Scanning electron microscopic analysis of endoscopic versus open vein harvesting techniques.

BACKGROUND: Endoscopic vein harvesting techniques are increasingly used for obtaining conduit for coronary artery bypass surgery. Although they offer advantages in healing over the conventional open technique, concern has been raised regarding the potential for trauma to the vein in the form of intimal disruption which would theoretically predispose to early graft thrombosis and/or development of stenoses. Unfortunately no long term data is yet available for determining if conduits harvested in this fashion are prone to such events. METHODS: We have examined vein segments harvested by both endoscopic and open techniques for evidence of intimal injury (either visible disruption of the intima and/or presence of thrombus) using scanning electron microscopy (SEM). Those harvesting the vein were unaware which patients were in the study, and both the SEM technician and cardiac pathologist who evaluated the scans were blinded to the technique used for harvesting. For each vein segment examined, views were obtained of four different sections and were analyzed at magnifications ranging from 10 yen to 100 yen. RESULTS: Both thrombus formation and visible intimal disruption were identified quite rarely, and overall were not linked significantly to the type of harvesting technique used. CONCLUSIONS: These results suggest that endoscopic vein harvesting techniques do not subject the conduits to more trauma than open techniques and therefore may not predispose to the development of earlier stenoses. This data will need to be confirmed by both other methods of identifying intimal injury and by long-term follow-up of conduit patency in both groups.

Phentolamine reduces myocardial injury and mortality in a rat model of phenylpropanolamine poisoning.

BACKGROUND: Phenylpropanolamine produces dose-related, life-threatening cardiovascular, and central nervous toxicity from alpha-adrenergic overstimulation. Although some recommend the alpha-adrenergic antagonist, phentolamine, as treatment for such toxicity, its therapeutic efficacy has not been previously studied. We sought to determine if pretreatment with phentolamine could reduce acute myocardial injury and mortality in rats administered an overdose of phenylpropanolamine. METHODS: In the mortality arm of the study, 28 unanesthetized, male Wistar rats (14 animals per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or an equal volume of normal saline diluent (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (150 mg/kg). Mortality was compared at 24 hours. In the myocardial injury arm of the study, 20 unanesthetized rats (10 per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or normal saline (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (75 mg/kg). Seventy-two hours after phenylpropanolamine administration, all surviving animals were sacrificed and transverse sections of their hearts were graded histologically for injury by a blinded cardiac pathologist. RESULTS: Twelve rats died within 6 hours of phenylpropanolamine administration. Mortality was significantly lower in the phentolamine-pretreated rats (2/14; 14%) as compared to the control group (10/14; 71%; p = 0.006). The degree of myocardial injury was significantly lower in the phentolamine-pretreated rats (0) as compared to the control group (1.4 +/- 1.6; p = 0.012). CONCLUSION: In this rat model, phentolamine pretreatment prevented acute myocardial injury and significantly reduced lethality from an intraperitoneal phenylpropanolamine overdose.

Chronic pulmonary artery balloon counterpulsation in sheep via percutaneous route.

BACKGROUND: In clinical practice pulmonary artery balloon counterpulsation (PABC) has been utilized only in the operative setting with the balloon housed in a graft attached to the pulmonary artery. Clearly, percutaneous insertion of a dedicated pulmonary artery balloon is a desirable goal for patients requiring temporary assist for right ventricular failure. METHODS: To address the question of right sided cardiopulmonary tolerance for a chronic indwelling pulmonary artery balloon, six adult ewes underwent percutaneous placement of an 11 ml pulmonary artery balloon, via the femoral vein. Effective pumping and timing were monitored for 48 hours at which time the animals were sacrificed. At autopsy gross and microscopic study of all right heart structures, the pulmonary arteries and the lungs were studied for adverse effects. RESULTS: There were inconsequential minor abrasions to right heart structures in most animals. The pulmonary artery in five of six animals revealed ecchymoses and some transmural hemorrhage, but no necrosis or perforation. There was no pulmonary injury that could not be ascribed to postoperative atelectasis. CONCLUSIONS: This study demonstrates that chronic pulmonary artery balloon counterpulsation can be carried out for a period of 48 hours without significant injury to right heart and pulmonary structures in the ovine model

Use of the saline infusion electrode catheter for improved energy delivery and increased lesion size in radiofrequency catheter ablation.

Although radiofrequency catheter ablation has undergone explosive growth as the treatment for a variety of arrhythmias, a limiting factor with the existing catheter delivery system has been the relatively small size of the lesions, which appears to be in part due to coagulum formation around the catheter tip, producing a rise in impedance and limiting energy delivery. In order to test the hypothesis that infusion of saline during radiofrequency current application can increase the lesion size and decrease the incidence of impedance rise, ten dogs were each given two radiofrequency ablation lesions to the left ventricular endocardium. One of these lesions was delivered with a standard 7 French quadripolar catheter with a 2-mm tip, and the second was done with a 7 French luminal electrode catheter (also with a 2-mm tip) for the infusion of normal saline during the delivery of radiofrequency energy. Energy was delivered for 60 seconds at either 10 or 20 watts at two distinct sites in the left ventricle for each animal. Four to 7 days following ablation, the animals were sacrificed for pathological examination. The lesions created with the saline infusion catheter were significantly bigger than those produced with a standard catheter (7.3 x 7.0 x 5.1 vs 5.2 x 4.9 x 3.5 mm, respectively, P < 0.001). At the lower energy level (10 W), none of the animals with the saline infusion catheter experienced an impedance rise versus 3 of 5 of the animals in whom the standard catheter was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol embolization to the coronary arteries resulting in acute myocardial infarction: A complication of coronary artery bypass grafting surgery.

Cholesterol emboli dislodged during coronary artery bypass surgery may be released downstream into the native coronary arteries and lead to the development of acute myocardial infarction. An autopsy-proven case of such an event occurring in a 79-year-old woman illustrates this complication of coronary artery bypass surgery. Awareness of this complication by pathologists may facilitate its recognition. Awareness by surgeons, on the other hand, may help to prevent it through decreased intraoperative manipulation of the involved vessels.

Abnormal left ventricular intracavitary flow acceleration in patients undergoing aortic valve replacement for aortic stenosis. A marker for high postoperative morbidity and mortality.

BACKGROUND: We examined the clinical and echocardiographic characteristics of patients undergoing aortic valve replacement for aortic stenosis whose continuous wave Doppler studies showed abnormal intracavitary flow acceleration. METHODS AND RESULTS: The clinical and Doppler echocardiographic records of 53 consecutive patients undergoing aortic valve replacement for aortic stenosis were reviewed. Doppler echocardiography was performed at a mean of 6.6 days (range, 0-22 days) after surgery. Thirteen patients (group 1) had a dagger-shaped high-velocity systolic flow signal indicative of abnormal intracavitary flow acceleration on their postoperative Doppler study; group 2 comprised 40 aortic stenosis patients who underwent aortic valve replacement but had no postoperative evidence of abnormal intracavitary flow acceleration. Group 1 postoperative abnormal intracavitary flow velocities ranged from 1.8 to 6.8 m/sec (mean, 4.9 +/- 0.9 m/sec): Resulting dynamic gradients ranged from 10 to 184 mm Hg (mean, 104.6 +/- 32 mm Hg). Compared with group 2, group 1 patients had a distinctive ventricular geometry with more-pronounced hypertrophy, smaller cavities, and higher ejection fraction. Systolic anterior motion of the mitral valve did not accompany abnormal intracavitary flow acceleration in any patient. Six of 13 group 1 patients suffered postoperative hemodynamic compromise characterized by severe hypotension despite adequate pulmonary capillary wedge pressures; group 1 postoperative mortality was significantly greater than that seen in group 2 patients (38% versus 12%, p less than 0.05). CONCLUSIONS: Abnormal intracavitary flow acceleration after aortic valve replacement for severe aortic stenosis is associated with a distinctive ventricular geometry and supernormal systolic function but not systolic anterior motion of the mitral valve. Such flow acceleration appears to be a marker for increased postoperative morbidity and mortality. Preoperative and postoperative Doppler echocardiography may be useful in risk stratification and guiding therapy.

Left ventricular free-wall rupture occurring during programmed ventricular stimulation in a patient with recent myocardial infarction.

In this report we describe a patient who died during programmed ventricular stimulation due to a rupture of the left ventricular free wall at the site of a recent myocardial infarction. The patient was a 75-year-old male who presented with an extensive anterior wall myocardial infarction complicated by sustained ventricular tachycardia occurring 8 days after admission. Cardiac catheterization revealed total occlusion of left anterior descending coronary artery and an anteroapical aneurysm. The patient died due to electromechanical dissociation during electrophysiological testing 11 days after myocardial infarction. Postmortem examination showed a rupture of the left ventricular free wall at the site of the myocardial infarction and distant from the site of catheter placement. It is suggested that caution be taken in choosing patients for electrophysiological studies who have had recent large myocardial infarctions with ventricular aneurysm.

The effect of neonatal treatment with capsaicin on focal arteriolar insudation.

There is evidence that peptide neurotransmitters (e.g., substance P, neurokinin A, vasoactive intestinal peptide, calcitonin gene-related peptide) from sensory nerves play a part in vasoregulation. We examined the effect of neonatal treatment with capsaicin, a procedure that causes permanent impairment of primary sensory neurons, on a recently described arteriolar response to inflammation, focal arteriolar insudation (FAI). FAI occurs at a distance from the site of injury, in arterioles supplying that area, and is first observed 6 hr after onset of inflammation and maximally at 24 hr; the affected arterioles show dilation, with increased endothelial permeability and occasional smooth muscle cell damage. In our model, inflammation is induced by implanting a sterile plastic disk in the connective tissue superficial to the rat cremaster muscle. When carbon black is injected intravenously 24 hr later, FAI in the cremaster arterioles can be detected on light microscopy as areas of carbon extravasation; and the length of affected segments is morphometrically measured. The capsaicin-pretreated group showed a marked decrease in FAI compared to the controls. Mean FAI in the capsaicin group (12 animals) was 1.8 +/- 2.4 (SD) mm/cremaster compared to 5.6 +/- 5.1 for the control group (12 animals). P less than 0.003. These results provide evidence that this arteriolar response to inflammation is modulated in part by capsaicin-sensitive neurons.

Capillary leakage in inflammation. A study by vascular labeling.

The local injection of pure inflammatory mediators induces venular leakage. To test the effect of endogenous mediators from dying tissue on vascular leakage, the authors devised an experimental model simulating an infarct, whereby living vessels would be exposed to fragments of organs undergoing aseptic necrosis. Tissues from donor rats were implanted aseptically in the cremasteric sac. Control rats were implanted with materials deemed to be as close as possible to nonirritating: boiled tissues and spheres of Teflon or glass. At different points the rats were injected intravenously with carbon black and killed an hour later. Whole cremaster mounts showed that vascular labeling was strictly venular up to 8 hours, mixed with capillary labeling between 12 and 24 hours, and mainly or exclusively capillary at 48 hours. Histology showed an acute inflammatory infiltrate in the labeled areas. A similar but weaker labeling pattern accompanied by milder inflammation was seen in controls. These results indicate that the vascular leakage in aseptic inflammation is biphasic, first venular, then capillary; and that the capillary phase is induced by the inflammatory reaction itself, possibly through a form of diffuse angiogenesis.

Multiple cholesterol emboli syndrome. Bowel infarction after retrograde angiography.

The two patients described in this article are among the first to have been diagnosed with extensive bowel infarction as a result of cholesterol embolization following cardiac catheterization. The presence of acute hypertension, renal insufficiency, livedo reticularis, and gangrenous skin changes are characteristic manifestations of the multiple cholesterol emboli syndrome. Additionally, gastrointestinal symptoms and melena may herald ischemia and infarction of the alimentary tract. Anticoagulation and thrombolytic therapy are relatively contraindicated in this syndrome and may, in fact, be a precipitating cause. The prognosis is usually poor; however, survival is possible with aggressive medical and surgical therapy, despite extensive infarction of the gastrointestinal tract and other organs. Prevention remains the most critical aspect of management of this potentially catastrophic illness.

Intimal changes in the aorta of prehypertensive rats.

Intimal changes were quantitated in several rat models of arterial hypertension. One kidney-one clip rats drinking water (1K-1C-water), one-kidney rats treated with deoxycorticosterone acetate and drinking 1% NaCl (1K-DOCA-salt), and two-kidney rats drinking 1% NaCl (2K-salt) were studied after 1 to 8 weeks. The thoracic aorta was examined en face and by electron microscopy. Surprisingly, all 2K-salt, most 1K-DOCA-salt (17 out of 19), and two-thirds of 1K-1C-water rats (12 out of 18) had normal arterial pressure at sacrifice. In these normotensive 2K-salt, 1K-1C-water, and 1K-DOCA-salt animals, intimal mononuclear cells (which emigrated from the blood) increased between three- and ninefold. In these same normotensive 1K-1C-water and 1K-DOCA-salt rats, endothelial cell mitoses increased three- to sixfold with a corresponding increase in endothelial cell numbers. In the latter two groups, there was no evidence of endothelial cell denudation or changes in aortic circumference, and the subendothelial space widened mainly with reticular basement membrane presumably synthesized by the endothelium. In normotensive 1K-DOCA-salt rats, most of the endothelial cells were thick and there were several intercellular gaps. Endothelial proliferation, synthesis of macromolecules, and gap formation, as well as increased mononuclear cell emigration, indicate functional changes in mononuclear cells and in endothelial cells. We suggest that the experimental procedures designed to produce hypertension also generate factor(s) which activates mononuclear cells and/or endothelial cells. This cellular activation leads to intimal changes independent of hypertension.

Focal arteriolar insudation. A response of arterioles to chronic nonspecific irritation.

The subcutaneous insertion of sterile, inert plastic pellets over the cremaster muscles of rats induces characteristic focal lesions of the arterioles at a distance from the pellets. These lesions appear with a delay of about 6 hours; by light microscopy they are characterized by a focal dilatation accompanied by endothelial damage and increased permeability. They are more severe if the pellets are loaded with histamine and are inhibited if the pellets are loaded with serotonin. Electron microscopy shows interendothelial gaps; the media is massively infiltrated with blood components and fibrin. The medial smooth muscle cells are stretched and at times necrotic; inflammatory cells are scarce. On the basis of these features the lesion was named focal arteriolar insudation (FAI). Although its pathogenesis is not yet clear, the data at hand suggest that it is caused by endogenous mediators affecting the smooth muscle cells and/or the endothelium. FAI appears to be a specific arteriolar response to chronic nonspecific irritation.

Cellular changes during hypertension: a quantitative study of the rat aorta.

Using rats made hypertensive by aortic ligation or by the one kidney--one clip method, we searched the aorta for morphologic clues that could explain why hypertension aggravates atherosclerosis. Both atherosclerosis and hypertension are characterized by an increased migration of mononuclear cells into the aortic intima; we therefore quantitated this phenomenon and studied its time course. In the thoracic aorta of hypertensive rats intimal cells (emigrated mononuclear cells) increased up to 15 times 2 weeks after surgery and remained stationary thereafter. In both control and experimental rats, leukocyte emigration was heavier in the thoracic aorta than in the abdominal region. A two- to threefold increase in medial smooth muscle herniae into the intima (myointimal herniae) was also found at 8 weeks, indicating a smooth muscle cell dysfunction. Electron microscopic study of the intima showed that its thickening was due to blood-borne material and also to extracellular matrix synthesized by the endothelium. Heightened secretion reflects cell activation, a condition that (in the endothelium) leads also to leukocyte adhesion. These data suggest that, in renovascular hypertension, the aortic endothelium is in an activated state, possibly through a hormonal stimulus.

Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model.

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Preliminary experience with synchronized coronary sinus retroperfusion in humans.

Synchronized coronary sinus retroperfusion (SCSR) with arterial blood has been extensively tested in animals. This intervention offers temporary support to areas of ischemic myocardium while a method of definitive revascularization is being sought. The feasibility and safety of this procedure for patients with unstable angina was therefore tested. A No. 7F autoinflatable retroperfusion balloon catheter (USCI) was inserted percutaneously into the coronary sinus of the study patients. Arterial blood was obtained through a No. 8F catheter placed in the femoral artery. Arterial blood was infused in a retrograde fashion into the coronary venous system during cardiac diastole by means of a piston-driven pump that was electrocardiographically synchronized with the drainage of the venous system during systole. This procedure was performed in five patients with unstable angina refractory to maximum medical therapy. SCSR significantly decreased the frequency of anginal episodes and the requirement for antianginal medications. SCSR also provided time for patient stabilization before diagnostic cardiac catheterization or therapeutic intervention. This preliminary experience suggests that synchronized coronary sinus retroperfusion is a feasible and safe procedure. It can be performed at the bedside with no apparent adverse effects to the patient. Retroperfusion also appears to be effective in relieving ischemic symptoms as assessed by clinical parameters. Based on our preliminary experience, further delineation of its clinical applications is warranted.

Platelets, fibroblasts, and inflammation: tissue reactions to platelets injected subcutaneously.

Evidence from the literature indicates that platelets contain (besides mediators of acute inflammation) factors capable of stimulating fibroblastic growth: namely, serotonin and "platelet factors" demonstrable by their effect on tissue cultures of fibroblasts. The purpose of this study was to find out whether an inflammatory and a fibroblast-stimulating effect could be demonstrated in vivo, in the rat, using a single subcutaneous injection of concentrated platelets (platelet pellet). For comparison, rat brain, heart, and kidney tissue were homogenized under sterile conditions, spun down, and injected subcutaneously. Platelet pellets caused intense edema and neutrophil infiltration; after 8 days they had assumed a spherical shape and were surrounded by typical myofibroblasts. The 30 pellets of tissue homogenates induced a much milder acute inflammatory reaction; only one (a heart pellet) induced a recognizable myofibroblast reaction. The delayed appearance of myofibroblasts around platelet pellets was probably mediated by the neutrophils, which accumulated in large amounts around platelet pellets. Using this in vivo model, a direct fibroblast-stimulating effect of platelets was not demonstrable. It is pointed out that there are analogies between cellular reactions induced by injected platelet pellets and by intravascular platelet thrombi.

Ultrastructure of the myocardium after pulmonary embolism. A study in the rat.

The purpose of this study was to find out whether acute massive pulmonary embolism can produce myocardial changes visible by light and electron microscopy. Ww therefore produced pulmonary embolism in rats using plastic microspheres (diameter, 15 +/- 5 mu). Two experimental protocols were used: lethal embolism, with a dose of microspheres known to kill in 3 to 15 hours (these rats were killed after 1 hour), and sublethal embolism, with a dose compatible with 100% survival (these rats were killed after 24 hours). In both groups, the left ventricle was normal. The right ventricle showed two tyes of changes: a) A distinctive lesion of the myocytes, more diffuse after lethal enbolism and different from the "zonal lesion" of shock. It consisted primarily in a localized shredding of the myofibrillar system; hence, the name shredding is proposed. Earlier stages of this lesion were represented by focal dissolution of the Z line (Z lysis). The pathogenesis of these lesions appeared to be primarily mechanical. b) Necrosis was already apparent at 1 hour and was more extensive after 24 hours. The pathogensis of the necrotic lesions is best explained by a temporary ischemia followed by delayed reflow; a possible potentiating role of endogenous catecholamines cannot be excluded. Most capilaries in the necrotic foci remained functional; this explains the rapid rate of the healing process of such lesions. A comparison is drawn between the observed foci of necrosis and the human myocardial lesions knowns as "miliary infarcts" and "myocytolysis." It is proposed that a factor common to all three is the preservation of the microcirculatory vessels and that our experimental model helps illuminate the pathogenesis of the human lesions. It is concluded that the right ventricle of acute cor pulmonale may develop cellular changes with a complex pathologenesis (mechanical, ischemic, and possibly hormonal). The nature of the changes found in our model could represent the morphologic substrate of right-sided failure; it can be correlated with the electrocardiographic abnormalities found in the comparable human condition.