Proximal Thoracic Aorta Research Articles

Cardiac Remodeling: Mechanism and Treatment

Barry Greenberg, MD, ed 569 pages. New York, NY: Taylor and Francis; 2006. $199.95. ISBN 0-8247-2387-2. The appreciation that the myocardium changes shape and structure in response to disease has been appreciated for more than a century. The German anatomists including Krehl, Romberg, Aschoff, and Tawara debated the morphological changes occurring in the heart related to function at the end of the last century. The seminal work of Linzbach1 described the changes in myocyte size in response to aging and to hypertension, valvular heart disease, and heart failure. Because the cardiomyocyte is considered to be “terminally differentiated,” it must respond to disease by adapting to change by modifying its molecular and …

The Swedish Heart Surgery Register: Data quality for proximal thoracic aortic operations

Objectives. To review the data quality and validity in the nationwide Swedish Heart Surgery register for patients operated on the proximal thoracic aorta. Design. Medical records from a random sample of 300 patients in The Swedish Heart Surgery register were reviewed with register data items systematically re-reported. Variable reporting frequency, proportion of adequately reported data, and number and correctness of diagnostic and procedural codes were analysed. Results. After exclusions, 251 patients (84%) remained in the analysis. Reporting frequency for individual items varied from 12% to 100% (median 61%). For core variables, reporting frequency was 96%–100%. In 40 of 43 (93%) reviewed variables, registry data were at least 85% correct. A total of 485 diagnoses and 673 procedures were reported, compared to 617 diagnoses and 758 procedures identified in the review process. Conclusions. The register data quality and validity for patients operated on the proximal thoracic aorta was satisfactory overall, but need further improvement for complications. The register coverage and completeness was very high. Register-based reports should be accompanied by review of data quality.

Aortic dilatation in patients with bicuspid aortic valve

The association of a bicuspid aortic valve (BAV) with abnormalities of the proximal thoracic aorta, including dilatation, aneurysm and dissection, has been previously described, leading to the hypothesis of a common underlying developmental defect involving the aortic valve and the aortic wall. Consequently, any patient with BAV should receive a careful assessment not only of the valve function, but also of the aortic root and the ascending aorta. Dilatation of the proximal thoracic aorta is a common finding in patients with BAV and is believed to be related to aortic rupture and dissection. Because progressive dilatation can occur, careful long-term surveillance of the aortic dimensions is required. Prophylactic surgical repair of the dilated aorta should be recommended more aggressively for patients with BAV than for those with a tricuspid aortic valve. However, the optimal timing of aortic surgery in BAV patients remains uncertain because of the limited data available on the natural history of asymptomatic aortic dilatation.

Angiotensin II infusion induces site-specific intra-laminar hemorrhage in macrophage colony-stimulating factor-deficient mice

Angiotensin II (AngII) infusion promotes macrophage infiltration into the aortic wall resulting in several forms of vascular pathology. To determine the causal role of macrophages in these vascular diseases, we used osteopetrotic ( op) male mice in which a natural mutation ablates production of M-CSF and results in severe depletion of monocytes. AngII infusion into apoE−/− mice resulted in increased atherosclerosis that was attenuated in op mice. AngII infusion in op mice unexpectedly produced grossly discernable thickening of the proximal thoracic aorta characterized by intra-mural hematoma. This pathology was also observed in apoE+/+ × op male mice, and therefore, independent of hyper-lipidemia. No perceptible structural properties of aortas from op mice could be discerned prior to AngII infusion. Regional effects in the contractile response to phenylephrine were noted in aortic rings with enhanced responsivity in the upper thoracic aortas of op mice compared to those from +/+ mice. No differences in contractile response were noted in aortic rings from the lower thorax. In conclusion, deficiency of M-CSF attenuated AngII-induced atherosclerosis but led to an unanticipated pathology of intra-laminar hemorrhage in the upper aortic regions.

Dilatation of the aorta in pure, severe, bicuspid aortic valve stenosis

Background Aortic complications are more frequent after bicuspid aortic valve (BAV) replacement (AVR), than tricuspid aortic valve replacement. We studied the size of the proximal thoracic aorta in patients with BAV undergoing AVR for pure, severe aortic stenosis, looking for dilatation in comparison with patients with a matched tricuspid aortic valve (TAV) and normograms of aortic size. Methods Aortic root and ascending aortic diameter measurements were taken at 3 levels, from electrocardiographic-gated multidetector row computed tomograms, in 28 patients with pure, severe aortic stenosis before AVR. The patients were divided in 2 groups (BAV, n = 10; TAV, n = 18). Patients with greater than mild aortic regurgitation or who were scheduled for aortic root replacement were excluded. Results Although patients in the BAV group were younger ( P <.0001) and less likely to have hypertension ( P <.005), their aortic diameters were larger than those of patients in the TAV group at all levels measured (aortic sinus, 41.1 ± 8.1 mm vs 33.8 ± 3.3 mm; sino-tubular junction, 39.0 ± 7.8 mm vs 31.1 ± 3.8 mm; right pulmonary artery level, 42.8 ± 7.1 mm vs 33.7 ± 4.3 mm; P <.005 for all). Whereas 60% (6/10) of patients in the BAV group had ≥1 aortic diameter measurements greater than the 95th age-adjusted percentile, 0% (0/18) of patients in the TAV group did. Conclusions Patients with BAV undergoing AVR with pure, severe aortic stenosis commonly have moderate dilatation of the thoracic aorta, whereas matched patients with a TAV do not. This finding may contribute to the increased frequency of aortic complications seen in follow up of patients with a BAV after AVR.

Change in the static rheological properties of the aorta in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits with progress of atherosclerosis

The rheological properties of the arterial wall have intimate connections with the fine structure of the wall. Alteration in fine structure due to cardiovascular disease, such as atherosclerosis, could affect the rheological characteristics of the wall. The present study was designed to investigate changes in the static rheological properties of the aorta in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits aged 10–12, 22–24 and 34–36 months in relation to histological alteration of the wall due to progression of atherosclerosis with age. Circumferential wall strips were excised from the ascending, proximal descending thoracic and proximal abdominal aortas and their stress/strain relationship was recorded. Tensile force of the wall showed a slight but insignificant decrease in the KHC rabbit group aged 10–12 months compared to that in the age-matched control group in the proximal thoracic aorta and increased significantly with ageing in the KHC rabbits in these aortic regions mainly at medium and high strain ranges. Wall stress was significantly smaller in the 10–12 months old KHC rabbit group than in the age-matched control group in the proximal thoracic and proximal abdominal aortas and increased significantly with ageing in the KHC rabbit groups chiefly at medium and high strain ranges. Incremental elastic modulus determined at 50% stretching of the initial length of the wall strip was also significantly lower in the KHC rabbit group aged 10–12 months in comparison to that in the age-matched control group and increased significantly with ageing in the KHC rabbit group. The intima thickened severely with abundant foam cells in the KHC rabbits aged 10–12 months. With increasing age, collagen and elastin fibres showed signs of gradual proliferation among the foam cells. The aortic wall in KHC rabbits was viscoelastic in the relatively early stage of atherosclerosis due to abundant foam cells, and thereafter increased in stiffness gradually with fibrous proliferation and calcification. We can conclude that the static rheological properties of the atherosclerotic aortic wall changed in association with alteration in the microstructure of the wall with progression of atherosclerosis.

Characteristic change in local pulse wave velocity in different segments of the atherosclerotic aorta in KHC rabbits

Background Pulse wave velocity, conventionally determined between the carotid and femoral arteries, is a useful measure to estimate stiffness of the aorta. We investigated local pulse wave velocity (LPWV) in different segments in the aorta with relatively early-stage atherosclerosis in relation to the extent and severity of atherosclerotic lesions. Methods Pressure waves were recorded in eight aortic positions using two catheters with one or two micromanometers to determine LPWV in the ascending aorta, distal end of the aortic arch, proximal, middle, and distal thoracic aortas, and proximal, middle, and distal abdominal aortas in Kurosawa and Kusanagi-hypercholesterolemic (KHC) and normal rabbits aged 10 to 12 months. Results The LPWV in the KHC rabbit was greatest in the aortic arch, decreased almost to the normal level in the middle and distal thoracic aorta, increased in the proximal abdominal aorta, and showed almost identical change to that in the normal rabbit in the middle and distal abdominal aortic regions. There was significant difference in LPWV in the aortic arch, proximal thoracic, and proximal abdominal aortas between the two rabbit groups. The sclerotic lesion was prominent in the aortic arch, proximal thoracic aorta, and proximal abdominal aortas. The wall was severely thickened with abundant foam cells. The significant increase in LPWV would be mainly related to the increased wall thickness in these aortic regions. Conclusions We can conclude that LPWV reflects well the distribution and severity of atherosclerotic lesion and the increased wall thickness in the local aortic region in which pulse waves were traveled.

Is aortic dilatation an atherosclerosis-related process?: Clinical, laboratory, and transesophageal echocardiographiccorrelates of thoracic aortic dimensions in the populationwith implications for thoracic aortic aneurysm formation

ObjectivesThe study determined, in a population-based setting, whether dilatation of the thoracic aorta is an atherosclerosis-related process. BackgroundThe role of atherosclerosis in thoracic aortic dilatation and aneurysm formation is poorly defined. MethodsThe dimensions of the thoracic aorta were measured with transesophageal echocardiography in 373 subjects participating in a population-based study (median age 66 years; 52% men). The associations between clinical and laboratory atherosclerosis risk factors, aortic atherosclerotic plaques, and aortic dimensions were examined. ResultsAge, male gender, and body surface area (BSA) jointly accounted for 41%, 31%, 38%, and 47% of the variability in diameters of the sinuses of Valsalva, ascending aorta, aortic arch, and descending aorta, respectively. Adjusting for age, gender, and BSA: 1) smoking was associated with a greater aortic arch diameter, and diastolic blood pressure and diabetes were each associated with a greater descending aorta diameter (p < 0.05); 2) atherosclerotic plaques in the descending aorta were associated with a greater descending aorta diameter (0.18 ± 0.08-mm increase in diameter per 1-mm increase in plaque thickness; p = 0.02); and 3) minor negative associations were noted between atherosclerotic plaques and risk factors for atherosclerosis and the dimensions of the proximal thoracic aorta. Notably, atherosclerosis risk factors and plaque variables each accounted for <2% of the variability in aortic dimensions, adjusting for age, gender, and BSA. ConclusionsAge, gender, and BSA are major determinants of thoracic aortic dimensions. Atherosclerosis risk factors and aortic atherosclerotic plaques are weakly associated with distal aortic dilatation, suggesting that atherosclerosis plays a minor role in aortic dilatation in the population.

Hemodynamics induced after acute reduction of proximal thoracic aorta compliance

Objective: to investigate the affect of reduced aortic compliance on cardiovascular hemodynamics. Materials and Method: fourteen Yucatan miniature swine were divided into two equal groups, a Sham Operated Group and a Banding Group. A Teflon prosthesis was wrapped around the aortic arc in order to limit proximal aortic compliance (Banding Group). Data were recorded operatively (after implantation of a pressure sensor and a flow probe in the ascending aorta), after banding (only in the Banding Group) and at 2 days postoperatively. Results: after banding, compliance decreased by 52 ± 13% (X̄ ± SEM) (p < 0.01) while systolic and pulse pressure increased by 37 ± 8% (p < 0.05) and 87 ± 31% (p < 0.01), respectively. Diastolic pressure, mean blood pressure, cardiac output and systemic vascular resistance did not change significantly. Aortic characteristic impedance increased nearly 2.5 times. Amplitudes of forward and reflected pressure waves (derived from the aortic pressure wave) increased by 96 ± 41% and 174 ± 46%, respectively (p < 0.05), while the time delay between the two decreased by 36 ± 7% (p < 0.05). Conclusions: about half of the total arterial compliance is located in the proximal thoracic aorta. Arterial reconstruction of the proximal aorta with a non-compliant graft results in a significant decrease in systemic arterial compliance, which in turn increases systolic and pulse pressure. The development of more compliant prosthesis, which matches the host artery compliance, is expected to reduce the hemodynamic changes induced after their implantation.Eur J Vasc Endovasc Surg 26, 195-204 (2003)

Update 2001: Dynamic descending thoracic aortomyoplasty: comparison with intraaortic balloon pump in a model of heart failure

As Originally Published in 1994:Dynamic Descending Thoracic Aortomyoplasty: Comparison With Intraaortic Balloon Pump in a Model of Heart Failure by Robert R. Lazzara, MD, Dennis R. Trumble, MS, and James A. Magovern, MD. Cardiothoracic Surgical Research, Allegheny-Singer Research Institute, Department of Surgery, Allegheny General Hospital, and Allegheny Campus, The Medical College of Pennsylvania, Pittsburgh, PennsylvaniaDescending thoracic aortomyoplasty (DTA) uses the latissimus dorsi muscle to compress the proximal descending thoracic aorta as an autogenous diastolic counterpulsator. We studied the hypothesis that DTA could confer hemodynamic benefits equivalent to those yielded by an intraaortic balloon pump (IABP) in dogs (n = 7) with heart failure. The left latissimus dorsi muscle was wrapped around the proximal thoracic aorta and subsequently electrically conditioned to induce fatigue resistance. Heart failure was produced by rapid ventricular pacing after muscle conditioning. Data were collected under three conditions: (1) after the induction of heart failure; (2) with the 20-mL IABP at 1:1; and (3) with the DTA stimulated at 1:1. Effective diastolic counterpulsation was achieved with both the IABP and the DTA. The mean diastolic aortic pressure increased from 66 ± 5 mm Hg at baseline to 90 ± 4 mm Hg with the IABP and to 75 ± 4 mm Hg with the DTA. The left ventricular peak and end-diastolic pressures decreased with IABP (95 ± 5 mm Hg versus 88 ± 4 mm Hg and 16 ± 4 mm Hg versus 12 ± 4 mm Hg, respectively; p < 0.05) and with DTA (95 ± 5 mm Hg versus 87 ± 4 mm Hg and 16 ± 4 mm Hg versus 12 ± 4 mm Hg, respectively; p < 0.05). Counter-pulsation with the IABP did not change the end-systolic pressure–volume relationship or the time constant for diastolic relaxation, whereas the DTA increased the end-systolic pressure-volume relationship (3.2 ± 0.6 mm Hg/mL versus 4.0 ± 0.7 mm Hg/mL; p < 0.05) and decreased the time constant for diastolic relaxation (49 ± 5 msec versus 45 ± 6 msec; p < 0.05). These data show that DTA using conditioned skeletal muscle can provide diastolic counterpulsation in animals with compromised cardiac function. In addition, the procedure appears to have an effect on left ventricular contractility that is independent of its effects on cardiac preload and afterload.

Mediastinal false aneurysm after thoracic aortic surgery

Background. Postoperative mediastinal false aneurysm is associated with a substantial morbidity and mortality. Surgical treatment is mandatory, although the individual approach varies according to the type of pathologic process, infection status, and site of origin of the aneurysm. Methods. Between April 1993 and February 1999, we treated 10 patients, aged 25 to 73 years, with anastomotic mediastinal false aneurysm originating from the proximal thoracic aorta. Nine had undergone prior operations on the ascending aorta (7, type A dissection repair; 1, aortitis; 1, root abscess) with a Dacron conduit (n = 5) or valved conduit (n = 4). The last patient had undergone valve replacement for excavating aortic root sepsis. False aneurysms were detected from 2 to 70 months after the most recent operation. Three patients had positive tissue cultures. The surgical procedure was direct suture repair of the disrupted anastomosis in 5, root or ascending aortic replacement with an aortic homograft in 4, and Dacron graft interposition in 1. Hypothermic low-flow perfusion with or without circulatory arrest was used in all patients. Results. There was one hospital death caused by staphylococcal mediastinitis. A false aneurysm recurred after direct suture repair in 2 patients with underlying type A dissection or aortitis. This resulted in one late death. One patient experienced a neurologic event during removal of an infected vascular graft. All 8 surviving patients are alive and well after a mean follow-up of 2 years. Three patients with mycotic false aneurysms remain free from infection after aortic homograft replacement. Conclusions. Mediastinal false aneurysms are surgically taxing. Low-flow hypothermic perfusion with or without circulatory arrest allows safe reentry. Radical surgery provides a satisfactory outcome in infected patients. Local repair of suture dehiscence in pathologic tissues may predispose to recurrence. We suspect that excessive use of formalin in gelatin-resorcin-formol glue may predispose to tissue necrosis.

Antegrade selective cerebral perfusion in operations on the proximal thoracic aorta

Background. To determine the factors that influence hospital death and neurologic complications after surgery on the thoracic aorta using circulatory arrest and antegrade selective cerebral perfusion. Methods. From May 1989 through April 1997, 106 patients underwent surgery on the thoracic aorta using circulatory arrest and antegrade selective cerebral perfusion. Mean age was 64.0 ± 11.5 years. Unilateral antegrade cerebral perfusion was used in 37 patients (35%), bihemispheric antegrade cerebral perfusion in 69 patients (65%). Mean antegrade cerebral perfusion time was 50.5 ± 20.5 minutes. Indication for surgery was atherosclerotic aneurysm in 60 (56.5%) patients, postdissection aneurysm in 26 (24.4%), acute type A dissection in 16 (15.1%), other in 4 (4.0%). Results. Hospital mortality was 8.5% (n = 9; 70% CL: 5.8%–11.2%). Independent predictors of hospital mortality were rethoracotomy (odds ratio 5.7, p = 0.02), postoperative temporary (odds ratio 17.3, p = 0.02) or permanent (odds ratio 7.5, p = 0.03) neurologic dysfunction, postoperative dialysis (odds ratio 9.9, p = 0.008). Bilateral antegrade selective cerebral perfusion had a favorable impact on hospital mortality (odds ratio 0.08, p = 0.007). Temporary neurologic dysfunction occurred in 3.8% of patients (n = 4; 70% CL: 2.0%–5.6%); preoperative hemodynamic instability (odds ratio 14.8, p = 0.05) and perioperative technical problems (odds ratio 22.2, p = 0.033) were independent determinants of temporary neurologic dysfunction. Permanent central neurologic damage occurred in 5.4% of patients (n = 6; 70% CL: 3.2%–7.6%). Preoperative hemodynamic instability (odds ratio 18.9, p = 0.009) and approach through a left thoracotomy (odds ratio 9.4, p = 0.031) were significant predictors of permanent neurologic damage. Conclusions. Hospital mortality is affected significantly by the choice of technique used for antegrade cerebral perfusion. The incidence of both temporary and permanent postoperative central neurologic damage is influenced by preoperative hemodynamic instability. Duration of cerebral perfusion had no influence on the postoperative neurologic outcome.

Regional characteristics of the harmonic components of the pressure pulse wave in the atherosclerotic aorta of the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit

Abstract We investigated the relationship between the severity and extent of atherosclerotic lesion and harmonic components of the pressure pulse waves at different aortic regions in the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit aged 10∼12 months. Frequency spectra of the pressure pulse waves recorded at nine positions from the ascending aorta to the left iliac artery were obtained for the first (Hc1) to fifteenth (Hc15) harmonic components with fast Fourier transformation. The amplitudes of Hc1, Hc2 and Hc3 progressively increased with distance along the aorta from the heart as observed in the normal rabbit, whereas the amplitudes of Hc4 to Hc6 were very slightly increased towards the peripheral aortic position. At any given aortic position, Hc1 and Hc2 showed higher amplitude in the KHC rabbit than in the normal rabbit except at the aortic region between the ascending aorta and the proximal thoracic aorta, in which sclerotic lesion was more severe and extensive than in any other aortic regions. These results suggest that the increased amplitude of the pressure pulse wave `peaking', apparent in the peripheral aortic region of the KHC rabbit, was mainly caused by the increase in the amplitudes of Hc1 and Hc2 of the pulse wave, and that the decrease in the amplitudes of Hc2 and Hc3 in the aortic arch was related to the severity and extent of atherosclerotic lesion.

Transesophageal Echocardiographic Correlates of Clinical Risk of Thromboembolism in Nonvalvular Atrial Fibrillation

Objectives. This study explored the mechanisms linking clinical and precordial echocardiographic predictors to thromboembolism in atrial fibrillation (AF) by assessing transesophageal echocardiographic (TEE) correlations.Background. Clinical predictors of thromboembolism in patients with nonvalvular AF have been identified, but their mechanistic links remain unclear. TEE provides imaging of the left atrium, its appendage and the proximal thoracic aorta, potentially clarifying stroke mechanisms in patients with AF.Methods. Cross-sectional analysis of TEE features correlated with low, moderate and high thromboembolic risk during aspirin therapy among 786 participants undergoing TEE on entry into the Stroke Prevention in Atrial Fibrillation III trial.Results. TEE features independently associated with increased thromboembolic risk were appendage thrombi (relative risk [RR] 2.5, p = 0.04), dense spontaneous echo contrast (RR 3.7, p < 0.001), left atrial appendage peak flow velocities ≤20 cm/s (RR 1.7, p = 0.008) and complex aortic plaque (RR 2.1, p < 0.001). Patients with AF with a history of hypertension (conferring moderate risk) more frequently had atrial appendage thrombi (RR 2.6, p < 0.001) and reduced flow velocity (RR 1.8, p = 0.003) than low risk patients. Among low risk patients, those with intermittent AF had similar TEE features to those with constant AF.Conclusions. TEE findings indicative of atrial stasis or thrombosis and of aortic atheroma were independently associated with high thromboembolic risk in patients with AF. The increased stroke risk associated with a history of hypertension in AF appears to be mediated primarily through left atrial stasis and thrombi. The presence of complex aortic plaque distinguished patients with AF at high risk from those at moderate risk of thromboembolism.

C014 Proximal thoracic aorta dimensions in hypertensive patients: Lack of correlation between ABPM data and 2D echocardiography

C014 Proximal thoracic aorta dimensions in hypertensive patients: Lack of correlation between ABPM data and 2D echocardiography

The Interstitium of the Human Arterial Wall Contains Very Large Amounts of Extracellular Superoxide Dismutase

The levels of the secreted, interstitially located extracellular superoxide dismutase (EC-SOD), the cytosolic copper-and-zinc-containing SOD (CuZn-SOD), and the mitochondrial manganese-containing SOD (Mn-SOD) were measured in the walls of human coronary arteries, proximal thoracic aortas, and saphenous veins. The blood vessel walls, particularly the arteries, were found to contain exceptionally large amounts of EC-SOD, whereas the levels of CuZn-SOD and Mn-SOD were relatively low compared with other tissues. Analysis of EC-SOD by immunohistochemistry indicates an even distribution in the vessel wall, including large amounts of the arterial intima. Arterial smooth muscle cells were found to secrete large amounts of EC-SOD and likely are the principal source of the enzyme in the vascular wall. The EC-SOD concentration in the human arterial wall extracellular space is high enough to efficiently suppress the putative pathological effects of the superoxide radical, such as oxidation of LDL and reaction with nitric oxide to form the deleterious peroxynitrite. The levels of EC-SOD in the aortic wall are found to vary widely among species and were on average 6440 U/g in humans, 4340 U/g in the cow, 2660 U/g in the pig, 160 U/g in the dog, 770 U/g in the mouse. There were only moderate differences in the amounts of CuZn-SOD and Mn-SOD. This wide variation in EC-SOD content suggests that the susceptibility to pathologies induced by superoxide radicals in the vascular wall interstitium should vary widely among species.

Nuclear microscopy of atherosclerotic tissue

Of the many proposed coronary disease risk factors, the link between heart disease and stored iron has been the subject of recent interest. Samples of proximal thoracic aorta were taken from rabbits fed with 1% cholesterol for 12 weeks, and also from control animals. Unstained freeze dried sections were scanned using the nuclear microscope at the National University of Singapore (NUS) and results indicate that there is an eightfold increase in iron (from 12 ppm to 90 ppm) within the atherosclerotic lesion compared with normal tissue. This result adds weight to the theory that iron may act as a factor in the oxidative modification of low-density lipoprotein (LDL), which induces the formation of foam cells, characteristic of early atherosclerotic lesions.

Dynamic descending thoracic aortomyoplasty: Comparison with intraaortic balloon pump in a model of heart failure

Descending thoracic aortomyoplasty (DTA) uses the latissimus dorsi muscle to compress the proximal descending thoracic aorta as an autogenous diastolic counterpulsator. We studied the hypothesis that DTA could confer hemodynamic benefits equivalent to those yielded by an intraaortic balloon pump (IABP) in dogs (n = 7) with heart failure. The left latissimus dorsi muscle was wrapped around the proximal thoracic aorta and subsequently electrically conditioned to induce fatigue resistance. Heart failure was produced by rapid ventricular pacing after muscle conditioning. Data were collected under three conditions: (1) after the induction of heart failure; (2) with the 20-mL IABP at 1:1; and (3) with the DTA stimulated at 1:1. Effective diastolic counterpulsation was achieved with both the IABP and the DTA. The mean diastolic aortic pressure increased from 66 ± 5 mm Hg at baseline to 90 ± 4 mm Hg with the IABP and to 75 ± 4 mm Hg with the DTA. The left ventricular peak and end-diastolic pressures decreased with IABP (95 ± 5 mm Hg versus 88 ± 4 mm Hg and 16 ± 4 mm Hg versus 12 ± 4 mm Hg, respectively; p < 0.05) and with DTA (95 ± 5 mm Hg versus 87 ± 4 mm Hg and 16 ± 4 mm Hg versus 12 ± 4 mm Hg, respectively; p < 0.05). Counterpulsation with the IABP did not change the end-systolic pressure-volume relationship or the time constant for diastolic relaxation, whereas the DTA increased the endsystolic pressure-volume relationship (3.2 ± 0.6 mm Hg/mL versus 4.0 ± 0.7 mm Hg/mL; p < 0.05) and decreased the time constant for diastolic relaxation (49 ± 5 msec versus 45 ± 6 msec; p < 0.05). These data show that DTA using conditioned skeletal muscle can provide diastolic counterpulsation in animals with compromised cardiac function. In addition, the procedure appears to have an effect on left ventricular contractility that is independent of its effects on cardiac preload and afterload.

Increased prevalence of aortic fatty streaks in cholesterol-fed rabbits administered intravenous cocaine: the role of vascular endothelium.

Several recent postmortem studies suggest an increased prevalence of atherosclerosis in young habitual cocaine abusers. However, little is known about the effects of cocaine abuse on the vascular endothelium and its relationship to atherosclerosis. Therefore, the consequence of chronic administration of intravenous cocaine on the induction of aortic sudanophilia was examined. Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 wk. During this period, animals were randomized to receive either cocaine-hydrochloride (0.25 mg/kg) intravenously (n = 17) twice daily; or an equivalent volume of 0.9% physiologic saline, control group (n = 16). Mean values for total circulating leukocytes and platelets and total plasma cholesterol and triglycerides were similar in both groups throughout the protocol. At the completion of the study, aortic sudanophilia was measured and expressed as a percentage of regional involvement (R1 = proximal 4 cm, R2 = middle 6 cm, and R3 = distal 10 cm). Statistical significance among groups was achieved in the proximal thoracic aorta (p = 0.057). No significant differences in sudanophilia were noted in the middle and distal segments. When animals were placed in subgroups according to percent total plaque involvement, there was a significant increased distribution of rabbits with a greater extent of sudanophilia in the cocaine-treated group as compared with control (p = 0.01, chi-square analysis). Immunocytochemical studies using the macrophage-specific and muscle actin-specific monoclonal antibodies demonstrated that sudanophilic areas in both groups were predominantly composed of macrophage-derived foam cells. Evaluation of plaque morphology showed an increase in intimal plaque thickness and in the number of macrophages and smooth muscle cells in cocaine-treated animals; however, group differences were not statistically significant. Because no significant differences were found in the cellular composition of atherosclerotic plaques between groups, further studies were performed to assess the effects of cocaine on the permeability function of cultured endothelial cell monolayers as a possible mechanism of increased sudanophilia. Cocaine (100 microM)-treated endothelial cell monolayers demonstrated an increased permeability to horseradish peroxidase during all time intervals studied (0-6 hr). Permeability differences were statistically significant at 30 min and 1 hr (p = 0.003 and 0.02, respectively). Collectively, these observations suggest that administration of cocaine to cholesterol-fed rabbits increases the prevalence of aortic sudanophilia via at least one possible mechanism involving enhanced vascular permeability.

Low-Dose Felodipine Treatment Attenuates Endothelial Dysfunction in Rabbits Fed an Atherogenic Diet

Loss of endothelium-dependent relaxation is an early step in atherogenesis. To test the effect of low-dose felodipine on the progression of this dysfunction, male New Zealand white rabbits were rendered hypercholesterolemic with a diet containing 0.25% cholesterol and 3% coconut oil. After a 1-month induction period on this diet, during which the rabbits were identified as low or normal responders to cholesterol, 0.46 mg/kg of felodipine (FELO) or placebo (CON) were given by gavage once daily for a further 3 months. This regimen established FELO plasma levels (14.2 +/- 1.3 nM, week 9) corresponding to therapeutic concentrations in humans and an average 13-fold increase in plasma cholesterol from below 1 mM. At the end of the treatment period, relaxation of norepinephrine (1 x 10(-8) M)-precontracted proximal thoracic aorta strips to acetylcholine (ACh: 1 x 10(-8)-1 x 10(-5) M) was determined. Cholesterol exposure was calculated as the area under the curve for serum cholesterol x time [AUC (mM x day 1)]. Despite equal cholesterol load [FELO (n = 17): 1,856 +/- 182 mM x day) and CON (n = 22): 1,851 +/- 167 mM x day], maximal relaxation to 1 x 10(-7) M ACh was well preserved in strips from FELO-treated rabbits (29.5 +/- 5.7%) but suppressed in strips from untreated rabbits (11.0 +/- 2.9%). For comparison, relaxation in strips from standard diet controls was 49.8 +/- 2.9% (n = 15). Moreover, there was a significant inverse correlation (r = -0.74) between percentage ACh relaxation and cholesterol exposure in FELO-treated rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)