D. O. Williams

Pharmacological mechanisms for left ventricular unloading in clinical congestive heart failure. Differential effects of nitroprusside, phentolamine, and nitroglycerin on cardiac function and peripheral circulation.

We compared cardiocircolatory actions of the com monly employed systemic vasodilators, intravenous (iv) nitroprusside (NP), Iv phentolamine (PH), and subliagoal nitroglycerin (NTG), causing left ventricular (LV) unloading in 29 chronic coronary subjects with congestive failure to determine whether they produce disparate responses in LV function by different relaxing actions on systemic resistance and capacitance beds. Each drug equally lowered systemic arterial pressures to a small extent, whereas heart rate rose slightly with NTG. Cardiac catbeterization showed a decline in end-diastolic pressure with NTG (19 to 8 mm Hg) which was greater (P < 0.05) than with NP and PH (21 to 11). Cardiac index increased (P < 0.05) during NP (2.68 to 2.93 liters/min per m2) and PH (2.60 to 3.02) but was unchanged (2.83) by NTG. Stroke work increased with PH, ejection fraction rose with NP and PH, and mean ejection rate increased with each, whereas pressure-time per minute fell and end-diastolic volume decreased with each agent. Total systemic vascular resistance declined (P < 0.001) during NP and PH (1,475 to 1,200 dynes sec cm-5) but was unchanged (1,487) by NTG. Plethysmographkally, forearm vascular resistance (FVR) decreased (P < 0.01) with NP and PH (61.6 to 39.1 mm Hg/ml per 100 g/min) bat not (52.4) by NTG. The decreases in venous tone (VT) with NTG (18.2 to 9.3 mn Hg/ml) and NP (183 to 9.8) were greater (P < 0.05) than with PH (18.8 to 13.1). FVR/VT percent changes of 0.%, 1.62, and 033 with NP, PH, and NTG indicated balanced systemic arteriolovenous relaxation by iv NP, greater arteriolar dilation with iv PH, and predominant venous dilation by sublingual NTG. Thus, vasodilators produce disparate modifications of LV function By their differing alterations of preload and impedance, which are dependent upon relative extents of relaxation of systemic resistance and capacitance vessels characteristic of each agent as used clinically.

Hemodynamic effects of nitroglycerin in acute myocardial infarction.

Nitroglycerin (NTG) has recently been suggested to decrease myocardial ischemia and enhance cardiac pump function during acute myocardial infarction (AMI). To evaluate the sublingual agnet in this condition, the hemodynamic effects of 0.4 mg NTG administered to 16 supine patients during the first 72 hours of AMI were determined serially 5, 10 to 15, and 20 to 30 minutes post-NTG. Data were evaluated for the entire group, as well as for six patients with normal pulmonary artery wedge pressure (PAW) (less than or equal to 12 mm Hg; mean 7) who formed group I and for ten patients with elevated PAW (greater than 12 MM Hg; mean 19) who comprised group II. In the 16 patients, NTG resulted in significant decreases in PAW (14 TO 7 MM Hg; P less than .01), mean systemic arterial pressure (MAP) (95 TO 82 MM Hg; P less than .01), cardiac index (CI) (1.79 TO 1.46 L/min/m-2; P less than .02), stroke index (SI) (24 TO 18 CC/M-2; P less than .01) and stroke work index (SWI) (27 TO 20 GM TIMES M/M-2; P less than .01). These alterations were significant in both subgroups, with the decline in PAW greater (P less than .05), while there was no change in group II. There was no significant change in total peripheral vascular resistance (TPVR) for the entire group or in the two subgroups. This study demonstrates that, regardless of initial left ventricular filling pressure, sublingual NTG given in the acute phase of AMI results in rapid fall in PAW, concomitant with decreases in systemic blood pressure, cardiac output and SWI, without changes in TPVR and with little or no effect on heart rate. Since TPVR was unaltered, the decline in MAP was due to fall in cardiac output. Thus, the principal action of sublingual NTG in AMI appears to be systemic venodilation with consequent reduction of ventricular preload. This effect is translated into decline ofpump output even in patients with high initial filling pressures. Although NTG may rapidly relieve pulmonary congestion and lower myocardial oxygen consumption, use of the agent sublingually is limited in AMI because these salutary effects are accomppanied by potentially deleterious fall in cardiac output and systemic blood pressure.

Hemodynamic assessment of oral peripheral vasodilator therapy in chronic congestive heart failure: prolonged effectiveness of isosorbide dinitrate.

To evaluate the effectiveness of oral vasodilator therapy in chronic congestive heart failure, 20 mg of isosorbide dinitrate or placebo was administered orally in double-blind fashion to 25 patients with congestive heart failure. In 15 patients receiving isosorbide dinitrate, pulmonary arterial wedge pressure decreased 5 minutes to 5 hours after drug administration; the peak reduction was observed at 1 hour (from 23 to 14 mm Hg; P less than 0.001). Wedge pressure decreased to normal (12 mm Hg or less) in 8 of the 15 patients (Group I) but remained greater than 12 mm Hg in 7 (Group II). Reductions in mean systemic arterial pressure, systemic vascular resistance and pressure-time per minute also occurred. Indexes of pump output were unchanged in the 15 who received isosorbide dinitrate but tended to decrease slightly in Group I. Stroke index (from 23 to 26 cc/m2) and stroke work index (from 21.4 to 24.1 g-m/m2) increased slightly but significantly (P less than 0.05) in Group II. Thus the prinicpal hemodynamic action of isorbide dinitrate is marked and sustained reduction in left ventricular filling pressure without pronounced effect on cardiac output. This agent should be used in congestive heart failure primarily for relief of congestive symptoms.

Hemodynamic effects of nitroglycerin in acute myocardial infarction: Decrease in preload at the expense of cardiac output

Nitroglycerin (NTG) has recently been suggested to decrease myocardial ischemia and enhance cardiac pump function during acute myocardial infarction (AMI). To evaluate the sublingual agnet in this condition, the hemodynamic effects of 0.4 mg NTG administered to 16 supine patients during the first 72 hours of AMI were determined serially 5, 10 to 15, and 20 to 30 minutes post-NTG. Data were evaluated for the entire group, as well as for six patients with normal pulmonary artery wedge pressure (PAW) (less than or equal to 12 mm Hg; mean 7) who formed group I and for ten patients with elevated PAW (greater than 12 MM Hg; mean 19) who comprised group II. In the 16 patients, NTG resulted in significant decreases in PAW (14 TO 7 MM Hg; P less than .01), mean systemic arterial pressure (MAP) (95 TO 82 MM Hg; P less than .01), cardiac index (CI) (1.79 TO 1.46 L/min/m-2; P less than .02), stroke index (SI) (24 TO 18 CC/M-2; P less than .01) and stroke work index (SWI) (27 TO 20 GM TIMES M/M-2; P less than .01). These alterations were significant in both subgroups, with the decline in PAW greater (P less than .05), while there was no change in group II. There was no significant change in total peripheral vascular resistance (TPVR) for the entire group or in the two subgroups. This study demonstrates that, regardless of initial left ventricular filling pressure, sublingual NTG given in the acute phase of AMI results in rapid fall in PAW, concomitant with decreases in systemic blood pressure, cardiac output and SWI, without changes in TPVR and with little or no effect on heart rate. Since TPVR was unaltered, the decline in MAP was due to fall in cardiac output. Thus, the principal action of sublingual NTG in AMI appears to be systemic venodilation with consequent reduction of ventricular preload. This effect is translated into decline ofpump output even in patients with high initial filling pressures. Although NTG may rapidly relieve pulmonary congestion and lower myocardial oxygen consumption, use of the agent sublingually is limited in AMI because these salutary effects are accomppanied by potentially deleterious fall in cardiac output and systemic blood pressure.

Chemically Tunable Full Spectrum Optical Properties of 2D Silicon Telluride Nanoplates

Silicon telluride (Si2Te3) is a two-dimensional, layered, p-type semiconductor that shows broad near-infrared photoluminescence. We show how, through various means of chemical modification, Si2Te3 can have its optoelectronic properties modified in several independent ways without fundamentally altering the host crystalline lattice. Substitutional doping with Ge strongly red-shifts the photoluminescence while substantially lowering the direct and indirect band gaps and altering the optical phonon modes. Intercalation with Ge introduces a sharp 4.3 eV ultraviolet resonance and shifts the bulk plasmon even while leaving the infrared response and band gaps virtually unchanged. Intercalation with copper strengthens the photoluminescence without altering its spectral shape. Thus, silicon telluride is shown to be a chemically tunable platform of full spectrum optical properties promising for optoelectronic applications.