A perspective on converting enzyme inhibitors and calcium channel antagonists in diabetic renal disease.

Hypertension and renal disease are major causes of morbidity and mortality in the diabetic population, with the presence of microalbuminuria established as a predictor of excess mortality. Numerous attempts, both pharmacologic and nonpharmacologic, have been made to intervene in the disease process. Experimental and clinical evidence suggests that the converting enzyme inhibitors and, more recently, certain calcium antagonists have beneficial effects on renal function above and beyond those simply due to blood pressure control. These effects are likely attributable to favorable systemic and renal hemodynamic changes as well as to direct cellular effects. However, intervention with these agents in various rat models of diabetes or hypertension is initiated very early. Hence, some of the beneficial renal effects may not be as dramatic in clinical practice because of the more commonly advanced stage seen at the time of intervention. We present an overview of the histologic, renal hemodynamic, and antiproteinuric effects of these agents in the experimental setting, as well as the clinical evidence supporting the use of angiotensin-converting enzyme inhibitors and certain classes of calcium antagonists in diabetic renal disease.

The signal-averaged electrocardiogram in cardiac transplantation. A noninvasive marker of acute allograft rejection.

Cardiac allograft rejection represents a major cause of morbidity and mortality in transplanted patients. Noninvasive markers of rejection have been sought, though transvenous endomyocardial biopsy remains the "gold standard" for the diagnosis of rejection. Sixty-one signal-averaged electrocardiograms (five in patients with rejection and 56 in patients without rejection) were obtained on 41 patients and prospectively analyzed in frequency domain via fast Fourier transform (FFT). Patients with acute allograft rejection demonstrate a significant increase in the high-frequency components of the QRS complex upon FFT analysis (QRS area ratio 203 +/- 57 vs. 66 +/- 10, P = 0.0007) compared with patients without rejection. Thus, frequency domain analysis may be a useful noninvasive marker of acute cardiac allograft rejection.

Prior arterial injury enhances luciferase expression following in vivo gene transfer.

We determined the time course of gene expression following DNA/Lipofectin transfection of normal or previously injured arterial segments using direct intraluminal infusion following surgical exposure. Constructs possessing the firefly luciferase cDNA regulated by Simian virus 40, Rous sarcoma virus, or alpha-actin promoter were incubated together with Lipofectin for 30 minutes. Arterial segments were assayed for luciferase activity following harvest at 2-21 days. Without prior injury, luciferase activity was only 2.5-fold greater than background two days following gene transfer. Arterial injury three days before gene transfer resulted in luciferase activity 12.5-fold over background levels. This observation has clinical implications with regard to gene therapy following angioplasty, a procedure that is associated with endothelial cell denudation and smooth muscle cell proliferation. Maintenance of gene expression for several days could ameliorate the early smooth muscle migration and proliferation following arterial injury.