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Biomedical subjects

F L Abel

Publications and source records attributed to F L Abel.

At least 19 recordsLinked to original sources
PubMed1995

Effects of pericardial pressure on systemic and coronary hemodynamics in dogs.

The effects of pericardial tamponade on coronary capacitance and coronary systemic hemodynamics were calculated in two groups of animals subjected to increases in pericardial pressure (PCP) up to approximately 20 mmHg. In one group (A), flow in the left circumflex artery was measured in the intact animal under conditions of increased PCP. In the second group (B), coronary artery perfusion pressure was maintained constant with a pump while PCP was increased. In group A increased PCP was accompanied by a decrease in arterial pressure. This resulted in a marked decrease in coronary blood flow after vasodilation but without a change in coronary vascular resistance. In group B there was no change in coronary flow or coronary vascular resistance with increased PCP. Microsphere distribution to the left ventricular wall showed less endocardial than epicardial flow but no change in going from low to high PCP. Characteristic impedance was altered in the group B animals after vasodilation at medium and high PCP, indicating a loss of reflection sites and probably increased vessel tethering. The coronary artery in a subgroup of group B animals was also perfused by left ventricular pressure, the time constants for coronary backflow showing an 8-12% decrease in capacitance with low and high PCP; these values represent minimal epicardial capacitances vs. total bed capacitance. A diastolic model for the values for resistance and capacitance in the coronary bed is suggested. As expected, most of the capacitance is in the venous bed and most of the resistance is in the arterial bed.

Animals↗
PubMed1995

Direct action of endotoxin on cardiac muscle.

While the cardiovascular effects of endotoxin include myocardial depression, presumably due to circulating myocardial depressant substances, endotoxin itself is supposed to have no direct effect on the heart. In these experiments, we compared the direct effects of endotoxin on the contractile response of feline papillary muscle to calcium with that seen after administration to the intact animal. The contractile state of the muscle was assessed from developed tension as extracellular calcium concentrations were varied from .5 to 8.0 mM. When endotoxin was administered to the intact animal as well as given to the muscle directly in the bathing solution, endotoxin- exposed muscles showed smaller increases in contractile tension with increasing calcium concentrations than control muscles after 70-85 min. NaOH-inactivated endotoxin produced results similar to the control experiments. Previous experimenters have reported myocardial depression only after endotoxin had circulated in the intact animal for 1-2h; these experiments show a direct depressant effect of endotoxin on cardiac muscle without the release of a substance elsewhere in the body.

Animals↗
PubMed1994

Effects of cardiac work on the threshold for ventricular fibrillation.

Ventricular fibrillation threshold (VFT) was measured in anesthetized dogs, while cardiac work was altered by changing arterial pressure (pressure work) or by opening an aorta to left atrial shunt (flow work). When VFT during pressure work was compared with that during flow work, at a constant heart rate, it was found that there was a negative correlation (a lower threshold for fibrillation) between VFT and flow work but not pressure work. VFT also had negative correlations with the rate of contraction and relaxation indexes; maximal +/- dp/dt and negative dp/dt were the most significant variables. On the other hand, coronary flow, oxygen consumption, end diastolic pressure, and tension time index were not correlated with VFTs. Thus, VFT depended on mechanical factors not necessarily correlated to alterations in myocardial perfusion.

Animals↗
PubMed1992

The effects of nimodipine on cocaine toxicity.

The response to nimodipine as an inhibitor of cocaine toxicity was investigated in pentobarbital-anesthetized dogs and in isolated dog heart preparations at constant heart rates. Nimodipine (10 micrograms/kg) markedly decreased peripheral and coronary vascular resistance and increased cardiac output, cardiac work, and coronary blood flow. When corrected for the change in afterload, nimodipine had a positive inotropic response, as measured by +/- maximal dP/dt, in the cocaine-depressed animal. Thus, cocaine toxicity was partially reversed by nimodipine. In the isolated heart preparation, nimodipine resulted in further cardiac depression similar to that seen with other calcium channel antagonists.

Analysis of Variance↗
PubMed1992

Contribution of extravascular compression to reduction of maximal coronary blood flow.

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.

Adenosine↗
PubMed1991

Effects of systole-specific pericardial pressure increases on coronary flow.

It has been postulated that intrathoracic pressure increases may impair cardiac function by decreasing coronary flow. To determine whether altered coronary flow causes or results from change in cardiac function, we used 14 anesthetized dogs in propranolol-induced heart failure following atrioventricular node ablation. After thoracoabdominal binding, the animals were paced and ventilated at the same frequency, and inspiration was synchronized with cardiac systole, resulting in systole-specific pericardial pressure increases (SSPPI). At SSPPI magnitudes of 15 and 30 mmHg, left atrial transmural pressure decreased and cardiac output increased, whereas decreases in left ventricular end-systolic transmural pressure and myocardial O2 consumption were directly related. Concurrent decreases in coronary sinus flow (CSF) and coronary arteriovenous O2 gradient with SSPPI 15 mmHg indicate autoregulation. However, the arteriovenous O2 gradient remained unaltered with SSPPI 30 mmHg, despite further decrease in CSF. Because the absolute diastolic aortic pressure decreased, a limit may exist for increasing SSPPI above which CSF may be directly affected.

Animals↗
PubMed1991

Portal venous compliance in canine endotoxin shock.

The response of the small intestinal vascular bed to endotoxin and ibuprofen was determined in mongrel dogs under pentobarbital anesthesia. Blood flow was measured in the superior mesenteric artery and pressures in the artery and portal vein. Venous compliance was calculated from the rate of pressure rise in the occluded portal vein at a constant arterial inflow. The response to endotoxin was followed for 1 hr, ibuprofen was given, and the response was followed for a second hour. Arterial pressure and mesenteric flow decreased after endotoxin, accompanied by an increase in venous compliance and in the compliance/resistance ratio. Treatment with ibuprofen increased arterial pressure but did not improve blood flow; however, it effectively reversed the changes in compliance. The results indicate a loss of arterial vasomotor tone in response to endotoxin which is not shared by the portal venous system. This may result in fluid loss into the intestinal bed. Ibuprofen restored arterial tone and released the venous constriction, but did not significantly alter the metabolic responses to endotoxin.

Animals↗
PubMed1990

Effects of dopamine D1 and dopamine D2 receptor agonists on coronary and peripheral hemodynamics.

This study evaluated the coronary dopamine receptors by using the dopamine D1 receptor agonist fenoldopam, dopamine D2 receptor agonist propylbutyldopamine, and their selective antagonists SCH23390 and domperidone. Left circumflex coronary flow (CF), coronary perfusion pressure at constant flow, left ventricular hemodynamics, and total peripheral vascular resistance (TPR) were measured in pentobarbital-anesthetized dogs at constant arterial pressures. At doses of 200, 500 and 5000 nM, both fenoldopam and propylbutyldopamine induced dose-related inotropic effects, as evidenced by maximal dp/dt and cardiac output, an increase in CF, decrease in coronary vascular resistance and a decrease in TPR. Fenoldopam was more potent in its cardiac and coronary effects while propylbutyldopamine was more potent peripherally. On the basis of dosage used, the positive inotropic effects of fenoldopam and propylbutyldopamine were much weaker than dopamine. After beta-receptor blockade, the inotropic and coronary effects of fenoldopam and propylbutyldopamine were extremely attenuated. Domperidone could largely antagonize the propylbutyldopamine-induced inotropic and coronary effects while SCH23390 showed no significant effect. In addition, under our experimental conditions, the fenoldopam- and propylbutyldopamine-induced decreases in TPR were markedly reduced by SCH23390 and domperidone, respectively. The results indicate that the coronary effects of fenoldopam and propylbutyldopamine result not from a primary coronary vasodilating action, but from vasodilation secondary to positive inotropic effects. Both dopamine D1 and dopamine D2 receptors are involved in the peripheral vascular hemodynamics.

Animals↗
PubMed1990

Effect of systemic endotoxin on skeletal muscle vascular conductance during high and low adrenergic tone.

The objective of this study was to determine the role of adrenergic tone on the peripheral vascular decompensation reported to occur during systemic endotoxemia. An in situ constant-flow double-canine gracilis muscle (GM) preparation allowed one GM to serve as an innervated control (GMc) for the contralateral denervated muscle (GMe). Group I (n = 9): normal inherent vascular tone; Group II (n = 7): adrenergic tone elevated by bilateral common carotid artery ligation. The GMc Group II vascular conductance was significantly lower than GMe at .0485 +/- .004 ml/min/100 g/mm Hg and .0636 +/- .005 ml/min/100 g/mm Hg respectively. GM denervation had no significant effect on Group I conductance suggesting a low level of baseline intrinsic adrenergic tone; however, denervation did increase the vascular conductance by more than 30% from .0485 +/- .004 to .0638 +/- .008 ml/min/100 g/mm Hg in Group II. A 2 mg/kg dose of endotoxin was infused i.v. over 30 min and data collected over an additional 60 min. The endotoxin caused a decrease in MAP from 129 +/- 5 to 73 +/- 6 mm Hg in Group I and from 177 +/- 16 to 92 +/- 14 mm Hg in Group II. both the GMc and GMe Group I GMs showed an initial increase in conductance to 115 +/- 9 and 117 +/- 8% respectively at 5 min followed by a reduction to 82 +/- 9 and 101 +/- 10% at 60 min. Group II (GMe) showed a significantly increased conductance following denervation to 125% which increased insignificantly to 140 +/- 15% at 60 min, while conductances either remained at about 100% or decreased slightly to 88 +/- 7% in the innervated Group II GMc. The data suggest that the baseline level of vascular tone may not be an important factor when evaluating the effect of systemic endotoxemia on the skeletal muscle peripheral vasculature.

Adrenergic Fibers↗
PubMed1990

Does the heart fail in endotoxin shock?

Evidence for a major participatory role of the myocardium in the hemodynamic response to endotoxemia and sepsis has been controversial. Early interpretations about in situ changes in cardiac performance during shock were confounded by the concomitant influence of uncontrolled pathophysiologic adjustments in cardioactive variables such as preload, afterload, sympathoadrenal discharge, left ventricular diastolic compliance (stiffness), and in some studies myocardial hypoperfusion/ischemia. Despite such complexities, many recent studies with intact subjects and isolated preparations consistently point toward a relatively early involvement of myocardial dysfunction in circulatory shock syndromes associated with gram-negative bacteria and sepsis. The cardiac dysfunction cannot be accounted for by a direct toxic effect of the endotoxin molecule itself on cardiac myocytes. Rather, evidence is compelling that endotoxin interacts first with other types of cellular or tissue elements. The latter evoke biologic reactions through some unknown pathway culminating in deleterious effects in the heart. Discovery of the casual mechanism(s) responsible for myocardial sequelae of endotoxemia and sepsis remains a key objective in experimental and clinical research in circulatory shock pathogenesis.

Animals↗
PubMed1989

Myocardial function in sepsis and endotoxin shock.

Myocardial function in sepsis and endotoxin shock is reviewed. Clinical, whole animal, and isolated tissue studies are compared to answer the question whether sepsis and/or endotoxin directly damage the myocardium. Myocardial performance is considered relative to control of preload, afterload, and heart rate. Despite the fact that these vary widely in different studies, there is overwhelming evidence that myocardial performance is depressed in both sepsis and endotoxin shock. The depression is dose related, occurs early after large doses of endotoxin but may follow a hyperdynamic phase in sepsis or after low doses of endotoxin. Endotoxin itself does not appear to be the depressant factor; the final depressant substance(s) is unknown. Calcium transport by the sarcoplasmic reticulum is depressed. This defect is more prominent in the endocardium than in the epicardium. Myocardial adenosinetriphosphatase (ATPase) and norepinephrine stores may be depleted. The septic myocardium has an increased dependence on sympathetic nerve stimulation. There is little evidence that the cause of the myocardial depression is an inadequate coronary blood flow.

Animals↗
PubMed1989

Influence of ibuprofen on renal function in acutely endotoxemic dogs.

Dogs were anesthetized with pentobarbital and instrumented to measure renal function. An inulin infusion was started; after an appropriate equilibration period one group was infused with endotoxin only (ETOX), a second group was pretreated with ibuprofen before (PRET) endotoxin, and a third group was post-treated with ibuprofen after (POST) endotoxin. Renal blood flow decreased in all animals, but renal vascular resistance increased only in the POST group animals. Urine flow and osmolar clearance decreased and free water clearance increased in the post-treated animals. Glomerular filtration rate as well as electrolyte excretion decreased in both the ETOX and POST group animals. Renal glucose output was unchanged in the ETOX and POST groups, but in the ibuprofen-pretreated animals there was significant net uptake, indicating increased utilization. Ibuprofen alone had no significant effect on blood flow, renal resistance, filtration rate, or solute and water handling. However, when ibuprofen was given 30 min after the induction of endotoxemia, the changes brought about by endotoxin alone were further intensified.

Animals↗
PubMed1989

Cocaine depresses the canine myocardium.

The effects of cocaine hydrochloride infusion on left ventricular function in the anesthetized dog were observed under controlled heart rate and blood pressure conditions. In every case an immediate decrease in performance, as evidenced by maximal + rate of change of ventricular pressure (dP/dt), occurred and was a linear function of cumulative dose. Maximal (-) dP/dt also declined, indicating a decreased rate of ventricular relaxation. Right atrial and left ventricular end diastolic pressure increased, with no change in cardiac output or cardiac work, whereas coronary flow decreased slightly. This small decrease in coronary flow was probably related to the decrease in contractile vigor rather than a direct effect of cocaine on vascular tone. Although plasma norepinephrine concentration initially increased, ventricular function did not increase and continued to decline with cumulative cocaine dose. Tissue norepinephrine levels measured in isolated heart-lung preparations were not depleted. These findings indicate a direct toxic action of cocaine on the myocardium, decreasing both contractile performance and relaxation state. Plasma cocaine levels were constant during continuous infusion of the drug, indicating that the progressive toxicity observed did not result from increased circulating cocaine.

Animals↗
PubMed1988

Canine peripheral vascular response to endotoxin shock at a constant cardiac output.

The peripheral vascular response to Escherichia coli endotoxin (1 mg/kg/i.v.) was measured for 2 hr in the pentobarbital anesthetized dog. Total venous return was collected and returned by a pump to the right atrium to maintain a constant cardiac output. Occlusion of the venous lines permitted estimation of venous compliance in the systems drained by the superior (SVC) and inferior vena cavae (IVC). After endotoxin administration, arterial pressure and total peripheral resistance rapidly dropped and remained low for 2 hr. IVC compliance was decreased at 10-30 min and SVC compliance at 10 min after endotoxin. The decrease in compliance is interpreted as venous dilation and probably venous pooling. The latter may account for a substantial portion of the total venous pooling reported in early endotoxin shock. After 30 min, compliance increased and by 60 min was equal to control. Left ventricular relaxation ability decreased as indicated by maximal negative dp/dt. Ibuprofen, 10 mg/kg, was administered at 120 min or earlier, depending on the state of the animal; rapid recovery of arterial pressure and ventricular function occurred without a significant change in venous compliance.

Animals↗
PubMed1988

Left ventricular performance in canine endotoxin shock.

Left ventricular performance was studied in 6 control and 7 experimental open-chest, heart-paced dogs before and after a single 1 mg/kg dose of E. coli endotoxin under pentobarbital anesthesia. Positive maximal dp/dt, time to peak ventricular pressure (PVP time), cardiac output, stroke work, tension-time index (TTI), coronary flow, and cardiac oxygen consumption were derived from left ventricular pressure, aortic flow, left atrial pressure, coronary sinus flow and A-V oxygen difference. During a control period and for 2 h post-endotoxin, while mean arterial pressure (afterload) and heart rate were held constant, +dp/dt max, PVP time, cardiac output, and cardiac work were related to left ventricular end diastolic pressure to obtain ventricular function curves. Positive maximal dp/dt was found depressed early (60 min) during the 2 h period of endotoxicosis studied (P less than .05). PVP time values increased after endotoxin administration but not significantly. Coronary sinus flow was found to be significantly elevated at 2 h post-endotoxin. The findings indicate the presence of early (60 min) and sustained depression of ventricular performance at elevated coronary blood flows during endotoxicosis.

Animals↗
PubMed1988

Relative importance of cardiac output and arterial pressure in determining myocardial oxygen consumption and coronary blood flow.

Oxygen consumption and coronary blood flow were measured in anesthetized dogs while cardiac work was altered by changing arterial pressure or by opening an aorta to left atrial shunt. When oxygen consumption during pressure work was compared with that during flow work, at a constant heart rate, it was found that flow work increased oxygen consumption as much, or more, than did increasing pressure work. Coronary blood flow, but not A-V oxygen difference, was correlated with oxygen consumption. The highest correlation with oxygen consumption, however, was obtained for left ventricular end-diastolic pressure, which was even more highly correlated than was cardiac work. The conclusion is that it may be the initial stretch of the myocardial fiber, rather than the arterial pressure or the cardiac output, that is the primary determinant of myocardial oxygen consumption at a constant heart rate.

Animals↗
PubMed1987

Effect of ibuprofen on the course of canine endotoxin shock.

Four groups of dogs were anesthetized, instrumented for measurement of blood pressures and flows across the liver, and, except for the control group, injected with 1 mg/kg endotoxin. The control group received only saline. One group received endotoxin only (ETOX) while animals in the other two groups received 10 mg/kg ibuprofen either 30 min before (PreIBU) or 30 min after endotoxin (PostIBU). Blood pressure, hepatic arterial and portal flow decreased after endotoxin injection in the ETOX and Post IBU animals but not in the PreIBU-injected animals. Pressure and flows returned to normal within 15 min after ibuprofen in the PostIBU animals but remained significantly lower in the ETOX animals. There was a transient increase in blood glucose concentration in the ETOX and PostIBU animals immediately after endotoxin injection, but not in the PreIBU group. Glucose then steadily decreased in all three experimental groups for the remainder of the experiment in spite of the fact that glucose production was elevated. Blood lactate and glycerol concentration increased in all three groups throughout the experiment. Ibuprofen was able to correct the pressure and flow changes caused by endotoxin, but did not prevent the hypoglycemia or accumulation of lactate and glycerol in plasma.

Animals↗