bluuebunny/crossref_metadata_2025 huggingface dataset:
Pericardial influences on ventricular filling in the conscious dog. An analysis based on pericardial pressure.
Authors: Tyson G S , Maier G W , Olsen C O , Davis J W , Rankin J S
Published: June 2012

Twenty-five dogs were chronically instrumented to investigate the effects of the normal pericardium on cardiac function. Pulse-transit ultrasonic transducers were implanted to measure multiple ventricular dimensions. The pericardium was incised transversely at the base of the heart and precisely reapproximated, so as to disturb its characteristics minimally. One week later, the dogs were studied in the conscious state, and left ventricular, right ventricular, pericardial, and pleural pressures were measured with matched micromanometers. Data were recorded before and after blood volume expansion. Absolute end-diastolic pericardial pressure varied directly with pleural pressure during the respiratory cycle. Transpericardial pressure (pericardial-pleural pressure) varied little with respiration and was related directly to ventricular diameter during the cardiac cycle with peak transpericardial pressure uniformly occurring at end-diastole. With volume infusion, normalized end-diastolic minor axis diameter and left ventricular transmural pressure (left ventricular-pleural pressure) increased significantly from 0.14 +/- 0.01 and 9.5 mm Hg +/- 1.0 mm Hg, respectively, in the control state to 0.20 +/- 0.01 and 19.3 mm Hg +/- 1.2 mm Hg after volume loading. End-diastolic transpericardial pressure also increased significantly from 2.3 +/- 0.5 mm Hg to 4.1 +/- 0.3 mm Hg, and represented approximately 21% of transmural left ventricular pressure. When measurements were obtained sequentially after implantation, transpericardial pressure was initially high but decreased with time, presumably due to pericardial creep. After volume loading, right ventricular end-diastolic transmural pressure averaged 9.6 mm Hg, and pericardial pressure constituted 42% of right ventricular pressure. Thus, pericardial restraining effects may predominantly influence right ventricular filling and affect the left ventricle through series interaction. In the normal conscious dog, transpericardial pressure remains low over the entire physiological range, and the direct influence of the normal pericardium on diastolic filling of the left ventricle appears to be minimal.
Long-term responses of atrial rate and peripheral resistance to changes in ventricular pacing rate in awake dogs with atrioventricular block.
Authors: Fisher S J , Scher A M , Wyss C R
Published: June 2012

We wished to see if a maintained change in pressure at the baroreceptors leads to a maintained or a transient change in heart rate and total peripheral resistance, and if long-term changes in rate and resistance paralleled one another. In awake dogs with intact baroreceptors and complete atrioventricular block, ventricular rate was held alternately at high (90 beats/min) and low (50 beats/min) levels, each for 2 days. This cycle was repeated several times. Data were recorded for 1.5 hours each day. With this change in ventricular rate, there was a maintained change over 2 days in arterial (14.4 +/- 1.0 mm Hg) and central venous (3.0 +/- 1.2 mm Hg) pressures. These changes in pressure were accompanied by a maintained change in atrial rate of 41.1 +/- 9.4 beats/min; peripheral resistance, however, changed only transiently. In three animals, the half-cycle length was 1 week. Changes in heart rate also persisted for this period. It appears from these studies that there is long-term control of heart rate, but not of peripheral resistance. Hypotheses to explain these results are presented.
Developmental aspects of the renal responses to hemorrhage during converting-enzyme inhibition in fetal lambs.
Authors: Gomez R A , Robillard J E
Published: June 2012

The role of the renin-angiotensin system in modulating the renal hemodynamic and functional responses to reductions of fetoplacental blood volume (8.8-35.5%) was studied in two groups of fetal lambs (less than 120 days and greater than 130 days gestation; term 145 days) during infusion of either captopril (experimental fetuses) or dextrose 5% in water (control fetuses). At high hemorrhage levels (level III), renal blood flow decreased and renal vascular resistance increased significantly in both groups of fetuses (less than 120 days and greater than 130 days), either treated or not treated with captopril. However, at low hemorrhage levels (levels I and II), and contrary to what was observed in young fetuses (less than 120 days), near-term fetuses (greater than 130 days) receiving captopril showed neither significant decreases in renal blood flow nor increases in renal vascular resistance, whereas untreated fetuses of the same gestational ages demonstrated significant decreases in renal blood flow and increases in renal vascular resistance. It was found in both less than 120 day and greater than 130 day fetuses that hemorrhage is associated with a decrease in urinary flow rate and free water clearance accompanied by an increase in urine osmolality and sodium reabsorption. It was shown that captopril does not modify this response. The present study also demonstrated that the blood pressure response to hemorrhage was characterized by a similar decrease in less than 120 day fetuses, whether treated or untreated with captopril. On the other hand, blood pressure did not change in control fetuses greater than 130 days, but decreased slightly in captopril-treated fetuses during hemorrhage. Taken together, the present results tend to suggest that the renin-angiotensin system may be an important modulator of the renal hemodynamic response to low level hemorrhage as fetuses approach term, and may be more important in controlling blood pressure in near-term than in young fetuses.
Complete reversibility of cat right ventricular chronic progressive pressure overload.
Authors: Cooper G , Marino T A
Published: June 2012

Chronic, progressive pressure overload of the cat right ventricle produces persistent, ongoing abnormalities of contractile, energetic, and biochemical function in vitro at a time when in vivo pump function is still normal. The present study tested the reversibility of the in vitro changes in this clinically relevant hypertrophy model. Fourteen sham-operated and 14 reversal cats were studied. After banding the animals as 1-kg kittens, right ventricular pressures were normal. Before band removal (25.2 +/- 0.5 weeks later for the control group and 25.5 +/- 0.3 weeks later for the hypertrophy reversal group), systolic right ventricular pressures were 24 +/- 1 mm Hg for controls and 71 +/- 5 mm Hg for the hypertrophy reversal group (P less than 0.05). At study, 19.5 +/- 1.1 weeks after a second sham operation for controls or 18.7 +/- 0.7 weeks after band removal for the hypertrophy reversal group, these pressures were 24 +/- 1 mm Hg for controls and 23 +/- 1 mm Hg for the hypertrophy reversal group (P = NS); cardiac output was 0.18 +/- 0.01 liters/kg per min for controls and 0.19 +/- 0.01 liters/kg per min for the hypertrophy reversal group (P = NS). The ratio of right ventricle to body weight was normal in both groups, as was the right ventricular papillary muscle myocyte cross-sectional area and the myocardial collagen concentration. A right ventricular papillary muscle from each cat was studied at 29 degrees C in a polarographic myograph. Preloaded shortening velocity was 0.79 +/- 0.04 muscle lengths/sec for controls and 0.86 +/- 0.03 muscle lengths/sec for the hypertrophy reversal group (P = NS); extent of shortening was 0.15 +/- 0.01 muscle lengths for controls and 0.16 +/- 0.01 muscle lengths for the hypertrophy reversal group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Altered coronary vascular responsiveness to leukotrienes in alloxan-diabetic rats.
Authors: Roth D M , Reibel D K , Lefer A M
Published: June 2012

Altered responsiveness to and metabolism of various eicosanoids in diabetic animals and patients has been reported by several investigators. The purpose of this investigation was to examine the coronary vascular responsiveness of alloxan-diabetic rats to the leukotrienes. Hearts from 12- to 16-week-old alloxan-diabetic rats and weight-matched controls were perfused at constant flow by the Langendorff method. Coronary vasoactivity to leukotrienes B4, C4, D4 and E4 was assessed by measuring the change in coronary perfusion pressure upon infusion of these eicosanoids. Hearts from diabetic rats showed increased responsiveness to leukotrienes C4 (4-40 nM) and D4 (10-100 nM). Both control and diabetic rat hearts were only slightly responsive to leukotriene E4, and no difference between the two groups existed in the reactivity to this leukotriene. Neither group was responsive to the chemotactic leukotriene, B4. Perfusion of the hearts with the cyclooxygenase inhibitor, ibuprofen, failed to alter the coronary vascular responses to the leukotrienes. The coronary constrictor effects of the leukotrienes are the primary effect of these agents on the rat heart, since heart rate does not change significantly, and changes in contractile force are secondary to the coronary vascular constriction. These alterations in responsiveness to leukotrienes may play a role in the cardiovascular complications associated with diabetes.
High energy phosphate depletion and lactate accumulation in the interventricular septum and left ventricular free wall of the dog after total coronary occlusion.
Authors: Dunn R B
Published: June 2012

We measured indices of energy metabolism in tissue samples taken from the interventricular septum and left ventricular free wall of open-chest dogs under control conditions and after a 20-second period of no coronary inflow. The heart was paced at 150 beats/min, and arterial pressure was controlled by aortic constriction. Each tissue sample was divided into three transmural regions and analyzed for creatine phosphate, adenosine triphosphate, and lactate. Data were also obtained in animals subjected to ventricular fibrillation, with ventricular pressures reduced to atmosphere and sampling delayed to 70 seconds, and with the pulmonary artery constricted prior to coronary artery occlusion. In control animals, there were no metabolite differences between the free wall and septum. Coronary occlusion produced a lactate gradient across both the free wall and septum, with the highest lactate concentrations occurring in the regions adjacent to the left ventricular cavity. The increase in tissue lactate above control was greater in the septum than in the free wall. Coronary occlusion decreased tissue creatine phosphate but not adenosine triphosphate. The decrease in creatine phosphate was greater in the septum than in the free wall. Coronary occlusion and ventricular fibrillation, or coronary occlusion and ventricular pressures reduced to atmosphere, produced neither transmural metabolite differences nor differences between the free wall and septum. Pulmonary artery constriction increased right and decreased left ventricular pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Vagal control of pacemaker periodicity and intranodal conduction in the rabbit sinoatrial node.
Authors: Slenter V A , Salata J J , Jalife J
Published: June 2012

Effects of brief vagal bursting on pacemaker periodicity and intranodal conduction were studied by recording transmembrane potentials in isolated rabbit sinoatrial preparations. Postganglionic vagal terminals were activated by applying brief (50- to 150-msec) trains of pulses (duration, 100 mu sec; frequency, 200 Hz) to the endocardial surface of the node. Sympathetic effects were prevented by superfusion with Tyrode's solution containing propranolol (1 microgram/ml). Vagal trains applied singly every 10 seconds produced brief hyperpolarizations in "true" pacemaker and transitional cells, and induced phasic changes in periodicity and conduction. These changes were out of phase with each other, and were dependent on the magnitude and duration of the vagal train, as well as on its position within the pacemaker period. When similar trains were applied repetitively at cycle lengths (200-1200 msec) that were independent of the pacemaker period, complex patterns of vagus-sinoatrial node interactions resulted. Hence, depending on the vagal stimulus cycle length, the sinoatrial pacemaker was forced to beat at stable and predictable harmonic (i.e., 1:1, 1:2, 2:1, etc.), subharmonic (3:2, 4:3, etc.), or more complex entrainment ratios. At some of these ratios, arrhythmic sinus patterns coexisted with intranodal conduction disturbances, including first- and second-degree block, Wenckebach phenomena, or combinations thereof. At other entrainment ratios, arrhythmias occurred in the absence of conduction changes. At still other ratios, conduction disturbances developed in the presence of apparently undisturbed sinus rhythm. These results provide insight into the mechanism of the dynamic vagal control of sinoatrial periodicity and conduction, and may have clinical implications as well.
Myosin types in the human heart. An immunofluorescence study of normal and hypertrophied atrial and ventricular myocardium.
Authors: Gorza L , Mercadier J J , Schwartz K , Thornell L E , Sartore S , Schiaffino S
Published: June 2012

Two distinct myosin heavy chain isoforms, referred to as alpha and beta, were identified in the human heart with specific antimyosin antibodies. By indirect immunofluorescence, myosin heavy chain alpha was found to be a major component of atrial myosin and a minor component of ventricular myosin, while heavy chain beta was found to be a major component of ventricular myosin and a minor component of atrial myosin. In the normal heart, there was marked individual variability in the proportion of ventricular myocytes reactive for heavy chain alpha. Atrial myocytes staining for heavy chain beta were rare in the left atrium and more numerous in the right atrium, especially in the crista terminalis and in the interatrial septum. Surgical and autoptic specimens from hypertrophied left ventricles of patients with mitral regurgitation showed a myosin immunoreactivity pattern similar to that of normal specimens. Very rare muscle cells reactive for heavy chain alpha were seen in the hypertrophied left ventricles of subjects with hypertension and in the hypertrophied right ventricles of subjects with tetralogy of Fallot. A dramatic transformation of myosin heavy chain composition was observed in hypertrophied left atria of patients with mitral stenosis, with a shift to heavy chain beta in a large proportion of atrial myocytes. The findings indicate that chronic exposure to hemodynamic overload can induce marked changes in the myosin heavy chain composition of human atria, whereas it affects only slightly that of the ventricles.
Short- and long-term determinants of baroreceptor function in aged normotensive and spontaneously hypertensive rats.
Authors: Andresen M C
Published: June 2012

In a variety of animal models, baroreceptor resetting during chronic hypertension has been correlated to vessel wall hypertrophy and decreased distensibility. In one possible mechanism of chronic resetting, termed the splinting hypothesis here, it has been suggested that a stiffer vessel wall might increase the minimum pressure required for activation of these mechanoreceptors (pressure threshold) and decrease suprathreshold pressure sensitivity. Lower vessel distensibility would alter baroreceptor function by preventing equivalent pressures from producing equivalent vessel distensions and, thus, receptor distortions. Recent studies have also suggested that the pressure threshold is strongly influenced by the most recent (minutes) history of blood pressure exposure during a process termed rapid resetting. Hypertension and advanced aging are associated with distensibility changes. The present study examines pressure and equivalent mechanical response characteristics of aortic baroreceptors from aged normotensive Wistar-Kyoto and spontaneously hypertensive rats. An in vitro aortic arch-aortic nerve preparation was used to assess the discharge properties from a number of baroreceptors and the pressure-diameter relationship of each aorta. Both control and rapid resetting protocols were used to study the baroreceptor characteristics. Aged Wistar-Kyoto rats were normotensive and averaged 115 weeks of age. Aged spontaneously hypertensive rats had systolic tail pressures of 187 mm Hg and averaged 76 weeks of age. Although aortic distensibility of aged WKYs was much lower than previously found in younger animals, the pressure threshold was unchanged. Aged spontaneously hypertensive rat receptors were chronically reset in proportion to their blood pressure. Decreased distensibility did not alter the rapid resetting process. It is concluded that baroreceptor pressure sensitivity is more closely related to aortic distensibility under several conditions altering vessel stiffness, whereas, the pressure threshold may be regulated additionally by mechanisms independent of distensibility. The results are inconsistent with the splinting hypothesis.
Block of inactivated sodium channels and of depolarization-induced automaticity in guinea pig papillary muscle by amiodarone.
Authors: Mason J W , Hondeghem L M , Katzung B G
Published: June 2012

The electrophysiological effects of amiodarone were studied in guinea pig papillary muscle by means of the single sucrose gap voltage clamp technique. The first time derivative of the upstroke of the action potential was measured as an indicator of the sodium current. The preparations were not voltage clamped during the action potential upstroke. Acute effects of amiodarone (4.4 X 10(-5) M and 8.8 X 10(-5) M; six experiments each) and effects of chronic administration at a single dose level (nine experimental vs. eight control animals) were studied. Results were qualitatively the same for all experimental conditions, and concentration dependent in the acute studies. Amiodarone caused marked use-dependent depression of the first time derivative of the upstroke of the action potential during stimulus trains. For example, at normal resting potential, chronic amiodarone treatment reduced the first time derivative of the upstroke of the action potential of the 16th beat of trains of cycle length 300 msec to 70 +/- 15% (mean +/- SD) of the initial value. This blocking effect was accentuated at more depolarized holding potentials and reduced at hyperpolarized holding potentials. Reduction of the first time derivative of the upstroke of the action potential was found to depend upon sodium channel inactivation. For all experiments, the mean normalized first time derivative of the upstroke of the action potential following a 1-second clamp in the -20 to +20 mV range was 0.92 +/- 0.08 in the control condition and 0.66 +/- 0.20 in the presence of amiodarone (less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Countercurrent diffusion in the renal cortex of the rabbit.
Authors: Effros R M , Taki K , Reid E , Silverman P
Published: June 2012

Evidence was obtained for countercurrent diffusion of 14C-n-butanol in the rabbit renal cortex. After injection into the renal artery of perfused, isolated rabbit kidneys, concentrations of both 14C-butanol and tritiated water in the initial samples collected from the renal venous outflow exceeded those of 125I-albumin when the rate of perfusion was low. When flow was increased, the 125I-albumin curve was shifted to earlier times relative to the other labels. These observations confirm the existence of arteriovenous diffusion of 14C-butanol and tritiated water in the kidney. In a second set of experiments, 14C-butanol and tritiated water were infused for 10 or 60 seconds into the renal arteries of anesthetized rabbits, and the kidneys were then removed and frozen in liquid nitrogen. Cores were cut from the kidney surface and sectioned in a cryostat, and the ratio of 14C-butanol to tritiated water was calculated at increasing depths in the cortex. This ratio rose from 0.54 +/- 0.03 (SEM) at the surface to 0.98 +/- 0.07 at 3 mm beneath the surface in kidneys perfused for 10 seconds. This gradient was less steep after 60 seconds of perfusion. The early appearance of 14C-butanol relative to tritiated water in the renal venous outflow and delayed equilibration of 14C-butanol in the outer renal cortical tissue are consistent with counter-current diffusion. It is suggested that this exchange may occur between adjoining interlobular arteries and veins in the cortex and may contribute to high carbon dioxide tensions found near the renal surface.
Determinants of postrepolarization refractoriness in depressed mammalian ventricular muscle.
Authors: Rozanski G J , Jalife J , Moe G K
Published: June 2012

Functional determinants of postrepolarization refractoriness were studied with microelectrodes in isolated cat and dog ventricular muscle preparations mounted in a three-chambered bath. Frequency-dependent conduction delay and block were readily manifested when the central segment (1 mm) was superfused with high potassium (20-30 mM) Tyrode's solution. Conduction disorders were attributed to postrepolarization refractoriness involving slow recovery in the amplitude of elicited subthreshold depolarizations in depressed fibers distal to the central blocked zone. Investigations of subthreshold phenomena in homogeneously depressed tissues indicated that a relatively large local response participated in the voltage displacement induced by subthreshold depolarizing currents. The local response was blocked by tetrodotoxin (10 micrograms/ml) or verapamil (2 micrograms/ml) when resting membrane potential was near -70 or -50 mV, respectively. At either level of reduced membrane potential, gradual recovery in diastolic excitability correlated closely with time-dependent recovery of the local response, the rate of which was also proportional to the current intensity applied. Thus, postrepolarization refractoriness in depressed ventricular muscle fibers is a function of the time for recovery of active subthreshold properties (the local response), as well as intensity of excitatory current input. These factors may play a role in the development of delayed conduction and reentry that occur at faster heart rates under ischemic conditions.
Lipid solubility modulates pH potentiation of local anesthetic block of Vmax reactivation in guinea pig myocardium.
Authors: Broughton A , Grant A O , Starmer C F , Klinger J K , Stambler B S , Strauss H C
Published: June 2012

Current theories envision recovery from local anesthetic block of sodium channels via slow hydrophilic and fast hydrophobic paths. Extracellular pH reduction which increases cationic/neutral anesthetic form should especially prolong recovery kinetics of highly lipid soluble compounds that could readily exit via the hydrophobic pathway at normal extracellular pH. To test this hypothesis, we compared the effects of three related compounds with similar pKa on the time course of Vmax reactivation in guinea pig papillary muscle at pHo 7.4 and 6.95. The compounds were lidocaine and its two desethylation products, monoethylglycinexylidide and glycinexylidide. Judged from the octanol:water partition coefficient, lidocaine was the most lipid soluble (log partition coefficient 2.39 +/- 0.10), followed by monoethylglycinexylidide (log partition coefficient 1.32 +/- 0.09) and glycinexylidide was the least lipid soluble (log partition coefficient 0.41 +/- 0.09). At 30 microM and pHo 7.4, the potency order for Vmax depression at zero diastolic interval was lidocaine (53 +/- 6%), monoethylglycinexylidide (17 +/- 3%), and then glycinexylidide (7.8 +/- 1.9%). The decay of Vmax block appeared monoexponential, and the time constant of recovery was dose independent. Most important is the fact that there were significant differences in the tau r increase with extracellular pH reduction (P less than 0.05; Scheffé contrasts). The increase was greatest with lidocaine [73 +/- 28% (mean +/- SD)], less with monoethylglycinexylidide (42 +/- 15%), and least with glycinexylidide (13 +/- 17%). The simplest interpretation of the differences in extracellular pH-dependence of recovery kinetics was that recovery from block due to the neutral form of these ionizable local anesthetics depended on lipid solubility, whereas recovery from block due to the protonated form depended on molecular weight.
Lack of evidence for the participation of tonin in the pathogenesis of one-kidney, one-clip renovascular hypertension.
Authors: Seto S , Rabito S F , Scicli A G , Carretero O A
Published: June 2012

It has been reported that immunization against tonin normalizes blood pressure, and that sialoadenectomy, during which the tonin-rich salivary glands are removed, decreases blood pressure in one-kidney, one-clip hypertension. To investigate the role of tonin on this form of hypertension further, we actively immunized one-kidney, one-clip hypertensive rabbits with tonin and measured both the blood pressure response and the titer of antibodies raised against tonin. In addition, because sialoadenectomy may alter food intake, we assessed the effect of sialoadenectomy on the blood pressure of one-kidney, one-clip hypertensive rats fed a liquid diet to facilitate eating. After immunization, all rabbits developed antitonin-antibody titers ranging from 1:300 to 1:56,000. However, in none of the rabbits did the blood pressure decrease significantly (114 +/- 3 mm Hg before immunization; 129 +/- 6 mm Hg at 16 weeks after immunization). In one-kidney, one-clip hypertensive rats, sialoadenectomy did not lower blood pressure (179 +/- 5 mm Hg before sialoadenectomy; 202 +/- 9 mm Hg 3 weeks after sialoadenectomy). Neither blood pressure nor body weight differed between sialoadenectomy and sham-sialoadenectomy one-kidney, one-clip hypertensive rats (n = 6). In conclusion, neither active immunization against tonin in one-kidney, one-clip hypertensive rabbits nor sialoadenectomy in one-kidney, one-clip hypertensive rats significantly reduced established hypertension. These results do not support the hypothesis that tonin is involved in the pathogenesis of one-kidney, one-clip hypertension in these animal models.
Modulation of canine myocardial sarcolemmal membrane fluidity by amphiphilic compounds.
Authors: Fink K L , Gross R W
Published: June 2012

Amphiphilic moieties such as lysophosphoglycerides and long-chain acyl carnitines accumulate in ischemic myocardium and potentially contribute to the sequelae of myocardial ischemia. To characterize alterations in membrane molecular dynamics produced by amphiphilic compounds, highly purified preparations of canine myocardial sarcolemma were spin-labeled with paramagnetic probes (5-, 12-, or 16-doxyl stearate), and alterations produced by amphiphilic compounds were quantified by electron spin resonance spectroscopy. Incorporation of 1.5, 3, or 6 mol % palmitoyl lysophosphatidylcholine resulted in a decrease of the order parameter of 16-doxyl stearate from 0.164 to 0.161, 0.155, and 0.145, respectively. Similar increases in membrane fluidity in the interior of the bilayer were present when palmitoyl lysophosphatidylethanolamine, L-palmitoyl carnitine, and platelet-activating factor were incorporated into sarcolemma. In contrast, incubation of sarcolemma with lysophosphatidylcholine did not result in significant change of the order parameter of 5-doxyl stearate, even at 6 mol %, demonstrating that lysophosphatidylcholine increases the transmembrane fluidity gradient. Sarcolemma treated with phospholipase A2 exhibited a time-dependent decrease in the rotational correlation time and order parameter when lysophospholipids constituted a small amount (6%) of sarcolemmal phospholipids. Furthermore, the effects of lysophosphatidylcholine were not dependent upon its physical state, since bilayers composed of gramicidin and lysophosphatidylcholine resulted in similar increases in membrane fluidity as micellar lysophosphatidylcholine. The results suggest that alterations in sarcolemmal molecular dynamics are one mechanism through which amphiphilic moieties mediate their multiple effects. Such alterations could contribute to the electrophysiological and biochemical sequelae of myocardial ischemia.
Development of collateral function with repetitive coronary occlusion in a canine model reduces myocardial reactive hyperemia in the absence of significant coronary stenosis.
Authors: Yamamoto H , Tomoike H , Shimokawa H , Nabeyama S , Nakamura M
Published: June 2012

The present study was designed to elucidate the role of collateral development, per se, on reactive hyperemia without persistent coronary stenosis in instrumented conscious dogs. Functional states of coronary collaterals were augmented by repetitive 2 minutes of coronary occlusion every 30 minutes for 2-9 days. Regional shortening measured sonomicrometrically recovered from -1.2 +/- 6.5% of the preocclusive state at the end of the first coronary occlusion to 100.5 +/- 1.2% (n = 8, P less than 0.01) after repeated coronary occlusions. Before and after collateral development, transient coronary occlusions of 5, 10, 20, 30, 60, 90, and 120 seconds were randomly performed. The degree of regional dysfunction and the following reactive hyperemic response were measured. Up to 20 seconds of coronary occlusion, the flow ratio and duration of coronary reactive hyperemia increased similarly, both before and after collateral development. However, when the duration of coronary occlusion was over 30 seconds, flow ratio and debt repayment ratio were reduced progressively after the collateral development. Among the indices exhibiting reactive hyperemia, debt repayment ratio decreased initially and correlated well with the recovery of regional dysfunction during coronary occlusion. Thus, the augmentation of collateral function after repetitive coronary occlusion reduces reactive hyperemia even in the absence of significant coronary stenosis.
Dynamic discharge characteristics of low pressure receptors in the rat.
Authors: Mifflin S , Kunze D
Published: June 2012

An in vitro preparation was used to examine the discharge of low pressure receptors in response to a pulsatile pressure stimulus. Both slowly adapting and rapidly adapting receptors were examined. After an increase in the mean level and/or dP/dt of a pulsatile pressure input, the discharge of slowly adapting receptors reached a steady state level within 2 minutes. An increase in mean pressure, with constant pulsatile amplitude and dP/dt, produced a sustained increase in the number of spikes/cycle, in the average number of spikes/second, and in the average frequency during the burst within the cycle. In slowly adapting receptors, an increase in dP/dt at a constant mean pressure and pulsatile amplitude produced a decrease in the number of spikes/cycle and an increase in both the average number of spikes/second and the frequency during the burst. Rapidly adapting receptors showed very different characteristics, responding to a pulsatile pressure input above threshold with an irregular discharge which averages approximately 1 spike/cycle at all mean pressure levels. Although rapidly adapting receptors transiently increased their discharge in response to an increase in mean pressure, within 60 seconds discharge returned to the pre-increase level. Rapidly adapting receptors continued to discharge with an average of 1 spike/cycle as dP/dt was increased. Since dP/dt was raised by increasing the frequency of the pulsatile input, the number of spikes/second increased. In the steady state, slowly adapting receptors transmit information reflecting mean pressure levels. They are also sensitive to the rate of change of pressure. Rapidly adapting receptors, on the other hand, are insensitive to mean pressure but do respond to the frequency of the stimulus.
Interaction of canine carotid sinus and aortic arch baroreflexes in the control of total peripheral resistance.
Authors: Brunner M J , Greene A S , Kallman C H , Shoukas A A
Published: June 2012

Interaction of carotid sinus and aortic arch reflex control of total peripheral resistance was studied in eight dogs anesthetized with sodium pentobarbital and placed on constant flow cardiac bypass. Carotid sinus and aortic arch baroreceptor areas were isolated and separately perfused at controlled pressures. Combinations of carotid sinus and aortic arch pressures were delivered at random in steps of 25 mm Hg over the 50-225 mm Hg pressure range, and systemic arterial pressure was measured. Changes in arterial pressure reflected changes in total peripheral resistance. A multiple linear regression showed that both carotid sinus and aortic arch pressures exhibited a sigmoidal relationship with arterial pressure. Independent of carotid and aortic baroreceptor pressures, arterial pressure was found to be a periodic function of time (period = 2 hours) in all dogs. The average carotid sinus reflex open loop gain was found to be 0.231 +/- 0.092, while average aortic arch open loop gain was 0.141 +/- 0.088. The gain of either the carotid sinus or aortic arch reflex was not influenced by the absolute pressure level of the other receptor area. In a separate series of experiments performed in the same dogs, we tested the hypothesis that a nonlinear temporal summation of the reflex control of total peripheral resistance might exist when the inputs to carotid and aortic baroreceptors are changed simultaneously. With both inputs held at the region of maximum gain, 25 mm Hg step changes were imposed first on carotid sinus pressure, then on aortic arch pressure, and then on both simultaneously. A temporal inhibition of the two reflexes showed that simultaneous excitation of both receptors resulted in a smaller reflex response than the sum of individual responses.
The role of vascular capacitance in the coronary arteries.
Authors: Lee J , Chambers D E , Akizuki S , Downey J M
Published: June 2012

When the left coronary artery was perfused with nonpulsatile pressure, the onset of diastole was accompanied by a capacitance overshoot in flow with an exponential decay back to a steady state. Time constant for that decay ranged from 55 msec when tone was present to 105 msec with maximal dilation. Since the transient resulted from a fall in tissue pressure, this represents an estimation of intramural arterial capacitance only. Transients in perfusion pressure, which would also affect epicardial arteries, yielded similar time constants. We concluded that most of the coronary capacitance resides in the small intramural vessels. Analysis of transients yielded a value for capacitance of between 0.01 and 0.05 ml/mm Hg per 100 g. We then used the data from the transients to construct coronary pressure flow curves which were free of any back flow from capacitance. When coronary tone was present, the curves indicated that flow ceased at 30 mm Hg. With maximal dilation, flow ceased at only 18 mm Hg. Long diastoles in those same hearts indicated that flow ceased at about 10 mm Hg higher pressure. Although capacitance causes critical closing pressure as determined by a long diastole to be artifactually high, critical closing pressure is still appreciable in the heart, and tone dependent. Finally, three computer models were built, one of which included only small vessel capacitances, the second, only vascular waterfalls, and the third, both of the above. Only model 3 was capable of reproducing the flow patterns which were actually seen.
Cardiovascular effects of leukotrienes in neonatal piglets. Role in hypoxic pulmonary vasoconstriction?
Authors: Leffler C W , Mitchell J A , Green R S
Published: June 2012

We investigated the effects of exogenous leukotriene D4, synthesis inhibitors, and a leukotriene receptor antagonist upon chloralose anesthetized, mechanically ventilated, neonatal piglets with constant left pulmonary blood flow and upon piglets with uncontrolled pulmonary blood flow. Leukotriene D4 (100-10,000 ng, intravenously) caused dose-dependent increases in peak tracheal pressure, pulmonary vascular resistance, and systemic arterial pressure. In a limited number of experiments, cardiovascular responses to exogenous leukotriene C4 were qualitatively similar but quantitatively less than those to leukotriene D4. Neither treatment with diethylcarbamazine or the lipoxygenase inhibitor nordihydroguaiaretic acid, nor with the leukotriene receptor antagonist, FPL55712, altered any baseline cardiovascular parameter measured, suggesting the absence of any influence of leukotrienes on resting hemodynamics. Hypoxia or hypoxia combined with mild hypercapnia caused pulmonary vasoconstriction. Neither treatment with diethylcarbamazine or the lipoxygenase inhibitor nordihydroguaiaretic acid, nor with the leukotriene receptor antagonist FPL55712, altered the pulmonary vasoconstrictor response to hypoxia or combined hypoxia/hypercapnia. We conclude that endogenous leukotrienes do not appear to have an influence on resting cardiovascular function, neither do they appear to be necessary for hypoxic pulmonary vasoconstriction in the neonatal piglet, although exogenous leukotrienes are capable of producing cardiovascular effects.
Fiber types and myosin types in human atrial and ventricular myocardium. An anatomical description.
Authors: Bouvagnet P , Leger J , Pons F , Dechesne C , Leger J J
Published: June 2012

Hybridomas were prepared from mice immunized with myosin from the enlarged left ventricle of a 53-year-old female with an obstructive cardiomyopathy. The specificity of 15 monoclonal antibodies to myosin heavy chains was assessed by the reactivity of muscle extracts and of chymotryptic myosin fragments of different sizes with these antibodies, as determined by the immune replicate technique; some of the monoclonal antibodies cross-reacted only with the ventricular V3-type myosin from hypothyroid rats, whereas the other antibodies cross-reacted both with the latter and with the ventricular V1-type myosins from normal young rats. Immunological heterogeneity of the fibers from human atrial muscles and from human ventricular muscles was detected by some of the antimyosin antibodies by means of indirect immunofluorescence. Histochemical fiber heterogeneity was also detected by adenosine triphosphatase staining of the same tissues. Because of the close correspondence observed between the immunological and histochemical responses of atrial fibers, it has been postulated that at least two distinct types of myosin exist in the human atrium, each myosin form being histochemically related to either alpha- or beta-like ventricular myosin heavy chains. In contrast, there was no direct correspondence between the two experimental approaches in human ventricles, and it is postulated that at least three distinct types of myosin exist within the human ventricles, one V1-type myosin, presumably corresponding to the very rare fibers with an alkaline-stable adenosine triphosphatase activity, and two other V3-type myosins corresponding to immunologically different fibers, each having an alkaline-labile adenosine triphosphatase activity. Monoclonal antibodies that can distinguish among the different myosin variants were further used to provide the basis for an anatomical description of fiber types and myosin types within the human atrial and ventricular myocardium in the whole hearts of two young boys who died sudden violent deaths. Small zones of myosin variation were seen to be scattered, but probably not randomly distributed, within large areas of myocardium in which the cellular distribution of myosin was constant; the large areas had one myosin distribution specific for each cardiac cavity. No clear-cut conclusions can yet be made concerning the physiological role of the regional variations observed in the distribution of the different molecular forms of myosin.
A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent.
Authors: Thomas G , Chung M , Cohen C J
Published: June 2012

Bay k 8644 is a structural analog of nifedipine with positive inotropic activity. The mechanism of drug action was evaluated by measuring the effects of Bay k 8644 on twitch tension, action potential configuration, and calcium channel currents in myocardial cells. Bay k 8644 increases twitch tension in guinea pig atria without changing the time course of tension development. The drug does not occlude the effect of isoproterenol on twitch tension. The effects of Bay k 8644 on atrial twitch tension are highly dependent on the frequency of stimulation. Maximal inotropic effects are observed at approximately 0.5 Hz, but no inotropic effect occurs at 0.003 Hz (a rested-state contraction). Since positive inotropic effects only occur with frequent electrical stimulation, they are not due to an intracellular action or to mechanisms that elevate cell calcium in quiescent muscle, such as inhibition of the Na,K-ATPase. Bay k 8644 increases the action potential duration of calf ventricular muscle and Purkinje fibers. Effects on action potential duration are occluded by 1 microM nisoldipine, which specifically blocks calcium channels. The interaction of Bay k 8644 with calcium channels in calf Purkinje fibers was studied using the two-microelectrode voltage clamp technique. Strontium was used as a charge carrier to minimize current through calcium-activated channels and to avoid changes in calcium conductance due to changes in intracellular calcium. Bay k 8644 increases strontium currents and alters the time- and voltage-dependence of channel opening. The greatest percent increase in strontium current occurs for weak depolarizations. For strong depolarizations, strontium current is increased most at the beginning of a test pulse. The drug-induced changes in calcium channel gating are inconsistent with a calcium- or cyclic adenosine monophosphate-mediated effect, and indicate a novel mechanism of action on calcium channels. Thus, Bay k 8644 is the first positive inotropic agent shown to act specifically and directly on calcium channels.
Influence of ribose, adenosine, and "AICAR" on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog.
Authors: Mauser M , Hoffmeister H M , Nienaber C , Schaper W
Published: June 2012

Recovery of adenosine triphosphate after myocardial ischemia is limited by the slow adenine nucleotide de novo synthesis and the availability of precursors of the nucleotide salvage pathways. We determined the adenine nucleotide de novo synthesis in the dog by infusion of [14C]glycine and the acceleration of adenine nucleotide built up by intracoronary infusion of ribose together with [14C]glycine or radiolabeled 5-amino-4-imidazolcarboxamide riboside or adenosine in the same animal model and with the same dosage of substrates (9 mmol) in postischemic and nonischemic myocardial tissue. After 45 minutes of occlusion of a side branch of the left coronary artery, the ischemic area was reperfused for 3 hours, and needle biopsies were taken for biochemical analysis. Adenine nucleotide de novo synthesis was found to be very slow (1.5 nmol/g wet weight per hour). The rate was doubled after ischemia. Adenine nucleotide synthesis was accelerated 5-fold by ribose, the basic substrate of the adenine nucleotide de novo synthesis, 9-fold by 5-amino-4-imidazolcarboxamide riboside, an intermediate of the adenine nucleotide de novo synthesis and 90-fold by adenosine, a substrate of the nucleotide salvage pathway. Therefore, only adenosine infusion resulted in a measurable increase of adenosine triphosphate levels after 3 hours of reperfusion, but over a longer time period, ribose or 5-amino-4-imidazol-carboxamide riboside also can be expected to replenish reduced myocardial adenosine triphosphate faster than adenine nucleotide de novo synthesis. Studies with radiolabeled 5-amino-4-imidazol-carboxamide riboside showed significant incorporation of radioactivity into 5-amino-4-imidazol-carboxamide ribose triphosphate which had also risen measurably during 5-amino-4-imidazol-carboxamide ribose infusion, and which is not normally found in heart muscle.
Identification and characterization of leukotriene C4 receptors in isolated rat renal glomeruli.
Authors: Ballermann B J , Lewis R A , Corey E J , Austen K F , Brenner B M
Published: June 2012

The immediate reduction of renal blood flow and glomerular filtration rate in response to intravenous infusion of leukotriene C4 in the rat prompted an analysis of isolated rat renal glomeruli for the presence of specific receptors for leukotriene C4. Specific binding of [3H]leukotriene C4 to glomeruli increased in a time-dependent manner, reached equilibrium after 60 minutes of incubation at 4 degrees C, and was 80% reversible upon addition of excess unlabeled leukotriene C4 at equilibrium. Specific binding of [3H]leukotriene C4 to glomeruli increased in a dose-dependent manner, approaching saturation at concentrations of 40-60 nM. Inhibition of binding of [3H]leukotriene C4 with increasing concentrations of unlabeled leukotriene C4 was dose dependent. The equilibrium dissociation constant for [3H]leukotriene C4 binding to glomeruli, calculated from saturation and competitive binding-inhibition studies, was 25 +/- 7 nM and 35 +/- 16 nM (mean +/- SEM), respectively, and glomerular leukotriene C4 receptor density was 8.5 +/- 1.5 and 9.0 +/- 3.0 pmol/mg protein, respectively. The other natural vasoactive sulfidopeptide leukotrienes, leukotriene D4 and leukotriene E4, the chemotactic agent, leukotriene B4, and the sulfidopeptide leukotriene antagonist, FPL 55712, competed for the receptor at concentrations 2-3 orders of magnitude higher than the homoligand, leukotriene C4. The binding and specificity characteristics of the glomerular leukotriene C4 receptor are similar to those previously reported for the DDT1 nonvascular smooth muscle cell line derived from hamster vas deferens, for guinea pig ileum smooth muscle, and for a subcellular fraction of rat lung homogenate, and represent the first characterization of such a receptor in a vascular tissue.
Postextrasystolic potentiation of the isolated canine left ventricle. Relationship to mechanical restitution.
Authors: Yue D T , Burkhoff D , Franz M R , Hunter W C , Sagawa K
Published: June 2012

We established, for the isolated, isovolumically beating canine left ventricle, a comprehensive description of postextrasystolic contractile strength (dP/dtmax) as a function of extrasystolic and postextrasystolic stimulus intervals. In contrast to previous studies of postextrasystolic beats in in situ hearts, these isolated ventricles contracted isovolumically so that dP/dtmax was not affected by fluctuations in preload and afterload and was therefore considered to be a reliable index of intrinsic contractility. With the interval preceding extrasystoles constant, postextrasystolic contractile strength increased monoexponentially to a plateau as the interval preceding postextrasystoles lengthened, with a mean time constant (+/- SD) of 182 +/- 44 msec (n = 53). The onset of this increase in postextrasystolic contractile strength coincided with repolarization of the extrasystolic action potential. With the interval preceding postextrasystoles held constant and long (1200 msec), postextrasystolic contractile strength decreased according to a monoexponential function as the interval preceding extrasystoles lengthened [mean time constant (+/- SD) of 176 +/- 18 msec (n = 10)]. These phenomena could be quantitatively summarized by a single equation description of postextrasystolic contractile strength which involved monoexponential functions with one time constant. The mathematical form of this description led us to a simple interpretation of these phenomena in terms of currently proposed excitation-contraction coupling models of the heart.