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Biomedical subjects

D D Lund

Publications and source records attributed to D D Lund.

At least 55 records · Page 3Linked to original sources
PubMed1986

Alterations in the baroreceptor reflex control of heart rate in streptozotocin diabetic rats.

Baroreflex control of heart rate was studied in conscious diabetic rats at 12, 24 and 48 weeks after the induction of diabetes with streptozotocin. Baseline blood pressure (mean arterial blood pressure) of diabetic rats was significantly lower at 12 weeks after the induction of diabetes when compared to age-matched control rats. However, at 24 and 48 weeks of diabetes, no difference in blood pressure was observed between diabetic and age-matched control rats. In contrast, bradycardia (prolongation of pulse interval) was a consistent feature of diabetic rats at all time points (12, 24, and 48 weeks). To assess parasympathetic control of heart rate, baroreceptor sensitivity was determined by infusing phenylephrine. Baroreflexes in diabetic rats were changed from an increased sensitivity at 12 and 24 weeks to decreased sensitivity at 48 weeks after the induction of diabetes. This suggests that alterations in baroreflex sensitivity might depend upon the length of time the animals were exposed to the diabetes. Insulin treatment in diabetic animals reversed hypotension, bradycardia and altered baroreflex sensitivity observed in 12-week diabetic rats. Non-diabetic rats, in which the development of diabetes was prevented by pretreatment with 3-0-methylglucose before streptozotocin injection, or rats which did not develop diabetes after streptozotocin injection showed a similar baseline blood pressure, heart rate and baroreflex sensitivity to those of age-matched control rats (12, 24 and 48 weeks). This data suggests that changes in blood pressure, heart rate and baroreflex sensitivity are due to the diabetic state, not to streptozotocin toxicity.

Animals↗
PubMed1986

Alterations in ventricular excitability in conscious dogs during development of chronic heart failure.

Arrhythmias in patients with heart failure may result from altered electrophysiological properties of the myocardium. To examine changes in ventricular excitability during cardiac failure and to relate these changes to ventricular structural and neurochemical abnormalities, right ventricular failure was produced in dogs by pulmonary artery banding and by creating tricuspid regurgitation. Right and left ventricular excitability thresholds were tested biweekly in heart failure (HF) and sham-operated conscious dogs by means of strength-duration curves (1-40 ms) at basic cycle lengths (BCL) of 300-500 ms until time of death (21-188 days). Marked increases in the excitability threshold of the right ventricle occurred in HF (mean maximum % increase, 205 +/- 42 at BCL 500 ms). Smaller, though significant increases in the left ventricular excitability threshold in HF were also seen (mean maximum % increase 103 +/- 36 at BCL 500 ms). Increases in the excitability threshold of the left as well as the right ventricles occurred, even though ventricular dilation (2-D Echo) was confined to the right ventricle. The time course of changes in the excitability threshold was variable (maximum occurrence at 21 +/- 3 days right ventricle, 23 +/- 11 days left ventricle). Tyrosine hydroxylase activity and norepinephrine content of the right ventricle were markedly depleted at death, when the excitability threshold was high. Similar though nonsignificant trends in reductions of these sympathetic neurochemicals were seen in the left ventricle. Levels of choline acetyltransferase and QNB binding in both ventricles were unaffected.

Animals↗
PubMed1986

Vagus nerve stimulation alters regional acetylcholine turnover in rat heart.

The turnover of neurotransmitter is a direct measure of neuronal function, varying with the impulse activity of the nerve. It is not known if vagal stimulation increases acetylcholine release uniformly throughout the heart, or if modification of neural signals occurs between the vagal nerve trunks and postganglionic synaptic terminals. The rate constant of acetylcholine turnover was measured in conduction and contractile regions of heart by quantifying the incorporation of [3H]choline into acetylcholine after labeling of the blood choline pool in urethane-anesthetized rats during two levels of vagal activity. Choline and acetylcholine were assayed by high pressure liquid chromatography with electrochemical detection of post-column enzymic reaction product, peroxide. The specific activities of choline and acetylcholine in the tissues at sacrifice were used to calculate the fractional turnover rates in cardiac regions. Supramaximal bilateral vagal stimulation for 20 minutes decreased heart rate (P less than 0.05), while mean arterial blood pressure remained constant. The rate constants for acetylcholine turnover in right atrial regions containing the sinoatrial node, left atrial tissues, and interatrial septum doubled from control values during vagal stimulation. In contrast, the fractional rate constants of acetylcholine turnover did not change in the right and left ventricles during vagal stimulation. We interpret these results to indicate general activation of postganglionic parasympathetic fibers to the atria and selective modulation of postganglionic parasympathetic neural function to the ventricles.

Acetylcholine↗
PubMed1986

Presynaptic regulation of cardiac sympathetic function in guinea pigs.

Cold stress (4 degrees C) induces a pressor response and variable increases in an index of sympathetic neural function, the rate constant of norepinephrine turnover, kNE. In heart, presynaptic cholinergic muscarinic and alpha-2 adrenergic influences may contribute to regional variation in responses of kNE to cold stress. Animals were pretreated with vehicle, a muscarinic cholinergic antagonist, quinuclidinyl benzilate (QNB), an alpha-2 adrenergic antagonist, yohimbine (YOH) or combined QNB + YOH. An increase in kNE was determined from incorporation of radiolabeled tyrosine into norepinephrine in a control period at 24 degrees C and again at 4 degrees C. The increment in kNE factored by the increment in blood pressure indicated the extent of increased sympathetic function in each cardiac region. In sino-atrial node, sympathetic function was increased significantly (P less than .05) by QNB + YOH compared to other treatments, suggesting that both cholinergic and alpha-2 adrenergic presynaptic influences were important. In contrast, in right and left ventricles, YOH or QNB + YOH, but not QNB alone, increased sympathetic function significantly, suggesting that only alpha-2 adrenergic influences were important. These data support the concept that presynaptic regulation of cardiac sympathetic function differs in sino-atrial node and ventricles of guinea pigs during activation with cold stress.

Animals↗
PubMed1984

In vitro adrenergic and cholinergic innervation of the developing rat myocyte.

We studied the development of selective adrenergic and cholinergic neuroeffector transmission in primary cultures of isolated ventricular muscle cells. Explants of either thoracolumbar sympathetic ganglia or sacrococcygeal spinal cord were added to newborn rat ventricular cultures harvested prior to the onset of in vivo autonomic innervation. Neuronal growth, migration, and the formation of neuromuscular junctions were observed with light and scanning electron microscopy. Glyoxylic acid histofluorescence, reflecting catecholamine synthesis, was found in only the sympathetic neuromuscular cultures. Choline acetyltransferase activity was detected in both spinal cord and sympathetic neuromuscular cultures, but was significantly higher in the spinal cord neuromuscular cultures. The isolated ventricular muscle cells remained at a constant spontaneous contraction frequency, regardless of the type of culture preparation. Guanethidine sulfate application produced a positive chronotropic response, blocked by propranolol, in the sympathetic neuromuscular cultures, but not in the spinal cord neuromuscular cultures. Bethanechol sulfate produced a negative chronotropic response, blocked by atropine, in the spinal cord neuromuscular cultures, but not in the sympathetic neuromuscular cultures. Isolated ventricular muscle cells in the absence of neurons failed to respond to either agent. Direct microelectrode stimulation of adrenergic or cholinergic neurons likewise respectively produced either a positive or negative ventricular muscle cell chronotropic response. These studies are the first to establish the selective production of functional cholinergic and adrenergic innervation of isolated cardiac muscle cells in vitro.

Adrenergic Fibers↗
PubMed1983

Increased choline acetyltransferase activity in pressure-overloaded right ventricles of guinea pigs.

Choline acetyltransferase activity, a biochemical indication of parasympathetic innervation, is increased in the hypertrophied right ventricle of guinea pigs after pulmonary artery constriction (PAC). The increase appears to be dependent on the severity and the duration of hypertrophy. This change in choline acetyltransferase activity suggests compensatory changes occur in the parasympathetic innervation of PAC guinea pigs which allows the right ventricle to maintain its level of parasympathetic innervation despite marked hypertrophy. Unlike the right ventricle, the SA node of PAC guinea pigs does not have detectable changes in choline acetyltransferase activity. This model of right ventricular hypertrophy also does not have detectable changes in baroreflex control of heart rate.

Animals↗
PubMed1983

Neurochemical indices of autonomic innervation of heart in different experimental models of heart failure.

Parasympathetic neural regulation of the failing heart is impaired. In order to investigate parasympathetic mechanisms in experimental heart failure, measurements were made of choline acetyltransferase (CAT) activity and [3H]-quinuclidinyl benzilate (QNB) binding in hearts of 1) hamsters with skeletal and cardiac myopathy, 2) dogs with pulmonary artery constriction and tricuspid avulsion, and 3) guinea pigs with pulmonary artery constriction. Tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities and norepinephrine levels served as indices of sympathetic innervation. In myopathic hearts, total CAT activity decreased (P less than 0.05) compared to age-matched controls. In canine and guinea pig right heart failure, total CAT activity was normal in contractile and specialized tissues. Alterations in [3H]-QNB binding paralleled CAT activity being decreased (P less than 0.05) only in myopathic hearts. In all three models, indices of sympathetic innervation were altered in ways qualitatively different from parasympathetic indices; TH and DBH activities were increased (P less than 0.05) in myopathic ventricles, decreased (P less than 0.05) in hypertrophied canine and guinea pig ventricles and non-hypertrophied canine ventricles, and normal in non-hypertrophied guinea pig ventricles. These results indicate that alterations in cardiac parasympathetic indices vary depending on the etiology of heart diseases and differ qualitatively from alterations in sympathetic indices. Selective determinants are necessary to explain the varied changes.

Animals↗
PubMed1983

Distribution of local repolarization changes produced by efferent vagal stimulation in the canine ventricles.

The purpose of this study was to compare the distribution of effects of right and left efferent vagal stimulation on ventricular recovery properties in the in situ heart. To measure these effects in many areas simultaneously, local repolarization changes (local QT intervals) were recorded with bipolar electrodes in nine ventricular sites from 38 anesthetized dogs. In initial experiments, this method was shown to correlate with effective refractory period changes measured in the same test site after QT recording; vagal nerve stimulation prolonged the local QT interval by 1 ms for each 0.82 ms prolongation in effective refractory period (r = 0.87). Simultaneous local QT recordings during vagal nerve stimulation demonstrated uniform prolongation with two exceptions. First, left vagal efferent stimulation prolonged local QT interval in the posterior left ventricular base more than did right vagal stimulation (5.9 +/- 1.0 mean +/- standard error of the mean versus 3.7 +/- 0.9%, p less than 0.05). This probably resulted from an interaction with the left sympathetic nerves because left stellate ganglionectomy or norepinephrine infusion eliminated differences between effects of right and left vagal stimulation. Second, it was also found that vagal stimulation from either side did not prolong local QT interval time in the anterior right ventricle despite attempts to augment vagal effects with bilateral vagal stimulation alone or during isoproterenol or physostigmine administration. These regional differences in ventricular repolarization exhibited in response to efferent vagal nerve stimulation in the dog may provide a basis for understanding how autonomic influences could contribute to the genesis of ventricular arrhythmias.

Animals↗
PubMed1982

Changes in parasympathetic and sympathetic neurochemical indices in hearts of myopathic hamsters.

Sympathetic neurochemical indices in heart are increased in Syrian golden hamsters with skeletal and cardiac myopathy. The possibility that parasympathetic neurochemical indices might be altered was investigated in myopathic and normal hearts by measuring activity of choline acetyltransferase involved in acetylcholine synthesis. Confirming a previous report, tyrosine hydroxylase activity increased in failing myopathic hearts and norepinephrine concentration decreased. Extending previous work, tyrosine hydroxylase and dopamine-beta-hydroxylase activities in myopathic hearts demonstrated progressive, age-related increases. These changes were associated with reduced choline acetyltransferase activity in hearts of older myopathic hamsters (180 to 300-plus days). Decreases tended to be more pronounced in hamsters with cardiac hypertrophy and fluid retention (290-360 days old). Neurochemical evidence of increased sympathetic indices (dopamine-beta-hydroxylase activity) was detected at 30 days of age. Evidence of decreased parasympathetic indices (choline acetyltransferase activity) was detected at 180 days of age and persisted through terminal phases of heart failure. This study demonstrated that there are abnormalities in cardiac parasympathetic as well as cardiac sympathetic indices in myopathic hamsters.

Aging↗
PubMed1982

Selective sympathetic neural changes in hypertrophied right ventricle.

Selective pressure overload of the right ventricle in guinea pigs resulted in early and sustained reductions in tyrosine hydroxylase and dopamine-beta-hydroxylase activities in the right ventricle. No changes in tyrosine hydroxylase activity were detected in stellate ganglia sinoatrial (SA) nodal region, atrioventricular (AV) nodal region, or left ventricle. Reductions in tyrosine hydroxylase activity in stressed right ventricle were similar regardless of duration of pulmonary artery constriction, extent of hypertrophy, presence or absence of hepatic congestion, and preservation or depletion of catecholamines. The changes may represent localized loss of sympathetic nerve fibers; factors involved directly in the process of pressure-overload-induced hypertrophy may be responsible. However, sympathetic nerves remaining in hypertrophied ventricle respond normally to cold-induced sympathetic activation. The reduction in tyrosine hydroxylase activity and the maintenance of norepinephrine turnover in residual innervation to hypertrophied right ventricle support the concept that sympathetic neural regulation of hypertrophied cardiac tissue is altered but not lost.

Animals↗
PubMed1982

Tyrosine hydroxylase and choline acetyltransferase activities in ischemic canine heart.

After coronary artery occlusion, enzymes involved in the synthesis of sympathetic and parasympathetic neurotransmitters may change disparately. We investigated this in the canine heart by measuring the activity of tyrosine hydroxylase (TH) and choline acetyltransferase (CAT) in normal and ischemic tissue. Myocardial blood flow in selected regions was measured by the microsphere technique. Dogs had either ligation of the anterior descending coronary artery (LAD) or sham ligation (S). In the ischemic zone 5 h after LAD ligation, TH activity was lower than in corresponding anterior apical zones of S dogs (5.1 +/- 1.7 vs. 13.5 +/- 2.3 nmol.g-1.h-1) (P less than 0.05) with a tendency for greater decreases in endocardium than in epicardium. In contrast, there were insignificant changes in CAT activity 2.5 and 5 h after LAD ligation. Thereafter, progressive and significant (P less than 0.05) decreases occurred in CAT activity at 25 and 170 h after LAD ligation. Thus there are early heterogeneous decreases in TH activity that correlate directly with heterogeneous deficits in blood flow. Although decreases in CAT are also heterogeneous and correlate with deficits in perfusion, these changes occur later. These results indicate differences in the effects of infarction on these biochemical indices of sympathetic and parasympathetic innervation in canine heart.

Animals↗
PubMed1982

Metabolic and cardiovascular adaptations in trained hypophysectomized rats.

Metabolic and cardiovascular changes resulting from acute and chronic exercise were examined in male Sprague-Dawley rats assigned to sham-control or hypophysectomized groups. Two weeks after surgery, the hypophysectomized rats had decreased their maximum oxygen consumption (VO2 max) and heart rate values by 4 ml X min-1 X kg-1 and 142 beats X min-1, respectively. Twenty weeks later, hypophysectomy was associated with a 22 ml X min-1 X kg-1 decrease in VO2 max and a 215 beat X min-1 decline in their maximal heart rates when compared with sham-control means. Endurance training was responsible for the significantly higher O2 consumption values. Additionally, trained animals exhibited longer run times, higher muscle cytochrome oxidase activity, and reduced food consumption. Measurements of right atrial choline acetyltransferase (CAT) activity and [3H]quinuclidinyl benzilate (QNB) binding revealed significantly higher CAT values and fewer muscarinic receptors. However, training had no significant effect on resting blood pressure, blood pressure changes with conditions of lower body negative pressure, muscle glycogen concentrations, CAT levels and QNB binding of the left atrium and ventricular regions, or receptor density. These results indicated that many of the adaptations that are characteristic of normal populations can occur in the absence of the hormones from the pituitary gland.

Adaptation, Physiological↗
PubMed1981

Regional distribution of tyrosine hydroxylase and dopamine beta-hydroxylase activities in guinea pig heart.

The sympathetic and parasympathetic autonomic nervous systems regulate heart rate and myocardial contractility. Using sensitive radioisotopic assays, we examined the regional distribution of tyrosine hydroxylase and dopamine beta-hydroxylase activity, which are markers for sympathetic autonomic innervation, in specialized pacemaker and conduction tissue and in contractile heart tissue. Of the 20 regions of guinea pig heart examined, we find that the highest activities occur in the sinoatrial node and the right atrial appendage. Intermediate activity occurs in the left atrium, interatrial septum and right ventricular papillary muscle. Activities in the remainder of the heart are lower and rather uniform. Comparing the enzyme markers for the parasympathetic [17] and sympathetic system, we find that these systems have different distributions. The former, for example, is closely associated with the specialized pacemaker and conduction system including the sinoatrial and atrioventricular nodes and regions rich in Purkinje fibers. The sympathetic system, on the other hand, is associated with both contractile and conducting tissue.

Adrenergic Fibers↗
PubMed1981

Hypoxia-induced changes in parasympathetic neurochemical markers in guinea pig heart.

Exposure of animals to hypoxia produces cardiovascular changes including right ventricular hypertrophy and alterations in heart rate. The activity of choline acetyltransferase, a neurochemical marker of parasympathetic innervation, and the density of muscarinic cholinergic receptors, measured by the binding of [3H]quinuclidinyl benzilate, were analyzed in the hearts of guinea pigs exposed to hypobaric hypoxia. We found a significant increase in the activity of choline acetyltransferase in the sinoatrial node in response to hypoxia after 7 or 14 days. In addition, we found significant decreases in the muscarinic receptor density in several contractile and conducting regions. The decrease in receptor density may reflect regulation by the level of occupancy; an increased occupancy may produce a decrease in muscarinic receptor number.

Acetylcholine↗
PubMed1979

Choline acetyltransferase activity in rat and guinea pig heart following vagotomy.

Choline acetyltransferase (CAT), which serves as a marker for the preganglionic and postganglionic parasympathetic cholinergic neurons in heart, was measured in heart regions in rats and guinea pigs after either a right or a left unilateral cervical vagotomy or a sham operation. One day after a left vagotomy in rat, CAT activity was decreased in the region of the SA and AV nodes. In rats killed on the 2nd, 4th, and 8th day after left vagotomy, the activity of CAT in these regions increased to the control level. CAT activity in the remainder of the heart did not decrease. In guinea pig 1 wk after a left vagotomy, CAT activity was decreased in the anterior interventricular septum but not in other regions. Selective increases in enzyme activity were noted in the right atrial appendage following left vagotomy and in the superior interventricular septum following right vagotomy. These results suggest that compensatory increases in CAT activity occur that may be related to collateral sprouting similar to that observed in the frog heart.

Animals↗