Flow In Dogs Research Articles

Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.

Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim of the present study was to examine the effect of systemically administered bFGF on collateral blood flow and to assess its pharmacokinetics and potential side effects. Forty-seven dogs were subjected to progressive ameroid-induced occlusion of the LCx, an intervention known to induce the development of collateral vessels. In phase I of the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n = 10) or saline (n = 9) as a left atrial injection for 4 weeks. Relative collateral blood flow was assessed serially with radiolabeled microspheres in the conscious state during maximal coronary vasodilatation. Initiation of bFGF treatment was temporally associated with a marked acceleration of collateral development; however, collateral flow in control dogs improved toward the end of the study, approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the investigation was a three-armed study of extended duration to determine whether bFGF caused a sustained increase in collateral function. Dogs were randomized to receive bFGF 1.74 mg/d for 9 weeks (n = 7), bFGF 1.74 mg/d for 5 weeks followed by placebo for 4 weeks (n = 11), or placebo for 9 weeks (n = 10). Relative and absolute collateral blood flow were assessed serially with microspheres during maximal coronary vasodilatation. Between the 10th and 17th days after ameroid placement, bFGF-treated dogs exhibited marked improvement in collateral flow such that maximal collateral conductance exceeded that of controls by 24% at the 5-week crossover point. Final collateral conductance was similar in dogs receiving bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF administration was associated with a 21% increase in final collateral conductance as well as a 49% increase in collateral zone vascular density. Prolonged bFGF administration was also associated with a decrease in arterial pressure, moderate thrombocytopenia, and moderate, reversible anemia. Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.

Pulmonary arterial contribution to airway blood flow after lung transplantation in dogs.

Despite the improved success of lung transplantation, ischemia of the donor bronchus continues to be the most important factor influencing airway healing. Recent studies have shown that at the level of the mainstem bronchi the pulmonary contribution to the airway blood flow may be equivalent to or greater than the systemic contribution and could therefore assist early healing of the newly anastomosed bronchus and, in addition, might facilitate the improved healing associated with omentopexy. The aim of this study was to measure the pulmonary contribution to airway blood flow in dogs after allotransplantation of the left lung and to determine whether omentopexy might improve the healing process. Using the radioactive microsphere technique, we measured the pulmonary contribution to airway blood flow in 25 dogs 1 week after allotransplantation of the left lung. Half the dogs had an omental wrap around the anastomotic site. Results showed that pulmonary blood flow increased progressively from lower trachea to distal mainstem bronchus and supplied the left mainstem bronchus above as well as below the anastomotic site. Omentopexy did not increase flow or enhance healing.

Effect of peptide YY on intestinal and hepatic blood flow in dogs

Objective: To investigate the effect of peptide YY (PYY) on the flow of splanchnic blood and bile in dogs. Methods: Under general anaesthesia, the dogs received porcine PYY at doses of 100, 400, or 800 pmol/kg/h for 1.5 h. Blood flow was measured in the subserosa of the jejunum, ileum, and colon as well as in the liver, using the hydrogen gas clearance method, before, during, and after PYY infusion. Choledochal bile was collected and its volume measured. Results: Colonic blood flow was significantly inhibited by 100, 400, and 800 pmol/kg/h PYY compared with the pre-infusion levels (P < 0.05, P < 0.05, and P < 0.01, respectively). It was also inhibited by 800 pmol/kg/h PYY (P < 0.05) compared with the non-infusion group

Evaluation of the single-injection plasma disappearance of technetium-99m mercaptoacetyltriglycine method for determination of effective renal plasma flow in dogs with normal or abnormal renal function

Summary Effective renal plasma flow (erpf) was evaluated, using continuous-infusion p-aminohippurate clearance (clpah) and single-injection plasma clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3; clmag3) methods. Simultaneous clearance determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after renal failure was induced by administration of amphotericin B. Linear regression analysis was used to derive an equation to estimate erpf from clmag3 after the single iv injection. A Student’s t-test was used to compare pharmacokinetics between the dogs when they were healthy and when they were in renal failure. An F-test was used to determine the appropriate Student’s t-test. Results indicated that clmag3 correlated reasonably well (r = 0.83, P &lt; 0.0001) with erpf obtained from the clpah value. The volume of distribution and elimination of 99mTc-MAG3 decreased during renal failure. Although there was minimal binding of 99mTc-MAG3 to erythrocytes, it was significantly (P = 0.0008) lower during renal failure. Protein binding was not significantly different during renal failure. All dogs had signs of nausea and emesis at variable times after injection of 99mTc-MAG3. Determination of clmag3 after a single injection provides an adequate means to rapidly assess erpf in dogs. The technique could easily be performed in dogs with renal disease, thus providing valuable information regarding progression of naturally acquired renal failure.

Effects of vasopressin on regional cerebral blood flow in dogs

Vasopressin may regulate the regional cerebral blood flow (rCBF) via two balancing effects: increased flow from the vessels dilated by nitric oxide from the endothelium, and decreased flow from the vessels contracted by direct stimulation of smooth muscle. The effect on the rCBF in anesthetized dogs following the intracisternal or intraarterial administration of vasopressin was investigated by laser flowmetry with the device placed on the dura over the parietal cortex. The intracisternal injection of 1 nmol vasopressin significantly increased the rCBF to 145.3 ± 27.3% of base line. In contrast, the intravertebral arterial injection of vasopressin had no significant effect on the rCBF. This can be explained by a difference in the affected vasculature; mainly large vessels in the subarachnoid space vs. whole vascular system supplied by the vertebral artery. The intracisternal injection of 10 μmol of N G-monomethyl- l-arginine ( l-NMMA) reduced the rCBF; pretreatment with this agent significantly suppressed the elevation in rCBF induced by vasopressin. The intraarterial injection of l-NMMA reduced the rCBF more than its intracisternal administration. It also suppressed the rCBF induced by vasopressin.

Effects of aging and dietary protein intake on uninephrectomized geriatric dogs

Summary Thirty-one clinically normal Cocker Spaniels, Miniature Schnauzers, and Doberman Pinschers (28 female, 3 male) 7 to 8 years old were uninephrectomized (month −2) to increase the risk of renal damage associated with reduction of renal mass. Two diets, differing principally in protein concentration, were used to test the hypothesis that high dietary protein intake causes renal damage in aging dogs. For 2 months after uninephrectomy, all dogs were fed diet A (18% protein). After glomerular filtration rate (gfr) was measured (month 0), 16 dogs were assigned to group A and were fed diet A for an additional 48 months. The other 15 dogs were assigned to group B, and were fed diet B (34% protein) for the subsequent 48 months. At 6-month intervals, GFR and urine protein-to-creatinine ratio (UP/C) were determined. At 48 months, terminal studies were done, survivors were euthanatized, and tissues were examined. Of 16 dogs in group A, 10 survived, compared with 13 of 15 in group B. Among survivors, a significant difference in GFR was not found between groups A and B, and decrease in GFR was not evident with time in either group. At 48 months, oral administration of casein caused minor acute effects on GFR and renal plasma flow in dogs of groups A and B. The UP/C values increased significantly (P = 0.001) from baseline values, but the increase was not progressive. The UP/C values were not affected by diet. Some dogs in both groups developed UP/C &gt; 1.0. Morphologic studies performed on kidneys removed at -2 months (nephrectomy) and at 48 months (necropsy) revealed increased kidney weight in both groups at month 48, compared with month −2 (P = 0.003); at month 48, kidney weight change was significantly (P = 0.004) greater in group-B than in group-A dogs. Increased glomerular area at month 48, compared with month −2, was significantly (P = 0.000) related to time, but not to diet. Significant (P = 0.000) increase in glomerular mesangial matrix, interstitial fibrosis (P = 0.001), cell infiltration (P = 0.000), and lesions of the renal pelvis (P = 0.04) was observed between month −2 and month 48. Time, representing combined effects of uninephrectomy and aging, was the major factor responsible for the morphologic changes. Diet effects were significance (P = 0.008) for cell infiltration, but did not reach significance for mesangial matrix accumulation, fibrosis, or pelvic lesions. Kidney mineral analysis revealed no renal mineralization in either group between −2 and 48 months. Results indicated that GFR did not decrease with time during the geriatric peroid studied, but severity of renal lesions was increased. Effects of time and uninephrectomy, although not separable, were more important than those of dietary protein intake on progression of renal lesions.

Regional blood flow distribution in endotoxin-treated dogs: Modification by ibuprofen

Purpose: The aim of this study was to determine whether the improved hemodynamic profiles reported with cyclooxygenase inhibition during sepsis include improvements in tissue perfusion is unknown. Our hypothesis was that cyclooxygenase inhibition with ibuprofen will prevent the endotoxin-induced alterations in regional blood flow distribution from developing and/or restore the endotoxin-induced loss of responsiveness to intravascular volume expansion. Methods: We measured cardiac output, regional blood flow, and total systemic shunt flow in dogs using radiolabeled 15-μm microspheres. These parameters were assessed in control (N = 10) and endotoxin-treated animals (N = 7). Additional endotoxin-treated animals (N = 7) were also pretreated with ibuprofen. Results: Compared with controls, endotoxin-treated animals exhibited marked reductions in blood flow to most systemic organs that were not reversed with large, intravenous saline infusions lie, isotonic saline; 40 mL/kg; N = 4). By contrast, although ibuprofen pretreatment (12.5 mg/kg; N = 7) completely prevented the reductions in mean arterial pressure caused by endotoxin from occurring, it did little to prevent the development of endotoxin-induced alterations in regional blood flow distribution. Nonetheless, in contrast to the endotoxin-treated animals, there were significant increases in cardiac output and blood flow to several organs after saline infusion in the ibuprofen-pretreated animals. Conclusions: Cyclooxygenase inhibition with ibuprofen has few direct effects on regional blood flow distribution after endotoxin. However, cyclooxygenase inhibition with ibuprofen does attenuate the endotoxin-induced decrease in vascular responsiveness to intravenous saline infusion.

COMPARISON OF THREE METHODS FOR CALCULATING PORTAL BLOOD FLOW VELOCITY IN DOGS USING DUPLEX‐DOPPLER ULTRASONOGRAPHY

Measurement of portal blood flow in dogs using duplex‐Doppler ultrasonography has potential clinical utility for diagnosis of cirrhosis and portosystemic shunts. Three methods for calculating portal blood flow were compared to identify a consistent method with minimal potential for intraoperator variation. Sixteen unsedated, normal beagles had their mean portal blood flow velocity determined using three methods: method 1 used a small Doppler sample volume positioned over the center of the portal vein and manual selection of data points on the resulting velocity spectra, followed by arithmetic correction of the calculated maximum velocity to mean velocity using the factor 0.57; method 2 used a small centrally‐located Doppler sample volume and computed maximum flow determination, again corrected using the factor 0.57; method 3 used a large Doppler sample volume that overlapped the walls of the portal vein followed by computed mean blood flow velocity determination. The calculated mean (SD) portal blood flow velocity was 15.8 (1.8), 15.1 (1.4), and 14.7 (2.5) cm/s using methods 1–3, respectively. There was no significant difference between the results of the three methods; however, method 3 (uniform insonation) was easier to use and produced a higher amplitude Doppler signal and therefore represents a useful alternative to the peak flow methods.

Effects of systemic cooling and rewarming on the evoked spinal cord potentials and local spinal cord blood flow in dogs.

Changes in evoked spinal cord potential (ESCP) and in local spinal cord blood flow (local SCBF) were measured simultaneously in eight dogs in the course of systemic cooling and rewarming using a water mattress. PaCO2 was maintained at 35-40 mm Hg (temperature-uncorrected values) by adjusting ventilatory volume every 1 degree C change of esophageal temperature under N2O (60%)-O2-isoflurane (1.15%) anesthesia. Local SCBF and arterial blood pressure decreased and ESCP latencies increased linearly with the decrease in body temperature to 23-24 degrees C. The conductive ESCPs (non-synaptic components) showed temporary augmentation in amplitude before eventual decrease under cooling. These showed a tendency to return to the precooling baselines after the initiation of rewarming. These results demonstrate that conductive ESCPs could be available for intraoperative monitoring of spinal function under hypothermia down to 23-24 degrees C.

Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is angiogenic in vitro and in vivo. It has been hypothesized that VEGF plays a role in myocardial collateral formation; however, the effects of VEGF on collateral flow to ischemic myocardium are unknown. We studied the effect of VEGF on collateral blood flow in dogs subjected to gradual occlusion of the left circumflex coronary artery (LCx). Beginning 10 days after placement of an LCx-constricting device, VEGF 45 micrograms (n = 9) or saline (n = 12) was administered daily via an indwelling catheter in the distal LCx, at a point just beyond the occlusion. Treatment was maintained for 28 days. Collateral blood flow was determined with microspheres 7 days before treatment, immediately before treatment (day 0), and 7, 14, 21, and 28 days into the treatment period. Collateral blood flow was quantified during chromonar-induced maximal vasodilation and expressed as a collateral zone/normal zone (CZ/NZ) ratio. Treatment with VEGF was associated with a 40% increase in collateral blood flow (final CZ/NZ blood flow ratios of 0.49 +/- 0.06 and 0.35 +/- 0.02 in the VEGF-treated and control groups, respectively, P = .0037) as well as an 89% increase in the numerical density of intramyocardial distribution vessels (> 20 microns diameter) in the CZ (6.6 +/- 1.4 versus 3.5 +/- 0.7 vessels/mm2 in VEGF-treated and control dogs, respectively, P < .05). We conclude that intracoronary VEGF enhances the development of small coronary arteries supplying ischemic myocardium, resulting in marked augmentation of maximal collateral blood flow delivery. These results demonstrate the feasibility of pharmacological enhancement of collateral growth and suggest a new therapeutic approach for the treatment of myocardial ischemia.

Basic fibroblast growth factor enhances myocardial collateral flow in a canine model.

Basic fibroblast growth factor (FGF) is a multifunctional peptide that may play an integral role in angiogenesis associated with coronary collateral formation and myocardial infarct healing. We sought to determine the effects of exogenously administered basic FGF on collateral blood flow to ischemic myocardium. Ameroid constrictors were used to cause gradual occlusion of the left circumflex coronary artery in dogs. Basic FGF (110 micrograms, n = 9) or saline (n = 12) was given as a daily bolus injection directly into the collateral-dependent zone, beginning 10 days after placement of the Ameroid and continuing for 28 days. Collateral flow was assessed weekly as the ratio of collateral to normal zone (CZ/NZ) blood flow during maximal pharmacologically induced coronary vasodilation. The CZ/NZ increased in both treated and control dogs as a function of time; however, transmural collateral flow in basic FGF-treated dogs significantly exceeded that of control dogs by the second week of treatment. Final CZ/NZ blood flow ratios were 0.49 +/- 0.05 and 0.35 +/- 0.02 in the treated and control groups, respectively (means +/- SE, P = 0.0002). Treatment with basic FGF was also associated with significant increases in the numerical density of distribution vessels and endothelial cell DNA synthesis within the CZ. We also found that basic FGF had acute effects as a coronary vasodilator. Thus exogenous administration of basic FGF enhances maximal collateral blood flow in dogs with myocardial ischemia secondary to single-vessel coronary occlusion, an effect that is likely mediated through the direct angiogenic effects of the peptide, although its acute vasodilatory effects may also play a role.

Impaired endothelium-dependent vasodilatory responses in hindlimb blood flow in dogs with congestive heart failure.

The vasodilatory response is known to be diminished in chronic heart failure. In the present study, we used dogs with chronic heart failure to investigate whether endothelium-dependent vasodilation in the resistance vessels in the hindlimb is decreased in chronic heart failure, and if so, to determine if endothelium-derived relaxing factor (EDRF) is involved in the mechanism. We induced heart failure in dogs by continuous rapid ventricular pacing. Under anesthesia, an internal carotid artery-femoral artery bypass system was established and perfusion pressure to the femoral artery was kept constant. Changes in hindlimb blood flow in response to various concentrations of acetylcholine (ACh), adenosine 5'-diphosphate disodium salt (ADP) and nitroglycerin (NTG) were examined in dogs with and without heart failure. The vasoconstrictive responses to L-NG-monomethyl L-arginine monoacetate (L-NMMA) were also studied. In dogs with heart failure, vasodilatory responses to both of the endothelium-dependent vasodilators, ACh and ADP, were decreased, while there were no differences in the responses to the endothelium-independent vasodilator NTG. The vasoconstrictive response to L-NMMA was diminished in heart failure. Thus, endothelium-dependent vasodilation in hindlimb resistance vessels is impaired in dogs with congestive heart failure. This impairment may be related to diminished EDRF/NO production or release in these vessels.

Research and development of ozagrel, a highly selective inhibitor of TXA2 synthase

Highly selective inhibitors of thromboxane (TX) A2 synthase were noted as a therapeutic agent for ischemic heart diseases, thromboembolic disorders, cerebral circulatory disorders, and asthma. The 1-substituted imidazoles and beta-substituted pyridines showed high inhibitory potency on TXA2 synthase. The structure-activity relationships of the imidazole and pyridine derivatives as inhibitors of TXA2 synthase were investigated. Introduction of various substituents into the carboxy-bearing side chain of 1-(7-carboxyheptyl) imidazole and beta-(7-carboxyheptyl) pyridine was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum in the region of 8.5 to 10 A for the inhibitory potency on TXA2 synthase. Among the tested imidazole and pyridine derivatives, (E)-4-(1-imidazolylmethyl)cinnamic acid (44) and (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid (56) showed the highest potency (IC50 = 1.1 x 10(-8) and 3 x 10(-9) M). The inhibition by these derivatives was highly selective for TXA2 synthase, since other enzymes which are involved in the arachidonic acid cascade, such as fatty acid cyclooxygenase, 5-lipoxygenase, prostacyclin (PGI2) synthase, and PGE2 isomerase were not affected. On the basis of the results obtained from the pharmacological, physicochemical and toxicological studies on the two compounds (44 and 56), (E)-4-(1-imidazolylmethyl) cinnamic acid (44; OKY-046, ozagrel) was selected as the best compound of highly selective inhibitors of TXA2 synthase. The pharmacological properties of ozagrel are as follows. The inhibition of TXA2 synthase by ozagrel was more effective on human and rabbit enzymes than those of other species. Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2, in various isolated cells and tissues perhaps via accumulated PG endoperoxides resulted by the inhibition of TXA2 synthase. Such an increase in PGI2 production by ozagrel was also observed in various experimental animals. We obtained the suggestion that, by the reduction of TXA2 production and increment of PGI2 production, ozagrel inhibits the spasms of basilar artery and the decreases in regional cerebral blood flow in dogs which received autologous blood into cisterna magna, and inhibits the decreases in motor function and regional cerebral blood flow, and the formation of infarcted area in the animals of cerebral ischemic treatment. It was also suggested that ozagrel inhibits leukotriene-, platelet-activating factor-, and antigen-induced bronchoconstriction in guinea-pigs and inhibits the induction of airway hyperresponsiveness by various stimuli in several species of animals by both mechanisms. The summarized results of ADME, toxicological, and clinical studies were also described.

Influence of heparin and systemic lysis on coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary thrombosis

Objectives. We sought to evaluate whether anticoagulation by an intravenous heparin infusion prevents deterioration of coronary blood flow restored by the novel recombinant plasminogen activator BM 06.022, and to compare the effects of profound fibrinogenolysis with those of an intravenous bolus injection of heparinBackground. Recent clinical studies indicate that heparin appears to be effective in reducing reocclusion when combined with recombinant tissue-type plasminogen activator (rt-PA), but that heparin is associated with an increased bleeding incidence. Therefore, the need for heparin has to be critically evaluated in the development of BM 06.022.Methods. BM 06.022 is an unglycosylated variant of human tissue-type plasminogen activator. Thrombus formation in anesthetized open chest dogs was induced by electrical injury. Left circumflex coronary artery blood flow was monitored for 4 h using an electromagnetic flow probe. Twenty dogs were randomized to receive intravenous heparin (100 IU/kg bolus plus 100 IU/kg per h) in group B or saline solution in group A before an intravenous bolus injection of 200 KU/kg (=0.34 mg/kg) BM 06.022 1 h after thrombus formation. Another 14 dogs were randomized to receive a single intravenous bolus injection of 200 IU/kg heparin plus 200 kU/kg BM 06.022 in group D or saline solution plus 1,000 kU/kg BM 06.022 in group C.Results. In the absence of a systemic lytic state, heparin infusion prolonged (p < 0.05) the cumulative patency time (sum of time intervals during which the coronary artery was patent) to 204.3 ± 7.4 min (group B) compared with 34.6 ± 10.8 min with saline solution (group A), and increased (p < 0.05) the area under the curve for coronary blood flow versus time (AUCFlow) to 34.0 ± 3.4 ml · h · min−1compared with 7.7 ± 4.6 ml · h · min−1. Profound fibrinogenolysis after administration of 1,000 kU/kg BM 06.022 (group C) and a single intravenous heparin injection (group D) did not differ in their effects on the cumulative patency time (182 ± 30.3 vs. 177.5 ± 25.4 min) and AUCFlow(36.0 ± 10.3 vs. 30.5 ± 4.8 ml · h · min−1), but these values were improved (p < 0.05) compared with those obtained after administration of saline solution plus 200 kU/kg BM 06.022 (group A).Conclusions. In the absence of a systemic lytic state, intravenous heparin is required as an adjunct to BM 06.022 to maintain coronary blood flow in dogs.

Coronary blood flow in dogs: effect of person.

Experiments on dogs with electromagnetic flow probes implanted around a coronary artery and the ascending aorta indicate that the entry of a person into the experimental chamber can cause a remarkable increase in coronary blood flow. Heart rate usually increases considerably, blood pressure increases only slightly, while aortic blood flow increases at variable times before and after coronary blood flow. It is not yet clear whether these cardiovascular effects are due purely to "effect of person" or to conditioning, with the person as the signal for the momentary coronary occlusion (which the person subsequently accomplishes by manually closing a snare).

Vasodilator effect of pituitary adenylate cyclase activating polypeptide (PACAP) on femoral blood flow in dogs

The effect of PACAP, a new VIP-like neuropeptide, on femoral arterial blood flow was studied in anesthetized beagle dogs. Intra-arterial infusion of PACAP38, PACAP27 or VIP (0.25–25 pmol/kg) induced a dose-related increase in femoral blood flow. The dose-response curve for PACAP27 or PACAP38 was similar to that for VIP, but the response to PACAP38 at 25 pmol/kg was significantly less than the others. The vasodilator effect of PACAP38, however, lasted three to four times longer than that of PACAP27 or VIP. Vascular effects of PACAP38 and PACAP38(COOH) did not differ. PACAP(1–15), PACAP(10–20), PACAP(27–38), and PACAP(27–38)NH 2 had little effect on blood flow. Thus, PACAP38 and PACAP27 are potent VIP-like vasodilators of the femoral arterial bed in dogs; PACAP38, but not PACAP27, differs from VIP in its prolonged vasodilator effect.

Effects of systemic and topical nicotine on pulpal blood flow in dogs

It has been suggested that nicotine exerts cardiovascular effects which are similar to stimulation of the sympathoadrenal system. If this observation is true, nicotine administration would decrease pulpal blood flow and possible alter the pulpal response to injury. The purpose of this study was to measure pulpal blood flow in dogs using the radiolabelled microsphere method following topical or systemic administration of nicotine for 28 days. Thirteen dogs were divided into three groups. Group one received topical nicotine (8 mg nicotine/kg/day) combined with orabase which was applied in two equal doses to the mandibular anterior gingiva. Group two received systemic nicotine (2.5 mg/kg/day) delivered by osmotic pumps implanted subcutaneously in the back of each animals' neck. Group three were controls, and these animals received either topical orabase twice daily applied to the mandibular anterior gingiva or saline via osmotic pumps. Results indicated pulpal blood flow increased from Day 0 to Day 28 in both nicotine treated groups. Group one (topical nicotine) exhibited a mean increase in blood flow of 21.8 ml/min/100 g, while group two exhibited a mean increase of 50.1 ml/min/100 g. Group three, the control animals, exhibited a mean decrease in pulpal blood flow of 22.1 ml/min/100 g over the 28-day interval. These changes were not statistically significant (p > 0.05).

Contrast‐enhanced first pass myocardial perfusion imaging: Correlation between myocardial blood flow in dogs at rest and during hyperemia

The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180 degrees inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T1-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI.

Positron emission tomography in the study of acute radiation effects on renal blood flow in dogs.

Renal blood flow measurements have been carried out by means of positron emission tomography (PET) to facilitate the detection of radiation-induced injuries. The advantages of the method employed in animal experiments are described.

Abstract #34 — Effects of systemic and topical nicotine on pulpal blood flow in dogs

Abstract #34 — Effects of systemic and topical nicotine on pulpal blood flow in dogs