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Local renin and angiotensin-converting enzyme (ACE) activity were recently implicated in development of intimal hyperplasia after vascular injury, but little is known about the local responses of angiotensin I/II (AI/AII) and local ACE activity in vein graft physiology. The activity of the local ACE system of experimental vein grafts was examined in this study. The right carotid artery was divided and bypassed in 21 New Zealand White rabbits, using the right external jugular vein. The left external jugular vein was used as a control. Veins and vein grafts were harvested after 14 days. Rings from both vessels were studied in vitro under isometric tension, and dose-response curves to AI and AII were obtained. AI responses were also measured in the presence of captopril. The tissue concentrations of ACE in both vessels were estimated by spectrophotometry and were localized by immunohistochemistry. The responses of the veins to AI and AII were multiphasic, whereas the responses of vein grafts were sigmoid-shaped. Incubation of vein grafts with captopril significantly decreased the sensitivity to AI (p < 0.0001). Immunohistochemical localization identified ACE in the endothelial layer of the veins and vein grafts, but also at a greater density in the intimal hyperplasia of the vein graft. The concentration of ACE was 1.92 +/- 0.16 U/g (wet weight; mean +/- SEM, n = 9) in vein grafts and 1.39 +/- 0.05 U/g in the veins (38% increase, p < 0.05, n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

A new radiopaque, highly flexible balloon-expandable tantalum stent was tested. Thirty-six of 40 stents were successfully deployed percutaneously in the coronary arteries of 31 dogs. The dogs were given aspirin before, intravenous heparin during, and aspirin alone after the procedure. One dog died at 24 hours because of coronary occlusion following traumatic implantation. Four dogs were put to death early, revealing re-endothelialization by 9 days. Eleven dogs were put to death from 2 weeks to 9 months during long-term follow-up, showing all vessels widely patent with the stent uniformly embedded within a stable neointimal layer. Follow-up arteriography showed patency in all remaining stents up to 1 year, with no perforation or aneurysm formation. Four stents were placed into canine peripheral arteries and were removed percutaneously after deployment. Pathology revealed no significant trauma to involved vessels. This tantalum stent exhibits feasibility of percutaneous deployment, early neointimal formation, low thrombogenicity on long-term aspirin therapy alone, and patency up to 1 year in this canine model.

In vitro vasomotor responses of saphenous veins of 15 patients undergoing peripheral vascular bypass procedures were studied. Vessels were harvested by standard techniques, sectioned into 4 mm rings, and suspended in organ baths under isometric tension. Stimulation with cumulative doses of norepinephrine revealed a -logED50 of 6.85 +/- 0.12 M and maximal tension of 8.64 +/- 1.77 g. Patient characteristics suggesting high maximal response (by univariate analysis) included male sex (male 11.69 +/- 2.49 g versus female 5.08 +/- 1.69 g; p = 0.058). Intact and denuded rings were additionally tested for endothelium-dependent relaxation following submaximal norepinephrine precontraction. The vessels relaxed in response to acetylcholine (maximal relaxation 31.1 +/- 10.7% at 1 x 10(-6) M), calcium ionophore A23187 (85.3 +/- 11.8% at 1 x 10(-5) M), and sodium nitroprusside (150.8 +/- 15.2% at 1 x 10(-5) M), but only acetylcholine relaxation was completely endothelium-dependent. Calcium ionophore A23187 relaxation was partially dependent on the endothelium while sodium nitroprusside relaxation was entirely endothelium-independent. Negligible relaxation was observed in response to adenosine diphosphate (ADP) (12.1 +/- 12.8% at 1 x 10(-5) M) while histamine and serotonin caused additional contraction only. We concluded that, in patients undergoing vascular surgical procedures, the saphenous vein (1) demonstrates variable contractile function which appears to be greater in males following spinal anesthesia, and (2) exhibits moderate endothelium-dependent relaxation in response to acetylcholine and calcium ionophore A23187 but not to ADP, histamine, or serotonin.

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.

This study examines the relative contributions of intraluminal pressure, blood flow, wall tension, and shear stress to the development of myointimal thickening in experimental vein grafts. To study these different hemodynamic parameters, several experimental models were created in 30 New Zealand White rabbits separated into six groups: common carotid interposition vein grafts harvested at 4 weeks (VG-4) or 12 weeks (VG-12), common carotid-linguofacial vein arteriovenous fistulas harvested at 4 weeks (AVF-4) or 12 weeks (AVF-12), AVFs with partial outflow obstruction harvested at 4 weeks (AVFobs), and combination VG-AVFs in series harvested at 4 weeks (VGAVF). Blood pressure and flow in the graft or vein were measured by use of a transducer-tipped pressure catheter and electromagnetic flow meter. At harvest, veins were perfusion-fixed and proximal, middle, and distal sections were subjected to computerized morphometric analysis. Vein grafts were characterized by a high mean pressure (VG-4, 51 +/- 4; VG-12, 62 +/- 3 mm Hg), low mean flow (VG-4, 17 +/- 1; VG-12, 16 +/- 4 ml/min), large luminal area (VG-4, 19.7 +/- 2.4; VG-12, 19.3 +/- 3.9 mm2), high wall tension (VG-4, 17.0 +/- 1.5; VG-12, 19.5 +/- 2.4 x 10(3) dyne/cm), low shear stress (VG-4, 0.75 +/- 0.13; VG-12, 0.96 +/- 0.38 dyne/cm2), and a high degree of myointimal thickening (VG-4, 5.89 +/- 0.90; VG-12, 4.72 +/- 0.83 mm2). Arteriovenous fistulas were characterized by a low mean pressure (AVF-4, 5 +/- 1, AVF-12, 6 +/- 2 mm Hg), elevated blood flow (AVF-4, 82 +/- 16; AVF-12, 82 +/- 17 ml/min), small luminal area (AVF-4, 2.43 +/- 0.58; AVF-12, 7.14 +/- 2.68), low wall tension (AVF-4, 0.62 +/- 0.19; AVF-12, 0.89 +/- 0.24 x 10(3) dyne/cm), elevated shear stress (AVF-4, 108 +/- 32; AVF-12, 71 +/- 50 dyne/cm2), and decreased myointimal area (AVF-4, 1.18 +/- 0.26; AVF-12, 1.90 +/- 0.55 mm2). The addition of outflow obstruction to AVFs (AVFobs) resulted in elevated pressure (48 +/- 2 mm Hg), decreased flow (17 +/- 4 ml/min), larger luminal area (8.71 +/- 2.31 mm2), elevated wall tension (10.3 +/- 1.7 x 10(3) dyne/cm), and a degree of myointimal thickening approaching that of vein grafts (3.79 +/- 0.66 mm2).(ABSTRACT TRUNCATED AT 400 WORDS)

Intimal hyperplasia is an important factor in the pathophysiology of vein graft failure. Local renin-angiotensin systems recently have been shown to modulate the development of intimal hyperplasia in arteries after intimal injury. The effect of chronic angiotensin-converting enzyme (ACE) inhibition on the development of intimal hyperplasia in experimental vein grafts was examined in this study. Ten New Zealand White rabbits received 10 mg/kg of captopril daily in their drinking water. One week later the right carotid artery was divided and bypassed with the reversed right external jugular vein in these rabbits and in 10 matched controls. Captopril was continued for 28 days after operation, when all the grafts were harvested. Five grafts from each group were perfusion fixed, and the intimal thickness in the proximal, middle, and distal segments was determined. Rings from the remaining grafts (n = 20 in each group) were studied in vitro under isometric tension, and their responses to norepinephrine (NE), histamine (HIST), serotonin (5-HT), angiotensin I (AI), and angiotensin II (AII) was measured. The intimal thickness of the proximal, middle, and distal segments of the captopril-treated grafts were significantly less than controls, being reduced in all segments by approximately 40% (p less than 0.0001). With regard to vasoreactivity, the captopril-treated grafts were hypersensitive to 5-HT (control ED50 5.5 +/- 0.5 X 10(-7) mol/L vs. captopril-treated 1.1 +/- 0.2 X 10(-6) mol/L; p less than 0.005) although the maximal response was significantly reduced (control 1.6 +/- 0.3 g vs. captopril-treated 0.8 +/- 0.1 g; p less than 0.05). There were no differences in sensitivity between control and captopril-treated rings with respect to NE, HIST, AI, or AII. Four of the ten captopril-treated segments, however, failed to respond to AI, and the maximal active tension of the responders was significantly reduced (control 0.47 +/- 0.06 g vs. 0.20 +/- 0.05 g; p less than 0.02). These results suggest that ACE is involved in the modulation of vein graft intimal hyperplasia, and that ACE inhibitors may have therapeutic applications in patients undergoing vein bypass procedures.

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.

Hypertension is an established risk factor for atherosclerosis, a disease that is important in the pathophysiology of vein graft failure. Hypertension can also alter arterial vasoreactivity. The vasomotor function and histologic characteristics of autogenous vein grafts in hypertensive rabbits were assessed in this study. Hypertension was induced in 13 male New Zealand white rabbits by use of the Goldblatt one clip two kidney method. The right carotid artery was divided and bypassed with the reversed right external jugular vein 7 days later in these animals and in 13 normotensive controls. Blood pressure and renal function were assessed serially, and all the grafts were harvested after 28 days. Three grafts in each group were examined by light microscopy. The responses of the remaining grafts to norepinephrine, histamine, serotonin, and angiotensin II were determined in vitro under isometric tension. Endothelium-dependent relaxation to acetylcholine and calcium ionophore (A23187) was assessed in precontracted grafts. The mean arterial pressure was significantly increased after the Goldblatt procedure was performed. Intimal hyperplasia was observed in both groups, but the grafts in the hypertensive groups showed increased adventitial and medial fibrosis and a reduced number of vasa vasora. The grafts in the hypertensive rabbits were hypersensitive to all agonists as indicated by a significant reduction in their median effective dose values, and their maximal responses to all agonists were also significantly reduced. No graft relaxed in response to acetylcholine, and whereas precontracted grafts in normotensive rabbits had a maximal relaxation of 24% +/- 6% of precontraction with A23187, this was absent in the grafts in the hypertensive rabbits. The results suggest that angiotensin-induced hypertension may adversely affect vein graft patency by inducing hypersensitivity to physiologically important agonists and reducing the effect of receptor-independent endothelium-derived relaxation on vasomotor tone.

Rabbit external jugular veins, normally unresponsive to serotonin (5-HT), develop a constrictive response when grafted into the arterial circulation. The mechanisms responsible for this alteration were examined in this study. The right external jugular vein was grafted into the right carotid artery in 37 New Zealand white rabbits. The vein grafts were harvested at 3, 7, 9, 14, and 28 days after operation; contralateral external jugular veins were harvested at 9 days in six animals. Rings of these vessels were mounted under isometric tension, and dose-response curves to 5-HT were obtained. None of the grafts harvested at day 3 responded to 5-HT. All the grafts harvested from day 7 through day 28 constricted to 5-HT. The maximal response increased from 258 +/- 30 mg at 7 days to 734 +/- 108 mg at 28 days. No change occurred in the sensitivity to 5-HT with time. The increase in maximal response was paralleled by a linear increase in percent intimal area (intimal area/intimal + media areas) from 11.6% +/- 2.1% at 3 days to 48.7% +/- 1.9% at 28 days. Preincubation with ketanserin, a 5-HT2 and alpha 1-adrenergic antagonist, produced a concentration-dependent rightward shift in the 5-HT dose-response curve. The median effective dose for 5-HT increased progressively from 1.9 +/- 0.3 x 10(-6) mol/L (in the absence of ketanserin) to 6.1 +/- 1.7 x 10(-5) mol/L (ketanserin 8 x 10(-7) mol/L; p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Synthetic conduits have not been suitable for microvascular reconstruction owing primarily to their high thrombogenicity. Vein replacements are the most vulnerable to thrombosis because of their low shear rates and low pressure. Experimental replacement of microvenous segments with prosthetic segments has shown little success. Recent technological advances in biomaterials and control of thrombogenesis provide the potential for success in the development of venous prostheses. The purpose of this study was to assess the use of nonbiodegradable composite polyurethane microvascular prostheses for reconstruction of rat femoral veins. Rat femoral venous defects of 10 mm were reconstructed with autogenous vein (n = 12), unprocessed plain polyurethane (n = 5), and nonbiodegradable composite polyurethane (n = 31). Patency was evaluated by direct observation and proximal venous milking tests. The patency rate of composite grafts was not significantly different from that of isotopic vein (p = 0.5, Fisher's exact test), and both had higher patency than unprocessed polyurethane (p less than 0.01). Composite grafts were examined sequentially using light and scanning electron microscopy. Grafts were fully endothelialized between the first and third months. The neointimal, neomedial, and neoadventitial layers could be seen more distinctly over time. New opportunities in reconstructive microsurgery may be opened by microvascular prostheses that are complaint and thromboresistant.

Previous studies have demonstrated that vein storage in normal saline leads to significant mechanical morphological, and biochemical aberrations. However, little information is available regarding the functional damage that occurs. The purpose of this study was to evaluate the effect of saline storage on venous smooth muscle and endothelial function. Segments of ten external jugular veins from male New Zealand White rabbits were placed nondistended in either modified Krebs solution at 37 degrees C (Krebs-stored, KS) or heparinized normal saline at room temperature (saline-stored, SS) for 1 h. Segments 4 mm in length were then simultaneously studied in vitro under isometric tension. There was no difference in maximum tension or sensitivity to either bradykinin or histamine. Acetylcholine-induced relaxation in KS segments was not significantly different from relaxation in a historical cohort of nonstored segments (nonstored 87.4 +/- 1.0% vs. KS 84.5 +/- 2.0%; p = NS). However, there were significant attenuations in SS segment endothelium-dependent relaxation in response to both acetylcholine (KS 84.5 +/- 2.0% vs. SS 76.4 +/- 2.7%, p less than 0.02) and adenosine diphosphate (KS 47.9 +/- 2.9% vs. SS 40.6 +/- 3.7%, p less than 0.002). Relaxant responses to sodium nitroprusside (endothelium-independent) were not significantly different in the two groups (KS 94.6 +/- 1.6% vs. SS 95.7 +/- 2.2%; p = NS). Electron microscopic evaluation of SS segments revealed endothelial cell disruption with cellular edema and loss of intact junctions.(ABSTRACT TRUNCATED AT 250 WORDS)

Replantation after crush amputation has a relatively low success rate. An arterial crush injury was produced in rats under a range of pressure (8.5 to 2,551 g/mm2) and durations (10 to 60 minutes). The degrees of vessel injury and thrombus formation were evaluated as functions of both crush force and duration, and the healing process was followed for 8 weeks. Crushing resulted in morphologic damage to the arterial wall but did not impair patency. Damage was directly proportional to crush pressure and duration. Intimal denudation caused flat platelet adhesion but no thrombus formation or thrombosis. Re-endothelialization was completed by 2 weeks. Intimal hyperplasia appeared at 1 week and consisted of endothelia in the most luminal layers and smooth muscle in the deeper layers. the internal elastic lamina was intact in all specimens and was thought to minimize platelet aggregation on the arterial wall after denudation of the intima.

The ideal method for the preservation of donor hearts for transplantation is unclear. To assess the optimal temperature for donor myocardium preservation, the recovery of isolated canine hearts (n = 20) exposed to 4 hours of either standard ice-chest hypothermia (0-4 degrees C) or constant moderate hypothermia (12 degrees C) were compared. Functional and metabolic data were acquired before hypothermia and every 30 minutes during 3 hours of reperfusion with oxygenated blood. Mean end-systolic pressure-volume slopes were 2.11 +/- 0.06 and 2.09 +/- 0.06 mm Hg/ml for ice-chest hypothermia and constant moderate hypothermia, respectively (p = NS), which were unchanged from control. All y intercepts during reperfusion were decreased compared with control (p = 0.002) without any differences between groups. End-diastolic pressures were greater than control throughout the reperfusion period for both groups (p = 0.02), but there was a difference in change of end-diastolic pressures with time between groups (p = 0.04). Dry/wet ratios were similar after preservation and reperfusion in both groups. ATP recovered to control levels during reperfusion for both groups although energy charge ratios were greater for hearts exposed to constant moderate hypothermia (p = 0.007). These data indicate that intracellular energy stores are well maintained by preservation using either technique. Changes in function appear to be related to altered compliance irrespective of preservation temperature. These data suggest that a wide range of temperatures may be acceptable for donor heart preservation.

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%.

Recent studies have shown that calcium antagonists exert an antiatherogenic effect in animals fed cholesterol. Vein graft intimal hyperplasia is believed to be an early event in atherosclerotic lesion formation, which is a significant cause of graft failure. Altered vasoreactivity has also been postulated in the etiology of vein graft failure. Therefore this study examined the effect of verapamil treatment on the development of intimal hyperplasia and the vasoreactivity of experimental vein bypass grafts. The right external jugular vein was grafted into the right carotid artery of 30 male New Zealand white rabbits fed normal rabbit chow. The left external jugular vein was used as the control vein. Fifteen animals received verapamil (1.25 mg/day for 28 days) via the femoral vein by means of an osmotic pump. In 15 control animals the pump contained saline. Plasma verapamil concentration was 50.9 +/- 13.2 ng/mL (x +/- SEM), a dose that showed no effect on either blood pressure, total serum cholesterol, or in vitro platelet aggregation to ADP. Fourteen of fifteen grafts were patent in each group, for a patency rate of 93%. Histologic examination using computer morphometry showed significant reduction of intimal hyperplasia at the proximal, middle, and distal graft segments (p less than 0.05). In addition in vitro isometric tension studies of the vein grafts and control veins showed that verapamil causes enhanced reactivity of both vein grafts and control veins in response to norepinephrine and histamine (p less than 0.05). Reactivity of vein grafts to serotonin was unaltered. While none of the normal veins in the control group responded to serotonin, normal veins treated with verapamil contracted readily in response to serotonin. Endothelial-dependent relaxation to acetylcholine was absent in both control and verapamil-treated vein grafts, while normal veins from both groups responded to the same extent to acetylcholine. Because we could not demonstrate any difference in platelet or endothelium function between untreated and verapamil-treated animals, we examined the direct effect of verapamil on smooth muscle. Verapamil significantly inhibited [3H]-thymidine incorporation into DNA in vascular smooth muscle cells in culture in a dose-dependent manner. Verapamil treatment significantly reduces intimal hyperplasia in experimental vein grafts and inhibits smooth muscle cell proliferation in culture. Furthermore the enhanced reactivity to norepinephrine and histamine in the verapamil-treated vessels has no detrimental effect on the patency rate at 4 weeks. Thus by inhibiting intimal hyperplasia, calcium antagonists may improve the long-term patency of vein bypass grafts.

Dogs subjected to hemorrhagic"shock" followed by infusion of shed blood develop portal hypertension and small bowel mucosal hemorrhage. Administration of verapamil during shock prevents both of these sequelae and prolongs survival. It is suggested that portal hypertension may exacerbate the mucosal hemorrhage and contribute to the earlier onset irreversibility.

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.

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.

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.

During autogenous vascular grafting endothelial cell damage inevitably occurs. In this study we examined the functional and morphologic integrity of experimental arterial grafts. The right external iliac artery was grafted into the right carotid artery of 12 male New Zealand white rabbits. The left external iliac artery was used as the control artery. Four weeks after surgery, isometric tension studies were performed on rings of control artery and arterial graft. Control arteries and arterial grafts precontracted with norepinephrine demonstrated endothelium-dependent relaxation of 28.3% +/- 5.6% and 16.1% +/- 1.7%, respectively, in response to acetylcholine (5 x 10(-6) mol/L). Both control arteries and arterial grafts contracted in response to norepinephrine, histamine, and serotonin. The median effective dose (ED50) of norepinephrine was 4.1 +/- 1.3 x 10(-7) mol/L for control arteries and 62.1 +/- 17.9 x 10(-7) mol/L for arterial grafts (p less than 0.005). Similarly, arterial grafts were less sensitive to histamine; the ED50 of histamine for control arteries was 4.6 +/- 1.3 x 10(-7) mol/L and 51.4 +/- 13.0 x -7 mol/L for arterial grafts (p less than 0.005). In contrast, reactivity to serotonin was unaltered. The ED50 was 4.1 +/- 1.3 x 10(-7) mol/L for control arteries and 4.5 +/- 1.3 x 10(-7) mol/L for arterial grafts. Scanning and transmission electron microscopy revealed a largely intact endothelial surface. These data are markedly different from our previous findings with vein grafts in which serotonin supersensitivity was associated with an absence of endothelium-mediated relaxation to acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study was designed to test the hypothesis that the vasoconstrictive effects of alpha-adrenergic receptors are responsible, at least in part, for the lack of a maximal vasodilatation of coronary arteries during hemorrhagic shock. Open-chested, anesthetized, mongrel dogs were bled so as to reach an arterial pressure level of 44 mm Hg, and were monitored using an electromagnetic, non-cannulating flowmeter. During shock, two intracoronary injections were made, one of saline, the other of phenoxybenzamine (Dibenzyline). Control dogs had 2 injections of saline. Following phenoxybenzamine, coronary blood flow increased by 32%. These results indicate that although coronary blood flow may be mainly under local control, the sympathetic nervous system limits maximal coronary vasodilatation during hemorrhagic shock by virtue of activated alpha-adrenergic receptors.

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.

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.

The efficacies of standard heparin (SH), low molecular weight heparin (LMWH), and a mixture of sulfated glycosaminoglycans (Org 10172) were investigated with respect to their inhibitory effects on intimal thickening after endothelial injury in the common carotid artery of the rat. The injury was induced by air infusion into an isolated segment of the artery; the pharmacologic agents were administered by continuous intravenous infusion. After 2 weeks the animals were killed and the arteries examined. The control animals developed a marked intimal thickening. A dose-dependent decreases in the intima to media area (I-M) ratio was seen after SH, with approximately 50% and 90% inhibition of intimal thickening at doses of 5 and 50 USP U/kg/hr, respectively. At these effective doses, the effect of SH was associated with reendothelialization of the injured area. The effects of LMWH and Org 10172 were similar to that of SH at doses of 50 anti-Xa U/kg/hr, but these agents had only about 40% inhibition at doses of 15 anti-Xa U/kg/hr. The activated partial thromboplastin times were slightly prolonged in the animals treated with 50 USP/anti-Xa U/kg/hr of SH, LMWH, and Org 10172, whereas significant anti-Xa levels were observed at doses higher than 15 USP/anti-Xa U/kg/hr. It is concluded that SH, LMWH, and Org 10172 have significant inhibitory effects of intimal thickening after injury even at nonanticoagulant levels, with SH being the most potent.

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.

The differences between myocardial infarct (MI) size, amount, and type of conduction fiber injury and outcome in patients with acute anterior or posterior (inferior) MI with or without complete heart block (CHB) were compared. In patients with acute anterior MIs with CHB the infarcts were larger, CHB was more persistent, necrosis involved the more anterior portions of the conduction system, and the terminal event was cardiogenic shock; whereas in the smaller acute posterior MIs with CHB, the CHB was usually transient, necrosis involved the more posterior portions of the conduction system, and terminal arrhythmias were the main cause of death. This is the first quantitative study that documents the larger size of anterior infarcts with complete heart block in comparison with posterior infarcts with complete heart block.