Artery Of Dogs Research Articles

Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis.

Angiogenic peptides like VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) have entered clinical trials for coronary artery disease. Attempts are being made to devise clinically relevant means of delivery and to effect site-specific delivery of these peptides to the cardiac tissue, in order to limit systemic side-effects. We characterized the response of the pericardium to delivery of a replication-deficient adenovirus carrying the cDNA for AdCMV.VEGF165, and assessed the effect of pericardial VEGF165 on myocardial collateral development in a canine model of progressive coronary occlusion. Ameroid constrictors were placed on the proximal left circumflex coronary artery of mongrel dogs. Ten days later, 6 x 10(9) pfu AdCMV.VEGF165 (n = 9). AdRSV.beta-gal (n = 9), or saline (n = 7) were injected through an indwelling pericardial catheter. Transfection efficiency was assessed by X-gal staining. Pericardial and serum VEGF levels were measured serially by ELISA. Maximal myocardial collateral perfusion was quantified with radiolabeled or fluorescent microspheres 28 days after treatment. In AdRSV.beta-gal-treated dogs, there was extensive beta-gal staining in the pericardium and epicardium, with minimal beta-gal staining in the mid-myocardium and endocardium. Pericardial delivery of AdCMV.VEGF165 resulted in sustained (8-14 day) pericardial transgene expression, with VEGF levels peaking 3 days after infection (> 200 ng/ml) and decreasing thereafter. There was no detectable increase in serum VEGF levels. Maximal collateral perfusion, a principal correlate of collateral development and angiogenesis, was equivalent in all groups. Adenoviral-mediated gene transfer is capable of inducing sustained VEGF165 expression in the pericardium; however, locally targeted pericardial VEGF delivery failed to improve myocardial collateral perfusion in this model.

The effects of recombinant tissue-type plasminogen activator (rt-PA) on canine cadaver lung transplantation.

The intrapulmonary thrombi that form after the cessation of circulation are thought to be one of the major causes of graft function failure. We evaluated the effect of recombinant tissue-type plasminogen activator (rt-PA) in a canine cadaver lung transplant model. Donor dogs were killed by the intravenous administration of pancuronium bromide without heparinization, and left for 2 h at room temperature. The donor lungs were then flushed with low potassium dextran glucose (LPDG) solution, being subjected to a total ischemic time of 3 h. Following left lung transplantation, the contralateral pulmonary artery of the recipient dogs was ligated. In group 1 (n = 6), chloride solution was administered from the main pulmonary artery for 90 min, commencing 15 min prior to reperfusion. In group 2 (n = 6), 2.5 microg/kg per min of rt-PA, and in group 3 (n = 6), 5.0 microg/kg per min of rt-PA, were continuously infused in the same manner as in group 1. Lung function, including arterial blood gases and pulmonary hemodynamics, was measured for 3 h. The side effects of rt-PA were evaluated by measuring the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, alpha2-plasmin inhibitor (alpha2-PI), plasminogen, and fibrin/fibrinogen degradation product (FDP). All of the animals in the three groups survived throughout the observation period. The group 3 animals had significantly better gas exchange than the group 1 animals, and the pulmonary hemodynamics were significantly better in the group 2 and 3 animals than in the group 1 animals. The FDP levels in the group 2 and 3 animals were significantly higher than those in the group 1 animals, while the PT and APTT were significantly prolonged in the group 3 animals. These findings led us to conclude that rt-PA improves early lung function, particularly pulmonary hemodynamics.

Levcromakalim decreases cytoplasmic Ca2+ and vascular tone in basilar artery of SAH model dogs.

We investigated the effects of levcromakalim, a K+ channel opener, on [Ca2+]i and the contractile force of basilar arteries obtained from normal dogs and subarachnoid hemorrhage (SAH) dogs. The responsiveness to serotonin was increased more in the SAH group than in the control group. Levcromakalim decreased the resting [Ca2+]i and force more profoundly than did a Ca2+ channel blocker, nicardipine, and these effects were more prominent in the SAH group than in the control group. Levcromakalim diminished the increases in [Ca2+]i and contractile force induced by serotonin more profoundly than nicardipine did, and these effects were equal in both groups. The effects of levcromakalim were not inhibited by iberiotoxin but were antagonized completely by glibenclamide. These results suggest that levcromakalim-induced opening of adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channels reduces [Ca2+]i more effectively than does nicardipine and that levcromakalim exerts the vasodilator effects under the condition in which large conductance Ca2+-activated K+ (BK) channels are blocked with iberiotoxin. Consequently, K+ channel openers like levcromakalim may be useful drug candidates to treat delayed cerebral vasospasm after SAH.

Vasorelaxing effects of atrial and brain natriuretic peptides on coronary circulation in heart failure.

Natriuretic peptide (NP) receptor has been postulated to be downregulated under a high concentration of atrial NP (ANP) in congestive heart failure (CHF), but limited information is available on how the vascular functional responsiveness to NPs is altered in coronary circulation during CHF. We assessed the relaxant effects of ANP, brain NP (BNP), and other vasodilators in isolated coronary arteries obtained from dogs with and without severe CHF induced by rapid right ventricular pacing. In CHF dogs, plasma ANP and cGMP concentrations were elevated compared with control dogs. In CHF arteries the relaxant effects of ANP and BNP (10(-8) and 10(-7) mol/l) were suppressed compared with control arteries. Nitroglycerin, nitric oxide, 8-bromo-cGMP, and beraprost sodium produced similar concentration-response curves in both arteries. The addition of 10(-7) mol/l ANP increased the level of tissue cGMP in control arteries, but not in CHF arteries. We conclude that there was a specific reduction in the relaxant effects of ANP and BNP in isolated coronary arteries in severe CHF dogs, which suggests the possibility of the downregulation of NP receptors coupled to guanylate cyclase.

Tranilast suppresses vascular chymase expression and neointima formation in balloon-injured dog carotid artery.

Activation of vascular chymase plays a major role in myointimal hypertrophy after vascular injury by augmenting the production of angiotensin (ANG) II. Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be downregulated by tranilast, a mast cell-stabilizing antiallergic agent. We have assessed inhibitory effects of tranilast on neointima formation after balloon injury in the carotid artery of dogs, which share a similar ANG II-forming chymase with humans, and further explored the pathophysiological significance of vascular chymase. Either tranilast (50 mg/kg BID) or vehicle was orally administered to beagles for 2 weeks before and 4 weeks after balloon injury. Four weeks after the injury, remarkable neointima was formed in the carotid arteries of vehicle-treated dogs. Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjured arteries. Angiotensin-converting enzyme (ACE) activity was slightly increased in the injured arteries, whereas ACE mRNA levels were not. Tranilast treatment completely prevented the increase in chymaselike activity, reduced the chymase mRNA levels by 43%, and decreased the carotid intima/media ratio by 63%. In vehicle-treated injured arteries, mast cell count in the adventitia showed a great increase, which was completely prevented by the tranilast treatment. Vascular ACE activity and mRNA levels were unaffected by tranilast. Tranilast suppressed chymase gene expression, which was specifically activated in the injured arteries, and prevented neointima formation. Suppression of the chymase-dependent ANG II-forming pathway may contribute to the beneficial effects of tranilast.

Ranolazine:an Antiischemic Drug with a Novel Mechanism of Action

It has been generally accepted that the primary mechanism of action of antianginal drugs is the improvement of the myocardial oxygen balance between supply and demand in the ischemic heart, by either an increase in coronary flow or a decrease in cardiac mechanical function, or both. Therefore, nitrates, b-adrenoceptor antagonists, and Ca channel blockers, which are thought to improve the myocardial oxygen balance through changes in hemodynamic parameters, have been widely used to treat patients with ischemic heart disease. Ranolazine (RS-43285) is a piperazine derivative developed by Syntex Laboratories (Edinburgh, UK). In 1987, Allely et al. (3) found that ranolazine attenuated metabolic derangements of the myocardium that were induced by the occlusion of the coronary artery in dogs. Subsequently, the antiischemic action of ranolazine has been demonstrated in both in vivo (2) and in vitro (14,23,24,45) animal studies. Clinical findings suggest that ranolazine is an orally active agent that is useful for therapy of angina pectoris (16,33, 54,59). Interestingly, the antiischemic (14,23,24,45) or antianginal action (16,33,53,59) of ranolazine can be produced without any detectable alterations in hemodynamics, and therefore the pharmacological property of ranolazine differes from that of nitrates, b-adrenoceptor antagonists, and Ca channel blockers. Recent studies have demonstrated that the cardioprotective action of ranolazine is associated with the modulation of the myocardial metabolism (15,45,46). Ranolazine may, therefore, belong to a new group of antiischemic drugs. In the present review, we outline the pharmacological profile of ranolazine and discuss the mechanism of the antiischemic (or antianginal) action of the drug. A preceding review has been published by McCormack et al. (46).

A canine model of chronic ischemic cardiomyopathy: characterization of regional flow-function relations.

The controversy regarding the mechanism(s) of left ventricular (LV) dysfunction in chronic coronary artery disease is, in part, related to the lack of an appropriate animal model for this condition. We have developed such a model by placing Ameroid constrictors on proximal portions of coronary arteries in dogs who were euthanized (mean of 6 wk) after the development of severe global LV dysfunction noted on two-dimensional echocardiography. The LV end-systolic size nearly doubled (P < 0.001) over the observation period, and the percent change in LV size from end diastole to end systole decreased by >50% (P < 0.001). Regional dysfunction was noted in 23 of 24 myocardial beds analyzed within regions showing no gross evidence of infarction. In 10 of these beds, severe dysfunction was noted without a decrease in radiolabeled microsphere-derived myocardial blood flow (MBF). In 13 myocardial beds, decrease in function was associated with a decrease in MBF (P < 0.001), with close coupling noted between percent wall thickening and MBF. In the beds that exhibited an ultimate decrease in MBF, the decrease in function preceded the decrease in MBF. In conclusion, we describe chronic LV dysfunction in a canine model of multivessel stenosis that closely mimics chronic ischemic LV dysfunction in humans. Whereas regional function is severely reduced in this model, MBF is varied in different segments and at different times during the observation period. These results provide new insights regarding flow-function relations in chronic ischemic LV dysfunction.

Relationship between coronary blood flow velocity waveform and transmural distribution of myocardial blood flow in coronary artery.

It is important to know the transmural distribution of myocardial blood flow in assessing the severity of ischemia in coronary heart disease. We analyzed the relation between phasic waveform of epicardial coronary flow velocity with a Doppler flow probe in the left anterior descending artery in dogs and regional myocardial blood flow using a colored microsphere technique. Time-velocity integral in an average of 5 cardiac cycles was measured as an index of coronary blood flow during diastole (TVId) and systole (TVIs). The diastolic fraction of coronary blood flow (%DF) was defined as TVId/(TVId + TVIs). Myocardial specimens were divided into inner (subendocardial), middle, and outer (subepicardial) layers, and the inner layer to outer layer myocardial blood flow ratio (endo/epi ratio) was used as an index of transmural distribution of myocardial perfusion. The mean endo/epi ratio and the mean %DF decreased as the pressure gradient increased. There was a moderate but significant correlation (r = 0.57) between the endo/epi ratio and the %DF. In conclusion, analysis of the phasic pattern of coronary blood flow velocity provides some information about the transmural distribution of blood flow in the myocardium. The %DF may be a useful index for evaluating subendocardial ischemia.

Changes of Incompletely Embolized Aneurysm with Tungsten Coils: An Experimental Study in Dogs

Purpose : To evaluate changes of residual aneurysms according to the size of aneurysmal neck andthrombogenicity of a tungsten coil after incomplete embolization of experimental lateral aneurysms. Materials andMethods : Eleven experimental lateral aneurysms with different aneurysmal neck size were created in the commoncarotid arteries of mongrel dogs. They were then divided into narrow-neck(n=3), wide-neck(n=6) and spontaneouslythrombosed control(n=2) groups. After confirmation of aneurysmal patency, incomplete embolizations of varyingdegrees (about 30% to near total occlusion) were performed using 5mm-diameter tungsten coils. Angiography wasperformed immediately before and after, and one and six weeks after embolizations. The size of residual aneurysmwas measured on each angiogram. After the last angiography, embolized aneurysms were excised and examined underlight and electron microscopes. Results : On angiograms obtained 6 weeks after embolization, all residual narrowneck aneurysms were completely occluded, whereas in those with a wide-neck, therre was either no change (n=4) or aslight increase in size(n=2). On light microscopy, all narrow-neck aneurysms showed total organized fibrosis whileall control aneurysms and half those with a wide neck showed unorganized thrombi. The embolized group showed ahigher degree of organization in the aneurysmal cavity than did the control group. Neointima formation was seen inall embolized aneurysms, but no aneurysm showed foreign body reaction. On electron microscopy, uniform thicknessof plasma coatings was noted on the surface of the tungsten coils. Conclusion : A wide-neck residual aneurysm maypersist or increase in size, while one with a narrow-neck can be thrombosed after incomplete embolization withtungsten coils in a lateral aneurym. Careful consideration might be necessary in the embolization of wide-neckaneurysms. With plasma coatings on its surface and organized fibrosis, tungsten coil can be an useful forembolization of an aneurysm.

Angiotensin II Type 1 Receptor Antagonist, TCV-116, Prevents Neointima Formation in Injured Arteries in the Dog

We investigated the effect of an angiotensin (Ang) II antagonist, (+/−)-1-(cyclohexyloxy-carbonyloxy)-ethyl 2-ethoxy-1-[[2-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116), on neointima formation in dog artery injured by a balloon catheter. Dogs were orally treated with 10 mg/kg TCV-116 or placebo twice a day for 5 weeks. After treatment with these drugs for 1 week, the right carotid artery was injured by a balloon catheter. The left carotid artery was regarded as the control. In the group treated with placebo, neointima formation in the injured arteries was observed. The activities of angiotensin converting enzyme (ACE) and chymase in the injured carotid arteries were increased 2.56- and 3.26-fold compared with those in the non-injured arteries, respectively. The neointimal area in dogs treated with placebo and TCV-116 were 0.51±0.07 and 0.21±0.07 mm2, respectively, and this difference was significant. In conclusion, an Ang II antagonist, TCV-116, prevented neointima formation by blocking the action of Ang II generated by both ACE and chymase in the injured arteries.

Diastolic Suction During Acute Coronary Occlusion

To the Editor: We congratulate Bell et al on the recent publication of their study1 that presents evidence indicating a decrease in forces responsible for diastolic suction during an acute occlusion of the left anterior descending coronary artery in dogs. Their experimental preparation is elegant, and we agree with their principal interpretation of their data: the acute loss of regional cardiac contractile function due to myocardial ischemia can result in a decrease in the mechanical generation and storage of elastic forces available to induce ventricular suction during early diastole. In our view, the authors’ introductory remark that “One determinant of filling that may be altered during coronary occlusion but has not previously been studied is the ability of the LV to fill by suction” is an incomplete representation of the literature. In a previous publication,2 we described in detail the form of intraventricular pressure gradients found in the normal canine left ventricle during early diastole. In that report, we argued that the pattern of these early diastolic pressure gradients could only be present in a structure that filled by the process of mechanical suction. In a follow-up to that study, we hypothesized …

Effect of platelet activation on coronary collateral blood flow.

The platelet products thromboxane A2 and serotonin have been shown to cause constriction of well-developed coronary collateral vessels. This study was performed to determine whether intravascular platelet activation produced with platelet activating factor (PAF) can cause a decrease in coronary collateral blood flow. Collateral vessel growth was induced by embolization of a hollow stainless steel plug into the left anterior descending coronary artery (LAD) of adult dogs. The animals were returned to the laboratory 3 to 6 weeks later for surgical instrumentation and measurement of collateral blood flow. Collateral flow was assessed by measuring retrograde blood flow from the cannulated collateral-dependent artery. PAF (10 nmol) was injected into the left main coronary artery to allow products of platelet activation to reach collateral vessels arising from the left coronary system. PAF caused a vasoconstrictor response, which became maximal 3 minutes after injection and resulted in a 40.3+/-7.4% decrease in retrograde blood flow (32.1+/-2.1 to 19.6+/-3.2 mL/min; P<0.05). By 15 minutes after the PAF injection, both retrograde blood flow and transcollateral resistance had returned to normal. After pretreatment with the thromboxane A2 receptor antagonist SQ30, 741, the vasoconstrictor response to PAF was abolished and, in contrast to the decrease in retrograde blood flow from PAF alone, a weak vasodilator effect was unmasked. PAF caused a decrease in coronary collateral blood flow. This vasoconstrictor response required the participation of thromboxane A2.

Interleukin-6 and development of vasospasm after subarachnoid haemorrhage.

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.

Endothelial sodding of the permaflow prosthetic coronary artery bypass conduit

Background. Experiments were designed to determine the feasibility of sodding an endothelial monolayer within the lumen of a prosthetic conduit applied to the canine coronary circulation. Methods. Autologous endothelial cells were sodded onto the luminal surface of the Permaflow conduit and immediately implanted to bypass the left circumflex coronary artery in adult mongrel dogs (n = 9). Unsodded Permaflow conduits were implanted as controls (n = 8). At 3 weeks, grafts were explanted and examined by scanning electron microscopy and immunostained for canine von Willebrand factor. Results. Sodded grafts contained a confluent endothelial cell layer devoid of adherent thrombus or platelets and stained positively for canine von Willebrand factor. Unsodded grafts contained no endothelium and retained adherent platelets, collagen, and fibrin. Effluent from sodded grafts stimulated with calcium ionophore A23187 caused a significantly greater relaxation of its bioassay ring than effluent from unsodded grafts (60% ± 21% versus 12% ± 5%; n = 8, p < 0.03). Conclusions. Sodding of endothelial cells onto a Permaflow coronary artery bypass graft results in a confluent, viable, nonthrombogenic, endothelial monolayer and releases vasodilator substances in response to calcium ionophore A23187. Endothelial sodding may optimize prosthetic grafts.

Novel vascular sealing device for closure of percutaneous vascular access sites.

To investigate the hemostatic capabilities of a novel vascular sealing device consisting of a balloon catheter and procoagulant, vascular sheaths were placed percutaneously in the femoral arteries of dogs. The sealing device was evaluated using the balloon catheter alone in six femoral arteries and with the addition of a procoagulant, in 21 femoral arteries. The balloon catheter alone was successfully deployed in six of six femoral arteries achieving immediate hemostasis. In a second study in which the procoagulant was delivered following balloon placement, the sealing device was successfully deployed and hemostasis was achieved in 20 of 21 attempts (95%) despite removal of the balloon catheter. In a subset of fully anticoagulated animals, hemostasis was achieved in the sealing device-treated arteries at 6.5+/-3.4 minutes, but in none of the controls (P < 0.001). This novel vascular sealing device successfully achieves rapid hemostasis in normal and anticoagulated dogs following percutaneous vascular procedures.

Arterial uptake of biodegradable nanoparticles for intravascular local drug delivery: Results with an acute dog model

Biodegradable nanoparticles (NP) with a spherical diameter ranging from 70 to 160 nm were investigated for potential usefulness for the local intraluminal therapy of restenosis, the disease process responsible for arterial reobstruction following angioplasty. NPs containing a water-insoluble anti-proliferative agent U-86983 (U-86, Pharmacia and Upjohn, Kalamazoo, MI) were formulated from oil–water emulsions using biodegradable polymers such as poly(lactic acid–co-glycolic acid) (PLGA), and specific additives after particle formation, to enhance arterial retention using either heparin, didodecylmethylammonium bromide (DMAB), or fibrinogen, or combinations. Femoral and carotid arteries of male mongrel dogs were isolated in situ, and were then subjected to a balloon angioplasty. A NP suspension of a predetermined concentration was then infused into the artery for various durations. This was followed by a 30 min restoration of blood flow through the vessel. The arterial segments were excised and analyzed for drug levels. From the drug loading of the NP and the drug levels in the artery, the quantity of nanoparticles retained was calculated and expressed as μg per 10 mg dry arteries. In general, repeated short infusions of nanoparticle suspension (15 s×4) were two-fold more effective in terms of higher arterial U-86 levels than a single prolonged infusion (60 s). A single 15 s infusion was not significantly different than a 60 s infusion on NP arterial uptake. NPs modified with either DMAB or fibrinogen had about 2.5-fold higher uptake levels compared to non-modified NPs (39.2±2.5 and 49.1±2.4 vs. 21.5±0.6, μg/10 mg mean±s.e., respectively). A comparably enhanced NP uptake was noted with a combined heparin/DMAB modification. Increasing the concentration of NP in infusate from 5 to 30 mg ml −1 significantly increased arterial NP uptake level (from 22.5±3.5 to 83.7±1.4 μg/10 mg). Thus, the results support the view that modified nanoparticles along with optimized infusion conditions could enhance arterial wall drug concentrations of agents to treat restenosis.

Regional peripheral vascular supply based on the superficial temporal artery in dogs and cats.

Cutaneous arterial blood supply to the temporal region was evaluated in 8 dogs and 8 cats. Subtraction radiography and angiography of the carotid and superficial temporal arteries were used in 4 dogs and 4 cats to determine arterial blood supply to the temporal region and frontalis muscle. A myocutaneous axial pattern flap based on the superficial temporal artery and frontalis muscle may be indicated for cosmetic reconstruction in dogs and cats following surgical resection of neoplastic lesions or traumatic wounds in the maxillofacial region. The frontalis muscle was identified as the thin subcutaneous continuation of the platysma muscle extending cranially and rostrally. Dissection of the temporal region in 4 dogs and 4 cats revealed the subcutaneous location of the superficial temporal artery as it continues rostrally from the caudal aspect of the zygomatic arch.

Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction.

Nitric oxide release from the endothelium plays an important role in regulation of vascular tone, inhibition of both platelet and leukocyte aggregation and adhesion, and inhibition of cell proliferation. These properties suggest that the level of NO production by the endothelium may play a pivotal role in the regulation of vascular disease. Analysis using mass spectrometry has revealed that NO is produced by NOS from the terminal guanidino nitrogen of the precursor amino acid L-arginine. Thus, utilization of L-arginine and conversion to NO may establish a regulatory site in the development of endothelial dysfunction. Endothelial dysfunction is characterized by defective endothelium-dependent relaxation, and some reviews regarding endothelial dysfunction in diabetes have been published. These reviews have focused on factors that might contribute to defective relaxation, some of which will not be addressed in detail in this review. The purpose of the present review is to summarize evidence that specifically supports either decreased NO production by diabetic vascular endothelium and/or impaired NO-mediated endothelium-dependent relaxation. Second, this review provides reasonable alternatives to explain some of the controversies in this research area. Third, since there is growing evidence that arginine appears to have some benefits for diabetes-associated abnormalities, this review summarizes the current state of knowledge of effects of acute and chronic administration of L-arginine on diabetesinduced endothelial dysfunction and discusses potential NOdependent and -independent mechanisms whereby therapeutic intervention with L-arginine might benefit the diabetic endothelium.

High-spatial-resolution and real-time medical imaging using a high-sensitivity HARPICON camera.

A HARPICON(TM) camera has been applied to a digital angiography system with fluorescent-screen optical-lens coupling. It uses avalanche multiplication in the photoconductive layer for high-sensitivity imaging. The limiting spatial resolutions in the 1050 scanning-line mode of the camera are about 30 and 50 micro m at input field sizes of 20 x 20 and 50 x 50 mm on the screen, respectively. For high-speed imaging, the 525 scanning-line mode at a rate of 60 images s(-1) can be selected. High-quality images of coronary arteries in dogs were obtained by intra-aortic coronary angiography and superselective coronary angiography using a single-energy X-ray above the iodine K-edge energy.

Intravenous Administration of the Glycoprotein IIb-IIIa Receptor Antagonist 7E3 Induces Reperfusion of an Acute Thrombotic Occlusion of the Canine Coronary Artery

The ability of the F(ab’) 2 fragment of the murine monoclonal antibody 7E3 directed against the platelet glycoprotein IIb-IIIa receptor complex, to cause reperfusion of a totally occluding coronary artery thrombus was examined alone and in combination with aspirin and heparin in a canine model of coronary artery thrombosis. A localized thrombus was produced in the left circumflex coronary artery in open-chest dogs by electrolytic injury of the endothelium. Intravenous administration of a single injection of 5.0 mg/kg aspirin and heparin (80 U/kg bolus plus 30 U/kg/hr×2hr) maintained vessel patency for approximately 101±15 minutes. After vessels had been completely occluded for 5 minutes (in the presence of aspirin+heparin), a single intravenous injection of saline (10 ml) or 0.8 mg/kg 7E3 was administered. Reperfusion was observed in all dogs (6 of 6) receiving 7E3; 4 of 6 dogs maintained vessel patency throughout the course of the 2 hour observation period. Activated partial thromboplastin and thrombin times were elevated 1.4 and 9 fold, respectively, in groups that received heparin. Template bleeding times were significantly elevated in the groups receiving 7E3. In the control group, 2 of 5 dogs reperfused briefly, however neither were patent at the end of the observation period. A third group of 4 dogs which did not receive the aspirin+heparin regimen was allowed to occlude and 5 minutes later received a single intravenous injection of 0.8 mg/kg 7E3. None of the 4 dogs in this group reperfused at any time during the study. There were no significant differences between groups in regards to hematological or hemodynamic measurements during the experiment. We concluded from these findings that the monoclonal antibody, 7E3 can promote the dissolution of friable coronary artery thrombi that evolve during standard anticoagulant and antiplatelet therapy.