Administration of the calcium agonist BAY K 8644 in endotoxic shock.

Septic shock is characterized by a decreased vascular tone and a depressed myocardial function. An impairment in cellular calcium availability has been incriminated in both phenomenons. The effects of BAY K 8644, a dihydropyridine-derivative agent acting as a slow calcium-channel activator, were studied and compared to those of norepinephrine (NE) on an experimental endotoxin shock model in the dog. Thirty minutes after intravenous administration of E. coli endotoxin (3 mg/kg), fluid therapy with normal saline was initiated to restore and maintain pulmonary artery capillary wedge pressure at baseline level. In the first part of the study (8 dogs), the effects of increasing doses of 1, 2, 4, and 8 mcg/kg/min of BAY K 8644 were evaluated. BAY K 8644 administration resulted in an increase in mean arterial pressure (MAP) (65 +/- 16 to 116 +/- 24 mmHg, P less than 0.001), systemic vascular resistance (SVR) (1,451 +/- 526 to 2,632 +/- 804 dynes.sec.cm-5, P less than 0.01), and left ventricular stroke work (LVSW) (0.08 +/- 0.04 to 0.16 +/- 0.07 g.m/kg, P less than 0.05), without change in mean pulmonary artery pressure, cardiac output, O2 transport, or O2 consumption (VO2). In the second part of the study (10 dogs), BAY K 8644 and NE were administered in a randomized order at increasing doses to achieve an identical increase in MAP. For a 20 mmHg increase in MAP, BAY K 8644 increased more SVR than NE (1,284 +/- 299 to 1,717 +/- 551 vs. 1,415 +/- 312 to 1,470 +/- 603 dynes.sec.cm-5, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hemodynamic effects of alpha human atrial natriuretic polypeptide in patients with congestive heart failure

Acute hemodynamic and humoral effects of synthesized alpha human atrial natriuretic polypeptide (alpha-hANP, 0.025 microgram/kg/min for 40 min) on 6 patients with severe congestive heart failure were assessed. Plasma alpha-hANP concentration was high in patients and increased further (from 463 +/- 360 to 1,282 +/- 670 pg/ml, mean +/- SD, p less than 0.01) following alpha-hANP infusion, but plasma norepinephrine (1,030 +/- 865 to 971 +/- 785 pg/ml) was not changed. Increases in urine output (1.0 +/- 0.8 to 2.6 +/- 2.3 ml/min) and Na+ excretion rate (87 +/- 89 to 257 +/- 211 mEq/min/m2) were statistically insignificant. A significant reduction was induced in mean aortic pressure (99 +/- 25 to 96 +/- 26 mmHg, p less than 0.05), mean right atrial pressure (11 +/- 9 to 7 +/- 8 mmHg, p less than 0.01), mean pulmonary arterial pressure (39 +/- 13 to 33 +/- 12 mmHg, p less than 0.05) and mean pulmonary capillary wedge pressure (27 +/- 8 to 20 +/- 7 mmHg, p less than 0.01). Heart rate, cardiac index, systemic vascular resistance and pulmonary vascular resistance were not altered. In conclusion, alpha-hANP induced decreases in left ventricular filling pressure and rightside heart pressure which were attributed to venodilatation rather than natriuresis in patients with congestive heart failure. Preserved cardiac output with decreased preload suggested that alpha-hANP improved cardiac function.     

Effect of prostacyclin and prazosin in the treatment of congestive heart failure; with special reference to the sympathetic nervous system

Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacyclin (PG I2) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22 +/- 11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0 +/- 7.9 to 15.0 +/- 6.6 mmHg (p less than 0.001), mean arterial pressure from 98.9 +/- 12.8 to 76.2 +/- 7.0 mmHg (p less than 0.001), systemic vascular resistance from 2,574 +/- 384 to 1,368 +/- 283 dynes X sec X cm-5 (p less than 0.001), pulmonary vascular resistance from 1,008 +/- 451 to 443 +/- 135 dynes X sec X cm-5 (p less than 0.001) and pulmonary arteriolar resistance from 330 +/- 111 to 189 +/- 73 dynes X sec X cm-5 (p less than 0.001). The cardiac index increased from 2.0 +/- 0.37 to 3.2 +/- 0.59 l/min/m2 (p less than 0.001), and the stroke index from 27.6 +/- 8.69 to 42.0 +/- 0.62 ml/m2 (p less than 0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nifedipine on hemodynamics and cardiac function in patients with normal left ventricular ejection fraction already treated with propranolol

The interaction between nifedipine and propranolol on cardiac hemodynamics and function was investigated in 9 patients with normal left ventricular (LV) function who were undergoing cardiac catheterization for complaints of chest pain. Only 2 patients had angiographic evidence of significant coronary artery disease but no patient had clinical evidence of ischemia during the study. All patients were pre-treated with propranolol, 30 to 320 mg/day (mean +/- standard deviation 210 +/- 122); the propranolol serum level ranged from 43 to 246 ng/ml (mean 203 +/- 62). The administration of nifedipine resulted in a decrease in blood pressure (from 94 +/- 11 to 85 +/- 13 mm Hg, p less than 0.05), increase in heart rate (from 59 +/- 6 to 65 +/- 7 beats/min, p less than 0.05), and an increase in both mean right atrial and mean pulmonary artery wedge pressures (from 8 +/- 3 to 9 +/- 3 mm Hg and from 13 +/- 3 to 14 +/- 4 mm Hg, respectively, both p less than 0.05). Cardiac index increased (from 2.3 +/- 0.3 to 2.7 +/- 0.2 liters/min/m2, p less than 0.01). Stroke volume index also increased significantly (from 39 +/- 5 to 43 +/- 6 ml/m2) and systemic vascular resistance decreased (from 1,715 +/- 369 to 1,255 +/- 271 dynes s cm-5, p less than 0.01). No significant change was noted in pulmonary vascular resistance (148 +/- 94 vs 140 +/- 62 dynes s cm-5), LV stroke work index (44 +/- 9 vs 42 +/- 10 g-m/m2), LV end-diastolic pressure (15 +/- 2 vs 16 +/- 2 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Central and renal hemodynamic effects of a new agonist at peripheral dopamine- and beta-2 adrenoreceptors (dopexamine) in patients with heart failure

The effect of dopexamine, a new dopamine analogue, on central and renal hemodynamics was evaluated in nine patients with chronic, congestive heart failure caused by severe left ventricular (LV) systolic dysfunction. The administration of the maximally tolerated dose (7.2 +/- 4 micrograms/kg/min) resulted in a significant increase in cardiac index from 1.9 +/- 0.4 L/min/m2 to 2.6 +/- 0.9 L/min/m2 (p less than 0.05). This increase in cardiac index was largely a result of increase in heart rate (from 88 +/- 20 beats/min to 104 +/- 24 beats/min, p less than 0.05), because stroke volume index demonstrated only a small change (from 23 +/- 10 ml/m2 to 27 +/- 11 ml/m2, p not significant) in spite of a significant fall in systemic vascular resistance from 1992 +/- 717 dynes.sec.cm-5 to 1361 +/- 524 dynes.sec.cm-5 (p less than 0.05) and diastolic blood pressure (from 89 +/- 15 mm Hg to 80 +/- 17 mm Hg, p less than 0.05). No change was seen during dopexamine infusion in systolic blood pressure, right and left ventricular filling pressures, and LV stroke work index. Both renal blood flow and glomerular filtration rate were impaired at baseline in most patients. Dopexamine administration resulted in a significant increase (2x coefficient of variation) in renal blood flow in two patients only. Mean values of both renal blood flow and glomerular filtration rate did not show significant change (485 +/- 183 ml/min vs 563 +/- 221 ml/min and 89 +/- 39 ml/min vs 93 +/- 34 ml/min, respectively, p not significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac energetics after intravenous enoximone in idiopathic dilated cardiomyopathy

The acute effects of enoximone on left ventricular (LV) function, myocardial oxygen metabolism and central and systemic hemodynamics were investigated in 12 patients with idiopathic dilated cardiomyopathy. Enoximone was administered intravenously at a rate of 12.5 mg/min; the average dose was 1.42 mg/kg. LV systolic pressure decreased significantly (p less than 0.01) from 128 +/- 18 to 96 +/- 16 mm Hg (mean +/- standard deviation), LV end-diastolic pressure from 16 +/- 3 to 5 +/- 3 mm Hg, LV end-diastolic volume from 288 +/- 43 to 210 +/- 58 ml, LV end-diastolic wall stress from 33 +/- 15 to 11 +/- 5 10(3) dynes/cm2 and LV peak systolic wall stress from 243 +/- 73 to 159 +/- 42 10(3) dynes/cm2. Heart rate increased from 86 +/- 18 to 100 +/- 20 beats/min, ejection fraction from 43 +/- 7 to 52 +/- 14% (p less than 0.05). Cardiac index, stroke volume index and dP/dtmax did not change significantly. Systemic vascular resistance decreased significantly (p less than 0.01) from 1,311 +/- 444 to 1,027 +/- 356 dynes s cm-5, mean pulmonary artery pressure from 13 +/- 6 to 8 +/- 2 mm Hg, mean right atrial pressure from 4 +/- 2 to 2.6 +/- 2 mm Hg and mean arterial pressure from 95 +/- 13 to 74 +/- 13 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hydralazine on pressure-volume and stress-volume relations in congestive heart failure secondary to idiopathic dilated cardiomyopathy

The mechanism by which hydralazine improves cardiac function in patients with heart failure is not well characterized. Hydralazine may improve left ventricular (LV) function by decreasing afterloading wall stress or by increasing myocardial contractility. The effect of intravenous hydralazine was assessed in 8 patients with severe idiopathic dilated cardiomyopathy. Hydralazine increased stroke volume index (from 24 +/- 8 to 40 +/- 9 ml/m2, p less than 0.01) and decreased systemic vascular resistance from 1,603 +/- 619 to 810 +/- 317 dynes s cm-5, p less than 0.01) and peak LV wall stress (from 476 +/- 118 to 410 +/- 68 kdynes/cm2, p = 0.02). Two groups were defined by normal or high LV wall stress. Patients with high LV stress had higher LV end-diastolic pressure (38 +/- 12 vs 17 +/- 8 mm Hg, p less than 0.01), LV end-diastolic volume index (184 +/- 24 vs 149 +/- 7 ml/m2, p less than 0.01) and systemic vascular resistance (1,423 +/- 686 vs 846 +/- 293 dynes s cm-5, p = 0.01). Hydralazine decreased stress more in these patients (-101 +/- 57 vs -6 +/- 9 kdynes/cm2, p = 0.02), LV end-diastolic pressure (-12 +/- 7 vs 2 +/- 2 mm Hg, p = 0.02), systolic pressure (-15 +/- 13 vs 3 +/- 4 mm Hg, p = 0.03) and systemic vascular resistance (-1,053 +/- 247 vs -363 +/- 83 dynes s cm-5, p less than 0.01) than in patients with normal LV stress. Decreased LV stress was caused by decreased systolic and diastolic pressures and/or volumes. Late systolic pressure-volume relations in patients with normal LV stress suggested increased myocardial contractility, but this was not confirmed by LV dP/dt. Hydralazine improves LV function in patients with dilated cardiomyopathy by reducing elevated LV wall stress, with little inotropic effect.     

Effects of propafenone on coronary and systemic hemodynamics

This study was undertaken to evaluate the effects of intravenous Propafenone (2 mg/kg over 5') on Left Ventricular (LV) function and coronary blood flow. Twelve patients with coronary artery disease and post-ischemic LV disfunction were examined during routine cardiac catheterization. Serial measurements of central hemodynamics, LV high-fidelity pressure and coronary blood flow were recorded at rest and every 10' after Propafenone administration. Heart rate was unchanged, suggesting that Propafenone did not affect sympathetic tone. Cardiac index slightly decreased (from 3.3 +/- 0.9 L/min/m2 to 3.1 +/- 0.6 L/min/m2 at 10', p = ns), LV end-diastolic pressure rose significantly (from 17.7 +/- 2.1 mmHg to 22.7 +/- 4.2 mmHg at 20', p less than 0.01) and dP/dt max fell from 1897 +/- 291 mmHg/sec to 1577 +/- 312 mmHg/sec (p less than 0.02). Systemic vascular resistances had only minimal changes. Concomitantly, coronary vascular resistances decreased (from 0.77 +/- 0.17 mmHg/ml/min to 0.61 +/- 0.12 mmHg/ml/min, p less than 0.02) and coronary blood flow increased (from 138 +/- 29 ml/min to 172 +/- 21 ml/min, p less than 0.01). No significant difference was noted in myocardial oxygen consumption. No symptoms related to LV failure were observed during the study. In conclusion hemodynamic effects of Propafenone are characterized by moderate LV depression and by coronary artery dilatation, probably due to a calcium blocker-like activity.     

Sublingual nifedipine: acute effects in severe chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy

Nine patients with chronic, severe (New York Heart Association class III to IV) congestive heart failure were studied to determine the acute effects of 10 mg of sublingual nifedipine on left ventricular (LV) function. Hemodynamic and echocardiographic data were obtained at rest and 30 minutes, 1, 2, 4 and 6 hours after nifedipine. Measurements at rest reflected LV dysfunction with elevation of end-diastolic volume index (102 +/- 46 ml/m2), pulmonary capillary wedge pressure (17 +/- 8 mm Hg), systemic vascular resistance (1,547 +/- 439 dynes s cm-5) and reduction of cardiac index (2.8 +/- 0.5 liters/min/m2). There were no adverse effects noted with administration of sublingual nifedipine. Initial changes through 1 hour reflected an unloading effect of nifedipine with reduction in pulmonary capillary wedge pressure (11 +/- 5 mm Hg) (p less than 0.05), systemic vascular resistance (1,179 +/- 289 dynes s cm-5) (p less than 0.01), end-diastolic volume index (91 +/- 37 ml/m2 [difference not significant]) and an increase in cardiac index (3.6 +/- 0.7 ml liters/min/m2) (p less than 0.01). Subsequently the cardiac index, systemic vascular resistance and end-diastolic volume index returned toward baseline. Only the pulmonary capillary wedge and pulmonary artery pressures demonstrated a sustained reduction through the 6-hour study period suggesting an effect of nifedipine on LV relaxation. Thus, sublingual nifedipine administered acutely to patients with clinical congestive heart failure is a safe and efficacious vasodilator.     

Regional distribution of cardiac output at rest and during exercise in patients with exertional angina pectoris before and after nifedipine therapy

The short-term effects of sublingual nifedipine (20 mg) on cardiac output and its distribution at rest and during exercise were evaluated by measurement of iliofemoral blood flow and cardiac output in 10 men with stable angina pectoris controlled by metoprolol. At rest, nifedipine significantly decreased iliofemoral vascular resistance from 294 +/- 36 to 165 +/- 29 dynes.s.cm-5.10(2) (p less than 0.01) and significantly increased iliofemoral blood flow from 0.34 +/- 0.04 to 0.57 +/- 0.11 liters/min (p less than 0.05). Systemic vascular resistance was reduced from 19 +/- 1 to 13 +/- 1 dynes.s.cm-5.10(2) (p less than 0.001) and cardiac output increased significantly from 4.7 +/- 0.3 to 5.8 +/- 0.5 liters/min (p less than 0.05). Mean arterial pressure decreased significantly and heart rate increased significantly. During maximal upright bicycle exercise during nifedipine therapy, iliofemoral vascular resistance and leg blood flow were unchanged compared with control (23 +/- 2 versus 21 +/- 3 dynes.s.cm-5.10(2) and 4.7 +/- 0.5 versus 4.4 +/- 0.6 liters/min), cardiac output remained significantly increased (12.8 +/- 0.8 to 15.2 +/- 1.2 liters/min, p less than 0.05) and systemic vascular resistance remained significantly reduced (8 +/- 1 to 5 +/- 1 dynes.s.cm-5.10(2); p less than 0.001). The proportion of cardiac output distributed to the working lower limbs was significantly reduced at all exercise levels. In summary, nifedipine caused a redistribution of cardiac output by vasodilating nonexercising vascular beds without altering the locally mediated vasodilation in exercising muscle. In patients with coronary artery disease given nifedipine therapy, an increase in exercise tolerance is due to relief of myocardial ischemia rather than to increased peripheral oxygen delivery.     

Effect of the leukotriene receptor antagonist LY-171883 on endotoxemia in awake sheep

The effect of the leukotriene D4, leukotriene E4 (LTD4/E4) receptor antagonist LY-171883 was studied in endotoxemia. Eighteen awake sheep were divided into three groups. In Group (n = 4) 4 mg/kg LY-171883 was twice injected intravenously. In Group II (n = 9) 1 microgram/kg E. coli endotoxin was administered intravenously. In Group III (n = 5) 4 mg/kg LY-171883 was given 15 min before, and 30 min after endotoxin. Infusion of LY-171883 in Group I did not alter baseline hemodynamic and pulmonary measurements. Infusion of endotoxin in Group II was followed by an initial rise of pulmonary artery pressure (PAP) to 51 torr (P less than 0.001), pulmonary microvascular pressure (Pmv) to 25 torr (P less than 0.005), pulmonary vascular resistance (PVR) to 1,019 dynes sec. cm-5 (P less than 0.001), systemic vascular resistance (SVR) to 2,830 dynes sec. cm-5 (P less than 0.001), plasma thromboxane B2 (TXB2) to 4,971 pg/ml (P less than 0.001), lymph TXB2 to 5,500 pg/ml (P less than 0.001), plasma 6-Keto PGF1 alpha to 1,469 pg/ml (P less than 0.005), and lymph 6-Keto PGF1 alpha to 2,518 pg/ml (P less than 0.005). The cardiac index (CI) fell to 100 ml/min. kg (P less than 0.01), PaO2 to 61 torr (P less than 0.01), and circulating WBC to 2,800 microliter (P less than 0.001). This was followed by a rise in pulmonary lymph flow (QL) to 35 ml/h (P less than 0.01) and lymph protein clearance (L/P.QL) to 23 ml/h (P less than 0.01). Pretreatment with LY-171883 in Group III resulted in rise of PAP to 35 torr (P less than 0.005), PmV to 18 torr (P less than 0.05), PVR to 398 dynes sec. cm-5 (P less than 0.01), SVR to 1,732 dynes sec. cm-5 (P less than 0.05), and CI increased to 170 ml/min.kg (P less than 0.005). L/P.QL, QL, Hgb, WBC, PaO2, PaCO2, Qs/QT, plasma and lymph TXB2, and plasma and lymph 6-Keto PGF1 alpha were not significantly changed by LY-171883. It is concluded that LY-171883 inhibited the smooth muscle effects of endotoxin, namely reduced PAP, Pmv, PVR, and SVR and increased cardiac output. Hypoxemia and increased pulmonary vascular permeability were unaffected by this leukotriene receptor antagonist.     

Experimental coxsackie B3 virus myocarditis in golden hamsters. II. Evaluation of left ventricular function in intact in situ heart 14 months after inoculation

The hemodynamic changes of the left ventricle (LV) of golden hamsters surviving for 14 months after acute coxsackie B3 virus myocarditis were assessed with the use of a high fidelity micromanometer pressure system. Of 25 infected hamsters, 10 survived to the 14th month, and 4 of these had cardiomegaly. Body weight (BW) was 150.0 +/- 20.7 g (mean +/- SD) (controls, 164.5 +/- 20.1 g, NS); heart weight (HW), 0.499 +/- 0.084 g (controls, 0.448 +/- 0.035 g, NS); and HW/BW, 3.39 +/- 0.79 X 10(-3) (controls, 2.74 +/- 0.23 X 10(-3), p less than 0.05). The hemodynamic data under anesthesia were: HR, 378 +/- 42 (controls, 414 +/- 43, NS); LVSP, 108 +/- 16 mmHg (controls, 126 +/- 16, NS); LVDP, 4.0 +/- 4.8 mmHg (controls, 0.6 +/- 0.7, NS); LVEDP, 9.7 +/- 7.5 mmHg (controls, 3.4 +/- 1.4, NS); peak positive dp/dt, 4960 +/- 1431 mmHg/sec (controls, 6714 +/- 1326, p less than 0.05); (dp/dt)/DP40, 56.8 +/- 9.8 sec-1 (controls, 73.1 +/- 7.0, p less than 0.01); peak negative dp/dt, 3876 +/- 1072 mmHg/sec (controls, 4971 +/- 599, p less than 0.05); and time constant T of LV pressure fall, 7.7 +/- 1.3 msec (controls, 5.9 +/- 0.7, p less than 0.01). Five hamsters had congestion of the lungs and liver with or without an elevation of LVEDP. One of them had an organizing thrombus in the left atrium, and one had an aneurysm in the LV free wall. Though markedly varied in extent, residual myocardial fibrosis was always evident in the hearts in which isovolumic contractility and early diastolic relaxation of the LV were significantly impaired. In a clinical extension of these findings, it may be that some cases of dilated cardiomyopathy in man develop in a way similar to the pathological processes noted in this experiment.     

Static exercise with congestive heart failure and the response to vasodilating drugs

The hemodynamic response to static exercise in 28 patients with congestive heart failure (CHF) was compared with that in 8 control subjects. Static handgrip exercise at 50% of the maximal voluntary contraction was performed to fatigue. In patients with CHF, pulmonary arterial wedge pressure increased from 20 +/- 18 to 31 +/- 10 mm Hg (p less than 0.001) (mean +/- standard deviation) and systemic vascular resistance increased from 1,730 +/- 454 to 2,151 +/- 724 dynes s cm-5 (p less than 0.001). Although cardiac index did not change significantly, stroke volume index and stroke work index decreased from 24 +/- 6 to 20 +/- 6 ml/m2 (p less than 0.001) and 28 +/- 11 to 25 +/- 12 g-m/s2 (p less than 0.05), respectively. In control subjects, pulmonary arterial wedge pressure did not change significantly; cardiac index increased from 3.6 +/- 0.3 to 4.0 +/- 0.4 liters/min/m2 (p less than 0.05) and systemic vascular resistance increased slightly, from 1,011 +/- 186 to 1,106 +/- 180 dynes s cm-5 (p less than 0.05). The effects of arterial dilation with hydralazine on the response to static exercise were assessed in 10 of the patients with CHF. Compared with predrug exercise, cardiac index increased 68% (p less than 0.01), stroke volume index increased 76% (p less than 0.01) and systemic vascular resistance decreased 47% (p less than 0.01) after administration of hydralazine. Thus, static exercise can have adverse effects on cardiac performance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic mechanism of the elevation in blood pressure following the improvement of anemia with recombinant human erythropoietin

Following the administration of recombinant human erythropoietin (rHuEPO) to 18 patients undergoing hemodialysis, the hematocrit (Ht) increased from 19.7 +/- 1.8 to 31.0 +/- 2.0%. The incidence of hypertension according to the criteria of WHO was 11.1%. The systolic blood pressure (SBP) increased significantly from 120 +/- 21 to 129 +/- 26 mmHg (p less than 0.01) and diastolic blood pressure (DBP) increased from 67 +/- 14 to 73 +/- 12 mmHg (p less than 0.05). The cardiac index (CI) decreased significantly from 4.07 +/- 1.13 to 3.56 +/- 0.88 L/min/m2 (p less than 0.05). Total peripheral resistance index (TPRI) and blood volume (BV) increased significantly from 1,725 +/- 406 to 2,170 +/- 643 dynes/sec/cm-5/m2 (p less than 0.001) and from 78.9 +/- 11.2 to 87.8 +/- 14.8 ml/kg (p less than 0.005) respectively. Pulse rate (PR) decreased significantly from 73.0 +/- 10.7 to 65.9 +/- 7.8 beats/min (p less than 0.01). Patients who developed a blood pressure (BP) elevation of 10% or more for the mean blood pressure (MBP) showed a slight and insignificant decrease in CI from 3.65 +/- 1.12 to 3.49 +/- 1.06 L/min/m2, which clearly contrasted to that in another group of patients who showed a reduced increase in MBP and a significant reduction in CI from 4.50 +/- 1.03 to 3.63 +/- 0.72 L/min/m2 (p less than 0.05). Stroke volume index (SVI) was unchanged in both groups but PR decrease significantly in the latter group. A significant increase in TPRI or BV was observed equally in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects at rest and exertion of a new partial beta-agonist (cicloprolol) in moderated cardiac failure

The haemodynamic effects of cicloprolol, a new partial beta 1-adrenoceptor agonist, were investigated at rest and during exercise in 10 patients with moderate heart failure. At rest, cicloprolol (0.10 mg/kg i.v.) increased heart rate by 8 p. 100 (80.6 +/- 5.7 vs 74.7 +/- 11.9 beats/min; p less than 0.05), cardiac index by 17 p. 100 (3.74 +/- 0.57 vs 3.20 +/- 0.41 l/min/m2; p less than 0.001) and stroke index by 6 p. 100 (46.3 +/- 8.3 vs 43.7 +/- 8.8 ml/beat/m2; p less than 0.05). Left ventricular end-diastolic pressure was reduced by 35 p. 100 (9.9 +/- 5.0 vs 15.2 +/- 7.4 mmHg; p less than 0.01). There were no significant changes in aortic pressure. Systemic vascular resistance decreased by 15 p. 100 (1,030.8 +/- 234.6 vs 1,209.6 +/- 319.7 dynes.s.cm-5; p less than 0.01). During moderate exercise (114 +/- 13 watts) in supine position, cicloprolol induced a 10 p. 100 reduction of tachycardia (99.7 +/- 10.2 vs 112.2 +/- 16.5 beats/min; p less than 0.01), a 6 p. 100 decrease of mean aortic pressure (112.4 +/- 19.7 vs 119.5 +/- 19.2 mmHg; p less than 0.01) and an 8 p. 100 decrease of cardiac index (5.42 +/- 0.63 vs 5.88 +/- 0.75 l/min/m2; p less than 0.001). There were no significant changes in left ventricular filling pressure and stroke index. When data obtained at rest and during exercise were pooled, an inverse linear relationship (p less than 0.01) was found between heart rate before treatment with cicloprolol and cicloprolol-induced variations in heart rate and cardiac index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal hemodynamic effects of vasodilation with nifedipine and hydralazine in patients with heart failure

The central and renal hemodynamic effects of nifedipine were evaluated in nine patients with severe chronic congestive heart failure. Oral nifedipine (34 +/- 22 mg, mean +/- standard deviation) was associated with a decrease in systemic vascular resistance from 1,748 +/- 436 to 1,321 +/- 302 dynes . s . cm-5 (p less than 0.001) and mean arterial blood pressure from 96 +/- 11 to 87 +/- 6 mm Hg (p less than 0.05) and with an increase in cardiac output from 4.2 +/- 1.1 to 4.9 +/- 1.2 liters/min (p less than 0.001). Although renal vascular resistance decreased from 11,988 +/- 2,256 to 10,286 +/- 3,011 dynes . s . cm-5 (p less than 0.05), no significant change was seen in renal blood flow (599 +/- 120 to 640 +/- 162 ml/min), glomerular filtration rate (62 +/- 18 to 62 +/- 17 ml/min), filtration fraction (18 +/- 5 to 17 +/- 6%), the ratio of renal/systemic vascular resistance (7.0 +/- 1.0 to 7.9 +/- 1.8) and the ratio of renal blood flow/cardiac output (0.15 +/- 0.02 to 0.13 +/- 0.03). Intravenous hydralazine (10 +/- 5 mg), given to eight of the patients in a randomized crossover design, resulted in a larger increase in cardiac output than did nifedipine (38 +/- 7 versus 19 +/- 10%, p less than 0.001) and in an increase in total renal blood flow from 570 +/- 152 to 645 +/- 174 ml/min (p less than 0.001). Renal vascular resistance decreased from 12,080 +/- 2,934 to 10,153 +/- 2,372 dynes . s . cm-5 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential hemodynamic effects of Hypaque-76 and Renografin-76 during coronary angiography: the role of calcium-binding additives

Hypaque-76 (H76) and Renografin-76 (R76) are nearly identical ionic contrast media, except that R76 binds more calcium than H76 because of the presence of sodium citrate and EDTA in R76. To determine whether the calcium-binding additives in ionic contrast media contribute to the hemodynamic effects of contrast media during coronary angiography, left coronary angiography was performed in anesthetized dogs. In nine closed-chest dogs, 10 cc of H76 and R76 were injected in each dog in a blinded, randomized fashion. The effect of H76 and R76 on left ventricular systolic pressure (LVSP) and left ventricular diastolic pressure (LVDP), on mean aortic pressure (MAP), and on left ventricular (LV) dp/dt was recorded. Compared with H76, R76 produced a greater decrease in the LVSP (77 +/- 25 mmHg vs 48 +/- 17 mmHg P less than .05), MAP (72 +/- 24 mmHg vs 38 +/- 18 mmHg P less than .01), and LV dp/dt (747 +/- 87 mmHg/sec vs 460 +/- 81 mmHg/sec P less than .01). In nine additional open-chest dogs, left coronary angiography was performed 1 hour after occlusion of the proximal LAD coronary artery. Seven cc R76 produced a 35 +/- 15 mmHg decrease in LVSP, compared with 20 +/- 9 mmHg with H76 (P less than .01). The LV dp/dt decreased 720 +/- 387 mmHg/sec with R76, compared with 462 +/- 222 mmHg/sec with H76 (P less than 0.05). Thus, R76 produces significantly greater hemodynamic abnormalities than H76. Contrast media lacking calcium-binding agents may be preferable for coronary angiography.     

Acute hemodynamic and coronary effects of captopril in chronic cardiac failure

The acute effects of captopril on haemodynamics, coronary flow and myocardial metabolism were studied in 12 patients with chronic severe cardiac failure (primary cardiomyopathy: 10 cases; ischaemic: 2 cases) in functional Classes III or IV of the NYHA. All patients were male and their average age was 51.3 +/- 14.1 years (range 27 to 68 years). Measurements were carried out under basal conditions and 90 minutes after a single dose of 50 mg (5 cases) or 100 mg (7 cases) of captopril. Captopril administration leads to an increase in cardiac index from 2.05 +/- 0.32 to 2.34 +/- 0.35 l/min/m2 (p less than 0.05) and a greater increase in systolic index from 23.9 +/- 6.7 to 29.8 +/- 6.9 ml/syst/m2 (p less than 0.01), because the heart rate decreased slightly (p less than 0.05). These changes were the result of a decrease in afterload: mean aortic pressure fell from 85 +/- 11.8 to 68 +/- 19.6 mmHg (p less than 0.01) and systemic arterial resistance fell from 2 886 +/- 745 to 2 010 +/- 610 dynes/cm-5/sec/m-2 (p less than 0.01). Captopril also led to a fall in venous tone, i.e. pre-load: left ventricular end diastolic pressure fell from 26.9 +/- 6.1 to 20.8 +/- 6.6 mmHg: p less than 0.01. There was no change in contractility as shown by the absence of variation of the V.max (0.92 +/- 0.18 under basal conditions, and 0.90 +/- 0.15 after 90 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of denopamine on hemodynamics and blood gases in secondary pulmonary hypertension]

The acute hemodynamic and blood gas changes caused by denopamine (2 micrograms/kg/min, d.i.) were investigated in 13 patients with chronic respiratory failure and secondary pulmonary hypertension. Denopamine significantly reduced mean pulmonary arterial pressure from 25 +/- 7 to 23 +/- 7 mmHg (p less than 0.05), and pulmonary vascular resistance from 314 +/- 166 to 276 +/- 168 dyne/sec/cm-5 (p less than 0.05), while mean systemic arterial pressure and systemic vascular resistance showed no significant change. Pulmonary-systemic vascular resistance ratio was reduced significantly from 0.22 +/- 0.09 to 0.18 +/- 0.09 (p less than 0.05). These findings suggest that denopamine has more marked effects on the pulmonary artery than on systemic arteries. Arterial oxygen tension (PaO2) increased significantly from 59.0 +/- 8.1 to 62.5 +/- 10.5 Torr (p less than 0.01), and arterial carbon dioxide tension (PaCO2) decreased significantly from 49.1 +/- 6.8 to 44.6 +/- 7.0 Torr (p less than 0.01) by denopamine. Mixed venous oxygen tension (PvO2), which is an indicator of tissue oxygenation, increased significantly from 33.3 +/- 3.5 to 34.4 +/- 3.3 Torr (p less than 0.05). We conclude that denopamine is thought to be useful for the improvement of hemodynamics and tissue oxygenation in patients with secondary pulmonary hypertension. However, further long-term studies are necessary to establish its therapeutic efficacy.     

Effect of xamoterol on myocardial energetics in man

We analyzed the effect of xamoterol (beta 1-partial agonist) on myocardial energetics in 8 patients with normal left ventricular function. We measured resting systemic and coronary hemodynamics before and after a single intravenous injection of xamoterol (0.1 mg/kg). This agent increased heart rate from 70 +/- 7 to 80 +/- 11 beats/min (p less than 0.05) and cardiac index from 2.9 +/- 0.5 to 3.2 +/- 0.5 L/min.m2 (p less than 0.01), respectively. Left ventricular peak positive dp/dt (1870 +/- 350 vs 2620 +/- 580 mmHg/sec (p less than 0.01) and left ventricular ejection fraction (62 +/- 7 vs 70 +/- 7% (p less than 0.01] also increased, while left ventricular end-diastolic pressure (9 +/- 3 vs 5 +/- 3 mmHg (p less than 0.01] and volume index (70 +/- 14 vs 58 +/- 16 ml/m2 (p less than 0.01] decreased. Coronary blood flow and total myocardial oxygen consumption did not change significantly after intervention. As a result, xamoterol enhanced left ventricular external mechanical work versus myocardial oxygen consumption ratio (mechanical efficiency) from 20 +/- 4 to 24 +/- 5% (p less than 0.01). Myocardial oxygen extraction ratio decreased significantly (p less than 0.01) from 66 +/- 5 to 62 +/- 5% after xamoterol. We conclude that xamoterol augments left ventricular mechanical efficiency accompanied by a decrease in coronary vascular tone in patients with normal cardiac function.