Robert S. Schwartz

Enhanced Endothelin-Mediated Coronary Vasoconstriction and Attenuated Basal Nitric Oxide Activity in Experimental Hypercholesterolemia

BACKGROUNDnExperimental hypercholesterolemia is associated with coronary vasomotor dysfunction. This study was designed to test the hypothesis that experimental hypercholesterolemia is characterized by altered coronary vasomotor responses to endothelin and inhibition of the endogenous NO pathway.nnnMETHODS AND RESULTSnEndothelin-1 (ET-1) at 5 ng x kg(-1) x min(-1) or N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase (NOS), at 50 microg x kg(-1) x min(-1) was infused into the left anterior descending coronary artery in pigs before and after 10 weeks of cholesterol diet. There was a significant increase in serum cholesterol. At 10 weeks, ET-1 resulted in an accentuated decrease in coronary blood flow (CBF) and coronary artery diameter (CAD) compared with baseline (-88+/-6% versus -45+/-9%, P<.05, and -77+/-14% versus -18+/-8%, P<.05, respectively) and an increase in coronary vascular resistance (CVR) (242+/-18% versus 110+/-17%, P<.05); ET receptor density and binding affinity in epicardial coronary arteries were unchanged. The effect of L-NMMA on CBF, CAD, and CVR was attenuated at 10 weeks (-7+/-8% versus -48+/-4%, -2+/-3% versus -17+/-5%, and 16+/-10% versus 125+/-32%; each P<.05). Immunohistochemistry staining for constitutive NOS revealed a decrease in immunoreactivity in the coronary arteries of hypercholesterolemic pigs.nnnCONCLUSIONSnThe present study demonstrates an enhanced coronary vasoconstrictive response to pathophysiological doses of endothelin and an attenuated response to the inhibition of endogenous NO activity, suggesting an alteration in coronary vascular reactivity in experimental hypercholesterolemia.

Histopathology of postpercutaneous transluminal coronary angioplasty remodeling in human coronary arteries.

BACKGROUNDnWe studied the histomorphometric correlates of long-term successful coronary balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA]). Restenosis after PTCA may occur secondary to the failure of compensatory arterial enlargement or post-PTCA arterial constriction. The histopathology of this process in human subjects remains poorly defined.nnnMETHODSnForty-two coronary segments from 41 patients treated with PTCA 60 +/- 58 weeks before death were studied. The histomorphometric findings at the PTCA site were compared with those obtained at a proximal reference site.nnnRESULTSnHistologic long-term success was seen in 18 (43%) of 42 arteries. Histologically successful PTCA arteries (PTCA site lumen of >/=50% of the reference lumen) demonstrated a larger acute lumen, smaller plaque size (normalized to the internal elastic lamina area), and thinner adventitia compared with histologic failures. Relative to the reference sites, histologically successful PTCA showed expansion of the external elastic lamina. In contrast, histologic failures showed a reduced external elastic lamina area, suggesting constrictive remodeling. Neointimal area correlated with the extent of internal elastic lamina disruption, but neither variable was related to histologic PTCA success or failure.nnnCONCLUSIONSnThese data provide histomorphometric confirmation of the hypothesis that constrictive remodeling, not neointimal formation, determines the long-term outcome of PTCA.

Does intracoronary infusion of fluosol-DA 20% prevent left ventricular diastolic dysfunction during coronary balloon angioplasty?

Distal intracoronary infusion of the perfluorochemical Fluosol-DA 20% has been shown to prevent systolic dysfunction during coronary artery balloon occlusion in coronary angioplasty. To assess its effect on global diastolic dysfunction, a randomized, single-blind, crossover protocol comparing intracoronary infusion of Fluosol or no infusion (control) was performed during 60 s balloon inflations in 10 patients (mean age 67 years) undergoing coronary angioplasty. Assessment of global systolic and diastolic function was obtained with high fidelity micromanometer measurements of left ventricular pressure. Eighteen pairs of balloon inflations (Fluosol versus control) were analyzed. Patients reported significantly less severe chest pain during inflations accompanied by Fluosol compared with control. However, during coronary balloon occlusion, no significant differences in the changes from baseline values were observed between Fluosol and control with regard to ventricular relaxation, including the time constant of early ventricular relaxation (tau) and maximal rate of fall in left ventricular pressure (maximal negative dP/dt). No differences between Fluosol and control were observed in terms of the increase in end-diastolic pressure or minimal diastolic pressure during balloon inflation. Mean systolic pressure decrease from baseline values was greater during control than during Fluosol inflations (-9.0 +/- 3.3 mm Hg, p = 0.013), but no significant difference was observed in the change in maximal rate of rise in left ventricular pressure (maximal positive dP/dt). These results suggest that Fluosol does not preserve global left ventricular diastolic function during coronary balloon occlusion, possibly because of its limited oxygen delivery capability relative to arterial blood.

Treatment and Prognosis in Congenital Arteriovenous Malformation of the Extremity

This retrospective study was designed to determine the location, symptoms, and long-term results of surgical versus medical therapy in congenital arteriovenous malformation of the extremity. In reviewing all such case records at the Mayo Clinic for the years 1931 through 1980 we found 100 females and 85 males with 74% of lesions in the lower extremity, 22% in the upper extremity, and 4% in combination. Less than 1% were asymptomatic, while 43% had skin discoloration followed by 37% having pain as the presenting complaint. Cases with secondary congestive heart failure, while rare (3%), had a high associated mortality. Regarding treatment and prognosis, asymptomatic patients rarely progressed in severity. Medical therapy rarely (8%) yielded significant improvement and most frequently resulted in an unchanged condition. Conversely, surgery resulted in improvement in 48% of cases with worse results occurring about as frequently as with medical treatment (4% vs. 5% respectively). Surgery furthermore did not result in lesion recurrence more than non-surgical treatment. Multiple operations can be anticipated in some cases, with good outcome as a final result. We conclude that congenital arteriovenous malformations do not progress unrelentingly, and that surgery often has a better result than non-surgical treatment.