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J D Port

Publications and source records attributed to J D Port.

51 records · Page 3Linked to original sources
PubMed1990

Beta-adrenergic pathways in nonfailing and failing human ventricular myocardium.

beta-Adrenergic pathways in the human ventricular myocardium mediate the powerful positive inotropic effects of released neurotransmitters (norepinephrine) and circulating hormones (epinephrine) and the response to therapeutically administered beta-agonists. Two genetically and pharmacologically distinct receptors, beta 1 and beta 2, mediate the contractile effects of catecholamines in a similar manner. The biologic signal produced by the occupancy of beta-adrenergic receptors by catecholamine agonists is transduced, amplified, and regulated by a family of guanine nucleotide-binding proteins (G proteins), which serve both stimulatory and inhibitory functions. Although the major biochemical effector of beta-adrenergic receptors is the enzyme protein--coupled directly to ion channels that regulate inotropic and electrophysiological effects. In human ventricular myocardium, heart failure produces changes in the beta-adrenergic receptor pathways that have the collective effect of reducing the degree of inotropic stimulation that may be produced by a given amount of beta-agonist. These changes include downregulation of beta 1-adrenergic receptors, uncoupling of beta 2-adrenergic receptors, and an increase in the functional activity of the inhibitory G protein. These effects in turn are probably caused by exposure to increased amounts of neurotransmitter resulting from a complex series of changes in the cardiac sympathetic nervous system. Finally, the components of the beta-receptor-G protein system may be both acutely and chronically modulated by certain kinds of pharmacological therapy. These observations underscore the importance of the adrenergic nervous system in heart failure, and they create the potential for the development of new interventional strategies designed to alter the natural history of heart muscle disease and heart failure.

Adenylyl Cyclases↗
PubMed1989

The beta-adrenergic receptor-adenylate cyclase complex as a target for therapeutic intervention in heart failure.

In the human heart the beta-adrenergic pathways are the primary means of increasing cardiac performance in response to acute or chronic stress. Control of beta pathway function is achieved by changes in the receptors themselves, and to a lesser degree by adjustments in the inhibitory G protein (Gi). In heart failure myocardial beta-receptor function is substantially reduced, but the beta-receptor pathways are so powerful that they remain capable of supporting inotropic function. Certain therapeutic interventions that improve exercise performance in heart failure can partially restore beta-receptor pathway function to normal; these interventions include beta-blocker therapy and treatment with angiotensin converting enzyme inhibitors. Other types of therapy, such as chronic administration of beta-adrenergic agonists, may produce undesirable effects by increasing beta-receptor subsensitivity; however, the effects of beta-agonists on beta-receptor function are somewhat unpredictable and certain beta-agonists do not appear to produce much desensitization. Finally, the failing human heart is in effect partially denervated due to depletion of neuronal norepinephrine, and consequently in advanced heart failure beta-agonists that possess an indirect component of action will be less effective than exclusively direct-acting agents. These observations indicate that the baseline status and the intervention-associated behaviour of the human myocardial beta-adrenergic receptor systems need to be considered in developing therapeutic strategies in congestive heart failure.

Adenylyl Cyclases↗
PubMed1989

Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium.

Prenalterol (beta 1-agonist), denopamine (beta 1-agonist), and zinterol (beta 2-agonist) were partial agonists of adenylate cyclase (AC) stimulation in human ventricular myocardium obtained from nonfailing chambers whose beta 1/beta 2 receptor subtype ratio was approximately 80/20. At a concentration less than its low affinity (beta 2) Kl, betaxolol, a highly selective beta 1-antagonist, inhibited isoproterenol (non-selective agonist), denopamine, and prenalterol stimulation of AC, indicating that isoproterenol, denopamine, and prenalterol are all capable of stimulating AC through beta 1-receptor activation. At a concentration less than its low affinity (beta 1) Kl, ICI 118,551, a highly selective beta 2-agonist, inhibited both isoproterenol and zinterol stimulation of AC, indicating that isoproterenol and zinterol stimulate AC through beta 2-receptors. Zinterol stimulation of AC was mediated entirely by beta 2-receptors, inasmuch as 10(-7) M betaxolol had no effect on the zinterol dose-response curve and ICI 118,551 produced a degree of blockade (KB = 5.2 +/- 1.6 X 10(-9) M), consistent with the beta 2-receptor Kl of the latter (2.0 +/- .4 X 10(-9) M, p, not significant). In nonfailing myocardium, analysis of beta 1 versus beta 2 stimulation by the nonselective agonist isoproterenol revealed that the numerically small (19% of the total) beta 2 fraction accounted for the majority of the total adenylate cyclase stimulation. In failing ventricular chambers with a beta 1/beta 2 receptor subtype ratio reduced from 82/19 (nonfailing) to 64/36 (p less than 0.001) and a beta 1-receptor density reduced by 61% (p less than 0.001), maximal denopamine stimulation was reduced by 49% (p less than 0.001). Moreover, in preparations from failing heart, the component of denopamine stimulation that was inhibited by 10(-7) M betaxolol (beta 1 component) was reduced by 77% (p less than 0.05). Finally, in preparations derived from failing ventricular myocardium, beta 2-receptor density was not significantly decreased, but zinterol stimulation of AC was reduced by 32% (p less than 0.05). We conclude that heart failure results in subsensitivity to both selective beta 1 and beta 2 stimulation of adenylate cyclase, with beta 1 subsensitivity due to selective beta 1 receptor down-regulation and beta 2 subsensitivity due to partial uncoupling of beta 2 receptors from subsequent events in the beta 2-adrenergic pathway.

Adenylyl Cyclases↗
PubMed1988

Preservation of the ischemic canine myocardium: a comparison of hypothermia, lidoflazine, and ketanserin.

The purpose of this study was to determine whether ketanserin protects the globally ischemic canine heart and whether such protection, if present, is independent of that provided by hypothermia or calcium channel blockade with lidoflazine. Forty mongrel dogs, anesthetized with halothane, were divided into eight groups of five and subjected to one hour of global myocardial ischemia during hypothermic (30 degrees C; groups 1 to 4) or normothermic (37 degrees C; groups 5 to 8) cardiopulmonary bypass (CPB). Dogs in groups 1 and 5 served as controls with respect to prebypass myocardial protective therapy, and received only placebo (a normal saline bolus) prior to CPB. Before bypass, dogs in groups 2 and 6 received lidoflazine, 1.25 mg/kg intravenously (IV); those in groups 3 and 7 received ketanserin, 5 mg IV bolus, followed by a continuous infusion at 33 microg/min during bypass. Animals in groups 4 and 8 were given both lidoflazine and ketanserin according to the dosing schedules above. No type of pharmacologic or mechanical cardiovascular support was provided after termination of CPB. Postbypass hemodynamic performance and survival of the unsupported animal were assumed to reflect the degree of myocardial protection during CPB. One minute after bypass, mean arterial pressure and cardiac output were decreased in all groups. Cardiac output was lower in groups 5 to 8 (normothermic CPB) than in groups 1 to 4 (hypothermic CPB). After CPB, left ventricular filling pressures were elevated in all groups kept normothermic and in group 3 (hypothermic CPB plus ketanserin). By 15 minutes after CPB, there were no survivors in groups 5, 7, and 8. Sixty percent of animals in group 6 (normothermic CPB plus lidoflazine) survived to the end of the study. Relative odds of survival were increased 110-fold by hypothermia and sevenfold by lidoflazine. Conversely, treatment with ketanserin was associated with an increased likelihood of nonsurvival. It is concluded that, at the doses studied, ketanserin does not protect the canine myocardium against ischemic injury and may exert a detrimental effect when combined with calcium channel blockade in this setting.

Animals↗
PubMed1988

Hyperkalemia after dantrolene and verapamil-dantrolene administration in dogs.

The concurrent administration of dantrolene and verapamil has the theoretical advantage of being more efficacious than dantrolene alone in the treatment of malignant hyperthermia. However, the combination has been reported to cause fatal hyperkalemia in pigs. The present study evaluated the serum concentrations of cations, serum osmolarity, and cardiovascular responses in 20 mongrel dogs after dantrolene with and without the concurrent administration of verapamil. The dogs were randomly classified into four groups of five dogs each: group 1 received neither dantrolene nor verapamil; group 2 received three successive intravenous doses of dantrolene (1, 3, and 6 mg/kg) at 30-minute intervals; group 3 received verapamil 0.1 mg/kg IV bolus, followed by a continuous infusion of 5 micrograms.kg-1.hr-1; and group 4 received verapamil as in group 3, followed by dantrolene as in group 2. Measurements were made at 15-minute intervals for 2 1/2 hours. Progressive and similar statistically significant increases in mean serum potassium occurred after 105 minutes in dogs given dantrolene (group 2, mean peak serum potassium levels 5.4 +/- 0.5 mmol/L) and after 90 minutes in dogs given verapamil-dantrolene (group 4, 5.2 +/- 1.6 mmol/L). A statistically significant decrease in serum sodium levels was also found in groups 2 and 4. One dog in group 4 developed intermittent second-degree heart block after the final dose of dantrolene. Serum calcium levels (ionized and total) tended to decrease in groups 2 and 4. There were no statistically significant differences in osmolarities, cardiac outputs, or mean arterial blood pressures among groups. In summary, significant elevations of serum potassium were observed in this dog model given dantrolene with and without verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Is fentanyl an anesthetic in the dog?

The authors used the absence of vocalization and movement during application of a hemostat clamped to the first ratchet at the base of the tail as an indication of anesthesia for evaluation of the anesthetic properties of fentanyl in the dog. Eighty-six unpremedicated, unrestrained, untrained mongrel dogs were given one of eight doses of fentanyl citrate (125, 250, 500, 750, 1000, 1500, 2000, and 3000 micrograms/kg) as a single intravenous bolus injection. Dogs breathed spontaneously without oxygen supplementation. Anesthesia was assessed every 5 min until absence of anesthesia was recorded for two consecutive evaluations. Venous plasma samples were obtained in two or three dogs receiving each of the doses of fentanyl 5 min after fentanyl injection and again when application of the tail clamp elicited either vocalization or movement (positive response). Fentanyl resulted in recumbency in all animals except two receiving 125 micrograms/kg. Although all doses of fentanyl produced anesthesia in at least one animal 5 min after injection, the duration of anesthesia was short, responses unpredictable, and anesthesia achieved in all animals only with a dose of 3000 micrograms/kg. Increasing doses of fentanyl resulted in higher plasma fentanyl concentrations 5 min after injection and at the time of the first positive response to tail clamp but there was great variability. All doses of fentanyl caused statistically significant decreases in heart and respiratory rates but none produced apnea or a PaCO2 higher than 67 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1983

Ketanserin prevents platelet aggregation and endotoxin-induced pulmonary vasoconstriction.

Pulmonary hypertension secondary to sepsis is due, in part, to release of serotonin from platelets. This study examines the effects of ketanserin, a new, highly specific serotonin antagonist, on platelet aggregation and the cardiovascular changes associated with bacterial endotoxemia in dogs. Ketanserin markedly inhibits in vitro platelet aggregation induced by mixing serotonin and epinephrine. When ketanserin is administered to animals before endotoxin infusion, cardiac output is greater and mean pulmonary artery pressure (MPAP), pulmonary and systemic vascular resistance (PVR and SVR) and arteriovenous oxygen content difference [C(a-v)O2] are less than in animals not receiving ketanserin. Similar results for PVR, SVR, and C(a-v)O2 are obtained when ketanserin is administered after endotoxin infusion. The data indicate that ketanserin inhibits serotonin-induced platelet aggregation and modifies many cardiovascular changes associated with bacterial endotoxemia.

Animals↗
PubMed1983

The effect of ketanserin, a specific serotonin antagonist, on burn shock hemodynamic parameters in a porcine burn model.

A number of vasoactive substances, including serotonin, have been implicated in the pathophysiology of burn shock. Ketanserin, a specific serotonin antagonist, was investigated in a porcine burn shock model. Fifteen swine were given a mean 44% total body surface area full-thickness scald burn and received fluid resuscitation with Ringer's lactate for 24 hours postburn. The swine were divided into three groups: Group I (control group) received no ketanserin; Group II received ketanserin as a single intramuscular dose preburn and continuously via intravenous drip postburn; and Group III received ketanserin continuously via intravenous drip postburn only. The ketanserin-treated groups demonstrated improved cardiac index, decreased pulmonary artery pressures, and smaller arteriovenous oxygen content differences compared to the control group in the early postburn period. Ketanserin should be investigated further as a possible adjunctive therapeutic agent during burn shock resuscitation.

Animals↗
PubMed1983

Cardiovascular responses to asphyxial challenge in chronically hypokalemic dogs.

To study the physiological tolerance to asphyxia and hypokalemia during anesthesia, the cardiovascular responses to clamping of the endotracheal tube during mechanical ventilation were evaluated in ten anesthetized mongrel dogs before and after they had been made hypokalemic by administration of furosemide, 10 mg X kg-1 X day-1 for 3-4 weeks. Furosemide reduced the serum potassium to 2.93 +/- 0.03 from 4.16 +/- 0.07 mEq/L. The animals were anesthetized with halothane in N2O-O2 (60/40) and mechanically ventilated to a PaCO2 of approximately 30 torr during continuous monitoring of heart rate, mean arterial pressure, ECG, and periodic determinations of serum electrolyte levels and arterial blood-gas tensions. The endpoint for unclamping of the endotracheal tube and reestablishing ventilation of the lungs was when mean arterial pressure decreased to levels present before clamping the trachea, approximately 100 torr, after an initial response of hypertension and tachycardia. The duration of clamping was not significantly different in normokalemic (8.41 +/- 1.47 min) and hypokalemic (9.01 +/- 0.47 min) dogs, but the time required to regain circulatory stability and normal ECG rhythm was longer for the hypokalemic group (2.95 +/- 0.44 min vs 2.17 +/- 0.47). In addition, while all normokalemic dogs survived, three of the hypokalemic dogs could not be resuscitated. The results suggest that chronic hypokalemia reduces the tolerance of the cardiovascular system to severe physiologic trespass.

Anesthesia, General↗
PubMed1982

Epinephrine-induced arrhythmias during halothane anesthesia with the addition of nitrous oxide, nitrogen, or helium in dogs.

The arrhythmogenicity of epinephrine was examined in 34 male mongrel dogs awake and during 1.1 MAC steady state halothane-O2 anesthesia with the addition of 50% N2O, nitrogen, or helium. All anesthetized dogs required more epinephrine than did awake dogs to produce ventricular extrasystoles. Dogs given halothane-N2O were more sensitive to the epinephrine infusion than those given halothane-nitrogen or halothane-helium. The dogs given halothane-N2O also showed a small, but statistically significant difference from dogs given halothane-O2. These results suggest that the addition of N2O to halothane increases the cardiac arrhythmic potential of epinephrine in the dog.

Animals↗
PubMedDate not supplied

Single neurons with both form/color differential responses and saccade-related responses in the nonretinotopic pulvinar of the behaving macaque monkey.

The nonretinotopic portion of the macaque pulvinar complex is interconnected with the occipitoparietal and occipitotemporal transcortical visual systems where information about the location and motion of a visual object or its form and color are modulated by eye movements and attention. We recorded from single cells in and about the border of the dorsal portion of the lateral pulvinar and the adjacent medial pulvinar of awake behaving Macaca mulatta in order to determine how the properties of these two functionally dichotomous cortical systems were represented. We found a class of pulvinar neurons that responded differentially to ten different patterns or broadband wavelengths (colors). Thirty-four percent of cells tested responded to the presentation of at least one of the pattern or color stimuli. These cells often discharged to several of the patterns or colors, but responded best to only one or two of them, and 86% were found to have statistically significant pattern and/or color preferences. Pattern/color preferential cells had an average latency of 79.1 +/- 46.0 ms (range 31-186 ms), responding well before most inferotemporal cortical cell responses. Visually guided and memory-guided saccade tasks showed that 58% of pattern/color preferential cells also had saccade-related properties, e.g. directional presaccadic and postsaccadic discharges, and inhibition of activity during the saccade. In the pulvinar, the mean presacadic response latency was earlier, and the mean postsaccadic response latency was later, than those reported for parietal cortex. We also discovered that the strength of response to patterns or colors changed depending upon the behavioral setting. In comparison to trials in which the monkey fixated dead ahead during passive presentations of pattern and color stimuli, 92% of the cells showed attenuated responses to the same passive presentation of patterns and colors during fixation when these trials were interleaved with trials which also required active saccades to pattern and color targets in the periphery. We conclude that properties which represent the functionally dichotomous object and spatial visual systems are found together in single pulvinar neurons and that the responses of these cells to pattern or color stimuli are influenced by the focus of spatial attention. The pulvinar is the first structure in the brain shown to have neurons which integrate both object and spatial properties and the response latencies indicate that this information is processed before that in cortex. These results are discussed in terms of role of the pulvinar in visual attention as well as its unique role in providing both object feature and spatial location information to the inferotemporal cortex.

Animals↗
PubMedDate not supplied

Quantification and minimization of magnetic susceptibility artifacts on GRE images.

PURPOSE: The purpose of this work was to determine the optimal imaging parameters for minimization of metallic susceptibility artifacts during gradient echo (GRE) imaging. METHOD: We performed GRE imaging of titanium screws in a nickel-doped agarose gel phantom, systematically varying several parameters to characterize and quantify susceptibility artifacts. RESULTS: The greatest reduction in artifact size came from using a short TE; increasing the frequency matrix and decreasing the slice thickness also contributed substantially to reducing the artifact size. Whenever possible, implanted prostheses should be aligned with the main magnetic field to minimize artifact size. Parameters with negligible effect on artifact size included bandwidth, phase encode matrix, and field of view. CONCLUSION: Radiologists can easily adjust the above parameters in their imaging protocols to improve GRE image quality in patients with implanted metallic devices.

Artifacts↗
PubMedDate not supplied

Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction.

Several cerebral pathologic processes thought to result from derangements in vascular autoregulatory mechanisms show reversible abnormalities on computed tomographic and magnetic resonance images. The hypertensive encephalopathies are characterized by intracranial abnormalities due to subacutely elevated blood pressure; these entities include hypertensive encephalopathy, preeclampsia and eclampsia, and cyclosporine toxicity. Imaging studies reveal symmetric confluent lesions with mild mass effect and patchy enhancement centered in the immediate subcortical white matter of the occipital lobes. The uremic encephalopathies are characterized by intracranial abnormalities due to an elevated level of blood urea nitrogen; these entities include uremia and glomerulonephritis, hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura. Imaging studies reveal multiple areas of symmetric edema in the basal ganglia; in severe cases, focal infarcts with or without hemorrhage can be seen. As radiologists become more familiar with these entities, cases can be recognized earlier in the disease process, allowing more timely initiation of appropriate therapy.

Adult↗
PubMedDate not supplied

Coronary risk factor behavior change in hospital personnel following a screening program.

We conducted a worksite cardiovascular disease (CVD) awareness and education program at a large medical center. The program consisted of employee screening for blood pressure and total serum cholesterol level, dissemination of information on risk factors for CVD, counseling on behavior change, and evaluation of the screening event as an educational tool. During this five-day event, 2,284 employees were screened for hypertension and hypercholesterolemia. Consenting employees completed a health risk appraisal survey (n = 2,255) and received counseling on their results and CVD risk factors. Appropriate referrals to health care professionals and educational programs were made according to national guidelines. We developed three-month and six-month follow-up surveys and distributed them to all participating employees. The analysis of these data suggests some positive impact upon behavior change within this employee population. In addition to the two follow-up surveys, we held a second blood pressure and serum cholesterol screening eight months after the initial screening. Comparison of the levels taken from both screenings (n = 234) suggests that worksite screening programs may influence significant serum cholesterol and blood pressure reductions in high-risk employees.

Adult↗