Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure

Concern persists about the potential negative inotropic effects of calcium channel blockers in patients with severely depressed myocardial function. Therefore, intravenous diltiazem (100 to 200 micrograms/kg per min infusion) was administered for 40 minutes followed by oral diltiazem (90 to 120 mg/8 hours) for 24 hours to patients with advanced congestive heart failure (New York Heart Association class III to IV, mean ejection fraction 26 +/- 4 [SD]). Intravenous diltiazem (eight patients) increased cardiac index 20% (2.05 +/- 0.8 to 2.47 +/- 0.8 liters/min per m2, p less than 0.01), stroke volume index 50% (22 +/- 9 to 33 +/- 12 ml/m2, p less than 0.001) and stroke work index 27% (19 +/- 10 to 24 +/- 10 g-m/m2, p less than 0.05); while reducing heart rate 23% (97 +/- 18 to 75 +/- 11 beats/min, p less than 0.01), mean arterial pressure 18% (95 +/- 13 to 78 +/- 7 mm Hg) and pulmonary wedge pressure 34% (29 +/- 9 to 19 +/- 7 mm Hg), without altering maximal first derivative of left ventricular pressure (dP/dtmax). Oral diltiazem (seven patients) produced equivalent hemodynamic effects. Transient junctional arrhythmias were observed in three of eight patients with intravenous diltiazem and one of seven patients with oral diltiazem. It is concluded that intravenous and short-term oral diltiazem improve left ventricular performance and reduce myocardial oxygen demand by heart rate and afterload reduction without significantly depressing contractile function in severe congestive heart failure. Caution should be exercised to avoid potential adverse, drug-induced electrophysiologic effects in such patients.     

Immediate effects of hydralazine-isosorbide dinitrate combination on exercise capacity and exercise hemodynamics in patients with left ventricular failure.

Resting hemodynamics improve during vasodilator administration in patients, with congestive heart failure (CHF), but the effects of these agents on exercise is unknown. Twenty-two patients with class II or III CHF performed bicycle exercise to symptomatic maximum before and 90 minutes after random double-blind administration of oral hydralazine (100 mg) and isosorbide dinitrate (40 mg) (11 patients, group 1) or placebo (11 patients, group 2). Exercise duration was unchanged after treatment in either group. Maximal oxygen consumption changed insignificantly in both groups, from 12.6 +/- 1.2 (SEM) to 13.6 +/- 1.6 ml/kg/min in group 1, and from 11.7 +/- 1.4 to 13.4 +/- 1.7 ml/kg/min in group 2. Maximal cardiac index was unchanged in both group 1 (4.00 +/- 0.33 to 4.41 +/- 0.29 l/min/m2) and group 2 (4.11 +/- 0.43 to 4.14 +/- 0.42 l/min/m2). Systemic vascular resistance at peak exercise was also unchanged in both group 1 (14.1 +/- 1.6 to 11.8 +/- 1.0 units) and group 2 (14.7 +/- 1.6 to 13.5 +/- 1.6 units). at submaximal exercise (300 kilopond-meters/min), however, cardiac index after treatment increased in group 1 (0.51 +/- 0.18 l/min/m2, p less than 0.05) and systemic vascular resistance decreased (-3.3 +/- 1.3 units, p less than 0.05), but were unchanged in group 2. Thus, although vasodilators do not improve maximal exercise capacity acutely, they can improve hemodynamics at lower work loads which may, therefore, be better tolerated in patients with CHF.     

Comparative systemic and renal effects of dopamine and angiotensin-converting enzyme inhibition with enalaprilat in patients with heart failure

Renal and systemic hemodynamics were measured during titration of dopamine and serially after intravenous administration of enalaprilat in nine patients with chronic severe congestive heart failure. During titration of dopamine, renal blood flow increased by 99%, from 304 +/- 120 to 604 +/- 234 ml/min (p less than .01) at a dose of dopamine of 2.1 micrograms/kg/min, which produced only a 21% increase in cardiac index, from 1.96 +/- 0.36 to 2.38 +/- 0.35 liters/min/m2 (p less than .05). Cardiac index was increased maximally at a dose of 4.0 micrograms/kg/min dopamine; however, renal blood flow was not further augmented. In contrast, after intravenous administration of enalaprilat, peak improvement of renal blood flow and cardiac index occurred concomitantly. Renal blood flow increased by 35%, from 316 +/- 97 to 427 +/- 107 ml/min (p less than .05), and cardiac index increased by 18%, from 1.99 +/- 0.40 to 2.35 +/- 0.40 liters/min/m2 (p less than .05). At similar increases in cardiac index, dopamine produced a greater increase in renal blood flow than enalaprilat: 604 +/- 234 vs 427 +/- 107 ml/min (p less than .05). Mean systemic arterial pressure, however, was greater with dopamine than with enalaprilat (78.1 +/- 16.7 vs 70.2 +/- 17.2 mm Hg; p less than .05) at peak effect. Thus, although both drugs appear to be potent renal vasodilators in patients with severe congestive heart failure, dopamine may be more effective in augmenting renal blood flow.     

Fat feeding decreases insulin responsiveness of adipose tissue lipoprotein lipase

The acute effect of fat feeding on the insulin-mediated stimulatory response of adipose tissue lipoprotein lipase (ATLPL) was examined in normal-weight subjects. After two days of isocaloric-formula feeding, subjects were divided into the following four groups: intravenous (IV) saline alone (sal) (n = 5), IV saline and 67 g of oral corn oil ingested at the outset of the infusion (sal/fat) (n = 5), IV insulin (40 mU/m2/min) and glucose to maintain euglycemia (ins/glu) (n = 9), and IV insulin and glucose and oral corn oil (ins/glu/fat) (n = 8). Triglycerides fell less in the ins/glu/fat group than in the ins/glu group (0 +/- 8% v 35 +/- 5%, means +/- SEM, at three hours, P less than 0.01; 15 +/- 8% v 43 +/- 6% at six hours, P less than 0.02). ATLPL in the sal and sal/fat groups did not change during the six-hour period. When the responsiveness of ATLPL was compared between ins/glu/fat subjects and ins/glu subjects, decreases were seen at both three and six hours (-0.3 +/- 3.0 v 15.1 +/- 5.4 nEq/g/min, P less than 0.05; 6.7 +/- 2.7 v 27.9 +/- 3.9 nEq/g/min, P less than 0.001). The glucose infusion rates needed to maintain euglycemia were also decreased by fat feeding, 229 +/- 18 v 287 +/- 20 mg/m2/min (P less than 0.05). Thus, fat feeding with insulin and glucose infusions diminishes the insulin responsiveness of ATLPL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered water excretion in healthy elderly men

The renal and vasopressin (AVP) response to a standard oral water load (20 ml/kg) was examined in a group of water-replete healthy elderly men (n = 6). Two groups, respectively, of water-replete and water-deprived young healthy volunteers acted as controls. After 2 h, the old group had excreted 41 +/- 2.4% (mean +/- SEM) of the water load compared to 100.7 +/- 8.8% in the water-replete young group and 70 +/- 3.8% in the water-deprived young group (P less than 0.01). Similarly, peak diuresis (7.01 +/- 0.48 ml/kg) and peak free-water clearance (5.7 +/- 0.48 ml/min) as determined from hourly sampling in the old group were delayed and significantly less than both young groups (P less than 0.01) (peak diuresis, young water-replete, 10.86 +/- 0.56 ml/kg, young water-deprived, 10.2 +/- 0.64 ml/kg, peak free-water clearance, young water-replete 8.4 +/- 0.72 ml/min, young water-deprived 9.5 +/- 0.88 ml/min). When these indices were adjusted for reduced creatinine clearance (Ccr) in the elderly, there was no significant difference between the young and old groups. Plasma AVP decreased similarly in all three groups following ingestion of water but there was no significant difference in mean plasma AVP between the young and old subjects throughout the study period. We therefore conclude that ability to excrete excess water promptly is impaired in healthy elderly men. This defect is due, at least in part, to an age-related reduction in glomerular filtration rate.     

Early goal-directed therapy in moderate to high-risk cardiac surgery patients

Early goal-directed therapy is a term used to describe the guidance of intravenous fluid and vasopressor/inotropic therapy by using cardiac output or similar parameters in the immediate post-cardiopulmonary bypass in cardiac surgery patients. Early recognition and therapy during this period may result in better outcome. In keeping with this aim in the cardiac surgery patients, we conducted the present study. The study included 30 patients of both sexes, with EuroSCORE >or=3 undergoing coronary artery bypass surgery under cardiopulmonary bypass. The patients were randomly divided into two groups, namely, control and early goal-directed therapy (EGDT) groups. All the subjects received standardized care; arterial pressure was monitored through radial artery, central venous pressure through a triple lumen in the right internal jugular vein, electrocardiogram, oxygen saturation, temperature, urine output per hour and frequent arterial blood gas analysis. In addition, cardiac index monitoring using FloTrac and continuous central venous oxygen saturation using PreSep was used in patients in the EGTD group. Our aim was to maintain the cardiac index at 2.5-4.2 l/min/m2 , stroke volume index 30-65 ml/beat/m2 , systemic vascular resistance index 1500-2500 dynes/s/cm5/m2 , oxygen delivery index 450-600 ml/min/m2 , continuous central venous oximetry more than 70%, stroke volume variation less than 10%; in addition to the control group parameters such as central venous pressure 6-8 mmHg, mean arterial pressure 90-105 mmHg, normal arterial blood gas analysis values, pulse oximetry, hematocrit value above 30% and urine output more than 1 ml/kg/h. The aims were achieved by altering the administration of intravenous fluids and doses of inotropic or vasodilator agents. Three patients were excluded from the study and the data of 27 patients analyzed. The extra volume used (330+/-160 v/s 80+/-80 ml, P=0.043) number of adjustments of inotropic agents (3.4+/-1.5 v/s 0.4+/-0.7, P=0.026) in the EGDT group were significant. The average duration of ventilation (13.8+/-3.2 v/s 20.7+/-7.1 h), days of use of inotropic agents (1.6+/-0.9 v/s 3.8+/-1.6 d), ICU stay (2.6+/-0.9 v/s 4.9+/-1.8 d) and hospital stay (5.6+/-1.2 v/s 8.9+/-2.1 d) were less in the EGDT group, compared to those in the control group. This study is inconclusive with regard to the beneficial aspects of the early goal-directed therapy in cardiac surgery patients, although a few benefits were observed.     

Intravenous and oral MDL 17043 (a new inotrope-vasodilator agent) in congestive heart failure: hemodynamic and clinical evaluation in 38 patients

To evaluate the potential benefit of MDL 17043, a new inotrope-vasodilator agent, in the short- and long-term management of severe heart failure, its hemodynamic effects were determined after both intravenous (cumulative average dose 3.7 mg/kg) and oral (average 18.4 mg/kg) administration in 38 patients with severe intractable heart failure. After both intravenous and oral therapy, cardiac index increased from a control value of 2.1 +/- 0.4 to 3.6 +/- 0.9 liters/min per m2, p less than 0.001 (intravenous) and from 2.2 +/- 0.5 to 3.4 +/- 0.6 liters/min per m2, p less than 0.001 (oral). Pulmonary capillary wedge pressure decreased from 26 +/- 6 to 14 +/- 7 mm Hg (p less than 0.001) and from 26 +/- 7 to 18 +/- 8 mm Hg (p less than 0.001) after intravenous and oral routes, respectively. Stroke volume index and stroke work index increased, and right atrial and pulmonary arterial pressures and systemic vascular resistance decreased by similar magnitude after both intravenous and oral MDL 17043 (all p less than 0.001). The hemodynamic effects persisted during 4 hours of observation. Thirty-seven patients were discharged while receiving MDL 17043 therapy and were followed up for a mean of 5.6 months (range 0.5 to 13). Thirty-three of the 37 patients had short-term improvement clinically by at least one New York Heart Association functional class. Undesirable effects, including nausea (35%), anorexia (27%), fluid retention (24%) and thrombocytopenia (less than 1%), necessitated discontinuation of therapy in 11 patients (30%) who were receiving multiple drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic and regional hemodynamic effects of isosorbide dinitrate in patients with liver cirrhosis and portal hypertension

In a group of 17 cirrhotic patients with portal hypertension, we have investigated the effects of 5 mg sublingual administration of isosorbide dinitrate (IDN) on central hemodynamics, on regional (hepatic and renal) hemodynamics and on blood gases. Fifteen min after drug administration, we observed a decrease in the right atrial mean pressure from 4 +/- 1 to 3 +/- 1 mmHg (mean +/- S.E.M., P less than 0.02) and of pulmonary arterial wedge pressure from 7 +/- 1 to 4 +/- 1 mmHg (P less than 0.001) with decreases of the cardiac index from 4.2 +/- 0.2 to 3.7 +/- 0.2 l/min/m2 (P less than 0.001) and the mean arterial pressure from 89 +/- 4 to 72 +/- 3 mmHg (P less than 0.001) and an increase in heart rate from 86 +/- 4 to 94 +/- 5 beats/min (P less than 0.001). Arterial PO2 decreased from 73 +/- 2 to 66 +/- 2 mmHg (P less than 0.001). As a consequence of both cardiac index and arterial PO2 reductions, O2 transport to the tissues was reduced from 602 +/- 32 to 518 +/- 26 ml/min.m2 (P less than 0.001). The hepatic venous pressure gradient decreased from 17 +/- 1 to 14 +/- 1 mmHg (P less than 0.001) and hepatic vein PO2 did not change. The hepatic blood flow (HBF) determined in 7 patients remained unchanged. Renal blood flow (RBF) determined in 5 patients decreased from 0.76 +/- 0.11 to 0.68 +/- 0.11 l/min (P less than 0.001). In conclusion, isosorbide dinitrate reduces portal hypertension in patients with liver cirrhosis without compromising hepatic perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate and short-term hemodynamic effects of diltiazem in patients with hypertension

The immediate effects of intravenous diltiazem effects and short-term (4 weeks) of the oral drug on systemic and regional hemodynamics, cardiac structure, and humoral responses were evaluated by previously reported methods in nine patients with mild-to-moderate essential hypertension and in one patient with primary aldosteronism. Diltiazem was first administered in three intravenous doses of 0.06, 0.06, and 0.12 mg/kg, respectively; patients were then treated for 4 weeks with daily doses ranging from 240 to 360 mg (average 300 mg). Intravenous diltiazem immediately reduced mean arterial pressure (from 115 +/- 3 to 96 +/- 3 mm Hg; p less than .01) through a fall in total peripheral resistance index (from 37 +/- 3 to 23 +/- 2 U/m2; p less than .01) that was associated with an increase in heart rate (from 66 +/- 2 to 77 +/- 3 beats/min; p less than .01) and cardiac index (from 3.3 +/- 0.3 to 4.3 +/- 0.4 liters/min/m2; p less than .01). These changes were not associated with changes in plasma levels of catecholamines or aldosterone or in plasma renin activity. After 4 weeks the significant decrease in mean arterial pressure persisted (104 +/- 3 mm Hg; p less than .01) and there were still no changes in the humoral substances or plasma volume. Renal blood flow index increased (from 368 +/- 52 to 462 +/- 57 ml/min/m2; p less than .01) and renal vascular resistance index decreased (from 0.37 +/- 0.06 to 0.26 +/- 0.04 U/m2; p less than .01), while splanchnic hemodynamics did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of CI-914 in congestive heart failure due to coronary artery disease or idiopathic cardiomyopathy

The hemodynamic effects of CI-914, a phosphodiesterase inhibitor, were studied in 12 patients with left ventricular (LV) dysfunction who were undergoing diagnostic cardiac catheterization. CI-914 was infused intravenously at a rate of 0.8 to 7.0 micrograms/kg/min for 30 to 60 minutes; hemodynamic values were measured every 10 minutes. No effect was seen in the patient receiving 0.8 microgram/kg/min. At infusion rates of 1.2 to 2.4 micrograms/kg/min, cardiac index increased by 14% (p less than 0.025). At infusion rates of 4.5 to 7.0 micrograms/kg/min, cardiac index increased by 21% (n = 8, difference not significant [NS]). Among 4 patients (group B) with an initial pulmonary artery wedge pressure greater than 20 mm Hg and cardiac index less than 2.5 liters/min/m2, cardiac index increased by 50% (p less than 0.001); it did not change among the 4 patients with an initial pulmonary artery wedge pressure of less than 20 mm Hg and cardiac index of more than 2.5 liters/min/m2 (group A). Although systemic vascular resistance decreased in all 8 patients by 26% (p less than 0.01), the reduction was greater in group B (33%, p less than 0.01) than in group A (16%, NS). Peak +dP/dt increased in all 8 patients by 13% (p less than 0.01). Mean stroke work index increased from 29 +/- 15 to 34 +/- 13 g-m/m2; the double product fell from 101 +/- 31 to 91 +/- 23 (NS). In all 12 patients, a linear correlation between peak venous blood concentration and peak effect on cardiac index, systemic vascular resistance and pulmonary artery wedge pressure was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Right and left ventricular volume characteristics in common atrioventricular canal

Right (RV) and left (LV) ventricular volume characteristics were determined from biplane cineangiography in 29 patients with atrioventricular canal (AVC). The patients were classified into two groups: group I (N = 19), uncomplicated AVC; group II (N = 10), AVC associated with RV obstruction. In group I, LV end-diastolic volume (EDV) [177 +/- 9 (SEM)% of normal] and RVEDV (125 +/- 9%) both were greater than normal (P is less than 0.001 and less than 0.01, respectively). LV ejection fraction (EF) was decreased (0.59 +/- 0.02, P is less than 0.001) but RVEF was normal (0.58 +/- 0.03). LV stroke volume index (SVI) was increased (48 +/- 3 ml/m2, P is less than 0.005), and RVSVI was normal (34 +/- 3 ml/m2). One patient had a markedly small RVEDV (45%). In group II, LVEDV and RVEDV were not different from normal (119 +/- 11% and 97 +/- 15%, respectively). LVEF was depressed (0.52 +/- 0.04, P is less than 0.001) and RVEF was normal (0.55 +/- 0.05). LVSVI was normal (38 +/- 5 ml/m2) and RVSVI was slightly decreased (29 +/- 4 ml/m2, P is less than 0.025). Two patients had a markedly small RVEDV (31%, 55%). EDV correlated with the pulmonary-to-systemic flow ratio (LV, r = 0.71; RV, r = 0.68). The data show that in most patients with AVC, LV and RV are enlarged in the uncomplicated form but not in the form with RV obstruction. LV function is more compromised than RV in both groups. RV hypoplasia is rare but was documented in both uncomplicated forms and forms with RV obstruction.     

Acute hemodynamic effect of oral nifedipine in severe chronic congestive heart failure

The temporal hemodynamic effects of oral nifedipine after a single dose of 20 to 40 mg were evaluated in 11 patients with severe chronic congestive heart failure (left ventricular ejection fraction 0.22 +/- 0.7 [mean +/- standard deviation]). Nifedipine significantly reduced systemic vascular resistance, from 1,850 +/- 493 to 1,315 +/- 398 dynes s cm-5 at 1 hour (29%), to 1,410 +/- 246 at 3 hours and to 1,523 +/- 286 at 6 hours (p less than 0.05). Cardiac index increased 21%, from 2.07 +/- 0.46 to 2.51 +/- 0.83 liters/min/m2 at 1 hour, to 2.38 +/- 0.53 liters/min/m2 at 3 hours (p less than 0.05) and to 2.24 +/- 0.41 liters/min/m2 at 6 hours. The group response of stroke volume to nifedipine was smaller. A peak increase of 17% was seen 3 hours after initiation of therapy (22.6 +/- 7.2 versus 25.5 +/- 6.1 ml/m2). This difference did not reach statistical significance. Mean blood pressure declined significantly, from 94 +/- 20 to 80 +/- 13 mm Hg at 1 hour, to 83 +/- 15 mm Hg at 3 hours and to 86 +/- 17 mm Hg at 6 hours (p less than 0.05) and was associated with no significant change in heart rate. The marked decrease in blood pressure resulted in a decrease in rate-pressure product from 12,272 +/- 4,230 to 10,500 +/- 2,074 mm Hg/min at 1 hour, to 10,374 +/- 2,735 mm Hg/min at 3 hours and to 11,047 +/- 3,813 mm Hg/min at 6 hours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Venous admixture in human septic shock: comparative effects of blood volume expansion, dopamine infusion and isoproterenol infusion on mismatching of ventilation and pulmonary blood flow in peritonitis.

A hemodynamic study with blood gas analysis was performed so we could observe changes induced by blood volume expansion, dopamine infusion and isoproterenol infusion in 20 adult patients suffering from peritonitis complicated with septic shock and acute respiratory failure. Blood volume expansion increased cardiac index (from 2.6 +/- 1.21/min/m2 to 3.4 +/- 1.31/min/m2; p less than 0.001), but also enhanced venous admixture (QS/QT) from 27 +/- 14% to 36 +/- 13%; p less than 0.01). Dopamine infusion increased cardiac index (from 2.6 +/- 0.9 1/min/m2 to 3.4 +/- 1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 25 +/- 11% to 31 +/- 12%, p less than 0.001). Isoproterenol infusion increased cardiac index (from 2.6 +/- 0.9 l/min/m2 to 3.6 +/- 1.1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 27 +/- 12% to 33 +/- 11%; p less than 0.001). This worsening in mismatching of ventilation and blood flow is correlated with the enhancement in pulmonary blood flow obtained by these three therapeutic procedures.     

Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in thyrotoxicosis: a minimal model analysis

In order to evaluate simultaneously in thyrotoxic subjects the relative contributions of insulin secretion, insulin-sensitivity (SI) and glucose-mediated (SG) glucose disposal to overall glucose tolerance, seven non-obese patients with thyrotoxicosis were studied by the minimal model analysis of the frequently sampled intravenous glucose tolerance test, before and greater than 1 month after being rendered euthyroid, and compared with eight healthy control subjects. Basal glucose, C-peptide and glucagon levels were similar in all groups but, in the toxic and euthyroid states, basal insulin levels were significantly elevated compared to the control group (11.2 +/- 2.0 and 7.9 +/- 1.1 vs 5.1 +/- 0.6 microU/ml, mean +/- SE, P less than 0.02). FFA levels were raised in the thyrotoxic subjects prior to treatment (0.95 +/- 0.11 vs 0.68 +/- 0.08 and 0.54 +/- 0.08 mmol/l, P less than 0.02). Glucose tolerance (Kg) was reduced in the thyrotoxic subjects compared to the euthyroid state (1.16 +/- 0.12 vs 1.44 +/- 0.13 per min, P less than 0.025) and control group (1.44 +/- 1.0 per min, 0.05 less than P less than 0.1). First phase (phi 1) and second phase (phi 2) insulin release were both significantly elevated in the thyrotoxic and euthyroid states compared to the control group (phi 1 7.10 +/- 1.88 and 5.29 +/- 1.03 vs 1.72 +/- 0.17 microU/mg/min X 10(-2), P less than 0.01; phi 2 18.64 +/- 3.14 and 16.74 +/- 4.48 vs 9.23 +/- 0.74 microU/mg/min X 10(-2) respectively, P less than 0.02). SG was similar in all groups but SI was significantly reduced in the thyrotoxic subjects compared to the control group (2.24 +/- 0.62 vs 5.92 +/- 1.50/min/microU/ml X 10(4), P less than 0.02) and rose post-treatment in the euthyroid subjects (4.23 +/- 1.75/min/microU/ml X 10(4)). In the thyrotoxic subjects before and after treatment, log SI correlated negatively with basal FFA levels (r = -0.57, P less than 0.05) and with phi 2 (r = -0.58, P less than 0.05). The fractional clearance rate of insulin was unaltered by the thyrotoxic state. It is concluded that in thyrotoxicosis the impairment of Kg is due to reduced insulin sensitivity in the presence of enhanced insulin secretion, but glucose-mediated glucose disposal is unaltered by the toxic state.     

Effects of hypocaloric diet and insulin therapy on metabolic control and mechanisms of hyperglycemia in obese non-insulin-dependent diabetic subjects

We studied the effects of hypocaloric diet (500 kcal/d) and insulin therapy in 15 obese (body mass index greater than 30.0 kg/m2) non-insulin-dependent diabetic patients with secondary drug failure and poor metabolic control. The patients were randomly allocated either to hypocaloric diet (n = 8) or to insulin treatment (n = 7). After 2 weeks of treatment there was a significant improvement in the fasting blood glucose, in the mean diurnal glucose, in glucosuria, and in glucose response to a 75-g oral glucose load in both groups. No change in insulin secretion was seen in either group. Glucose disposal rates (GDR) improved significantly both in the diet-treated group (from 2.34 +/- 0.15 to 4.01 +/- 0.40 mg/kg/min, P less than .01) and in the insulin-treated group (from 2.46 +/- 0.33 to 2.77 +/- 0.29 mg/kg/min, P less than .01). The improvement was greater in the diet-treated group (71%) than in the insulin-treated group (13%, P less than .05). The increase of GDR in the diet-treated group was due to an increase of nonoxidative GDR (from 1.18 +/- 0.17 to 2.98 +/- 0.39 mg/kg/min, P less than .001) as assessed by indirect calorimetry. In the insulin-treated group there was a small increase both in oxidative and nonoxidative GDR, but the changes were not statistically significant. Hepatic glucose output (HGO) in a postabsorptive state decreased significantly both in the diet-treated group (from 2.49 +/- 0.15 to 2.04 +/- 0.10 mg/kg/min, P less than .01) and in the insulin-treated group (from 2.63 +/- 0.23 to 2.05 +/- 0.12 mg/kg/min, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hemodynamic effects of intravenous isradipine

The acute hemodynamic effects of isradipine, a new dihydropyridine calcium antagonist, were evaluated in 16 men referred for elective cardiac catheterization. Low-dose (0.007 mg/kg, n = 8) and high-dose (0.015 mg/kg, n = 8) isradipine was administered intravenously over 10 minutes and the hemodynamic alterations assessed 10 minutes after completion of infusion. Low-dose isradipine caused increases in heart rate (68 +/- 9 to 79 +/- 12 beats/min, p less than 0.001) (mean +/- standard deviation), cardiac index (3.0 +/- 0.7 to 4.1 +/- 0.9 liter/min/m2, p less than 0.001) and coronary sinus blood flow (114 +/- 27 to 162 +/- 74 ml/min, p less than 0.01), and significant decreases in mean aortic pressure (104 +/- 17 to 92 +/- 10 mm Hg, p less than 0.01), systemic and coronary vascular resistance. High-dose isradipine caused similar effects: the heart rate increased (72 +/- 6 to 84 +/- 14 beats/min, p less than 0.005), as did the cardiac index (3.0 +/- 0.6 to 4.6 +/- 0.9 liter/min/m2, p less than 0.001) and coronary sinus blood flow (122 +/- 48 to 166 +/- 47 ml/min, p less than 0.025). In addition, there were increases in the stroke volume index (43 +/- 10 to 55 +/- 8 ml/m2, p less than 0.001) and left ventricular stroke work index (69 +/- 12 to 79 +/- 12 g-m/m2, p = 0.05) after the high-dose infusion. Vascular resistance declined significantly in the systemic, pulmonary and coronary beds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and oxygen transport variables in cardiogenic shock secondary to acute myocardial infarction, and response to treatment

There are few data on oxygen transport in cardiogenic shock after acute myocardial infarction. This prospective study examined oxygen transport variables in 19 such patients and assessed their responses to treatment. Femoral and pulmonary arterial catheters were inserted before any therapy except correction of hypoxemia by mechanical ventilation in 8 patients, defibrillation (3 patients) or pacing (5 patients). In 3 patients mean arterial pressure was greater than 80 mm Hg and cardiac index greater than 2.1 liters/min/m2 with normal mixed venous oxygen saturation despite simultaneous clinical shock. They recovered with no further treatment. Sixteen patients were treated with varying combinations of intravenous fluids and dobutamine (37 +/- 25 mu/kg/min) and 14 survived long enough for a second set of measurements to be completed. Mean heart rate increased from 83 +/- 22 to 101 +/- 20 beats/min and mean cardiac index from 1.4 +/- 0.5 to 2.5 +/- 0.4 liters/min/m2 (p less than 0.001). Oxygen consumption (VO2) was maintained even when oxygen delivery (DO2) was less than 330 ml/min/m2. After treatment DO2 increased from 230 +/- 69 to 397 +/- 60 ml/min/m2 (p less than 0.001) and VO2 from 103 +/- 31 to 124 +/- 27 ml/min/m2 (p less than 0.05). Mean mixed venous oxygen saturation increased from 54 +/- 16 to 69 +/- 8% (p less than 0.001) and mean oxygen extraction ratio decreased from 48 +/- 16 to 31 +/- 6% (p less than 0.001). There was no correlation between cuff systolic blood pressure and mean arterial pressure before or after resuscitation. Thirteen patients survived to hospital discharge. When cardiogenic shock responds to treatment, large increases in DO2 lead to small increases in VO2 but large increases in mixed venous oxygen saturation, reflecting improved tissue oxygen availability.     

Hemodynamic and clinical evaluation of piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure

To assess the potential utility of piroximone (MDL-19,205), an investigational inotrope-vasodilator agent, in severe heart failure, 15 patients with severe left ventricular failure refractory to conventional agents were enrolled in an acute hemodynamic study. After incremental intravenous dosing (mean total dose 1.8 +/- 0.4 mg/kg body weight), cardiac index increased (1.7 +/- 0.3 to 2.6 +/- 0.6 liters/min per m2; p less than 0.001) and left ventricular filling pressure decreased (25 +/- 7 to 19 +/- 7 mm Hg; p less than 0.001). Also decreasing significantly were right atrial pressure (13 +/- 6 to 7 +/- 5 mm Hg; p less than 0.005) and systemic vascular resistance (1,633 +/- 394 to 1,183 +/- 278 dynes.s.cm-5; p less than 0.001). Heart rate and mean arterial pressure did not change, whereas stroke work index increased significantly (13.3 +/- 4.3 to 21.6 +/- 7.3 g.m/m2; p less than 0.005). The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone. Similar responses were obtained after incremental doses of piroximone in oral solution. After oral doses of piroximone tablets, cardiac index also increased significantly (2.1 +/- 0.6 to 2.4 +/- 0.5 liters/min per m2; p less than 0.05), although this magnitude of increase was comparatively low. In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01).     

Influence of angiotensin-induced change in afterload on hemodynamics in mitral valve insufficiency. A 2-dimensional and color-coded Doppler echocardiography study

This study assesses the consequences of angiotensin I-induced afterload-stress on mitral regurgitation by two-dimensional and color-coded Doppler echocardiography. During continuous intravenous infusion of angiotensin I in increasing doses of 0.5, 2, and 4 micrograms/min, blood pressure increased significantly from 119 +/- 7/73 +/- 3 mm Hg up to 145 +/- 8/91 +/- 4 mm Hg (+22% resp. +25%; p less than 0.0001 resp. p less than 0.0001). Heart rate did not change significantly (84 +/- 2 min-1 resp. 88 +/- 4 min-1). The enddiastolic volume index, determined by two-dimensional echocardiography, did not change significantly (104 +/- 10 ml/m2 resp. 112 +/- 3 ml/m2), the endsystolic volume index increased from 57 +/- 10 ml/m2 to 75 +/- 13 ml/m2 (+32%; p less than 0.01), the ejection fraction fell from 47 +/- 4% to 36 +/- 4% (p less than 0.001). In the RAO-equivalent view the maximal jet-length, determined by color-coded Doppler echocardiography, increased from 2.6 +/- 0.2 cm to 3.9 +/- 0.3 cm (+50%; p less than 0.001), the maximal jet-area rose from 3.4 +/- 0.6 cm2 to 7.0 +/- 1.0 cm2 (+106%; p less than 0.001); in the parasternal long axis view the maximal jet-length increased from 2.3 +/- 0.2 cm to 3.5 +/- 0.3 cm (+52%; p less than 0.001), the maximal jet-area from 2.6 +/- 0.5 cm2 to 4.9 +/- 0.8 cm2 (+89%; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure

The effects of dobutamine and intravenous milrinone on systemic hemodynamics, coronary blood flow and myocardial metabolism were studied in 11 patients with severe congestive heart failure. Although milrinone and dobutamine similarly increased cardiac index from 1.9 +/- 0.4 to 2.5 +/- 0.4 liters/min per m2 (p less than 0.001) and from 1.9 +/- 0.4 to 2.8 +/- 0.8 liters/min per m2 (p less than 0.001), respectively, milrinone decreased left ventricular end-diastolic pressure to a greater extent than dobutamine, that is, from 26 +/- 6 to 12 +/- 8 mm Hg (p less than 0.001) versus 26 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001). In contrast to dobutamine, milrinone significantly reduced mean systemic arterial and right atrial pressures. Dobutamine increased the first derivative of left ventricular pressure (dP/dt) from 1,013 +/- 309 to 1,360 +/- 538 mm Hg/s (p less than 0.01) but milrinone did not. Similarly, blood flow and myocardial oxygen consumption were increased by dobutamine from 152 +/- 87 to 187 +/- 118 ml/min (p less than 0.05) and from 17.7 +/- 10.9 to 21.5 +/- 14.9 ml O2/min (p less than 0.05), respectively, but were unchanged by milrinone. Both drugs significantly decreased coronary vascular resistance and myocardial oxygen extraction but did not change myocardial lactate extraction. Thus, dobutamine and milrinone produce similar improvement in cardiac index. However, dobutamine increases myocardial oxygen consumption, whereas milrinone does not. This difference can probably be explained by the substantial vasodilating properties of milrinone.