats. In two further experiments the specificity of this effect was demonstrated. Lesion of the dorsal root nerves on the side of nephrectomy did not significantly lower blood pressure of non-clipped rats, and contralateral dorsal rhizotomy did not lower the blood pressure of clipped rats. These results demonstrate that the renal afferent nerves significantly contribute to one-kidney, one-clip renovascular hypertension in the rat.
Ultrastructure and function of isolated myocytes after calcium depletion and repletion
Authors: Frank J. S. , Brady A. J. , Farnsworth S. , Mottino G.
Published: December 2017

We describe a system in which the contractile response of a single isolated Ca-tolerant rat myocyte can be monitored while stimulated in Ca-free (37 degrees C) and then Ca-containing medium. This same cell is then processed for ultrastructural analysis. We find unattached isolated Ca-tolerant myocytes can withstand Ca depletion and repletion. They respond to stimulation after Ca repletion with healthy twitches and are structurally intact. The cell surface of the isolated myocyte appears similar to that seen in the intact myocytes even after 15 min in Ca-free solution. This is in marked contrast to myocardial cells in tissue where Ca depletion causes separation of the layers of the glycocalyx. When the cell is attached to a fine pipette so that some of the sarcolemma is under stress, the sequence of Ca depletion and repletion drives the cell into hypercontracture and loss of structural integrity that is characteristic of the Ca paradox.
Two electrophysiologically distinct types of cultured pacemaker cells from rabbit sinoatrial node
Authors: Nathan R. D.
Published: December 2017

Previous investigations employing multicellular nodal preparations (i.e., mixtures of dominant and subsidiary pacemaker cells) have suggested that the fast transient inward sodium current (iNa) either is not present in dominant pacemaker cells or is present but inactivated at the depolarized take-off potentials that these cells exhibit. In the present study, this question was resolved by voltage clamp analysis of single pacemaker cells isolated from the sinoatrial node and maintained in vitro for 1-3 days. Two types of cells, each with a different morphology, exhibited two modes of electrophysiological behavior. Type I cells (presumably dominant pacemakers) displayed only a tetrodotoxin (TTX)-resistant (but cadmium-sensitive) slow inward current, whereas type II cells (presumably subsidiary pacemakers) exhibited two components of inward current, a TTX-sensitive, fast transient inward current and a TTX-resistant (but cadmium-sensitive) slow inward current. Three other voltage-gated currents, 1) a slowly developing inward current activated by hyperpolarization (if, ih, delta ip), 2) a transient outward current activated by strong depolarization (ito, iA), and 3) a delayed outward current, were recorded in both types of pacemaker cells.
Continuous blood densitometry: fluid shifts after graded hemorrhage in animals
Authors: Hinghofer-Szalkay H.
Published: December 2017

To evaluate rapid fluid shifts after graded hemorrhage in splenectomized animals, four pigs and two dogs were bled 15-23 ml/kg body wt in steps of 2.2-6.0 ml/kg. Arterial blood density (BD), mean arterial pressure (MAP), and central venous pressure (CVP) were recorded continuously, and arterial plasma density (PD) and hematocrit (Hct) were determined from blood samples. Erythrocyte density was computed from PD, BD, and Hct. Starting with stable control conditions, MAP, CVP, and BD fell from the beginning of hemorrhage. Each blood withdrawal was followed by an immediate and rapid decrease in BD, even at the lowest (less than 3 ml/kg) initial blood losses. The time course of BD change mirrored that of the volume replacement, with time constants of 3.0-9.6 min and amplitudes depending on the magnitude of the relative volume loss. The PD decrease was significant (P less than 0.01) after 5.4 +/- 0.7 ml/kg hemorrhage. At 15 ml/kg blood loss the mean PD and BD had dropped by 0.99 +/- 0.15 and 2.42 +/- 0.26 g/l, respectively, and Hct had dropped by 2.40 +/- 0.47 units. Calculations suggest that either the inward-shifted fluid has a higher density than normal ultrafiltrate and/or there is a rise of the whole-body-to-large vessel Hct (F cell ratio). The rapid fluid replacement ranged from 5.8 +/- 0.8 to 10.6 +/- 2.0% of the initial plasma volume, or one-fifth to one-third of the lost volume with a 20% hemorrhage. Transvascular fluid shifts can be monitored with continuous high-precision blood densitometry.
Automaticity in atrioventricular valve leaflets of rabbit heart
Authors: Rozanski G. J. , Jalife J.
Published: December 2017

Microelectrode techniques were used to study the electrophysiological properties of pacemaker fibers in isolated atrioventricular valves of the rabbit heart. In spontaneously beating tricuspid and mitral valve preparations superfused with normal Tyrode solution, leading pacemaker activity was generated by fibers located on the valve leaflet. Impulse conduction from the automatic focus to atrial myocardium was slow, and in approximately 50% of preparations, exit block occurred. Valve pacemaker fibers had significantly different action potential characteristics compared with the primary pacemaker cells of the sinoatrial node. However, the activity of both pacemaker types was largely insensitive to tetrodotoxin but readily suppressed by verapamil. Endogenous neurotransmitters, released from postganglionic nerve endings in the vicinity of valve pacemaker fibers, exerted profound chrono- and dromotropic effects. Brief cholinergic stimuli strongly influenced valve pacemaker cycle length in a phase-dependent manner, qualitatively similar to that in the sinoatrial node. During overdrive of valve pacemaker fibers with external bipolar stimuli, locally released neurotransmitters modified automaticity and conduction which, under certain conditions, favored pacemaker escape. These data demonstrate that the atrioventricular valve leaflets contain cardiac fibers capable of generating spontaneous impulses and that intrinsic autonomic nerves may play a role in precipitating premature extrasystoles.
Influence of pacing site on canine left ventricular force-interval relationship
Authors: Burkhoff D. , Sagawa K.
Published: December 2017

We tested the hypothesis that while absolute extrasystolic (ES) and postextrasystolic (PES) dP/dtmax would be influenced by pacing site, if these values were normalized by the steady-state dP/dtmax obtained with the same pacing site, they would be independent of pacing site. We employed an isovolumetrically contracting isolated heart preparation with a balloon placed in the left ventricle. Pacing electrodes were placed on the atrium and four different epicardial ventricular sites. While pacing from each site separately, a steady mechanical state was established at a constant rate, and the interval between beats was then perturbed. The same pacing sequence was used while pacing from each of the five sites. On each ES and PES beat, dP/dtmax was expressed as a percentage of the steady-state dP/dtmax. The normalized responses measured with each ventricular pacing site (DPventr) were plotted as a function of the normalized responses obtained with atrial pacing (DPatr). On average, DPventr = 1.02 DPatr - 3.2% (n = 6, with r2 = 0.989), indicating that pacing site did not significantly influence the "normalized" force-interval relationship. Thus the basic information retrievable from measurements of the ventricular force-interval relationship is independent of the site from which the heart is paced.
Differences in affinity of cardiac beta-adrenergic receptors for [3H]dihydroalprenolol
Authors: Muntz K. H. , Calianos T. A. , Vandermolen D. T. , Willerson J. T. , Buja L. M.
Published: December 2017

We performed quantitative light microscopic autoradiography of [3H]dihydroalprenolol (DHA) binding to frozen sections of canine myocardium to test the hypothesis that there are differences in the density or affinity of beta-adrenergic receptors on various tissue compartments. In one study, with concentrations of [3H]DHA from 0.34 to 5.1 nM, specific binding to cardiac myocytes was saturable, whereas nonspecific binding was linear with ligand concentration. Arterioles had more specific grain counts than muscle cells (P less than 0.0001), and Scatchard analysis showed that the arterioles had a much higher affinity for [3H]DHA than myocytes. In a second study with lower concentrations of [3H]DHA (0.19-1.98 nM), binding to the arterioles saturated, whereas binding to the cardiac myocytes did not. Specific binding to arterioles was significantly higher (P less than 0.0001) than binding to myocytes at all concentrations of [3H]DHA. The dissociation constants for the subendocardial and subepicardial myocytes were 1.57 and 1.71 nM, respectively, while the dissociation constant for the arterioles was 0.26 nM. The maximum number of binding sites was 911 grains/0.9 X 10(-2) mm2 for subepicardial myocytes, 936 for subendocardial myocytes, and 986 for arterioles. The large nerves accompanying an epicardial artery also demonstrated specific [3H]DHA binding. Thus this study has demonstrated major differences in the distribution and affinity of beta-adrenergic receptors, which may help to explain various physiological responses to beta-adrenergic stimulation.
Rhythmic coronary arterial contractions: changes with time and membrane potential
Authors: Keef K. D. , Ross G.
Published: December 2017

Responses of isolated rabbit coronary artery segments to KCl and 2-(2-aminoethyl)-pyridine (AEP) were studied. Vessels stored at 2 degrees C for 24 h developed spontaneous rhythmic contractions during the first 20 min in Krebs solution at 37 degrees C. The contractile response to KCl or AEP declined to a minimum at 60 min [i.e., time zero (to) +60], increased to a peak at to +150 and then again declined. Resting membrane potential (Em) was less than or equal to -40 mV at to +20, -70 mV at to +30-60 and -50 mV at to +240-360 min. Rhythmic contractile responses were frequent and were associated with changes in Em. Vessels that were not cold stored did not hyperpolarize, nor did they show the early decline in response. Vessels stored at 2 degrees C for 24 h and then tested at 22-23 degrees C exhibited a similar pattern of changes in contraction but the time course was more protracted. We conclude that contractile responses are initially modulated by changes in Em associated with an increase then decrease in the activity of the sodium pump. Later changes in reactivity are due to a different mechanism.
Cardiovascular and renal responses to chronic vasopressin infusion
Authors: Brown A. J. , Lohmeier T. E. , Carroll R. G. , Meydrech E. F.
Published: December 2017

Arginine vasopressin (AVP) was infused into the renal artery of seven uninephrectomized conscious dogs at successive rates of 0.09, 0.36, and 1.46 ng X kg-1 X min-1 for 18, 9, and 5 days, respectively; subsequently, the nonpressor analogue of AVP, 1-desamino-8-D-arginine vasopressin (DDAVP), was infused intrarenally for 7 additional days. The lowest infusion rate of AVP produced a high concentration of AVP in the renal circulation (maximal antidiuresis) with only a relatively moderate increase in peripheral plasma AVP concentration. For comparison, the effects of a comparable increase in peripheral plasma AVP concentration during intravenous infusion at this same rate were observed in an additional group of dogs. Acutely, when this low dose of AVP was infused either intrarenally or intravenously, there was marked antidiuresis, but there were no significant changes in mean arterial pressure (MAP), renal hemodynamics, or urinary electrolyte excretion. Chronically, in both groups of animals, cumulative water balance was positive, and glomerular filtration rate, effective renal plasma flow, and MAP (16-18 mmHg) all increased; plasma renin activity decreased. Similar changes were observed during DDAVP infusion. When elevated peripheral plasma levels of AVP were achieved during the higher infusion rates of AVP, natriuresis and diuresis occurred, but, otherwise there was little change in the above variables, including MAP. Thus the hydrosmotic effects of AVP appear to account for its moderate hypertensive activity. Further, the failure of AVP to produce prominent hypertension, even when pronounced systemic vasoconstrictor effects are manifested, may be a result of its inability to promote significant renal vasoconstriction and antinatriuresis.