Enantioselective synthesis of (R)- and (S)-2-methyl-[3,3,2-2H3] alanines

The synthesis of optically pure (R)- and (S)-2-methyl-[3,3,3-²H₃] alanines of biological interest is described. The stereochemistry of the reaction of the lithio derivative of (R)-(©)-2,5-dimethoxy-3-benzyl-3-methyl-3, 6-dihydropyrazine with alkyl and deuterated alkyl iodides is discussed. The configuration of the newly formed center of chirality in (R)- and (S)-2-methyl-[3,3,3-²H₃] alanines is derived from ¹ H NMR.     

Right Ventricular Volumetry by Catheter Measurement of Conductance

The electrical conductivity of blood is sufficiently higher than that of myocardium to make feasible the detection of cardiac volume changes hy measurement of intraventricuiar fluid conductance. An eight-electrode catheter was used to inject an aiternating current (100 μA or less, at 1500 Hz) via the two electrodes nearest the ventricular base and apex, then the resulting five voltage differences between adjacent pairs of the six intervening electrodes were measured. When current amplitude was held constant, the cross-sectional area of the ventricuiar cavity slice defined hy planes perpendicular to the catheter through the relevant pair of electrodes was inversely proportional (to the first order) to the voltage difference. Measurement of multiple segments compensated for isovolumic cavity shape changes. The technique had previously been shown to measure left ventricular volume successfully, but the geometry of the right ventricle made this measurement more problematical. Using open-chested, anesthetized greyhounds, we compared the catheter-measured right ventricuiar volume change with stroke volume as measured by a pulmonary arterial electromagnetic blood flowmeter. With optimal catheter placement, good correlation between stroke volume and catheter-measured volume changes was achieved when stroke volume was perturbed on a heat-to-heat hasis. In six data records from three dogs, involving two different means of varying stroke volume (rapid injection of blood and sinus node irritation), the correlations yielded r² values between 0.82 and 0.98. The method detected ineffective (nonejecting) beats associated with normal-appearing QRS complexes and was thus a more reliable indicator of cardiac mechanical function than an eiectrocardiogram.     

Modification of Patient Driving Behavior After Implantation of a Cardioverter Defibrillator

Driving habits among recipients of ICDs have not been well characterized previously, yet such information may have implications for development of national policy. This study was undertaken to characterize driving behavior after defibrillator implantation in our patient population. From 1988–1993, 82 ICDs were implanted at the University of Florida. All patients received defibrillator teaching preoperatively and postoperatively with particular emphasis placed on driving restrictions. A standardized questionnaire was developed to ascertain driving behavior, compliance with restrictions, and occurrence of motor vehicle accidents following implantation. The patients were divided into two groups according to whether or not they had received a shock from their device since implantation. Group I patients did, and Group II patients did not. Fifty-two out of 82 (63%, Group I) patients had at least one shock. The remaining 30 patients had received no shocks. Mean age and gender were no different between the two groups. Mean time since implantation was 6 ± 1.3 years in Group I, compared to 4 ± 1.5 years In Group II (P = 0.001). Forty-seven out of 52 (90%) and 26 out of 30 (87%) in Groups I and II, respectively, resumed driving after defibrillator implantation. There was no difference in the amount of time that passed prior to resumption of driving. Group I patients drove more, 20.5 ± 27 miles/day compared to patients in Group II, 8.3 ± 9.7 miles/day (P = 0.02). No patient experienced device discharge during driving; likewise, no patient was involved in a motor vehicle accident secondary to their device firing. Sixty-seven out of 82 (82%) patients complied with the instructions they thought they heard; seven patients in Group I and eight patients in Group II deliberately did not follow our advice. The majority of patients do comply with physician instructions, although the instructions they remember are not always the instructions given. If a national policy is created to prohibit driving after ICD implantation, effective enforcement may be difficult.