Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CONSCIOUSNESS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,675 records · Page 93Linked to original sources
PubMed2005

Effects of angiotensin II on autonomic components of nasopharyngeal stimulation in male conscious rabbits.

Angiotensin II (ANG II) is known to activate central sympathetic neurons. In this study we determined the effects of ANG II on the autonomic components of the cardiovascular responses to stimulation of nasopharyngeal receptors with cigarette smoke. Experiments were carried out in conscious New Zealand White rabbits instrumented to record arterial pressure and heart rate. Rabbits were exposed to 50 ml of cigarette smoke before and after subcutaneous osmotic minipump delivery of ANG II at a dose of 50 ng.kg(-1).min(-1) for 1 wk in one group and intracerebroventricular (icv) infusion at a dose of 100 pmol/min for 1 h in a second group. The responses were compared before and after heart rate was controlled by pacing. Autonomic components were evaluated by intravenous administration of atropine methyl bromide (0.2 mg/kg) and prazosin (0.5 mg/kg). ANG II given either systemically or icv significantly blunted the pressor response to smoke (P < 0.05) when the bradycardic response was prevented. This blunted response was not due to an absolute increase in baseline blood pressure after ANG II infusion (71.64 +/- 11.6 vs. 92.1 +/- 19.8 mmHg; P < 0.05) because normalization of blood pressure with sodium nitroprusside to pre-ANG II levels also resulted in a significantly blunted pressor response to smoke. The effect of smoke was alpha(1)-adrenergic receptor-mediated because it was essentially abolished by prazosin in both the pre- and the post-ANG II states (P < 0.05). These results suggest that elevations in central ANG II reduce the sympathetic response to smoke in conscious rabbits. This effect may be due to an augmentation of baseline sympathetic outflow and a reduction in reflex sensitivity similar to the effect of ANG II on baroreflex function.

Angiotensin II↗
PubMed2000

Activity of hindlimb motor units during locomotion in the conscious rat.

This paper compares the activity of hindlimb motor units from muscles mainly composed of fast-twitch muscle fibers (medial and lateral gastrocnemius: MG/LG, tibialis anterior: TA) to motor units from a muscle mainly composed of slow-twitch muscle fibers (soleus: SOL) during unrestrained walking in the conscious rat. Several differences in the activation profiles of motor units from these two groups of muscles were observed. For example, motor units from fast muscles (e.g., MG/LG and TA) fired at very high mean frequencies of discharge, ranging from 60 to 100 Hz, and almost always were recruited with initial doublets or triplets, i.e., initial frequencies >/=100 Hz. In contrast, the majority of SOL units fired at much lower mean rates of discharge, approximately 30 Hz, and had initial frequencies of only 30-60 Hz (i.e., there were no initial doublets/triplets >/=100 Hz). Thus the presence of initial doublet or triplets was dependent on the intrinsic properties of the motor unit, i.e., faster units were recruited with a doublet/triplet more often than slower units. Moreover, in contrast to units from the slow SOL muscle, the activity of single motor units from the fast MG/LG muscle, especially units recruited midway or near the end of a locomotor burst, was unrelated to the activity of the remainder of the motoneuron pool, as measured by the corresponding gross-electromyographic (EMG) signal. This dissociation of activity was suggested to arise from a compartmentalized recruitment of the MG/LG motoneuron pool by the rhythm-generating networks of the spinal cord. In contrast, when comparing the rate modulation of simultaneously recorded motor units within a single LG muscle compartment, the frequency profiles of unit pairs were modulated in a parallel fashion. This suggested that the parent motoneurons were responsive to changes in synaptic inputs during unrestrained walking, unlike the poor rate modulation that occurs during locomotion induced from brain stem stimulation. In summary, data from this study provide evidence that the firing behavior of motor units during unrestrained walking is influenced by both the intrinsic properties of the parent motoneuron and by synaptic inputs from the locomotor networks of the spinal cord. In addition, it also provides the first extensive description of motor-unit activity from different muscles during unrestrained walking in the conscious rat.

Action Potentials↗
PubMed2002

Evidence for a central inhibitory role of growth hormone secretagogues and ghrelin on gastric acid secretion in conscious rats.

We examined the possible central and peripheral effects of synthetic growth hormone secretagogues (GHS), hexarelin (Hexa) and EP 40737 (D-Thr-D-Trp (2-Me)-Ala- Trp-D-Phe-Lys-NH2), and of their endogenous counterpart, ghrelin, on gastric acid secretion. The compounds were administered intracerebroventricularly (i.c.v.) or subcutaneously (s.c.) in conscious male rats and the volume of gastric secretion and gastric acid output were examined 3 h after pylorus ligation (Shay-test). Central Hexa, EP 40737 and ghrelin administration (from 0.1 pmol to 1 nmol/rat, i.c.v.) significantly inhibited gastric acid secretion. The maximum inhibitory effect on gastric acid output was detected at the dose of 10 pmol/rat, i.c.v. for Hexa (-51.3%), of 100 pmol/rat, i.c.v. for EP 40737 (-70%) and of 1 pmol/rat, i.c.v. for ghrelin (-60%). All peptides were less effective at the highest dose used (1 nmol/rat, i.c.v.). Hexa, EP 40737 and ghrelin injected s.c. did not modify gastric acid secretion. The inhibitory action of Hexa on gastric acid secretion seems to involve brain somatostatinergic system since Hexa (10 pmol/rat, i.c.v.) did not inhibit gastric acid secretion in rats pretreated (4 h before) with cysteamine (300 mg/kg, s.c.), a depletor of endogenous somatostatin. These results show that synthetic GHS and ghrelin exert a central long-lasting inhibitory effect on gastric acid secretion in conscious pylorus-ligated rats. The fact that very low doses of ghrelin and GHS inhibit gastric secretion, provide evidence for a tonic inhibitory role of the peptides in the central control of gastric secretory function.

Animals↗
PubMed2004

Rapid neurosecretory and cardiovascular response to osmotic stimulation in conscious mice.

Experiments were performed to evaluate the neuroendocrine and cardiovascular effects of osmotic stimulation in mice. Hypertonic saline (HS) was administered centrally or via the blood stream to conscious mice during measurement of blood pressure (BP), heart rate (HR) and plasma vasopressin (VP) and oxytocin (OT). A test of hypovolemia on VP secretion was also performed. Chronic carotid arterial cannulas were inserted for blood sampling, cardiovascular monitoring and vascular injections. Intracerebroventricular (ICV) cannulas were used for central injections. Vascular injection of HS (30 microl, 3.4 M NaCl) caused rapid and transient increases in plasma VP and OT. Plasma VP increased from 5.6 +/- 0.9 to 10.0 +/- 1.0 pg/ml, while plasma OT increased from 1.5 +/- 0.6 to 8.6 +/- 2.4 pg/ml at the earliest time point, immediately after ICV injection. ICV osmotic stimulation produced a rapid and sustained increase in plasma VP, with no change in OT. Plasma VP levels were increased from basal levels of 5.1 +/- 1.5 to 13.1 +/- 4.6, 11.4 +/- 1.5, 12.6 +/- 1.7 pg/ml at 0, 1 and 5 min after injection, respectively. ICV HS also increased plasma corticosterone. BP was increased by both vascular and central osmotic stimulation. Vascular HS increased BP immediately (Delta15.3 +/- 1.7 mm Hg, 0 min) and transiently (Delta-3.9 +/- 4.6 mm Hg, 5 min) while central HS produced a sustained increase in BP (Delta10 +/- 1.4 and Delta9.8 +/- 1.9 mm Hg, 0 and 5 min). Osmotic stimulation produced no significant changes in HR. Acute hemorrhage (approximately 10% decrease in blood volume) increased plasma VP (4.9 +/- 1.0 vs. 8.4 +/- 2.2 pg/ml). These results show the pattern of endocrine and cardiovascular responses to osmotic stimulation in conscious mice. They demonstrate that (1) there are extremely rapid changes in plasma VP and OT; (2) plasma OT is increased only after peripheral vascular hypertonic injection, and (3) central and peripheral osmotic stimulations are associated with pressor responses.

Analysis of Variance↗
PubMed1991

Naloxone increases the release of oxytocin, but not vasopressin, within limbic brain areas of conscious parturient rats: a push-pull perfusion study.

The influence of naloxone on the release in limbic brain areas of both oxytocin (OXT) and vasopressin, measured by radioimmunoassay, was studied in conscious parturient rats. Three consecutive 30-min push-pull perfusions (20 microliters artificial CSF/min) were made, via previously implanted guide cannulae, within the medio-lateral septum and dorsal hippocampus of parturient animals given saline or naloxone hydrochloride (5 mg/kg body weight) after delivery of the second pup. OXT release in the hippocampus, but not in the septum, was increased during parturition, compared to day 1 post partum. During the first 30-min collection period following naloxone administration, release of OXT was significantly elevated within the septum (44% compared to saline controls, p less than 0.002), but not in the dorsal hippocampus; vasopressin release was not affected. In contrast, on day 1 post partum, naloxone, administered 5 min after starting two consecutive perfusions failed to alter OXT release in septum or hippocampus in conscious rats. Naloxone, known to increase the release of OXT also from the posterior pituitary during parturition, speeded the parturition process significantly between the birth of pups 4 and 8 during push-pull perfusion of septum or hippocampus. The data suggest that endogenous opioid inhibition is involved in the regulation of central OXT release, but not vasopressin release, during parturition. Together with previous studies on OXT release from the posterior pituitary, it seems that during parturition there is coordinated endogenous opioid action on the release of OXT both into blood and into the brain.

Animals↗
PubMed1983

Effect of histamine on respiratory chemosensitivity in conscious goats.

The effect of histamine on occlusion pressure and electrical activity of the diaphragm was studied in 5 conscious goats under conditions of changing respiratory drive by exposing the animals in separate trials to progressive hypercapnia produced by rebreathing technique. Both electrical activity of the diaphragm and occlusion pressure increased with hypercapnia. At any level of PCO2, occlusion pressure and diaphragm electrical activity were greater after histamine than in the control state at the same level of chemical stimulation. Both parameters changed proportionally, and a linear correlation was found between them (r greater than 0.9). These results in conscious unsedated animals indicate that (1) histamine causes an increase of inspiratory neuromuscular drive, and (2) occlusion pressure satisfactorily indicates changes in respiratory neuron motor output.

Animals↗
PubMed1976

Comparison of natural and synthetic prostaglandins on gastric and pancreatic secretions and peptic ulcer formation in conscious cats.

In conscious cats with chronic gastric and pancreatic fistulas, the natural prostaglandins (PGs) of the E (PGE1 and PGE2) and F (PGF1 alpha and PGF2 alpha) series and synthetic 15-methyl analog of PGE2, 15(S) 15-methyl-PGE2 methylester were compared with regard to their action on gastric and pancreatic secretions and peptic ulcer formation. This study indicates that in comparison with natural PGs, the synthetic 15-methyl analog of PGE, is a more potent inhibitor of gastric secretion regardless of the route of administration and the mode of gastric stimulation. It more effectively prevents the formation of peptic ulcers in conscious cats.

Animals↗
PubMed1987

Proglumide stimulates basal pancreatic secretion in the conscious rat.

The effect of proglumide, a glutaramic acid derivative, on pancreatic secretion was examined in vivo in the conscious rat with and without the return of bile-pancreatic juice (BPJ) to the intestine. Intravenous infusion of both 300 and 60 mg/kg proglumide significantly decreased protein output in a dose-related manner during BPJ diversion, but did not completely abolish the pancreatic hypersecretory response to BPJ diversion. Conversely, during basal secretion with BPJ being returned to the intestine, 300 mg/kg/h of proglumide increased the protein output. Dibutyryl cyclic GMP infused simultaneously with proglumide did not abolish the stimulatory effect of proglumide on basal secretion. It was concluded that proglumide inhibits pancreatic protein output during stimulated secretion by means of the luminal feedback mechanism but increases protein output during basal (BPJ returned) secretion in the conscious rat.

Animals↗
PubMed2002

Role of cyclic guanosine monophosphate in late preconditioning in conscious rabbits.

BACKGROUND: Although NO has been shown to serve both as the trigger and the mediator of the late phase of ischemic preconditioning (PC), it is unknown whether NO acts via activation of soluble guanylate cyclase (sGC). The objective of this study was to investigate the role of sGC in late PC in conscious rabbits using the selective sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). METHODS AND RESULTS: A total of 172 conscious rabbits were used. When nonpreconditioned rabbits were subjected to a sequence of 4-minute coronary occlusion/4-minute reperfusion cycles, myocardial cyclic guanosine monophosphate (cGMP) levels increased significantly at the end of the third and sixth occlusions. In rabbits preconditioned 24 hours earlier (on day 1) with six occlusion/reperfusion cycles, myocardial cGMP levels on day 2 were significantly higher than in nonpreconditioned rabbits even before ischemia but did not increase further during a second sequence of 4-minute occlusion/reperfusion cycles. Administration of ODQ before the six occlusion/reperfusion cycles on day 1 did not prevent the development of late PC against either stunning or infarction on day 2. In contrast, administration of ODQ on day 2 completely ablated the late PC effect against both stunning and infarction. CONCLUSIONS: These results indicate that enhanced synthesis of cGMP by sGC is not necessary for ischemia to trigger a late PC effect but is required for the protection to become manifest 24 hours later. This implies that NO participates in late PC via two distinct mechanisms; ie, it triggers late PC on day 1 via a cGMP-independent mechanism and it mediates late PC on day 2 via a cGMP-dependent mechanism.

Animals↗
PubMed1983

Dipyridamole dilates large coronary arteries in conscious dogs.

The effects of 0.25 mg/kg dipyridamole on left ventricular (LV) pressures, LV dP/dt, heart rate, aortic pressures, left circumflex coronary blood flow, and left circumflex coronary arterial diameters and on calculations of late diastolic coronary resistance and large coronary cross-sectional area were studied in 15 conscious dogs. Injection of dipyridamole, a drug that has a mechanism of action dependent on myocardial adenosine production, caused sustained increases in mean coronary blood flow (244 +/- 28%), large coronary arterial cross-sectional area (28 +/- 3.2%), heart rate (32 +/- 3.6%), and LV dP/dt (23 +/- 3.0%) and reductions in late diastolic coronary resistance (73 +/- 2.4%) and mean arterial pressure (14 +/- 1.9%). Neither beta-adrenergic-receptor blockade alone nor in conjunction with constant heart rate affected the dilation of large coronary arteries to dipyridamole significantly. Ganglionic blockade with hexamethonium also had little effect on the response of large and small coronary vessels to dipyridamole. Surprisingly neither beta-adrenergic-receptor nor ganglionic blockade abolished the rise in LV dP/dt observed after dipyridamole. Aminophylline, however, effectively eliminated the dilation of large coronary arteries and resistance coronary vessels in response to dipyridamole. In summary, as long as dipyridamole does not induce severe sustained hypotension it exerts potent effects on both coronary arterial resistance and large coronary arteries in the conscious dog. The coronary dilation is independent of reflex adrenergic activation, but appears dependent on myocardial adenosine production.

Adenosine↗
PubMed1988

Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction.

We have suggested that among conscious dogs with a healed anterior wall myocardial infarction (MI) a depressed baroreflex sensitivity (BRS) carries a higher risk of developing ventricular fibrillation during a brief ischemic episode associated with an exercise stress test. The clinical and pathophysiological implications of our previous findings prompted the present study, which addressed three major questions: 1) Is, indeed, analysis of BRS after MI a specific and sensitive marker for sudden death-risk stratification? 2) Does MI modify BRS? 3) Does analysis of BRS before MI provide information about outcome during ischemic episodes occurring after MI? An anterior MI was produced in 301 dogs, and 4 weeks later, a 2-minute circumflex coronary artery occlusion beginning during the last minute of an exercise stress test could be performed in 192 animals. Ventricular fibrillation occurred in 106 (55%) dogs (susceptible to sudden death), whereas 86 (45%) dogs (resistant to sudden death) survived. BRS was assessed by the phenylephrine method and was expressed by the regression line relating RR intervals to blood-pressure changes. BRS was significantly lower among susceptible than among resistant dogs (9.1 +/- 6.0 vs. 17.7 +/- 6.5 msec/mm Hg, p less than 0.0001). The risk for sudden death increased from 20% (15 of 73 dogs) for a BRS greater than 15 msec/mm Hg to 91% (62 of 68 dogs) for a BRS less than 9 msec/mm Hg (p less than 0.001). An internal control study in 55 animals showed that BRS was reduced 4 weeks after MI compared with control conditions (13.5 +/- 6.7 vs. 17.8 +/- 6.6 msec/mm Hg, p less than 0.001) and that a reduction occurred in 73% of animals. Susceptible dogs and those that spontaneously died after MI had a lower BRS even before the MI (16.2 +/- 5.9 vs. 22.2 +/- 6.2 msec/mm Hg, p less than 0.001). The risk for sudden death after MI increased from 35% (nine of 26 dogs) for a BRS before MI greater than 20 msec/mm Hg to 85% (17 of 20 dogs) for a BRS before MI less than 14 msec/mm Hg (p less than 0.001). This study demonstrates that the presence of a reduced BRS is associated with a greater susceptibility to ventricular fibrillation during subsequent ischemic episodes. In the majority of dogs, BRS is reduced after an MI. The results in 192 conscious dogs with a healed MI indicate that analysis of BRS is a powerful tool for risk stratification not only after, but even before, the occurrence of an MI.

Animals↗
PubMed1989

Effects of graded reductions in coronary perfusion pressure on the diastolic pressure-segment length relation and the rate of isovolumic relaxation in the resting conscious dog.

To assess the relations between coronary perfusion pressure, blood flow, and the diastolic pressure-segment length relation in the conscious animal, circumflex pressure was incrementally decreased in 10 resting, chronically instrumented dogs by a hydraulic occluding cuff while monitoring left ventricular pressure and regional segment length (with piezoelectric crystals) in the circumflex and left anterior descending territories. In five dogs, regional blood flow was measured by microsphere injections at selected circumflex pressures. The diastolic portion of the pressure-segment length curve was unchanged when decrements in circumflex pressure were within the autoregulatory range, that is, unassociated with changes in blood flow or systolic function. Further decrements in circumflex pressure, which decreased blood flow and regional segment shortening (both p less than 0.05), caused a progressive downward and rightward shift of the pressure-segment length curve (p less than 0.05). The rate of relaxation, as measured by tau (the time constant of pressure decay during isovolumic relaxation, which is calculated assuming either a fixed or a variable asymptote) and peak negative dP/dt, decreased slightly during reductions in circumflex pressure within the autoregulatory range and greatly at lower pressure (all p less than 0.05). Thus, in the conscious animal, reductions in coronary perfusion pressure within the autoregulatory range do not affect the diastolic pressure-segment length curve but cause modest decreases in the rate of isovolumic relaxation. Further reductions in coronary perfusion pressure, below the limits of blood flow autoregulation, cause an increased extent of relaxation with a marked downward shift of the diastolic pressure-segment length curve as well as a large decrease in the rate of relaxation.

Animals↗
PubMed1992

Influence of the force-frequency relation on left ventricular function during exercise in conscious dogs.

BACKGROUND: The magnitude of the force-frequency effect on myocardial contractility in the conscious animal has been studied at rest, but it has not been assessed during exercise. METHODS AND RESULTS: The influence of heart rate (HR) changes were evaluated during treadmill exercise in eight preinstrumented, conscious dogs in which high-fidelity left ventricular (LV) pressure, LV volume (by sonomicrometry), and aortic pressure were measured. Under resting conditions, end-systolic pressure-volume relations were obtained using inferior vena caval occlusion. Dogs were run on a treadmill, and the intrinsic exercise HR was reduced by infusion of a specific bradycardic drug (UL-FS 49 0.5 mg/kg) during continuing exercise while HR was maintained at 240 beats per minute by atrial pacing. At 6 minutes of running at a fixed, paced HR when a stable drug effect had been achieved, no effects of UL-FS 49 on measures of LV contractility were detected compared with exercise before drug administration. HR was then reduced stepwise from 240 to 210, 180, or 150 beats per minute in a random manner, returning to 240 beats per minute between steps. Progressive reductions in measures of myocardial contractility occurred as the HR was slowed, and reduction of rate from 240 to 150 beats per minute reduced the LV maximum positive dP/dt by 31% and (dP/dt)DP40 by 21% despite increases in LV end-diastolic pressure. The entire end-systolic pressure-volume could not be determined during exercise, but beat-averaged end-systolic pressure-volume points during exercise were progressively shifted to the right and downward by slowing the exercise HR. Thus, a pronounced negative inotropic influence of slowing the heart was observed during exercise, and the rate of ventricular relaxation (tau) was also significantly prolonged. CONCLUSIONS: These findings indicate that force-frequency effects on the inotropic state of the intact LV are markedly enhanced by exercise.

Animals↗
PubMed1994

Nitric oxide mediates flow-dependent epicardial coronary vasodilation to changes in pulse frequency but not mean flow in conscious dogs.

BACKGROUND: Although epicardial coronary arteries dilate in response to changes in flow, the mechanisms responsible for this and the mechanical stimuli that are sensed by the endothelium are not completely defined. We performed the present study to determine the importance of nitric oxide in eliciting epicardial dilation to sustained changes in mean flow and pulse frequency in the coronary circulation of conscious dogs. METHODS AND RESULTS: Dogs were chronically instrumented with a circumflex coronary occluder, piezoelectric crystals to measure epicardial diameter, and a coronary artery catheter placed distal to the crystals for intracoronary drug infusion. Studies were conducted in dogs in the conscious state. We inhibited nitric oxide production by administering the arginine analog N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg IV), which attenuated the epicardial artery diameter changes to left atrial infusions of acetylcholine (10 micrograms/min) from 140 +/- 23 (+/- SEM) to 46 +/- 20 microns (P < .05). Epicardial dilation to sustained increases in mean coronary artery at a constant heart rate. Intracoronary adenosine increased mean flow to the same extent (180 +/- 21 versus 177 +/- 24 mL/min after L-NAME, P = NS), but inhibiting nitric oxide production had no effect on flow-mediated epicardial dilation, with coronary diameter increasing by 264 +/- 36 microns under control conditions and 294 +/- 67 microns after L-NAME (P = NS). In contrast, when pulse frequency was increased by pacing to a rate of 200 beats per minute, mean coronary flow increased to a similar level (78 +/- 9 versus 75 +/- 9 mL/min after L-NAME), but the epicardial diameter change to pacing was attenuated from 170 +/- 29 microns under control conditions to 54 +/- 23 microns after L-NAME (P < .01). CONCLUSIONS: These results demonstrate that in vivo, nitric oxide production is primarily responsible for eliciting epicardial coronary vasodilation to endothelium-dependent agonists and changes in coronary flow pulse frequency. The failure of L-NAME to affect epicardial vasodilation during sustained increases in mean flow when pulse frequency is held constant suggests that additional mechanisms are involved in flow-mediated vasodilation of epicardial coronary arteries.

Acetylcholine↗
PubMed1995

Disparate effects of early pressure overload hypertrophy on velocity-dependent and force-dependent indices of ventricular performance in the conscious baboon.

BACKGROUND: The effects of early pressure overload on left ventricular (LV) chamber mechanics in the primate heart are poorly understood. METHODS AND RESULTS: To test the hypothesis that early LV pressure overload hypertrophy is associated with depression of velocity-dependent indices of LV systolic (LV dP/dt) and diastolic function (time constant of relaxation, tau) but unchanged systolic elastance (Ees), we studied six conscious baboons instrumented with LV micromanometers and LV dimension and wall thickness sonomicrometers. Loading conditions were altered by pharmacological angiotensin II generation both before and 12 weeks after producing renovascular hypertension (2 kidney, 1 clip). The LV systolic pressure (149 +/- 11 [SD] versus 114 +/- 5 mm Hg) and LV mass (125 +/- 25 versus 91 +/- 20 g) were greater 12 weeks after than before (both P < .05). Both Ees and Ees normalized for LV mass were similar before versus 12 weeks after (23.0 +/- 9.6 versus 22.3 +/- 9.8 mm Hg/mL and 26.5 +/- 14.5 versus 19.8 +/- 12.5 mm Hg/mL, respectively; both P = NS). At matched LV systolic and diastolic pressures, LV fractional shortening was similar (18.6 +/- 6.8% versus 21.6 +/- 4.9%), but the time constant of LV isovolumic relaxation was significantly longer (42.3 +/- 5.3 versus 31.4 +/- 7.0 ms, P < .05) and LV dP/dt and Vcf were significantly less (1891 +/- 352 versus 2342 +/- 284 mm Hg/s and 0.9 +/- 0.4 versus 1.1 +/- 0.3 circ/s, respectively; both P < .05) 12 weeks after than before. CONCLUSIONS: In conscious baboons with systemic arterial hypertension and early LV hypertrophy, there is depression of velocity-dependent indices of LV contraction and relaxation but unaltered force-dependent measures of contractility.

Animals↗
PubMed1995

Arrhythmias and death after coronary artery occlusion in the rat. Continuous telemetric ECG monitoring in conscious, untethered rats.

BACKGROUND: The onset of acute myocardial infarction (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. The aim of this study was to assess the continuous arrhythmia profile during the initial 48 hours after coronary artery ligation in the rat in relation to time course, mortality, and infarct size. METHODS AND RESULTS: Continuous ECG recording were obtained in 26 conscious, untethered rats for 24 hours before and 48 hours after coronary ligation by use of an implantable telemetry system. All episodes of ventricular tachycardia and fibrillation were counted and their durations summed. Infarct size was measured at 48 hours after MI or after spontaneous death. After ligation, two distinctly active arrhythmogenic periods developed (A1, 0 to 0.5 hours; A2, 1.5 to 9 hours), each followed by a quiescent phase of low ectopy (Q1, 0.5 to 1.5 hours; Q2, 10 to 48 hours). The total mortality rate of 65% was found within the two active periods, with 13 of 15 deaths occurring in A2. Rats with larger infarcts (> or = 50%) and nonsurvivors tended to have increased arrhythmia frequency and duration compared with both animals with smaller MIs (< 50%) and survivors. CONCLUSIONS: Two distinct arrhythmogenic periods occur in rats with acute MI that may be caused by different mechanisms and correspond to the bimodal arrhythmia time course seen in dogs and humans after acute MI. Telemetric monitoring of the ECG in the conscious rat after infarction will be useful in assessment of the differential effects of therapeutic interventions on these two arrhythmogenic periods and in the study of potential mechanisms for the spontaneous resolution of ventricular ectopy and risk of sudden death.

Animals↗
PubMed1998

Nitric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits.

BACKGROUND: Despite intense investigation, the effector of the infarct-limiting protection observed during the late phase of ischemic preconditioning (PC) remains unknown. The goal of this study was to test the hypothesis that late PC against myocardial infarction is mediated by the activity of nitric oxide synthase (NOS). METHODS AND RESULTS: Conscious rabbits underwent a 30-minute coronary occlusion followed by 3 days of reperfusion. In group I (control group, n= 10), infarct size (tetrazolium staining) averaged 56.8+/-5.3% of the risk region, which was decreased to 27.6+/-2.5% (P<0.05) in rabbits preconditioned 24 hours earlier with a sequence of six 4-minute occlusion/4-minute reperfusion cycles (group II, n= 10). When preconditioned rabbits were given the nonselective NOS inhibitor N(omega)-nitro-L-arginine (L-NA, 13 mg/kg i.v. [group III, n=8]) or the selective iNOS inhibitor aminoguanidine (AG, 150 mg/kg SC [group V, n=7]) before the 30-minute occlusion, the protective effect of late PC was completely abrogated; that is, infarct size (59.9+/-4.5% and 65.8+/-3.3%, respectively) was similar to that measured in the control group. Measurements of systolic wall thickening (sonomicrometry) demonstrated that L-NA and AG also abolished the improved recovery of myocardial function effected by late PC in group II. When rabbits were given L-NA or AG without prior PC (group IV [n=8] and group VI [n=6], respectively), infarct size did not differ from that observed in controls (53.8+/-4.3% and 59.8+/-4.3%, respectively), demonstrating that L-NA and AG do not increase the extent of cell death in nonpreconditioned myocardium. CONCLUSIONS: Taken together, these results indicate that in the conscious rabbit, the infarct-sparing effect of the late phase of ischemic PC is mediated by the activity of NOS and suggest that the specific isoform primarily responsible for this cardioprotective phenomenon is iNOS. Thus, NO appears to be a pivotal component of the pathophysiological cascade of late PC.

Analysis of Variance↗
PubMed2002

Central ghrelin modulates sympathetic activity in conscious rabbits.

Ghrelin is an orexigenic peptide originally isolated from the stomach. Intravenous administration of ghrelin has been shown to elicit a decrease in arterial pressure without a significant change in heart rate (HR), suggesting that ghrelin may act on the central nervous system to modulate sympathetic activity. The aim of the present study was to determine the central effects of ghrelin on cardiovascular and sympathetic responses in conscious rabbits. Intravenous injection of ghrelin elicited dose-related decreases in arterial pressure and HR, without a significant change in renal sympathetic nerve activity. On the other hand, intracerebroventricular injection of 1 nmol of ghrelin decreased arterial pressure, HR, and renal sympathetic nerve activity. Peak depressor or sympathoinhibitory responses of mean arterial pressure and renal sympathetic nerve activity (-19.0+/-1.5 mm Hg and -43.3+/-5.4%) were observed at 50 and 40 minutes, respectively, after intracerebroventricular injection of 1 nmol of ghrelin. Furthermore, a subdepressor dose of intracerebroventricular infusion of ghrelin (0.3 nmol/150 micro L per hour) significantly augmented the baroreflex sensitivities assessed by renal sympathetic nerve activity and HR compared with those of vehicle infusion (G(max); -17.8+/-3.1 versus -9.4+/-1.6%/mm Hg, P<0.05; -12.5+/-1.8 versus -6.6+/-1.2 bpm/mm Hg, P<0.05; respectively). These results suggest that intravenous injection of ghrelin acts, at least in part, on the central nervous system to decrease arterial pressure and renal sympathetic nerve activity, and that central ghrelin participates in the regulations of the sympathetic nerve activity to the kidney and the baroreceptor reflex in conscious rabbits.

Animals↗