Publications

UNLABELLED

STUDY OBJECTIVES AND DESIGN: Arterial vasoconstriction is thought to play a role in the etiology of cocaine-induced cardiovascular complications, but little is known about the immediate effects of cocaine on the thoracic aorta and coronary arteries. To examine these effects, we used transesophageal echocardiography to examine the thoracic aorta and coronary arteries before and immediately after intravenous (i.v.) cocaine (1.2 mg/kg) in 15 subjects.

MEASUREMENTS AND RESULTS

Immediately after cocaine infusion, average heart rate, systolic BP, and double product were increased compared with baseline (22%, 15%, 35%, respectively). There was no significant change in the diameters of the ascending aorta (27.5 vs 27.1 mm; p = 0.85), the descending aorta (19.8 vs 20.4 mm; p = 0.62), or the left main coronary artery (4.3 vs 4.7 mm; p = 0.15). However, there was a trend for an increase in coronary blood flow immediately after cocaine (226 vs 309 mL/min; p = 0.10).

CONCLUSIONS

We conclude that in the 15 subjects studied, there was no evidence of thoracic aorta of coronary artery vasoconstriction immediately after i.v. cocaine. Instead, we found that the diameters of the thoracic aorta and the left main coronary artery were unchanged, and that there was a trend for augmentation of coronary artery blood flow.

A biologic role for the 72-kDa gelatinase A (matrix metalloproteinase 2; MMP-2), beyond simple extracellular matrix turnover, was evaluated in glomerular mesangial cells. To determine the significance of MMP-2 secretion for the acquisition of the inflammatory phenotype, we reduced the constitutive secretion of MMP-2 by cultured mesangial cells with antisense RNA expressed by an episomally replicating vector or with specific anti-MMP-2 ribozymes expressed by a retroviral transducing vector. The phenotype of the transfected, or retrovirally infected, cells was profoundly altered from the activated state and closely approximated that of quiescent cells in vivo. The prominent differences included a change in the synthesis and organization of the extracellular matrix, loss of activation markers, and a virtually total exit from the cell cycle. Reconstitution with exogenous active, but not latent MMP-2, induced a rapid return to the inflammatory phenotype in vitro. This effect was specific to MMP-2, because the closely related MMP-9 did not reproduce these changes. Furthermore, this pro-inflammatory effect of MMP-2 is dependent upon the active form of the enzyme, which can be produced by an autocatalytic activation process on the mesangial cell plasma membrane. It is concluded that MMP-2 acts directly upon mesangial cells to permit the development of an inflammatory phenotype. Specific inhibition of MMP-2 activity in vivo may represent an alternate means of ameliorating complex inflammatory processes by affecting the phenotype of the synthesizing cells, per se.

To determine the accuracy of the cardiovascular physical examination for the diagnosis of asymptomatic valvular heart disease (VHD), we prospectively studied 143 subjects, 68 apparent normal subjects and 75 patients with diseases known to produce VHD. All subjects underwent a complete physical examination with dynamic cardiac auscultation by a physician blinded to clinical data and compared with the results of transesophageal color Doppler echocardiography (TEE). By TEE, 33 subjects (23%), and by physical examination, 25 subjects (17%) had at least 1 form of VHD. Despite a high frequency of mild valve abnormalities and a 31% prevalence of functional murmurs, the physical examination showed a sensitivity of 70%, a specificity of 98% (confidence interval = 0.51 to 0.84, and 0.94 to 0.99, respectively), and a positive and negative predictive value of 92% for the diagnosis of VHD. Only 2 of the 10 patients with VHD by TEE, but not by physical examination, had clinically important VHD. We conclude that the physical examination is a sensitive and highly specific method of screening for VHD in subjects without cardiac symptoms. Therefore, its use should be encouraged rather than the routine application of echocardiography.