Charles R. Lambert

Influence of left ventricular mass on left ventricular diastolic filling in normotensive morbid obesity

To identify factors influencing left ventricular (LV) diastolic filling in patients with morbid obesity, we performed transthoracic and Doppler echocardiography on 50 subjects whose actual body weight was > or = twice their ideal body weight and on 50 normal lean control subjects. The transmitral Doppler E/A ratio and E wave deceleration half-time were used to assess LV diastolic filling. Significant negative correlations were seen between the E/A ratio and the LV internal dimension in diastole (r = 0.819, p = 0.0001), systolic blood pressure (r = 0.751, p = 0.0001), LV end-systolic wall stress (r = 0.782, p = 0.0001), and LV mass/height index (r = 0.901, p = 0.0001). Significant positive correlations were seen between the E wave deceleration half-time and the LV internal dimension in diastole (r = 0.743, p = 0.0001), systolic blood pressure (r = 0.789, p = 0.0001), LV end-systolic wall stress (r = 0.828, p = 0.0001), and LV mass/height index (r = 0.831, p = 0.0001). No correlation was seen between diastolic blood pressure and either index of LV diastolic filling. Thus increasing LV mass is associated with progressive impairment of LV diastolic filling in morbidly obese individuals. The aforementioned alterations in LV loading conditions may contribute to impairment of LV diastolic filling directly or by increasing LV mass.

Time-series analysis of long-term ambulatory myocardial ischemia: Effects of β-adrenergic and calcium channel blockade

We have previously demonstrated the utility of time-series analysis applied to 72-hour ambulatory electrocardiographic data in patients with coronary artery disease. The present investigation applied time-series analysis to long-term (120-hour) ambulatory electrocardiographic data to determine the minimal period of monitoring needed (1) to detect periodicity of ischemia-related variables in ambulatory patients, (2) to describe auto-correlation and cross-correlation functions for heart rate and ischemia, and (3) to describe the effects of beta-adrenergic and calcium channel blockade on circadian characteristics and coupling of heart rate and ischemia. A double-blind crossover design was used to obtain 120-hour recordings during placebo, atenolol (200 mg/day), and diltiazem (360 mg/day) administration. During all three treatment periods, distinct circadian variation of heart rate was documented by autocorrelation and Fourier analysis. Ischemia did not exhibit clear periodicity as indexed by autocorrelation in any period; however, it was coupled to heart rate in all treatment periods as reflected in cross-correlation analysis. Although diltiazem did not quantitatively alter the circadian characteristics of heart rate or ischemia, atenolol produced a shift in the coupling between remaining ischemia and heart rate in time. Significant autocorrelation was detected for all treatment periods after 72 hours of monitoring, suggesting that 72 hours is the minimum amount of time needed for analysis of ambulatory electrocardiographic data in patients with coronary artery disease.

Hemodynamic and angiographic comparison of intravenous nitroglycerin and nicardipine mainly in subjects without coronary artery disease

Twenty patients were studied during cardiac catheterization to compare hemodynamic and quantitative angiographic effects of intravenous nicardipine and nitroglycerin. After baseline measurements, nicardipine or nitroglycerin was administered by randomized continuous infusion beginning at 10 micrograms/min titrated to achieve a 10 to 12% reduction in systemic arterial pressure. Hemodynamic measurements and angiography were then repeated. Nicardipine did not change heart rate, and a small decrease (82 +/- 4 vs 75 +/- 4 beats/min) was observed with nitroglycerin, whereas mean arterial pressure decreased similarly (-11%) in both groups. Nicardipine increased (+13%) and nitroglycerin decreased (-21%) cardiac output. Although both drugs were associated with significant reductions in pulmonary artery wedge and pulmonary artery pressures, changes were greater with nitroglycerin for pulmonary artery wedge (-49% vs -26%) and pulmonary artery (-39% vs -13%) pressures, whereas only nitroglycerin reduced right atrial pressure significantly. Neither drug altered left ventricular ejection fraction or pulmonary vascular resistance, and only nicardipine decreased systemic vascular resistance significantly. Quantitative coronary angiography (videodensitometry) showed dilation of the left main, proximal, mid and distal anterior descending and circumflex segments by both nitroglycerin and nicardipine. Nicardipine dilated small (< 2 mm2) and large (> 2) arterial segments equally, whereas nitroglycerin showed a proportionately greater effect on small vessels.

New vascular sheath for subcutaneous drug administration: Design, animal testing, and clinical application for pain prevention after angioplasty

A new vascular sheath design (anesthesia infusion sleeve or AIS) was developed to enable administration of local anesthetics or other medications into the subcutaneous tissue around the insertion site without any additional needle sticks or other manipulation. Design of the system was based upon anatomic measurements of femoral artery depth in 150 patients. Animal studies of prototypes verified subcutaneous delivery using both radiographic methods and direct dissection. The pharmacokinetic profile of plasma lidocaine was also studied in three pigs to document subcutaneous delivery with the AIS. Subsequently a clinical trial of the AIS versus a standard sheath was done in 20 patients undergoing coronary angioplasty. Pain associated with sheath removal was graded using a verbal scale at baseline, during infiltration of the area, and at 1-min intervals during compression for 15 min. Baseline pain was identical in both groups, whereas, during infiltration with lidocaine, pain increased in the standard sheath group and decreased in the AIS group. Pain increased slightly in both groups with initial compression; however, it was significantly less in the AIS group. This difference persisted for several minutes after initial compression. The AIS represents a simple addition to standard sheath protocol offering superior pain control compared to standard technique for sheath removal without the need for systemic analgesics or other medications.

New sheath for vascular access and subcutaneous drug administration: Multicenter clinical trial for pain prevention after cardiac catheterization

A new vascular sheath design (anesthesia infusion sleeve, or AIS) was developed to enable administration of local anesthetics or other medications into the subcutaneous tissue around an arterial or venous insertion site without any additional needle sticks or manipulation. Design, animal testing, and an initial small single-site clinical study have previously been published. The current study was multicenter and randomized 80 patients to use of a standard sheath for vascular access or the AIS. Pain associated with sheath placement, postprocedure pain, and pain associated with sheath removal before and during manual compression was recorded. Baseline pain was identical in both the standard and AIS groups. Pain during infiltration and with initial femoral artery compression was significantly lower in the AIS group. A quality of life questionnaire indicated that the AIS sheath was associated with less discomfort and was preferred over a standard sheath in patients who had had a previous procedure performed. The AIS represents a simple addition to standard sheath design, offering superior pain control during removal compared to the standard technique, without the need for systemic analgesics or additional needle punctures.

Fluid Dynamics of Catheter Delivery: Effects on Delivery Efficiency and Localization

The preceding chapter in this volume has addressed several different technologies which have been developed for localized delivery of bioactive substances to vascular segments. Although some overlap is inevitable, our focus shall be more general, with reference to specific catheters or devices when needed to illustrate problems and principles we have found to be important in evaluating transcatheter site-specific therapy in our laboratories. At the present time, three devices have been approved by the FDA for intraluminal drug administration which were actually developed with intramural drug delivery in mind. These devices are being used for intramural therapy both in the US and in other countries with very limited animal investigation to guide optimal clinical application Intramural sitespecific therapy is a relatively old idea in the laboratory but a new idea in the clinical arena. Local delivery in the coronary arteries may be useful for therapy of restenosis, in situ thrombosis, stent thrombosis, prevention of atherosclerosis, modification of coronary artery spasm, induction of angiogenesis and other applications as well. Nevertheless, very few published data are available regarding the basic functionality of catheter and non-catheter delivery systems. Efficiencies cf these systems for acute delivery and retention of marker substances is very low and certain systems have the potential to induce arterial trauma which may not only lead to acute clinical problems but also exacerbate the proliferative response to injury targeted by local therapy in the first place. In this chapter we hope to outline our approach to some of these issues which may aid in understanding the efficacy or lack thereof for certain catheter systems and which also may be useful in guiding new designs. Our primary focus shall be application of catheters using hydraulic delivery mechanisms or diffusion in the coronary circulation, however, the principles involved are applicable to arterial delivery in general.