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Biomedical subjects

D Ramage

Publications and source records attributed to D Ramage.

15 recordsLinked to original sources

Establishing an endovascular abdominal aortic program--decisions, decisions, decisions: The London Health Sciences Centre experience.

The endovascular repair of abdominal or thoracic aortic aneurysms is an alternative approach to conventional repair in the compromised patient. Although the long-term efficacy of these procedures has yet to be proved, there is growing interest among vascular surgeons and interventional radiologists throughout North America and Europe in the more frequent use of this technique. Starting an endovascular program necessitates extensive cooperation of the interdisciplinary vascular team. Decisions regarding patient selection, equipment, supplies, staff education, and the location of the procedure must be based on sound principles. This article demonstrates how a program can be planned, implemented, and evaluated by the use of a "decision tree." The experience of the London Health Sciences Centre will be used as a benchmark in the discussion of relative merits of branch points in program development. The article gives persons contemplating a program a structured process in decision making to avoid potential pitfalls.

Angioplasty↗

Leukocyte adhesion to the coronary microvasculature during ischemia and reperfusion in an in vivo canine model.

BACKGROUND: Prompt reperfusion of ischemic myocardium or myocardium that is in the process of becoming infarcted is a cornerstone of current therapy for coronary artery disease. Paradoxically, experimental evidence suggests that cardiac damage may be caused by the reperfusion itself. Leukocyte attachment to the coronary vascular endothelium during reperfusion may be an initiating step in this detrimental process. Leukocyte adhesion to microvascular endothelium has never been demonstrated directly in a cardiac model of ischemia and reperfusion. METHODS AND RESULTS: Fluorescent videomicroscopy through a special "floating" objective that allows a series of lenses to move in unison with the beating dog heart was used on the left ventricular surface of open-chest dogs. Epicardial microvessels (25 to 130 microm), in focus throughout the cardiac cycle, were recorded after infusion of acridine orange (to fluorescently label leukocytes) during either 1 hour of ischemia followed by 2 hours of reperfusion, 3 hours of ischemia, or 3 hours of no ischemia. The amount of net fluorescence recorded along microvessel walls, which represented leukocyte accumulation, significantly increased in dogs during reperfusion (n = 8) compared with the same time period in the animals that were kept ischemic (n=5) (21.0 +/- 3.8 versus 10.9 +/- 4.5 gray scale; P = .0001). The rapid increase in fluorescence during reperfusion was also significantly different from values in the same group during the preceding period of ischemia (21.0 +/- 3.8 versus 5.1 +/- 2.1 gray scale; P =.0001), whereas no significant increase was seen over the same time periods in the animals that remained ischemic throughout the protocol. CONCLUSIONS: Reperfusion, compared with ischemia alone, promotes the rapid accumulation of leukocytes in the coronary microvasculature of dogs.

Animals↗

Vasoactive intestinal peptide: electrophysiologic activity in the newborn heart.

We performed intracardiac electrophysiologic studies of the effects of vasoactive intestinal peptide (VIP, 0.125 micrograms/kg/min) on sinus and atrioventricular (AV) nodal function, intracardiac conduction, and myocardial refractoriness in two groups of neonatal dogs (aged 6-16 d). Group I consisted of eight neonates in whom VIP was administered after bilateral vagotomy and beta-blockade with propranolol. Group II consisted of five neonates studied after vagotomy and propranolol, plus total chemical sympathectomy (6-hydroxydopamine). In both groups, VIP resulted in a significant shortening of sinus cycle length. AV nodal conduction time, measured as the AH interval (the time from the onset of the atrial electrogram to the onset of the His bundle electrogram in the His electrode catheter) during atrial pacing, also shortened after VIP. His-Purkinje conduction time and atrial effective refractory periods were unchanged by VIP. In other experiments, the direct chronotropic effect of VIP was evaluated in five isolated neonatal canine hearts using a modified Langendorff technique. In these hearts, the spontaneous cycle length decreased from 403 +/- 88 to 293 +/- 69 ms, or -28 +/- 4% (mean +/- SD), after exposure to 0.1-0.5 nmol of VIP (p < 0.001). In nine other newborns (aged 4-16 days), the effect of selective alpha 1- and alpha 2-adrenergic receptor blockade on the positive chronotropic effect of VIP was evaluated. The effect of VIP on sinus cycle length was not altered by the alpha 1-adrenergic receptor blocker prazosin or by the alpha 2-adrenergic receptor blocker yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pituitary adenylate cyclase activating polypeptide: a neuropeptide with potent inotropic and coronary vasodilatory effects in neonatal pig hearts.

Cardiac effects of the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) have not previously been reported. We investigated the influence of PACAP, vasoactive intestinal polypeptide (68% homology with PACAP) and the beta-adrenergic receptor agonist isoproterenol on contractile function and coronary vascular tone in isolated piglet hearts (1 to 5 d of age). Paced (180 beats/min) isovolumically beating hearts underwent retrograde aortic perfusion at constant coronary flow (approximately 3 mL.min-1.g-1) with an erythrocyte-enriched (hematocrit 15 to 20%) solution (37 degrees C). Agonists were injected into the aortic root of hearts, and the positive (+) and negative (-) changes in maximum rate of change of systolic pressure with respect to time (dP/dtmax) and in coronary perfusion pressure (that reflected alterations in vascular tone) were measured. PACAP (n = 8, 0.1 and 0.5 nmol) increased (+) dP/dtmax from 944 +/- 59 to 1519 +/- 206 mm Hg/s and from 867 +/- 40 to 2010 +/- 226 mm Hg/s (p < 0.05); increased (-) dP/dtmax from 1114 +/- 41 to 1439 +/- 95 mm Hg and from 999 +/- 37 to 1668 +/- 145 mm Hg/s (p < 0.05); and decreased perfusion pressure from 61.4 +/- 3.1 to 48.9 +/- 2.3 mm Hg and from 60.5 +/- 2.4 to 43.9 +/- 2.3 mm Hg (p < 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

Histochemical distribution of carbonic anhydrase in rat and rabbit lacrimal gland.

PURPOSE: The purpose of this study was to examine the histochemical distribution of carbonic anhydrase (CA) in lacrimal glands from rats and rabbits; and to determine if age- and/or sex-related differences exist in the amount and distribution of CA in the rat lacrimal gland. METHODS: Lacrimal glands from young (3-12 wk) and aged (2-2.5 yr), male and female F344 rats and male rabbits were fixed in 1% paraformaldehyde and embedded in glycolmethacrylate. CA histochemistry was performed on 2-microns sections. The distribution of CA activity was determined by morphometric analysis. RESULTS: In rat lacrimal gland, CA activity was distributed in a discontinuous, mosaic fashion among the acinar cells. In tissue from young males and females as well as from aged females, about 10% of the acinar tissue displayed CA activity. Significantly more activity was present in tissue from aged male rats. CA was present in the ductal lumina, suggesting that it is a secretory product of the acinar cells. In rabbits, CA activity was associated with the basolateral membranes of the terminal acinar cells only. CONCLUSIONS: In rat, the presence of CA activity in certain acinar cells and in ductal lumina suggests that CA is actively secreted by the lacrimal gland. An age-related increase in the amount of CA activity in the male glands exists that may be under gender-specific hormonal influences. In the rabbit lacrimal gland, the membrane-associated CA found uniquely with the terminal acinar cells suggests that these cells have special transport functions associated with the primary secretion of lacrimal fluid.

Animals↗

Acetylcholine-induced coronary vasoconstriction and negative inotropy in the neonatal pig heart.

We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP, bradykinin, and substance P on coronary vascular tone in isolated, neonatal pig hearts (less than or equal to 4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion, with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (approximately 2.5 mL/min/g) corresponding to a perfusion pressure of approximately 60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 microL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilation) by 16.9 +/- 1.2, 25.3 +/- 4.4, 18.3 +/- 1.2, 18.9 +/- 1.4, and 7.1 +/- 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 +/- 0.8 and 3.8 +/- 0.5 mm Hg, respectively, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pressure (vasoconstriction) by 16.7 +/- 2.7, 48.2 +/- 8.2, and 85.3 +/- 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pressure from 108.7 +/- 5.0 to 69.2 +/- 4.6, 56.3 +/- 6.1, and 48.2 +/- 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10(-6) M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87%, 66%, and 48%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

The effects of milrinone in the neonatal pig heart.

Milrinone, a selective inhibitor of phosphodiesterase (PDE), was examined in neonatal hearts and in ventricular myocytes. Isolated, paced (180 beats/min), isovolumically beating hearts from pigs, less than 3 days of age, were perfused with an erythrocyte-enriched solution. In one group (control, n = 6), milrinone was studied at perfusate concentrations of 1, 10, and 100 micrograms/ml. In a second group (postischemia, n = 10), hearts were subjected to 30 minutes of no-flow ischemic arrest, prior to the addition of milrinone. Left ventricular peak systolic pressure (PSP) and end-diastolic pressure, coronary flow (CF), heart rate (HR), and myocardial oxygen consumption (MVO2) were measured. The PSP averaged approximately 100 mmHg during the baseline periods for both groups and decreased to approximately 85 mmHg in those hearts subjected to ischemic arrest. In both groups, PSP increased approximately 14% at the 1 micrograms/ml concentration of milrinone. No additional increases in PSP were observed in the control group at the higher concentrations. However, PSP increased 28% and 41% (p less than 0.05), in the postischemia group at the 10 and 100 micrograms/ml concentrations, respectively. The CF averaged approximately 3 ml/min/g during the baseline periods of both groups and increased significantly at each milrinone concentration. The HR in both groups increased to approximately 200 and approximately 250 beats/min at the 10 and 100 micrograms/ml concentrations, respectively. Additionally, milrinone's effects in intact hearts were found to be comparable to those of isobutylmethyl xanthine (IBMX), a nonspecific PDE inhibitor. In isolated myocytes, however, milrinone produced only modest increases in cAMP levels, compared to IBMX.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

Platelet function after intramuscular diclofenac.

A randomised double-blind controlled study was performed to examine the effect of diclofenac on skin bleeding time and in vitro whole blood platelet aggregation. Twenty thoracotomy patients were studied; 10 were given diclofenac 75 mg intramuscularly at induction of anaesthesia, and 10 formed a control group. Skin bleeding times and platelet aggregation tests were performed the day before and repeated one hour after induction of anaesthesia. Diclofenac prolonged skin bleeding time and reduced platelet aggregation. There were no significant changes in the control group.

Adult↗

Mechanical function and fatty acid oxidation in the neonatal pig heart with ischemia and reperfusion.

We investigated mechanical function and exogenous fatty acid oxidation in neonatal pig hearts subjected to ischemia, followed by reperfusion. Isolated, isovolumically-beating hearts, from pigs 12 h to 2 days of age, were perfused with an erythrocyte-enriched (hematocrit approximately 15%) solution (37 degrees C). All hearts were studied for 30 min. with a perfusion pressure of 60 mmHg (pre-ischemia). One group of hearts (low-flow ischemia, N = 12) was then perfused for 30 min. with a perfusion pressure of approximately 12 mmHg. In the other group (no-flow ischemic arrest, N = 9), the perfusion pressure was zero for 30 min. Following ischemia in both groups, the perfusion pressure was restored to 60 mmHg for 40 min. (reperfusion). Pre-ischemia parameters for all hearts averaged: left ventricular peak systolic pressure, 99.0 +/- 2.0 mmHg; end diastolic pressure, 1.9 +/- 0.2 mmHg; coronary flow, 3.4 +/- 0.1 ml/min per g; myocardial oxygen consumption, 56.6 +/- 1.6 microliter/min per g and fatty acid oxidation, 33.4 +/- 1.4 nmol/min per g. During low-flow ischemia, hearts released lactate, and the corresponding parameters decreased to: 30.7 +/- 0.9 mmHg; 1.2 +/- 0.3 mmHg; 0.8 +/- 0.1 ml/min per g; 26.6 +/- 2.3 microliters/min per g and 12.9 +/- 1.1 nmol/min per g, respectively. Early in reperfusion in both groups, all parameters, except for fatty acid oxidation, exceeded pre-ischemia values, before recovering to near pre-ischemia values. Late in reperfusion, however, rates of fatty acid oxidation exceeded pre-ischemia rates by approximately 60%. Thus, the neonatal pig heart demonstrated similar recovery following 30 min of low-flow ischemia or no-flow ischemic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Importance of fatty acid oxidation in the neonatal pig heart with hypoxia and reoxygenation.

We investigated mechanical and metabolic responses in isolated, isovolumically-beating, pig hearts (n = 7), 12 h to 2 days of age; subjected to hypoxia followed by reoxygenation. Hearts were perfused with an erythrocyte-enriched (hematocrit approximately 15%) solution during 3 consecutive 30-min periods: pre-hypoxia, arterial perfusate [O2] = 7.6 +/- 0.2 vol% (PO2 approximately 270 torr); hypoxia, [O2] = 0.6 +/- 0.1 vol% (approximately 10% hemoglobin saturation) and reoxygenation. Prehypoxia parameters averaged: left ventricular peak systolic pressure, 107.1 +/- 2.9 mmHg and end-diastolic pressure, 0.9 +/- 0.3 mmHg; coronary flow, 2.8 +/- 0.2 ml/min per g; myocardial O2 consumption, 59.4 +/- 1.6 microliters/min per g and fatty acid oxidation, 37.1 +/ 1.1 nmol/min per g. Fatty acid oxidation was determined using [14C]palmitate. Early in hypoxia, coronary flow increased 3-4 fold but then decreased. Throughout hypoxia, hearts released lactate yet continued to oxidize fatty acids (45-50% of myocardial O2 consumption). By the end of the hypoxia period, hearts exhibited mechanical failure (peak systolic pressure approximately 55 mmHg and end-diastolic pressure approximately 19 mmHg). After 30 min of reoxygenation, peak systolic pressure recovered to 80.6 +/- 2.6 mmHg and end-diastolic pressure remained elevated at 6.1 +/- 1.9 mmHg. However, fatty acid oxidation rates were 90-95% above pre-hypoxia values. Thus, during 30 min of severe hypoxia neonatal pig hearts exhibited mechanical dysfunction, yet continued to oxidize exogenously supplied fatty acids. Moreover, fatty acid oxidation was enhanced during reoxygenation.

Animals↗