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Biomedical subjects

J X Thomas

Publications and source records attributed to J X Thomas.

At least 37 records · Page 2Linked to original sources
PubMed1988

One hour of myocardial ischemia in conscious dogs increases beta-adrenergic receptors, but decreases adenylate cyclase activity.

An increased myocardial beta-adrenergic receptor density has been reported following myocardial ischemia. However, it is not clear whether these receptors are effectively coupled to adenylate cyclase which would be necessary for enhanced physiological responsiveness. We, therefore, examined the effects of myocardial ischemia in six conscious dogs (4 intact and 2 with posterior wall denervation) in which the left circumflex coronary artery was occluded. Ischemia was verified by measurement of regional blood flow by radioactive microspheres. After 1 h of coronary artery occlusion, the dogs were anesthetized with pentobarbital and the left ventricle was divided into normal, intermediate and ischemic regions. A crude membrane fraction was prepared from each region. beta-Adrenergic receptors were quantitated with 125I-cyanopindolol binding and adenylate cyclase activity was measured. In all six animals studied, beta-adrenergic receptor density increased progressively and adenylate cyclase activity decreased progressively, when the ischemic myocardium was compared to the intermediate and the non-ischemic myocardium. Since adenylate cyclase activity declined, these results do not support the concept that the increased beta-receptor density induced by myocardial ischemia is causally related to enhanced beta-adrenergic sensitivity.

Adenylyl Cyclases↗
PubMed1988

Sympathetic activation induces asynchronous contraction in awake dogs with regional denervation.

To determine effects of regional left ventricular (LV) denervation on regional contractile responses to sympathetic activation, dogs with posterior LV wall denervation (posterior wall-denervated group) and dogs with innervated posterior LV walls (intact group) were studied during excitement, exercise, bilateral sympathetic nerve stimulation, and norepinephrine infusion. In intact conscious dogs, all modes of sympathetic activation increased the magnitude and decreased the time of onset of systolic wall thickening (WT) similarly in the anterior and posterior wall. In the denervated group, excitement failed to increase posterior WT during systole but instead elicited asynchronous contraction, i.e., postsystolic WT, as well as delayed onset of contraction. Asynchronous contraction was not observed with excitement after beta-adrenergic receptor blockade. Asynchronous contraction of the posterior wall was also observed during the initial phase of exercise in conscious dogs and during bilateral stellate stimulation in anesthetized dogs in the posterior wall-denervated group. In comparison to neural activation, adrenergic receptor activation with norepinephrine (0.2 microgram/kg-1.min-1 iv) induced a supersensitive increase in systolic WT in the denervated posterior wall (36 +/- 5%) compared with the anterior wall (17 +/- 2%) and a delay in the end of contraction in the anterior region. Thus asynchronous contraction can be elicited in dogs with regional LV denervation as a result of an early and enhanced contraction in the innervated region during neural sympathetic activation. The reverse was observed with systemic administration of norepinephrine because of catecholamine supersensitivity in the denervated posterior wall.

Animals↗
PubMed1988

Responses to coronary artery occlusion in conscious dogs with selective cardiac denervation.

The extent to which cardiac denervation alters responses to myocardial ischemia remains controversial. This study compared responses to 24-h coronary artery occlusion (CAO) on measurements of wall thickness (ultrasonic crystals), regional myocardial blood flow (microspheres), and infarct size (triphenyltetrazolium chloride technique) in three groups of conscious dogs with 1) selective posterior left ventricular (LV) wall denervation, 2) selective ventricular denervation, or in 3) intact dogs. After CAO, hemodynamic changes were not different among the three groups. Wall thickening in the ischemic zone became akinetic or paradoxical early after CAO and did not recover in any group over the 24-h monitoring period. Blood flow in the area at risk fell similarly in all groups. Infarct size, as a percentage of the area at risk, was 45 +/- 7% in intact, 48 +/- 6% in posterior LV wall-denervated, and 48 +/- 8% in ventricular-denervated group. There was, however, a lower (P less than 0.05) frequency of arrhythmic beats per minute after 3 h of CAO in the ventricular-denervated group (3.2 +/- 1.4) compared with the intact (11.3 +/- 4.1) or posterior wall-denervated (12.6 +/- 3.2) group. An additional group of ventricular-denervated dogs was studied to determine the effects of sequential, brief 2-min CAO at 2, 4, and 8 wk after denervation. Responses of regional wall thickening to CAO were not affected significantly even after 8 wk following ventricular denervation. Thus, in conscious dogs, neither selective ventricular denervation nor selective denervation of the posterior LV wall improved collateral blood flow, affected regional function favorably, or reduced infarct size after CAO.

Animals↗
PubMed1987

Effects of myocardial ischemia on regional function and stiffness in conscious dogs.

The extent to which cardiac nerves influence responses of regional ventricular function to acute myocardial ischemia was investigated in conscious dogs with intact cardiac innervation (N) and dogs with chronic cardiac denervation (D). Following coronary artery occlusion (CAO) left ventricular (LV) end-diastolic pressure increased more (P less than 0.01) in D (18 +/- 3.2 mmHg) than in N dogs (3.4 +/- 0.7 mmHg), whereas heart rate increased more in N (32 +/- 4.8 beats/min) than in D dogs (16 +/- 3.0 beats/min). In nonischemic zones of D dogs there were greater increases, P less than 0.05, in end-diastolic segment length, systolic segment shortening, and velocity of shortening than in N dogs. In ischemic zones, significantly greater increases in end-diastolic segment length were also observed in the D group, but similar reductions in segmental shortening occurred in both N (-116 +/- 2.8%) and D (-108 +/- 5.2%) dogs. The time constant of isovolumic relaxation was not different in the two groups. However, in ischemic zones of N dogs myocardial stiffness constant (k) increased by 109 +/- 24 from 33 +/- 4.9 and end-diastolic stiffness (Eed) rose by 1527 +/- 310 from 253 +/- 34 mmHg, whereas k increased significantly less (P less than 0.05) in D dogs. Eed of ischemic zones also rose significantly less (P less than 0.05) in D dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of left circumflex coronary flow transducer implantation on posterior wall innervation.

To determine whether dissection around a coronary artery and implantation of a flow transducer resulted in partial regional denervation of the heart, the effects of bilateral stimulation of the ansae subclaviae were evaluated on regional left ventricular (LV) wall thickening (WT) and tissue norepinephrine content in four groups of dogs following 1) sham operations (n = 6),2) implantation of a Doppler flow transducer on the left circumflex coronary artery (n = 6), 3) selective circumflex coronary artery denervation with topical phenol application (n = 5), and 4) selective denervation of the posterior LV wall by extensive surgical stripping of the left circumflex coronary artery and local application of phenol (n = 6). One week later after anesthesia (chloralose 100 mg/kg) and a second thoracotomy for implantation of ultrasonic WT crystals, stimulation of the ansae subclaviae increased posterior WT by 67 +/- 9% in the sham group, 71 +/- 14% in the flow probe group, and did not increase systolic WT in the denervated group. In the posterior LV wall, norepinephrine levels were reduced (P less than 0.01) in the denervated group (6 +/- 4 pg/mg) but not in the flow probe group (629 +/- 4 pg/mg) compared with the sham group (589 +/- 88 pg/mg). Selective left circumflex coronary artery denervation did not result in either diminished norepinephrine levels in the posterior LV wall nor diminished response of WT to sympathetic nerve stimulation. Thus chronic instrumentation applied properly to the left circumflex coronary artery does not result in significant regional denervation of the posterior myocardium.

Animals↗
PubMed1985

Increased myocardial contractility during endotoxin shock in dogs.

The slope of the left ventricular (LV) end-systolic pressure-diameter relationship (Ees) was analyzed in open-chest, pentobarbital-anesthetized dogs before and after endotoxin administration. A lead II electrocardiogram, systemic arterial pressure, LV pressure, LV dP/dt, and LV minor axis diameter were measured. After control measurements were taken, dogs were given either 1 mg/kg Salmonella enteritidis endotoxin (n = 5) or an equivalent volume of saline (n = 4). Control dogs were followed for 240 min. Endotoxic dogs were monitored until death (246 +/- 44 min). There were no significant changes in Ees in control dogs (17 +/- 3 mmHg/mm), which were hemodynamically stable for 4 h. Ees was significantly increased in endotoxic dogs even into the late stages of shock (41 +/- 11 mmHg/mm, P less than 0.01). Only during the terminal phase did Ees fall significantly below control (11 +/- 2 mmHg/mm, P less than 0.05). End-diastolic diameter decreased following endotoxin administration (P less than 0.05) but returned toward control by the terminal stage. Peak + LV dP/dt was depressed following endotoxin injection. Myocardial contractility was not depressed except as a terminal event. Early depression of cardiovascular performance in endotoxic dogs was therefore due to decreased preload and not cardiac dysfunction.

Animals↗
PubMed1985

Glucose dyshomeostasis and cardiovascular failure in endotoxic dogs.

Fasted mongrel dogs were anesthetized with pentobarbital sodium and instrumented for the on-line measurement of blood glucose (BG), a lead II electrocardiogram, and pressures in the left ventricle and pulmonary and systemic artery concomitant with on-line monitoring of BG. Serum insulin was measured by radioimmunoassay, and cardiac output (CO) was determined by thermodilution. Stroke work (SW) and pulmonary and systemic resistances were calculated. After a 30-min control period dogs were treated with Escherichia coli endotoxin (E) or normal saline (S) and then observed for 10 h or until death. Preinjection control BG was maintained in S dogs, and early hyperglycemia (H) was observed in six dogs; in contrast 10 E dogs showed no hyperglycemia (NH). During the late stages all E dogs were markedly hypoglycemic. In both groups of E dogs an early hyperinsulinemia occurred. CO and SW were depressed in both groups of E dogs. These variables were significantly lower in NH than in H dogs. Pulmonary and systemic resistance progressively increased in NH dogs after endotoxin administration. The results suggest that the ability to increase blood glucose levels after endotoxin injection is important for the maintenance of cardiovascular function. Glucose dyshomeostasis leading to hypoglycemia, however, may be a factor in the development of endotoxic cardiovascular failure.

Animals↗
PubMed1985

Glucose clamping and cardiovascular function in endotoxic dogs.

Fasted mongrel dogs were anesthetized with pentobarbital sodium and instrumented for the continuous measurement of blood glucose (BG), a lead II electrocardiogram, and pressures in the left ventricle (LV), pulmonary artery, and aorta. Cardiac output was measured every 15 min using thermodilution and LV stroke work, and pulmonary and systemic resistances were calculated. After a 30-min pretreatment period, glucose clamping was initiated. The desired glucose levels were reached within 45 min (hypoglycemic 20 +/- 1 mg/dl, n = 11; normoglycemic 85 +/- 1, n = 7; hyperglycemic 156 +/- 3, n = 7). At this point dogs were treated with either endotoxin (8 mg/kg to 6 hypoglycemic, 4 normoglycemic, and 4 hyperglycemic) or saline (5 hypoglycemic, 3 normoglycemic, and 3 hyperglycemic). All infusions were terminated after 2 h glucose clamping, and all dogs were monitored either until death or for a maximum of 10 h. Hypoglycemic clamping curtailed survival in endotoxic dogs. Hyperglycemic clamping markedly prolonged survival. Normoglycemic clamping left survival time unchanged compared with untreated dogs. The effects of glucose clamping on cardiovascular function during endotoxic shock paralleled the effects on survival. Cardiovascular function was also depressed in hypoglycemic-clamped saline dogs. It is concluded that glucose dyshomeostasis may be a crucial factor in the development of fatal cardiovascular dysfunction and shock after endotoxin administration.

Animals↗
PubMed1985

Adverse effects of chronic cardiac denervation in conscious dogs with myocardial ischemia.

The extent to which total chronic cardiac denervation protects the ischemic myocardium was investigated in conscious dogs. The major hemodynamic difference after coronary artery occlusion was that left ventricular end-diastolic pressure rose significantly more, P less than 0.01, in the denervated group (12 +/- 1.5 mm Hg) than in the normal group (4.4 +/- 1.4 mm Hg). Blood flow (radioactive microspheres) in the ischemic endo- and epicardium fell to similar levels at 3-5 minutes after coronary occlusion, but was significantly less (P less than 0.01) in denervated dogs at 3 hours after occlusion in the endo- (0.05 +/- 0.01) and epicardium (0.30 +/- 0.02 ml/min per g), than in the endo- (0.13 +/- 0.03) and epicardium (0.42 +/- 0.05 ml/min per g) in the normal group. A subgroup of normal dogs was also studied, with left ventricular end-diastolic pressure increased by volume loading to levels similar to those observed in the denervated group after coronary occlusion; in these dogs, blood flow was similar to that in the other two groups 3-5 minutes after coronary artery occlusion, but, at 3 hours, was significantly more depressed (P less than 0.01) than that observed in normal dogs without volume loading in both endo- (0.03 +/- 0.01) and epicardial (0.25 +/- 0.03 ml/min per g) layers. Infarct size, as a fraction of the area at risk, was significantly greater (P less than 0.05) in the denervated group (60 +/- 4.3%) and in the subgroup of normal dogs with elevated left ventricular end-diastolic pressure (73 +/- 5.8%), compared with the normal group without volume loading (37 +/- 8.1%). Thus, in conscious dogs, total chronic cardiac denervation exerts an adverse effect on infarct size which may be related to the sustained elevation in left ventricular end-diastolic pressure and consequent impairment of collateral perfusion.

Animals↗
PubMed1983

Autonomic influences on atrioventricular conduction in conscious dogs.

Autonomic innervation of the atrioventricular (AV) junction modulates conduction of the cardiac impulse, the sympathetic nerves facilitating and parasympathetic nerves impeding conduction. Experiments assessed the relative importance of parasympathetic vs. sympathetic control by pharmacologic blockade with atropine (0.2 mg/kg) or propranolol (1.0 mg/kg) while pacing the right atrium (100-400 beats/min) in normal, conscious resting dogs and in dogs that had undergone chronic, intrapericardial cardiac denervation. Maximum pacing rate with 1:1 atrioventricular conduction was termed Rmax. Control Rmax at rest was 125.69 +/- 9.49 beats/min and was slightly reduced after propranolol to 118.28 +/- 10.98 (P = 0.043). After atropine, Rmax was significantly increased to 344 beats/min. Propranolol and atropine together resulted in an Rmax of 308 beats/min, which was significantly less than after atropine alone. Rmax in cardiac-denervated dogs was 301 beats/min, which was not significantly different from that following total pharmacologic blockade. In conscious, resting, unsedated dogs, the upper limit of AV nodal conduction is associated with the level of parasympathetic rather than sympathetic tone; during exercise the sympathetics assume greater importance.

Animals↗
PubMed1983

Selective denervation of the heart.

Total denervation of the canine heart consisted of intrapericardial neural dissection of the left atrium, left superior pulmonary vein, and main pulmonary artery and cutting of the ventrolateral cardiac nerve (stage I). The fat pad and all nerves were removed from between the pulmonary artery and aorta (stage II). Dissection proceeded from the pericardial reflection along the superior vena cava to the azygos vein, which was cleared, double tied, and cut. The right pulmonary artery was cleaned, and the superior right atrium was dissected to its intersection with the left atrium (stage III). Denervation was tested by electrical stimulation of both vagi and stellate ganglia, while recording inotropic, chronotropic, and dromotropic events, before and after each stage. Stage I deleted most left autonomic input to the heart without interrupting right sympathetics. Stage II completed left autonomic denervation but preserved much of the right sympathetic input. Large nerves along the dorsal surface of the pulmonary artery carried inputs from both left and right sympathetics. Stage III completed the denervation of atrioventricular and sinoatrial nodal structures and removed all remaining ventricular inotropic influences. Selective denervation of atrioventricular and sinoatrial nodal regions appears feasible for preparation of chronic canine models.

Animals↗
PubMed1982

Effects of individual cardiac nerve stimulation on atrioventricular conduction.

This study investigated the effects of individual canine cardiac nerve stimulation on atrioventricular conductions as measured by His bundle electrograms. A-H and H-V intervals were measured before and during stimulation of each nerve in paced hearts (200 beats/min) and before and after blocking doses of either atropine or propranolol. Increases in A-H or H-V intervals were evidence of parasympathetic innervation; decreases in intervals were evidence of sympathetic innervation. Separation by autonomic composition produced 3 categories: sympathetic, parasympathetic, and mixed input to the atrioventricular junction. The sympathetic nerves were the left and right ansae subclavia, the ventrolateral cardiac nerve, and the right stellate cardiac nerve. The parasympathetic nerve was the right thoracic vagus, and the mixed nerves were the left thoracic vagus, and the innominate, ventromedial, craniovagal, caudovagal, and right recurrent cardiac nerves. The cardiac nerves eliciting a major response were the left and right ansae subclavia, the ventrolateral, right recurrent, craniovagal, and caudovagal cardiac nerves, and the left and right thoracic vagi. In theory, the nerves of the right side, because of their innervation of both sinoatrial and atrioventricular nodes, may be expected to elicit a balanced heart rate-atrioventricular conduction response when stimulated, thus matching atrial and ventricular rates. On the other hand, stimulation of the ventrolateral cardiac nerve regularly produces dysrhythmia, due to increased automaticity at the atrioventricular junction. Production of such arrhythmias indicates the possible implication of imbalanced autonomic activity in arrhythmogenesis. Three cardiac nerves produced little or no effect on atrioventricular conduction. These were the innominate, ventromedial, and right stellate cardiac nerves. Because of its limited distribution and marked sinus rate effects, the right stellate cardiac nerve can be considered almost a purely positive chronotropic nerve. Its possible role in heart rate-atrioventricular conduction mismatching has not been delineated but, because of its nearly exclusive action at the sinoatrial node, may be of considerable importance.

Animals↗
PubMed1982

Regional coronary vasoconstriction in response to stimulation of stellate ganglia.

Recent experiments have demonstrated that direct and reflex sympathetic stimulation elicit coronary vasoconstriction when the inotropic and chronotropic effects are blocked with beta-adrenergic blocking agents. This vasoconstriction can be blocked with alpha-adrenergic blocking agents. Regional variations in the flow reduction produced by right (RSS) vs. left (LSS) stellate stimulation were delineated in this study. Open-chest pentobarbital-anesthetized dogs were given propranolol (1 mg/kg iv). Hearts were neurally decentralized and paced just above the spontaneous heart rate. Radiolabeled microspheres (15 +/- 2 micrometers) were injected into the left atrium before and during RSS (n = 11) or LSS (n = 11). RSS produced relatively little vasoconstriction confined to anterior left ventricle. In contrast, LSS produced significant vasoconstriction in all areas of the right and left ventricles. In the endocardial half of the left ventricle the flow decrease was uniformly distributed among the regions studied. In the epicardial half of the flow decrease was more pronounced in posterior than in anterior regions. No significant change occurred in the endo-epi ratios with RSS, but with LSS there was a significant change in three areas. The changes were related to regional variations in the degree of epicardial constriction. Thus RSS and LSS have differential effects (quantitatively) on regional coronary blood flow.

Animals↗
PubMed1981

Protective effect of chronic versus acute cardiac denervation on contractile force during coronary occlusion.

The effects of acute coronary artery (CA) occlusion on myocardial contractile force were studied in mongrel dogs with (1) chronically denervated hearts (n = 10), (2) acutely denervated hearts (n = 5), and (3) normally innervated hearts (n = 6). Contractile force was measured in ischemic and nonischemic areas using Walton-Brodie strain gauge arches sutured to the epicardium. Coronary occlusion was accomplished by ligating several small branches of the left anterior descending and the circumflex arteries supplying the apical region on the left ventricle. Following occlusion, contractile force in the ischemic area decreased by 66.8% in the control group, by 73.6% in the acutely denervated group, but only by 21.6% (P less than 0.001) in the chronically denervated group. These results demonstrate that chronic cardiac denervation protects from the severe loss of contractile force in the ischemic area. This salutary effect is not seen with acute cardiac denervation.

Animals↗