Association of polymorphonuclear leukocytes with sites of aortic catheter-induced injury in rabbits.

The kinetics of the association of polymorphonuclear leukocytes (PMNs) with arterial balloon catheter-induced injury have been examined. An average of 6 X 10(7) PMNs were isolated from 20 ml of blood and labelled with 111In-oxine for reinfusion into the donor rabbit. The cells remained viable as demonstrated by both in vitro and in vivo tests of cell function. The abdominal aorta of rabbits was denuded of endothelium and immediately, 24 h, or 5 weeks later, exposed to autologous radiolabelled PMNs for 1 h. The presence of PMNs at sites of denudation was demonstrated by detection of the radioactive label and was confirmed by light and electron microscopy after 24 h, but not at 5 weeks. Immediately following denudation radioactivity was 2.44 +/- 0.33 times control (P = 0.006); 2.52 +/- 0.18 at 24 h (P = 0.005); and 1.88 +/- 0.32 times control at 5 weeks (P = 0.045). The presence of PMNs, or their products, 5 weeks after denudation suggests a more complex role of PMNs and possibly a direct involvement in the long term changes resulting from arterial balloon catheter injury.

Correlation of clinical history with quantitative histology of lower extremity atheroma biopsies obtained with the Simpson atherectomy catheter.

The purpose of this study was to compare the histologic variability of atheromas resected from patients with various risk factors for vascular disease. Twenty-seven plaques obtained using the Simpson atherectomy catheter were studied. The results of this light and electron microscopic study indicate that patients with diabetes mellitus had increased numbers of smooth muscle cells in their plaques (P less than 0.05) and a trend toward denser, less fatty connective tissue matrix (P less than 0.07) when compared with non-diabetics, and that female diabetics had more smooth muscle cells in their plaques than male diabetics (P less than 0.05). The female patients, regardless of risk factors, had more smooth muscle cells in their plaques than male patients (P less than 0.004). Patients with poor distal runoff had more neovascularization of plaque (P less than 0.001). Tobacco use and age did not have statistically significant correlations with histologic patterns.

Histopathologic examination of material from angioplasty balloon catheters used in vivo in human coronary arteries.

Reports on vascular pathology post-PTCA in both human and animal coronary vessels have revealed medial and intimal cracks and tears, thrombus formation, platelet accumulation, and loss of endothelial cells. The extent and type of damage can currently be assessed in vivo at the macro level by means of coronary artery angiography. However, this technique cannot define vessel wall characteristics at the cellular level. Our hypothesis is that vessel wall material may adhere to the balloon and thus provide a source for coronary artery cytological investigation in vivo. Ten balloon catheters were evaluated to discern any material which was dislodged from the coronary artery and which remained attached to the balloon catheter or guide wire. Our results indicate that angioplasty catheter balloons frequently have adherent collagen, endothelial cells, organized thrombus, and plaque with obvious cholesterol clefts, that can be retrieved and examined histologically. We conclude that material is often dislodged from the plaque during PTCA. In addition, plaque material removed by the balloon catheter offers an unusual opportunity to analyze the morphologic characteristics of cells from the human coronary artery in vivo.

Accuracy of digital angiography for quantitation of normal coronary luminal segments in excised, perfused hearts.

The accuracy of coronary artery diameter determination by digital angiography was assessed by imaging 39 coronary segments of excised dog and human hearts and comparing these segments with pathologic sections 0.76 to 3.31 mm in luminal diameter. Digital images were obtained postmortem both during contrast injection using a fixed-pressure coronary perfusion system and after fixation when the coronary size was maintained by injection of a barium-gelatin casting mixture. Digital data were analyzed with commercially available, automated edge-detection software using a coronary catheter as the calibration standard. Coronary diameter measured during contrast injection was not significantly different from that measured after casting and fixation. Digital data from both methods correlated well with diameters from pathologic sections (injected, r = 0.85; fixed, r = 0.91). Linear regression parameters comparing pathologic diameters with the contrast injection method were slope = 0.82, intercept = 0.42 mm, and standard error of the estimate = 0.27 mm. Parameters for the comparison of pathology with casted coronary data were slope = 0.95, intercept = 0.16 mm, and standard error of the estimate = 0.23 mm. Intra- and interobserver variability were 3% (0.05 mm) and 4% (0.07 mm), respectively. These data indicate that when a coronary catheter as a calibration standard is used, coronary artery dimensions can be accurately measured by automated digital angiography techniques.

Sensitivity of a set of myocardial infarction screening criteria in patients with anatomically documented single and multiple infarcts.

A subset of 3 screening criteria (Q wave greater than or equal to 30 ms in lead aVF, any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV in lead V2, and R wave greater than or equal to 40 ms in V1) has been proposed to identify single nonacute myocardial infarcts. Cumulatively, these 3 criteria achieved 95% specificity, and 84 and 77% sensitivities for inferior and anterior myocardial infarcts, respectively, among patients identified by coronary angiography and left ventriculography. This study establishes the true sensitivities of the set of screening criteria in 71 patients with anatomically proven single myocardial infarcts and 32 patients with multiple myocardial infarcts. In the single inferior infarct group, the aVF criterion was 90% sensitive. The V2 criterion (any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV) was 67% sensitive in the single anterior infarct group. No single criterion proved sensitive in identifying a posterolateral infarct. The set of screening criteria performed just as well for multiple infarcts as it did for single infarcts, with a cumulative sensitivity of 72%. The overall sensitivity of the screening set in the 103 patients in all groups was 71%.

Correlation of the complete version of the Selvester QRS scoring system with quantitative anatomic findings for multiple left ventricular myocardial infarcts.

The correlation between myocardial infarct size estimated by the complete version of the Selvester QRS scoring system and that documented by pathoanatomic studies has been reported for single anterior, inferior and posterolateral infarcts. Although previous studies described electrocardiographic changes in patients with multiple infarcts, no quantitative documentation of the ability of such changes to estimate the total amount of left ventricular infarction has been reported. This study of 32 patients with anatomically documented multiple infarcts shows a significant correlation between QRS-estimated and anatomically documented sizes (r = 0.44; p = 0.01), which is less than that previously reported for single infarcts in the anterior, inferior and posterolateral locations. Several of the 54 electrocardiographic criteria were never satisfied. Criteria for posterior infarction were seldom present, suggesting "cancellation effect" of coexisting anterior infarction. These results will be the basis for future modification of QRS criteria for estimating myocardial infarct size.

Effects of distention and short-term grafting on vasoreactivity in rabbit external jugular veins.

The relative effects of distention, intraluminal pressure, and wall tension on venous smooth muscle and endothelial cell function were examined in 40 external jugular veins from New Zealand white rabbits. Vein grafts (n = 5) were interposed in the common carotid artery and explanted after 10 minutes. Distended veins were inflated in vitro with modified Krebs' solution at 37 degrees C for 10 minutes at pressures of either 20 mm Hg (D-20; n = 5) or 80 mm Hg (D-80; n = 5). Externally supported veins (ES-80; n = 5) were inflated at 80 mm Hg pressure, but distention was prevented by covering with a 3 mm internal diameter polytetrafluoroethylene sleeve. Bradykinin-induced in vitro maximal tension was attenuated significantly in vein grafts (0.13 +/- 0.04 g) and D-80 rings (0.27 +/- 0.07 g) compared with D-20 rings (1.20 +/- 0.14 g), ES-80 rings (0.99 +/- 0.13 g), or nondistended control rings (n = 40; 1.19 +/- 0.10 g; p less than 0.001). The attenuation in contraction in the vein graft and D-80 groups was nonspecific (i.e., similar results were obtained with respect to other smooth muscle agonists). Contractile function was inversely associated with wall tension, the product of pressure and radius (r2 = 0.7438; p = 0.06). In contrast, there were no differences in endothelium-dependent or endothelium-independent relaxation among the five groups. It is concluded that, in this experimental system, (1) venous smooth muscle function is significantly attenuated after short-term in vitro distention or grafting although endothelial function is largely preserved, and (2) the decrement in contraction is due to elevated wall tension.

Norepinephrine-induced vasoconstriction is increased in intimal hyperplastic arteries of the dog.

Norepinephrine-induced arterial contraction in vitro is known to be increased after endothelial denudation and during the subsequent development of intimal hyperplasia. We now report the response to norepinephrine in intimal-thickened iliac vessels in conscious dogs. Seven dogs underwent balloon catheter deendothelialization of the right iliac artery. Three weeks later, ultrasonic transducers were implanted on both iliac arteries to record dynamic vessel dimension. A catheter was inserted into the terminal abdominal aorta for drug infusion and blood pressure monitoring. The dogs were studied unsedated 2 days after instrumentation. Norepinephrine was infused at doses that did not affect blood pressure (0.01 to 0.05 micrograms/kg/min). Control vessel diameter decreased from 5.2 mm +/- 0.3 to 5.1 mm +/- 0.3 (2.4% +/- 1.0% when standardized to baseline diameter) and intimal hyperplastic vessels from 6.2 mm +/- 0.4 to 5.7 mm +/- 0.4 (7.6% +/- 1.7%). The difference between control and intimal hyperplastic vessel vasoconstriction was significant at p less than 0.0025. The calculated reduction in total vessel cross-section area for control vessels was 4.5% +/- 1.9%. In intimal hyperplastic vessels total cross-sectional area was reduced by 14.5% +/- 3.3% by vasoconstriction and the luminal cross-sectional area was reduced by 17.9% +/- 0.7% by the intimal hyperplasia. These data suggest that luminal compromise due to intimal hyperplasia is compounded by increased sensitivity to norepinephrine. This effect, demonstrated in a large elastic artery shortly after endothelial denudation, may be of even greater significance in a smaller vessel with advanced intimal hyperplasia.

Mast cell infiltration: a possible mechanism for vein graft vasospasm.

Mast cell infiltration of the arterial wall has been demonstrated in atherosclerotic vessels and implicated in coronary artery spasm. Spasm of vein bypass grafts has also been reported. In this study we performed vein bypass grafting of the carotid arteries in rabbits and examined the grafts for the presence of mast cells. We also determined vein graft vasoreactivity to histamine, to assess whether mediators of mast cells may have a functional role in vivo. In the control veins no mast cells were identified in 80 high-power fields (400X). In the vein bypass grafts an average of 2.6 +/- 0.8 (p = 0.01) mast cells were identified in the same number of high-power fields. Isometric tension studies of control vein and vein bypass grafts treated with histamine resulted in sigmoid dose-response curves. The ED50 for control vein was 4.69 +/- 0.63 X 10(-5) mol/L. Compared with control vein, the vein bypass grafts showed a rightward shift in the dose-response curve to histamine (ED50 11.6 +/- 1.7 X 10(-5) mol/L, p = 0.01). The histaminergic response in both vessels was blocked by the H1 receptor antagonist pyrilamine (10(-7) mol/L) and was not altered by the H2 receptor antagonist cimetidine (10(-5) mol/L). The decreased sensitivity of vein bypass grafts to histamine suggests receptor down-regulation and is possibly the result of increased histamine in the vein bypass grafts. The presence of mast cells and histamine receptors, as well as altered histamine sensitivity, in vein bypass grafts suggests that infiltration by these cells may contribute to vein bypass graft vasospasm.

Increased vascular contraction and sensitivity to norepinephrine after endothelial denudation is inhibited by prazosin.

The vasomotor function of rabbit aorta was examined after deendothelialization with a Fogarty balloon catheter and during the subsequent development of intimal hyperplasia. Helical strips of injured lower abdominal aortic tissue showed an increase in norepinephrine-induced contraction when compared with control strips from normal upper abdominal aorta. This increase was 235% +/- 40% of control immediately after injury and 341% +/- 51% at 28 days after injury. Standardized dose-response curves demonstrated that the injured tissue was increasingly sensitive over time to norepinephrine and that this was more marked at physiologic levels of norepinephrine. Contraction was blocked by prazosin hydrochloride but not by yohimbine or propranolol. Furthermore, a single intramuscular dose of prazosin hydrochloride 2 hours before injury significantly (p = 0.001) reduced the maximal contraction and sensitivity. These results imply an increase in vasomotor reactivity after deendothelialization mediated through the alpha 1-adrenergic receptor. These functional changes are related to the pertinent morphologic observations.

Anatomical problems with identification and interruption of posterior septal Kent bundles.

To gain insight into the cause of the complex anatomical problems associated with posterior septal Kent bundles, 20 cadaver hearts were carefully examined and the operative results in 22 patients analyzed. The following important anatomical relationships were noted. The posterior right atrium overlies the left ventricle and muscular septum. The coronary sinus wall contains myocardium continuous with both atria. The posterior superior process of the left ventricle connects the mitral annulus to the muscular septum. The epicardium of the crux can be 2.5 to 3.5 cm from the right fibrous trigone. A Kent bundle can originate in either atrium, the atrial septum, or the coronary sinus and connect with the left ventricle or muscular septum. At operation, antegrade and retrograde activation sequences were used for identification. Antegrade maps could not be recorded in 4 patients. Two operations were used, right atrial and left atrial. The initial right atrial operation was successful in 12 patients--all 7 with earliest antegrade activation over the midpart of the muscular septum or its right side and 3 with activation on its left side. Among the 6 patients with more than one operative approach, 5 had Kent bundle division. One of the patients probably had a left free wall pathway. Two pathways thought to be free wall turned out to be septal. The Kent bundles were divided in 18 patients and missed in 4, 2 of the latter having His interruption. There were no deaths. The conclusions are that the right atrial operation is reliable when the pathways are clearly posterior septal. Surgical problems occur because Kent bundles in the posterior left free wall sometimes cannot be separated from Kent bundles in the posterior septal area. Both right atrial and left atrial operations are needed if there is doubt about the location of a pathway.

Argon beam coagulation compared with cryoablation of ventricular subendocardium.

The Argon Beam Coagulator uses radiofrequency energy to excite argon gas that may be used for ventricular ablation. The effects of power level and number of applications of the Argon Beam Coagulator were compared wtih cryothermia. Ten mongrel dogs underwent cardiac extirpation. The endocardial surfaces of 5 hearts were used for the creation of lesions using the Argon Beam Coagulator at five power levels with either one or two applications. Five hearts were used for endocardial and epicardial lesions using cryothermia (15-mm-diameter probe at -70 degrees C) for 1, 2, 3, or 4 minutes. The Argon Beam Coagulator lesions showed an increase in depth with increasing power levels (2.25 +/- 1.05 mm at 50 W to 6.64 +/- 0.75 mm at 150 W) and number of applications (maximum depth of 6.64 +/- 0.75 mm with one application, 11.2 +/- 1.1 mm with two applications). Cryothermia lesions were similar in depth regardless of duration or site of application (range, 6.1 to 10.2 mm). Both techniques resulted in homogeneous and well-demarcated lesions. These data show that the Argon Beam Coagulator results in discrete endocardial lesions, which may be created quickly and reproducibly. This may be a useful alternative for the operative ablation of endocardial scar in the treatment of ventricular tachycardia.

Cardiac denervation and adrenalectomy. Its effects on myocardial lesions of hemorrhagic shock in dogs.

Myocardial lesions were seen in dogs subjected to experimental hemorrhagic shock. In contrast, dogs that had been previously surgically treated by cardiac denervation and adrenalectomy, showed less myocardial damage. The latter group also had a substantially decreased myocardial I-norepinephrine content and a much lower plasma I-norepinephrine response to shock when compared with the control shock dogs. In contrast, "sham shock" dogs had no myocardial lesions, and normal myocardial and plasma I-norepinephrine contents.

The effect of interstitial air on the in vitro thrombogenicity of ePTFE vascular grafts.

Gas trapped in the interstices of the biomaterials used for vascular prostheses causes thrombosis, and the process of eliminating this gas is known as denucleation. An apparatus was developed for testing in the in vitro effects of denucleation on 4 mm I.D. expanded polytetrafluoroethylene (ePTFE) Vitagraft (Johnson and Johnson). The apparatus was designed to ensure that neither the blood nor the grafts came in contact with air. Blood from a single donor was incubated with control and denucleated grafts for 5, 10, 15, 20, and 30 minutes. The thrombus volume in the graft lumen was measured with a computer assisted videometric system. Little thrombus formed by 5 or 10 minutes, but there was less thrombus in the denucleated graft than in the control graft at all times. The differences were statistically significant at 15 and 20 minutes (p < 0.05). Denucleation nearly doubled the thrombus formation time. Thrombus was more adherent to denucleated grafts than to control grafts. These results are consistent with in vivo observations in the rat where denucleation decreased thrombus formation and increased patency duration.

Treatment of hemorrhagic shock in dogs with verapamil: effects on survival and on cardiovascular lesions.

Dogs were subjected to a standardized hemorrhagic shock procedure. Some were treated with verapamil and others were untreated. It was found that the dogs treated with verapamil were protected from the damaging effects of hemorrhagic shock on the heart. This was true even in treated dogs that had a rapid heart rate maintained by means of an intracardiac pacing electrode. In addition, the treated dogs did not show the intestinal hemorrhage that is usually seen in dogs subjected to hemorrhagic shock. Finally, it was found that verapamil treatment increased the survival rate of shocked dogs in comparison with control dogs which were not treated.

Antiplatelet therapy reduces aortic intimal hyperplasia distal to small diameter vascular prostheses (PTFE) in nonhuman primates.

While the use of prosthetic grafts in small diameter arterial reconstruction is required when suitable autogenous graft material is unavailable, late occlusion of prosthetic grafts caused by proliferative lesions has been described. This study evaluated the suitability of 3-mm (ID) microporous polytetrafluoroethylene (PTFE) Gore-Tex grafts inserted in the abdominal aorta of eight nonhuman primates (Macaca fascicularis), and the effects of prolonged antiplatelet treatment on both graft patency and the development of intimal hyperplasia in the adjacent vasculature. Four monkeys received antiplatelet medication consisting of aspirin (163 mg twice daily) and dipyridamole (25 mg twice daily). When killed at four months following graft insertion, all four grafts in the antiplatelet medicated group were patent, while in the control group, only two of four grafts were patent. Histologic examination and quantitative photogravitometric evaluation of the degree of luminal narrowing were performed on all grafts and the adjacent vasculature. These studies revealed that while all graft and aortic segments showed varying amounts of intimal thickening, occlusions in the control animals were related to intimal hyperplasia in the host aorta at the site of the distal anastomosis. Intimal hyperplasia in all aortic segments examined distal to the graft was significantly reduced by antiplatelet therapy. Electronmicroscopy showed that smooth muscle cells were the predominant cells of the intimal thickening of the aorta (intimal hyperplasia), and that proliferation of these cells did not extend into the graft itself. The predominant cell population of the intimal thickening of the graft were of the myofibroblast type (neointimal hyperplasis). The luminal surface of the graft was lined with cells that had some but not all of the characteristics of mature endothelial cells. In vitro studies confirmed global interference with platelet function and arachidonic acid metabolism in medicated animals. Medication inhibited platelet cyclo-oxygenase without affecting platelet lipoxygenase, thromboxane synthetase, or prostacyclin-like activity in undisturbed arteries. This study shows that severe intimal hyperplasia develops rapidly in the recipient vessel adjacent to small diameter Gore-Tex grafts, and that the severity of the response is reduced by antiplatelet agents. Histologic examination revealed that the intimal thickening in the graft and the adjacent aortic segments were composed of cells that were not morphologically identical, suggesting two separate aetiologies and the possible need to use different approaches in their prevention.

Effects of verapamil on heart and circulation in hemorrhagic shock in dogs.

Myocardial blood flow and left ventricular oxygen utilization were studied in verapamil-treated and untreated pentobarbital-anesthetized dogs subjected to hemorrhagic shock. Blood loss was similar in both groups. The dogs treated with verapamil (n = 15) during shock had a slower heart rate and lower left ventricular oxygen utilization than the untreated dogs (n = 14). Nevertheless, the treated dogs had a significantly higher myocardial blood flow and were able to maintain a higher cardiac index. Thus, verapamil has beneficial hemodynamic and metabolic effects that preserve myocardial function. These effects may explain the improved survival and protection of the heart against anatomic lesions, which have been demonstrated previously in dogs treated with verapamil during hemorrhagic shock.

Responsiveness of vein bypass grafts to stimulation with norepinephrine and 5-hydroxytryptamine.

The in vitro reactivity of vein bypass grafts to norepinephrine (NE) and 5-hydroxytryptamine (5-HT) was studied in 20 rabbits undergoing bypass grafting. In these animals the right external jugular vein was grafted into the right carotid artery. The cumulative dose-response to NE and 5-HT of rings of vein grafts 2, 4, and 6 weeks after insertion was compared with that of rings from the normal contralateral jugular vein by means of an organ bath to measure changes in isometric tension. With NE there was no significant difference in the response of vein grafts harvested at 2 weeks and control veins. However, at 4 and 6 weeks there was a progressive decrease in the sensitivity of the grafts to NE. The difference in ED50 values (ED50 defined as concentration of agonist required to elicit 50% of the maximal response) between control veins and vein grafts at 4 weeks was twofold and at 6 weeks it was fivefold. None of the control veins responded to 5-HT stimulation. However, the vein grafts contracted with 5-HT, exhibiting sigmoid dose-response curves. The vein grafts showed intimal hyperplasia, which was maximal after 4 weeks. These results show that vein grafts undergo a progressive decrease in their sensitivity to norepinephrine and develop a marked, sustained increase in sensitivity to 5-HT. This finding is in contrast to previous observations in intimal hyperplastic rabbit aorta, suggesting a fundamental difference in the functional expression of arterial and venous intimal hyperplasia.